bluuebunny/crossref_metadata_2025 huggingface dataset:
An X-ray and optical study of the outbursting behaviour of the SMC Be X-ray binary SXP 91.1
Authors: Monageng I M , Coe M J , Kennea J A , Townsend L J , Buckley D A H , McBride V A , Udalski A , Evans P A , Roche P D
Published: August 2019

In this paper we report on the optical and X-ray behaviour of the Be X-ray binary, SXP 91.1, during a recent type I outburst. We monitored the outburst using the Neil Gehrels Swift Observatory. These data were supported by optical data from the Southern African Large Telescope and the Optical Gravitational Lensing Experiment (OGLE) to show the circumstellar disc activity. Matter from this disc accretes on to the neutron star, giving rise to the X-ray outburst as seen in the synchronous evolution of the optical and X-ray light curves. Using data taken with OGLE we show that the circumstellar disc has exhibited stable behaviour over two decades. A positive correlation is seen between the colour and magnitude from the OGLE and massive compact halo object observations, which indicates that the disc is orientated at relatively low-inclination angles. From the OGLE and Swift data, we demonstrate that the system has shown relative phase offsets that have persisted for many years. The spin period derivative is seen to be at maximum spin-up at phases when the mass accretion rate is at maximum. We show that the neutron star in SXP 91.1 is an unusual member of its class in the sense that it has had a consistent spin period derivative over many years, with the average spin-up rate being one of the highest for known Small Magellanic Cloud pulsars. The most recent measurements of the spin-up rate reveal higher values than the global trend, which is attributed to the recent mass accretion event leading to the current outburst.
Accumulation of advanced glycation end products in follicles is associated with poor oocyte developmental competence
Authors: Takahashi Nozomi , Harada Miyuki , Azhary Jerilee M K , Kunitomi Chisato , Nose Emi , Terao Hiromi , Koike Hiroshi , Wada-Hiraike Osamu , Hirata Tetsuya , Hirota Yasushi , Koga Kaori , Fujii Tomoyuki , Osuga Yutaka
Published: August 2019

Advanced glycation end products (AGEs) affect the follicular microenvironment. The close relationship between AGEs, proinflammatory cytokine production and activation of the unfolded protein response (UPR), which involves activating transcription factor 4 (ATF4), is crucial for regulation of various cellular functions. We examined whether accumulation of AGEs in follicles was associated with proinflammatory cytokine production and activation of the UPR in granulosa cells and decreased oocyte developmental competence. Concentrations of AGEs, soluble receptor for AGE (sRAGE), interleukin (IL)-6 and IL-8 in follicular fluid (FF) were examined by ELISAs in 50 follicles. mRNA expression of ATF4, IL-6 and IL-8 in cumulus cells (CCs) were examined by quantitative RT-PCR in 77 samples. Cultured human granulosa-lutein cells (GLCs) were treated with AGE-bovine serum albumin (BSA) alone or following transfection of ATF4-targeting small interfering RNA. The AGE concentration and the AGE/sRAGE ratio in FF were significantly higher in follicles containing oocytes that developed into poor-morphology embryos (group I) than those with good-morphology embryos (group II). When compared with sibling follicles from the same patients, the AGE/sRAGE and concentrations of IL-6 and IL-8 in FF, as well as ATF4, IL-6 and IL-8 mRNA expression in CCs, were significantly higher in group I follicles than group II. AGE treatment increased mRNA expression of ATF4, IL-6 and IL-8 in cultured GLCs. Knockdown of ATF4 abrogated the stimulatory effects of AGE on mRNA expression and protein secretion of IL-6 and IL-8. Our findings support the idea that accumulation of AGEs in follicles reduces oocyte competence by triggering inflammation via activation of ATF4 in the follicular microenvironment.
RNA degradomes reveal substrates and importance for dark and nitrogen stress responses of Arabidopsis XRN4
Authors: Nagarajan Vinay K , Kukulich Patrick M , von Hagel Bryan , Green Pamela J
Published: August 2019

XRN4, the plant cytoplasmic homolog of yeast and metazoan XRN1, catalyzes exoribonucleolytic degradation of uncapped mRNAs from the 5′ end. Most studies of cytoplasmic XRN substrates have focused on polyadenylated transcripts, although many substrates are likely first deadenylated. Here, we report the global investigation of XRN4 substrates in both polyadenylated and nonpolyadenylated RNA to better understand the impact of the enzyme in Arabidopsis. RNA degradome analysis demonstrated that xrn4 mutants overaccumulate many more decapped deadenylated intermediates than those that are polyadenylated. Among these XRN4 substrates that have 5′ ends precisely at cap sites, those associated with photosynthesis, nitrogen responses and auxin responses were enriched. Moreover, xrn4 was found to be defective in the dark stress response and lateral root growth during N resupply, demonstrating that XRN4 is required during both processes. XRN4 also contributes to nonsense-mediated decay (NMD) and xrn4 accumulates 3′ fragments of select NMD targets, despite the lack of the metazoan endoribonuclease SMG6 in plants. Beyond demonstrating that XRN4 is a major player in multiple decay pathways, this study identified intriguing molecular impacts of the enzyme, including those that led to new insights about mRNA decay and discovery of functional contributions at the whole-plant level.
A Means to an End and an End in Itself: Select Committee Membership, Parliamentary Roles and Parliamentary Careers, 1979–Present
Authors: McKay Stephen , Goodwin Mark , Holden Bates Stephen
Published: August 2019

Committees are important vehicles for parliamentary careers both as means to a (ministerial) end and as an end in themselves. This article explores the relationship between select committee membership and parliamentary career by analysing committee membership and frontbench appointments for the 2130 Members of Parliament (MPs) first elected since 1979. We focus on two of Donald Searing’s four informal backbench roles—Policy Advocates and Parliament Men and Women—and three of the four formal leadership roles—Whips, Junior Ministers and Ministers. The membership patterns of select committees suggest that MPs approach this aspect of their parliamentary work in different ways concomitant with the roles of Generalist and Specialist Policy Advocates and Good House of Commons Men and Women. The membership patterns also suggest that different groups of MPs—by party, gender and ethnicity—often (choose or are forced to) approach committee work in different ways. We also find membership of some committees is more strongly associated with leadership roles than others.
Plant Specialized Metabolism Regulated by Jasmonate Signaling
Authors: Chen Xueying , Wang Dan-Dan , Fang Xin , Chen Xiao-Ya , Mao Ying-Bo
Published: August 2019

As sessile and autotrophic organisms, plants have evolved sophisticated pathways to produce a rich array of specialized metabolites, many of which are biologically active and function as defense substances in protecting plants from herbivores and pathogens. Upon stimuli, these structurally diverse small molecules may be synthesized or constitutively accumulated. Jasmonate acids (JAs) are the major defense phytohormone involved in transducing external signals (such as wounding) to activate defense reactions, including, in particular, the reprogramming of metabolic pathways that initiate and enhance the production of defense compounds against insect herbivores and pathogens. In this review, we summarize the progress of recent research on the control of specialized metabolic pathways in plants by JA signaling, with an emphasis on the molecular regulation of terpene and alkaloid biosynthesis. We also discuss the interplay between JA signaling and various signaling pathways during plant defense responses. These studies provide valuable data for breeding insect-proof crops and pave the way to engineering the production of valuable metabolites in future.
Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis
Authors: Choy Ernest H
Published: August 2019

Fatigue is a common and debilitating symptom in patients with RA. Since 2007, fatigue has been included as one of the core outcome measures in RA. Clinical trials of biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have included fatigue as a secondary endpoint. A Cochrane review in 2016 concluded that the bDMARDs have a moderate effect on improving fatigue in RA. More recent clinical trials of the new biologic agent sarilumab and the Janus kinase inhibitors tofacitinib and baricitinib showed similar benefits. It remains unclear whether the effect of bDMARDs and tsDMARDs on fatigue is mediated by direct effects or through a reduction in inflammation. As fatigue was a secondary endpoint, many analyses did not adjust for potential confounding factors, including pain, mood and anaemia, which is a significant limitation.
Aberrant reward dynamics in trait anticipatory anhedonia
Authors: Zhou Shiyu , Nie Lu , Wang Zhao , Wang Mengyao , Zheng Ya
Published: August 2019

As a cardinal feature of several psychiatric disorders, anhedonia includes a consummatory component (deficits in hedonic response to rewards) and an anticipatory component (a reduced motivation to pursue them). Although being conceptualized as impairments of reward system, the neural characterization of reward processing in anhedonia is hampered by the enormous heterogeneity in the reward phase (‘wanting’ vs ‘liking’) and comorbidity (inherent to disease states). The current event-related potential (ERP) study examined the reward dynamics of anticipatory anhedonia in a non-clinical sample. Anticipatory and consummatory ERP components were assessed with a monetary incentive delay task in a high anticipatory anhedonia (HAA) group and a low anticipatory anhedonia (LAA) group. HAA vs LAA group showed a diminished reward-related speeding during behavioral performance and reported overall reduced positive affect during anticipation and receipt of outcomes. Importantly, neural dynamics underlying reward processing were negatively associated with anticipatory anhedonia across the anticipatory phase indexed by the contingent negative variation and the consummatory phase indexed by the feedback P3. Our results suggest that anticipatory anhedonia in non-clinical individuals is linked to a poor modulation during both anticipatory and consummatory phases of reward processing.
Sleep duration and post-traumatic stress disorder symptoms: a twin study
Authors: McCall Catherine A , Turkheimer Eric , Tsang Siny , Avery Ally , Duncan Glen E , Watson Nathaniel F
Published: August 2019

Study Objectives

Long and short sleep duration are associated with greater risk of developing post-traumatic stress disorder (PTSD); however, it is unknown how genetic and environmental influences affect this relationship. Thus, we investigated the association between sleep duration and PTSD symptoms using twin models.

Methods

Data were obtained from 1865 monozygotic and 758 dizygotic twin pairs enrolled in the community-based Washington State Twin Registry. PTSD symptoms were assessed using the Impact of Events Scale (IES). A classical twin model decomposed the variances of sleep duration and IES score into additive genetic, shared environmental, and unique environmental components. We used correlated factor models to examine the moderation of variance components of sleep duration and IES.

Results

Shorter and longer sleep duration were associated with higher IES scores with a quadratic association (p < 0.001). The heritability of sleep duration was 36%, and IES 31%. Variance in sleep duration attributable to shared (b1C1 = 2.91, 95% CI = 1.40 to 4.43; p < 0.001) and unique (b1E1 = 0.18, 95% CI = 0.10 to 0.27; p < 0.001) environment was moderated by IES score. Similarly, but to a lesser extent, variance in IES attributable to additive genetics (b1A2 = −0.23, 95% CI = −0.45 to 0.00; p = 0.048) was moderated by sleep duration.

Conclusions

Greater PTSD symptom severity was associated with short and long sleep duration. Increasing PTSD symptoms increased variability in sleep duration primarily via shared environmental factors, whereas decreasing sleep duration increased variability in PTSD symptoms primarily via additive genetic factors. This suggests childhood experiences affect variability of sleep duration and genetic factors affect the variability of PTSD symptoms in trauma-exposed individuals.
Sleep stage prediction with raw acceleration and photoplethysmography heart rate data derived from a consumer wearable device
Authors: Walch Olivia , Huang Yitong , Forger Daniel , Goldstein Cathy
Published: August 2019

Wearable, multisensor, consumer devices that estimate sleep are now commonplace, but the algorithms used by these devices to score sleep are not open source, and the raw sensor data is rarely accessible for external use. As a result, these devices are limited in their usefulness for clinical and research applications, despite holding much promise. We used a mobile application of our own creation to collect raw acceleration data and heart rate from the Apple Watch worn by participants undergoing polysomnography, as well as during the ambulatory period preceding in lab testing. Using this data, we compared the contributions of multiple features (motion, local standard deviation in heart rate, and “clock proxy”) to performance across several classifiers. Best performance was achieved using neural nets, though the differences across classifiers were generally small. For sleep-wake classification, our method scored 90% of epochs correctly, with 59.6% of true wake epochs (specificity) and 93% of true sleep epochs (sensitivity) scored correctly. Accuracy for differentiating wake, NREM sleep, and REM sleep was approximately 72% when all features were used. We generalized our results by testing the models trained on Apple Watch data using data from the Multi-ethnic Study of Atherosclerosis (MESA), and found that we were able to predict sleep with performance comparable to testing on our own dataset. This study demonstrates, for the first time, the ability to analyze raw acceleration and heart rate data from a ubiquitous wearable device with accepted, disclosed mathematical methods to improve accuracy of sleep and sleep stage prediction.
Triclabendazole in the treatment of human fascioliasis: a review
Authors: Gandhi Preetam , Schmitt Esther K , Chen Chien-Wei , Samantray Sanjay , Venishetty Vinay Kumar , Hughes David
Published: August 2019

Fascioliasis occurs on all inhabited continents. It is caused by Fasciola hepatica and Fasciola gigantica, trematode parasites with complex life cycles, and primarily affects domestic livestock. Humans become infected after ingestion of contaminated food (typically wild aquatic vegetables) or water. Fascioliasis may be difficult to diagnose as many symptoms are non-specific (e.g. fever, abdominal pain and anorexia). Treatment options are limited, with older effective therapies such as emetine and bithionol no longer used due to safety issues and unavailability, and most common anthelminthics having poor efficacy. Clinical trials conducted over a 25-year period, together with numerous case reports, demonstrated that triclabendazole has high efficacy in the treatment of human fascioliasis in adults and children and in all stages and forms of infection. Triclabendazole was approved for human use in Egypt in 1997 and in France in 2002 and a donation program for the treatment of fascioliasis in endemic countries was subsequently established by the manufacturer and administered by the World Health Organization. Here the published data on triclabendazole in the treatment of human fascioliasis are reviewed, with a focus on more recent data, in light of the 2019 US Food and Drug Administration approval of the drug for use in human infections.
The caudal skeleton of Batrachoidiformes (Teleostei: Percomorphacea): a study of morphological diversity, intraspecific variation, and phylogenetic inferences
Authors: Vaz Diego F B , Hilton Eric J
Published: August 2019

The caudal-fin skeleton is a primary data source for systematics of fishes, with characters from this complex being proposed as synapomorphies at many taxonomic levels. Batrachoidiformes is recognized as monophyletic, although intraordinal relationships are unclear. Likewise, interrelationships of Batrachoidiformes to other percomorphs are not well established. The caudal skeleton of Batrachoidiformes has not been thoroughly studied and is poorly represented in recent phylogenetic analyses. In this study, we examined the caudal-fin skeleton of 55 of the 82 species and 22 of the 23 genera of Batrachoidiformes, emphasizing the detection of intraspecific variation to recognize morphological characters with phylogenetic significance. Intraspecific variation is high, especially in the shape of epurals and the parhypural flange. A dorsal prezygapophysis on the first ural centrum and the acute articular edge of the parhypural flange are interpreted as putative synapomorphies of Porichthyinae. The anterior epural supporting two procurrent fin rays is found only in some Halophryninae, but is absent in Allenbatrachus, Batrachomeus, Batrichthys and Halophryne. Among Batrachoidiformes, a hypurapophysis-like process on the first ural centrum is found in Thalassophryninae and Barchatus, Batrichthys, Bifax, Chatrabus, Colletteichthys, Halobatrachus, Perulibatrachus and Riekertia. Caudal-fin ray counts are phylogenetically informative at several taxonomic levels. Distal caudal cartilages are described for Batrachoidiformes for the first time.
MdWRKY46-Enhanced Apple Resistance to Botryosphaeria dothidea by Activating the Expression of MdPBS3.1 in the Salicylic Acid Signaling Pathway
Authors: Zhao Xian-Yan , Qi Chen-Hui , Jiang Han , Zhong Ming-Shuang , Zhao Qiang , You Chun-Xiang , Li Yuan-Yuan , Hao Yu-Jin
Published: August 2019

Salicylic acid (SA) is closely related to disease resistance of plants. WRKY transcription factors have been linked to the growth and development of plants, especially under stress conditions. However, the regulatory mechanism of WRKY proteins involved in SA production and disease resistance in apple is not clear. In this study, MdPBS3.1 responded to Botryosphaeria dothidea and enhanced resistance to B. dothidea. Electrophoretic mobility shift assays, yeast one-hybrid assays, and chromatin immunoprecipitation and quantitative PCR demonstrated that MdWRKY46 can directly bind to a W-box motif in the promoter of MdPBS3.1. Glucuronidase transactivation and luciferase analysis further showed that MdWRKY46 can activate the expression of MdPBS3.1. Finally, B. dothidea inoculation in transgenic apple calli and fruits revealed that MdWRKY46 improved resistance to B. dothidea by the transcriptional activation of MdPBS3.1. Viral vector-based transformation assays indicated that MdWRKY46 elevates SA content and transcription of SA-related genes, including MdPR1, MdPR5, and MdNPR1 in an MdPBS3.1-dependent way. These findings provide new insights into how MdWRKY46 regulates plant resistance to B. dothidea through the SA signaling pathway.
CE: Original Research: Are Milk and Molasses Enemas Safe for Hospitalized Adults? A Retrospective Electronic Health Record Review
Authors: Wangui-Verry Jackline , Farrington Michele , Matthews Grace , Tucker Sharon J.
Published: August 2019

Background: Constipation in hospitalized patients is common. As a treatment of last resort for unresolved constipation, a milk and molasses enema is often used by nursing staff. But there has been little research investigating the safety and efficacy of this approach.

Purpose: The purpose of this retrospective study was to evaluate the safety of milk and molasses enemas for hospitalized adults with constipation that remained unresolved after standard treatment options were exhausted.

Methods: Data were extracted from the electronic health records (EHRs) of 615 adult patients who had received a milk and molasses enema between July 2009 and July 2013 at a large midwestern academic medical center. Data analysis occurred for a random subset of this group.

Participant characteristic variables included age, sex, admitting diagnosis, diet orders, medications, laxatives and enemas administered before the milk and molasses enema, and laboratory values. Serious complication variables included bacteremia, bowel perforation, electrolyte abnormalities, allergic reaction, abdominal compartment syndrome, cardiac arrhythmia, dehydration, and death.

Findings: The final sample of 196 adults had a mean age of 56 years; 61.2% were female and 38.8% were male. Of 105 admitting diagnoses, the most frequent (9.7%) was abdominal pain, unspecified site. Of the 14 discharge dispositions, the most frequent was home or self-care (50.5%). A laxative order was present for 97.4% of patients and a stool softener order was present for 86.2%. Sodium and potassium levels remained within normal limits during hospitalization. For the subset of patients who had these values measured within 48 hours before and after milk and molasses enema administration, no significant changes were found. No cases of nontraumatic abdominal compartment syndrome or other serious adverse enema-related events were documented in the EHR.

Conclusions: No safety concerns were identified from this retrospective EHR review of hospitalized adults who received a milk and molasses enema for constipation relief. The findings indicate that this treatment is safe, although further study examining its efficacy in this population is needed.
Sensory Function and Pain Experience in Arthritis, Complex Regional Pain Syndrome, Fibromyalgia Syndrome, and Pain-Free Volunteers
Authors: Palmer Shea , Bailey Jacqueline , Brown Christopher , Jones Anthony , McCabe Candy S.
Published: August 2019

Objectives:

This study aimed to identify relationships between sensory function and pain in 3 common pain conditions (arthritis, Complex Regional Pain Syndrome [CRPS] and fibromyalgia syndrome [FMS]) and pain-free participants. Sensory abnormalities are known to be concomitant with some types of chronic pain but comparison across pain conditions using existing research is difficult due to methodological differences. Pragmatic Quantitative Sensory Testing (QST) methods were used.

Materials and Methods:

Hot and cold sensitivity, light touch threshold (LTT), two-point discrimination and pain threshold were assessed in 143 participants (n=37 pain-free, n=34 arthritis, n=36 CRPS, n=36 FMS). Outcomes were assessed in the index (“affected” or right) and contralateral arm. Participants also completed the Brief Pain Inventory and the McGill Pain Questionnaire.

Results:

There were statistically significant differences between groups for all QST outcomes except two-point discrimination. Relative to pain-free participants, FMS displayed heat hyperesthesia in both arms and cold hyperesthesia in the contralateral arm. CRPS demonstrated no changes in thermal sensitivity. Both CRPS and FMS exhibited bilateral pressure hyperalgesia. LTT hypoesthesia was observed bilaterally for CRPS but only in the contralateral arm for FMS. CRPS and FMS had pressure hyperalgesia in the index arm relative to arthritis patients. There were no differences between arthritis and pain-free participants for any QST outcome. In CRPS, there were significant correlations between LTT and pain outcomes bilaterally.

Discussion:

People with FMS and CRPS demonstrate extensive sensory dysfunction. Arthritis patients had sensory profiles closer to pain-free participants. LTT may provide a clinically relevant and accessible assessment for CRPS.
The Effects of Breast Reduction on Back Pain and Spine Measurements: A Systematic Review
Authors: Papanastasiou Constantine , Ouellet Jean A. , Lessard Lucie
Published: August 2019

Background:

The aim of this review article was to synthesize the literature on reduction mammaplasty and its effects on the spine. The particular focus was to find these few radiological studies and those investigating changes in spinal angles, posture, center of gravity, and back pain reduction.

Methods:

We performed a thorough review of the literature, searching the Medline database for all relevant published data studying reduction mammaplasty and the spine. The search yielded 107 articles of which 11 articles met our specific inclusion criteria. The primary outcome measures of the studies and their respective results were tabulated, contrasted, and compared.

Results:

The 11 cohort studies included in this review cover the period from 2005 to 2015 and focus on breast hypertrophy and spine. According to these 11 quantitative studies, breast hypertrophy causes objective, quantitative, measurable disturbances to women living with this condition. Reduction mammaplasty produces an unmistakable improvement in signs, symptoms, and quantifiable measures. Although the majority of included articles in this review described postoperative improvement in spinal angles, there remain discrepancies of results between them.

Conclusions:

The studies included in this review did offer a promising glimpse into the complex interaction between breast hypertrophy and the spine. However, future research initiatives can improve upon what these investigators have begun with more refined, objective, radiological evidence. More specifically, we aim to clarify some of the basic hypotheses in our center with the use of EOS.
Transcriptional survey of peripheral blood links lower oxygen saturation during sleep with reduced expressions of CD1D and RAB20 that is reversed by CPAP therapy
Authors: Sofer Tamar , Li Ruitong , Joehanes Roby , Lin Honghuang , Gower Adam C. , Wang Heming , Kurniansyah Nuzulul , Cade Brian E. , Lee Jiwon , Williams Stephanie , Mehra Reena , Patel Sanjay R. , Quan Stuart F. , Liu Yongmei , Rotter Jerome I. , Rich Stephen S. , Spira Avrum , Levy Daniel , Gharib Sina A. , Redline Susan , Gottlieb Daniel J.
Published: August 2019

Sleep Disordered Breathing (SDB) is associated with a wide range of physiological changes due, in part, to the influence of hypoxemia during sleep. We studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. We performed discovery association analysis in two community-based studies, the Framingham Offspring Study (FOS; N=571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580). An association with false discovery rate (FDR) q < 0.05 in one study was considered “replicated” if a p < 0.05 was observed in the other study. Those genes that replicated across MESA and FOS, or with FDR q < 0.05 in meta-analysis, were used for analysis of gene expression in the blood of 15 participants from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. HeartBEAT participants had moderate or severe obstructive sleep apnea (OSA) and were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses. Twenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated in response to CPAP treatment (HeartBEAT).

One Sentence Summary

We studied the association of gene expression in blood with obstructive sleep apnea traits, including oxygen saturation during sleep, and identified mechanisms that are reversed by treatment with Continuous Positive Airway Pressure.
Associations of childcare type, age at start, and intensity with body mass index trajectories from 10 to 42 years of age in the 1970 British Cohort Study
Authors: Costa Silvia , Bann David , Benjamin-Neelon Sara E , Adams Jean , Johnson William
Published: August 2019

Background

Attending childcare is related to greater childhood obesity risk, but there are few long-term follow-up studies. We aimed to examine the associations of childcare type, duration, and intensity with BMI trajectories from ages 10-42 years.

Methods

The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), duration (4-5, 3-3.99, 0-2.99 years old when started), and intensity (1, 2, 3, 4-5 days/week) reported at age five years and 32563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample-average BMI trajectory, with covariate adjustment. A combined duration and intensity exposure was also examined.

Results

Childcare attendance and type were not strongly related to BMI trajectories. Among participants who attended childcare 1-2 days a week, those who started when 3-3.99 years old had a 0.197 (-0.004, 0.399) kg/m2higher BMI at age 10 years than those who started when 4-5 years old, and those who started when 0-2.99 years old had a 0.289 (0.049, 0.529) kg/m2higher BMI. A similar dose-response pattern for intensity was observed when holding duration constant. By age 42 years, individuals who started childcare at age 0-2.99 years and attended 3-5 days/week had a 1.356 kg/m2(0.637, 2.075) higher BMI than individuals who started at age 4-5 years and attended 1-2 days/week.

Conclusions

Children who start childcare earlier and/ or attend more frequently may have greater long-term obesity risk.
Immunoglobulin E as a biomarker for the overlap of atopic asthma and chronic obstructive pulmonary disease
Authors: Hersh Craig P. , Zacharia Soumya , Arivu Chelvan Ram Prakash , Hayden Lystra P. , Mirtar Ali , Zarei Sara , Putcha Nirupama ,   the COPDGene Investigators
Published: August 2019

Asthma-COPD overlap (ACO) is a common clinical syndrome, yet there is no single objective definition. We hypothesized that Immunoglobulin E measurements could be used to refine the definition of ACO. In baseline plasma samples from 2870 subjects in the COPDGene Study, we measured total IgE levels and specific IgE levels to six common allergens. Compared to usual COPD, subjects with ACO had higher total IgE levels (median 67.0 vs 42.2 IU/ml) and more frequently had at least one positive specific IgE (43.5 vs 24.5%). We previously used a strict definition of ACO in subjects with COPD, based on self-report of a doctor’s diagnosis of asthma before the age of 40. This strict ACO definition was refined by the presence of atopy, determined by total IgE >100 IU/ml or at least one positive specific IgE, as was a broader definition of ACO based on any asthma history. Subjects will all three ACO definitions were younger (mean age 60.0-61.3), were more commonly African American (36.8-44.2%), had a higher exacerbation frequency (1.0-1.2 in the past year), and had more airway wall thickening on quantitative analysis of chest CT scans. Among subjects with clinical ACO, 37-46% did not have atopy; these subjects had more emphysema on chest CT scan. Based on associations with exacerbations and CT airway disease, IgE did not clearly improve the clinical definition of ACO. However, IgE measurements could be used to subdivide subjects with atopic and non-atopic ACO, who might have different biologic mechanisms and potential treatments.
Evaluating the relationships between the legal and illegal international wildlife trades
Authors: Tittensor Derek P. , Harfoot Michael , McLardy Claire , Britten Gregory L. , Kecse-Nagy Katalin , Landry Bryan , Outhwaite Willow , Price Becky , Sinovas Pablo , Blanc Julian , Burgess Neil D. , Malsch Kelly
Published: August 2019

The international legal trade in wildlife can provide economic and other benefits, but when unsustainable can be a driver of population declines. This impact is enhanced by the additional burden of illegal trade. We combined law-enforcement time-series of seizures of wildlife goods imported into the United States (US) and the European Union (EU) with data on reported legal trade to evaluate the evidence for any relationships. Our analysis examined 28 (US) and 20 (EU) taxon-products with high volume and frequency of reported trade and seizures. On average, seizures added 28% and 9% to US and EU reported legal trade levels respectively, and in several cases exceeded legal imports. We detected a significant but weak overall positive relationship between seizure volumes and reported trade imported to the US over time, but none in the EU. Our findings suggest a complex and nuanced temporal association between the illegal and legal wildlife trades.
Geostatistical visualization of ecological interactions in tumors
Authors: Boyce Hunter , Mallick Parag
Published: August 2019

Recent advances in our understanding sof cancer progression have highlighted the important role played by proteomic heterogeneity and the tumor microenvironment. Single-cell measurement technologies have enabled deep investigation of tumor heterogeneity. However, tools to visualize and interpret single-cell data have lagged behind experimental methods; currently, dimensionality reduction and clustering techniques, such as t-sne and SPADE, are the most prevalent visualization techniques. However, such techniques do not enable the visualization of the super-cellular structures that arise either via microenvironmental forces (e.g. hypoxia) or through cell-cell interactions. They additionally do not allow the visualization of ecological niches that are critical to understanding tumor behavior. The advent of novel experimental hyperplex immunostaining platforms, capable of measuring the in situ protein expression of dozens of proteins simultaneously, necessitates novel computational tools to quantify and visualize spatial patterns in the tumor microenvironment. Here, we introduce an approach to visualize tumor heterogeneity that integrates multiple geostatistics to capture both global and local spatial patterns. We assess the utility of this approach using an agent-based model of tumor growth under four ecological contexts; predation, mutualism, commensalism, and parasitism. Spatial patterns are visualized in real time as the models progress. This application introduces both an ecological framework for characterizing cellular interactions in cancer and novel way of quantifying and visualizing spatial patterns in cancer.
Insights on aquatic microbiome of the Indian Sundarbans mangrove areas
Authors: Dhal Paltu Kumar , Kopprio Gérmán A. , Gärdes Astrid
Published: August 2019

Background

Anthropogenic perturbations have strong impact on water quality and ecological health of mangrove areas of Indian Sundarbans. Diversity in microbial community composition is important causes for maintaining the healthy of the mangrove ecosystem. However, microbial communities of estuarine water in Indian Sundarbans mangrove areas and environmental determinants that contribute to those communities were seldom studied.

Methods

Nevertheless, this study attempted first to report bacterial and archaeal communities simultaneously in the water from Matla River and Thakuran River of Maipith coastal areas more accurately using 16S rRNA gene-based amplicon approaches. Attempt also been made to assess the capability of the environmental parameters for explaining the variation in microbial community composition.

Results

Our investigation indicates the dominancy of halophilic marine bacteria from families Flavobacteriaceae and OM1 clade in the water with lower nutrient load collected from costal regions of a small Island of Sundarban Mangroves (ISM). At higher eutrophic conditions, changes in bacterial communities in Open Marine Water (OMW) were detected, where some of the marine hydrocarbons degrading bacteria under families Oceanospirillaceae and Spongiibacteraceae were dominated. While most abundant bacterial family Rhodobacteracea almost equally (18% of the total community) dominated in both sites. Minor variation in the composition of archaeal community was also observed between OMW and ISM. Redundancy analysis indicates a combination of total nitrogen and dissolved inorganic nitrogen for OMW and for ISM, salinity and total nitrogen was responsible for explaining the changes in their respective microbial community composition.

Conclusions

Our study can serve as baseline approaches, which should focused on how do multiple environmental/anthropogenic stressors (salinity, pollution, eutrophication, land-use) affect the estuary water and consequently the microbial communities in concert. However, systematic approaches with more samples for evaluating the effect of environmental pollutions on mangrove microbial communities are recommended.
DeepRF: Ultrafast population receptive field mapping with deep learning
Authors: Thielen Jordy , Güçlü Umut , Güçlütürk Yagmur , Ambrogioni Luca , Bosch Sander E. , van Gerven Marcel A. J.
Published: August 2019

Population receptive field (pRF) mapping is an important asset for cognitive neuroscience. The pRF model is used for estimating retinotopy, defining functional localizers and to study a vast amount of cognitive tasks. In a classic pRF, the cartesian location and receptive field size are modeled as a 2D Gaussian kernel in visual space and are estimated by optimizing the fit between observed responses and predicted responses. In the standard framework this is achieved using an iterative gradient descent algorithm. This optimization is time consuming because the number of pRFs to fit (e.g., fMRI voxels) is typically large. This computation time increases further with the complexity of the pRF model (e.g., adding HRF parameters, surround suppression and uncertainty measures). Here, we introduce DeepRF, which uses deep convolutional neural networks to estimate pRFs. We compare the performance of DeepRF with that of the conventional method using a synthetic dataset for which the ground truth is known and an empirical dataset. We show that DeepRF achieves state-of-the-art performance while being more than 3 orders of magnitude faster than the conventional method. This enables easier and faster modeling of more complex pRF models, resolving an important limitation of the conventional approach.
Anticipating critical transitions in epithelial-hybrid-mesenchymal cell-fate determination
Authors: Sarkar Sukanta , Sinha Sudipta Kumar , Levine Herbert , Jolly Mohit Kumar , Dutta Partha Sharathi
Published: August 2019

In the vicinity of a tipping point, critical transitions occur when small changes in an input condition causes sudden, large and often irreversible changes in the state of a system. Many natural systems ranging from ecosystems to molecular biosystems are known to exhibit critical transitions in their response to stochastic perturbations. In diseases, an early prediction of upcoming critical transitions from a healthy to a disease state by using early warning signals is of prime interest due to potential application in forecasting disease onset. Here, we analyze cell-fate transitions between different phenotypes (epithelial, hybrid epithelial/mesenchymal (E/M) and mesenchymal states) that are implicated in cancer metastasis and chemoresistance. These transitions are mediated by a mutually inhibitory feedback loop microRNA-200/ZEB driven by the levels of transcription factor SNAIL. We find that the proximity to tipping points enabling these transitions among different phenotypes can be captured by critical slowing down based early warning signals, calculated from the trajectory of ZEB mRNA level. Further, the basin stability analysis reveals the unexpectedly large basin of attraction for a hybrid E/M phenotype. Finally, we identified mechanisms that can potentially elude the transition to a hybrid E/M phenotype. Overall, our results unravel the early warning signals that can be used to anticipate upcoming epithelial-hybrid-mesenchymal transitions. With the emerging evidence about the hybrid E/M phenotype being a key driver of metastasis, drug resistance, and tumor relapse; our results suggest ways to potentially evade these transitions, reducing the fitness of cancer cells and restricting tumor aggressiveness.

Significance Statement

Epithelial-hybrid-mesenchymal transitions play critical roles in cancer metastasis, drug resistance, and tumor relapse. Recent studies have proposed that cells in a hybrid epithelial/mesenchymal phenotype may be more aggressive than those on either end of the spectrum. However, no biomarker to predict upcoming transitions has been identified. Here, we show that critical slowing down based early warning signals can detect sudden transitions among epithelial, hybrid E/M, and mesenchymal phenotypes. Importantly, our results highlight how stable a hybrid E/M phenotype can be, and how can a transition to this state be avoided. Thus, our study provides valuable insights into restricting cellular plasticity en route metastasis.
Transcriptome-based molecular staging of human stem cell-derived retinal organoids uncovers accelerated photoreceptor differentiation by 9-cis retinal
Authors: Kaya Koray D. , Chen Holly Y. , Brooks Matthew J. , Kelley Ryan A. , Shimada Hiroko , Nagashima Kunio , de Val Natalia , Drinnan Charles T. , Gieser Linn , Kruczek Kamil , Erceg Slaven , Li Tiansen , Lukovic Dunja , Adlakha Yogita K. , Welby Emily , Swaroop Anand
Published: August 2019

Retinal organoids generated from human pluripotent stem cells exhibit considerable variability in temporal dynamics of differentiation. To assess the maturity of neural retina in vitro, we performed transcriptome analyses of developing organoids from human embryonic and induced pluripotent stem cell lines. We show that the developmental variability in organoids was reflected in gene expression profiles and could be evaluated by molecular staging with the human fetal and adult retinal transcriptome data. We also demonstrated that addition of 9-cis retinal, instead of widely-used all-trans retinoic acid, accelerated rod photoreceptor differentiation in organoid cultures, with higher rhodopsin expression and more mature mitochondrial morphology evident by day 120. Our studies thus provide an objective transcriptome-based modality for determining the differentiation state of retinal organoids, which should facilitate disease modeling and evaluation of therapies in vitro.

Summary Statement

Three-dimensional organoids derived from human pluripotent stem cells have been extensively applied for investigating organogenesis, modeling diseases and development of therapies. However, substantial variations within organoids pose challenges for comparison among different cultures and studies. We generated transcriptomes of multiple distinct retinal organoids and compared these to human fetal and adult retina gene profiles for molecular staging of differentiation state of the cultures. Our analysis revealed the advantage of using 9-cis retinal, instead of the widely-used all-trans retinoic acid, in facilitating rod photoreceptor differentiation. Thus, a transcriptome-based comparison can provide an objective method to uncover the maturity of organoid cultures across different lines and in various study platforms.
Detection of genomic alterations in breast cancer with circulating tumour DNA sequencing
Authors: Kleftogiannis Dimitrios , Ho Danliang , Liew Jun Xian , Poon Polly , Gan Anna , Ng Raymond Chee-Hui , Tan Benita Kiat-Tee , Tay Kiang Hiong , Lim Swee-Ho , Tan Gek San , Shih Chih Chuan , Lim Tony , Lee Ann Siew-Gek , Tan Iain , Yap Yoon-Sim , Ng Sarah
Published: August 2019

Analysis of circulating cell-free DNA (cfDNA) data has opened new opportunities for characterizing tumour mutational landscapes with many applications in genomic-driven oncology. We developed a customized targeted cfDNA sequencing approach for breast cancer (BC) using unique molecular identifiers (UMIs) for error correction. Our assay, spanning a 284.5 kb target region, is combined with freely-available bioinformatics pipelines that provide ultra-sensitive detection of single nucleotide variants (SNVs), and reliable identification of copy number variations (CNVs) directly from plasma DNA. In a cohort of 35 BC patients, our approach detected actionable driver and clonal SNVs at low (~0.5%) frequency levels in cfDNA that were concordant (83.3%) with sequencing of primary and/or metastatic solid tumour sites. We also detectedERRB2gene CNVs used for HER2 subtype classification with 80% precision compared to immunohistochemistry. Further, we evaluated fragmentation profiles of cfDNA in BC and observed distinct differences compared to data from healthy individuals. Our results show that the developed assay addresses the majority of tumour associated aberrations directly from plasma DNA, and thus may be used to elucidate genomic alterations in liquid biopsy studies.
Cerebral Dopamine Neurotrophic Factor regulates multiple neuronal subtypes and behavior
Authors: Chen Yu-Chia , Baronio Diego , Semenova Svetlana , Abdurakhmanova Shamsiiat , Panula Pertti
Published: August 2019

Cerebral Dopamine Neurotrophic Factor (CDNF) protects dopaminergic neurons against toxic damage in the rodent brain, and is in clinical trials to treat Parkinson’s disease patients. Yet the underlying mechanism is poorly understood. To examine its mode of action and significance, we examined the development of neurotransmitter systems from larval to adult mutant zebrafish lacking cdnf. Although a lack of cdnf did not affect overall brain dopamine levels, dopaminergic neuronal clusters showed significant abnormalities. The number of histamine neurons that surround the dopaminergic neurons was significantly reduced. Expression of tyrosine hydroxylase 2 in the brain was elevated in cdnf mutants throughout their lifespan. There were abnormally few GABA neurons in the hypothalamus in the mutant larvae, and expression of glutamate decarboxylase was reduced throughout the brain. cdnf mutant adults showed a range of behavioral phenotypes, including increased sensitivity to pentylenetetrazole-induced seizures. Shoaling behavior of mutant adults was abnormal, and they did not display social attraction to conspecifics. CDNF plays a profound role in shaping the neurotransmitter circuit structure, seizure susceptibility, and complex behaviors in zebrafish. These findings are informative for dissecting the diverse functions of this poorly understood factor in human conditions related to Parkinson’s disease and complex behaviors