bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Search Fixation Strategies in a 3D Image Set: An Eye-Tracking Study
Authors: Kyritsis Markos , Gulliver Stephen R , Feredoes Eva
Published: July 2020

In this study, we explore whether the inclusion of monocular depth within a pseudo-3D picture gallery negatively affects visual search strategy and performance. Experimental design facilitated control of (i) the number of visible depth planes and (ii) the presence of semantic sorting. Our results show that increasing the number of visual depth planes facilitates efficiency in search, which in turn results in a decreased response time to target selection and a reduction in participant average pupil dilation—used for measuring cognitive load. Furthermore, results identified that search strategy is based on sorting, which implies that an appropriate management of semantic associations can increase search efficiency by decreasing the number of potential targets.
A case study of the 1115 waiver using population health informatics to address disparities
Authors: Sitapati Amy M , Berkovich Barbara , Arellano April Moreno , Scioscia Angela , Friedman Lawrence S , Millen Marlene , Maysent Patricia , Tai-Seale Ming , Longhurst Christopher A
Published: June 2020

As participants in the California Medicaid 1115 waiver, the University of California San Diego Health (UCSDH) used population health informatics tools to address health disparities. This case study describes a modern application of health informatics to improve data capture, describe health disparities through demographic stratification, and drive reliable care through electronic medical record-based registries. We provide a details in our successful approach using (1) standardized collection of race, ethnicity, language, sexual orientation, and gender identity data, (2) stratification of 8 quality measures by demographic profile, and (3) improved quality performance through registries for wellness, social determinants of health, and chronic disease. A strong population health platform paired with executive support, physician leadership, education and training, and workflow redesign can improve the representation of diversity and drive reliable processes for care delivery that improve health equity.
Performance Characteristics of a Lumen-Apposing Metal Stent for Pancreatic Fluid Collections: A Prospective Cohort Study
Authors: Dhillon Amit , Li Suqing , Sandha Simrat , D’Souza Pernilla , Sandha Gurpal
Published: July 2020

Background

Endoscopic ultrasound-guided transmural drainage is the preferred management of pancreatic fluid collections (PFCs). Optimizing drainage is important and there remains debate as to the choice of stent. A recent trend towards the use of lumen-apposing metal stents (LAMS) has emerged.

Aim

To evaluate the performance characteristics of a LAMS based on a prospective protocol (CT scan 1 week after placement to assess for resolution and need for necrosectomy followed by stent removal within 3 weeks).

Methods

This is a descriptive prospective cohort study performed at a single centre. The primary outcome was clinical success. Secondary outcomes were technical success, procedure time, total number of endoscopic procedures with or without necrosectomy, stent indwell time, stent functionality and adverse events.

Results

Thirty-seven patients (21 males, mean age 46.5 years) underwent placement of LAMS for 41 PFCs (median size 12 cm). There were 18 pseudocysts and 23 walled-off necrosis. Clinical success was seen in 33 of 41 (80%) PFCs. Of the remaining eight patients, six underwent surgery and two patients died from underlying malignant disease (although their PFC had completely resolved). Technical success and stent functionality were 100%. The median procedure time was 14 min (interquartile range 11 min to 20 min). Of the 23 walled-off necrosis, 9 (39%) required necrosectomy. The median stent indwell time was 19 days (interquartile range 14 to 22 days). There were no serious adverse events.

Conclusions

Our protocol demonstrates excellent performance characteristics of LAMS. Their clinical efficacy and favourable safety profile suggest that they may be the preferred modality for endoscopic ultrasound-guided management of PFCs.
Numbers of Axons in Spared Neural Tissue Bridges But Not Their Widths or Areas Correlate With Functional Recovery in Spinal Cord-Injured Rats
Authors: Rink Svenja , Pavlov Stoyan , Wöhler Aliona , Bendella Habib , Manthou Marilena , Papamitsou Theodora , Dunlop Sarah A , Angelov Doychin N
Published: June 2020

The relationships between various parameters of tissue damage and subsequent functional recovery after spinal cord injury (SCI) are not well understood. Patients may regain micturition control and walking despite large postinjury medullar cavities. The objective of this study was to establish possible correlations between morphological findings and degree of functional recovery after spinal cord compression at vertebra Th8 in rats. Recovery of motor (Basso, Beattie, Bresnahan, foot-stepping angle, rump-height index, and ladder climbing), sensory (withdrawal latency), and bladder functions was analyzed at 1, 3, 6, 9, and 12 weeks post-SCI. Following perfusion fixation, spinal cord tissue encompassing the injury site was cut in longitudinal frontal sections. Lesion lengths, lesion volumes, and areas of perilesional neural tissue bridges were determined after staining with cresyl violet. The numbers of axons in these bridges were quantified after staining for class III β-tubulin. We found that it was not the area of the spared tissue bridges, which is routinely determined by magnetic resonance imaging (MRI), but the numbers of axons in them that correlated with functional recovery after SCI (Spearman’s ρ > 0.8; p < 0.001). We conclude that prognostic statements based only on MRI measurements should be considered with caution.
Exploring DNA Methylation for Prognosis and Analyzing the Tumor Microenvironment in Pleomorphic Xanthoastrocytoma
Authors: Tang Karen , Kurland David , Vasudevaraja Varshini , Serrano Jonathan , Delorenzo Michael , Radmanesh Alireza , Thomas Cheddhi , Spino Marissa , Gardner Sharon , Allen Jeffrey C , Nicolaides Theodore , Osorio Diana S , Finlay Jonathan L , Boué Daniel R , Snuderl Matija
Published: June 2020

Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that affects children and young adults. Molecular prognostic markers of PXAs remain poorly established. Similar to gangliogliomas, PXAs show prominent immune cell infiltrate, but its composition also remains unknown. In this study, we correlated DNA methylation and BRAF status with clinical outcome and explored the tumor microenvironment. We performed DNA methylation in 21 tumor samples from 18 subjects with a histological diagnosis of PXA. MethylCIBERSORT was used to deconvolute the PXA microenvironment by analyzing the associated immune cell-types. Median age at diagnosis was 16 years (range 7–32). At median follow-up of 30 months, 3-year and 5-year overall survival was 73% and 71%, respectively. Overall survival ranged from 1 to 139 months. Eleven out of 18 subjects (61%) showed disease progression. Progression-free survival ranged from 1 to 89 months. Trisomy 7 and CDKN2A/B (p16) homozygous deletion did not show any association with overall survival (p = 0.67 and p = 0.74, respectively). Decreased overall survival was observed for subjects with tumors lacking the BRAF V600E mutation (p = 0.02). PXAs had significantly increased CD8 T-cell epigenetic signatures compared with previously profiled gangliogliomas (p = 0.0019). The characterization of immune cell-types in PXAs may have implications for future development of immunotherapy.
8-Hydroxyquinoline 1,2,3-triazole derivatives with promising and selective antifungal activity
Authors: da Silva Nailí Moreira , Gentz Caroline de Bem , Reginatto Paula , Fernandes Thaís Helena Maciel , Kaminski Taís Fernanda Andrzejewski , Lopes William , Quatrin Priscilla M , Vainstein Marilene Henning , Abegg Maxwel Adriano , Lopes Marcela Silva , Fuentefria Alexandre Meneghello , de Andrade Saulo Fernandes
Published: July 2020

Fungal infections that affect humans and plants have increased significantly in recent decades. However, these pathogens are still neglected when compared to other infectious agents. Due to the high prevalence of these infections, the need for new molecules with antifungal potential is recognized, as pathogenic species are developing resistance to the main drugs available. This work reports the design and synthesis of 1,2,3-triazole derivatives of 8-hydroxyquinoline, as well as the determination of their activities against a panel of fungal species: Candida spp., Trichosporon asahii, Magnusiomyces capitatus, Microsporum spp., Trichophyton spp. and Fusarium spp. The triazoles 5-(4-phenyl-1H-1,2,3-triazol-1-yl)quinolin-8-ol (12) and 5-(4-(cyclohex-1-en-1-yl)-1H-1,2,3-triazol-1-yl)quinolin-8-ol (16) were more promising, presenting minimum inhibitory concentration (MIC) values between 1–16 µg/ml for yeast and 2–4 µg/ml for dermatophytes. However, no relevant anti-Fusarium spp. activity was observed. In the time-kill assays with Microsporum canis, 12 and 16 presented time-dependent fungicide profile at 96 h and 120 h in all evaluated concentrations, respectively. For Candida guilliermondii, 12 was fungicidal at all concentrations at 6 h and 16 exhibited a predominantly fungistatic profile. Both 12 and 16 presented low leukocyte toxicity at 4 µg/ml and the cell viability was close to 100% after the treatment with 12 at all tested concentrations. The sorbitol assay combined with SEM suggest that damages on the fungal cell wall could be involved in the activity of these derivatives. Given the good results obtained with this series, scaffold 4-(cycloalkenyl or phenyl)-5-triazol-8-hydroxyquinoline appears to be a potential pharmacophore for exploration in the development of new antifungal agents.
A redshift-dependent IRX–β dust attenuation relation for TNG50 galaxies
Authors: Schulz Sebastian , Popping Gergö , Pillepich Annalisa , Nelson Dylan , Vogelsberger Mark , Marinacci Federico , Hernquist Lars
Published: July 2020

We study the relation between the UV slope, β, and the ratio between the infrared- and UV luminosities (IRX) of galaxies from TNG50, the latest installment of the IllustrisTNG galaxy formation simulations. We select 7280 star-forming main-sequence (SFMS) galaxies with stellar mass ≥109 M⊙ at redshifts 0 ≤ z ≤ 4 and perform radiative transfer with skirt to model effects of interstellar medium dust on the emitted stellar light. Assuming a Milky Way dust type and a dust-to-metal ratio of 0.3, we find that TNG50 SFMS galaxies generally agree with observationally derived IRX–β relations at z ≲ 1. However, we find a redshift-dependent systematic offset with respect to empirically derived local relations, with the TNG50 IRX–β relation shifting towards lower β and steepening at higher redshifts. This is partially driven by variations in the dust-uncorrected UV slope of galaxies, due to different star formation histories of galaxies selected at different cosmic epochs; we suggest the remainder of the effect is caused by differences in the effective dust attenuation curves of galaxies as a function of redshift. We find a typical galaxy-to-galaxy variation of 0.3 dex in infrared excess (IRX) at fixed β, correlated with intrinsic galaxy properties: galaxies with higher star formation rates, star formation efficiencies, gas metallicities and stellar masses exhibit larger IRX values. We demonstrate a degeneracy between stellar age, dust geometry, and dust composition: z = 4 galaxies with a Small Magellanic Cloud dust type follow the same IRX–β relation as low-redshift galaxies with MW dust. We provide a redshift-dependent fitting function for the IRX–β relation for MW dust based on our models.
On the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCF
Authors: Meseguer Alberto , Årman Filip , Fornes Oriol , Molina-Fernández Ruben , Bonet Jaume , Fernandez-Fuentes Narcis , Oliva Baldo
Published: July 2020

Cis2-His2 zinc finger (C2H2-ZF) proteins are the largest family of transcription factors in human and higher metazoans. To date, the DNA-binding preferences of many members of this family remain unknown. We have developed a computational method to predict their DNA-binding preferences. We have computed theoretical position weight matrices (PWMs) of proteins composed by C2H2-ZF domains, with the only requirement of an input structure. We have predicted more than two-third of a single zinc-finger domain binding site for about 70% variants of Zif268, a classical member of this family. We have successfully matched between 60 and 90% of the binding-site motif of examples of proteins composed by three C2H2-ZF domains in JASPAR, a standard database of PWMs. The tests are used as a proof of the capacity to scan a DNA fragment and find the potential binding sites of transcription-factors formed by C2H2-ZF domains. As an example, we have tested the approach to predict the DNA-binding preferences of the human chromatin binding factor CTCF. We offer a server to model the structure of a zinc-finger protein and predict its PWM.
Seasonal variation in the incidence of primary CNS lymphoma
Authors: Gibson Alec W , Bonm Alipi V , Barber Jason , Graber Jerome J
Published: July 2020

Background

Primary CNS lymphoma is a rare and aggressive cancer that can develop in immunocompetent individuals, but little is known about risk factors and causes of disease. Previous studies have demonstrated seasonal patterns for lymphomas and brain tumors. This study examined the seasonal incidence pattern for primary CNSlymphoma.

Methods

A retrospective review was performed for patients diagnosed with primary CNS lymphoma from 2000 through 2018 at our tertiary referral center. A total of 156 patients were categorized based on month of symptom onset, month of diagnosis, and month of recurrence if they experienced a relapse of their disease. The distributions were then analyzed for seasonal patterns.

Results

There was a significant, bimodal seasonal incidence pattern based on month of symptom onset (P < .001), with peaks in July (n = 19) and December (n = 23) and troughs in March (n = 4) and September (n = 5). There were no significant differences in patients’ sex, age at presentation, length of follow-up, and progression-free survival across months. There were no seasonal patterns based on month of diagnosis (P = .450) or month of disease recurrence (P = .572).

Conclusion

The incidence of primary CNS lymphoma has bimodal peaks in midsummer and early winter, which could provide insight into causative agents and mechanisms of disease.
Effect of fructose instead of glucose or sucrose on cardiometabolic markers: a systematic review and meta-analysis of isoenergetic intervention trials
Authors: Fattore Elena , Botta Francesca , Bosetti Cristina
Published: June 2020

Context

Free, or added, sugars are considered important determinants in the pandemics of obesity and associated chronic diseases, and fructose has emerged as the sugar of main concern.

Objective

The aim of this review was to assess the evidence of the effects of isoenergetic replacement of fructose or high-fructose corn syrup (HFCS) for glucose or sucrose on cardiometabolic markers in controlled dietary intervention trials.

Data Sources

The electronic databases PubMed/MEDLINE, the Cochrane Library, and Embase were searched from 1980 to May 5, 2020.

Study Selection

Studies were eligible if they measured at least one of the following outcomes: total cholesterol, low- and high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, systolic blood pressure, diastolic blood pressure, fasting glucose, and body weight.

Data Extraction

For each outcome, the mean values and the corresponding measure of dispersion were extracted after the intervention or control diet.

Data Analysis

Fixed-effects and random-effects models were used to pool study-specific estimates. Between-study heterogeneity was assessed by the χ2 test and the I2 statistic and publication bias by the Egger test and funnel plots.

Results

Twenty-five studies involving 1744 volunteers were identified. No significant effects were found when fructose or HFCS was substituted for glucose, except for a slight decrease in diastolic blood pressure when fructose was substituted for glucose. Similarly, no effects were found when fructose or HFCS was substituted for sucrose, except for a small increase, of uncertain clinical significance, of apolipoprotein B when HFCS was substituted for sucrose.

Conclusions

Isoenergetic substitution of fructose or HFCS for glucose or sucrose has no significant effect on most of the cardiometabolic markers investigated; however, some results were affected by residual between-study heterogeneity and studies with high or unclear risk of bias.

Systematic Review Registration

PROSPERO registration number CRD42016042930.
History of nutrition policy in Japan
Authors: Shobayashi Tokuaki
Published: July 2020

Why has Japan become the longest-lived country in the world? The longevity is often attributed to Japan’s economic growth, but Japan experienced an extended life expectancy prior to achieving such economic growth. During and after the Second World War when the General Headquarters of the Supreme Commander for the Allied Powers was occupying Japan, the welfare administration system was drastically reformed, resulting in dramatic improvements in the hygiene status, which led to an increase in the average life expectancy in Japan. Here, this background is reviewed, along with an explanation of how Japan has become the world's longest-lived country.
Cryptic Patterns of Speciation in Cryptic Primates: Microendemic Mouse Lemurs and the Multispecies Coalescent
Authors: Poelstra Jelmer W , Salmona Jordi , Tiley George P , Schüßler Dominik , Blanco Marina B , Andriambeloson Jean B , Bouchez Olivier , Campbell C Ryan , Etter Paul D , Hohenlohe Paul A , Hunnicutt Kelsie E , Iribar Amaia , Johnson Eric A , Kappeler Peter M , Larsen Peter A , Manzi Sophie , Ralison JosÉ M , Randrianambinina Blanchard , Rasoloarison Rodin M , Rasolofoson David W , Stahlke Amanda R , Weisrock David W , Williams Rachel C , Chikhi LounÈs , Louis Edward E , Radespiel Ute , Yoder Anne D
Published: July 2020

Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported—a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. [Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.]
Feed and production efficiency of young crossbred beef cattle stratified on a terminal total merit index1
Authors: Kelly David N , Conroy Stephen B , Murphy Craig P , Sleator Roy D , Berry Donagh P
Published: July 2020

Few studies have attempted to quantify the association between a terminal total merit index with phenotypic feed and production efficiency in beef cattle, particularly when feed efficiency is itself explicitly absent as a goal trait in the index. The objective of the present study was to quantify the differences in phenotypic performance for feed intake, feed efficiency, and carcass traits of crossbred bulls, steers, and heifers differing in a terminal total merit index. A validation population of 614 bulls, steers, and heifers that were evaluated for feed intake and efficiency in the same feedlot and subsequently slaughtered at the end of their test period was constructed. The Irish national genetic evaluations for a terminal index of calving performance, docility, feed intake, and carcass traits were undertaken with the phenotypic records of animals present in the validation population masked. The validation population animals were subsequently stratified into four groups, within sex, according to their terminal index value. Mixed models were used to quantify the association between terminal genetic merit and phenotypic performance; whether the associations differed by sex were also investigated. The regression coefficient of phenotypic feed intake, carcass weight, carcass conformation, or carcass fat on its respective estimated breeding values was 0.86 kg dry matter 0.91 kg, 1.01 units, and 1.29 units, respectively, which are close to the expectation of one. On average, cattle in the very high terminal index stratum had a 0.63 kg DM/d lower feed intake, a 25.05 kg heavier carcass, a 1.82 unit better carcass conformation (scale 1 to 15), and a 1.24 unit less carcass fat score (scale 1 to 15), relative to cattle in the very low terminal index stratum. Cattle of superior total genetic merit were also more feed efficient (i.e., had a lower energy conversion ratio, lower residual feed intake, and greater residual gain), had a greater proportion of their live-weight as carcass weight (i.e., better dressing percentage) and were slaughtered at a younger age relative to their inferior total genetic merit counterparts. This study provides validation of an all-encompassing total merit index and demonstrates the benefits of selection on a total merit index for feed and production efficiency, which should impart confidence among stakeholders in the contribution of genetic selection to simultaneous improvements in individual animal performance and efficiency.
Arsenic Directs Stem Cell Fate by Imparting Notch Signaling Into the Extracellular Matrix Niche
Authors: Anguiano Teresa , Sahu Amrita , Qian Baoli , Tang Wan-Yee , Ambrosio Fabrisia , Barchowsky Aaron
Published: July 2020

Compromise of skeletal muscle metabolism and composition may underlie the etiology of cardiovascular and metabolic disease risk from environmental arsenic exposures. We reported that arsenic impairs muscle maintenance and regeneration by inducing maladaptive mitochondrial phenotypes in muscle stem cells (MuSC), connective tissue fibroblasts (CTF), and myofibers. We also found that arsenic imparts a dysfunctional memory in the extracellular matrix (ECM) that disrupts the MuSC niche and is sufficient to favor the expansion and differentiation of fibrogenic MuSC subpopulations. To investigate the signaling mechanisms involved in imparting a dysfunctional ECM, we isolated skeletal muscle tissue and CTF from mice exposed to 0 or 100 μg/l arsenic in their drinking water for 5 weeks. ECM elaborated by arsenic-exposed CTF decreased myogenesis and increased fibrogenic/adipogenic MuSC subpopulations and differentiation. However, treating arsenic-exposed mice with SS-31, a mitochondrially targeted peptide that repairs the respiratory chain, reversed the arsenic-promoted CTF phenotype to one that elaborated an ECM supporting normal myogenic differentiation. SS-31 treatment also reversed arsenic-induced Notch1 expression, resulting in an improved muscle regeneration after injury. We found that persistent arsenic-induced CTF Notch1 expression caused the elaboration of dysfunctional ECM with increased expression of the Notch ligand DLL4. This DLL4 in the ECM was responsible for misdirecting MuSC myogenic differentiation. These data indicate that arsenic impairs muscle maintenance and regenerative capacity by targeting CTF mitochondria and mitochondrially directed expression of dysfunctional regulators in the stem cell niche. Therapies that restore muscle cell mitochondria may effectively treat arsenic-induced skeletal muscle dysfunction and compositional decline.
Far Lateral/Extraforaminal Approaches for Microdiscectomy and Foraminal Decompression in the Lumbar Spine
Authors: Boody Barrett S. , Sasso Rick C. , Smucker Joseph D.
Published: July 2020

Far lateral approaches to the lumbar spine are uncommon procedures but are essential techniques for spine surgeons to understand and master for the treatment of extraforaminal disk herniations and foraminal stenosis. We present our preferred approaches for open and minimally invasive techniques to perform extraforaminal decompressions and/or discectomies in the lumbar spine.
A Quality Improvement Project to Standardize Surfactant Delivery in the Era of Noninvasive Ventilation
Authors: Kim Jeong Eun , Brewer Mariana , Spinazzola Regina , Wallace Elfriede , Casatelli Joanne , Beachy Joanna , Weinberger Barry , Perveen Shahana
Published: July 2020

Introduction:

Continuous positive airway pressure (CPAP) and surfactant both improve outcomes for premature infants with respiratory distress syndrome. However, prolonged trials of CPAP, as well as observation periods after intubation, may delay the administration of surfactant. Late surfactant treatment likely increases the incidence of bronchopulmonary dysplasia, which leads to significant morbidity and healthcare utilization.

Methods:

We aimed to decrease time from meeting standard criteria (start of a continuous run of FiO2 > 40% or PaCO2 > 65 for >90 min) to intubation, and from intubation to surfactant administration, for infants <1,500 g or younger than 32 weeks gestation. Retrospective data collection from the electronic medical record assessed those process measures as the primary endpoints. Balancing measures were the adverse outcomes of asymmetric lung disease, the inappropriate position of the endotracheal tube, or pneumothorax on the first x-ray (within 24 h) after surfactant.

Results:

Mean time to intubation for infants 28–32 weeks gestation decreased from 321 to 81 minutes in response to a literature review for physicians and free-text orders for notification. Time to intubation for infants younger than 28 weeks gestation did not change. Administration of surfactant within 1 hour of intubation improved from 78% to 100% after a program for trainees and coordination with radiology. There were no adverse occurrences.

Conclusions:

Educational interventions and targeted process change can successfully implement standard criteria for intubation and surfactant administration for premature infants. Determination of an acceptable range of evidence-based practice is essential for the engagement of medical staff. Timely intubation and surfactant may decrease bronchopulmonary dysplasia.
Church attendance and alloparenting: an analysis of fertility, social support and child development among English mothers
Authors: Shaver John H. , Power Eleanor A. , Purzycki Benjamin G. , Watts Joseph , Sear Rebecca , Shenk Mary K. , Sosis Richard , Bulbulia Joseph A.
Published: June 2020

Many aspects of religious rituals suggest they provide adaptive benefits. Studies across societies consistently find that investments in ritual behaviour return high levels of cooperation. Another line of research finds that alloparental support to mothers increases maternal fertility and improves child outcomes. Although plausible, whether religious cooperation extends to alloparenting and/or affects child development remains unclear. Using 10 years of data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC), we test the predictions that church attendance is positively associated with social support and fertility (n= 8207 ton= 8209), and that social support is positively associated with fertility and child development (n= 1766 ton= 6561). Results show that: (i) relative to not attending, church attendance is positively related to a woman's social network support and aid from co-religionists, (ii) aid from co-religionists is associated with increased family size, while (iii) fertility declines with extra-religious social network support. Moreover, while extra-religious social network support decreased over time, co-religionist aid remained constant. These findings suggest that religious and secular networks differ in their longevity and have divergent influences on a woman's fertility. We find some suggestive evidence that support to mothers and aid from co-religionists is positively associated with a child's cognitive ability at later stages of development. Findings provide mixed support for the premise that ritual, such as church attendance, is part of a strategy that returns high levels of support, fertility and improved child outcomes. Identifying the diversity and scope of cooperative breeding strategies across global religions presents an intriguing new horizon in the evolutionary study of religious systems.

This article is part of the theme issue ‘Ritual renaissance: new insights into the most human of behaviours'.
Initial Feasibility and Clinical Implementation of Daily MR-guided Adaptive Head and Neck Cancer Radiotherapy on a 1.5T MR-Linac System: Prospective R-IDEAL 2a/2b Systematic Clinical Evaluation of Technical Innovation
Authors: McDonald Brigid A. , Vedam Sastry , Yang Jinzhong , Wang Jihong , Castillo Pamela , Lee Belinda , Sobremonte Angela , Ding Yao , Mohamed Abdallah S.R. , Balter Peter , Hughes Neil , Thorwarth Daniela , Nachbar Marcel , Philippens Marielle E.P. , Terhaard Chris H.J. , Zips Daniel , Böke Simon , Awan Musaddiq J. , Christodouleas John , Fuller Clifton D.
Published: July 2020

Introduction

This prospective study is the first report of daily adaptive radiotherapy (ART) for head & neck cancers (HNC) using a 1.5T MR-linac, with particular focus on safety & feasibility and dosimetric results of an on-line rigid registration-based adapt-to-position (ATP) workflow.

Methods

Ten HNC patients received daily ART on a 1.5T/7MV MR-linac, six using ATP only and four using ATP with one off-line adapt-to-shape re-plan. Setup variability with custom immobilization masks was assessed by calculating the average systematic error (M), standard deviation of the systematic error (∑), and standard deviation of the random error (σ) of the isocenter shifts. Quality assurance was performed with a cylindrical diode array using 3%/3mm γ criteria. Adaptive treatment plans were summed for each patient to compare delivered dose with planned dose from the reference plan. The impact of dosimetric variability between adaptive fractions on the summation plan doses was assessed by tracking the number of optimization constraint violations at each individual fraction.

Results

The random errors (mm) for the x, y, and z isocenter shifts, respectively, were M = − 0.3, 0.7, 0.1; ∑ = 3.3, 2.6, 1.4; and σ = 1.7, 2.9, 1.0. The median γ pass rate was 99.9% (range: 90.9%-100%). The differences between the reference and summation plan doses were within [-0.61%, 1.78%] for the CTV and [-11.74%, 8.11%] for organs at risk (OARs), though percent increases in OAR dose above 2% only occurred in three cases, each for a single OAR. All cases had at least two fractions with one or more constraint violations. However, in nearly all instances, constraints were still met in the summation plan despite multiple single-fraction violations.

Conclusion

Daily ART on a 1.5T MR-linac using an on-line ATP workflow is safe and clinically feasible for HNC and results in delivered doses consistent with planned doses.
Temporal placental genome wide expression profiles reflect three phases of utero-placental blood flow during early to mid human gestation
Authors: Breen James , McAninch Dale , Jankovic-Karasoulos Tanja , McCullough Dylan , Smith Melanie D , Bogias K Justinian , Wan Qianhui , Choudhry Awais , Hin Nhi , Pederson Stephen M , Bianco-Miotto Tina , Roberts Claire T
Published: June 2020

During early human placental development, extravillous cytotrophoblasts (EVT) invade the uterine vasculature to sequester a maternal blood supply. The impact of this on placental gene expression has not been established for normal pregnancy. Using RNA sequencing, we profiled placental chorionic villous tissues from 96 pregnancies at 6-23 weeks of gestation. We identified 1,048 genes that were differentially expressed between 6-10 weeks’ and 11-23 weeks’ of gestation. These are predominantly genes that are enriched in transcription factor signalling, inflammatory response and cell adhesion. Using a co-expression network and gene set enrichment analyses, we reveal three distinct phases of gene expression coincident with phases of maternal blood flow to the placenta that impact immune function and are likely driven by oxygen tension, potentially in a sex-specific manner. These data represent a comprehensive transcriptional profile of early placental development and point to significant environmental, genetic and regulatory triggers that drive gene expression.
VGLUT3-p.A211V variant fuses stereocilia bundle and elongates synaptic ribbons in the human deafness DFNA25
Authors: Joshi Yuvraj , Miot Stéphanie , Guillet Marie , Sendin Gaston , Bourien Jérôme , Wang Jing , Pujol Rémy , El Mestikawy Salah , Puel Jean-Luc , Nouvian Régis
Published: June 2020

DFNA25 is an autosomal-dominant and progressive form of human deafness caused by mutations in theSLC17A8gene, which encodes the vesicular glutamate transporter type 3 (VGLUT3). To resolve the mechanisms underlying DFNA25, we studied the phenotype of the mouse harboring the p.A221V mutation in human (corresponding to p.A224V in mouse). Using auditory brainstem response and distortion products of otoacoustic emissions, we showed that VGLUT3A224V/A224Vmouse replicates the DFNA25 progressive hearing loss with intact cochlear amplification. Scanning electron microscopy examinations demonstrated fused stereocilia bundle of the inner hair cells (IHCs) as the primary cause for DFNA25. In addition, the IHC ribbon synapses undergo structural and functional modifications at later stages. Using super-resolution microscopy, we observed oversized synaptic ribbons associated with an increase in the rate of the sustained releasable pool of exocytosis. These results indicate that the primary defect in DFNA25 stems from a failure in the mechano-transduction followed by a change in synaptic transfer. The VGLUT3A224V/A224Vmouse model opens the way to a deeper understanding and to a potential treatment of DFNA25.
Inclusion of a 3D-printed Hyperelastic bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold
Authors: Dewey Marley J. , Nosatov Andrey V. , Subedi Kiran , Shah Ramille , Jakus Adam , Harley Brendan A.C.
Published: June 2020

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regenerationin vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized collagen scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into collagen scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential.
Axonal TAU sorting requires the C-terminus of TAU but is independent of ANKG and TRIM46 enrichment at the AIS
Authors: Bell M. , Bachmann S. , Klimek J. , Langerscheidt F. , Zempel H.
Published: June 2020

Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer’s disease and related tauopathies. Cultured rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming and/or require the sacrification of animals. In this study, we evaluated four differentiation procedures to generate mature neuron cultures from human SH-SY5Y neuroblastoma cells, in comparison to mouse primary neurons, and tested their TAU sorting capacity. We show that SH-SY5Y-derived neurons, differentiated with sequential RA/BDNF treatment, are suitable for investigating axonal TAU sorting. These human neurons show pronounced neuronal polarity, axodendritic outgrowth, expression of the neuronal maturation markers TAU and MAP2, and, importantly, efficient axonal sorting of endogenous and transfected human wild type TAU, similar to primary neurons. We demonstrate that axonal TAU enrichment requires the presence of the C-terminal half, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Moreover, SH-SY5Y-derived neurons do not show formation of a classical axon initial segment (AIS), indicated by the lack of Ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results suggest i) that SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting, which is readily accessible at low cost and without animal need, and that ii) the mechanisms of axonal TAU targeting require the TAU C-terminal half but are independent of ANKG or TRIM46 enrichment at the proximal axon.
The mitochondrial genomes of 11 aquatic macroinvertebrate species from Cyprus
Authors: Macher Jan-Niklas , Drakou Katerina , Papatheodoulou Athina , van der Hoorn Berry , Vasquez Marlen
Published: June 2020

Aquatic macroinvertebrates are often identified based on morphology, but molecular approaches like DNA barcoding, metabarcoding and metagenomics are increasingly used for species identification. These approaches require the availability of DNA references deposited in public databases. Here we report the mitochondrial genomes of 11 aquatic macroinvertebrates species from Cyprus, a European Union island country in the Mediterranean. Only three of the molecularly identified species could be assigned to a species name, highlighting the need for taxonomic work that leads to the formal description and naming of species, and the need for further genetic work to fill the current gaps in reference databases containing aquatic macroinvertebrates.

Graphical Abstract
MAP Kinase OsMEK2 and OsMPK1 Signaling for Ferroptotic Cell Death in Rice-Magnaporthe oryzaeInteractions
Authors: Dangol Sarmina , Singh Raksha , Nguyen Khoa Nam , Chen Yafei , Wang Juan , Lee Hyeon Gu , Hwang Byung Kook , Jwa Nam-Soo
Published: June 2020

Mitogen-activated protein kinase (MAPK) signaling is required for plant cell death responses to invading microbial pathogens. Ferric ions and reactive oxygen species (ROS) accumulate in rice (Oryza sativa) tissues undergoing cell death duringMagnaporthe oryzaeinfection. Here, we report that rice MAP kinase (OsMEK2 and OsMPK1) signaling cascades are involved in iron- and ROS-dependent ferroptotic cell death responses of rice toM. oryzaeinfection. OsMEK2 interacted with OsMPK1 in the cytoplasm, and OsMPK1 moved from the cytoplasm into the nucleus to bind to the OsWRKY90 transcription factor.OsMEK2expression may trigger OsMPK1-OsWRKY90 signaling pathways in the nucleus. AvirulentM. oryzaeinfection inΔOsmek2mutant rice did not trigger iron and ROS accumulation and lipid peroxidation, and also downregulatedOsMPK1,OsWRKY90,OsRbohB, andOsPR-1bexpression. However,OsMEK2overexpression induced ROS-and iron-dependent cell death in rice duringM. oryzaeinfection. The downstream MAP kinase (OsMPK1) overexpression induced ROS- and iron-dependent ferroptotic cell death in the compatible rice-M.oryzaeinteraction. These data suggest that the OsMEK2-OsMPK1-OsWRKY90 signaling cascade is involved in the ferroptotic cell death in rice. The small-molecule inducer erastin triggered iron- and lipid ROS-dependent, butOsMEK2-independent, ferroptotic cell death inΔOsmek2mutant plants duringM. oryzaeinfection. Disease-related cell death was lipid ROS-dependent and iron-independent in theΔOsmek2mutant plants. These combined results suggest thatOsMEK2andOsMPK1expression positively regulates iron- and ROS-dependent ferroptotic cell death via OsMEK2-OsMPK1-OsWRKY90signaling pathways, and blast disease (susceptibility)-related cell death was ROS-dependent but iron-independent in rice-M. oryzaeinteractions.
Novel microRNA multivariate biomarkers of response to immunotherapy against HPV E6 oncogene
Authors: Fleeman Rebecca M. , Deiter Gina , Lambert Kristen , Proctor Elizabeth A. , Phaëton Rébécca
Published: June 2020

Cervical cancer is caused by the persistent infection high-risk types of human papillomavirus (HPV) in over 99.9% of cases. To favor malignant transformation, HPV E6 and E7 oncogenes disrupt both p53 and retinoblastoma (Rb) respectively and control microRNA (miR) networks. We have previously demonstrated the therapeutic potential of anti-HPV E6 monoclonal antibodies (mAbs) in experimental models of human cervical cancer; yet the underlying mechanism remains unclear. Here, we sought to determine if anti-HPV E6 mAbs modulate the miR signatures of HPV E6 oncogenes. To this end, we performed qRT-PCR to measure the expression of thirty-four miRs and found that univariate analysis is not able to identify novel interactions characteristic of complex biological systems. Thus, we utilized partial least squares discriminant analysis (PLSDA) to identify signatures of co-varying miRs specific to mAb treatment. These miR signatures predictively discriminate between anti-HPV E6 mAb response and control mAb treatment, which may provide mechanistic insight into the action of anti-HPV E6 mAbs.
RecombinantHelicobacter pyloriCagA protein induces endoplasmic reticulum stress and autophagy in human cells
Authors: Nami Babak , Azzawri Ali , Ucar Vasfiye B , Acar Hasan
Published: June 2020

Helicobacter pylori(Hp) CagA protein has a key role in the development of gastric cancer by the intruding in many intracellular processes of host human cell. Endoplasmic reticulum (ER) stress is an essential process for cellular homeostasis that modulates survival and death and is linked to several complex diseases including cancer. CagA protein is found in the serum ofHp-positive individuals and also in the supernatant ofHpculture. Limited studies report that recombinant CagA can alter gene expression and signaling pathways and induce the death of human cells. In this study, we investigated the effect of exogenous recombinant CagA protein treatment on ER stress and autophagy of human cell. AGS, MKN45, and HEK293 cells were treated with 1 µg/ml of recombinant CagA protein and then ER stress was studied by quantitative-PCR of spliced XBP-1 mRNA, immunofluorescence staining of ATF6 protein nuclear localization and real-time quantitative-PCR and/or western blot expression of GRP78, GRP94, ATF4 and CHOP genes. Autophagy was studied by western blot assessment of the conversion of LC3-I to LC3-II and LC3 aggregation. Cell proliferation and death were investigated by MTT assay and trypan blue staining respectively. As result, treatment with recombinant CagA enhanced XBP-1mRNA splicing, nuclear localization of ATF6, and the expression of ER stress signaling target genes in the cells. Recombinant CagA also induced LC3 protein conversion and aggregation in the cells. Reduced cell proliferation and increased cell death were determined in the cells treated with recombinant CagA. These results show that exogenous recombinant CagA protein causes cell death by inducing ER stress and autophagy in human cells. We conclude that CagA protein exogenously localizes in/on human cells and induces ER stress via disturbing protein machinery leading the human cell to death, however, the mechanism of CagA-host cell interaction is to be investigated.
Dissipation During the Gating Cycle of the Bacterial Mechanosensitive Ion Channel Approaches the Landauer’s Limit
Authors: Çetiner Uǧur , Raz Oren , Sukharev Sergei
Published: June 2020

The Landauer’s principle sets a thermodynamic bound ofkBTln 2 on the energetic cost of erasing each bit of information. It holds for any memory device, regardless of its physical implementation. It was recently shown that carefully built artificial devices can saturate this bound. In contrast, biological computation-like processes, e.g., DNA replication, transcription and translation use an order of magnitude more than their Landauer’s minimum. Here we show that saturating the Landauer bound is nevertheless possible with biological devices. This is done using a mechanosensitive channel of small conductance (MscS) fromE. colias a memory bit. MscS is a fast-acting osmolyte release valve adjusting turgor pressure inside the cell. Our patch-clamp experiments and data analysis demonstrate that under a slow switching regime, the heat dissipation in the course of tension-driven gating transitions in MscS closely approaches its Landauer’s limit. We discuss the biological implications of this physical trait.