bluuebunny/crossref_metadata_2025 huggingface dataset:
Training in robotic surgery, replicating the airline industry. How far have we come?
Authors: Collins Justin William , Wisz Pawel
Published: October 2019

Introduction

As the role of robot-assisted surgery continues to expand, development of standardised and validated training programmes is becoming increasingly important. We aim to compare current robotic training curricula with training in aviation, to evaluate current similarities and to provide insight into how healthcare can further learn from replicating initiatives in aviation training.

Methods

A systematic literature review of the current evidence was conducted online and relevant publications and information were identified. Evaluation and comparison between training in robotic surgery and the aviation industry was performed.

Results

There are significant similarities between modern robotic training curricula and pilot training. Both undergo basic training before proceeding to advanced training. Aviation training methods include classroom instruction, e-learning and practical training, in both the aircraft and flight simulation training devices. Both surgeon and pilot training include technical and procedural instruction as well as training in non-technical skills such as crisis management, decision making, leadership and communication. However, there is more regulation in aviation, with international standards for training curricula, simulation devices and instructors/trainers that are legally binding. Continuous learning with re-qualification with benchmarked high stakes tests are also mandatory throughout a pilot’s and instructor’s career.

Conclusion

Robotic surgeons and pilots roles have many fundamental similarities. Both work with expensive and complex technology requiring high levels of skills, within working environments with high physiological and psychological stress levels. Whilst many initiatives in aviation training have already been replicated in surgical training there remain considerable differences in regulation. Adopting established and proven aviation methods of assessment and regulation could help robotic surgical training become more efficient, more effective and ultimately safer.
Multilevel allometric modelling of maximal stroke volume and peak oxygen uptake in 11–13-year-olds
Authors: Armstrong Neil , Welsman Jo
Published: October 2019

Purpose

To investigate (1) whether maximal stroke volume (SVmax) occurs at submaximal exercise intensities, (2) sex differences in SVmax once fat-free mass (FFM) has been controlled for, and, (3) the contribution of concurrent changes in FFM and SVmax to the sex-specific development of peak oxygen uptake $$ \left( {{\dot{\text{V}}\text{O}}_{2} } \right) $$V˙O2.

Methods

The peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2 s of 61 (34 boys) 11–12-year-olds were determined and their SV determined during treadmill running at 2.28 and 2.50 m s−1 using carbon dioxide rebreathing. The SVmax and peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2 of 51 (32 boys) students who volunteered to be tested treadmill running at 2.50 m s−1 on three annual occasions were investigated using multilevel allometric modelling. The models were founded on 111 (71 from boys) determinations of SVmax, FFM, and peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2.

Results

Progressive increases in treadmill running speed resulted in significant (p < 0.01) increases in $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2, but SV levelled-off with nonsignificant (p > 0.05) changes within ~ 2–3%. In the multilevel models, SVmax increased proportionally to FFM0.72 and with FFM controlled for, there were no significant (p > 0.05) sex differences. Peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2 increased with FFM but after adjusting for FFM0.98, a significant (p < 0.05) sex difference in peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2 remained. Introducing SVmax to the multilevel model revealed a significant (p < 0.05), but small additional effect of SVmax on peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2.

Conclusions

Fat-free mass explained sex differences in SVmax, but with FFM controlled for, there was still a ~ 5% sex difference in peak $$ {\dot{\text{V}}\text{O}}_{2} $$V˙O2. SVmax made a modest additional contribution to explain the development of peak $$ {\dot{\text{V}}\text{O}}_{2} , $$V˙O2, but there remained an unresolved sex difference of ~ 4%.
Creation of a new genus in the family Secoviridae substantiated by sequence variation of newly identified strawberry latent ringspot virus isolates
Authors: Dullemans A. M. , Botermans M. , de Kock M. J. D. , de Krom C. E. , van der Lee T. A. J. , Roenhorst J. W. , Stulemeijer I. J. E. , Verbeek M. , Westenberg M. , van der Vlugt R. A. A.
Published: October 2019

To obtain insight into the sequence diversity of strawberry latent ringspot virus (SLRSV), isolates from collections and diagnostic samples were sequenced by high-throughput sequencing. For five SLRSV isolates, the complete genome sequences were determined, and for 18 other isolates nearly complete genome sequences were determined. The sequence data were analysed in relation to sequences of SLRSV and related virus isolates available in the NCBI GenBank database. The genome sequences were annotated, and sequences of the protease-polymerase (Pro-Pol) region and coat proteins (CPs) (large and small CP together) were used for phylogenetic analysis. The amino acid sequences of the Pro-Pol region were very similar, whereas the nucleotide sequences of this region were more variable. The amino acid sequences of the CPs were less similar, which was corroborated by the results of a serological comparison performed using antisera raised against different isolates of SLRSV. Based on these results, we propose that SLRSV and related unassigned viruses be assigned to a new genus within the family Secoviridae, named “Stralarivirus”. Based on the phylogenetic analysis, this genus should include at least three viruses, i.e., SLRSV-A, SLRSV-B and lychnis mottle virus. The newly generated sequence data provide a basis for designing molecular tests to screen for SLRSV.
Integrating habitat- and species-based perspectives for wetland conservation in lowland agricultural landscapes
Authors: Guareschi Simone , Laini Alex , Viaroli Pierluigi , Bolpagni Rossano
Published: October 2019

Wetlands are among the most endangered ecosystems worldwide with multiple direct and indirect stressors, especially in human-altered areas like intensive agricultural landscapes. Conservation management and efforts often focus on species diversity and charismatic taxa, but scarcely consider habitats. By focusing on a complex formed by 107 permanent wetlands at 18 Natura 2000 sites in the Emilia-Romagna region (northern Italy), the patterns of habitats of conservation concern were investigated and the concordance with threatened species patterns was analysed. Wetlands were characterised in terms of morphology, connectivity, land use and management as drivers of assemblage and richness patterns of habitats. Our results showed a strong concordance between the distribution and richness patterns of both habitats and threatened taxa (birds, mammals, amphibians, reptiles, fish, invertebrates, and plants). Thus, habitats seem an effective proxy of species patterns. The variables related with perimeter, environmental heterogeneity and presence of water bodies were the most important ones associated with habitat richness patterns. The presence of aquatic systems (measured as the percentage of wetland area occupied by an aquatic surface) and their position in the hydrographic network were associated mostly with habitats distribution. Low richness wetlands (in habitat terms) were not complementary as no new habitat types were supported. The results stressed the relevance of wetlands with wide water body perimeters composed of diverse systems as being key for biodiversity conservation in a simplified agricultural matrix. Integrating habitat- and species-based perspectives seems a promising field and may provide a rapid assessment tool to acquire effective information for wetlands conservation and assessment.
Demolishing Prejudices to Get to the Foundations: A Criterion of Demarcation for Fundamentality
Authors: Del Santo Flavio , Cardelli Chiara
Published: October 2019

In this paper, we reject commonly accepted views on fundamentality in science, either based on bottom-up construction or top-down reduction to isolate the alleged fundamental entities. We do not introduce any new scientific methodology, but rather describe the current scientific methodology and show how it entails an inherent search for foundations of science. This is achieved by phrasing (minimal sets of) metaphysical assumptions into falsifiable statements and define as fundamental those that survive empirical tests. The ones that are falsified are rejected, and the corresponding philosophical concept is demolished as a prejudice. Furthermore, we show the application of this criterion in concrete examples of the search for fundamentality in quantum physics and biophysics.
Children with an Autism Spectrum Disorder and Their Caregivers: Capturing Health-Related and Care-Related Quality of Life
Authors: ten Hoopen Leontine W. , de Nijs Pieter F. A. , Duvekot Jorieke , Greaves-Lord Kirstin , Hillegers Manon H. J. , Brouwer Werner B. F. , Hakkaart-van Roijen Leona
Published: October 2019

This study investigated health-related QoL (HRQoL) and care-related quality of life (CarerQol) in clinically referred children with an autism spectrum disorder (ASD), and their primary and secondary caregivers. The EuroQol five-dimensional (EQ-5D) and the CarerQol questionnaires were used to respectively measure health-related QoL and care-related QoL. Primary caregivers reported pain/discomfort (42%) and anxiety/depression (40%). In caring, they mostly experienced problems in the relationship with the child (84%), and in combining care with daily activities (51%). Children with ASD had a relevantly lower QoL. Despite negative effects, almost all caregivers (96%) derived fulfillment from caring for their affected children. HRQoL and CarerQol reports of primary caregivers and children were correlated, both providing useful information to ASD measurement and treatment.
The industrialization of ablation: a highly standardized and reproducible workflow for radiofrequency ablation of atrial fibrillation
Authors: De Potter Tom , Hunter Tina D. , Boo Lee Ming , Chatzikyriakou Sofia , Strisciuglio Teresa , Silva Etel , Geelen Peter
Published: October 2019

Background or Purpose

The purpose of this analysis was to report on efficacy of a standardized workflow for atrial fibrillation (AF) ablation using technology advances such as 3D imaging and contact force sensing in a real-world setting.

Methods

Consecutive AF ablations from 2014 to 2015 at a high-volume site in Belgium were included. The workflow consisted of a pre-specified procedure sequence including 3D modeling followed by radiofrequency encircling of the pulmonary veins (25 W posterior wall, 35 W anterior wall) with a THERMOCOOL SMARTTOUCH® Catheter guided by CARTO VISITAG™ Module (2.5 mm/5 s stability, 50% > 7 g) and ablation index (targets: 550 anterior wall, 400 posterior wall). Efficiency endpoints were procedure time, fluoroscopy time, and radiation dose. The primary effectiveness endpoint was freedom from atrial arrhythmia recurrence.

Results

A total of 605 paroxysmal AF (PAF) and 182 persistent AF (PsAF) patients were followed for 436 ± 199 days. Mean procedure times were short (PAF: 96.1 ± 26.2 min; PsAF: 109.2 ± 35.6 min) with most procedures (90.6% PAF; 81.3% PsAF) completed in ≤ 120 min. Minimal fluoroscopy was utilized (PAF: 6.1 ± 3.8 min, 5.9 ± 3.4 Gy*cm2; PsAF: 6.9 ± 4.7 min, 7.4 ± 4.9 Gy*cm2). Freedom from atrial arrhythmia recurrence was higher for PAF than PsAF patients (OR: 2.0, 95% CI: 1.4–2.9, p = 0.0003), but adjusted mean rates were high in both groups (81.0% vs. 67.9%). Rates were adjusted for prior ablation and age (at 65 years).

Conclusion

AF ablation using a standardized workflow resulted in low procedure times and variability, with minimal fluoroscopy exposure. Long-term freedom from atrial arrhythmia recurrence was high in both PAF and PsAF populations.
Pre-operative Static Anterior Tibial Translation Assessed on MRI does not Influence Return to Sport or Satisfaction after Anterior Cruciate Ligament Reconstruction
Authors: Marom Niv , Kleeblad Laura J. , Ling Daphne , Nwachukwu Benedict U. , Marx Robert G. , Potter Hollis G. , Pearle Andrew D.
Published: October 2019

Background

It has been suggested that the degree of anterior tibial translation (ATT) as measured passively on imaging studies (static ATT) after an anterior cruciate ligament (ACL) injury may influence outcomes after ACL reconstruction. However, there is a lack of evidence supporting these suggestions.

Questions/Purposes

The purpose of this retrospective prognostic study was to assess the predictive value of pre-operative static ATT in knees with ACL injury on return to sport and in satisfaction after ACL reconstruction. Our hypothesis was that greater static ATT would be associated with lower rates of return to sport and lower levels of satisfaction.

Methods

Patients treated with ACL reconstruction were identified from an institutional registry and assigned to one of three groups according to their ACL injury type: acute ACL injury, chronic ACL injury, and failed ACL reconstruction. ATT in each knee compartment was measured using magnetic resonance imaging, and a retrospective telephone questionnaire was used to investigate post-ACL reconstruction return to sport and subjects’ satisfaction.

Results

One hundred thirty patients (52 acute with ACL injury, 29 with chronic ACL injury, and 49 with failed ACL reconstruction) completed the questionnaire, with a mean follow-up of 5.67 years. Ninety-seven patients (74.6%) returned to their primary sport, of whom 63 (65%) returned to the same level of sport. The mean time to return to sport was 10.1 months (range, 2 to 24 months). Overall, 113 patients (87%) were either very satisfied or satisfied with their outcomes. No difference in medial or lateral ATT was found between patients who returned to sport and those who did not. The failed-ACL reconstruction group had significantly lower rates of return to sport than did acutely and chronically injured patients (60.4% versus 88.5% and 75.9%, respectively).

Conclusion

The degree of pre-operative ATT in an ACL-deficient knee was not correlated with return to sport or satisfaction after ACL reconstruction. In this study cohort, only failed-ACL reconstruction patients undergoing revision ACL reconstruction were significantly less likely to return to their main sport. They were also less likely to return to sport at their pre-operative level, if they did return to sport.
Functionalized coconut husks for rhodamine-B dye sequestration
Authors: Bello Olugbenga Solomon , Adegoke Kayode Adesina , Fagbenro Samuel Oluwaseun , Lameed Olasunkanmi Seun
Published: October 2019

This study investigates the efficacy of acid activated coconut husk (CHA) for the removal of rhodamine-B (Rh-B) dye from aqueous solutions. The CHA prepared was characterized using various techniques: SEM, FTIR EDX, Boehm titration and pHpzc, respectively. The effects of different operational parameters including initial concentration, contact time and solution temperatures were examined. Kinetic data for Rh-B dye adsorption onto CHA fitted best to pseudo-second-order kinetic model considering the correlation regression (R2) and the sum of squares of error values. Adsorption data were fitted to Langmuir, Freundlich, Dubinin–Radushkevich and Temkin isotherm models. Langmuir isotherm was the most fitted among all the models used with maximum monolayer sorption capacity of 1666.67 mg g−1and the highest regression value of 0.99 indicating that CHA has greater affinity for Rh-B dye adsorption due to increased pore development via acid activation. Thermodynamic studies revealed an endothermic adsorption process with the ΔH0value of 62.77 kJ mol−1. Spontaneity was ascertained based on the negative values of ΔGo(ranging from − 26.38 kJ mol−1to − 20.93 kJ mol−1). The positive value of ΔS0(0.276 kJ mol−1 K−1) suggests increased randomness that exists between CHA and Rh-B dye. Cost analysis results revealed that CHA is six times cheaper than commercial activated carbon (CAC), providing a savings of 217 US$ kg−1. CHA adsorbent was found to be suitable for Rh-B dye removal from aqueous solution.
On the existence of dual solutions for Lorentzian cost functions
Authors: Kell Martin , Suhr Stefan
Published: October 2019

The dual problem of optimal transportation in Lorentz-Finsler geometry is studied. It is shown that in general no solution exists even in the presence of an optimal coupling. Under natural assumptions dual solutions are established. It is further shown that the existence of a dual solution implies that the optimal transport is timelike on a set of full measure. In the second part the persistence of absolute continuity along an optimal transportation under obvious assumptions is proven and a solution to the relativistic Monge problem is provided.
The impact of surgical site infections on hospital contribution margin—a European prospective observational cohort study
Authors: von Strauss Marco , Marti Walter R. , Mujagic Edin , Coslovsky Michael , Diernberger Katharina , Hall Peter , Zeindler Jasmin , Salm Lilian A. , Soysal Savas D. , Mechera Robert , von Holzen Urs , Weber Walter P.
Published: October 2019

Background:

Surgical site infections (SSIs) are common surgical complications that lead to increased costs. Depending on payer type, however, they do not necessarily translate into deficits for every hospital.

Objective:

We investigated how surgical site infections (SSIs) influence the contribution margin in 2 reimbursement systems based on diagnosis-related groups (DRGs).

Methods:

This preplanned observational health cost analysis was nested within a Swiss multicenter randomized controlled trial on the timing of preoperative antibiotic prophylaxis in general surgery between February 2013 and August 2015. A simulation of cost and income in the National Health Service (NHS) England reimbursement system was conducted.

Results:

Of 5,175 patients initially enrolled, 4,556 had complete cost and income data as well as SSI status available for analysis. SSI occurred in 228 of 4,556 of patients (5%). Patients with SSIs were older, more often male, had higher BMIs, compulsory insurance, longer operations, and more frequent ICU admissions. SSIs led to higher hospital cost and income. The median contribution margin was negative in cases of SSI. In SSI cases, median contribution margin was Swiss francs (CHF) −2045 (IQR, −12,800 to 4,848) versus CHF 895 (IQR, −2,190 to 4,158) in non-SSI cases. Higher ASA class and private insurance were associated with higher contribution margins in SSI cases, and ICU admission led to greater deficits. Private insurance had a strong increasing effect on contribution margin at the 10th, 50th (median), and 90th percentiles of its distribution, leading to overall positive contribution margins for SSIs in Switzerland. The NHS England simulation with 3,893 patients revealed similar but less pronounced effects of SSI on contribution margin.

Conclusions:

Depending on payer type, reimbursement systems with DRGs offer only minor financial incentives to the prevention of SSI.
Molecular pathway analysis associates alterations in obesity-related genes and antipsychotic-induced weight gain
Authors: Corfitsen Henrik Thyge , Krantz Betina , Larsen Agnete , Drago Antonio
Published: October 2019

Objective:

Antipsychotics often induce excessive weight gain. We hypothesised that individuals with genetic variations related to known obesity-risk genes have an increased risk of excessive antipsychotic-induced weight gain (AIWG). This hypothesis was tested in a subset of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial data set.

Methods:

The CATIE trial compared effects and side effects of five different antipsychotics through an 18-month period. Based on the maximum weight gain recorded, excessive weight gain was defined as >7% weight gain. Cytoscape and GeneMANIA were instrumental in composing a molecular pathway from eight selected genes linked to obesity. Genetic information on a total of 495.172 single-nucleotide polymorphisms (SNPs) were available from 765 (556 males) individuals. Enrichment test was conducted through ReactomePA and Bioconductor. A permutation test was performed, testing the generated pathway against 105permutated pathways (p≤ 0.05). In addition, a standard genome-wide association study (GWAS) analysis was performed.

Result:

GWAS analysis did not detect significant differences related to excessive weight gain. The pathway generated contained 28 genes. A total of 2067 SNPs were significantly expressed (p< 0.01) within this pathway when comparing excessive weight gainers to the rest of the sample. Affected genes includingPPARGandPCSK1were not previously related to treatment-induced weight gain.

Conclusions:

The molecular pathway composed from high-risk obesity genes was shown to overlap with genetics of patients who gained >7% weight gain during the CATIE trial. This suggests that genes related to obesity compose a pathway of increased risk of excessive AIWG. Further independent analyses are warranted that may confirm or clarify the possible reasoning behind.
Petrography and geochemistry of the Lower Silurian sandstones from the Angzanggou Formation in the North Qilian Belt, China: implications for provenance, weathering and tectonic setting
Authors: Hou Qian , Mou Chuanlong , Han Zuozhen , Wang Qiyu , Tan Zhiyuan , Ge Xiangying
Published: October 2019

The North Qilian Orogenic Belt is on the northeastern margin of the Tibetan Plateau. It is connected with the Alxa Block in the north and the Tethyan orogenic assemblage in the south. The Lower Silurian Angzanggou Formation, deposited in the northern area of the North Qilian Orogenic Belt, is the most important for revealing the architecture and orogenic processes of the North Qilian Belt. Provenance analysis of the Angzanggou Formation can reveal not only the tectonic evolution of the central orogenic belt of China but also Palaeozoic Asia plate reconstructions. Petrographic analysis indicated that the compositional and textural maturity of the sandstones was low. The detrital composition of the Angzanggou Formation samples consists of quartz (8–14 %), feldspar (6–29 %) and lithic fragments (56–86 %). The sandstones could be classified as litharenites or feldspathic litharenites. The detrital modal composition suggests that these sandstones were probably deposited in a fore-arc basin. The element ratios and some discrimination diagrams based on geochemistry indicate that felsic and intermediate rocks were the main source rocks. The SiO2/Al2O3 ratio, the index of chemical variability and the Th/Sc versus Zr/Sc discrimination diagram suggest that the compositional maturity and degree of recycling were moderate to low. The index of alteration (CIA) and the A–CN–K diagram indicate the intensity of weathering was moderate. The discrimination diagrams based on major and trace elements and petrographic discrimination diagrams imply that the Angzanggou Formation rocks were derived from a continental island arc, and a sedimentary cover probably overlaid the volcanic arc. Therefore, we infer that during Early Silurian time the North Qilian Belt sediments accumulated in a fore-arc basin.
Set to Music, Exoplanets Reveal Insights on Their Formation
Authors: Redd Nola
Published: October 2019

Sonification hints at how some Kepler planets may have been configured in the late stages of their development.
Niche partitioning of methane-oxidizing bacteria along the oxygen–methane counter gradient of stratified lakes
Authors: Mayr Magdalena J , Zimmermann Matthias , Guggenheim Carole , Brand Andreas , Bürgmann Helmut
Published: October 2019

Lakes are a significant source of atmospheric methane, although methane-oxidizing bacteria consume most methane diffusing upward from anoxic sediments. Diverse methane-oxidizing bacteria form an effective methane filter in the water column of stratified lakes, yet, niche partitioning of different methane-oxidizing bacteria along the oxygen–methane counter gradient remains poorly understood. In our study, we reveal vertical distribution patterns of active methane-oxidizing bacteria along the oxygen–methane counter gradient of four lakes, based on amplicon sequencing analysis of 16S rRNA and pmoA genes, and 16S rRNA and pmoA transcripts, and potential methane oxidation rates. Differential distribution patterns indicated that ecologically different methane-oxidizing bacteria occupied the methane-deficient and oxygen-deficient part above and below the oxygen–methane interface. The interface sometimes harbored additional taxa. Within the dominant Methylococcales, an uncultivated taxon (CABC2E06) occurred mainly under methane-deficient conditions, whereas Crenothrix-related taxa preferred oxygen-deficient conditions. Candidatus Methylomirabilis limnetica (NC10 phylum) abundantly populated the oxygen-deficient part in two of four lakes. We reason that the methane filter in lakes is structured and that methane-oxidizing bacteria may rely on niche-specific adaptations for methane oxidation along the oxygen–methane counter gradient. Niche partitioning of methane-oxidizing bacteria might support greater overall resource consumption, contributing to the high effectivity of the lacustrine methane filter.
Host genetic effects upon the early gut microbiota in a bovine model with graduated spectrum of genetic variation
Authors: Fan Peixin , Bian Beilei , Teng Lin , Nelson Corwin D , Driver J , Elzo Mauricio A , Jeong Kwangcheol C
Published: October 2019

Multiple synergistic factors affect the development and composition of mammalian gut microbiota, but effects of host genetics remain unclear. To illuminate the role of host genetics on gut microbiota, we employed animals with a graduated spectrum of genetic variation with minimal environmental influences. We bred 228 calves with linearly varying breed composition from 100% Angus (Bos taurus) to 100% Brahman (Bos indicus), as a proxy for genetic variation, and then raised the offspring in the same environment with identical diets. We hypothesized each breed would harbor distinct gut microbiota due to genetic influence. We found that the gut microbiota of preweaning calves at 3 months old is significantly affected by host genetics, profoundly by paternal genome. We also demonstrate that single nucleotide polymorphisms in host mucin-encoding genes, critical for gut mucosal health, are significantly correlated with both breed composition and mucin-degrading gut bacteria. We further demonstrate host genetics indirectly changes gut microbiota composition via microbe–microbe interactions. These findings indicate a strong contribution by host genetics in shaping the gut microbiota during early life stages, shedding light on impact of animal breeding on gut microbiota, which is associated with animal growth and health.
Consistent host and organ occupancy of phyllosphere bacteria in a community of wild herbaceous plant species
Authors: Massoni Julien , Bortfeld-Miller Miriam , Jardillier Ludwig , Salazar Guillem , Sunagawa Shinichi , Vorholt Julia A
Published: October 2019

Bacteria colonizing the aerial parts of plants (phyllosphere) are linked to the biology of their host. They impact plant–pathogen interactions and may influence plant reproduction. Past studies have shown differences in composition and structure of the leaf, flower, and host microbiota, but an investigation of the impact of individual taxa on these variations remains to be tested. Such information will help to evaluate disparities and to better understand the biology and evolution of the plant–microbe associations. In the present study, we investigated the community structure, occupancy of host and organ, and the prevalence of phyllosphere bacteria from three host species collected at the same location. Almost all (98%) of bacterial taxa detected in the phyllosphere were not only shared across leaves and flowers, or different plant species but also had a conserved prevalence across sub-environments of the phyllosphere. We also found nonrandom associations of the phylogenetic diversity of phyllosphere bacteria. These results suggest that the phyllosphere microbiota is more conserved than previously acknowledged, and dominated by generalist bacteria adapted to environmental heterogeneity through evolutionary conserved traits.
Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder
Authors: Gudmundsson Olafur O. , Walters G. Bragi , Ingason Andres , Johansson Stefan , Zayats Tetyana , Athanasiu Lavinia , Sonderby Ida Elken , Gustafsson Omar , Nawaz Muhammad S. , Jonsson Gudbjorn F. , Jonsson Lina , Knappskog Per-Morten , Ingvarsdottir Ester , Davidsdottir Katrin , Djurovic Srdjan , Knudsen Gun Peggy Strømstad , Askeland Ragna Bugge , Haraldsdottir Gyda S. , Baldursson Gisli , Magnusson Pall , Sigurdsson Engilbert , Gudbjartsson Daniel F. , Stefansson Hreinn , Andreassen Ole A. , Haavik Jan , Reichborn-Kjennerud Ted , Stefansson Kari
Published: October 2019

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.
Clinical-learning versus machine-learning for transdiagnostic prediction of psychosis onset in individuals at-risk
Authors: Fusar-Poli Paolo , Stringer Dominic , M. S. Durieux Alice , Rutigliano Grazia , Bonoldi Ilaria , De Micheli Andrea , Stahl Daniel
Published: October 2019

Predicting the onset of psychosis in individuals at-risk is based on robust prognostic model building methods including a priori clinical knowledge (also termed clinical-learning) to preselect predictors or machine-learning methods to select predictors automatically. To date, there is no empirical research comparing the prognostic accuracy of these two methods for the prediction of psychosis onset. In a first experiment, no improved performance was observed when machine-learning methods (LASSO and RIDGE) were applied—using the same predictors—to an individualised, transdiagnostic, clinically based, risk calculator previously developed on the basis of clinical-learning (predictors: age, gender, age by gender, ethnicity, ICD-10 diagnostic spectrum), and externally validated twice. In a second experiment, two refined versions of the published model which expanded the granularity of the ICD-10 diagnosis were introduced: ICD-10 diagnostic categories and ICD-10 diagnostic subdivisions. Although these refined versions showed an increase in apparent performance, their external performance was similar to the original model. In a third experiment, the three refined models were analysed under machine-learning and clinical-learning with a variable event per variable ratio (EPV). The best performing model under low EPVs was obtained through machine-learning approaches. The development of prognostic models on the basis of a priori clinical knowledge, large samples and adequate events per variable is a robust clinical prediction method to forecast psychosis onset in patients at-risk, and is comparable to machine-learning methods, which are more difficult to interpret and implement. Machine-learning methods should be preferred for high dimensional data when no a priori knowledge is available.
Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy
Authors: Cheung Chantal Hoi Yin , Hsu Chia-Lang , Tsuei Chao-Yin , Kuo Tzu-Ting , Huang Chen-Tsung , Hsu Wen-Ming , Chung Yun-Hsien , Wu Hsin-Yi , Hsu Cheng-Chih , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: October 2019

MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.
Disordered zero-index metamaterials based on metal-induced crystallization
Authors: Galinski Henning , Wyss Andreas , Seregni Mattia , Ma Huan , Schnabel Volker , Sologubenko Alla , Spolenak Ralph
Published: October 2019

Zero-index (ZI) materials are synthetic optical materials with a vanishing effective permittivity and/or permeability at a given design frequency. Recently, it has been shown that the permeability of a zero-index host material can be deterministically tuned by adding photonic dopants. Here, we apply metal-induced crystallization (MIC) in quasi-random metal–semiconductor composites to fabricate large-area zero-index materials. Using Ag–Si as a model system, we demonstrate that the localized crystallization of the semiconductor at the metal/semiconductor interface can be used as a design parameter to control light interaction in such a disordered system. The induced crystallization generates new zero-index states corresponding to a hybridized plasmonic mode emerging from selective coupling of light to the Ångstrom-sized crystalline shell of the semiconductor. Photonic doping can be used to enhance the transmission in these disordered metamaterials, as shown by simulations. Our results establish novel large-area zero-index materials for wafer-scale applications and beyond.
Enhanced spin orbit interaction of light in highly confining optical fibers for mode division multiplexing
Authors: Gregg P. , Kristensen P. , Rubano A. , Golowich S. , Marrucci L. , Ramachandran S.
Published: October 2019

Light carries both orbital angular momentum (OAM) and spin angular momentum (SAM), related to wavefront rotation and polarization, respectively. These are usually approximately independent quantities, but they become coupled by light’s spin-orbit interaction (SOI) in certain exotic geometries and at the nanoscale. Here we reveal a manifestation of strong SOI in fibers engineered at the micro-scale and supporting the only known example of propagating light modes with non-integer mean OAM. This enables propagation of a record number (24) of states in a single optical fiber with low cross-talk (purity > 93%), even as tens-of-meters long fibers are bent, twisted or otherwise handled, as fibers are practically deployed. In addition to enabling the investigation of novel SOI effects, these light states represent the first ensemble with which mode count can be potentially arbitrarily scaled to satisfy the exponentially growing demands of high-performance data centers and supercomputers, or telecommunications network nodes.
UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells
Authors: Dong Juan , Wang Xiaoli , Cao Congcong , Wen Yujiao , Sakashita Akihiko , Chen Si , Zhang Jin , Zhang Yue , Zhou Liquan , Luo Mengcheng , Liu Mingxi , Liao Aihua , Namekawa Satoshi H. , Yuan Shuiqiao
Published: October 2019

DNA methylation, repressive histone marks, and PIWI-interacting RNA (piRNA) are essential for the control of retrotransposon silencing in the mammalian germline. However, it remains unknown how these repressive epigenetic pathways crosstalk to ensure retrotransposon silencing in the male germline. Here, we show that UHRF1 is responsible for retrotransposon silencing and cooperates with repressive epigenetic pathways in male germ cells. Conditional loss of UHRF1 in postnatal germ cells causes DNA hypomethylation, upregulation of retrotransposons, the activation of a DNA damage response, and switches in the global chromatin status, leading to complete male sterility. Furthermore, we show that UHRF1 interacts with PRMT5, an arginine methyltransferase, to regulate the repressive histone arginine modifications (H4R3me2s and H3R2me2s), and cooperates with the PIWI pathway during spermatogenesis. Collectively, UHRF1 regulates retrotransposon silencing in male germ cells and provides a molecular link between DNA methylation, histone modification, and the PIWI pathway in the germline.
Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation
Authors: Klein Brianna J. , Jang Suk Min , Lachance Catherine , Mi Wenyi , Lyu Jie , Sakuraba Shun , Krajewski Krzysztof , Wang Wesley W. , Sidoli Simone , Liu Jiuyang , Zhang Yi , Wang Xiaolu , Warfield Becka M. , Kueh Andrew J. , Voss Anne K. , Thomas Tim , Garcia Benjamin A. , Liu Wenshe R. , Strahl Brian D. , Kono Hidetoshi , Li Wei , Shi Xiaobing , Côté Jacques , Kutateladze Tatiana G.
Published: October 2019

Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.
Multi-strategic RNA-seq analysis reveals a high-resolution transcriptional landscape in cotton
Authors: Wang Kun , Wang Dehe , Zheng Xiaomin , Qin Ai , Zhou Jie , Guo Boyu , Chen Yanjun , Wen Xingpeng , Ye Wen , Zhou Yu , Zhu Yuxian
Published: October 2019

Cotton is an important natural fiber crop, however, its comprehensive and high-resolution gene map is lacking. Here we integrate four complementary high-throughput techniques, including Pacbio long read Iso-seq, strand-specific RNA-seq, CAGE-seq, and PolyA-seq, to systematically explore the transcription landscape across 16 tissues or different organ types in Gossypium arboreum. We devise a computational pipeline, named IGIA, to reconstruct accurate gene structures from the integrated data. Our results reveal a dynamic and diverse transcriptional map in cotton: tissue-specific gene expression, alternative usage of TSSs and polyadenylation sites, hotspot of alternative splicing, and transcriptional read-through. These regulated events affect many genes in various aspects such as gain or loss of functional RNA motifs and protein domains, fine-tuning of DNA binding activity, and co-regulation for genes in the same complex or pathway. The methods and findings provide valuable resources for further functional genomic studies such as understanding natural SNP variations for plant community.
The evolution of parental care diversity in amphibians
Authors: Furness Andrew I. , Capellini Isabella
Published: October 2019

Parental care is extremely diverse across species, ranging from simple behaviours to complex adaptations, varying in duration and in which sex cares. Surprisingly, we know little about how such diversity has evolved. Here, using phylogenetic comparative methods and data for over 1300 amphibian species, we show that egg attendance, arguably one of the simplest care behaviours, is gained and lost faster than any other care form, while complex adaptations, like brooding and viviparity, are lost at very low rates, if at all. Prolonged care from the egg to later developmental stages evolves from temporally limited care, but it is as easily lost as it is gained. Finally, biparental care is evolutionarily unstable regardless of whether the parents perform complementary or similar care duties. By considering the full spectrum of parental care adaptations, our study reveals a more complex and nuanced picture of how care evolves, is maintained, or is lost.
Correlation between manganese dissolution and dynamic phase stability in spinel-based lithium-ion battery
Authors: Liu Tongchao , Dai Alvin , Lu Jun , Yuan Yifei , Xiao Yinguo , Yu Lei , Li Matthew , Gim Jihyeon , Ma Lu , Liu Jiajie , Zhan Chun , Li Luxi , Zheng Jiaxin , Ren Yang , Wu Tianpin , Shahbazian-Yassar Reza , Wen Jianguo , Pan Feng , Amine Khalil
Published: October 2019

Historically long accepted to be the singular root cause of capacity fading, transition metal dissolution has been reported to severely degrade the anode. However, its impact on the cathode behavior remains poorly understood. Here we show the correlation between capacity fading and phase/surface stability of an LiMn2O4cathode. It is revealed that a combination of structural transformation and transition metal dissolution dominates the cathode capacity fading. LiMn2O4exhibits irreversible phase transitions driven by manganese(III) disproportionation and Jahn-Teller distortion, which in conjunction with particle cracks results in serious manganese dissolution. Meanwhile, fast manganese dissolution in turn triggers irreversible structural evolution, and as such, forms a detrimental cycle constantly consuming active cathode components. Furthermore, lithium-rich LiMn2O4with lithium/manganese disorder and surface reconstruction could effectively suppress the irreversible phase transition and manganese dissolution. These findings close the loop of understanding capacity fading mechanisms and allow for development of longer life batteries.
Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation
Authors: Esfahani Khashayar , Al-Aubodah Tho-Alfakar , Thebault Pamela , Lapointe Réjean , Hudson Marie , Johnson Nathalie A. , Baran Dana , Bhulaiga Najwa , Takano Tomoko , Cailhier Jean-François , Piccirillo Ciriaco A. , Miller Wilson H.
Published: October 2019

Immune checkpoint inhibitor (ICI) use remains a challenge in patients with solid organ allografts as most would undergo rejection. In a melanoma patient in whom programmed-death 1 (PD-1) blockade resulted in organ rejection and colitis, the addition of the mTOR inhibitor sirolimus resulted in ongoing anti-tumor efficacy while promoting allograft tolerance. Strong granzyme B+, interferon (IFN)-γ+ CD8+ cytotoxic T cell and circulating regulatory T (Treg) cell responses were noted during allograft rejection, along with significant eosinophilia and elevated serum IL-5 and eotaxin levels. Co-treatment with sirolimus abated cytotoxic T cell numbers and eosinophilia, while elevated Treg cell numbers in the peripheral blood were maintained. Interestingly, numbers of IFN-γ+ CD4+ T cells and serum IFN-γ levels increased with the addition of sirolimus treatment likely promoting ongoing anti-PD-1 efficacy. Thus, our results indicate that sirolimus has the potential to uncouple anti-PD-1 therapy toxicity and efficacy.
Colonizing multidrug-resistant bacteria and the longitudinal evolution of the intestinal microbiome after liver transplantation
Authors: Annavajhala Medini K. , Gomez-Simmonds Angela , Macesic Nenad , Sullivan Sean B. , Kress Anna , Khan Sabrina D. , Giddins Marla J. , Stump Stephania , Kim Grace I. , Narain Ryan , Verna Elizabeth C. , Uhlemann Anne-Catrin
Published: October 2019

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.
The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner
Authors: Srikantan Subramanya , Deng Yilun , Cheng Zi-Ming , Luo Anqi , Qin Yuejuan , Gao Qing , Sande-Docor Glaiza-Mae , Tao Sifan , Zhang Xingyu , Harper Nathan , Shannon Chris E. , Fourcaudot Marcel , Li Zhi , Kasinath Balakuntalam S. , Harrison Stephen , Ahuja Sunil , Reddick Robert L. , Dong Lily Q. , Abdul-Ghani Muhammad , Norton Luke , Aguiar Ricardo C. T. , Dahia Patricia L. M.
Published: October 2019

Understanding the molecular components of insulin signaling is relevant to effectively manage insulin resistance. We investigated the phenotype of the TMEM127 tumor suppressor gene deficiency in vivo. Whole-body Tmem127 knockout mice have decreased adiposity and maintain insulin sensitivity, low hepatic fat deposition and peripheral glucose clearance after a high-fat diet. Liver-specific and adipose-specific Tmem127 deletion partially overlap global Tmem127 loss: liver Tmem127 promotes hepatic gluconeogenesis and inhibits peripheral glucose uptake, while adipose Tmem127 downregulates adipogenesis and hepatic glucose production. mTORC2 is activated in TMEM127-deficient hepatocytes suggesting that it interacts with TMEM127 to control insulin sensitivity. Murine hepatic Tmem127 expression is increased in insulin-resistant states and is reversed by diet or the insulin sensitizer pioglitazone. Importantly, human liver TMEM127 expression correlates with steatohepatitis and insulin resistance. Our results suggest that besides tumor suppression activities, TMEM127 is a nutrient-sensing component of glucose/lipid homeostasis and may be a target in insulin resistance.