bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpersonal Problems Associated With Passive-Aggressive Personality Disorder
Authors: Laverdière Olivier , Ogrodniczuk John S. , Kealy David
Published: September 2019

With a controversial history, passive-aggressive personality disorder (PAPD) was eventually removed from the latest edition of the Diagnostic and Statistical Manual for Mental Disorders. Despite its demise from diagnostic nomenclature, clinicians continue to regard it as a clinically relevant construct, and some researchers argue for its resurrection. Toward this end, it is important to empirically demonstrate the relevance of the passive-aggressive personality construct, including demonstrating its association with impaired functioning. Consistent with contemporary emphasis on interpersonal functioning in personality pathology, the current study aims to explore interpersonal problems that are associated with PAPD in a large clinical sample. Before beginning treatment, 240 patients completed assessments of personality psychopathology and interpersonal functioning. Results showed that higher levels of PAPD were significantly associated with greater level of interpersonal distress, especially regarding interpersonal problems of a vindictive nature. The findings are consistent with clinical descriptions of the core conflictual relational issues of patients with PAPD and lend some support to further considering PAPD as a valid diagnostic construct.
Personality and the Expression of Symptomatology in Schizophrenia and Bipolar Disorder
Authors: Urošević Snežana , Halverson Tate , Sponheim Scott R.
Published: September 2019

Researchers and clinicians have begun using dimensions rather than categories to classify psychopathology with a reliance on personality questionnaires to tap traits that can inform dimensional characterizations. A neglected concern is whether in severe psychopathology questionnaire-based assessments of personality reflect a lifetime propensity toward a diagnosis, as some personality-psychopathology models posit, or reflect the transient effects of current symptoms, as a complication model of personality-psychopathology would suggest. Accurate characterization of psychopathology is necessary to understand etiology and prescribe clinical care. We studied 127 adults with schizophrenia, schizoaffective, or bipolar disorder who completed well-validated measures of personality, current symptomatology, and lifetime psychopathology. We found that normative personality traits were related to current symptoms but unrelated to lifetime symptomatology, whereas the schizotypal trait of cognitive-perceptual distortions predicted lifetime psychosis severity. Questionnaire-based assessments of normative personality are likely affected by current symptom states and may fail to yield a stable characterization of psychopathology.
Integration of Physical Examination, Old and New Biomarkers, and Ultrasonography by Using Neural Networks for Pediatric Appendicitis
Authors: Akgül Fatma , Er Anıl , Ulusoy Emel , Çağlar Aykut , Çitlenbik Hale , Keskinoğlu Pembe , Şişman Ali R. , Karakuş Osman Z. , Özer Erdener , Duman Murat , Yılmaz Durgül
Published: September 2019

Objective

The objective of this study was to evaluate physical examinations, imaging, and laboratory analyses individually and combined using innovative statistical analysis methods for the accurate diagnosis of pediatric appendicitis.

Methods

Patients admitted to hospital with symptoms of abdominal pain whose pediatric appendicitis scores greater than 3 were included in the study. Clinical, radiologic, and laboratory findings and as a new biomarker calprotectin (CPT) concentrations were evaluated individually and combined using artificial neural networks (ANNs), which revealed latent relationships for a definitive diagnosis.

Results

Three hundred twenty patients were evaluated (190 appendicitis [43 perforated] vs 130 no appendicitis). The mean ± SD age was 11.3 ± 3.6 years and 63% were male. Pediatric appendicitis scores, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP) level, procalcitonin (PCT) and CPT concentrations were higher in the appendicitis group; however, only WBC and ANC were higher in first 24 hours of pain. White blood cells and CRP were diagnostic markers in patients whose appendix could not be visualized using ultrasonography (US). On classic receiver operating characteristic (ROC) analysis, the areas under the curve (AUCs) were not strong enough for differential diagnosis (WBC, 0.73; ANC, 0.72; CRP, 0.65; PCT and CPT, 0.61). However, when the physical examination, US, and laboratory findings were analyzed in a multivariate model and the ROC analysis obtained from the variables with ANN, an ROC curve could be obtained with 0.91 AUC, 89.8% sensitivity, and 81.2% specificity. C-reactive protein and PCT were diagnostic for perforated appendicitis with 0.83 and 0.75 AUC on ROC.

Conclusions

Although none of the biomarkers were sufficient for an accurate diagnosis of appendicitis individually, a combination of physical examination and laboratory and US was a good diagnostic tool for pediatric appendicitis.
Hopkins Syndrome
Authors: Gateau Kameelah L. , David Henry , Lowe Calvin G.
Published: September 2019

We report a rare case of a 22-month-old who developed flaccid paralysis of her right arm shortly after she was hospitalized for an asthma exacerbation. There are many etiologies of acute flaccid paralysis; however, because of the uncommon presentation of a focalized finding, establishing the diagnosis of this patient was difficult in the emergency department setting. Associated with asthma exacerbations, Hopkins syndrome is a paralytic illness that resembles poliomyelitis. This case highlights the challenges of evaluating a child with monoparesis and establishing an association with asthma amyotrophy.
Orbital Decompression for Treatment of Acute Visual Loss After Facial Trauma
Authors: Ruiz Samuel , Lim Rizal
Published: September 2019

Injury to the orbital region represents a significant proportion of emergency department attendances and it is a common injury in patients with multisystem trauma. To date, trauma remains a leading cause of monocular blindness.

Traumatic optic neuropathy may be caused by direct trauma to the optic nerve and from compression caused by foreign bodies and bone fragments. Indirect trauma can lead to visual loss from transmitted force to the optic canal by blunt facial trauma without associated fractures. Occasionally traumatic optic neuropathy is due to reversible changes, such as edema or contusion.

High-dose intravenous steroids and surgical decompression of the optic canal have been advocated for the management of acute traumatic optic neuropathy, but the efficacy and safety of these treatments have been questioned.

The authors present 3 patients with traumatic optic nerve injury, 1 due to a gunshot wound to the face and 2 caused by blunt facial trauma, where fragments of bone intrude into the orbit leading to compression of its content. These injuries where successfully treated with both preoperative intravenous steroids followed by acute surgical decompression of the orbit with return of visual function.
Comprehensive Learning Curve of Robotic Surgery
Authors: Kim Min Seo , Kim Won Jun , Hyung Woo Jin , Kim Hyoung-Il , Han Sang-Uk , Kim Young-Woo , Ryu Keun Won , Park Sungsoo
Published: September 2019

Objective:

To evaluate the complication-based learning curve and identify learning-associated complications of robotic gastrectomy.

Summary Background Data:

With the increased popularity of robotic surgery, a sound understanding of the learning curve in the surgical outcome of robotic surgery has taken on great importance. However, a multicenter prospective study analyzing learning-associated morbidity has never been conducted in robotic gastrectomy.

Methods:

Data on 502 robotic gastrectomy cases were prospectively collected from 5 surgeons. Risk-adjusted cumulative sum analysis was applied to visualize the learning curve of robotic gastrectomy on operation time and complications.

Results:

Twenty-five cases, on average, were needed to overcome complications and operation time-learning curve sufficiently to gain proficiency in 3 surgeons. An additional 23 cases were needed to cross the transitional phase to progress from proficiency to mastery. The moderate complication rate (CD ≥ grade II) was 20% in phase 1 (cases 1–25), 10% in phase 2 (cases 26–65), 26.1% in phase 3 (cases 66–88), and 6.4% in phase 4 (cases 89–125) (P < 0.001). Among diverse complications, CD ≥ grade II intra-abdominal bleeding (P < 0.001) and abdominal pain (P = 0.01) were identified as major learning-associated morbidities of robotic gastrectomy. Previous experience on laparoscopic surgery and mode of training influenced progression in the learning curve.

Conclusions:

This is the first study suggesting that technical immaturity substantially affects the surgical outcomes of robotic gastrectomy and that robotic gastrectomy is a complex procedure with a significant learning curve that has implications for physician training and credentialing.
Systematic Review and Meta-Analysis of the Associations Between Body Mass Index, Prostate Cancer, Advanced Prostate Cancer and Prostate Specific Antigen
Authors: Harrison Sean , Tilling Kate , Turner Emma L. , Martin Richard M. , Lennon Rosie , Lane J. Athene , Donovan Jenny L. , Hamdy Freddie C. , Neal David E. , Bosch J.L.H. Ruud , Jones Hayley E.
Published: September 2019

Purpose

The relationship between body-mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA.

Methods

We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome.

Results

In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of −5.88% (95% CI −6.87% to −4.87%). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI −5.57% to −1.23%), and obese men were 12.9% lower (95% CI −15.2% to −10.7%). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations.

Conclusion

There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.
Influenza-associated mortality for different causes of death during the 2010-2011 through the 2014-2015 influenza seasons in Russia
Authors: Goldstein Edward
Published: September 2019

Background

There is limited information on the volume of influenza-associated mortality in Russia.

Methods

Using previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, circulatory causes, and for certain infectious and parasitic diseases (available from the Russian Federal State Statistics Service (Rosstat)) linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on levels of ILI/ARI consultations and the percent of respiratory specimens testing positive for influenza A/H3N2, A/H1N1 and B), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends.

Results

For the 2010/11 through the 2014/15 seasons, influenza circulation was associated with an average annual 11106 (95% CI (4321,17892)) deaths for circulatory causes, 4552 (3744,5360) deaths for respiratory causes, and 343 (63,624) deaths for certain infectious and parasitic diseases, with influenza A/H3N2 being responsible for the majority of influenza-associated respiratory deaths and influenza B making a substantial contribution to influenza-associated mortality for circulatory causes.

Conclusions

Influenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths. Those results support the potential utility of influenza vaccination (with the role played by influenza B in circulatory mortality pointing to the benefit of quadrivalent influenza vaccines), as well as of administration of antiviral drugs for high-risk individuals during periods of active influenza circulation.
The purine pathway in liver tissue biopsies from donors for transplantation is associated to immediate graft function and survival
Authors: Xu Jin , Hassan-Ally Mohammad , Casas-Ferreira Ana María , Suvitaival Tommi , Ma Yun , Vilca-Melendez Hector , Rela Mohamed , Heaton Nigel , Jassem Wayel , Legido-Quigley Cristina
Published: September 2019

Background & Aims

The current shortage of livers for transplantation has increased the use of organs sourced from donation after circulatory death (DCD). These organs are prone to higher incidence of graft failure, but the underlying mechanisms are largely unknown. Here we aimed to find biomarkers of liver function before transplantation to better inform clinical evaluation.

Methods

Matched pre- and post-transplant liver biopsies from DCD (n=24) and donation after brain death (DBD, n=70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. First, a discrimination analysis DCD vs DBD was used to parse metabolites associated to DCD. Then a data-driven approach was used to predict Immediate Graft Function (IGF). The metabolites were tested in models to predict survival.

Results

Five metabolites in the purine pathway were selected and investigated. The ratios of: adenine monophosphate (AMP), adenine, adenosine and hypoxanthine to urate, differed between DBD and DCD biopsies at pre-transplantation stage (q<0.05). The ratios of AMP and adenine to urate also differed in biopsies from recipients undergoing IGF (q<0.05). Using random forest a panel composed by alanine aminotransferase (ALT) and AMP, adenine, hypoxanthine ratio to urate predicted IGF with AUC 0.84 (95% CI [0.71, 0.97]). In comparison AUC 0.71 (95%CI [0.52, 0.90]) was achieved by clinical measures. Survival analysis revealed that the metabolite classifier could stratify 6-year survival outcomes (p = 0.0073) while clinical data and donor class could not.

Conclusions

At liver pre-transplantation stage, a panel composed of purine metabolites and ALT in tissue could improve prediction of IGF and survival.

Lay summary

New liver function biomarkers could help clinicians assess livers before transplantation. Purines are small molecules that are found in healthy livers, and in this work we found that their levels changed critically in livers from cardiac death donors. Measuring them before transplantation improved the prediction of the liver’s immediate graft function.

Graphic abstract

Highlights

The ratios of purine metabolites to urate differ between DCD and DBD in liver tissue at pre-transplantation.

The ratios of purine metabolites to urate and ALT pre-transplantation can improve prediction of IGF after transplantation.

Purine metabolites ratios to urate stratified 6-year survival outcome better than clinical data and donor class.
Associations between reasons for vaping and current vaping and smoking status: Evidence from a UK based cohort
Authors: Khouja Jasmine N. , Taylor Amy E. , Munafò Marcus R.
Published: September 2019

Background

This study aimed to discover which young adults vape, the reasons given for vaping, and which reasons for vaping are associated with continued vaping/smoking.

Methods

In a UK cohort of 3,994 young adults, we explored the association of retrospectively-recalled reasons for vaping by 23 years with vaping/smoking status at 24 years. Using logistic regression, we assessed the association with vaping behaviour among ever vapers who had ever smoked (n=668), and with smoking behaviour among individuals who regularly smoked prior to vaping (n=412).

Results

Vaping to quit smoking was associated with higher likelihood of vaping (odds ratio [OR] = 3.51, 95% confidence interval [95%CI] = 2.29 to 5.38), but lower likelihood of smoking at 24 years (OR = 0.50, 95%CI = 0.32 to 0.78). Vaping to cut down smoking was associated with higher likelihood of vaping (OR = 2.90, 95%CI = 1.87 to 4.50) and smoking at 24 years (OR = 1.62, 95%CI = 1.02 to 2.58). Vaping out of curiosity was associated with lower likelihood of vaping at 24 years (OR = 0.41, 95%CI = 0.26 to 0.63) but higher likelihood of smoking at 24 years (OR = 1.66, 95%CI = 1.04 to 2.65).

Conclusions

Intention to quit smoking appears important for young adults to stop smoking using e-cigarettes; vaping to cut down is associated with continued smoking, but smoking to quit is associated with discontinued smoking. Vaping out of curiosity is less likely to lead to a change in smoking/vaping behaviour (i.e., current smokers continue to smoke).
Analysis of corneal real astigmatism changes and high order aberration after lower eyelid epiblepharon repair surgery
Authors: Lee Dong Cheol
Published: September 2019

Objective

To investigate changes in corneal low and high order aberrations (LOA and HOA), which cause visual disturbances after lower eyelid epiblepharon repair surgery.

Methods and analysis

This was a retrospective, cross-sectional study, which included 108 eyes from 54 patients. Wavefront analyses for calibrated LOAs and HOAs (root mean square, coma, three-piece aberrations [Trefoil], secondary astigmatisms, and spherical aberrations [SA]) were performed via a Galilei G4 Dual Scheimpflug Analyzer preoperatively, at the first and second follow-ups (f/u), and at G1, G2, and G3 (<45 days, 45–75 days, and >75 days post-surgery). Several risk factors (age, sex, body mass index, and corneal keratitis presence) were assessed.

Results

In LOAs, flat keratometer (K) and axis values decreased significantly from baseline at the first f/u. At the second f/u, mean K and axis decreased. In HOAs, coma and trefoil increased from baseline at the first f/u and normalized by the second f/u. SA decreased at the second f/u and in G3. The various risk factors did not affect postoperative outcomes, axis, and secondary astigmatisms. After correcting for risk factors, at the first f/u, cylinder, coma, trefoil, and SA increased significantly from the baseline, while axis and flat K decreased. At the second f/u, cylinder increased, while axis and mean K decreased significantly from the baseline.

Conclusion

Epiblepharon repair surgery may impact axis changes. Flat K, coma, and trefoil may be affected by mechanical force changes immediately following surgery. Mean K and SA may change with cornea state changes during healing.
Global Effects of Feature-based Attention Depend on Surprise
Authors: Smout Cooper A. , Garrido Marta I. , Mattingley Jason B.
Published: September 2019

Recent studies have shown that prediction and attention can interact under various circumstances, suggesting that the two processes are based on interdependent neural mechanisms. In the visual modality, attention can be deployed to the location of a task-relevant stimulus (‘spatial attention’) or to a specific feature of the stimulus, such as colour or shape, irrespective of its location (‘feature-based attention’). Here we asked whether predictive processes are influenced by feature-based attention outside the current spatial focus of attention. Across two experiments, we recorded neural activity with electroencephalography (EEG) as human observers performed a feature-based attention task at fixation and ignored a stream of peripheral stimuli with predictable or surprising features. Central targets were defined by a single feature (colour or orientation) and differed in salience across the two experiments. Task-irrelevant peripheral patterns usually comprised one particular conjunction of features (standards), but occasionally deviated in one or both features (deviants). Consistent with previous studies, we found reliable effects of feature-based attention and prediction on neural responses to task-irrelevant patterns in both experiments. Crucially, we observed an interaction between prediction and feature-based attention in both experiments: the neural effect of feature-based attention was larger for surprising patterns than it was for predicted patterns. These findings suggest that global effects of feature-based attention depend on surprise, and are consistent with the idea that attention optimises the precision of predictions by modulating the gain of prediction errors.

Significance Statement

Two principal mechanisms facilitate the efficient processing of sensory information: prediction uses prior information to guide the interpretation of sensory events, whereas attention biases the processing of these events according to their behavioural relevance. A recent theory proposes to reconcile attention and prediction under a unifying framework, casting attention as a ‘precision optimisation’ mechanism that enhances the gain of prediction errors. Crucially, this theory suggests that attention and prediction interact to modulate neural responses, but this hypothesis remains to be tested with respect to feature-based attention mechanisms outside the spatial focus of attention. Here we show that global effects of feature-based attention are enhanced when stimuli possess surprising features, suggesting that feature-based attention and prediction are interdependent neural mechanisms.
Re-definition of claudin-low as a breast cancer phenotype
Authors: Fougner Christian , Bergholtz Helga , Norum Jens Henrik , Sørlie Therese
Published: September 2019

The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors were distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflected characteristics of their intrinsic subtype. Finally, we have developed an alternative method for identifying claudin-low tumors and thereby uncovered potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.

Contact information

C.F. christian.fougner@rr-research.no

H.B. helga.bergholtz@rr-research.no

J.H.N. jens.henrik.norum@rr-research.no

T.S. therese.sorlie@rr-research.no
Draft genome of the invasive coral Tubastraea sp.
Authors: Soares-Souza Giordano Bruno , Amaral Danielle , Torres André Q. , Batista Daniela , Romão-Dumaresq Aline Silva , Leomil Luciana , Uliano-Silva Marcela , Dondero Francesco , de Freitas Rebelo Mauro
Published: September 2019

Corals have been attracting huge attention due to the impact of climate change and ocean acidification on reef formation and resilience. Nevertheless, some coral species have been spreading very fast, replacing native species and affecting local biodiversity. Despite some focal efforts to understand the biology of these organisms, they remain understudied at the molecular level. This knowledge gap hinders the development of cost-effective strategies for management of invasive species. Here, we present the first Tubastraea sp. genome in one of the most comprehensive biological studies of a coral, that includes morphology, flow cytometry, karyotyping, transcriptomics, genomics, and phylogeny. The Tubastraea sp. genome is organized in 23 chromosome pairs and has 1.4 Gb making it the largest coral and Cnidaria genome sequenced to date. The hybrid assembly using short and long-reads has a N50 of 180,044 pb, 12,320 contigs and high completeness estimated as 91.6% of BUSCO complete genes. We inferred that almost half of the genome consists of repetitive elements, mostly interspersed repeats. Gene content was estimated as about 94,000, a high number that warrants deeper scrutiny. The Tubastraea sp. genome is a fundamental study which promises to provide insights not only about the genetic basis for the extreme invasiveness of this particular coral species, but to understand the adaptation flaws of some reef corals in the face of anthropic-induced environmental disturbances. We expect the data generated in this study will foster the development of efficient technologies for the management of corals species, whether invasive or threatened.
Chemical variations in Quercus pollen as a tool for taxonomic identification: implications for long-term ecological and biogeographical research
Authors: Muthreich Florian , Zimmermann Boris , Birks H. John B. , Vila-Viçosa Carlos M. , Seddon Alistair W.R
Published: September 2019

vi.

Aim

Fossil pollen is an important tool for understanding biogeographic patterns in the past, but the taxonomic resolution of the fossil-pollen record may be limited to genus or even family level. Chemical analysis of pollen grains has the potential to increase the taxonomic resolution of pollen, but present-day chemical variability is poorly understood. This study aims to investigate whether a phylogenetic signal is present in the chemical variations of Quercus L. pollen and to assess the prospects of chemical techniques for identification in biogeographic research.

Location

Portugal

Taxon

Six taxa (five species, one subspecies) of Quercus L., Q. faginea, Q. robur, Q. robur ssp. estremadurensis, Q. coccifera, Q. rotundifolia and Q. suber belonging to three sections: Cerris, Ilex, and Quercus (Denk, Grimm, Manos, Deng, & Hipp, 2017)

Methods

We collected pollen samples from 297 individual Quercus trees across a 4° (∼450 km) latitudinal gradient and determined chemical differences using Fourier-transform infrared spectroscopy (FTIR). We used canonical powered partial least-squares regression (CPPLS) and discriminant analysis to describe within- and between-species chemical variability.

Results

We find clear differences in the FTIR spectra from Quercus pollen at the section level (Cerris: ∼98%; Ilex: ∼100%; Quercus: ∼97%). Successful discrimination is based on spectral signals related to lipids and sporopollenins. However, discrimination of species within individual Quercus sections is more difficult: overall, species recall is ∼76% and species misidentifications within sections lie between 18% and 31% of the test-set.

Main Conclusions

Our results demonstrate that subgenus level differentiation of Quercus pollen is possible using FTIR methods, with successful classification at the section level. This indicates that operator-independent FTIR approaches can surpass traditional morphological techniques using the light microscope. Our results have implications both for providing new insights into past colonisation pathways of Quercus, and likewise for forecasting future responses to climate change. However, before FTIR techniques can be applied more broadly across palaeoecology and biogeography, our results also highlight a number of research challenges that still need to be addressed, including developing sporopollenin-specific taxonomic discriminators and determining a more complete understanding of the effects of environmental variation on pollen-chemical signatures in Quercus.
Neuro-Current Response Functions: A Unified Approach to MEG Source Analysis under the Continuous Stimuli Paradigm
Authors: Das Proloy , Brodbeck Christian , Simon Jonathan Z. , Babadi Behtash
Published: September 2019

Characterizing the neural dynamics underlying sensory processing is one of the central areas of investigation in systems and cognitive neuroscience. Neuroimaging techniques such as magnetoencephalography (MEG) and Electroencephalography (EEG) have provided significant insights into the neural processing of continuous stimuli, such as speech, thanks to their high temporal resolution. Existing work in the context of auditory processing suggests that certain features of speech, such as the acoustic envelope, can be used as reliable linear predictors of the neural response manifested in M/EEG. The corresponding linear filters are referred to as temporal response functions (TRFs). While the functional roles of specific components of the TRF are well-studied and linked to behavioral attributes such as attention, the cortical origins of the underlying neural processes are not as well understood. In this work, we address this issue by estimating a linear filter representation of cortical sources directly from neuroimaging data in the context of continuous speech processing. To this end, we introduce Neuro-Current Response Functions (NCRFs), a set of linear filters, spatially distributed throughout the cortex, that predict the cortical currents giving rise to the observed ongoing MEG (or EEG) data in response to continuous speech. NCRF estimation is cast within a Bayesian framework, which allows unification of the TRF and source estimation problems, and also facilitates the incorporation of prior information on the structural properties of the NCRFs. To generalize this analysis to M/EEG recordings which lack individual structural magnetic resonance (MR) scans, NCRFs are extended to free-orientation dipoles and a novel regularizing scheme is put forward to lessen reliance on fine-tuned coordinate co-registration. We present a fast estimation algorithm, which we refer to as the Champ-Lasso algorithm, by leveraging recent advances in optimization, and demonstrate its utility through application to simulated and experimentally recorded MEG data under auditory experiments. Our simulation studies reveal significant improvements over existing methods that typically operate in a two-stage fashion, in terms of spatial resolution, response function reconstruction, and recovering dipole orientations. The analysis of experimentally-recorded MEG data without MR scans corroborates existing findings, but also delineates the distinct cortical distribution of the underlying neural processes at high spatiotemporal resolution. In summary, we provide a principled modeling and estimation paradigm for MEG source analysis tailored to extracting the cortical origin of electrophysiological responses to continuous stimuli.
Genetic Basis ofDe NovoAppearance of Carotenoid Ornamentation in Bare-Parts of Canaries
Authors: Anna Gazda Małgorzata , Toomey Matthew B. , Araújo Pedro M. , Lopes Ricardo J. , Afonso Sandra , Myers Connie A. , Serres Kyla , Kiser Philip D. , Hill Geoffrey E. , Corbo Joseph C. , Carneiro Miguel
Published: September 2019

ABSTRACT

Unlike wild and domestic canaries (Serinus canaria), or any of the three dozen species of finches in genusSerinus, the domestic urucum breed of canaries exhibits bright red bills and legs. This novel bare-part coloration offers a unique opportunity to understand how leg and bill coloration evolve in birds. To identify the causative locus, we resequenced the genome of urucum canaries and performed a range of analyses to search for genotype-to-phenotype associations across the genome. We identified a nonsynonymous mutation in the geneBCO2(beta-carotene oxygenase 2, also known asBCDO2), an enzyme involved in the cleavage and breakdown of full-length carotenoids into short apocarotenoids. Protein structural models andin vitrofunctional assays indicate that the urucum mutation abrogates the carotenoid cleavage activity of BCO2. Consistent with the predicted loss of carotenoid cleavage activity, urucum canaries had increased levels of full-length carotenoid pigments in bill tissue and a significant reduction in levels of carotenoid cleavage products (apocarotenoids) in retinal tissue compared to other breeds of canaries. We hypothesize that carotenoid-based bare-part coloration might be readily gained, modified, or lost through simple switches in the enzymatic activity or regulation ofBCO2and this gene may be an important mediator in the evolution of bare-part coloration among bird species.
Null models for community dynamics: Beware of the cyclic shift algorithm
Authors: Kalyuzhny Michael
Published: September 2019

Aim

Temporal patterns of community dynamics are drawing increasing interest due to their potential to shed light on assembly processes and anthropogenic effects. However, interpreting such patterns considerably benefits from comparing observed dynamics to the reference of a null model. For that aim, the cyclic shift permutations algorithm, which generates randomized null communities based on empirically observed time series, has recently been proposed. The use of this algorithm, which shifts each species time series randomly in time, has been justified by the claim that it preserves the temporal autocorrelation of single species. Hence it has been used to test the significance of various community patterns, in particular excessive compositional changes, biodiversity trends and community stability.

Innovation

Here we critically study the properties of the cyclic shift algorithm for the first time. We show that, unlike previously suggested, this algorithm does not preserve temporal autocorrelation due to the need to “wrap” the time series and assign the last observations to the first years. Moreover, this algorithm scrambles the initial state of the community, making any dynamics that results from deviations from equilibrium seem excessive. We exemplify that these two issues lead to a highly elevated type I error rate in tests for excessive compositional changes and richness trends.

Conclusions

Caution is needed when using the cyclic shift permutation algorithm and interpreting results obtained using it. Interpretation is further complicated because the algorithm removes all correlations between species. We suggest guidelines for using this method and discuss several possible alternative approaches. More research is needed on the best practices for using null models for temporal patterns.
Differences in the chitinolytic activity of mammalian chitinases on soluble and crystalline substrates
Authors: Barad Benjamin A. , Liu Lin , Diaz Roberto Efrain , Basilio Ralp , Van Dyken Steven J. , Locksley Richard M. , Fraser James S.
Published: September 2019

Chitin is an abundant polysaccharide used by a large range of organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Vertebrates do not produce chitin, but do express chitin degrading enzymes. Acidic mammalian chitinase, the primary enzyme involved in the degradation of environmental chitin in mammalian lungs, is a processive glycosyl hydrolase that may be able to make multiple hydrolysis events for each binding event. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion of the enzyme in mice results in significantly increased morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a directed evolution screening approach using commercial fluorogenic substrates, we identified mutations with consistent increases in activity. To determine whether the activity increases observed with oligomeric substrates were consistent with more biologically relevant chitin substrates, we developed new assays to quantify chitinase activity with colloidal crystalline chitin, and identified a high throughput fluorogenic assay that gives sufficient signal to noise advantages to quantify changes to activity due to the addition or removal of a chitin binding domain to the enzyme. We show that the activity increasing mutations derived from our directed evolution screen were lost when crystalline substrates were used. In contrast, naturally occurring gain-of-function mutations gave similar results with oligomeric and crystalline substrates. We also show that the activity differences between acidic mammalian chitinase and chitotriosidase are reduced in the context of crystalline substrate, suggesting that previously reported activity differences with oligomeric substrates may have been largely driven by differential substrate specificity for the oligomers. These results highlight the need for assays against more physiological substrates when engineering complex metabolic enzymes, and provide a new approach that may be broadly applicable to engineering glycosyl hydrolases.
Integrated evolutionary and structural analysis reveals xenobiotics and pathogens as the major drivers of mammalian adaptation
Authors: Slodkowicz Greg , Goldman Nick
Published: September 2019

Understanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our integrative analysis shows that positively selected sites tend to co-localise on protein structures and that positively selected clusters are found in functionally important regions of proteins, indicating that positive selection can contravene the well-known principle of evolutionary conservation of functionally important regions. This unexpected finding, along with our discovery that positive selection acts on structural clusters, opens new strategies for the development of better models of protein evolution. Remarkably, proteins where we detect the strongest evidence of clustering belong to just two functional groups: components of immune response and metabolic enzymes. This gives a coherent picture of immune response and xenobiotic metabolism as the drivers of adaptive evolution of mammals.
Early pathological signs in youngdysf−/−mice are improved by halofuginone
Authors: Barzilai-Tutsch Hila , Genin Olga , Pines Mark , Halevy Orna
Published: September 2019

Dysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from youngdysf−/−mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-weekolddysf−/−mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-olddysf−/−mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and better generation of force and muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life.
AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB
Authors: Preciado-Llanes Lorena , Aulicino Anna , Canals Rocío , Moynihan Patrick , Zhu Xiaojun , Jambo Ndaru , Nyirenda Tonney , Kadwala Innocent , Owen Siân V. , Veerapen Natacha , Besra Gurdyal S. , Gordon Melita A. , Hinton Jay C. D. , Napolitani Giorgio , Salio Mariolina , Simmons Alison
Published: September 2019

Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defence. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with a selective absence of MAIT cells have not been identified. We report that typhoidal and non-typhoidalS. entericastrains generally activate MAIT cells. However, African invasive disease-associated multidrug-resistantS.Typhimurium sequence type 313 lineage 2 strains escape MAIT cell recognition through overexpression ofribB, a bacterial gene that encodes the 4-dihydroxy-2-butanone 4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. This MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose thatribBoverexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis ofS.Typhimurium sequence type 313 lineage 2in vivo.
A unified simulation model for understanding the diversity of cancer evolution
Authors: Niida Atsushi , Hasegawa Takanori , Innan Hideki , Shibata Tatsuhiro , Mimori Koshi , Miyano Satoru
Published: September 2019

Because cancer evolution underlies the therapeutic difficulties of cancer, it is clinically important to understand the evolutionary dynamics of cancer. Thus far, a number of evolutionary processes have been proposed to be working in cancer evolution. However, there exists no simulation model that can describe the different evolutionary processes in a unified manner. In this study, we constructed a unified simulation model for describing the different evolutionary processes and performed sensitivity analysis on the model to determine the conditions in which cancer growth is driven by each of the different evolutionary processes. Our sensitivity analysis has successfully provided a series of novel insights into the evolutionary dynamics of cancer. For example, we found that, while a high neutral mutation rate shapes neutral intratumor heterogeneity (ITH) characterized by a fractal-like pattern, a stem cell hierarchy can also contribute to shaping neutral ITH by apparently increasing the mutation rate. Although It has been reported that the evolutionary principle shaping ITH shifts from selection to accumulation of neutral mutations during colorectal tumorigenesis, our simulation revealed the possibility that this evolutionary shift is triggered by drastic evolutionary events that occur in a a short time and confer a marked fitness increase on one or a few cells. This result helps us understand that each process works not separately but simultaneously and continuously as a series of phases of cancer evolution. Collectively, this study serves as a basis to understand in greater depth the diversity of cancer evolution.
Accuracy of serological tests for diagnosis of chronic pulmonary aspergillosis: a systematic review and meta-analysis
Authors: Chaves Cláudia Elizabeth Volpe , do Valle Leone de Oliveira Sandra Maria , Venturini James , Grande Antonio Jose , Sylvestre Tatiane Fernanda , Mendes Rinaldo Poncio , Paniago Anamaria Mello Miranda
Published: September 2019

Chronic pulmonary aspergillosis (CPA) is a disease that benefits from cavities as after-effects of tuberculosis, presenting a high mortality rate. Serological tests like double agar gel immunodiffusion test (DID) or the counterimmunoelectrophoresis (CIE) test have been routinely used for CPA diagnosis in the absence of positive cultures; however, they have been replaced by enzyme-linked immunoassay (ELISA), with a variety of methods.

This systematic review aims to compare the accuracy of the ELISA test with the reference test (DID and/or CIE) in CPA diagnosis. It was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA).

The study was registered in PROSPERO under the registration number CRD42016046057. We searched the electronic databases MEDLINE (PubMed), EMBASE (Elsevier), LILACS (VHL), Cochrane library, and ISI Web of Science. Gray literature was researched in Google Scholars and conference abstracts. We included articles with patients or serum samples from CPA patients who underwent two serological tests: ELISA (index test) and IDD and/or CIE (reference test), using the accuracy of the tests as a result. Original articles were considered without a restriction of date or language. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated.

We included 13 studies in the review, but only four studies were included in the meta-analysis. The pooled sensitivities and specificities were 0.93 and 0.97 for the ELISA test. For the reference test (DID and/or CIE), these values were 0.64 and 0.99. Analyses of summary receiver operating characteristic curves yielded 0.99 for ELISA and 0.99 for the reference test (DID and/or CIE). Our meta-analysis suggests that the diagnostic accuracy of ELISA is greater than that of the reference tests (DID and/or CIE) in early detection of CPA.
Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure
Authors: Heinla Indrek , Heijkoop Roy , Houwing Danielle J. , Olivier Jocelien D.A. , Snoeren Eelke M.S.
Published: September 2019

SSRIs are commonly used to treat pregnant women with depression. However, SSRIs can cross the placenta and affect the development of the fetus. The effects of perinatal SSRI exposure, and especially the effects on social behavior, are still incompletely documented. This study first aims to investigate whether rats show prosocial behavior in the form of consolation behavior. Secondly, it aims to investigate whether perinatal SSRI exposure affects this prosocial behavior. At last, we investigate whether the behavior changed after the rats had been exposed to an additional white-noise stressor.

Rat dams received 10 mg/kg/d fluoxetine (FLX) or vehicle (CTR) via oral gavage from gestational day 1 until postnatal day 21. At adulthood, the rat offspring were housed in four cohorts of 4 females and 4 males in a seminatural environment. As prosocial behaviors are more prominent after stressful situations, we investigated the behavioral response of rats immediately after natural aggressive encounters (fights). Additionally, we studied whether a stressful white-noise exposure would alter this response to the aggressive encounters.

Our study indicates that CTR-female rats are able to show third party prosocial behavior in response to witnessing aggressive encounters between conspecifics in a seminatural environment. In addition, we showed that perinatal FLX exposure impairs the display of prosocial behavior in female rats. Moreover, we found no signs of prosocial behavior in CTR- and FLX-males after natural aggressive encounters. After white-noise exposure the effects in third party prosocial behavior of CTR-females ceased to exist. We conclude that female rats are able to show prosocial behavior, possibly in the form of consolation behavior. In addition, the negative effects of perinatal fluoxetine exposure on prosocial behavior could provide additional evidence that SSRI treatment during pregnancy could contribute to the risk for social impairments in the offspring.