bluuebunny/crossref_metadata_2025 huggingface dataset:
E-Cigarette Dependence in Youth
Authors: Pienkowski Martha , Chaiton Michael , Dubray Jolene , Schwartz Robert
Published: December 2021

Introduction

The majority of e-cigarette vaping youth use nicotine when vaping. Some then become dependent on the nicotine, which can result in subsequent health effects. There has been limited evaluation of convergent validity of e-cigarette dependence measures for use specifically in youth. The aim of this study was to investigate and validate various e-cigarette dependence measures for use in youth populations.

Aims and Methods

One thousand two hundred and five Canadian youth aged 16–24 who completed a cross-sectional online survey reported vaping at least monthly and were thus included in the analysis. E-cigarette dependence was assessed using a modified Penn State Electronic Cigarette Dependence Index (PS-ECDI), the E-Cigarette Dependence Scale (EDS), a self-perceived vaping dependence question, and time to first vape after waking. Internal consistency, convergent validity, and concurrent validity of the measures were assessed.

Results

Both the PS-ECDI and the EDS exhibited a good degree of internal consistency (α = 0.8472 and 0.8405, respectively). All measures exhibited convergent validity against each other and against time to first vape upon waking (p < .001), as well as concurrent validity against vaping frequency and nicotine concentration (p < .001). The PS-ECDI was inferior to the EDS, self-perceived measure, and time from waking when predicting daily vaping frequency, but, along with the self-perceived measure, was superior to the EDS and time from waking when predicting monthly vaping.

Conclusions

All measures exhibit convergent and concurrent validity, as well as internal consistency. Depending on the needs of the study, it would be appropriate to use any of these measures when assessing e-cigarette dependence in adolescent and young-adult populations.

Implications

The PS-ECDI and the self-perceived measure are equally effective in predicting monthly vaping, but the self-perceived measure was superior in predicting daily vaping. Thus, the one-item self-perceived measure of dependence is appropriate for use and preferable to the 11-item PS-ECDI or the 4-item EDS in situations of limited time or where subjects are at risk of respondent fatigue, and is superior to time to first vape after waking to predict vaping frequency.
Density-functional theory of material design: fundamentals and applications-I
Authors: Singh Prashant , Harbola Manoj K
Published: December 2021

This article is part-I of a review of density-functional theory (DFT) that is the most widely used method for calculating electronic structure of materials. The accuracy and ease of numerical implementation of DFT methods has resulted in its extensive use for materials design and discovery and has thus ushered in the new field of computational material science. In this article, we start with an introduction to Schrödinger equation and methods of its solutions. After presenting exact results for some well-known systems, difficulties encountered in solving the equation for interacting electrons are described. How these difficulties are handled using the variational principle for the energy to obtain approximate solutions of the Schrödinger equation is discussed. The resulting Hartree and Hartree–Fock theories are presented along with results they give for atomic and solid-state systems. We then describe Thomas–Fermi theory and its extensions which were the initial attempts to formulate many-electron problem in terms of electronic density of a system. Having described these theories, we introduce modern DFT by discussing Hohenberg–Kohn theorems that form its foundations. We then go on to discuss Kohn–Sham (KS) formulation of DFT in its exact form. Next, local density approximation (LDA) is introduced and solutions of KS equation for some representative systems, obtained using the LDA, are presented. We end part-I of the review describing the contents of part-II.
Physical Therapists' Knowledge, Skills, Beliefs, and Organizations Impact Physical Activity Promotion: A Systematic Review and Meta-Analysis
Authors: Rethorn Zachary D , Covington J Kyle , Cook Chad E , Bezner Janet R
Published: December 2021

Objective

The purpose of this study was to characterize factors that influence physical therapists’ physical activity (PA) promotion practices and map these factors to the Theoretical Domains Framework (TDF) to inform future implementation efforts.

Methods

Six databases (MEDLINE, EMBASE, Scopus, CINAHL, PsychInfo, and Web of Science) were searched from inception to March 11, 2021. Studies were included if they reported physical therapists’ PA promotion practices and factors influencing these practices. Study quality was assessed with a modified Newcastle-Ottawa Scale and the Critical Appraisal Skills Programme checklist. Studies were excluded if they did not separate physical therapist PA promotion practices and influencing factors from other health professionals.

Results

The search yielded 12,835 references and 27 included studies. Twenty studies were included in a meta-analysis of proportions, whereas 15 studies were included in a meta-analysis of correlations. Very-low to moderate-quality evidence suggests that factors at the individual and organizational levels have very small to moderate associations with PA promotion practices.

Conclusion

Efforts to improve PA promotion by physical therapists should consider incorporating combinations of individual and organizational factors. Limitations to the body of evidence highlight the need for future research.

Impact

With PA projected to decrease in the general population by an additional 20% by 2050, PA promotion is urgently needed to maximize physical therapists’ impact on the health of society. This study identifies factors that may prove useful for guiding the development of strategies to encourage greater engagement in PA promotion by physical therapists.
Finance Leases: In the Shadow of Banks
Authors: Chang Jeffery (Jinfan) , Yang Ting , Shi Yanping
Published: December 2021

By analyzing a hand-collected transaction-level dataset on the finance leases of China’s public firms for the period 2007–19, this article sheds light on China’s leasing market, the second largest in the world. We find that banks use their affiliated leasing firms to provide credit to clients in order to circumvent the government’s targeted credit tightening policy. In contrast to conventional view of regulatory arbitrage, our evidence shows that, rather than hiding risk and gambling for profit, banks-affiliated leasing firms have prudent risk control and efficient pricing. These bank-affiliated institutions are used by banks to play strategic role in relationship banking. Moreover, the ownership of the lessor also matters for the financing choice of the lessee.
Medial Plating in Open Pilon Fractures May Be Indicated in the Right Patient
Authors: Haller Justin
Published: December 2021

Clinical vignette:

A 55-year-old retired overweight male contractor with controlled type 2 diabetes is performing repairs on his barn when he slips and falls from a ladder. He catches his foot in the rungs and sustains a type 2 open pilon fracture with metaphyseal comminution (OTA/AO 43-C family) and an associated fibula fracture. The 6-cm open wound is located medially and is contaminated with clothing but not the surrounding environment. One of your partners performs a thorough surgical debridement, is able to close the wound, and applies a spanning ankle external fixator and asks you to care for the patient to provide a definitive operation. Please argue for and against inclusion of a medially based plate in the fixation construct through the open wound at the time of definitive fixation.
Rovalpituzumab tesirine resistance: analysis of a corresponding small cell lung cancer and circulating tumor cell line pair
Authors: Rath Barbara , Plangger Adelina , Krenbek Dagmar , Hochmair Maximilian , Stickler Sandra , Tretter Verena , Hamilton Gerhard
Published: December 2021

Small cell lung cancer (SCLC) is frequently found disseminated at first presentation and holds a poor prognosis due to emerging resistance to first-line platinum-based and second-line topotecan chemotherapy. The present investigation tested the antitumor activity of rovalpituzumab tesirine (ROVA-T), a cytotoxic anti-DLL3 drug conjugate, against two SCLC and a corresponding SCLC CTC cell line established from a ROVA-T-resistant patient to characterize the mechanism of recurrence. Two cell lines were established from an SCLC patient progressing under ROVA-T therapy and characterized with respect to chemosensitivity against this drug as well as against currently applied chemotherapeutics and for their delta-like 3 (DLL3) expression. The chemosensitivity assays demonstrate that most SCLC lines show IC50 values exceeding the ROVA-T in-vivo concentrations and that slow-growing cells and lines showing spheroidal growth or proliferation as corresponding circulating tumor cells (CTCs) exhibit higher resistance. Chemosensitivity of the cell lines is not correlated with DLL3 protein expression possibly due to toxicity of the free payload in tissue culture. The clinical trials and experimental results demonstrate that refractoriness to ROVA-T is linked to a low initial tumor expression of DLL3, loss of DLL3 expression, higher chemoresistance to ROVA-T and the putative formation of resistant spheroids by the SCLC cells.
Estimating long-term average household air pollution concentrations from repeated short-term measurements in the presence of seasonal trends and crossover
Authors: Keller Joshua P. , Clark Maggie L.
Published: December 2021

Estimating long-term exposure to household air pollution is essential for quantifying health effects of chronic exposure and the benefits of intervention strategies. However, typically only a small number of short-term measurements are made. We compare different statistical models for combining these short-term measurements into predictions of a long-term average, with emphasis on the impact of temporal trends in concentrations and crossover in study design. We demonstrate that a linear mixed model that includes time adjustment provides the best predictions of long-term average, which have lower error than using household averages or mixed models without time, for a variety of different study designs and underlying temporal trends. In a case study of a cookstove intervention study in Honduras, we further demonstrate how, in the presence of strong seasonal variation, long-term average predictions from the mixed model approach based on only two or three measurements can have less error than predictions based on an average of up to six measurements. These results have important implications for the efficiency of designs and analyses in studies assessing the chronic health impacts of long-term exposure to household air pollution.
Iris Atrophy After Administration of Intracameral Dexycu in Routine Cataract Surgery: A Case Series
Authors: Bergman Zachary , Thompson Ryan , Malouf Alan , Swamy Ramya
Published: December 2021

Dexycu (Icon Bioscience INC, Newark, CA) is an FDA-approved single-dose, sustained release intracameral steroid designed to mitigate postoperative inflammation after cataract surgery as an alternative to topical steroid therapy. The purpose of this study was to look at long-term and adverse events associated with Dexycu use. Eighteen eyes from nine patients who underwent cataract surgery were included. Patients were followed for an average of 97 days (range 28–319 days) after surgery on the first eye. Thirteen eyes were treated with Dexycu, and the other five eyes were treated with standard postoperative anti-inflammatory drops. Four of the thirteen eyes receiving Dexycu developed clinically evident iris atrophy (30.7%). None of the five eyes treated with traditional anti-inflammatory drops developed iris atrophy. The Dexycu intraocular dexamethasone implant was designed to mitigate postoperative inflammation and reduce need for topical therapy but may be associated with other potential adverse effects that warrant consideration.
A clinical tool to predict severe pain during wound dressing changes
Authors: Gardner Sue E. , Bae Jaewon , Ahmed Bootan H. , Abbott Linda I. , Wolf Jessica S. , Hein Maria , Carter Cheryl , Hillis Stephen L. , Tandy LuAnn M. , Rakel Barbara A.
Published: December 2021

Dressing changes cause severe pain (ie, 8-10 on a 10-point scale) for approximately one-third (36%) of patients with open skin wounds. No tool exists that allows nurses to predict which patients are likely to experience severe pain during dressing changes. The aim of this study was to develop a clinical tool to predict severe pain during dressing changes using clinically accessible wound and pain predictors and to evaluate the diagnostic validity of this model. Using a cross-sectional design, a one-time study dressing change was conducted by the same wound care nurse on 445 subjects while concurrently measuring patient and wound predictors and pain intensity during the dressing change. Three predictors came out of the study as most useful for a clinical prediction tool: type of dressing, resting wound pain, and expected pain. Algorithms based on these predictors are presented, which can be applied in other settings to predict patients likely to experience severe pain during a dressing change. This is the first study to systematically examine a comprehensive set of wound and patient predictors for their individual and collective associations with pain during dressing changes using precisely defined and rigorously measured study variables. The ability to predict which patients are likely to have severe pain during dressing changes is critically needed so that they can be targeted for preventive pain control strategies.
Cognitive biases among those with frequent or chronic headaches or migraines: a systematic review and meta-analysis
Authors: O'Hara Robert , Sharpe Louise , Todd Jemma
Published: December 2021

The aim of this systematic review and meta-analysis was to determine the pattern of cognitive processing biases (ie, attentional, interpretation, and memory bias) towards headache and pain information observed in individuals with frequent or chronic headaches or migraines, compared with individuals without. We identified 11 studies (total N = 841). Most studies (10 of 11) assessed attentional bias. For reaction time–based attentional bias (k = 8), significant group differences were observed, with small (500 ms; g = 0.200) to medium (≥ 1000 ms; g = 0.544) effects. Those with chronic headaches showed an absolute attentional bias towards headache and pain information. In 2 eye-tracking studies, both found significant medium-to-large group differences on initial orientation. Interpretation and memory bias research was also reviewed. A medium-to-large effect was found for interpretation bias (k = 2; g = 0.708), whereas the effect for recall memory bias (k = 3) was not significant. Overall, the findings confirm an attentional bias for headache-related stimuli among people with headache, with some evidence for interpretation bias but equivocal evidence for a memory bias. For attentional biases, eye-tracking studies found evidence for biases in initial orienting. We provide suggestions for how to extend the current research to better understand cognitive biases in chronic headache.
Pain mechanisms in carpal tunnel syndrome: a systematic review and meta-analysis of quantitative sensory testing outcomes
Authors: Sobeeh Mohamed G. , Ghozy Sherief , Elshazli Rami M. , Landry Marc
Published: December 2021

Carpal tunnel syndrome (CTS) is the most common nerve compression in the arm. A mix of peripheral and central contributions on quantitative sensory testing (QST) has been reported in the literature. Thus, this systematic review or meta-analysis aimed to identify the dominant sensory phenotype and draw conclusive evidence about the presence of central sensitization (CS) in CTS. Based on an a priori published protocol and using PRISMA guidelines, 7 databases were searched (Embase, Web of Science, Scopus, PubMed, SAGE, EBSCOhost, and ProQuest). Eligible studies compared the QST findings of individuals with subacute and chronic CTS with those of healthy controls through thermal, mechanical, and vibration detection thresholds; thermal, pressure, and mechanical pain thresholds; mechanical pain sensitivity; presence of allodynia; wind-up ratio; and conditioned pain modulation. Thirty-seven studies were included in the qualitative analysis. Results showed a significant loss of all detection thresholds of hand median nerve territories and hand extramedian areas (little finger and hand dorsum) in CTS (P < 0.05) but no significant difference (P > 0.05) in wind-up ratio, cold, heat, or mechanical pain thresholds of the median nerve territories. Furthermore, there was a significant increase in mechanical pain sensitivity in median nerve territories and remotely in the forearm (P < 0.05) and a significant gain in pressure and heat pain thresholds in the carpal area (P < 0.05). Conditioned pain modulation was impaired in CTS. Hypoesthesia and increased thermal and mechanical pain ratings are the dominant sensory phenotype with inconclusive evidence about CS in CTS due to the heterogenous results of thermal and mechanical pain thresholds.
Liver Transplantation for Hepatitis D Virus in the United States: A UNOS Study on Outcomes in the MELD Era
Authors: Kushner Tatyana , Da Ben L. , Chan Aryana , Dieterich Douglas , Sigel Keith , Saberi Behnam
Published: December 2021

Background.

Without available curative therapies for delta hepatitis (hepatitis delta virus [HDV]), hepatic decompensation and hepatocellular carcinoma (HCC) among HDV patients often necessitates liver transplantation (LT). The objective of this study was to evaluate outcomes of LT among hepatitis B virus (HBV)/HDV patients in the United States.

Methods.

We performed the first US-based retrospective study of patients who underwent LT for HDV compared with HBV (monoinfection) in the years 2002–2019. We evaluated posttransplant survival and predictors of survival.

Results.

We identified a total of 152 HBV/HDV and 5435 HBV patients who underwent LT. HDV patients were younger at transplant (52 versus 55, P < 0.001), less commonly Asian (16% versus 36%, P < 0.001), more likely to be HCV Ab positive (42% versus 28%, P < 0.001), and less likely to be listed for LT with HCC (38% versus 51%, P = 0.001), more likely to have ascites (73% versus 64%, P = 0.019), had worse coagulopathy (mean INR 2.0 versus 1.82, P = 0.04), and were more likely to receive a HCV-positive donor organ (7% versus 3%, P = 0.001). Post-LT overall survival and graft survival were similar between HDV and HBV patients, including among patients with HCC. Older age, HCV coinfection, HCC, and higher model for end-stage liver disease at transplant were associated with higher posttransplant mortality.

Conclusions.

HDV patients were sicker and more likely to be listed for LT for decompensated disease compared with HBV patients. Post-LT survival was similar between HDV and HBV patients, in contrast to prior international studies that suggested worse post-LT survival in HBV patients due to higher rates of HBV reactivation.
Nocardioides donggukensis sp. nov. and Hyunsoonleella aquatilis sp. nov., isolated from Jeongbang Waterfall on Jeju Island
Authors: Kim Inhyup , Chhetri Geeta , Kim Jiyoun , Kang Minchung , So Yoonseop , Lee Byungjo , Jang Wonhee , Seo Taegun
Published: December 2021

Two bacterial strains, designated MJB4T and SJ7T, were isolated from water samples collected from Jeongbang Falls on Jeju Island, Republic of Korea. Phylogenetic analysis of 16S rRNA gene sequences indicated that the two strains belonged to the genera

Nocardioides

and

Hyunsoonleella

, owing to their high similarities to

Nocardioides jensenii

DSM 29641T (97.5 %) and

Hyunsoonleella rubra

FA042 T (96.3 %), respectively. These values are much lower than the gold standard for bacterial species (98.7 %). The average nucleotide identity values between strains MJB4T, SJ7T and the reference strains,

Nocardioides jensenii

DSM 29641T,

Nocardioides daejeonensis

MJ31T and

Hyunsoonleella flava

T58T were 77.2, 75.9 and 75.4 %, respectively. Strains MJB4T and SJ7T and the type strains of the species involved in system incidence have average nucleotide identity and average amino acid threshold values of 60.1–82.6 % for the species boundary (95–96 %), which confirms that strains MJB4T and SJ7T represent two new species of genus

Nocardioides

and

Hyunsoonleella

, respectively. Based on phylogenetic and phenotypic data, strains MJB4T and SJ7T are considered to represent novel species of the genus

Nocardioides

and

Hyunsoonleella

, respectively, for which the names Nocardioides donggukensis sp. nov. (type strain MJB4T=KACC 21724T=NBRC 114402T) and Hyunsoonleella aquatilis sp. nov., (type strain SJ7T=KACC 21715T=NBRC 114486T) have been proposed.
A variety of highly divergent eukaryotic ssDNA viruses in sera of pigs
Authors: Tochetto Caroline , Cibulski Samuel Paulo , Muterle Varela Ana Paula , Cerva Cristine , Alves de Lima Diane , Fumaco Teixeira Thais , Quoos Mayer Fabiana , Roehe Paulo Michel
Published: December 2021

Over the last decade, viral metagenomics has been established as a non-targeted approach for identifying viruses in stock animals, including pigs. This has led to the identification of a vast diversity of small circular ssDNA viruses. The present study focuses on the investigation of eukaryotic circular Rep-encoding single-stranded (CRESS) DNA viral genomes present in serum of commercially reared pigs from southern Brazil. Several CRESS DNA viral genomes were detected, including representatives of the families Smacoviridae (n=5), Genomoviridae (n=3), Redondoviridae (n=1), Nenyaviridae (n=1) and other yet unclassified genomes (n=9), plus a circular DNA molecule, which probably belongs to the phylum Cressdnaviricota. A novel genus within the family Smacoviridae, tentatively named ‘Suismacovirus’, comprising 21 potential new species, is proposed. Although the reported genomes were recovered from pigs with clinical signs of respiratory disease, further studies should examine their potential role as pathogens. Nonetheless, these findings highlight the diversity of circular ssDNA viruses in serum of domestic pigs, expand the knowledge on CRESS DNA viruses’ genetic diversity and distribution and contribute to the global picture of the virome of commercially reared pigs.
Position-specific secondary acylation determines detection of lipid A by murine TLR4 and caspase-11
Authors: Harberts Erin M. , Grubaugh Daniel , Akuma Daniel C. , Shin Sunny , Ernst Robert K. , Brodsky Igor E.
Published: December 2021

Immune sensing of the Gram-negative bacterial membrane glycolipid lipopolysaccharide (LPS) is both a critical component of host defense against Gram-negative bacterial infection, and a contributor to hyper-inflammatory response, leading to sepsis and death. Innate immune activation by LPS is due to the lipid A moiety, an acylated di-glucosamine molecule that can activate inflammatory responses via the extracellular sensor TLR4/MD2 or the cytosolic sensor caspase-11 (Casp11). The number and length of acyl chains present on bacterial lipid A structures vary across bacterial species and strains, which affects the magnitude of TLR4 and Casp11 activation. TLR4 and Casp11 are thought to respond similarly to various lipid A structures, as tetra-acylated lipid A structures do not activate either sensor, whereas hexa-acylated structures activate both sensors. However, direct analysis of extracellular and cytosolic responses to the same sources and preparations of LPS/lipid A structures have been limited, and the precise features of lipid A that determine the differential activation of each receptor remain poorly defined. To address this question, we used rationally engineered lipid A isolated from a series of bacterial acyl-transferase mutants that produce novel, structurally defined molecules. Intriguingly, we find that the location of specific secondary acyl chains on lipid A resulted in differential recognition by TLR4- or Casp11, providing new insight into the structural features of lipid A required to activate either TLR4- or Casp11. Our findings indicate that TLR4 and Casp11 sense non-overlapping areas of lipid A chemical space, thereby constraining the ability of Gram-negative pathogens to evade innate immunity.
A self-generated Toddler gradient guides mesodermal cell migration
Authors: Stock Jessica , Kazmar Tomas , Schlumm Friederike , Hannezo Edouard , Pauli Andrea
Published: December 2021

The sculpting of germ layers during gastrulation relies on coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by the uniformly expressed and secreted protein Toddler/ELABELA/Apela, acting as a self-generated gradient. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor-based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.

One sentence summary

Aplnr has a dual role to self-generate and sense a Toddler gradient directing mesodermal cells during zebrafish gastrulation.
Loss of Depalmitoylation Exaggerates Synaptic Upscaling and Leads to Neuroinflammation in a Lysosomal Storage Disease
Authors: Koster Kevin P , Flores-Barrera Eden , de la Villarmois Emilce Artur , Nguyen Thu T. A. , Niqula Amanda , Noriega-González Lorena Y , Fyke Zach , Caballero Adriana , Cologna Stephanie M. , Tseng Kuei Y. , Yoshii Akira
Published: December 2021

Palmitoylation and depalmitoylation are the dichotomic processes of lipid modification regulating protein trafficking, recycling, and degradation, thereby controlling proteostasis. Despite our understanding of palmitoylation, depalmitoylation is far less studied. Here, we study a lysosomal depalmitoylating enzyme, palmitoyl-protein thioesterase 1 (PPT1), associated with the devastating neurodegenerative condition CLN1 disease and show that dark-rearing Ppt1-/- mice, which induces synaptic upscaling in vivo, worsen the symptoms. In Ppt1-/- cortical neurons, upscaling induction triggers exaggerated responses of synaptic calcium-permeable AMPA receptors composed of palmitoylated GluA1 subunits. Consequently, Ppt1-/- visual cortex exhibits hypersynchrony in vivo. Remarkably, we also find an overload of palmitoylated A-kinase anchor protein 5 (Akap5) in Ppt1-/- mouse brains, leading to microglial activation through NFAT. These findings indicate Ppt1 acts as a gatekeeper of homeostatic plasticity by regulating the proteostasis of palmitoylated synaptic proteins. Moreover, our results suggest that perturbed depalmitoylation results in neuroinflammation, which is common to neurodegenerative diseases.
Towards a global perspective for Salvia L: Phylogeny, diversification, and floral evolution
Authors: Moein Fatemeh , Jamzad Ziba , Rahiminejad Mohammadreza , Landis Jacob B. , Mirtadzadini Mansour , Soltis Douglas E. , Soltis Pamela S.
Published: December 2021

Premise of this study

Salvia is the most species-rich genus in Lamiaceae, encompassing approximately 1000 species distributed all over the world. We sought a new evolutionary perspective for Salvia by employing macroevolutionary analyses to address the tempo and mode of diversification. To study the association of floral traits with speciation and extinction, we modeled and explored the evolution of corolla length and the lever-mechanism pollination system across our Salvia phylogeny.

Methods

We reconstructed a multigene phylogeny for 366 species of Salvia in the broad sense including all major recognized lineages and numerous species from Iran, a region previously overlooked in studies of the genus. Our phylogenetic data in combination with divergence time estimates were used to examine the evolution of corolla length, woody vs. herbaceous habit, and presence vs. absence of a lever mechanism. We investigated the timing and dependence of Salvia diversification related to corolla length evolution through a disparity test and BAMM analysis. A HiSSE model was used to evaluate the dependency of diversification on the lever-mechanism pollination system in Salvia.

Key Results

Based on recent investigations and classifications, Salvia is monophyletic and comprises ∼1000 species. Our inclusion, for the first time, of a comprehensive sampling for Iranian species of Salvia provides higher phylogenetic resolution for southwestern Asian species than obtained in previous studies. A medium corolla length (15-18mm) was reconstructed as the ancestral state for Salvia with multiple shifts to shorter and longer corollas. Macroevolutionary model analyses indicate that corolla length disparity is high throughout Salvia evolution, significantly different from expectations under a Brownian motion model during the last 28 million years of evolution. Our analyses show evidence of a higher diversification rate of corolla length for some Andean species of Salvia compared to other members of the genus. Based on our tests of diversification models, we reject the hypothesis of a direct effect of the lever mechanism on Salvia diversification.

Conclusions

Using a broader species sampling than previous studies, we obtained a well- resolved phylogeny for southwest Asian species of Salvia. Corolla length is an adaptive trait throughout the Salvia phylogeny with a higher rate of diversification in the South American clade. Our results suggest caution in considering the lever-mechanism pollination system as one of the main drivers of speciation in Salvia.
Evolutionary traits of Tick-borne encephalitis virus: Pervasive non-coding RNA structure conservation and molecular epidemiology
Authors: Kutschera Lena S. , Wolfinger Michael T.
Published: December 2021

Tick-borne encephalitis virus (TBEV) is the etiological agent of tick-borne encephalitis, an infectious disease of the central nervous system that is often associated with severe sequelae in humans. While TBEV is typically classified into three subtypes, recent evidence suggests a more varied range of TBEV subtypes and lineages that differ substantially in the architecture of their 3’ untranslated region (3’UTR). Building on comparative genomics approaches and thermodynamic modelling, we characterize the TBEV UTR structureome diversity and propose a unified picture of pervasive non-coding RNA (ncRNA) structure conservation. Moreover, we provide an updated phylogeny of TBEV, building on more than 220 publicly available complete genomes, and investigate the molecular epidemiology and phylodynamics with Nextstrain, a web-based visualization framework for real-time pathogen evolution.
Variation in the transcriptome response and detoxification gene diversity drives pesticide tolerance in fishes
Authors: Lawrence M.J. , Grayson P. , Jeffrey J.D. , Docker M.F. , Garroway C.J. , Wilson J.M. , Manzon R.G. , Wilkie M.P. , Jeffries K.M.
Published: December 2021

Pesticides are critical for invasive species management, but often have negative effects on non-target native biota. Tolerance to pesticides should have an evolutionary basis, but this is poorly understood. Invasive sea lamprey (Petromyzon marinus) populations in North America have been controlled with a pesticide lethal to them at lower concentrations than native fishes. We addressed how interspecific variation in gene expression and detoxification gene diversity confer differential pesticide sensitivity in two fish species. We exposed sea lamprey and bluegill (Lepomis macrochirus), a tolerant native species, to TFM, a pesticide commonly used in sea lamprey control, and used whole-transcriptome sequencing of gill and liver to characterize the cellular response. Comparatively, bluegill exhibited a larger number of detoxification genes expressed and a larger number of responsive transcripts overall, which likely contributes to greater tolerance to TFM. Understanding the genetic and physiological basis for pesticide tolerance is crucial for managing invasive species.
LTBP1 promotes fibrillin incorporation into the extracellular matrix
Authors: Przyklenk Matthias , Georgieva Veronika S. , Metzen Fabian , Mostert Sebastian , Kobbe Birgit , Sengle Gerhard , Brachvogel Bent , Mecham Robert P. , Paulsson Mats , Wagener Raimund , Koch Manuel , Schiavinato Alvise
Published: December 2021

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillinmicrofibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and −2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.
Multi-omics subtyping of hepatocellular carcinoma patients using a Bayesian network mixture model
Authors: Suter Polina , Dazert Eva , Kuipers Jack , Ng Charlotte K.Y. , Boldanova Tuyana , Hall Michael N. , Heim Markus H. , Beerenwinkel Niko
Published: December 2021

Comprehensive molecular characterization of cancer subtypes is essential for predicting clinical outcomes and searching for personalized treatments. We present bnClustOmics, a statistical model and computational tool for multi-omics unsupervised clustering, which serves a dual purpose: Clustering patient samples based on a Bayesian network mixture model and learning the networks of omics variables representing these clusters. The discovered networks encode interactions among all omics variables and provide a molecular characterization of each patient subgroup. We conducted simulation studies that demonstrated the advantages of our approach compared to other clustering methods in the case where the generative model is a mixture of Bayesian networks. We applied bnClustOmics to a hepatocellular carcinoma (HCC) dataset comprising genome (mutation and copy number), transcriptome, proteome, and phosphoproteome data. We identified three main HCC subtypes together with molecular characteristics, some of which are associated with survival even when adjusting for the clinical stage. Cluster-specific networks shed light on the links between genotypes and molecular phenotypes of samples within their respective clusters and suggest targets for personalized treatments.

Author summary

Multi-omics approaches to cancer subtyping can provide more insights into molecular changes in tumors compared to single-omics approaches. However, most multi-omics clustering methods do not take into account that gene products interact, for example, as parts of protein complexes or signaling networks. Here we present bnClustOmics, a Bayesian network mixture model for unsupervised clustering of multi-omics data, which can represent dependencies among molecular changes of various omics types explicitly. Unlike other approaches that use data from public interaction databases as ground truth, bnClustOmics learns the dependencies between genes from the analyzed multi-omics dataset. At the same time, our approach can also account for prior knowledge from public interaction databases and use it to guide network learning without losing the ability to learn new dependencies. We applied bnClustOmics to a multi-omics HCC dataset and identified three subtypes similar to those identified in other HCC studies. The cluster-specific networks learned by bnClustOmics revealed additional insights into the molecular characterization of the discovered subgroups and highlighted the changes in signaling networks leading to distinct HCC phenotypes.
Numerical methods for the detection of phase defect structures in excitable media
Authors: Kabus Desmond , Arno Louise , Leenknegt Lore , Panfilov Alexander V. , Dierckx Hans
Published: December 2021

Electrical waves that rotate in the heart organize dangerous cardiac arrhythmias. Finding the region around which such rotation occurs is one of the most important practical questions for arrhythmia management. For many years, the main method for finding such regions was so-called phase mapping, in which a continuous phase was assigned to points in the heart based on their excitation status and defining the rotation region as a point of phase singularity. Recent analysis, however, showed that in many rotation regimes there exist phase discontinuities and the region of rotation must be defined not as a point of phase singularity, but as a phase defect line. In this paper, we use this novel methodology and perform a comparative study of three different phase definitions applied to in silico data and to experimental data obtained from optical voltage mapping experiments on monolayers of human atrial myocytes. We introduce new phase defect detection algorithms and compare them with those that appeared in literature already. We find that the phase definition is more important than the algorithm to identify sudden spatial phase variations. Sharp phase defect lines can be obtained from a phase derived from local activation times observed during one cycle of arrhythmia. Alternatively, similar quality can be obtained from a reparameterization of the classical phase obtained from observation of a single timeframe of transmembrane potential. We found that the phase defect line length was (35.9 ± 6.2) mm in the Fenton-Karma model and (4.01 ± 0.55) mm in cardiac human atrial myocyte monolayers. As local activation times are obtained during standard clinical cardiac mapping, the methods are also suitable to be applied to clinical datasets. All studied methods are publicly available and can be downloaded from an institutional web-server.
Psilocybin modulation of dynamic functional connectivity is associated with plasma psilocin and subjective effects
Authors: Olsen Anders S. , Lykkebo-Valløe Anders , Ozenne Brice , Madsen Martin K. , Stenbæk Dea S. , Armand Sophia , Mørup Morten , Ganz Melanie , Knudsen Gitte M. , Fisher Patrick M.
Published: December 2021

Background

Psilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state dynamic functional connectivity implicates network-level connectivity motifs that may underlie acute and lasting behavioral and clinical effects.

Aim

Evaluate the association between resting-state dynamic functional connectivity (dFC) characteristics and plasma psilocin level (PPL) and subjective drug intensity (SDI) before and right after intake of a psychedelic dose of psilocybin in healthy humans.

Methods

Fifteen healthy individuals completed the study. Before and at multiple time points after psilocybin intake, we acquired 10-minute resting-state blood-oxygen-level-dependent functional magnetic resonance imaging scans. Leading Eigenvector Dynamics Analysis (LEiDA) and diametrical clustering were applied to estimate discrete, sequentially active brain states. We evaluated associations between the fractional occurrence of brain states during a scan session and PPL and SDI using linear mixed-effects models. We examined associations between brain state dwell time and PPL and SDI using frailty Cox proportional hazards survival analysis.

Results

Fractional occurrences for two brain states characterized by lateral frontoparietal and medial fronto-parietal-cingulate coherence were statistically significantly negatively associated with PPL and SDI. Dwell time for these brain states was negatively associated with SDI and, to a lesser extent, PPL. Conversely, fractional occurrence and dwell time of a fully connected brain state was positively associated with PPL and SDI.

Conclusion

Our findings suggest that the acute perceptual psychedelic effects induced by psilocybin may stem from drug-level associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs in exchange for increases in a uniform connectivity structure. We apply and argue for a modified approach to modeling eigenvectors produced by LEiDA that more fully acknowledges their underlying structure. Together these findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics.

Highlights

We examined psilocybin effects on resting-state fMRI dynamic functional connectivity

Diametrical clustering described as improved strategy for LEiDA-defined brain states

Individual brain state dynamics defined by fractional occurrence and dwell time

Two frontoparietal states and a fully connected brain state affected by psilocybin

Brain state dynamics associated with psilocin level and subjective experience
Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing
Authors: Li Zhibin , Sun Chengcheng , Wang Fei , Wang Xiran , Zhu Jiacheng , Luo Lihua , Ding Xiangning , Zhang Yanan , Ding Peiwen , Wang Haoyu , Pu Mingyi , Li Yuejiao , Wang Shiyou , Qin Qiuyu , Wei Yanan , Sun Jian , Wang Xiangdong , Luo Yonglun , Chen Dongsheng , Qiu Wei
Published: December 2021

Background

Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited.

Methods

In this study, we compared the single-cell transcriptomes of 77□957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells.

Results

Results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalk and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells.

Conclusions

This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders.
The interaction of climate history and evolution impacts alpine biodiversity assembly differently in freshwater and on land
Authors: Jardim-deQueiroz Luiz , Doenz Carmela J. , Altermatt Florian , Alther Roman , Borko Špela , Gossner Martin M. , Graham Catherine , Matthews Blake , McFadden Ian R. , Pellissier Loïc , Schmitt Thomas , Selz Oliver M. , Villalba Soraya , Rüber Lukas , Zimmermann Niklaus , Seehausen Ole
Published: December 2021

Quaternary climate fluctuations can affect biodiversity assembly through speciation in two non-mutually-exclusive ways: a glacial species pump, where isolation in glacial refugia accelerates allopatric speciation, and adaptive radiation during ice-free periods. Here we detected biogeographic and genetic signatures associated with both mechanisms in the generation of the European Alps biodiversity. Age distributions of endemic and widespread species within aquatic and terrestrial taxa (amphipods, fishes, amphibians, butterflies and flowering plants) revealed that endemic fish evolved only in lakes, are highly sympatric and mainly of Holocene age, consistent with adaptive radiation. Endemic amphipods are ancient, suggesting preglacial radiation with limited range expansion and local Pleistocene survival, perhaps facilitated by a groundwater-dwelling lifestyle. Terrestrial endemics are mostly of Pleistocene age, and are thus more consistent with the glacial species pump. The lack of evidence for Holocene adaptive radiation in the terrestrial biome may be attributable to a faster range expansion of these taxa after glacial retreats, though fewer stable environments may also have contributed to differences between terrestrial areas and lakes. The high proportion of young, endemic species make the Alps vulnerable to climate change, but the mechanisms and consequences of species loss will likely differ between biomes because of their distinct histories.
Global plant-frugivore trait matching is shaped by climate and biogeographic history
Authors: McFadden Ian R. , Fritz Susanne A. , Zimmermann Niklaus E. , Pellissier Loïc , Kissling W. Daniel , Tobias Joseph A. , Schleuning Matthias , Graham Catherine H.
Published: December 2021

Species interactions are influenced by the trait structure of local multi-trophic communities. However, it remains unclear whether mutualistic interactions in particular can drive trait patterns at the global scale, where climatic constraints and biogeographic processes gain importance. Here we evaluate global relationships between traits of frugivorous birds and palms (Arecaceae), and how these relationships are affected, directly or indirectly, by assemblage richness, climate and biogeographic history. We leverage a new and expanded gape size dataset for nearly all avian frugivores, and find a positive relationship between gape size and fruit size, i.e., trait matching, which is influenced indirectly by palm richness and climate. We also uncover a latitudinal gradient in trait matching strength, which increases towards the tropics and varies among zoogeographic realms. Taken together, our results suggest trophic interactions have consistent influences on trait structure, but that abiotic, biogeographic and richness effects also play important, though sometimes indirect, roles in shaping the functional biogeography of mutualisms.