bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress
Authors: Li Liuying , Zheng Gang , Cao Chengjian , Cao Wenzhai , Yan Hui , Chen Shumin , Ding Conghua , Gan Daohui , Yuan Jing , Che Deya , Zhu Fengya
Published: August 2022

Vascular calcification (VC), which currently cannot be prevented or treated, is an independent risk factor for cardiovascular events. We aimed to investigate the ameliorative effect of berberine on VC via the activation of Akt signaling and inhibition of endoplasmic reticulum stress (ERS). The VC model was induced by high-dose Vitamin D3 in rats and beta-glycerophosphate in primary vascular smooth muscle cells of rat aortas, which were evaluated by Alizarin red staining to determine the calcium content and alkaline phosphatase activity. ERS was determined by the levels of GRP78 and CHOP, whereas that of the Akt signaling pathway was determined by the levels of phosphorylated Akt and GSK3β. VC was significantly ameliorated by berberine treatment in vivo and in vitro, and the inhibition of ERS and the activation of the Akt/GSK3 signaling pathway. In the vascular smooth muscle cells of primary rats, tunicamycin, an ERS activator, blocked the ameliorative effect of berberine on VC and ERS, but not the activation of Akt/GSK3. The ameliorative effects of berberine on VC, ERS, and the Akt signaling pathway were all prevented by inhibitor IV. Four-phenylbutyric acid, an ERS inhibitor, can restore the ameliorative effect of berberine on VC and ERS that was blocked by inhibitor IV. Our results are the first to demonstrate the ameliorative effect of VC that was mediated by the activation of the Akt signaling pathway and inhibition of ERS. These results may provide a new pharmaceutical candidate for the prevention and treatment of VC.
Blunt Eye Trauma: Epidemiology, Prognostic Factors and Visual Outcome—A 10-Year Retrospective Study
Authors: Özer Ömer , Tuncer Muhammet L.
Published: August 2022

The aim of this study is to define the accompanying prognostic factors and evaluate the final visual acuity of patients presenting with blunt eye trauma. The data of this study included the demographic characteristics of the patients, the mechanism of injury, initial and final visual acuities and accompanying pathologies. A total of 259 eyes of 259 patients who presented with blunt eye trauma were included. Eighty-three percent of the patients were male. The most common mechanisms are beaten, accidents, and falls. The visual acuity of the patient at admission was no perception of light, and the final visual acuity was also no perception of light. The incidence of blunt eye trauma was more common in males and in advanced age. A higher final visual acuity level is achieved with successful management of concomitant pathologies.
Reconstruction of Acquired Segmental Mandibular Defects Using Pedicled Mandibular Muscle Flap and Evaluation of Speech Function and Aesthetic Outcomes
Authors: Huang Zhuo-shan , Liao Jun-kun , Chen Wei-liang , Wang Yu-jia , Wu Hong
Published: August 2022

Purpose:

The purpose of this study was to investigate the clinical effect of pedicled mandibular osteomuscular flap in the reconstouring of repair of acquired segmental mandibular defects.

Patients and Methods:

Thirteen patients with acquired segmental mandibular defects requiring secondary repair were included into the study. Pedicled mandibular osteomuscular flap was applied with strong internal fixation to repair the mandibular defects. The patients’ speech, swallowing function, and aesthetic changes were evaluated upon follow-up.

Results:

The flaps were viable in all patients. Average speech function score was 7.6±0.6. All patients had a drinking test rating of grade I or II with good masticatory efficiency. The postoperative self-assessment Visual Analog Scale score of appearance was 7.8±0.8.

Conclusions:

Pedicled mandibular osteomuscular flap is a viable choice in the secondary repair and reconstruction of mandibular acquired segmental defects. This flap could achieve better oral function with good aesthetic results.
Risk Reduction Strategy to Decrease Incidence of Retained Surgical Items
Authors: Kaplan Harrison J , Spiera Zachary C , Feldman David L , Shamamian Peter , Portnoy Bonnie , Ioannides Paula , Leitman I Michael
Published: August 2022

BACKGROUND:

Retained surgical items (RSIs) are rare but serious events associated with significant morbidity and costs. We assessed the effectiveness of radiofrequency (RF) detection technology and Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) in reducing the incidence of RSIs.

STUDY DESIGN:

All RSIs reported to the New York Patient Occurrence Reporting and Tracking System at five large urban teaching hospitals from 2007 to 2017 were analyzed. In 2012, TeamSTEPPS training was provided to all perioperative staff at each site, and use of RF detection became required in all procedures. The incidence of events before and after the interventions were compared using odds ratios.

RESULTS:

A total of 997,237 operative procedures were analyzed. After the interventions, the incidence of RSIs decreased from 11.66 to 5.80 events per 100,000 operations (odds ratio [OR] [95% CI] = 0.50 [0.32 to 0.78]). The frequency of RSIs involving RF-detectable items decreased from 5.21 to 1.35 events per 100,000 operations (OR [95% CI] = 0.26 [0.11 to 0.60]). The difference in RSIs involving non-RF-detectable surgical items was not statistically significant.

CONCLUSIONS:

The incidence of RSIs was significantly lower during the time period after implementing RF detection technology and after TeamSTEPPS training, primarily driven by a decrease in retained RF-detectable items. RF detection technology may be worth pursuing for hospitals looking to decrease RSI frequency. The benefit of TeamSTEPPS training alone may not result in a reduction of RSIs.
Association Between Statewide Medicaid Opioid Policy and Postoperative Opioid Prescribing among Surgeons at a Large Safety-Net Hospital
Authors: Zhang Irene Y , Wong Edwin S , Rosen Joshua E , Gordon Debra B , Flum David R , Liao Joshua M
Published: August 2022

BACKGROUND:

Restrictive state and payer policies may be effective in reducing opioid prescribing by surgeons, but their impact has not been well studied. In 2017, Washington Medicaid implemented an opioid prescribing limit of 42 pills, prompting a large regional safety-net hospital to implement a decision support intervention in response. We aimed to evaluate the effects on surgeons’ prescribing.

STUDY DESIGN:

We retrospectively studied postoperative opioid prescribing (quantity of pills prescribed at discharge) to opioid-naïve surgical patients at a regional safety-net hospital from 2016 to 2020. We investigated associations between the policy and opioid prescribing by using interrupted time series analysis, adjusting for clinical and sociodemographic factors.

RESULTS:

A total of 12,799 surgical encounters involving opioid-naïve patients (59% male, mean age 52) were analyzed. Opioids were prescribed for 75%. From 2016 to 2020, the mean prescribed opioid quantity decreased from 36 pills to 17 pills. In interrupted time series analysis, the Medicaid policy implementation was associated with an immediate change of –8.4 pills (95% CI –12 to –4.7; p < 0.001) per prescription and a subsequent rate of decrease similar to that prepolicy. In a comparison of changes between patients insured through Medicaid vs Medicare, Medicaid patients had an immediate change of –9.8 pills (95% CI –19 to –0.76; p = 0.03) after policy implementation and continued decreases similar to those prepolicy. No immediate or subsequent policy-related changes were observed among Medicare patients.

CONCLUSION:

In a large regional safety-net institution, postoperative opioid prescriptions decreased in size over time, with immediate changes associated with a state Medicaid policy and corresponding decision support intervention. These findings pose implications for surgeons, hospital leaders, and payers seeking to address opioid use via judicious prescribing.
Deep Neural Network for the Prediction of KRAS Genotype in Rectal Cancer
Authors: Ghareeb Waleed M , Draz Eman , Madbouly Khaled , Hussein Ahmed H , Faisal Mohammed , Elkashef Wagdi , Emile Mona Hany , Edelhamre Marcus , Kim Seon Hahn , Emile Sameh Hany ,   for the Anam Hospital KRAS Research Group
Published: August 2022

Background:

KRAS mutation can alter the treatment plan after resection of colorectal cancer. Despite its importance, the KRAS status of several patients remains unchecked because of the high cost and limited resources. This study developed a deep neural network (DNN) to predict the KRAS genotype using hematoxylin and eosin (H&E)–stained histopathological images.

Study design:

Three DNNs were created (KRAS_Mob, KRAS_Shuff, and KRAS_Ince) using the structural backbone of the MobileNet, ShuffleNet, and Inception networks, respectively. The Cancer Genome Atlas was screened to extract 49,684 image tiles that were used for deep learning and internal validation. An independent cohort of 43,032 image tiles was used for external validation. The performance was compared with humans, and a virtual cost–saving analysis was done.

Results:

The KRAS_Mob network (area under the receiver operating curve [AUC] 0.8, 95% CI 0.71 to 0.89) was the best-performing model for predicting the KRAS genotype, followed by the KRAS_Shuff (AUC 0.73, 95% CI 0.62 to 0.84) and KRAS_Ince (AUC 0.71, 95% CI 0.6 to 0.82) networks. Combing the KRAS_Mob and KRAS_Shuff networks as a double prediction approach showed improved performance. KRAS_Mob network accuracy surpassed that of two independent pathologists (AUC 0.79 [95% CI 0.64 to 0.93], 0.51 [95% CI 0.34 to 0.69], and 0.51 (95% CI 0.34 to 0.69]; p < 0.001 for all comparisons).

Conclusion:

The DNN has the potential to predict the KRAS genotype directly from H&E-stained histopathological slide images. As an algorithmic screening method to prioritize patients for laboratory confirmation, such a model might possibly reduce the number of patients screened, resulting in significant test-related time and economic savings.
A psycho-cognitive model for exertional heatstroke: theory and preliminary testing using self-report measures in a case-control study
Authors: Verdonk Charles , Mellier Camille , Charlot Keyne , Jouvion Arnaud , Trousselard Marion , Sagui Emmanuel , Tardo-Dino Pierre-Emmanuel , Malgoyre Alexandra
Published: August 2022

Background

Exertional heatstroke (EHS) stands as the most severe manifestation within the spectrum of heat-related illnesses arising during sport competition or physical activity within specific contexts such as military training. Despite substantial progress in comprehending the physiological aspects of EHS, current evidence underscores the necessity for a more comprehensive perspective that incorporates psycho-cognitive factors.

Methods

The present study introduces a psycho-cognitive model for EHS and initiates its empirical validation through self-report measures in a case-control study. Our central hypothesis suggests that EHS may emanate from a disruption in the cost-benefit trade-off associated with prolonged physical activity. Specifically, we propose that EHS could be a consequence ofovervaluingthe benefits linked to physical activity due to excessive motivation to succeed andundervaluingeffort exertion costs resulting from low interoceptive awareness, characterized by disrupted processing of signals related to the body’s internal state.

Results

Analysis of our psychometric data revealed that individuals with a history of EHS (cases, N=51) self-report diminished interoceptive awareness compared to their healthy counterparts (controls, n=43). There was no significant difference in the global motivation trait between cases and controls. Furthermore, cases exhibited a less developed trait mindfulness compared to controls.

Conclusion

Our study establishes theoretical foundations and offers preliminary support for a psycho-cognitive model of EHS. The results suggest that relatively straightforward measures, such as self-report questionnaires, can be instrumental in identifying intrinsic (i.e., individual-specific) risk factors for EHS. The psycho-cognitive approach to understanding EHS holds promise for informing innovative prevention strategies aimed at mitigating its risk in sports competitions and military settings.
Explainable-AI to Discover Associated Genes for Classifying Hepato-cellular Carcinoma from High-dimensional Data
Authors: Hasan Easin , Mostafa Fahad , Hossain Md S , Loftin Jonathon
Published: August 2022

Knowledge-based interpretations are essential for understanding the omic data set because of its nature, such as high dimension and hidden biological information in genes. When analyzing gene expression data with many genes and few samples, the main problem is to separate disease-related information from a vast quantity of redundant data and noise. This paper uses a reliable framework to determine important genes for discovering Hepato-cellular Carcinoma (HCC) from micro-array analysis and eliminating redundant and unnecessary genes through gene selection. Several machine learning models were applied to find significant predictors responsible for HCC. As we know, classification algorithms such as Random Forest, Naive Bayes classifier, or a k-Nearest Neighbor classifier can help us to classify HCC from responsible genes. Random Forests shows 96.53% accuracy with p < 0.00001, which is better than other discussed Machine Learning(ML) approaches. Each gene is not responsible for a particular patient. Since ML approaches are like black boxes and people/practitioners do not rely on them sometimes. Artificial Intelligence(AI) technologies with high optimization interoperability shed light on what is happening inside these systems and aid in the detection of potential problems; including causality, information leakage, model bias, and robustness when determining responsible genes for a specific patient with a high probability score of almost 0.99, from one of the samples mentioned in this study.
Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY
Authors: Russell Mark D , Galloway James B , Andrews Colm D , MacKenna Brian , Goldacre Ben , Mehrkar Amir , Curtis Helen J , Butler-Cole Ben , O’Dwyer Thomas , Qureshi Sumera , Ledingham Joanna M , Mahto Arti , Rutherford Andrew I , Adas Maryam A , Alveyn Edward , Norton Sam , Cope Andrew P , Bechman Katie ,   OpenSAFELY Collaborative
Published: August 2022

Objective

To use the OpenSAFELY platform to replicate key metrics from a national clinical audit, and assess the impact of COVID-19 on disease incidence and care delivery for inflammatory arthritis (IA) in England.

Design

Population-based cohort study, with the approval of NHS England.

Setting

Primary care and linked hospital outpatient data for more than 17 million people registered with general practices in England that use TPP electronic health record software.

Participants

Adults (18-110 years) with new diagnoses of IA (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) between 1 April 2019 and 31 March 2022.

Main outcome measures

The following outcomes were explored before and after April 2020: 1) incidence of IA diagnoses; 2) time from primary care referral to first rheumatology assessment; 3) time to first prescription of a disease-modifying anti-rheumatic drug (DMARD) in primary care.

Results

From a reference population of 17,683,500 adults, there were 31,280 incident IA diagnoses between April 2019 and March 2022. The incidence of IA decreased by 20.3% in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). For those who presented with IA, the time to first rheumatology assessment was shorter during the pandemic (median 18 days; interquartile range 8 to 35 days) than before (21 days; 9 to 41 days). Overall, the proportion of patients prescribed DMARDs in primary care was comparable during the pandemic to before; however, the choice of medication changed, with fewer people prescribed methotrexate or leflunomide during the pandemic, and more people prescribed sulfasalazine or hydroxychloroquine.

Conclusions

The incidence of IA diagnoses in England decreased markedly during the early COVID-19 pandemic. However, for people who sought medical attention, the impact of the pandemic on service delivery was less marked than might have been anticipated. This study demonstrates that it is feasible to use routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality for long-term conditions on a national scale, without the need for manual data collection.
Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state
Authors: Maiti Atanu , Hedger Adam K. , Myint Wazo , Balachandran Vanivilasini , Watts Jonathan K. , Schiffer Celia A. , Matsuo Hiroshi
Published: August 2022

APOBEC3 proteins (A3s) are enzymes that catalyze deamination of cytidine to uridine in single-stranded DNA (ssDNA) substrates, thus playing a key role in innate antiviral immunity. However, APOBEC3 family has also been linked to many mutational signatures in cancer cells, which has led to intense interest to develop inhibitors of A3’s catalytic activity as therapeutics as well as tools to study A3’s biochemistry, structure and cellular function. Recent studies have shown that ssDNA containing 2′-deoxy-zebularine (dZ-ssDNA) is an inhibitor of A3s such as A3A, A3B and A3G, although atomic determinants of this activity remained unknown. To fill this knowledge gap, we determined a 1.5 Å resolution structure of a dZ-ssDNA inhibitor bound to active A3G. The crystal structure revealed that the activated dZ/H2O mimics the transition state by coordinating the active site Zn2+ and engaging in additional stabilizing interactions, such as the one with the catalytic residues E259. Therefore, this structure allowed us to capture the first snapshot of the A3’s transition state, and suggests that developing transition-state mimicking inhibitors may provide a new opportunity to design more targeted molecules for A3s in the future.
Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration
Authors: Norris Alessandra M. , Appu Ambili Bai , Johnson Connor D. , Zhou Lylybell Y. , McKellar David W. , Renault Marie-Ange , Hammers David , Cosgrove Benjamin D. , Kopinke Daniel
Published: August 2022

Successful muscle regeneration relies on the interplay of multiple cell populations. However, the signals required for this coordinated intercellular crosstalk remain largely unknown. Here, we describe how the Hedgehog (Hh) signaling pathway controls the fate of fibro/adipogenic progenitors (FAPs), the cellular origin of intramuscular fat (IMAT) and fibrotic scar tissue. Using conditional mutagenesis and pharmacological Hh modulatorsin vivoandin vitro, we identify DHH as the key ligand that acts as a potent adipogenic brake by preventing the adipogenic differentiation of FAPs. Hh signaling also impacts muscle regeneration, albeit indirectly through induction of myogenic factors in FAPs. Our results also indicate that ectopic and sustained Hh activation forces FAPs to adopt a fibrogenic fate resulting in widespread fibrosis. In this work, we reveal novel post-developmental functions of Hh signaling in balancing tissue regeneration and fatty fibrosis. Moreover, they provide the exciting possibility that mis-regulation of the Hh pathway with age and disease could be a major driver of pathological IMAT formation.
Nutrients and flow shape the cyclic dominance games betweenEscherichia colistrains
Authors: Kuhn Thierry , Pilar Junier , Bshary Redouan , Terrettaz Céline , Gonzalez Diego , Richter Xiang-Yi Li
Published: August 2022

Evolutionary game theory has provided various models to explain the coexistence of competing strategies, one of which is the rock-paper-scissors (RPS) game. A system of threeEscherichia colistrains—a toxin-producer, a resistant, and a sensitive—has become a classic experimental model for studying RPS games. Previous experimental and theoretical studies, however, often ignored the influence of ecological factors such as nutrients and toxin dynamics on the evolutionary game dynamics. In this work, we combine experiments and modeling to study how these factors affect competition dynamics. Using 3D-printed mini-bioreactors, we tracked the frequency of the three strains in different culturing media and under different flow regimes. Although our experimental system fulfilled the requirements of cyclic dominance, we did not observe clear cycles or long-term coexistence between strains. We found that both nutrients and flow rates strongly impacted population dynamics. In our simulations, we explicitly modeled the release, removal and diffusion of toxin. We showed that the amount of toxin that is retained in the system is a simple indicator that can predict competition outcomes across broad parameter space. Moreover, our simulation results suggest that high rates of toxin diffusion might have prevented cyclic patterns from emerging in our experimental system.
Identification of cell barcodes from long-read single-cell RNA-seq with BLAZE
Authors: You Yupei , Prawer Yair D.J. , De Paoli-Iseppi Ricardo , Hunt Cameron P.J. , Parish Clare L. , Shim Heejung , Clark Michael B.
Published: August 2022

Single-cell RNA sequencing (scRNA-seq) has revolutionised our ability to profile gene expression. However, short-read (SR) scRNAseq methodologies such as 10x are restricted to sequencing the 3’ or 5’ ends of transcripts, providing accurate gene expression but little information on the RNA isoforms expressed in each cell. Newly developed long-read (LR) scRNA-seq enables the quantification of RNA isoforms in individual cells but LR scRNA-seq using the Oxford Nanopore platform has largely relied upon matched short-read data to identify cell barcodes and allow single cell analysis. Here we introduce BLAZE (Barcode identification from long-reads for AnalyZing single-cell gene Expression), which accurately and efficiently identifies 10x cell barcodes using only nanopore LR scRNA-seq data. We compared BLAZE to existing tools, including cell barcodes identified from matched SR scRNA-seq, on differentiating stem cells and 5 cancer cell lines. BLAZE outperforms existing tools and provides a more accurate representation of the cells present in LR scRNA-seq than using matched short-reads. BLAZE provides accurate cell barcodes over a wide range of experimental read depths and sequencing accuracies, while other methodologies commonly identify false-positive barcodes and cell clusters, disrupting biological interpretation of LR scRNA-seq results. In conclusion, BLAZE eliminates the requirement for matched SR scRNA-seq to interpret LR scRNA-seq, simplifying procedures and decreasing costs while also improving LR scRNA-seq results. BLAZE is compatible with downstream tools accepting a cell barcode whitelist file and is available at https://github.com/shimlab/BLAZE.
Extracellular vesicles induce aggressive lung cancer via non-canonical integrin-EGFR-KRAS signaling
Authors: Rubio Karla , Romero-Olmedo Addi J. , Sarvari Pouya , Günther Stefan , Mehta Aditi , Bassaly Birgit , Braubach Peter , Dobreva Gergana , Wygrecka Malgorzata , Gattenlöhner Stefan , Braun Thomas , Tresch Achim , Graumann Johannes , Barreto Guillermo
Published: August 2022

Small cell lung cancer (SCLC) is an extremely aggressive lung cancer type with a patient median survival of 6-12 months. Epidermal growth factor (EGF) signaling plays an important role in triggering SCLC. In addition, growth factor-dependent signals and alpha-, beta-integrin (ITGA, ITGB) heterodimer receptors functionally cooperate and integrate their signaling pathways. However, the precise role of integrins in EGF receptor (EGFR) activation in SCLC has remained elusive. We analyzed RNA-sequencing data, human precision-cut lung slices (hPCLS), retrospectively collected human lung tissue samples and cell lines to demonstrate that non-canonical ITGB2 signaling activates EGFR and RAS/MAPK/ERK signaling in SCLC. Further, we identified a novel SCLC gene expression signature consisting of 93 transcripts that were induced by ITGB2, which might be used for stratification of SCLC patients, prognosis prediction of LC patients and development of patient-tailored therapies. We also found by proteomic analysis a cell-cell communication mechanism based on extracellular vesicles (EVs) containing ITGB2, which were secreted by SCLC cells and induced in control human lung tissue RAS/MAPK/ERK signaling and SCLC markers. We uncovered a mechanism of ITGB2-mediated EGFR activation in SCLC that explains EGFR-inhibitor resistance independently of EGFR mutations, suggesting the development of therapies targeting ITGB2 for patients with this extremely aggressive lung cancer type.
Synchronicity of viral shedding in molossid bat maternity colonies
Authors: Hoarau Axel O. G. , Köster Marie , Dietrich Muriel , Minter Gildas Le , Joffrin Léa , Ramanantsalama Riana V. , Mavingui Patrick , Lebarbenchon Camille
Published: August 2022

Infection dynamics in vertebrates are driven by biological and ecological processes. For bats, population structure and reproductive cycles have major effects on RNA virus transmission. On Reunion Island, previous studies have shown that parturition of pregnant females and aggregation of juvenile Reunion free-tailed bats (Mormopterus francoismoutoui) are associated to major increase in the prevalence of bats shedding viruses. The synchronicity of such shedding pulses, however, is yet to be assessed, between viruses but also maternity colonies. Based on 3422 fresh faeces collected every two to five weeks during four consecutive birthing seasons, we report the prevalence of bats shedding astroviruses (AstVs), coronaviruses (CoVs), and paramyxoviruses (PMVs) in two maternity colonies on Reunion Island. We found that the proportion of bats shedding viruses is highly influenced by sampling collection dates, and therefore by the seasonality of parturition. We highlight that virus shedding patterns are reproducible among years and colonies for CoVs and at a lesser extent for PMVs, but not for AstVs. We also report 1% of bats harbouring double infections, mostly CoVs and PMVs, but none shedding simultaneously AstVs, CoVs and PMVs.
Kinase Suppressor of RAS 1 (KSR1) maintains the transformed phenotype of BRAFV600E mutant human melanoma cells
Authors: Liu Zhi , Krstic Aleksandar , Neve Ashish , Rauch Nora , Wynne Kieran , Cassidy Hilary , McCann Amanda , Kavanagh Emma , McCann Brendan , Blanco Alfonso , Rauch Jens , Kolch Walter
Published: August 2022

KSR1 is a scaffolding protein for the RAS-RAF-MEK-ERK pathway, which is one of the most frequently altered pathways in human cancers. Previous results have shown that KSR1 has a critical role in mutant RAS mediated transformation. Here, we examined the role of KSR1 in mutant BRAF transformation. We used CRISPR/Cas9 to knock out KSR1 in a BRAFV600E transformed melanoma cell line. KSR1 loss produced a complex phenotype characterized by impaired proliferation, cell cycle defects, decreased transformation, decreased invasive migration, increased cellular senescence, and increased apoptosis. To decipher this phenotype, we used a combination of proteomic ERK substrate profiling, global protein expression profiling, and biochemical validation assays. The results suggest that KSR1 directs ERK to phosphorylate substrates that have a critical role in ensuring cell survival. The results further indicate that KSR1 loss induces the activation of p38 Mitogen-Activated Protein Kinase (MAPK) and subsequent cell cycle aberrations and senescence. In summary, KSR1 function plays a key role in oncogenic BRAF transformation.
Species-specific traits mediate avian demographic responses under past climate change
Authors: Germain Ryan R , Feng Shaohong , Chen Guangji , Graves Gary R. , Tobias Joseph A. , Rahbek Carsten , Lei Fumin , Fjeldså Jon , Hosner Peter A. , Gilbert M. Thomas P. , Zhang Guojie , Nogués-Bravo David
Published: August 2022

Anticipating species’ responses to environmental change is a pressing mission in biodiversity conservation. Despite decades of research investigating how climate change may affect population sizes, historical context is lacking and the traits which mediate demographic sensitivity to changing climate remain elusive. We use whole-genome sequence data to reconstruct the demographic histories of 263 bird species over the past million years and identify networks of interacting morphological and life-history traits associated with changes in effective population size (Ne) in response to climate warming and cooling. Our results identify direct and indirect effects of key traits representing dispersal, reproduction, and survival on long-term demographic responses to climate change, thereby highlighting traits most likely to influence population responses to on-going climate warming.

One-Sentence Summary

Interacting traits influence sensitivity of bird population sizes to climate warming and cooling over the past million years.
Systematic analysis of the genomic features involved in the binding preferences of transcription factors
Authors: Romero Raphaël , Menichelli Christophe , Marin Jean-Michel , Lèbre Sophie , Lecellier Charles-Henri , Bréhélin Laurent
Published: August 2022

Transcription factors (TFs) orchestrate gene expression and are at the core of cell-specific phenotypes and functions. One given TF can therefore have different binding sites depending on cell type and conditions. However, the TF core motif, as represented by Position Weight Matrix for instance, are often, if not invariably, cell agnostic. Likewise, paralogous TFs recognize very similar motifs while binding different genomic regions. We propose a machine learning approach called TFscope aimed at identifying the DNA features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two cell types or treatments or two paralogous TFs. TFscope systematically investigates differences in i) core motif, ii) nucleotide environment around the binding site and iii) presence and location of co-factor motifs. It provides the main DNA features that have been detected, and the contribution of each of these features to explain the binding differences. TFscope has been applied to more than 350 pairs of ChIP-seq. Our experiments showed that the approach is accurate and that the genomic features distinguishing TF binding in two different settings vary according to the TFs considered and/or the conditions. Several samples are presented and discussed to illustrate these findings. For TFs in different cell types or with different treatments, co-factors and nucleotide environment often explain most of the binding-site differences, while for paralogous TFs, subtle differences in the core motif seem to be the main reason for the observed differences in our experiments.

The source code (python), data and results of the experiments described in this article are available athttps://gite.lirmm.fr/rromero/tfscope.
Understanding inhibitors to XBRL adoption: an empirical investigation
Authors: Singh Harmandeep , Singh Arwinder
Published: August 2022

Purpose

This study aims to investigate the awareness of extensible business reporting language (XBRL) and the perception of chartered accountants of India concerning the inhibitors of XBRL adoption, namely, environmental, organizational and innovation factors developed by Troshani and Rao (2007) from Rogers’ innovation diffusion theory. In addition, the analysis also investigated the relationship between the perception of issues regarding XBRL adoption and individual characteristics (training, age, gender and professional experience).

Design/methodology/approach

A Web-based questionnaire was circulated through e-mail to chartered accountants registered with the Institute of Chartered Accountants India (ICAI) and 233 chartered accountants responded to the questionnaire. The data was analyzed using reliability statistics and multivariate regression analyses.

Findings

The results indicate that accountants perceived that environmental, organizational and innovational factors were challenging in adopting XBRL. Interestingly, training and experience were significant factors in explaining respondents’ perceptions.

Practical implications

From a practical panorama, the significance of issues implies that associations such as XBRL International, XBRL India, ICAI and the Ministry of Corporate Affairs should collectively take the appropriate steps to sustain and ameliorate the reliability and adoption of XBRL.

Social implications

The results can motivate ICAI/Institute of Company Secretaries of India (ICSI) courses to teach academic content about XBRL.

Originality/value

The present study differs from previous research because it examines the inhibitors in adopting XBRL, namely, environmental, organizational and innovation factors, in an empirical setting. Moreover, to the best of the author’s knowledge, this is the first study to analyze the influence of individual factors on accountants’ perceptions about inhibitors of XBRL adoption.
Circular textiles innovation during COVID-19: not the silver lining some had hoped for
Authors: Sugg Bethany
Published: August 2022

Purpose

The COVID-19 pandemic has caused irrefutable devastation globally. Yet, academic and trade commentators have claimed that this disruption could have had a silver lining by presenting the fashion industry with the opportunity to reassess and rebuild in a slower, more considered way. Part of this reassessment, some have argued, may have been allowing the industry's pre-COVID sustainability buzz to come to fruition by nudging the fashion industry to go circular. This paper explores if, and how, the COVID-19 pandemic was (not) nudging the industry towards circularity using the case study of circular textiles.

Design/methodology/approach

Serial, semi-structured, qualitative interviews were conducted with three buyers and sourcers working for three UK-based fashion retailers. Each participant was involved in three interviews in June 2020 following the UK's first national lockdown.

Findings

The research findings suggest that, at the time this research was undertaken, these retailers were focussed on regaining profit, protecting their supply chains and producing “safe” designs whilst cutting back and becoming more risk averse. These actors suggested that, in contrast to the suppositions made by academic and media commentators, the COVID-19 pandemic was acting as a hindrance to circularity, not a helping hand, as retailers were less willing to invest in circular textiles at that time than they were pre-pandemic.

Originality/value

This paper offers valuable insight into the COVID-19 pandemic's impact on circular innovation within fashion retail whilst contributing to broader understandings of the principles of the circular economy within textiles and design.
Excess cash holding and audit pricing: a further consideration of precautionary motives and other factors
Authors: Ramachandran Jayalakshmy , Kannan Yezen H. , Benjamin Samuel Jebaraj
Published: August 2022

Purpose

This paper aims to investigate auditors’ pricing of excess cash holdings and the variation in their pricing decisions in light of the precautionary motives of cash holdings and certain firm-specific conditions and during periods of crisis.

Design/methodology/approach

The authors conduct the two-stage-least-squares multivariate analysis using a sample of publicly listed non-financial US firms for the period 2003 to 2021 (42,413 firm-year observations).

Findings

The findings show a significant positive relationship between excess cash and audit fee. Next, the authors find that audit pricing of excess cash is significantly higher for firms with lower financial constraints. However, the authors do not find evidence to suggest that auditors price excess cash significantly higher for firms with lower hedging needs. In additional analysis, the authors find evidence to suggest that auditors charge significantly less for excess cash in firms that report financial loss and firms operating in industries with high litigation risk. The additional analysis also reveals excess cash is not positively and significantly priced by auditors as a result of the global financial crisis and Covid-19 pandemic.

Originality/value

Most researchers have analyzed excess cash holding from the perspective of managers, i.e. agency conflict or managerial prudence, while somewhat neglecting auditors’ perception of the embedded risk of excess cash holdings. The authors provide new insights on auditors’ perspective of excess cash holding and identify certain factors/situation/conditions that cause variation in the audit fee premium. The findings offer useful insights for managers and shareholders who are interested in assessing the effects of excess cash holdings policies on the audit fee premium.
Can downside-risk measures help to explain the reluctance of households to invest in XTFs? An empirical study using the SHS-base
Authors: Wanger Hans Philipp , Oehler Andreas
Published: August 2022

Purpose

The purpose of this paper is to investigate whether downside-risk measures help to explain why households largely refrain from investing in Exchange Traded Funds that replicate broad and internationally diversified market indices, so-called XTFs, although studies frequently recommend to do so.

Design/methodology/approach

The paper analyzes whether evaluating risk in terms of downside-risk measures which reflect households' interpretation of risk closer than the standard deviation (SD) of returns, yields less risk-return-enhancements, and thus, fewer incentives for households to invest in XTFs. Household portfolios are compiled by combining stylized portfolio compositions that involve multiple asset classes and German households' security holdings. The data set covers the period from January 2014 to December 2016 and includes 47,388 securities.

Findings

The results indicate that none of the downside-risk measures can help to explain the reluctance of households to invest in XTFs. On the flip side, the results show that all stylized household portfolios can enhance the risk-return position from employing XTFs, regardless of the underlying risk measure. This supports the advice to invest in XTFs and extends it upon households that evaluate risk in terms of downside-risk.

Originality/value

To the best of the authors' knowledge, this study is the first to investigate risk-return-enhancements from XTFs while simultaneously considering various downside-risk measures and multiple asset classes of household portfolios.
Excessive nutrient input induces an ecological cost for aphids by modifying their attractiveness towards mutualist ants
Authors: Lescano María N. , Quintero Carolina , Farji‐Brener Alejandro G. , Balseiro Esteban
Published: August 2022

Enhanced soil nutrient availability often favours herbivore performance by bringing the carbon:nutrient ratio of plants closer to herbivore requirements. However, a surplus of nutrients can promote a too low carbon:nutrient ratio in plants, making them of poor quality for herbivores. In addition, increased soil nutrients can trigger cascading effects altering higher trophic levels, resulting in indirect costs for herbivores.

Through experiments under three increasing fertilization levels (unfertilized, NPK‐rich, and 2NPK‐rich soils), we studied how the enhancement of soil nutrient availability, by modifying the C:N ratio of thistles, affects the performance and homeostatic response of the aphids, and the consequent ant attraction.

Fertilized soils increased the biomass and reduced the C:N ratio of thistles, also increasing aphid abundance. The stoichiometric homeostasis of aphids was modulated through changes in honeydew production and composition; fertilization treatments reduced by more than half the quantity of honeydew secreted and lead to 2.5–6.4 times higher honeydew N concentration compared with the unfertilized treatment. In addition, in the highest fertilization treatment, the aphids increased the content of uric acid (a waste toxic compound involved in amino acid deamination) excreted in their honeydew. Aphid‐infested thistles had the highest number of aphid‐tending ants when they grew on intermediate rich‐substrates. Ants selected honeydew with a lower C:N ratio (compared to unfertilized plants), but fewer workers patrolled plants with the highest fertilization treatment likely due to increased uric acid in the honeydew.

We showed that enhanced soil nutrients brought plant C:N ratio closer to aphid requirements, enhancing their performance and promoting ant attendance. But a disproportionate increase in fertilization did not further improve aphid performance while it decreases the attraction of protective ants, which would make aphid populations more vulnerable to attack by natural enemies, inducing an ecological cost.

This study highlights the complex role of bottom‐up cascading effects triggered by increases in soil nutrient availability and the importance of evaluating not only the physiological and population cost and benefits of it but also the ecological ones; especially when it alters mutualistic interactions.

Read the free Plain Language Summary for this article on the Journal blog.
Reliable online measurement of population dynamics for filamentous co‐cultures
Authors: Palacio‐Barrera Ana M. , Schlembach Ivan , Finger Maurice , Büchs Jochen , Rosenbaum Miriam A.
Published: August 2022

Understanding population dynamics is a key factor for optimizing co‐culture processes to produce valuable compounds. However, the measurement of independent population dynamics is difficult, especially for filamentous organisms and in presence of insoluble substrates like cellulose. We propose a workflow for fluorescence‐based online monitoring of individual population dynamics of two filamentous microorganisms. The fluorescent tagged target co‐culture is composed of the cellulolytic fungus Trichoderma reesei RUT‐C30—mCherry and the pigment‐producing bacterium Streptomyces coelicolor A3(2)—mNeonGreen (mNG) growing on insoluble cellulose as a substrate. To validate the system, the fluorescence‐to‐biomass and fluorescence‐to‐scattered‐light correlation of the two strains was characterized in depth under various conditions. Thereby, especially for complex filamentous microorganisms, microbial morphologies have to be considered. Another bias can arise from autofluorescence or pigments that can spectrally interfere with the fluorescence measurement. Green autofluorescence of both strains was uncoupled from different green fluorescent protein signals through a spectral unmixing approach, resulting in a specific signal only linked to the abundance of S. coelicolor A3(2)—mNG. As proof of principle, the population dynamics of the target co‐culture were measured at varying inoculation ratios in presence of insoluble cellulose particles. Thereby, the respective fluorescence signals reliably described the abundance of each partner, according to the variations in the inocula. With this method, conditions can be fine‐tuned for optimal growth of both partners along with natural product formation by the bacterium.
Comparative ontogenetic and transcriptomic analyses shed light on color pattern divergence in cichlid fishes
Authors: Kratochwil Claudius F. , Liang Yipeng , Gerwin Jan , Franchini Paolo , Meyer Axel
Published: August 2022

Stripe patterns are a striking example for a repeatedly evolved color pattern. In the African adaptive radiations of cichlid fishes, stripes evolved several times independently. Previously, it has been suggested that regulatory evolution of a single gene, agouti‐related‐peptide 2 (agrp2), explains the evolutionary lability of this trait. Here, using a comparative transcriptomic approach, we performed comparisons between (adult) striped and nonstriped cichlid fishes of representatives of Lake Victoria and the two major clades of Lake Malawi (mbuna and non‐mbuna lineage). We identify agrp2 to be differentially expressed across all pairwise comparisons, reaffirming its association with stripe pattern divergence. We therefore also provide evidence that agrp2 is associated with the loss of the nonstereotypic oblique stripe of Mylochromis mola. Complementary ontogenetic data give insights into the development of stripe patterns as well as vertical bar patterns that both develop postembryonically. Lastly, using the Lake Victoria species pair Haplochromis sauvagei and Pundamilia nyererei, we investigated the differences between melanic and non‐melanic regions to identify additional genes that contribute to the formation of stripes. Expression differences—that most importantly also do not include agrp2—are surprisingly small. This suggests, at least in this species pair, that the stripe phenotype might be caused by a combination of more subtle transcriptomic differences or cellular changes without transcriptional correlates. In summary, our comprehensive analysis highlights the ontogenetic and adult transcriptomic differences between cichlids with different color patterns and serves as a basis for further investigation of the mechanistic underpinnings of their diversification.
Change in parent and child psychopathology following obesity treatment and maintenance: A secondary data analysis
Authors: Grammer Anne Claire , Best John R. , Fowler Lauren A. , Stein Richard I. , Kolko Conlon Rachel P. , Balantekin Katherine N. , Welch R. Robinson , Perri Michael G. , Epstein Leonard H. , Wilfley Denise E.
Published: August 2022

Background

General and eating disorder (ED) psychopathology are common among children and adults with overweight/obesity; few studies have examined their course of change throughout family‐based behavioural obesity treatment (FBT) and maintenance.

Objectives

Examine: (1) the changes in the parent and child general and ED psychopathology during FBT and maintenance interventions; (2) the associations between change in psychopathology and change in weight among children or parents; (3) the associations between change in psychopathology within parent–child dyads.

Methods

172 parent–child dyads participated in 4‐month FBT and were subsequently randomized to one of three 8‐month maintenance interventions. General psychopathology (child anxiety/depressive symptoms, parent severity of global psychological distress), ED psychopathology (shape/weight concern), and percent overweight were assessed at baseline, post‐FBT, and post‐maintenance. Separate linear mixed‐effects models evaluated change in general and ED psychopathology, including an interaction between maintenance condition and time. Partial correlations examined associations between change in psychopathology and percent overweight among children or parents, and associations between change in psychopathology within parent–child dyads.

Results

Among children, significant reductions were observed from baseline to post‐FBT in all forms of psychopathology and from post‐FBT to post‐maintenance in general psychopathology. Among parents, significant reductions were observed from baseline to post‐FBT in all forms of psychopathology; reductions were maintained from post‐FBT to post‐maintenance. There was no significant interaction between maintenance condition and time. Correlations between change in most forms of parent or child psychopathology and percent overweight were observed.

Conclusions

Participation in FBT and maintenance was associated with improvements in general and ED psychopathology in both parents and children.