bluuebunny/crossref_metadata_2025 huggingface dataset:
Convolutional Neural Network Models for Automatic Preoperative Severity Assessment in Unilateral Cleft Lip
Authors: McCullough Meghan , Ly Steven , Auslander Allyn , Yao Caroline , Campbell Alex , Scherer Stefan , Magee William P.
Published: June 2021

Background:

Despite the wide range of cleft lip morphology, consistent scales to categorize preoperative severity do not exist. Machine learning has been used to increase accuracy and efficiency in detection and rating of multiple conditions, yet it has not been applied to cleft disease. The authors tested a machine learning approach to automatically detect and measure facial landmarks and assign severity grades using preoperative photographs.

Methods:

Preoperative images were collected from 800 unilateral cleft lip patients, manually annotated for cleft-specific landmarks, and rated using a previously validated severity scale by eight expert reviewers. Five convolutional neural network models were trained for landmark detection and severity grade assignment. Mean squared error loss and Pearson correlation coefficient for cleft width ratio, nostril width ratio, and severity grade assignment were calculated.

Results:

All five models performed well in landmark detection and severity grade assignment, with the largest and most complex model, Residual Network, performing best (mean squared error, 24.41; cleft width ratio correlation, 0.943; nostril width ratio correlation, 0.879; severity correlation, 0.892). The mobile device–compatible network, MobileNet, also showed a high degree of accuracy (mean squared error, 36.66; cleft width ratio correlation, 0.901; nostril width ratio correlation, 0.705; severity correlation, 0.860).

Conclusions:

Machine learning models demonstrate the ability to accurately measure facial features and assign severity grades according to validated scales. Such models hold promise for the creation of a simple, automated approach to classifying cleft lip morphology. Further potential exists for a mobile telephone–based application to provide real-time feedback to improve clinical decision making and patient counseling.
Diagnostic Performance of COVID-19 Reporting and Data System Classification Across Residents and Radiologists: A Retrospective Study
Authors: Koşar Tunç Melis , Kış Naciye , İnce Okan , Kurtul Yıldız Hülya , Önder Hakan
Published: June 2021

Objective

The aim of the study was to evaluate the interobserver agreement and diagnostic accuracy of COVID-19 Reporting and Data System (CO-RADS), in patients suspected COVID-19 pneumonia.

Methods

Two hundred nine nonenhanced chest computed tomography images of patients with clinically suspected COVID-19 pneumonia were included. The images were evaluated by 2 groups of observers, consisting of 2 residents-radiologists, using CO-RADS. Reverse transcriptase–polymerase chain reaction (PCR) was used as a reference standard for diagnosis in this study. Sensitivity, specificity, area under receiver operating characteristic curve (AUC), and intraobserver/interobserver agreement were calculated.

Results

COVID-19 Reporting and Data System was able to distinguish patients with positive PCR results from those with negative PCR results with AUC of 0.796 in the group of residents and AUC of 0.810 in the group of radiologists. There was moderate interobserver agreement between residents and radiologist with κ values of 0.54 and 0.57.

Conclusions

The diagnostic performance of CO-RADS for predicting COVID-19 pneumonia showed moderate interobserver agreement between residents and radiologists.
Imaging of Aberrant Internal Carotid Arteries
Authors: Altay Sedat
Published: June 2021

Objective

Aberrant internal carotid arteries (ICAs) may take abnormal courses in the cervical region. We present the ICA imaging features that suggest the presence of a submucosal mass in the posterior pharyngeal wall caused by such an aberration.

Methods

Cervical computed tomography angiography images of 2400 patients obtained over 5 years were retrospectively reviewed. The ICA courses at the levels of the hypopharynx and oropharynx were evaluated. Aberrant ICAs running posterior to the pharynx were selected. Vessel location was classified into 3 types: lateral to the vertebral foramen (normal, type I); between the lateral foramen and the uncovertebral joint (type II); and medial to the uncovertebral joint (type III). Medical records were examined, and relationships between symptoms, the ICA variations, and imaging features evaluated.

Results

Cervically aberrant ICAs of type II were detected in 45 patients and aberrations of type III in 18. In the latter group, the mean patient age was 66 years, 12 were men and 6 were women. Six (33%) patients (4 men) had clinical symptoms associated with their aberrant ICA courses. In 2 men (11%), both ICAs took aberrant courses. Otherwise, the right ICA was affected in 9 (50%) cases and the left ICA in 7 (39%).

Discussion

Parapharyngeal ICA aberrations were both common and asymptomatic. Such ICAs may be damaged during pharyngeal surgery or intubation. The ICA location should be investigated before any interventional procedure.
Chyloid Fat Carried Adipose-Derived Mesenchymal Stem Cells Accelerate Wound Healing Via Promoting Angiogenesis
Authors: Geng Yinan , Yang Jinxiu , Li Shiyi , Chen Minliang
Published: June 2021

Impaired wound healing is responsible for significant morbidity and mortality worldwide. It is necessary to find a stable, efficient, and safe method to promote soft tissue wound healing. Fat grafting has become increasingly popular in contouring procedures. However, more recently, there has been an emphasis on its regenerative potential. In this study, we established the wound healing model using nude mice. Hematoxylin and eosin and Masson stainings were performed to assess the effect of chyloid fat on the histology of wound healing. A laser Doppler perfusion imager was used to evaluate the blood perfusion of wounds. Immunohistochemistry was carried out to detect the expression of CD31 in wound tissues. The results suggested that after treatment with granule fat or chyloid fat, wound healing was accelerated and blood perfusion was promoted. In addition, granule fat or chyloid fat treatment promoted the angiogenesis of the wound. In addition, we evaluated the amount of adipose-derived mesenchymal stem cells in chyloid fat and granule fat. It was found that chyloid fat contained more adipose-derived mesenchymal stem cells than granule fat did. In conclusion, we proved that chyloid fat could significantly accelerate the wound healing process via promoting angiogenesis. The adipose-derived mesenchymal stem cell plays a critical role in this effect of chyloid fat.
Secondary Surgeries After Oncoplastic Reduction Mammoplasty
Authors: Brown Ciara A. , Mercury Oblaise A. , Hart Alexandra M. , Carlson Grant W. , Losken Albert
Published: June 2021

Purpose

The oncoplastic reduction approach is a popular option for women with breast cancer and macromastia. Although the benefits of this approach are numerous, data on the need for secondary surgeries are limited. We evaluated the need for all secondary surgeries after oncoplastic reduction in an attempt to understand the incidence and indications.

Methods

All patients with breast cancer who underwent an oncoplastic breast reduction at the time of the tumor resection were queried from a prospectively maintained database from 1998 to 2020 (n = 547) at a single institution. Secondary surgical procedures were defined as any unplanned return to the operating room. Demographic and clinical variables were analyzed, and secondary surgeries were classified and evaluated. The timing and rates of secondary surgery were evaluated and compared with clinical variables.

Results

There were 547 patients included in this series with a mean age of 55 years and body mass index of 33.5. Mean duration of follow-up was 3.8 years. One hundred and seventeen (21%) patients underwent 235 secondary surgeries, with an average of 1.4 operations until stable reconstruction was obtained. The reason for the secondary surgery was involved margins (7.5%), major complications (8.6%), aesthetic improvement (13.3%), and completion mastectomy (5.3%). Age 65 years and younger age was associated with any subsequent procedure (P = 0.023) and revision for cosmesis (P = 0.006). Patients with body mass index greater than 35 had increased secondary surgeries for operative complications (P = 0.026).

Conclusions

Secondary surgeries after oncoplastic breast reduction procedures are common. Management of margins and complications, such as hematoma and infection, are early indications, with aesthetic improvement, wound healing complications, fat necrosis, and recurrence being late reasons. The most common reason for reoperation is aesthetic improvement, especially in younger patients. Attention to surgical technique and patient selection will help minimize secondary surgeries for the nononcological reasons.
Independent or Integrated Plastic Surgery Residency Pathways
Authors: Erpenbeck Sarah P. , Bustos Samyd S. , Smith Brandon T. , Egro Francesco M. , Nguyen Vu T.
Published: June 2021

Introduction

The training pathway for plastic surgery has evolved in recent years with the adoption and rise in popularity of the integrated model. Studies have demonstrated that there may be differences between integrated graduates and independent graduates, specifically in career choices and type of practice. This study seeks to understand if there are differences in representation at academic and leadership positions between graduates of the 2 pathways.

Methods

A cross-sectional study was conducted in June of 2018 to assess integrated and independent pathway graduate's representation in academic plastic surgery in the United States. Factors examined were career qualifications, academic productivity, faculty positions, and influence of pathway on career advancement.

Results

A total of 924 academic plastic surgeons were analyzed, 203 (22.0%) of whom were integrated graduates and 721 (78.0%) of whom were independent graduates. Independent graduates had greater National Institutes of Health funding (integrated, $40,802; independent, $257,428; P = 0.0043), higher h-index (integrated, 7.0; independent, 10.0; P < 0.001), and higher publication number (integrated, 17; independent, 25; P = 0.0011). Integrated graduates were more likely to be assistant professors (integrated, 70%; independent, 40.7%; P < 0.001) and required a shorter postresidency time to reach all positions examined compared with independent graduates.

Conclusions

Residency training pathway influences academic plastic surgeons in research output, qualifications, and academic positions. This is likely due to the relatively new nature of the integrated program compared with the independent, as well as the shorter length of training for integrated graduates. However, trends are moving toward integrated graduates showing increased interest and productivity in academic medicine.
When the human brain goes diving: using near-infrared spectroscopy to measure cerebral and systemic cardiovascular responses to deep, breath-hold diving in elite freedivers
Authors: McKnight J. Chris , Mulder Eric , Ruesch Alexander , Kainerstorfer Jana M. , Wu Jingyi , Hakimi Naser , Balfour Steve , Bronkhorst Mathijs , Horschig Jörn M. , Pernett Frank , Sato Katsufumi , Hastie Gordon D. , Tyack Peter , Schagatay Erika
Published: June 2021

Continuous measurements of haemodynamic and oxygenation changes in free living animals remain elusive. However, developments in biomedical technologies may help to fill this knowledge gap. One such technology is continuous-wave near-infrared spectroscopy (CW-NIRS)—a wearable and non-invasive optical technology. Here, we develop a marinized CW-NIRS system and deploy it on elite competition freedivers to test its capacity to function during deep freediving to 107 m depth. We use the oxyhaemoglobin and deoxyhaemoglobin concentration changes measured with CW-NIRS to monitor cerebral haemodynamic changes and oxygenation, arterial saturation and heart rate. Furthermore, using concentration changes in oxyhaemoglobin engendered by cardiac pulsation, we demonstrate the ability to conduct additional feature exploration of cardiac-dependent haemodynamic changes. Freedivers showed cerebral haemodynamic changes characteristic of apnoeic diving, while some divers also showed considerable elevations in venous blood volumes close to the end of diving. Some freedivers also showed pronounced arterial deoxygenation, the most extreme of which resulted in an arterial saturation of 25%. Freedivers also displayed heart rate changes that were comparable to diving mammals both in magnitude and patterns of change. Finally, changes in cardiac waveform associated with heart rates less than 40 bpm were associated with changes indicative of a reduction in vascular compliance. The success here of CW-NIRS to non-invasively measure a suite of physiological phenomenon in a deep-diving mammal highlights its efficacy as a future physiological monitoring tool for human freedivers as well as free living animals.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
Mesobaculum littorinae gen. nov., sp. nov., a novel bacterium isolated from a sea snail Littorina scabra
Authors: Li Fei , Huang Yuanlin , Hu Wenjin , Li Zhe , Wang Qiaozhen , Huang Shushi , Yu Lian , Liu Shaowei , Sun Chenghang , Pan Xinli
Published: June 2021

Members within the family Rhodbacteraceae are morphologically and genetically highly diverse, and originate mostly from coastal marine environments. In this study, a novel species of this family, designated M0103T, was isolated from the surface of a sea snail Littorina scabra. Strain M0103T is Gram-stain-negative, halophilic, non-motile and non-Bacteriochlorophyll a-producing bacterium. Several phenotypic characteristics of the isolate were similar to other species within this family, such as the sole respiratory quinone Q-10 and major fatty acid components C18 : 1
 ω7c, C18 : 0 and C16 : 0. Strain M0103T contains a diphosphatidylglycerol, a phosphatidylglycerol, a phosphatidylcholine, a phosphatidy ethanolamine, a phosphatidylinositol, five unidentified phospholipids and four unidentified polar lipids. Based on the 16S rRNA gene sequence analysis, this isolate showed the closest phylogenetic relationship with ‘

Palleronia pontilimi

’ GH1-23T (95.1 %). Values of average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) of genome sequences were of 70.1–76.4 % and 18.3–20.9 % between the isolate and 24 closely related type strains. Analysis the 4.0 Mb genome of strain M0103T revealed several putative genes associated with cellular stress resistance, which may play protective roles for the isolate in the adaptation to a marine environment. Phylogenetic, phenotypic and chemotaxonomic analyses suggested that strain M0103T represents a novel genus and novel species of the family

Rhodobacteraceae

, for which the name Mesobaculum littorinae gen. nov., sp. nov. is proposed. The type strain is M0103T (=MCCC 1K03619T=KCTC 62358T).
The development and usability testing of digital knowledge translation tools for parents of children with bronchiolitis
Authors: Le Anne , Hartling Lisa , Scott Shannon D.
Published: June 2021

Bronchiolitis is an acute infection of the lower respiratory tract that predominantly affects children less than two years old. Although self-limiting, symptoms of bronchiolitis can be distressing for young children. Research has demonstrated that parents may not have the necessary information to be able to identify bronchiolitis symptoms, resulting in emergency department (ED) visits and hospitalizations. Parents have expressed that they feel unprepared, afraid, and that they lack information on their child’s condition. Digital knowledge translation (KT) tools have the potential to convey complex health information to parents to support their healthcare decision-making needs.

We worked with parents of children with bronchiolitis to develop and evaluate three digital tools on bronchiolitis (whiteboard animation video, infographic, and e-Book). Following prototype completion, usability testing was conducted using iPads in two Alberta ED waiting rooms. Parents were randomized to one out of the three tools. Overall, the tools were highly rated, suggesting that arts-based digital tools are useful in delivering complex health information to parents.
Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring
Authors: Gunn Sophia , Wainberg Michael , Song Zeyuan , Andersen Stacy , Boudreau Robert , Feitosa Mary F. , Tan Qihua , Montasser May E. , O’Connell Jeffrey R. , Stitziel Nathan , Price Nathan , Perls Thomas , Schork Nicholas J. , Sebastiani Paola
Published: June 2021

A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWAS results into a measure of genetic risk that can better predict risk of disease than individual significant variants alone.

We selected 54 polygenic risk scores (PRSs) developed for a variety of outcomes and we calculated their values in individuals from the New England Centenarian Study (NECS, N = 4886) and the Long Life Family Study (LLFS, N = 4577). We compared the distribution of these PRSs among exceptionally long-lived individuals (ELLI), their offspring and controls and we also examined their predictive values, using t-tests and regression models adjusting for sex and principal components reflecting ancestral background of the individuals (PCs). In our analyses we controlled for multiple testing using a Bonferroni-adjusted threshold for 54 traits.

We found that only 4 of the 54 PRSs differed between ELLIs and controls in both cohorts. ELLIs had significantly lower mean PRSs for Alzheimer’s disease (AD), coronary artery disease (CAD) and systemic lupus than controls, suggesting genetic predisposition to extreme longevity may be mediated by reduced susceptibility to these traits. ELLIs also had significantly higher mean PRSs for improved cognitive function. In addition, the PRS for AD was associated with higher risk of dementia among controls but not ELLIs (p = 0.0004, 0.3 in NECS, p = 0.03, 0.93 in LLFS respectively). Interestingly, ELLIs did not have a larger number of homozygous risk genotypes for AD (TNECS= -1.72, TLLFs= 0.83) and CAD (TNECS= -5.08, TLLFs= -0.31) in both cohorts, but did have significantly larger number of homozygous protective genotypes than controls for the two traits (AD: TNECS=3.10, TLLFs= 2.2, CAD: TNECS= 6.57, TLLFs=2.36, respectively).

ELLIs have a similar burden of genetic disease risk as the general population for most traits, but have significantly lower genetic risk of AD, CAD, and lupus. The lack of association between AD PRS and dementia among ELLIs suggests that their genetic risk for AD is somehow buffered by protective genetic or environmental factors.
Developmental Effects on Relative Use of PEPCK and NADP-ME Pathways of C4Photosynthesis in Maize
Authors: Arp Jennifer J. , Kambhampati Shrikaar , Chu Kevin L. , Koley Somnath , Jenkins Lauren M. , Mockler Todd C. , Allen Doug K.
Published: June 2021

C4photosynthesis is an adaptive photosynthetic pathway which concentrates CO2around Rubisco in specialized bundle sheath cells to reduce photorespiration. Historically, the pathway has been characterized into three different subtypes based on the decarboxylase involved, although recent work has provided evidence that some plants can use multiple decarboxylases, with maize in particular using both the NADP-malic enzyme (NADP-ME) pathway and phosphoenolpyruvate carboxykinase (PEPCK) pathway. Parallel C4pathways could be advantageous in balancing energy and reducing equivalents between bundle sheath and mesophyll cells, in decreasing the size of the metabolite gradients between cells and may better accommodate changing environmental conditions or source to sink demands on growth. The enzyme activity of C4decarboxylases can fluctuate with different stages of leaf development, but it remains unclear if the pathway flexibility is an innate aspect of leaf development or an adaptation to the leaf microenvironment that is regulated by the plant. In this study, variation in the two C4pathways in maize were characterized at nine plant ages throughout the life cycle. Two positions in the canopy were examined for variation in physiology, gene expression, metabolite concentration, and enzyme activity, with particular interest in asparagine as a potential regulator of C4decarboxylase activity. Variation in C4and C3metabolism was observed for both leaf age and canopy position, reflecting the ability of C4pathways to adapt to changing microenvironments.

One Sentence Summary

The proportion of the two C4pathways in maize plants is dependent on canopy position and not the age of the leaf.
Herbicidal activity of fluoroquinolone derivatives
Authors: Wallace Michael D. , Debowski Aleksandra W. , Sukhoverkov Kirill V. , Mylne Joshua S. , Stubbs Keith A.
Published: June 2021

Development of herbicides with novel modes of action are crucial for weed control and to hinder herbicide resistance. An attractive novel herbicidal target is plant DNA gyrase, which has been demonstrated to be effectively inhibited by the known antimicrobial ciprofloxacin. Despite this good herbicidal activity ciprofloxacin is not suitable as a herbicide due to its antimicrobial activity, therefore, a diverse library of analogues was analysed to gain insight into the aspects required for herbicidal activity. This analysis revealed significant structural modifications were tolerated and that the fluoride at C-6 and a cyclic amino group at C-7 were not crucial for herbicidal activity. The analysis also revealed that these modifications also affected the antibacterial activity with one compound demonstrating good herbicidal activity and weak antibacterial activity, against both Gram-positive and Gram-negative bacteria.
Pancreatic cancer risk predicted from disease trajectories using deep learning
Authors: Placido Davide , Yuan Bo , Hjaltelin Jessica X. , Zheng Chunlei , Haue Amalie D. , Chmura Piotr J , Yuan Chen , Kim Jihye , Umeton Renato , Antell Gregory , Chowdhury Alexander , Franz Alexandra , Brais Lauren , Andrews Elizabeth , Marks Debora S. , Regev Aviv , Ayandeh Siamack , Brophy Mary , Do Nhan , Kraft Peter , Wolpin Brian M. , Fillmore Nathanael , Rosenthal Michael , Brunak Søren , Sander Chris
Published: June 2021

Pancreatic cancer is an aggressive disease that typically presents late with poor patient outcomes. There is a pronounced medical need for early detection of pancreatic cancer, which can be addressed by identifying high-risk populations. Here we apply artificial intelligence (AI) methods to a dataset of 6 million patient records with 24,000 pancreatic cancer cases in the Danish National Patient Registry (DNPR) and, for comparison, a dataset of three million records with 3,900 pancreatic cancer cases in the United States Department of Veterans Affairs (US-VA) healthcare system. In contrast to existing methods that do not use temporal information, we explicitly train machine learning models on the time sequence of diseases in patient clinical histories and test the ability to predict cancer occurrence in time intervals of 3 to 60 months after risk assessment.

For cancer occurrence within 36 months, the performance of the best model (AUROC=0.88, DNPR), trained and tested on disease trajectories, exceeds that of a model without longitudinal information (AUROC=0.85, DNPR). Performance decreases when disease events within a 3 month window before cancer diagnosis are excluded from training (AUROC[3m]=0.83). Independent training and testing on the US-VA dataset reaches comparable performance (AUROC=0.78, AUROC[3m]=0.76). These results raise the state-of-the-art level of performance of cancer risk prediction on real-world data sets and provide support for the design of prediction-surveillance programs based on risk assessment in a large population followed by affordable surveillance of a relatively small number of patients at highest risk. Use of AI on real-world clinical records has the potential to shift focus from treatment of late-stage to early-stage cancer, benefiting patients by improving lifespan and quality of life.
GTL1 is required for a robust root hair growth response to avoid nutrient overloading
Authors: Shibata Michitaro , Favero David S. , Takebayashi Ryu , Kawamura Ayako , Rymen Bart , Hosokawa Yoichiroh , Sugimoto Keiko
Published: June 2021

Root hair growth is tuned in response to the environment surrounding plants. While most of previous studies focused on the enhancement of root hair growth during nutrient starvation, few studies investigated the root hair response in the presence of excess nutrients.

We report that the post-embryonic growth of wild-type Arabidopsis plants is strongly suppressed with increasing nutrient availability, particularly in the case of root hair growth. We further used gene expression profiling to analyze how excess nutrient availability affects root hair growth, and found that RHD6 subfamily genes, which are positive regulators of root hair growth, are down-regulated in this condition.

On the other hand, defects in GTL1 and DF1, which are negative regulators of root hair growth, cause frail and swollen root hairs to form when excess nutrients are supplied. Additionally, we observed that the RHD6 subfamily genes are mis-expressed in gtl1-1 df1-1. Furthermore, overexpression of RSL4, an RHD6 subfamily gene, induces swollen root hairs in the face of a nutrient overload, while mutation of RSL4 in gtl1-1 df1-1 restore root hair swelling phenotype.

In conclusion, our data suggest that GTL1 and DF1 prevent unnecessary root hair formation by repressing RSL4 under excess nutrient conditions.
Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens
Authors: Belyy Alexander , Merino Felipe , Mechold Undine , Raunser Stefan
Published: June 2021

Several bacterial human pathogens secrete nucleotidyl cyclase toxins, that are activated by interaction with actin of the eukaryotic host cells. However, the underlying molecular mechanism of this process which protects bacteria from self-intoxication is unclear. Here, we report structures of ExoY from Pseudomonas aeruginosa and Vibrio vulnificus in complex with their corresponding activators F-actin and profilin-G-actin. The structures reveal that in contrast to the apo state, two flexible regions become ordered and interact strongly with actin. The specific stabilization of these regions results in an allosteric stabilization of the distant nucleotide binding pocket and thereby to an activation of the enzyme. Differences in the sequence and conformation of the actin-binding regions are responsible for the selective binding to either F- or G-actin. This specificity can be biotechnologically modulated by exchanging these regions from one toxin to the other.

Other bacterial nucleotidyl cyclases, such as the anthrax edema factor and CyaA from Bortedella pertussis, that bind to calmodulin undergo a similar disordered-to-ordered transition during activation, suggesting that the allosteric activation-by-stabilization mechanism of ExoY is paradigmatic for all bacterial nucleotidyl cyclase toxins.
Distribution and molecular evolution of the anti-CRISPR family AcrIF7
Authors: Figueroa Wendy , Cazares Adrián , Cazares Daniel , Wu Yi , de la Cruz Ana , Welch Martin , Kameyama Luis , Nobrega Franklin L. , Guarneros Gabriel
Published: June 2021

Anti-CRISPRs are proteins capable of blocking CRISPR-Cas systems and typically encoded in mobile genetic elements. Since their discovery, numerous anti-CRISPR families have been identified. However, little is known about the distribution and sequence diversity of members within a family, nor how these traits influence the anti-CRISPR’s function and evolution. Here we use AcrIF7 to explore the dissemination and molecular evolution of an anti-CRISPR family. We uncovered five sub-clusters and prevalent anti-CRISPR variants within the group. Remarkably, AcrIF7 homologs display high similarity despite their broad geographical, ecological and temporal distribution. Although mainly associated with Pseudomonas aeruginosa, AcrIF7 was identified in distinct genetic backgrounds indicating horizontal dissemination, primarily by phages. Using mutagenesis, we recreated variation observed in databases but also extended the sequence diversity of the group. Characterisation of the variants identified residues key for the anti-CRISPR function and other contributing to its mutational tolerance. Moreover, molecular docking revealed that variants with affected function lose key interactions with its CRISPR-Cas target. Analysis of publicly available data and the generated variants suggests that the dominant AcrIF7 variant corresponds to the minimal and optimal anti-CRISPR selected in the family. Our study provides a blueprint to investigate the molecular evolution of anti-CRISPR families.
Bacterial filamentation is an in vivo mechanism for cell-to-cell spreading
Authors: Tran Tuan D , Ali Munira Aman , Lee Davin , Félix Marie-Anne , Luallen Robert J
Published: June 2021

Intracellular pathogens are challenged with limited space and resources while replicating in a single host cell. Mechanisms for direct invasion of neighboring host cells have been discovered in cell culture, but we lack an understanding of how bacteria directly spread from cell-to-cell in vivo. Here, we describe the discovery of a bacterial species that uses filamentation as an in vivo mechanism for intracellular spreading between the intestinal epithelial cells of its host, the rhabditid nematodeOscheius tipulae. In vitro and in vivo filamentation by this bacterium,Bordetella atropi, requires a highly conserved nutrient-sensing pathway used by divergent bacteria to detect rich conditions and inhibit the divisome. Thus,B. atropiuses a distinct mechanism for cell-to-cell spreading by coopting a pathway that normally regulates bacterial cell size to trigger filamentation inside host cells.
Modified defence peptides from horseshoe crab target and kill bacteria inside host cells
Authors: Amiss Anna S. , von Pein Jessica B. , Webb Jessica R. , Condon Nicholas D. , Harvey Peta J. , Phan Minh-Duy , Schembri Mark A. , Currie Bart J. , Sweet Matthew J. , Craik David J. , Kapetanovic Ronan , Henriques Sónia Troeira , Lawrence Nicole
Published: June 2021

Bacteria that occupy an intracellular niche can evade extracellular host immune responses and antimicrobial molecules. In addition to classic intracellular pathogens, other bacteria including uropathogenic Escherichia coli (UPEC) can adopt both extracellular and intracellular lifestyles. UPEC intracellular survival and replication complicates treatment, as many therapeutic molecules do not effectively reach all components of the infection cycle. In this study, we explored cell penetrating antimicrobial peptides from distinct structural classes as alternative molecules for targeting bacteria. We identified two β-hairpin peptides from the horseshoe crab, tachyplesin I and polyphemusin I, with broad antimicrobial activity toward a panel of pathogenic and non-pathogenic bacteria in planktonic form. Peptide analogues [I11A]tachyplesin I and [I11S]tachyplesin I maintained activity toward bacteria, but were less toxic to mammalian cells than native tachyplesin I. This important increase in therapeutic window allowed treatment with higher concentrations of [I11A]tachyplesin I and [I11S]tachyplesin I, to significantly reduce intramacrophage survival of UPEC in an in vitro infection model. Mechanistic studies using bacterial cells, model membranes and cell membrane extracts, suggest that tachyplesin I and polyphemusin I peptides kill UPEC by selectively binding and disrupting bacterial cell membranes. Moreover, treatment of UPEC with sublethal peptide concentrations increased zinc toxicity and enhanced innate macrophage antimicrobial pathways. In summary, our combined data show that cell penetrating peptides are attractive alternatives to traditional small molecule antibiotics for treating UPEC infection, and that optimization of native peptide sequences can deliver effective antimicrobials for targeting bacteria in extracellular and intracellular environments.
Genome-wide identification, expression and bioinformatic analyses of GRAS transcription factor genes in rice
Authors: Dutta Mouboni , Saha Anusree , Moin Mazahar , Kirti P.B.
Published: June 2021

Our group has previously identified the activation tagging of a GRAS transcription factor (TF)gene in the gain-of-function mutant population of rice (indicarice variety BPT 5204) screened for water use efficiency (Moin et al, 2016a). This family of GRAS transcription factors has been well known for their diverse roles in gibberellin signaling, light responses, root development, gametogenesis etc. Recent studies indicated their role in biotic and abiotic responses as well. Although this family of TFs received significant attention, not many genes were identified specifically for their roles in mediating stress tolerance in rice. OnlyOsGRAS23(here named asOsGRAS22) was reported to code for a TF that induces drought tolerance in rice. In the present study, we have analyzed the expression patterns of rice GRAS TF genes under abiotic (NaCl and ABA treatments) and biotic (leaf samples infected with pathogens,Xanthomonas oryzaepv.oryzaethat causes bacterial leaf blight andRhizoctonia solanithat causes sheath blight) stress conditions. In addition, their expression patterns were also analyzed in thirteen different developmental stages. We studied their spatio-temporal regulation and correlated them within-silicostudies. Fully annotated genomic sequences available in rice database have enabled us to study the protein properties, ligand interactions, domain analysis and presence ofcis-regulatory elements in a bioinformatics analysis. Most of the genes were induced immediately after the onset of stress particularly in the roots of ABA treated plants.OsGRAS39was found to be very highly expressive gene under sheath blight infection and both abiotic stress treatments whileOsGRAS8,OsSHR1andOsSLR1were also responsive. Our earlier functional characterization (Moin et al., 2016a) followed by the genome wide characterization of the GRAS gene family members in the present study clearly show that they are highly appropriate candidate genes for manipulating stress tolerance in rice and other crop plants.
Robust integration of single-cell cytometry datasets
Authors: Pedersen Christina Bligaard , Dam Søren Helweg , Barnkob Mike Bogetofte , Leipold Michael D. , Purroy Noelia , Rassenti Laura Z. , Kipps Thomas J. , Nguyen Jennifer , Lederer James Arthur , Gohil Satyen Harish , Wu Catherine J. , Olsen Lars Rønn
Published: June 2021

Combining single-cell cytometry datasets increases the analytical flexibility and the statistical power of data analyses. However, in many cases the full potential of co-analyses is not reached due to technical variance between data from different experimental batches. Here, we present cyCombine, a method to robustly integrate cytometry data from different batches, experiments, or even different experimental techniques, such as CITE-seq, flow cytometry, and mass cytometry. We demonstrate that cyCombine maintains the biological variance and the structure of the data, while minimizing the technical variance between datasets. cyCombine does not require technical replicates across datasets, and computation time scales linearly with the number of cells, allowing for integration of massive datasets. Robust, accurate, and scalable integration of cytometry data enables integration of multiple datasets for primary data analyses and the validation of results using public datasets.
Sparse connectivity for MAP inference in linear models using sister mitral cells
Authors: Tootoonian Sina , Schaefer Andreas , Latham Peter
Published: June 2021

Sensory processing is hard because the variables of interest are encoded in spike trains in a relatively complex way. A major goal in studies of sensory processing is to understand how the brain extracts those variables. Here we revisit a common encoding model in which variables are encoded linearly. Although there are typically more variables than neurons, this problem is still solvable because only a small number of variables appear at any one time (sparse prior). However, previous solutions require all-to-all connectivity, inconsistent with the sparse connectivity seen in the brain. Here we propose an algorithm that provably reaches the MAP (maximum a posteriori) inference solution, but does so using sparse connectivity. Our algorithm is inspired by the circuit of the mouse olfactory bulb, but our approach is general enough to apply to other modalities. In addition, it should be possible to extend it to nonlinear encoding models.

Sensory systems must infer latent variables from noisy and ambiguous input. MAP inference – choosing the most likely latent variable given the sensory input – is one of the simplest methods for doing that, but its neural implementation often requires all-to-all connectivity between the neurons involved. In common sensory contexts this can require a single neuron to connect to hundreds of thousands of others, which is biologically implausible. In this work we take inspiration from the ‘sister’ mitral cells of the olfactory system – groups of neurons associated with the same input channel – to derive a method for performing MAP inference using sparse connectivity. We do so by assigning sister cells to random subsets of the latent variables and using additional cells to ensure that sisters correctly share information. We then derive the circuitry and dynamics required for the sister cells to compute the original MAP inference solution. Our work yields a biologically plausible circuit that provably solves the MAP inference problem and provides experimentally testable predictions. While inspired by the olfactory system, our method is quite general, and is likely to apply to other sensory modalities.
Transcriptional milestones in Dictyostelium development
Authors: Katoh-Kurasawa Mariko , Hrovatin Karin , Hirose Shigenori , Webb Amanda , Ho Hsing-I , Zupan Blaž , Shaulsky Gad
Published: June 2021

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite the genetic, temporal, and developmental perturbations. The gene annotations in these groups validate known transitions and reveal new developmental events. For example, DNA replication genes are tightly coregulated with cell division genes, so they are expressed in mid-development although chromosomal DNA is not replicated. Our data set includes 486 transcriptional profiles that can help identify new relationships between transcription and development and improve gene annotations. We show its utility by showing that cycles of aggregation and disaggregation in allorecognition-defective mutants involve dedifferentiation. We also show sensitivity to genetic and developmental conditions in two commonly used actin genes, act6 and act15, and robustness of the coaA gene. Finally, we propose that gpdA is a better mRNA quantitation standard because it is less sensitive to external conditions than commonly used standards. The data set is available for democratized exploration through the web application dictyExpress and the data mining environment Orange.
Identifying focus areas to decode the decision to litigate contractual disputes in construction
Authors: Jagannathan Murali , Delhi Venkata Santosh Kumar
Published: June 2021

Purpose

Strong and independent judiciary symbolizes transparency and impartiality in the dispute resolution process. However, litigation is often time-consuming and affects the working relationship between the disputants. In the construction context, where projects typically have a short life span of three to four years, dispute resolution through litigation induces unaffordable process delays. Despite the inherent challenges associated with litigation, it is observed that disputing parties resort to litigation. This behavior, called the litigation dilemma, ostensibly appears counterintuitive to rational decision-making.

Design/methodology/approach

The study identifies 35 “decision to litigate” (DTL)-triggers from a review of the literature and court cases followed by expert interviews and groups them into thematic research domains using Exploratory Factor Analysis (EFA) followed by Confirmatory Factor Analysis (CFA).

Findings

DTL studies in construction stands benefited through interdisciplinary research. “Presumptuous decision-making,” “construction project characteristics,” “milieu influence,” “interest in amicable resolution,” “positional focus” and “opportunism” are the six focus areas to decode the DTL in construction.

Research limitations/implications

The study identifies factors that consolidate the knowledge from various fields with the substantive experience of construction professionals from across the world to help understand the dynamics behind the DTL in the context of contract-linked disputes in construction.

Originality/value

The findings from the domains of law, behavior, sociology and economics can help understand the above dilemma in the context of contractual disputes in construction. However, studies that explore the “decision to litigate” (DTL) contractual disputes in construction are limited, providing a vast scope for further research. The current study addresses a part of this gap.
Women founders in a high-tech incubator: negotiating entrepreneurial identity in the Indian socio-cultural context
Authors: Gupta Namrata , Etzkowitz Henry
Published: June 2021

Purpose

This study aims to understand the socio-cultural context of Indian women's high-tech entrepreneurial experience. Despite a small proportion of women entrepreneurs, and the traditional gender dynamics among the educated middle-classes that appears to be antithetical to female entrepreneurship; women-led high-tech start-ups are on the rise.

Design/methodology/approach

Semi-structured interviews were conducted with women founders at an academic incubator in an elite Indian Institute of Technology. The study was based on the post-structural feminist approach that women entrepreneurs are embedded in their socio-cultural and institutional context. During data collection, the Coronavirus lockdown provided a natural experiment, highlighting entrepreneurial response to unforeseen obstacles.

Findings

It finds that the context is significant in constructing opportunity, and in navigating challenges of gender and entrepreneurship. Further, in the process of construction of an entrepreneurial identity, women innovators not only reproduce, but also modify their context. Also, the experiences with academic incubator indicate positive results both for gender dynamics and enhancing an emergent entrepreneurial culture.

Practical implications

The study highlights that women's high-tech entrepreneurship has considerable potential for enhancing women's status in society through the support of academic incubator. This has certain implications for policy.

Originality/value

It provides an insight in to the hitherto neglected issue of women's high-tech entrepreneurship in India, and argues that a study of “social embeddedness” not only highlights constraints for women entrepreneurs unique to that context, but also the potential of women's entrepreneurship in advancing women's agency and gender equality.
The impact of intangible intensity on relevance of R&D information: evidence from India
Authors: Kumari Pooja , Mishra Chandra Sekhar
Published: June 2021

Purpose

This paper aims to examine the impact of the intangible intensity of the firm on the relevance of research and development (R&D) information to determine equity values in India. Additionally, the study compares the association of input information on R&D investment (the reported R&D cost) and output information on R&D investment (patent count) with equity values. Further, the study also examines the operational nature of the firm and patent count, which is the better proxy to measure the intangible intensity of the firm.

Design/methodology/approach

The authors compared the explanatory power of R&D information between intangible and non-intangible intensive firms. To estimate the value relevance of R&D information, the authors followed the statistical model based on the theoretical framework of the residual income model.

Findings

The results indicate that there is a significant moderating impact of the intangible intensity of the firm on the relevance of R&D information to determine equity values in India over the 25 years study period (from 1991 to 2016). Further, in India, the study finds that the input information of R&D outlay is more relevant than output information on R&D outlay to determine equity values, irrespective of the proxy measure of intangible intensity. Moreover, the study finds that the operational nature of the firm is a better proxy of the intangible intensity of the firm compared to patent counts.

Research limitations/implications

In this study, pooled cross-sectional data were used for analysis. In the future, longitudinal and panel data can be used for more insightful results.

Practical implications

The findings of the study provide direction to investors and creditors to find the intrinsic value of the investments in internally developed intangible assets, which will reduce the asymmetry between the market value and accounting value of equity.

Originality/value

The paper offers insights into the impact of intangible intensity on the relevance quality of R&D information in an emerging country.
Bank earnings management using loan loss provisions: comparing the UK, France, South Africa and Egypt
Authors: Ozili Peterson K.
Published: June 2021

Purpose

This paper aims to investigate bank earnings management using loan loss provision. The paper examines income smoothing, which is a type of earnings management. It compares the income smoothing behaviour of banks in the UK, France, South Africa and Egypt.

Design/methodology/approach

The study uses the panel fixed effect regression methodology to analyse bank income smoothing.

Findings

The findings show that bank income smoothing is present in the UK and Egypt and absent in France and South Africa. Banks in Egypt used LLPs to smooth income before the global financial crisis. Meanwhile, bank income smoothing is pronounced in France during and after the financial crisis but was absent in the pre-crisis period. Also, bank income smoothing is reduced in countries that (1) have strict banking supervision, (2) adopt common law particularly the United Kingdom, and by countries that adopt civil law, particularly France and Egypt. Bank earnings management is greater in countries that (3) adopt a mixed legal system, particularly South Africa, and in countries that adopt International Financial Reporting Standards accounting standards.

Research limitations/implications

The implication of the findings is that country differences may affect banks' incentive to smooth income using loan loss provision.

Originality/value

The novelty of this paper is that it explicitly analyses specific countries that have different supervisory regimes, different structure and accounting rules.