bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning enabled analysis of cardiac sphericity
Authors: Vukadinovic Milos , Kwan Alan C. , Yuan Victoria , Salerno Michael , Lee Daniel C. , Albert Christine M. , Cheng Susan , Li Debiao , Ouyang David , Clarke Shoa L.
Published: July 2022

Quantification of chamber size and systolic function is a fundamental component of cardiac imaging, as these measurements provide a basis for establishing both diagnosis and appropriate treatment for a spectrum of cardiomyopathies. However, the human heart is a complex structure with significant uncharacterized phenotypic variation beyond traditional metrics of size and function. Characterizing variation in cardiac shape and morphology can add to our ability to understand and classify cardiovascular risk and pathophysiology. We describe deep learning enabled measurement of left ventricle (LV) sphericity using cardiac magnetic resonance imaging data from the UK Biobank and show that among adults with normal LV volumes and systolic function, increased sphericity is associated with increased risk for incident atrial fibrillation (HR 1.31 per SD, 95% CI 1.23-1.38), cardiomyopathy (HR 1.62 per SD, 95% CI 1.29-2.02), and heart failure (HR 1.24, 95% CI 1.11-1.39), independent of traditional risk factors including age, sex, hypertension, and body mass index. Using genome-wide association studies, we identify four loci associated with sphericity at genome-wide significance. These loci harbor known and suspected cardiomyopathy genes. Through genetic correlation and Mendelian randomization, we provide evidence that sphericity may represent a subclinical manifestation of non-ischemic cardiomyopathy.
Integrative analysis of clinical health records, imaging and pathogen genomics identifies personalized predictors of disease prognosis in tuberculosis
Authors: Sambarey Awanti , Smith Kirk , Chung Carolina , Arora Harkirat Singh , Yang Zhenhua , Agarwal Prachi , Chandrasekaran Sriram
Published: July 2022

Tuberculosis (TB) afflicts over 10 million people every year and its global burden is projected to increase dramatically due to multidrug-resistant TB (MDR-TB). The Covid-19 pandemic has resulted in reduced access to TB diagnosis and treatment, reversing decades of progress in disease management globally. It is thus crucial to analyze real-world multi-domain information from patient health records to determine personalized predictors of TB treatment outcome and drug resistance. We conduct a retrospective analysis on electronic health records of 5060 TB patients spanning 10 countries with high burden of MDR-TB including Ukraine, Moldova, Belarus and India available on the NIAID-TB portals database. We analyze over 200 features across multiple host and pathogen modalities representing patient social demographics, disease presentations as seen in cChest X rays and CT scans, and genomic records with drug susceptibility features of the pathogen strain from each patient. Our machine learning model, built with diverse data modalities outperforms models built using each modality alone in predicting treatment outcomes, with an accuracy of 81% and AUC of 0.768. We determine robust predictors across countries that are associated with unsuccessful treatmentclinical outcomes, and validate our predictions on new patient data from TB Portals. Our analysis of drug regimens and drug interactions suggests that synergistic drug combinations and those containing the drugs Bedaquiline, Levofloxacin, Clofazimine and Amoxicillin see more success in treating MDR and XDR TB. Features identified via chest imaging such as percentage of abnormal volume, size of lung cavitation and bronchial obstruction are associated significantly with pathogen genomic attributes of drug resistance. Increased disease severity was also observed in patients with lower BMI and with comorbidities. Our integrated multi-modal analysis thus revealed significant associations between radiological, microbiological, therapeutic, and demographic data modalities, providing a deeper understanding of personalized responses to aid in the clinical management of TB.
Vaccine-enhanced competition permits rational bacterial strain replacement in the gut
Authors: Lentsch Verena , Woller Aurore , Rocker Andrea , Aslani Selma , Moresi Claudia , Ruoho Niina , Larsson Louise , Fattinger Stefan A. , Wenner Nicolas , Cappio Barazzone Elisa , Hardt Wolf-Dietrich , Loverdo Claude , Diard Mederic , Slack Emma
Published: July 2022

Colonization of the intestinal lumen precedes invasive infection for a wide range of enteropathogenic and opportunistic pathogenic bacteria. Here we show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion and strain replacement in the mouse gut lumen. This approach can be applied both prophylactically to prevent invasion of non-typhoidal Salmonella strains, or therapeutically to displace an established Escherichia coli. Both intact adaptive immunity and metabolic niche competition are necessary for efficient vaccine-enhanced competition. Our findings imply that mucosal antibodies have evolved to work in the context of gut microbial ecology, by influencing the outcome of competition. This has broad implications for the elimination of pathogenic and antibiotic-resistant bacterial reservoirs, and for rational microbiota engineering.
Accelerating genomic workflows using NVIDIA Parabricks
Authors: O’Connell Kyle A. , Yosufzai Zelaikha B. , Campbell Ross A. , Lobb Collin J. , Engelken Haley T. , Gorrell Laura M. , Carlson Thad B. , Catana Josh J. , Mikdadi Dina , Bonazzi Vivien R. , Klenk Juergen A.
Published: July 2022

Background

As genome sequencing becomes a more integral part of scientific research, government policy, and personalized medicine, the primary challenge for researchers is shifting from generating raw data to analyzing these vast datasets. Although much work has been done to reduce compute times using various configurations of traditional CPU computing infrastructures, Graphics Processing Units (GPUs) offer the opportunity to accelerate genomic workflows by several orders of magnitude. Here we benchmark one GPU-accelerated software suite called NVIDIA Parabricks on Amazon Web Services (AWS), Google Cloud Platform (GCP), and an NVIDIA DGX cluster. We benchmarked six variant calling pipelines, including two germline callers (HaplotypeCaller and DeepVariant) and four somatic callers (Mutect2, Muse, LoFreq, SomaticSniper).

Results

For germline callers, we achieved up to 65x acceleration, bringing HaplotypeCaller runtime down from 36 hours to 33 minutes on AWS, 35 minutes on GCP, and 24 minutes on the NVIDIA DGX. Somatic callers exhibited more variation between the number of GPUs and computing platforms. On cloud platforms, GPU-accelerated germline callers resulted in cost savings compared with CPU runs, whereas somatic callers were often more expensive than CPU runs because their GPU acceleration was not sufficient to overcome the increased GPU cost.

Conclusions

Germline variant callers scaled with the number of GPUs across platforms, whereas somatic variant callers exhibited more variation in the number of GPUs with the fastest runtimes, suggesting that these workflows are less GPU optimized and require benchmarking on the platform of choice before being deployed at production scales. Our study demonstrates that GPUs can be used to greatly accelerate genomic workflows, thus bringing closer to grasp urgent societal advances in the areas of biosurveillance and personalized medicine.
On the Genes, Genealogies, and Geographies of Quebec
Authors: Anderson-Trocmé Luke , Nelson Dominic , Zabad Shadi , Diaz-Papkovich Alex , Baya Nikolas , Touvier Mathilde , Jeffery Ben , Dina Christian , Vézina Hélène , Kelleher Jerome , Gravel Simon
Published: July 2022

Population genetic models only provide coarse representations of real-world ancestry. We use a pedigree compiled from four million parish records and genotype data from 2,276 French and 20,451 French Canadian (FC) individuals, to finely model and trace FC ancestry through space and time. The loss of ancestral French population structure and the appearance of spatial and regional structure highlights a wide range of population expansion models. Geographic features shaped migrations throughout, and we find enrichments for migration, genetic and genealogical relatedness patterns within river networks across Quebec regions. Finally, we provide a freely accessible simulated whole-genome sequence dataset with spatiotemporal metadata for 1,426,749 individuals reflecting intricate FC population structure. Such realistic populations-scale simulations provide new opportunities to investigate population genetics at an unprecedented resolution.

Lay Summary

We all share common ancestors ranging from a couple generations ago to hundreds of thousands of years ago. The genetic differences between individuals today mostly depends on how closely related they are. The only problem is that the actual genealogies that relate all of us are often forgotten over time. Some geneticists have tried to come up with simple models of our shared ancestry but they don’t really explain the full, rich history of humanity. Our study uses a multi-institutional project in Quebec that has digitized parish records into a single unified genealogical database that dates back to the arrival of the first French settlers four hundred years ago. This genealogy traces the ancestry of millions of French-Canadian and we have used it to build a very high resolution genetic map. We used this genetic map to study in detail how certain historical events, and landscapes have influenced the genomes of French-Canadians today.

One-Sentence Summary

We present an accurate and high resolution spatiotemporal model of genetic variation in a founder population.
Homologue Series Detection and Management in LC-MS data with homologueDiscoverer
Authors: Mildau Kevin , van der Hooft Justin J.J. , Flasch Mira , Warth Benedikt , Abiead Yasin El , Koellensperger Gunda , Zanghellini Jürgen , Büschl Christoph
Published: July 2022

Untargeted metabolomics data analysis is highly labor intensive and can be severely frustrated by both experimental noise and redundant features. Homologous polymer series are a particular case of features that can either represent large numbers of noise features, or alternatively represent features of interest with large peak redundancy. Here we present homologueDiscoverer, an R package which allows for the targeted and untargeted detection of homologue series as well as their evaluation and management using interactive plots and simple local database functionalities.

Availability

homologueDiscoverer is freely available at github https://github.com/kevinmildau/homologueDiscoverer.

Contact

kevin.mildau@univie.ac.at, christoph.bueschl@boku.ac.at, juergen.zanghellini@univie.ac.at
CCR2 identifies tendon resident macrophage and T cell populations while CCR2 deficiency impedes late tendon healing
Authors: Muscat Samantha , Nichols Anne E.C. , Gira Emma , Loiselle Alayna E.
Published: July 2022

During tendon healing, macrophages are thought to be a key mediator of scar tissue formation, which prevents successful functional restoration of the tendon. However, macrophages are critical for successful tendon healing as they aid in wound debridement, extracellular matrix deposition, and promote fibroblast proliferation. Recent work has sought to better define the multi-faceted functions of macrophages using depletion studies, while other studies have identified a tendon resident macrophage population. To begin to delineate the functions of tendon-resident versus circulation-derived macrophages, we examined the tendon healing phenotype in Chemokine Receptor 2 (CCR2) reporter (CCR2GFP/+), and knockout mice. CCR2 is a chemokine receptor primarily found on the surface of circulating bone marrow derived monocytes, with CCR2 being an important mediator of macrophage recruitment to wound environments. Surprisingly, CCR2GFP/+ cells were present in the tendon during adult homeostasis, and single cell RNA sequencing identified these cells as tendon-resident macrophages and T cells. During both homeostasis and healing, CCR2 knockout resulted in a substantial decrease in CCR2GFP+ cells and pan-macrophages. Additionally, loss of CCR2 resulted in reduced numbers of myofibroblasts and impeded functional recovery during late healing. This study highlights the heterogeneity of tendon-resident and recruited immune cells and their contributions following injury, and establishes an important role for CCR2 in modulating both the adult tendon cell environment and tendon healing process.
Grape-seed proanthocyanidin extract (GSPE) modulates diurnal oscillations of key hepatic metabolic genes and metabolites alleviating hepatic lipid deposition in cafeteria-fed obese rats in a time-of-day-dependent manner
Authors: Rodríguez Romina M , de Assis Leonardo Vinícius Monteiro , Colom-Pellicer Marina , Quesada-Vázquez Sergio , Cruz-Carrión Álvaro , Escoté Xavier , Oster Henrik , Aragonès Gerard , Mulero Miquel
Published: July 2022

Metabolic syndrome (MS) and its related diseases, including obesity and non-alcoholic fatty liver disease (NAFLD), have become a public health issue due to their increasing prevalence. Polyphenols, such as grape seed proanthocyanidin extract (GSPE), are bioactive compounds present in fruits and vegetables that show promise for MS treatment. We have previously demonstrated that the efficacy of this phenolic extract in the modulation of liver circadian clocks was affected by the time of the day at which it was ingested. Thus, we wondered if the beneficial effects of GSPE consumption in NAFLD could be mediated by diurnal modulation of hepatic lipid and glucose metabolism and whether GSPE effects on liver metabolism are impacted by the timing of administration. Results from hepatic lipid profiling, expression rhythm analysis of metabolic genes together with liver metabolomics in rats revealed that the CAF diet impaired glucose homeostasis and enhanced lipogenesis in the liver, leading to the generation of hepatosteatosis. Chronic consumption of GSPE at the onset of the active phase was able to restore the daily oscillation of liver mass and of key lipogenic and glycogenic genes, along with the reestablishment of liver metabolite rhythms, demonstrating hepatoprotective properties by decreasing triglyceride accumulation and lipid droplet formation in the liver, thus mitigating the development of CAF-induced NAFLD. Furthermore, in vitro data suggest that catechin, one of the main phenolic compounds found in the GSPE extract, may be involved in the ameliorating effects of GSPE against NAFLD.
Two canonically aerobic foraminifera express distinct peroxisomal and mitochondrial metabolisms
Authors: Powers Christopher , Gomaa Fatma , Billings Elizabeth B. , Utter Daniel R. , Beaudoin David J. , Edgcomb Virginia P. , Hansel Colleen M. , Wankel Scott D. , Filipsson Helena L. , Zhang Ying , Bernhard Joan M.
Published: July 2022

Certain benthic foraminifera are known to thrive in marine sediments with low oxygen or even without detectable oxygen. Potential survival avenues used by these supposedly aerobic protists include fermentation and anaerobic respiration, although details on their adaptive mechanisms remain somewhat elusive. To better understand the metabolic versatility of foraminifera, we studied two benthic species that thrive in oxygen-depleted marine sediments. Here we detail, via transcriptomics and metatranscriptomics, differential gene expression of Nonionella stella and Bolivina argentea, collected from Santa Barbara Basin, California, USA, in response to varied oxygenation and chemical amendments. Organelle-specific metabolic reconstructions revealed that these two species utilize adaptable mitochondrial and peroxisomal metabolism that reflect their differing lifestyles. N. stella, most abundant in anoxia and characterized by the lack of food vacuoles and the abundance of intracellular lipid droplets, was predicted to couple the putative peroxisomal beta-oxidation and glyoxylate cycle with a versatile electron transport system and a partial TCA cycle running in the reductive direction. In contrast, B. argentea, most abundant in hypoxia and contains food vacuoles, was predicted to utilize the putative peroxisomal gluconeogenesis and a full TCA cycle but lacks the expression of key beta-oxidation and glyoxylate cycle genes. These metabolic adaptations likely confer ecological success while encountering deoxygenation and illuminate the importance of metabolic modifications and interactions between mitochondria and peroxisomes in protists.

Importance

Foraminiferan protists are nearly ubiquitous in today’s oceans and likely were major components of the Neoproterozoic protistan community. While largely considered aerobic, certain foraminifera demonstrate surprising adaptability to hypoxia and anoxia, contributing to biogeochemical cycling in benthic environments. The analyses of Rhizarian adaptive metabolism set the stage for studying other microeukaryotes under increasing ocean deoxygenation. Revealing the metabolic roles of foraminifera in anaerobic biogeochemical cycling should spur reassessments of existing paleoecological datasets as well as new perspectives on the metabolic evolution of eukaryotic cells.
Phenome-wide Mendelian randomization study of plasma triglycerides and 2,600 disease traits
Authors: Park Joshua K. , Bafna Shantanu , Forrest Iain S. , Duffy Áine , Marquez-Luna Carla , Petrazzini Ben O. , Vy Ha My , Jordan Daniel M. , Verbanck Marie , Narula Jagat , Rosenson Robert S. , Rocheleau Ghislain , Do Ron
Published: July 2022

Background

Causality between plasma triglyceride (TG) levels and atherosclerotic cardiovascular disease (ASCVD) risk remains controversial despite more than four decades of study and two recent landmark trials, STRENGTH and REDUCE-IT. Further unclear is the association between TG levels and non-atherosclerotic diseases across organ systems.

Methods

Here, we conducted a phenome-wide, two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) regression to systematically infer the causal effects of plasma TG levels on 2,600 disease traits in the European ancestry population of UK Biobank. For replication, we externally tested 221 nominally significant associations (p < 0.05) in an independent cohort from FinnGen. To account for potential horizontal pleiotropy and the influence of invalid instrumental variables, we performed sensitivity analyses using MR-Egger regression, weighted median estimator, and MR-PRESSO. Finally, we used multivariable MR controlling for correlated lipid fractions to distinguish the independent effect of plasma TG levels.

Results

Our results identified 7 disease traits reaching Bonferroni-corrected significance in both the discovery (p < 1.92 × 10-5) and replication analyses (p < 2.26 × 10-4), supporting a causal relationship between plasma TG levels and ASCVDs, including coronary artery disease (OR 1.33, 95% CI 1.24-1.43, p = 2.47 × 10-13). We also identified 12 disease traits that were Bonferroni-significant in the discovery or replication analysis and at least nominally significant in the other analysis (p < 0.05), identifying plasma TG levels as a novel risk factor for 9 non-ASCVD diseases, including uterine leiomyoma (OR 1.19, 95% CI 1.10-1.29, p = 1.17 × 10-5).

Conclusions

Taking a phenome-wide, two-sample MR approach, we identified causal associations between plasma TG levels and 19 disease traits across organ systems. Our findings suggest unrealized drug repurposing opportunities or adverse effects related to approved and emerging TG-lowering agents as well as mechanistic insights for future study.
Data collection from crystals grown in microfluidic droplets
Authors: Babnigg Gyorgy , Sherrell Darren , Kim Youngchang , Johnson Jessica L. , Nocek Boguslaw , Tan Kemin , Axford Danny , Li Hui , Bigelow Lance , Welk Lukas , Endres Michael , Owen Robin L. , Joachimiak Andrzej
Published: July 2022

Protein crystals grown in microfluidic droplets have been shown to be an effective and robust platform for storage, transport and serial crystallography data collection with a minimal impact on diffraction quality. Single macromolecular microcrystals grown in nanolitre-sized droplets allow the very efficient use of protein samples and can produce large quantities of high-quality samples for data collection. However, there are challenges not only in growing crystals in microfluidic droplets, but also in delivering the droplets into X-ray beams, including the physical arrangement, beamline and timing constraints and ease of use. Here, the crystallization of two human gut microbial hydrolases in microfluidic droplets is described: a sample-transport and data-collection approach that is inexpensive, is convenient, requires small amounts of protein and is forgiving. It is shown that crystals can be grown in 50–500 pl droplets when the crystallization conditions are compatible with the droplet environment. Local and remote data-collection methods are described and it is shown that crystals grown in microfluidics droplets and housed as an emulsion in an Eppendorf tube can be shipped from the US to the UK using a FedEx envelope, and data can be collected successfully. Details of how crystals were delivered to the X-ray beam by depositing an emulsion of droplets onto a silicon fixed-target serial device are provided. After three months of storage at 4°C, the crystals endured and diffracted well, showing only a slight decrease in diffracting power, demonstrating a suitable way to grow crystals, and to store and collect the droplets with crystals for data collection. This sample-delivery and data-collection strategy allows crystal droplets to be shipped and set aside until beamtime is available.
Consumer responses toward LGBTQ+ diversity CSR: what differences do CSR levels and CSR fit make?
Authors: Kim Yeonsoo
Published: July 2022

Purpose

This study investigated consumer responses to LGBTQ+ specific diversity CSR, taking into account different levels of CSR engagement and perceived CSR fit. Perceived motives were considered as a mediator in the process.

Design/methodology/approach

An online experiment was conducted using real consumer samples (n = 376).

Findings

As companies actively demonstrate corporate values to promote LGBTQ+ human rights, consumers recognized that LGBTQ+ diversity CSR was being pursued out of altruistic motives for social good stemming from business ethics and morals. In addition, it was found that the more active the LGBTQ+ diversity CSR practice, the higher the evaluation of the company among consumers. Regarding CSR fit, perceived fit in LGBTQ+ diversity had a significant effect on both the consumer perception of CSR motive and the company evaluation. In addition to these direct impacts of CSR level and CSR fit, these two factors indirectly influenced corporate evaluation through perceived motivation and consequently affected purchase intention.

Originality/value

Despite drastic changes in the legal and social environment related to LGBTQ+ diversity, there are few studies on how consumers will react when companies actively or passively participate in or hesitate and oppose CSR on LGBTQ+ diversity. By presenting empirical evidence of consumer response to LGBTQ+ CSR, this study provided business managers and public relations professionals with the insights they need to make informed decisions about the extent to which they engage in LGBTQ+ diversity CSR.
Premature deindustrialization risk in Vietnam
Authors: Tsukada Yuta
Published: July 2022

Purpose

This study aims to examine the premature deindustrialization risk in Vietnam.

Design/methodology/approach

This study uses a manufacturing–income relationship to conduct an empirical estimation. The latecomer index is adopted in the regression model to identify a downward shift of latecomer's relationship.

Findings

The empirical analysis indicates that there is a risk of premature deindustrialization in the Northern Midlands and Mountain Areas. The provinces with low trade openness or foreign direct investment may experience risk of premature deindustrialization.

Practical implications

This study proposes technology diffusion as a policy direction to prevent premature deindustrialization. Furthermore, the Vietnamese government should improve the business environment in the Northern Midlands and Mountain Areas by promoting and attracting export-oriented foreign direct investment.

Originality/value

This study is the first to examine premature deindustrialization in Vietnam based on provincial-level data.
Can Arab-origin brands go global? An exploratory study
Authors: Farrag Dalia Abdel Rahman , Abu Gharara Sahar Raafat
Published: July 2022

Purpose

The purpose of this exploratory paper is to investigate and understand the most important factors that influence Arab-origin brands to go global and to appear in brand valuation studies.

Design/methodology/approach

Initially, content analysis on current literature has been conducted followed by qualitative research in the form of in-depth interviews with marketing experts that own or work for successful Arab-origin brands in Muslim countries. Data has been collected related to brands from Qatar, United Arab Emirates, Egypt, Kuwait and Saudi Arabia. A total of 20 in-depth interviews have been conducted by using face-to-face/online voice recorded method. Interviews have been transcribed, coded and analyzed.

Findings

Findings revealed that the main factors affecting the global branding process for Arab-origin brands are internal as compared to external factors. Some of the factors are common with factors in current literature such as dealing with local competition, however, many new factors as well have been identified like brand essence/meaning, internal marketing, top management support and entering mature markets. Cultural heritage plays a significant role in the strategy, creativity and leadership related to building global brands in Arab/Islamic countries. A preliminary model has been proposed based on the findings.

Research limitations/implications

This study is just a starting point for further research. The interaction and relationship between internal and external factors could be further investigated. For example, top management support can moderate the influence of local competition in global markets (Carpenter and Fredrickson, 2001). The proposed framework should be quantitatively measured across different brands for further analyzing the main factors that influence Arab/Islamic-origin brands to go global and generalizing findings. Furthermore, the role of each factor may differ from one industry to another. For example in service organizations, frontline employees are crucial to the success of the organization and challenging to standardize across global markets. Investigating the different combinations of strategy, creativity and leadership from one global market to another opens doors for further scholarly work in this area.

Originality/value

This is a pioneer study in attempting to understand the most relevant factors influencing Arab-origin brands to go global as compared to Western brands that are commonly researched in the literature. This study opens doors to further research related to Arab-origin brands globalization process as well as provides interesting insights to marketers and brand owners about the real reasons that may hinder and genuinely influence Arab-origin brands from taking their locally successful brands fully global.
The influence of humble leadership on employees’ work engagement: the mediating role of leader knowledge-sharing behaviour
Authors: Al Hawamdeh Nayel
Published: July 2022

Purpose

This paper empirically aims to investigate the mediating role of leader knowledge-sharing behaviour (LKSB) in the relationship between humble leadership (HL) and work engagement (WE).

Design/methodology/approach

The responses of 321 employees in hospitality organisations in Jordan were collected via an online survey. The study data was then analysed using structural equation modelling.

Findings

The study found that leaders showing humble behaviour were able to share knowledge that ultimately improved employees’ work engagement; thus, confirming that leaders sharing knowledge behaviour mediates the relationship between HL and all three dimensions of work engagement.

Originality/value

This study delves into and sheds further light on HL theory by proposing that LKSB serves as a motivational basis for the relationship between HL and employees’ work engagement. By bolstering the mediating mechanism of LKSB, the findings provide new, deeper insights into the influence of HL on all three dimensions of work engagement.
Species richness, functional traits and climate interactively affect tree survival in a large forest biodiversity experiment
Authors: Liu Xiaojuan , Huang Yuanyuan , Chen Lei , Li Shan , Bongers Franca J. , Castro‐Izaguirre Nadia , Liang Yu , Yang Bo , Chen Yuxin , Schnabel Florian , Tang Ting , Xue Yujie , Trogisch Stefan , Staab Michael , Bruelheide Helge , Schmid Bernhard , Ma Keping
Published: July 2022

Tree survival affects forest biodiversity, structure and functioning. However, little is known about feedback effects of biodiversity on survival and its dependence on functional traits and interannual climatic variability.

With an individual‐based dataset from a large subtropical forest biodiversity experiment, we evaluated how species richness, functional traits and time‐dependent covariates affected annual tree survival rates from age 3–12 (years) after planting 39 species across a diversity gradient from 1 to 2, 4, 8 and 16 tree species.

We found that overall survival rates marginally increased with diversity at the plot level, with large variation among plots within diversity levels. Significant variation among species in survival responses to diversity and changes in these responses with age were related to species functional traits and climatic conditions. Generally, survival rates of conservative species (evergreen, late‐successional species with thick leaves and high carbon to nitrogen ratio but low specific leaf area, leaf phosphorus and hydraulic conductivity) increased with diversity, age and yearly precipitation, whereas acquisitive species showed opposite responses.

Synthesis. Our results indicate that interactions between diversity, species functional traits and yearly climatic conditions can balance survival among species in diverse forests. Planting mixtures of species that differ in functional traits in afforestation projects may lead to a positive feedback loop where biodiversity maintains biodiversity, together with its previously reported beneficial effects on ecosystem functioning.
Pathological tumor long‐to‐short axis ratio as a prognostic factor in patients with thymic epithelial tumors
Authors: Tian Dong , Shiiya Haruhiko , Sato Masaaki , Shinozaki‐Ushiku Aya , Yan Hao‐Ji , Nakajima Jun
Published: July 2022

Background

Thymic epithelial tumors (TETs) exhibit irregular shapes reflective of the heterogeneity in tumor growth and invasive properties. We aimed to identify the prognostic value of the pathological tumor long‐to‐short axis (L/S) ratio in TETs.

Methods

A retrospective study was performed on patients with TETs who underwent extended thymectomy between January 1999 and December 2019 in our institute. Patients were divided into two groups according to the threshold of the L/S ratio. Overall survival (OS) and progression‐free survival (PFS) were evaluated by Kaplan‐Meier analysis. The independent prognostic factors of TETs were identified by multivariate analysis. The performance of prediction models for the above survival outcomes with and without the L/S ratio was evaluated using an integrated time‐dependent area under the curve (iAUC).

Results

Eligible patients were divided into two groups based on higher (n = 42) and lower (n = 94) L/S ratios according to a threshold value of 1.39. A significant difference was found between the two groups only in disease progression (p = 0.001). Poorer survival outcomes were found from Kaplan‐Meier curves in the higher L/S ratio group (p < 0.05). In the multivariable analysis, the L/S ratio showed significant effects on OS and PFS (p < 0.05). The performance of models with the L/S ratio was better than that without the L/S ratio in predicting survival outcomes.

Conclusions

The pathological tumor L/S ratio is an independent prognostic factor for OS and PFS in patients with TETs, and an L/S ratio >1.39 is associated with worse survival outcomes.
An Empirical Analysis of Patent Citation Relevance and Applicant Strategy
Authors: Schuster W. Michael , Valentine Kristen Green
Published: July 2022

Patent examination should ensure that only novel and nonobvious technologies are patented. This evaluation requires comparing the invention to technologies described in public documents—called “prior art.” Examiners and applicants have obligations to cite known prior art that is material to whether the patent is issued. Beyond documenting examination, citations are used as metrics in a significant body of research. The importance of citations as a predictive metric rests on the assumption that they provide evidence of continued development in the relevant field. Research indicates that some citations are, however, made for reasons beyond technological similarity. This undermines the notion that citations show continued growth of a technology. We analyze this assumption—and correct for inaccuracies—by employing similarity metrics to characterize the “relatedness” of technologies described in two patent documents (i.e., citing and cited references). To this end, we use a “Jaccard Index” to quantify textual similarity—and thus technological relatedness—of two documents. Using this method, we empirically analyze strategic behaviors in patent law that were previously only theoretically described in the literature. For example, some patent applicants “bury” relevant references—submitting many irrelevant references and a few relevant ones to hinder review of the important ones. Our Jaccard Index analysis is the first to empirically evaluate whether this practice benefits the applicant. Moreover, we improve upon patent value and grant rate analyses and demonstrate that citation relevance has a significant impact above and beyond a count of citations made.
How the Law Can Leverage Behavioral Economics to Protect Brick‐and‐Mortar Small Business Owners Against Location Risk
Authors: Bunting W.C.
Published: July 2022

This article examines how the law can help reduce retail vacancy rates in volatile urban real estate markets. Two potential drivers of high vacancy rates along retail corridors in otherwise healthy real estate markets are identified: (1) location risk, and (2) positive feedback effects. This article suggests that local governments can pursue a nudge‐based approach to encourage landlords and retail tenants, especially small business owners, to adopt percentage rent or some other form of profit‐sharing to more efficiently allocate location risk. To address positive feedback effects in which each storefront vacancy increases the likelihood of an additional storefront vacancy, a case is made for stronger government intervention.
Does anthropization affect physiology, behaviour and life‐history traits of Montagu's harrier chicks?
Authors: Rabdeau J. , Desbonnes M. , Bretagnolle V. , Moreau J. , Monceau K.
Published: July 2022

The last century has seen a steep decline in biodiversity, and anthropization is considered one of the major drivers of this decline. Anthropogenic disturbances, due to human presence and/or activities, may be perceived as chronic stressors by wildlife and potentially lead to deleterious effects on traits related to fitness. The main objective of the present study was to highlight the effects of these anthropogenic elements on wild birds on sparsely urbanized farmland, far less studied than in urbanized areas. We investigated during four successive breeding seasons whether the anthropization level, assessed by infrastructure density around nests, and the harvesting conditions around nests may impact physiological, behavioural and life‐history traits of Montagu's harrierCircus pygarguschicks. Higher anthropization levels were associated with higher basal corticosterone levels in nestlings during only one breeding season and a lower body condition at fledging for females, probably because they suffered from higher starvation than males. Nestlings reared in more anthropized areas or in harvested crops before their fledging harboured more fault bars on rectrices than those reared in less anthropized areas or in unharvested crops regardless of year and sex, which is suggestive of higher stress during development. Nestling behaviours were also impacted by anthropization level and harvesting conditions: chicks in harvested crops were more aggressive and in areas with higher anthropization levels more prone to escape than others. Because Montagu's harrier is a protected species, the impacts highlighted in the present study are a matter of concern, especially regarding farmland landscape modifications, and we advise limiting perturbations in areas where Montagu's harriers usually nest.
The effect of overlapping surgical scheduling on operating theatre productivity: a narrative review
Authors: Pandit J. J. , Ramachandran S. K. , Pandit M.
Published: July 2022

This article reviews the background to overlapping surgery, in which a single senior surgeon operates across two parallel operating theatres; anaesthesia is induced and surgery commenced by junior surgeons in the second operating theatre while the lead surgeon completes the operation in the first. We assess whether there is any theoretical basis to expect increased productivity in terms of number of operations completed. A review of observational studies found that while there is a perception of increased surgical output for one surgeon, there is no evidence of increased productivity compared with two surgeons working in parallel. There is potential for overlapping surgery to have some positive impact in situations where turnover times between cases are long, operations are short (<2 h) and where ‘critical portions’ of surgery constitute about half of the total operation time. However, any advantages must be balanced against safety, ethical and training concerns.
A phase 2, multicentre, open‐label trial (ACE‐LY‐003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma
Authors: Strati Paolo , Coleman Morton , Champion Rebecca , Ma Shuo , Patti Caterina , Levy Moshe Y. , Lossos Izidore S. , Geethakumari Praveen Ramakrishnan , Lam Selay , Calvo Roser , Higgins Kara , Budde Lihua E.
Published: July 2022

Acalabrutinib, a Bruton tyrosine kinase inhibitor, demonstrated greater selectivity and improved safety versus ibrutinib in a head‐to‐head trial in relapsed/refractory (R/R) chronic lymphocytic leukaemia. In the R/R marginal zone lymphoma (MZL) cohort (phase 2) of a phase 1b/2 trial (NCT02180711), 43 patients with MZL and at least one prior therapy received acalabrutinib 100 mg twice daily until disease progression or unacceptable toxicity [median age 69 years (range 42–84); median one (1–4) prior systemic regimens]. Median follow‐up was 13.3 months (range 0.5–45.5). Among 40 patients evaluable for response, investigator‐assessed overall response rate was 53% [95% confidence interval (CI) 36%–69%] with five (13%) complete responses. Tumour reduction occurred in 40 (93%) of the treated patients. Median time to response was 2.9 months (median duration of response not estimable). Estimated median progression‐free survival (PFS) was 27.4 months (12‐month PFS rate, 67%). Five patients died (disease progression, n = 4; septic shock, n = 1). Seventeen patients (40%) had grade 3 or higher adverse events (AEs), most commonly neutropenia (14%), anaemia, dyspnoea (7% each), fatigue and thrombocytopenia (5% each). Hypertension occurred in 5%; atrial fibrillation/flutter and major haemorrhage were not reported. AEs led to treatment discontinuation in three (7%) patients. Acalabrutinib was active and well tolerated in patients with R/R MZL.
Ultrasonography can be used to predict the location of manica flexoria tears in horses
Authors: Hibner‐Szaltys Maria , Cavallier Francesca , Cantatore Federica , Withers Jonathan M. , Marcatili Marco
Published: July 2022

Background

Manica flexoria (MF) tears are a well‐recognised cause of lameness in horses presenting with effusion of the digital flexor tendon sheath (DFTS). Ultrasonography (US) is a commonly used first line imaging modality during examination of horses presented with DFTS effusion. However, its reported sensitivity for detection of MF tears is low.

Objectives

To describe a novel US technique to predict the location of the MF tear.

Study design

Prospective descriptive observational study.

Methods

Twenty‐two horses (23 limbs) diagnosed with MF tears were included in the study. A standardised US protocol including examination with the limb weight bearing and non‐weight bearing was used. Furthermore, with the limb held in flexed position digital pressure was simultaneously applied to the medial and lateral proximal DFTS outpouchings in axial direction. The aim was to create turbulence of the synovial fluid within the DFTS and improve visualisation of the torn MF. The US examination was performed by one experienced operator and one junior clinician. All horses underwent tenoscopic examination.

Results

In all cases MF tear was diagnosed during tenoscopic examination of the DFTS. The location of the MF tear was correctly predicted in 91.3% (21/23) of the limbs. The main features used to predict location of the MF tear included floatation of the torn fibres of the MF within the synovial fluid, increased distance between DDFT and SDFT on the side at which the MF was torn and recoiling of the MF on the side contralateral to the tear.

Main limitations

Relatively small number of cases included.

Conclusions

The novel US technique was useful to identify the location of MF tear and facilitate identification of the previously described ultrasonographic features consistent with tears of the MF. The agreement between operators was perfect as from the data analysis.
Sixth Åland Island Conference on von Willebrand disease
Authors: Berntorp Erik , Trakymienė Sonata S. , Federici Augusto B. , Holstein Katharina , Corrales‐Medina Fernando F. , Pierce Glenn F. , Srivastava Alok , Prondzinski Mario von Depka , Johnsen Jill M. , Zupan Irena P. , Halimeh Susan , Nummi Vuokko , Roberts Jonathan C.
Published: July 2022

Introduction

The sixth Åland Islands Conference on von Willebrand disease (VWD) on the Åland Islands, Finland, was held from 20 to 22 September 2018.

Aim

The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD.

Results and discussion

The topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non‐haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.
Alterations in the structure and function of the brain in adolescents with new daily persistent headache: A pilot MRI study
Authors: Szabo Edina , Chang Yu‐Hsing Cindy , Shulman Julie , Sieberg Christine B. , Sethna Navil F. , Borsook David , Holmes Scott A. , Lebel Alyssa A.
Published: July 2022

Objective

The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain‐free, healthy controls.

Background

NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH.

Methods

In this cross‐sectional study, resting‐state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age‐ and sex‐matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored.

Results

Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = −0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions.

Conclusion

The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting‐state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.
Progression from early to advanced stage of immune‐related cholangitis
Authors: Hagiwara Satoru , Yoshida Takeshi , Nishida Naoshi , Ida Hiroshi , Ueshima Kazuomi , Minami Yasunori , Takita Masahiro , Aoki Tomoko , Morita Masahiro , Cishina Hirokazu , Komeda Yoriaki , Yoshida Akihiro , Hayashi Hidetoshi , Nakagawa Kazuhiko , Kudo Masatoshi
Published: July 2022

Aim

We report a rare case of immune‐related cholangitis in which the natural course could be demonstrated.

Case Presentation

Eight courses of pembrolizumab maintenance therapy were given as first‐line treatment for squamous cell lung cancer; however, the patient was subsequently hospitalized due to a rapid increase in hepatobiliary enzymes. On endoscopic ultrasound, the common bile duct was dilated to 11 mm, and the wall, throughout its length from the papilla, was thickened. Endoscopic retrograde cholangiopancreatography showed no obvious stenosis in the lower bile duct; however, a parapapillary diverticulum was found, and papillary incision and bile duct plastic stent insertion were carried out. However, the liver disorder did not improve and overt jaundice appeared subsequently; therefore, an immune‐related cholangitis was suspected, and prednisolone (PSL) 35 mg/day was introduced from day 59 of admission. Following PSL initiation, a decrease in serum bilirubin level was observed; however, significant decrease was not observed in alkaline phosphatase. Given the history of recurrent infectious cholangitis, magnetic resonance cholangiopancreatography was carried out on day 70 of admission. The intrahepatic bile duct showed stenosis and dilated findings, which was considered to be a factor for repeated infectious cholangitis.

Conclusion

No previous case reports have described the changes and progression in bile duct images in immune‐related adverse events. Therefore, this case is noteworthy for considering the progression of immune‐related cholangitis.