bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental drivers of habitat use by common bottlenose dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida, USA
Authors: Greller Rachael , Mazzoli Marilyn , Titcomb Elizabeth , Nelson Brandy , Paperno Richard , Markwith Scott H.
Published: November 2020

Anthropogenic impacts in estuarine systems can influence marine mammal habitat use, population dynamics, fitness, and mortality events. The objective was to examine habitat use among the resident common bottlenose dolphin (Tursiops truncatus) population inhabiting the Indian River Lagoon, Florida, and the influences of variation in environmental factors and prey availability in 2003–2015. We utilized photo‐identification surveys, stratified random samples of prey, and environmental variables collected monthly. Kernel density estimation was used to determine the magnitude‐per‐unit area of dolphins across the IRL by wet and dry seasons each year, the values were used as a response variable in classification and regression tree analyses with fish community and environmental variables as predictors. Spatial patterns in dolphin density in the IRL were associated with salinity and dissolved oxygen levels, which are in part associated with freshwater discharges of nutrient and algae laden waters from the region's storm water management system. These findings isolate locations of concern for management of dolphin habitat, and anthropogenic drivers of dolphin distributions requiring further research.
Invasive dermatophyte infection: A systematic review
Authors: Wang Ruojun , Huang Chen , Zhang Yi , Li Ruoyu
Published: November 2020

Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3–87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene‐deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis.
Diagnosis of allergic bronchopulmonary aspergillosis in patients with persistent allergic asthma using three different diagnostic algorithms
Authors: Mortezaee Vida , Mahdaviani Seyed Alireza , Pourabdollah Mihan , Hassanzad Maryam , Mirenayat Maryam Sadat , Mehrian Payam , Behnampour Naser , Yazdani Charati Jamshid , Peirovi Zahra , Sharifynia Somayeh , Seyedmousavi Seyedmojtaba , Hedayati Mohammad T.
Published: November 2020

Background

Allergic bronchopulmonary aspergillosis (ABPA) has been reported in various degrees among patients with persistent allergic asthma (PAA). Currently, there is no gold standard approach for diagnosis of ABPA.

Objectives

In the current study, we aimed the evaluation of three different mainly used algorithms as Rosenberg & Patterson (A), ISHAM Working Group (B) and Greenberger (C) for diagnosis of ABPA in 200 patients with underlying PAA.

Methods

All patients were evaluated using Aspergillus skin prick test (SPTAf), Aspergillus‐specific IgE (sIgEAf) and IgG (sIgGAf), total IgE (tIgE), pulmonary function tests, radiological findings and peripheral blood eosinophil count. The prevalence rate of ABPA in PAA patients was estimated by three diagnostic criteria. We used Latent Class Analysis for the evaluation of different diagnostic parameters in different applied ABPA diagnostic algorithms.

Results

Aspergillus sensitisation was observed in 30 (15.0%) patients. According to algorithms A, B and C, nine (4.5%), six (3.0%) and 11 (5.5%) of patients were diagnosed with ABPA, respectively. The sensitivity and specificity of criteria B and C were (55.6% and 99.5%) and (100.0% and 98.9%) respectively. sIgEAf and sIgGAf showed the high significant sensitivity. The performance of algorithm A, in terms of sensitivity and specificity, was somewhat better than algorithm B.

Conclusion

Our study demonstrated that the sensitivity of different diagnostic algorithms could change the prevalence rate of ABPA. We also found that all of three criteria resulted an adequate specificity for ABPA diagnosis. A consensus patterns combining elements of all three criteria may warrant a better diagnostic algorithm.
How to count structure
Authors: Barrett Thomas William
Published: November 2020

There is sometimes a sense in which one theory posits ‘less structure’ than another. Philosophers of science have recently appealed to this idea both in the debate about equivalence of theories and in discussions about structural parsimony. But there are a number of different proposals currently on the table for how to compare the ‘amount of structure’ that different theories posit. The aim of this paper is to compare these proposals against one another and evaluate them on their own merits.
Whole‐tree mesophyll conductance reconciles isotopic and gas‐exchange estimates of water‐use efficiency
Authors: Gimeno Teresa E. , Campany Courtney E. , Drake John E. , Barton Craig V.M. , Tjoelker Mark G. , Ubierna Nerea , Marshall John D.
Published: November 2020

Photosynthetic water‐use efficiency (WUE) describes the link between terrestrial carbon (C) and water cycles. Estimates of intrinsic WUE (iWUE) from gas exchange and C isotopic composition (δ13C) differ due to an internal conductance in the leaf mesophyll (gm) that is variable and seldom computed.

We present the first direct estimates of whole‐tree gm, together with iWUE from whole‐tree gas exchange and δ13C of the phloem (δ13Cph). We measured gas exchange, online 13C‐discrimination, and δ13Cph monthly throughout spring, summer, and autumn in Eucalyptus tereticornis grown in large whole‐tree chambers. Six trees were grown at ambient temperatures and six at a 3°C warmer air temperature; a late‐summer drought was also imposed.

Drought reduced whole‐tree gm. Warming had few direct effects, but amplified drought‐induced reductions in whole‐tree gm. Whole‐tree gm was similar to leaf gm for these same trees. iWUE estimates from δ13Cph agreed with iWUE from gas exchange, but only after incorporating gm. δ13Cph was also correlated with whole‐tree 13C‐discrimination, but offset by −2.5 ± 0.7‰, presumably due to post‐photosynthetic fractionations.

We conclude that δ13Cph is a good proxy for whole‐tree iWUE, with the caveats that post‐photosynthetic fractionations and intrinsic variability of gm should be incorporated to provide reliable estimates of this trait in response to abiotic stress.
Bitter and sweet make tomato hard to (b)eat
Authors: You Yaohua , van Kan Jan A.L.
Published: November 2020

The glycoalkaloid saponin α‐tomatine is a tomato‐specific secondary metabolite that accumulates to millimolar levels in vegetative tissues and has antimicrobial and antinutritional activity that kills microbial pathogens and deters herbivorous insects. We describe recent insights into the biosynthetic pathway of α‐tomatine synthesis and its regulation. We discuss the mode of action of α‐tomatine by physically interacting with sterols, thereby disrupting membranes, and how tomato protects itself from its toxic action. Tomato pathogenic microbes can enzymatically hydrolyze, and thereby inactivate, α‐tomatine using either of three distinct types of glycosyl hydrolases. We also describe findings that extend well beyond the simple concept of plants producing toxins and pathogens inactivating them. There are reports that toxicity of α‐tomatine is modulated by external pH, that α‐tomatine can trigger programmed cell death in fungi, that cellular localization matters for the impact of α‐tomatine on invading microbes, and that α‐tomatine breakdown products generated by microbial hydrolytic enzymes can modulate plant immune responses. Finally, we address a number of outstanding questions that deserve attention in the future.
An innovative approach to salvage a case of extensive iatrogenic growing skull fracture resulting from failed craniosynostosis surgeries
Authors: Jeyaraj Priya
Published: November 2020

Aim

The challenges encountered in management of severe cranial deformity and a large iatrogenic ‘growing skull fracture’ in a 10‐year‐old child, developing as the result of two previous unsuccessful craniosynostosis surgeries, are described.

Material and Methods

A novel surgical approach was employed with two goals in mind. The first was to relieve the raised intracranial pressure resulting from restenosis of the cranial sutures. This was achieved by fronto‐orbital advancement, which also created adequate space to allow for subsequent unhindered growth of the brain. The second goal was to bridge and reconstruct the large cranial defect that had formed as a result of the ‘growing skull fracture’ effect, resulting from the failed earlier surgeries, and to restore the herniating dura and brain parenchyma back within the cranial vault. This was achieved by raising a wide bifrontal calvarial bone flap, followed by its rotation, kerfing and recontouring before replacement, thus reducing the size of the extensive defect. This was accompanied by osteotomizing and repositioning smaller segments of the flap, to bridge the remaining gaps and restore the integrity and contour of the calvarial shield.

Results and Conclusion

This innovative and versatile combination surgery, comprising of advancement of the fronto‐orbital bandeau, and anterior crania vault reshaping by osteotomization and reassembly of the bifrontal bone flap, yielded excellent aesthetic and functional outcomes.
Genome‐wide association coupled gene to gene interaction studies unveil novel epistatic targets among major effect loci impacting rice grain chalkiness
Authors: Misra Gopal , Badoni Saurabh , Parween Sabiha , Singh Rakesh Kumar , Leung Hei , Ladejobi OluFunmilayo , Mott Richard , Sreenivasulu Nese
Published: November 2020

Rice varieties whose quality is graded as excellent have a lower percent grain chalkiness (PGC) of two per cent and below with higher whole grain yields upon milling, leading to higher economic returns for farmers. We have conducted a genome‐wide association study (GWAS) using a combined population panel of indica and japonica rice varieties, and identified a total of 746 single nucleotide polymorphisms (SNPs) that were strongly associated with the chalk phenotype, covered 78 Quantitative Trait Loci (QTL) regions. Among them, 21 were high‐value QTLs, as they explained at least 10 % of the phenotypic variance for PGC. A combined epistasis and GWAS was applied to dissect the genetics of the complex chalkiness trait, and its regulatory cascades were validated using gene regulatory networks. Promising novel epistatic interactions were found between the loci of chromosomes 6 (PGC6.1) and 7 (PGC7.8) that contributed to lower PGC. Based on haplotype mining only a few modern rice varieties confounded with a lower chalkiness, and they possess several PGC QTLs. The importance of PGC6.1 was validated through multi‐parent advanced generation intercrosses and several low‐chalk lines possessing superior haplotypes were identified. The results of this investigation have deciphered the underlying genetic networks that can reduce PGC to 2%, and will thus support future breeding programs to improve the grain quality of elite genetic material with high‐yielding potentials.
Ergosterol‐targeting fusion antifungal peptide significantly increases the Verticillium wilt resistance of cotton
Authors: Tong Sheng , Yuan Min , Liu Yu , Li Xianbi , Jin Dan , Cheng Xi , Lin Dongmei , Ling Haichun , Yang Danni , Wang Yang , Mao Ajing , Pei Yan , Fan Yanhua
Published: November 2020

Increasing the targeting ability of antifungal proteins towards specific components of fungal cells has the potential to improve their antifungal activity and reduce harmful effects to nontarget cells. To obtain effective disease resistance genes against cotton Verticillium wilt, we constructed several fusion genes, in which binding domains targeting chitin, sphingolipid or ergosterol in the fungal cell wall or cell membrane were individually fused to the antifungal peptide BbAFP1 from entomopathogenic fungus Beauveria bassiana. Transient expression of fusion genes in cotton cotyledons indicated that the BbAFP1::ErBD fusion peptide with an ergosterol binding domain exhibited better disease resistance against V. dahliae than wild‐type BbAFP1 and other fusion genes. BbAFP1::ErBD and BbAFP1 transgenic cotton were obtained and verified by Southern and Western blotting. Compared with BbAFP1‐expressing cotton, BbAFP1::ErBD‐expressing cotton showed higher disease resistance against V. dahliae, with smaller lesion areas (0.07 cm2 vs. 0.16 cm2) on the leaves and a lower disease index (23.9 vs. 34.5). Overexpression of BbAFP1::ErBD by transgenic tobacco also showed enhanced disease resistance against V. dahliae compared with that of the wild‐type gene. These results indicated that construction of fusion antifungal peptides that target fungal cells is a powerful strategy to obtain new anti‐disease genes, and the obtained fusion gene BbAFP1::ErBD has the potential to defend against plant fungal diseases.
Multiple rare‐earth magnet bead ingestion in a pediatric liver‐small bowel‐pancreas transplant recipient: A case report and lessons learned
Authors: Miri Ahmad , Nakayuenyongsuk Warapan , Vargas Luciano , Langnas Alan , Vo Hanh D.
Published: November 2020

Ingestion of rare‐earth magnet beads in children has been a public health concern. The potential risk of swallowing multiple magnets is related to magnet attraction to each other, resulting in serious gastrointestinal complications, such as entero‐enteric fistula formation, peritonitis, bowel ischemia or necrosis, bowel perforation, and potentially death. We describe the clinical outcome of a 10‐year‐old child with a liver‐small bowel‐pancreas transplant who swallowed 26 rare‐earth magnetic beads. The patient presented with fever and abdominal pain. Due to difficulty locating the magnets and post‐surgical anatomy changes, only 25 magnets were removed endoscopically. After the procedure, she continued to have abdominal distention and fever, leading to further investigation and subsequently an exploratory laparotomy, which confirmed a walled‐off perforation. She was treated conservatively with bowel rest and antibiotics, without the need for small bowel graft resection. She recovered well and was eventually discharged on her home enteral feeding regimen. This case emphasizes the importance of taking a good history and having a high index of suspicion to diagnose this dangerous clinical condition, especially in children with an associated predisposing condition for foreign body ingestion, such as developmental delay. Early diagnosis of multiple magnet bead ingestion and prompt detection of its complications in pediatric intestinal transplant recipients could help initiate appropriate intervention and prevent intestinal graft loss.
Do nest boxes breed the target species or its competitors? A case study of a critically endangered bird
Authors: Stojanovic Dejan , Owens Giselle , Young Catherine Mary , Alves Fernanda , Heinsohn Robert
Published: November 2020

Nest boxes are widely used for habitat restoration. Unfortunately, competitors of the target species may exploit nest boxes, creating perverse outcomes. Avoiding habitats preferred by nontarget species, while favoring those of the target species, requires an adaptive management approach if limited information about species preferences is available when deploying boxes. Using nest boxes intended for Swift Parrots Lathamus discolor, we identify factors associated with nontarget species occupancy (Common Starling Sturnus vulgaris and Tree Martin Petrochelidon nigricans) in newly deployed boxes in 2016, and then again after 3 years had elapsed in 2019. Box occupancy by different species depended on the interaction between distance of individual boxes to the forest edge and year. Although the target species exploited similar numbers of nest boxes in both years, competitors were the main beneficiaries of established boxes. A subordinate native nest competitor increased box occupancy likelihood at greater distances from forest edges in both years, but the relationship was stronger in 2019. Introduced Common Starlings S. vulgaris were most likely to occupy boxes close to forest edges, but the magnitude of this relationship was much greater for established than newly deployed boxes. We suggest that permanent box deployments for Swift Parrots may produce perverse outcomes by increasing nesting habitat for Common Starlings. We suggest that for species that only use cavities for part of their life cycle, managers should limit access to boxes outside of critical times to reduce the likelihood that pest populations can exploit restoration efforts and create new problems.
Plant–soil feedbacks and the introduction of Castanea (chestnut) hybrids to eastern North American forests
Authors: Coughlin Aeran O. , Shefferson Richard P. , Clark Stacy L. , Wurzburger Nina
Published: November 2020

The reintroduction of disease‐resistant hybrids is a commonly proposed solution to the introduction of pathogens and pests that weaken or eliminate native plant species. Plant interactions with soil biota result in plant–soil feedbacks (PSFs), which have consequences for individual plant growth and survival as well as broader community‐level processes, such as species diversity and coexistence. Because of their importance, species reintroduction should consider these interactions, yet little work has integrated this perspective. Here, we investigate the effects of hybrid Castanea (chestnut) reintroduction on PSFs and how these mechanisms may influence the recruitment of other species in contemporary forests. We also examine how blight‐resistant Castanea hybrids perform in the soil conditions of contemporary forests and we compare their belowground interactions with those of Castanea dentata. We conducted a reciprocal greenhouse experiment testing the effect of species‐specific soil inoculum on the growth and survival of C. dentata, Castanea hybrids, and other forest dominants. Our results suggest that C. dentata and hybrids had similar belowground interactions and were regulated by negative PSFs, meaning soil microbial communities reduced conspecific growth and survival. These negative PSFs may involve the presence of the non‐native pathogen Phytophthera cinnamomi. Soil inoculum of C. dentata and Castanea hybrids had similar effects on heterospecific growth, suggesting Castanea restoration will have neutral effects on natural regeneration in restoration plantings. We conclude that Castanea hybrids may fill a similar belowground niche to their parent species, and that site selection, screening for soil pathogens, and site planting density will be important to restoration.
Long‐chain fatty acids are bad in IPF, or are they?
Authors: McManus Bruce , Knight Darryl
Published: November 2020

See related article
Kinetics and clinical significance of human herpesvirus 6 DNA shedding in saliva after allogeneic hematopoietic stem cell transplantation
Authors: Ogata Masao , Kawano Rie , Satou Takako , Takata Hiroyuki , Yoshida Natsumi , Honda Shuhei , Nagamatsu Kentaro , Takano Kuniko , Kohno Kazuhiro , Kirihara Takehiko , Sato Keijiro , Hiroshima Yuki , Sumi Masahiko , Kurihara Taro , Takeda Wataru , Ueki Toshimitsu , Kobayashi Hikaru
Published: November 2020

Background

Little is known about the kinetics and clinical significance of saliva human herpesvirus‐6 (HHV‐6) DNA after hematopoietic stem cell transplantation (HSCT).

Methods

In this observational study, we quantified HHV‐6 DNA in serially collected plasma and saliva from allogeneic HSCT recipients. Associations between the status of salivary HHV‐6 DNA and the development of HHV‐6 encephalitis, depression, and oral mucosal graft‐versus‐host disease (GVHD) were retrospectively analyzed.

Results

A total of 787 plasma and 434 saliva samples were collected from 56 patients. The cumulative incidence of HHV‐6 DNA in plasma and saliva at 60 days after transplantation was 51.8% and 83.9%, respectively. The peak level of salivary HHV‐6 DNA was significantly higher in patients who displayed plasma HHV‐6 DNA than in those who did not (median, 51,584 copies/mL vs 587 copies/mL; P < .0001). Salivary HHV‐6 DNA levels increased after positive plasma HHV‐6 DNA was detected and remained high during observation period. Despite the frequent occurrence of positive salivary HHV‐6 DNA, no patient developed depression. Positivity of salivary HHV‐6 DNA was not significantly associated with the development of HHV‐6 encephalitis (P = 1.00, Fisher's exact test) or oral mucosal GVHD (P = .71, Grey's test). No significant relationship between salivary HHV‐6 DNA and these diseases was found even when comparing higher HHV‐6 DNA loads in saliva.

Conclusion

Salivary HHV‐6 DNA levels increased after HHV‐6 DNA was detected in the blood. However, no epidemiological evidence was shown to support a role of salivary HHV‐6 in the development of HHV‐6 encephalitis, depression, and oral mucosal GVHD.
RETRACTED: Potato CYCLING DOF FACTOR 1 and its lncRNA counterpart StFLORE link tuber development and drought response
Authors: Ramírez Gonzales Lorena , Shi Li , Bergonzi Sara Bergonzi , Oortwijn Marian , Franco‐Zorrilla José M. , Solano‐Tavira Roberto , Visser Richard G. F. , Abelenda José A. , Bachem Christian W. B.
Published: November 2020

Plants regulate their reproductive cycles under the influence of environmental cues, such as day length, temperature and water availability. In Solanum tuberosum (potato), vegetative reproduction via tuberization is known to be regulated by photoperiod, in a very similar way to flowering. The central clock output transcription factor CYCLING DOF FACTOR 1 (StCDF1) was shown to regulate tuberization. We now show that StCDF1, together with a long non‐coding RNA (lncRNA) counterpart, named StFLORE, also regulates water loss through affecting stomatal growth and diurnal opening. Both natural and CRISPR‐Cas9 mutations in the StFLORE transcript produce plants with increased sensitivity to water‐limiting conditions. Conversely, elevated expression of StFLORE, both by the overexpression of StFLORE or by the downregulation of StCDF1, results in an increased tolerance to drought through reducing water loss. Although StFLORE appears to act as a natural antisense transcript, it is in turn regulated by the StCDF1 transcription factor. We further show that StCDF1 is a non‐redundant regulator of tuberization that affects the expression of two other members of the potato StCDF gene family, as well as StCO genes, through binding to a canonical sequence motif. Taken together, we demonstrate that the StCDF1–StFLORE locus is important for vegetative reproduction and water homeostasis, both of which are important traits for potato plant breeding.
Inhibition of clathrin‐mediated endocytosis by knockdown of AP‐2 leads to alterations in the plasma membrane proteome
Authors: Tobys David , Kowalski Lisa Maria , Cziudaj Eva , Müller Stefan , Zentis Peter , Pach Elke , Zigrino Paola , Blaeske Tobias , Höning Stefan
Published: November 2020

In eukaryotic cells, clathrin‐mediated endocytosis (CME) is a central pathway for the internalization of proteins from the cell surface, thereby contributing to the maintenance of the plasma membrane protein composition. A key component for the formation of endocytic clathrin‐coated vesicles (CCVs) is AP‐2, as it sequesters cargo membrane proteins, recruits a multitude of other endocytic factors and initiates clathrin polymerization. Here, we inhibited CME by depletion of AP‐2 and explored the consequences for the plasma membrane proteome. Quantitative analysis revealed accumulation of major constituents of the endosomal‐lysosomal system reflecting a block in retrieval by compensatory CME. The noticeable enrichment of integrins and blockage of their turnover resulted in severely impaired cell migration. Rare proteins such as the anti‐cancer drug target CA9 and tumor markers (CD73, CD164, CD302) were significantly enriched. The AP‐2 knockdown attenuated the global endocytic capacity, but clathrin‐independent entry pathways were still operating, as indicated by persistent internalization of specific membrane‐spanning and GPI‐anchored receptors (PVR, IGF1R, CD55, TNAP). We hypothesize that blocking AP‐2 function and thus inhibiting CME may be a novel approach to identify new druggable targets, or to increase their residence time at the plasma membrane, thereby increasing the probability for efficient therapeutic intervention.
Transfusion of blood components containing ABO‐incompatible plasma does not lead to higher mortality in civilian trauma patients
Authors: Seheult Jansen N. , Dunbar Nancy M. , Hess John R. , Tuott Erin E. , Bahmanyar Mohammad , Campbell Jessica , Fontaine Magali , Khan Jenna , Ko Ara , Mi Jian , Murphy Michael F. , Nykoluk Tara , Poisson Jessica , Raval Jay S. , Shih Andrew , Sperry Jason L. , Staves Julie , Wong Michelle , Yan Matthew T. S. , Ziman Alyssa , Yazer Mark H. ,   The Biomedical Excellence for Safer Transfusion (BEST) collaborative
Published: November 2020

Background

This study investigated the effect on mortality of transfusing ABO‐incompatible plasma from all sources during trauma resuscitation.

Methods

Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO‐incompatible plasma from any blood product (incompatible group) or receipt of solely ABO‐compatible plasma (compatible group). The primary outcome was 30‐day mortality, while other outcomes included 6‐ and 24‐hour mortality. Mixed‐effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes.

Results

Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6‐hour, 24‐hour, and 30‐day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high‐volume group had higher 24‐hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low‐volume group did not have increased mortality at any of the time points in this adjusted model.

Conclusion

The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30‐day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.
Inflection points
Authors: Menitove Jay , Kaufman Richard
Published: November 2020

See commentary on page 2745–2747, in this issue
Towards input–output‐based measurements of trade creation and trade diversion
Authors: Muradov Kirill
Published: November 2020

This paper discusses a new approach to quantify trade creation and trade diversion that relies on the structural decomposition analysis in an inter‐country input–output framework. The proposed measure captures the contribution of trade creation (diversion) between two countries to the GDP growth of the home country, partner country and third countries. For a trial calculation, the author uses the 2016 release of the OECD inter‐country input–output tables and focuses on the period 2000–11. Creation, diversion, but also contraction of trade flows are shown to be intrinsic to any pair of countries that may or may not be linked by a trade agreement. There is no evidence that the rise of free trade agreements in 2000s is associated with higher magnitude of these trade effects for an average country pair. The proposed approach is thought to be a useful alternative to econometric estimates of trade creation and trade diversion available to date.
In vivo manipulation of muscle shape and tendinous stiffness affects the human ability to generate torque rapidly
Authors: Monte Andrea
Published: November 2020

New Findings

What is the central question of this study?

What are the determinants of muscle belly gearing, and how does it affect the torque rise?

What is the main finding and its importance?

Change in muscle thickness of the gastrocnemius medialis is related to variations in belly gearing. Belly gearing has a key role in the rise of muscle torque and rate of torque development (RTD). Besides, the increase of tendinous tissue stiffness could increase the torque rise as well, and in turn, the RTD. However, changes in the tendinous tissue stiffness showed no effects on muscle fascicle behaviour, suggesting a possible uncoupling between muscle and tendon mechanical properties.

During fixed‐end contractions, muscles bulge in thickness and/or width to maintain a constant volume, whereas tendons lengthen over the entire contraction period. These dynamic changes play a key functional role in modulating the generated torque. However, the literature has revealed a limited understanding of in vivo dynamic muscle–tendon changes during rapid contractions. Therefore, this study aimed to investigate the determinants of belly gearing (belly velocity/fascicle velocity) and its effects on rapid torque production during in vivo fixed‐end contractions. Twenty healthy males were recruited for the study. Muscle shape and tendon stiffness were manipulated by applying a transverse load (2–10 kg) and an ankle rotation manoeuvre, respectively. Ultrafast‐ultrasound was employed to quantify medial gastrocnemius architecture during evoked contraction and a dynamometer was used to measure the muscle torque and quantify the rate of torque development (RTD). Torque and RTD diminished by transverse load application, whereas they increased during the ankle rotation manoeuvre. Belly gearing declined with increasing transverse load but was unaffected by tendinous stiffness variations. Alterations in belly gearing were strongly related to variations in muscle thickness throughout any load applied and affected the torque rise rapidly. In contrast, changes in tendinous tissue stiffness affected the torque rise only but did not modify the muscle shape. These data may suggest that concurrent manipulation of the tendinous tissue stiffness and muscle shape does not affect the explosive rise in torque capacity, suggesting a possible uncoupling between mechanical properties of muscle and tendon.
Spontaneous Negative Entropy Increments in Granular Flows
Authors: Laudani Rossella , Ostoja-Starzewski Martin
Published: November 2020

The entropy inequality, commonly taken as an axiom of continuum mechanics, is found to be spontaneously violated in macroscopic granular media undergoing collisional dynamics. The result falls within the fluctuation theorem of nonequilibrium thermodynamics, which is known to replace the Second Law for finite systems. This phenomenon amounts to the system stochastically displaying negative increments of entropy. The focus is on granular media in Couette flows, consisting of monosized circular disks (with 10 to 104 disks of diameters 0.01 m to 1 m) with frictional-Hookean contacts simulated by molecular dynamics accounting for micropolar effects. Overall, it is determined that the probability of negative entropy increments diminishes with the Eulerian velocity gradient increasing, while it tends to increase in a sigmoidal fashion with the Young modulus of disks increasing. This behavior is examined for a very wide range of known materials: from the softest polymers to the stiffest (i.e., carbyne). The disks’ Poisson ratio is found to have a weak effect on the probability of occurrence of negative entropy increments.
Recycling of multilayer plastic packaging materials by solvent-targeted recovery and precipitation
Authors: Walker Theodore W. , Frelka Nathan , Shen Zhizhang , Chew Alex K. , Banick Jesse , Grey Steven , Kim Min Soo , Dumesic James A. , Van Lehn Reid C. , Huber George W.
Published: November 2020

A thermodynamically guided approach enables the solvent-based recycling of multilayer plastic packaging films.
Performance of the COVID19SEROSpeed IgM/IgG Rapid Test, an Immunochromatographic Assay for the Diagnosis of SARS-CoV-2 Infection: a Multicenter European Study
Authors: Plebani Mario , Parčina Marijo , Bechri Issam , Zehender Gianguglielmo , Terkeš Vedrana , Abdel Hafith Balqis , Antinori Spinello , Pillet Sylvie , Gonzalo Sylvie , Hoerauf Achim , Lai Alessia , Morović Miro , Bourlet Thomas , Torre Alessandro , Pozzetto Bruno , Galli Massimo
Published: November 2020

This study assessed the diagnostic performance of the new coronavirus disease 2019 (COVID-19) SEROSpeed IgM/IgG Rapid Test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders).
Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of Enterococcus faecalis
Authors: Gilmore Michael S. , Salamzade Rauf , Selleck Elizabeth , Bryan Noelle , Mello Suelen S. , Manson Abigail L. , Earl Ashlee M.
Published: November 2020

Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci.
Treatment-resistant cough: a rare manifestation of IgG4-related disease involving the larynx
Authors: Syed Azfar Shahid , Colombo Rhonda E , Syed Bakhtiar S , Henning Peter M
Published: November 2020

IgG4-related autoimmune diseases (IgG4 RD) are a relatively recently recognised group of disease processes that can affect multiple organ systems and result in protean symptoms. Here, we present a rare case of a 69-year-old man with a history of IgG4 RD affecting his lacrimal gland and pancreas who developed symptoms of severe laryngitis not responsive to usual therapy. He presented with non-productive cough, hoarseness and dyspnoea. Imaging findings suggestive of aortitis and laryngeal inflammation in the setting of his IgG4 RD history prompted treatment with rituximab, which resulted in resolution of his laryngeal symptoms. Subsequently, his cough returned and he required periodic rituximab infusions to stay symptom-free. IgG4 RD of the larynx is an uncommonly reported manifestation in literature. This disease is very responsive to anti-CD20 monoclonal antibody treatment. IgG4 RD should be considered in patients with airway symptoms that are especially refractory to usual therapy.
Primary synovial sarcoma of the lung: a rare presentation, diagnostic dilemma and review of literature
Authors: Pandey Laxman , Joseph Deepa , Pasricha Rajesh , Gupta Manoj Kumar
Published: November 2020

Primary synovial sarcoma of the lung (PSSL) is a rare tumour with only 0.5% incidence among other primary malignant lung tumours. Published medical literature regarding the natural history treatment protocol and clinical outcomes of PSSL remains limited. Here, we present a case of a 39-year-old man with primary synovial sarcoma with long-term follow-up, which was initially viewed as a metastasis from another unknown site. After evaluating histopathologically from the specimen post left lung metastasectomy and ruling out any other site for neoplastic changes, the diagnosis of PSSL was confirmed. Furthermore, this article reviews the literature and discusses various aspects of PSSL, including clinical presentation, radiological imaging and pathological characteristics, diagnostic dilemma, management and prognosis. This paper serves to provide an update and aims to enhance the understanding of PSSL. Timely diagnosis and treatment are imperative to achieve improved outcomes.
Multimethod, multidataset analysis reveals paradoxical relationships between sociodemographic factors, Hispanic ethnicity and diabetes
Authors: Knight Gabriel M , Spencer-Bonilla Gabriela , Maahs David M , Blum Manuel R , Valencia Areli , Zuma Bongeka Z , Prahalad Priya , Sarraju Ashish , Rodriguez Fatima , Scheinker David
Published: November 2020

Introduction

Population-level and individual-level analyses have strengths and limitations as do ‘blackbox’ machine learning (ML) and traditional, interpretable models. Diabetes mellitus (DM) is a leading cause of morbidity and mortality with complex sociodemographic dynamics that have not been analyzed in a way that leverages population-level and individual-level data as well as traditional epidemiological and ML models. We analyzed complementary individual-level and county-level datasets with both regression and ML methods to study the association between sociodemographic factors and DM.

Research design and methods

County-level DM prevalence, demographics, and socioeconomic status (SES) factors were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings and merged with US Census data. Analogous individual-level data were extracted from 2007 to 2016 National Health and Nutrition Examination Survey studies and corrected for oversampling with survey weights. We used multivariate linear (logistic) regression and ML regression (classification) models for county (individual) data. Regression and ML models were compared using measures of explained variation (area under the receiver operating characteristic curve (AUC) and R2).

Results

Among the 3138 counties assessed, the mean DM prevalence was 11.4% (range: 3.0%–21.1%). Among the 12 824 individuals assessed, 1688 met DM criteria (13.2% unweighted; 10.2% weighted). Age, gender, race/ethnicity, income, and education were associated with DM at the county and individual levels. Higher county Hispanic ethnic density was negatively associated with county DM prevalence, while Hispanic ethnicity was positively associated with individual DM. ML outperformed regression in both datasets (mean R2of 0.679 vs 0.610, respectively (p<0.001) for county-level data; mean AUC of 0.737 vs 0.727 (p<0.0427) for individual-level data).

Conclusions

Hispanic individuals are at higher risk of DM, while counties with larger Hispanic populations have lower DM prevalence. Analyses of population-level and individual-level data with multiple methods may afford more confidence in results and identify areas for further study.
Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial
Authors: Klein Allan L , Lin David , Cremer Paul C , Nasir Saifullah , Luis Sushil Allen , Abbate Antonio , Ertel Andrew , LeWinter Martin , Beutler Anna , Fang Fang , Paolini John F
Published: November 2020

Objective

Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.

Methods

This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).

Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).

Results

Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients. Secondary outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.

Conclusions

Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.

Trial registration number

NCT03980522.
Investigation of the prognostic value of CD4 T cell subsets expanded from tumor-infiltrating lymphocytes of colorectal cancer liver metastases
Authors: Kroemer Marie , Turco Celia , Spehner Laurie , Viot Julien , Idirène Idir , Bouard Adeline , Renaude Elodie , Deschamps Marina , Godet Yann , Adotévi Olivier , Limat Samuel , Heyd Bruno , Jary Marine , Loyon Romain , Borg Christophe
Published: November 2020

Background

The positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells.

Methods

Liver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients’ clinical outcomes.

Results

We successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3lowcultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007).

Conclusions

Our data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients’ survival, suggesting a particular role of this T cell subset in CRC immune contexture.

Trial registration number

NCT02817178.
Wrinkle in the plan: miR-34a-5p impacts chemokine signaling by modulating CXCL10/CXCL11/CXCR3-axis in CD4+, CD8+T cells, and M1 macrophages
Authors: Hart Martin , Nickl Laura , Walch-Rueckheim Barbara , Krammes Lena , Rheinheimer Stefanie , Diener Caroline , Taenzer Tanja , Kehl Tim , Sester Martina , Lenhof Hans-Peter , Keller Andreas , Meese Eckart
Published: November 2020

Background

In 2016 the first-in-human phase I study of a miRNA-based cancer therapy with a liposomal mimic of microRNA-34a-5p (miR-34a-5p) was closed due to five immune related serious adverse events (SAEs) resulting in four patient deaths. For future applications of miRNA mimics in cancer therapy it is mandatory to unravel the miRNA effects both on the tumor tissue and on immune cells. Here, we set out to analyze the impact of miR-34a-5p over-expression on the CXCL10/CXCL11/CXCR3 axis, which is central for the development of an effective cancer control.

Methods

We performed a whole genome expression analysis of miR-34a-5p transfected M1 macrophages followed by an over-representation and a protein–protein network analysis. In-silico miRNA target prediction and dual luciferase assays were used for target identification and verification. Target genes involved in chemokine signaling were functionally analyzed in M1 macrophages, CD4+and CD8+T cells.

Results

A whole genome expression analysis of M1 macrophages with induced miR-34a-5p over-expression revealed an interaction network of downregulated target mRNAs includingCXCL10andCXCL11.In-silico target prediction in combination with dual luciferase assays identified direct binding of miR-34a-5p to the 3′UTRs ofCXCL10andCXCL11. Decreased CXCL10 and CXCL11 secretion was shown on the endogenous protein level and in the supernatant of miR-34a-5p transfected and activated M1 macrophages. To complete the analysis of the CXCL10/CXCL11/CXCR3 axis, we activated miR-34a-5p transfected CD4+and CD8+T cells by PMA/Ionomycin and found reduced levels of endogenous CXCR3 and CXCR3 on the cell surface.

Conclusions

MiR-34a-5p mimic administered by intravenous administration will likely not only be up-taken by the tumor cells but also by the immune cells. Our results indicate that miR-34a-5p over-expression leads in M1 macrophages to a reduced secretion of CXCL10 and CXCL11 chemokines and in CD4+and CD8+T cells to a reduced expression of CXCR3. As a result, less immune cells will be attracted to the tumor site. Furthermore, high levels of miR-34a-5p in naive CD4+T cells can in turn hinder Th1 cell polarization through the downregulation of CXCR3 leading to a less pronounced activation of cytotoxic T lymphocytes, natural killer, and natural killer T cells and possibly contributing to lymphocytopenia.