bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical variations in Quercus pollen as a tool for taxonomic identification: Implications for long‐term ecological and biogeographical research
Authors: Muthreich Florian , Zimmermann Boris , Birks H. John B. , Vila‐Viçosa Carlos M. , Seddon Alistair W. R.
Published: February 2020

Aim

Fossil pollen is an important tool for understanding biogeographical patterns in the past, but the taxonomic resolution of the fossil‐pollen record may be limited to genus or even family level. Chemical analysis of pollen grains has the potential to increase the taxonomic resolution of pollen analysis, but present‐day chemical variability is poorly understood. This study aims to investigate whether a phylogenetic signal is present in the chemical variations of Quercus L. pollen and to assess the prospects of chemical techniques for identification in biogeographical research.

Location

Portugal.

Taxon

Six taxa (five species, one subspecies) of Quercus L., Q. faginea, Q. robur, Q. robur ssp. estremadurensis, Q. coccifera, Q. rotundifolia and Q. suber belonging to three sections: Cerris, Ilex and Quercus (Denk, Grimm, Manos, Deng, & Hipp, 2017).

Methods

We collected pollen samples from 297 individual Quercus trees across a 4° (~450 km) latitudinal gradient and determined chemical differences using Fourier‐transform infrared spectroscopy (FTIR). We used canonical powered partial least squares regression (CPPLS) and discriminant analysis to describe within‐ and between‐species chemical variability.

Results

We find clear differences in the FTIR spectra from Quercus pollen at the section level (Cerris: ~98%; Ilex: ~100%; Quercus: ~97%). Successful discrimination is based on spectral signals related to lipids and sporopollenins. However, discrimination of species within individual Quercus sections is more challenging: overall, species recall is ~76% and species misidentifications within sections lie between 18% and 31% of the test set.

Main Conclusions

Our results demonstrate that subgenus level differentiation of Quercus pollen is possible using FTIR methods, with successful classification at the section level. This indicates that operator‐independent FTIR approaches can surpass traditional morphological techniques using light microscopy. Our results have implications both for providing new insights into past colonization pathways of Quercus, and likewise for forecasting future responses to climate change. However, before FTIR techniques can be applied more broadly across palaeoecology and biogeography, our results also highlight a number of research challenges that still need to be addressed, including developing sporopollenin‐specific taxonomic discriminators and determining a more complete understanding of the effects of environmental variation on pollen‐chemical signatures in Quercus.
Use of Fall Risk–Increasing Drugs Around a Fall‐Related Injury in Older Adults: A Systematic Review
Authors: Hart Laura A. , Phelan Elizabeth A. , Yi Julia Y. , Marcum Zachary A. , Gray Shelly L.
Published: February 2020

OBJECTIVES

To examine: (1) prevalence of fall risk–increasing drug (FRID) use among older adults with a fall‐related injury, (2) which FRIDs were most frequently prescribed, (3) whether FRID use was reduced following the fall‐related healthcare episode, and (4) which interventions have reduced falls or FRID use in older adults with a history of falls.

DESIGN

Systematic review.

PARTICIPANTS

Observational and intervention studies that assessed (or intervened on) FRID use in participants aged 60 years or older who had experienced a fall.

MEASUREMENTS

PubMed and EMBASE were searched through June 30, 2019. Two reviewers independently extracted data and evaluated studies for bias. Discrepancies were resolved by consensus.

RESULTS

Fourteen of 638 articles met selection criteria: 10 observational studies and 4 intervention studies. FRID use prevalence at time of fall‐related injury ranged from 65% to 93%. Antidepressants and sedatives‐hypnotics were the most commonly prescribed FRIDs. Of the 10 observational studies, only 2 used a design adequate to capture changes in FRID use after a fall‐related injury, neither finding a reduction in FRID use. Three randomized controlled studies conducted in various settings (hospital, emergency department, and community pharmacy) with 12‐month follow‐up did not find a reduction in falls with interventions to reduce FRID use, although the study conducted in the community pharmacy setting was effective in reducing FRID use. In a nonrandomized (pre‐post) intervention study conducted in an outpatient geriatrics clinic, falls were reduced in the intervention group.

CONCLUSIONS

Limited evidence indicates high prevalence of FRID use among older adults who have experienced a fall‐related injury and no reduction in overall FRID use following the fall‐related healthcare encounter. There is a need for well‐designed interventions to reduce FRID use and falls in older adults with a history of falls. Reducing FRID use as a stand‐alone intervention may not be effective in reducing recurrent falls. J Am Geriatr Soc 68:1334–1343, 2020.
Comparing Morphological and Molecular Estimates of Species Diversity in the Freshwater Genus Synura (Stramenopiles): A Model for Understanding Diversity of Eukaryotic Microorganisms
Authors: Škaloud Pavel , Škaloudová Magda , Jadrná Iva , Bestová Helena , Pusztai Martin , Kapustin Dmitry , Siver Peter A.
Published: February 2020

We performed a comparison of molecular and morphological diversity in a freshwater colonial genus Synura (Chrysophyceae, Stramenopiles), using the island of Newfoundland (Canada) as a case study. We examined the morphological species diversity in collections from 79 localities, and compared these findings to diversity based on molecular characters for 150 strains isolated from the same sites. Of 27 species or species‐level lineages identified, only one third was recorded by both molecular and morphological techniques, showing both approaches are complementary in estimating species diversity within this genus. Eight taxa, each representing young evolutionary lineages, were recovered only by sequencing of isolated colonies, whereas ten species were recovered only microscopically. Our complex investigation, involving both morphological and molecular examinations, indicates that our knowledge of Synura diversity is still poor, limited only to a few well‐studied areas. We revealed considerable cryptic diversity within the core S. petersenii and S. leptorrhabda lineages. We further resolved the phylogenetic position of two previously described taxa, S. kristiansenii and S. petersenii f. praefracta, propose species‐level status for S. petersenii f. praefracta, and describe three new species, S. vinlandica, S. fluviatilis, and S. cornuta. Our findings add to the growing body of literature detailing distribution patterns observed in the genus, ranging from cosmopolitan species, to highly restricted taxa, to species such as S. hibernica found along coastal regions on multiple continents. Finally, our study illustrates the usefulness of combining detailed morphological information with gene sequence data to examine species diversity within chrysophyte algae.
Optimization of encapsulation of maltogenic amylase into a mixture of maltodextrin and beeswax and its application in gluten‐free bread
Authors: Haghighat‐Kharazi Sepideh , Kasaai Mohammad Reza , Milani Jafar Mohammadzadeh , Khajeh Khosro
Published: February 2020

In this work maltogenic amylase (MAase) was encapsulated into the mixture of maltodexrin and beeswax (BW) for retarding staling of gluten‐free bread. The effects of maltogenic amylase (MAase) concentration (8.2, 45, and 82 mg/ml), maltodextrin with dextrose equivalent (DE) 4–7 (MD) (1, 2.5, and 4%) and, BW (1, 2.5, and 4%) on the encapsulation efficiency (EE) of encapsulated enzyme were optimized using RSM. The optimized formulation was MAase with 8.2 mg/ml, MD 4% and BW 1%, leading to the highest EE (79.35%), thus chosen for subsequent experiments. The prepared particles were 1,190.50 nm with PDI of 0.336 and zeta potential of −8.30 mV. Surface morphologies of produced particles were almost spherical with layered appearance. Batter with this formulation led to higher cross over point in frequency sweep than free enzyme‐loaded batter. Lower weight loss, higher volume index, darker crust color, whiter crumb color, more aerated microstructure, less hardness in crumb, and higher sensorial acceptability on the first day and during storage period in the breads containing encapsulated MAase was observed.
Concurrent use of rabacfosadine and L‐asparaginase for relapsed or refractory multicentric lymphoma in dogs
Authors: Cawley Jacob R. , Wright Zachary M. , Meleo Karri , Post Gerald S. , Clifford Craig A. , Vickery Kathryn R. , Vail David M. , Bergman Philip J. , Thamm Douglas H.
Published: February 2020

Background

Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied.

Hypothesis/Objectives

To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma.

Animals

Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol.

Methods

Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB.

Results

The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis.

Conclusions and Clinical Importance

Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.
Neutrophil‐to‐lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib
Authors: Tada Toshifumi , Kumada Takashi , Hiraoka Atsushi , Michitaka Kojiro , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Kariyama Kazuya , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Fukunishi Shinya , Ohama Hideko , Kawata Kazuhito , Nakamura Shinichiro , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Hayama Korenobu , Arai Taeang , Imai Michitaka , Joko Kouji , Koizumi Yohei , Hiasa Yoichi
Published: February 2020

Background and aims

Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil‐to‐lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib.

Methods

A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut‐off NLR levels for associating overall survival using hazard ratio (HR) spline curves.

Results

Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097‐3.119), α‐foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188‐3.265) and modified albumin‐bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267‐3.555) were independently associated with overall survival. Cumulative progression‐free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268‐2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028‐2.236) were independently associated with progression‐free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0‐4.5 is an appropriate cut‐off for associating overall survival.

Conclusions

NLR can be associated with outcomes in patients with HCC treated with lenvatinib.
The C‐terminal domain of Corynebacterium glutamicum mycoloyltransferase A is composed of five repeated motifs involved in cell wall binding and stability
Authors: Dietrich Christiane , Li de la Sierra‐Gallay Ines , Masi Muriel , Girard Eric , Dautin Nathalie , Constantinesco‐Becker Florence , Tropis Maryelle , Daffé Mamadou , van Tilbeurgh Herman , Bayan Nicolas
Published: February 2020

The genomes of Corynebacteriales contain several genes encoding mycoloyltransferases (Myt) that are specific cell envelope enzymes essential for the biogenesis of the outer membrane. MytA is a major mycoloyltransferase of Corynebacterium glutamicum, displaying an N‐terminal domain with esterase activity and a C‐terminal extension containing a conserved repeated Leu‐Gly‐Phe‐Pro (LGFP) sequence motif of unknown function. This motif is highly conserved in Corynebacteriales and found associated with cell wall hydrolases and with proteins of unknown function. In this study, we determined the crystal structure of MytA and found that its C‐terminal domain is composed of five LGFP motifs and forms a long stalk perpendicular to the N‐terminal catalytic α/β‐hydrolase domain. The LGFP motifs are composed of a 4‐stranded β‐fold and occupy alternating orientations along the axis of the stalk. Multiple acetate binding pockets were identified in the stalk, which could correspond to putative ligand‐binding sites. By using various MytA mutants and complementary in vitro and in vivo approaches, we provide evidence that the C‐terminal LGFP domain interacts with the cell wall peptidoglycan‐arabinogalactan polymer. We also show that the C‐terminal LGFP domain is not required for the activity of MytA but rather contributes to the overall integrity of the cell envelope.
Nutritional challenges and countermeasures for space travel
Authors: Cahill T. , Hardiman G.
Published: February 2020

There has been a reinvigoration of public interest in space exploration in what has been deemed the new space race, which aims to eventually take humans to Mars in the 2030s. This type of Earth‐independent deep space mission presents a multitude of challenges for providing astronauts with adequate nutrition, which are not currently posed by our presence in low earth orbit. For example, there are technical challenges associated with providing enough food with sufficient nutrient content, bioavailability and increased shelf life. Environmental stressors may also impact physiology and in turn affect nutritional status. Increased exposure of radiation, for example, causes changes in the gut and liver that might facilitate nutrient deficiency. Current or potential countermeasures for these challenges are explored including the use of bio‐regenerative systems such as growing crops or biomass, or inducing torpor to reduce nutritional needs. Additionally, the beneficial role of nutrients has also been explored for alleviating the harmful effects of spaceflight exposure. It is clear that such countermeasures will be necessary to maintain astronaut health during long‐duration missions to potentially counteract physiological stresses and to allow us to continue pushing the boundaries of space exploration.
Cellular alteration and differential protein profile explain effects of GA3 and ABA and their inhibitor on Trichocline catharinensis (Asteraceae) seed germination
Authors: Lando Ana P. , Viana Willian G. , Vale Ellen M. , Santos Marisa , Silveira Vanildo , Steiner Neusa
Published: February 2020

Seed physiology of wild species has not been studied as deeply as that of domesticated crop species. Trichocline catharinensis (Asteraceae) is an endemic wildflower species from the high‐altitude fields of southern Brazil. This species is of interest as a source of genes to improve cultivated Asteraceae because of its ornamental features, disease resistance and ability to tolerate drought and poor soil conditions. We studied the effects of abscisic acid (ABA) and gibberellic acid (GA3) and their inhibitors, fluridone (FLU) and paclobutrazol (PAC), on seed germination. We individually assessed ultrastructural changes and differential protein accumulation. The principal component analysis explained 69.66% of differential accumulation for 32 proteins at phase II of seed germination in response to hormone and inhibitor treatment. GA3‐imbibed seed germination (98.75%) resulted in increased protein accumulation to meet energy demand, redox regulation, and reserve metabolism activation. FLU‐imbibed seeds showed a higher germination speed index as a consequence of metabolism activation. ABA‐imbibed seeds (58.75%) showed osmotolerance and flattened cells in the hypocotyl‐radicular axis, suggesting that ABA inhibits cell expansion. PAC‐imbibed seeds remained at phase II for 300 h, and germination was suppressed (7.5%) because of the increased signaling proteins and halted reserve mobilization. Therefore, our findings provide insight into the behavior of Asteraceae non‐dormant seed germination, which broadens our knowledge of seed germination in a wild and endemic plant species from a threatened ecosystem.
Comparing apples and oranges or different types of citrus fruits? Using wearable versus stationary devices to analyze psychophysiological data
Authors: Konstantinou Pinelopi , Trigeorgi Andria , Georgiou Chryssis , Gloster Andrew T. , Panayiotou Georgia , Karekla Maria
Published: February 2020

Wearable devices capable of capturing psychophysiological signals are popular. However, such devices have, yet, to be established in experimental and clinical research. This study, therefore, compared psychophysiological data (skin conductance level (SCL), heart rate (HR), and heart rate variability (HRV)) captured with a wearable device (Microsoft band 2) to those of a stationary device (Biopac MP150), in an experimental pain induction paradigm. Additionally, the present study aimed to compare two analytical techniques of HRV psychophysiological data: traditional (i.e., peaks are detected and manually checked) versus automated analysis using Python programs. Forty‐three university students (86% female; Mage = 21.37 years) participated in the cold pressor pain induction task. Results showed that the majority of the correlations between the two devices for the mean HR were significant and strong (rs > .80) both during baseline and experimental phases. For the time‐domain measure of mean RR (function of autonomic influences) of HRV, the correlations between the two devices at baseline were almost perfect (rs = .99), whereas at the experimental phase were significantly strong (rs > .74). However, no significant correlations were found for mean SCL (p> .05). Additionally, automated analysis led to similar features for HRV stationary data as the traditional analysis. Implications for data collection include the establishment of a methodology to compare stationary to mobile devices and a new, more cost efficient way of collecting psychophysiological data. Implications for data analysis include analyzing the data faster, with less effort and allowing for large amounts of data to be recorded.
On the Environmental Embeddedness of Redneck Identity and Politics: The Original Redneck Fishin’ Tournament and Invasive Species in a Rural Community
Authors: Besek Jordan Fox , Cunningham Jeanine
Published: February 2020

Here, we examine the environmental embeddedness of redneck identity and politics. To do so, we use data from 22 in‐depth, semi‐standardised interviews and participant observation from several rural Illinois River communities whose citizens have had to confront, interpret, and adapt to the arrival of Asian carp, an invasive species that has significantly altered life in the region. Moreover, some community members now organise the ‘Original Redneck Fishin’ Tournament’, an annual event geared toward challenging the continued invasion of Asian carp. We use this tournament as a window into the manner self‐identified redneck communities negotiate the co‐constitutive cultural, political, and material dynamism of local environmental relationships. Findings reveal a great diversity of nuanced ways a specifically redneck identity, politics, and environmental embeddedness build through each other, relationships that must be furthermore contextualised within broader socioenvironmental histories of state and urban interventions upon rural life.
Mitochondrial signalling is critical for acclimation and adaptation to flooding in Arabidopsis thaliana
Authors: Meng Xiangxiang , Li Lu , Narsai Reena , De Clercq Inge , Whelan James , Berkowitz Oliver
Published: February 2020

Mitochondria have critical functions in the acclimation to abiotic and biotic stresses. Adverse environmental conditions lead to increased demands in energy supply and metabolic intermediates, which are provided by mitochondrial ATP production and the tricarboxylic acid (TCA) cycle. Mitochondria also play a role as stress sensors to adjust nuclear gene expression via retrograde signalling with the transcription factor (TF) ANAC017 and the kinase CDKE1 key components to integrate various signals into this pathway. To determine the importance of mitochondria as sensors of stress and their contribution in the tolerance to adverse growth conditions, a comparative phenotypical, physiological and transcriptomic characterisation of Arabidopsis mitochondrial signalling mutants (cdke1/rao1 and anac017/rao2) and a set of contrasting accessions was performed after applying the complex compound stress of submergence. Our results showed that impaired mitochondrial retrograde signalling leads to increased sensitivity to the stress treatments. The multi‐factorial approach identified a network of 702 co‐expressed genes, including several WRKY TFs, overlapping in the transcriptional responses in the mitochondrial signalling mutants and stress‐sensitive accessions. Functional characterisation of two WRKY TFs (WRKY40 and WRKY45), using both knockout and overexpressing lines, confirmed their role in conferring tolerance to submergence. Together, the results revealed that acclimation to submergence is dependent on mitochondrial retrograde signalling, and underlying transcriptional re‐programming is used as an adaptation mechanism.
Determination of the lateral extent of the subcutaneous wound bed in canine cadavers after closure of skin defects to replicate tumor excision
Authors: Cunningham Devin P. , Skinner Owen T.
Published: February 2020

Objective

To determine the extent of subcutaneous involvement after primary closure of experimental skin defects.

Study design

Experimental study.

Animals

Eight large, mixed breed dog cadavers.

Methods

Standardized, circular skin defects with diameters of 2, 4, 6, or 8 cm were created at the lateral thorax or abdomen by using a matrix to ensure even distribution, with eight defects of each diameter. The wound beds were covered in 60% barium sulfate paste prior to primary closure. Computed tomography and a dedicated viewing program were used to measure the distance from the edge of the subcutaneous defect to the incision at set intervals along the incision.

Results

The mean ± SD maximum lateral extension was 6.4 ± 1.9, 14.1 ± 4.9, 18.5 ± 6.9, and 26.0 ± 9.6 mm for 2‐, 4‐, 6‐, and 8‐cm defects, respectively. Extension >2 cm from the incision occurred in zero of eight, one of eight, five of eight, and six of eight defects after closure of 2‐, 4‐, 6‐, and 8‐cm defects, respectively. Extension >3 cm from the incision occurred in zero of eight, zero of eight, two of eight, and five of eight defects after closure of 2‐, 4‐, 6‐, and 8‐cm defects, respectively.

Conclusion

The lateral extent of the subcutaneous wound bed extended past previously recommended revision margins of 2 to 3 cm in some defects measuring greater than 4 cm in diameter.

Clinical significance

Surgeons and radiation oncologists should consider the potential extent of the subcutaneous defect when planning revision therapy, especially after large resections.
Assessing the Seismic Resilience of Power Grid Systems Considering the Component Deterioration and Correlation
Authors: Wang Cao , Zhang Hao
Published: February 2020

Electricity transmission systems are essential to a community's functionalities but are susceptible to the aggressive environmental or operational factors such as the natural hazards and the environment-induced component deterioration during their service life. The service reliability of a power grid system shall be assessed under a probability-based framework taking into account the spatial uncertainty and correlation arising from both the component performance (i.e., plants, substations, and transmission lines) and the load effects. This paper estimates the resilience of a power grid system in the presence of the impacts of component deterioration and correlation, with an emphasis on the earthquake excitation hazards. The spatial variability of the component capacity and that associated with the earthquake ground motion are modeled by the Gaussian copula function. A posthazard performance indicator (PPI) is used to represent the seismic vulnerability of a grid system subjected to earthquake actions. With this, the statistics (mean value and variance) of the PPI conditional on the occurrence of an earthquake is estimated by a simulation-based method, and the resilience of the grid system (measured by a resilience index based on the recovery process of PPI) is assessed in a closed-form. The applicability of the proposed method is demonstrated through the seismic resilience assessment of an illustrative grid system.
Measuring the time–frequency properties of photon pairs: A short review
Authors: Gianani Ilaria , Sbroscia Marco , Barbieri Marco
Published: February 2020

Encoding information in the time–frequency domain demonstrates its potential for quantum information processing. It offers a novel scheme for communications with large alphabets, computing with large quantum systems, and new approaches to metrology. It is then crucial to secure full control on the generation of time–frequency quantum states and their properties. Here, the authors present an overview of the theoretical background and the technical aspects related to the characterization of time–frequency properties of two-photon states. The authors provide a detailed account of the methodologies that have been implemented for measuring frequency correlations and for the retrieval of the full spectral wavefunction. This effort has benefited enormously from the adaptation of classical metrology schemes to the needs of operating at the single-photon level.
Hypermutator Pseudomonas aeruginosa Exploits Multiple Genetic Pathways To Develop Multidrug Resistance during Long-Term Infections in the Airways of Cystic Fibrosis Patients
Authors: Colque C. A. , Albarracín Orio A. G. , Feliziani S. , Marvig R. L. , Tobares A. R. , Johansen H. K. , Molin S. , Smania A. M.
Published: February 2020

Pseudomonas aeruginosa
exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in
P. aeruginosa
isolates recovered from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic infections in CF patients. However, the within-patient genetic diversity of
P. aeruginosa
populations related to antibiotic resistance remains unexplored.
Amyloid-β and p-Tau Anti-Threat Response to Herpes Simplex Virus 1 Infection in Primary Adult Murine Hippocampal Neurons
Authors: Powell-Doherty Rebecca D. , Abbott Amber R. N. , Nelson Laura A. , Bertke Andrea S.
Published: February 2020

Growing evidence supports a link between HSV-1 infection and Alzheimer’s disease (AD). Although AD is clearly a complex multifactorial disorder, an infectious disease etiology provides alternative therapy opportunities for this devastating disease. Understanding the impact that HSV-1 has on mature neurons and the proteins most strongly associated with AD pathology may identify specific mechanisms that could be manipulated to prevent progression of neurodegeneration and dementia.
Staphylococcus epidermidis MSCRAMM SesJ Is Encoded in Composite Islands
Authors: Arora Srishtee , Li Xiqi , Hillhouse Andrew , Konganti Kranti , Little Sara V. , Lawhon Sara D. , Threadgill David , Shelburne Samuel , Hook Magnus
Published: February 2020

S. epidermidis
is an opportunistic bacterium that has established itself as a successful nosocomial pathogen. The modern era of novel therapeutics and medical devices has extended the longevity of human life, but at the same time, we also witness the evolution of pathogens to adapt to newly available niches in the host. Increasing antibiotic resistance among pathogens provides an example of such pathogen adaptation. With limited opportunities to modify the core genome, most of the adaptation occurs by acquiring new genes, such as virulence factors and antibiotic resistance determinants present in MGEs. In this study, we describe that the
sesJ
gene, encoding a recently discovered cell wall-anchored protein in
S. epidermidis
, is present in both ACME and the SCC element. The presence of virulence factors in MGEs can influence the virulence potential of a specific strain. Therefore, it is critical to study the virulence factors found in MGEs in emerging pathogenic bacteria or strains to understand the mechanisms used by these bacteria to cause infections.
Metagenomic and Metaproteomic Insights into Photoautotrophic and Heterotrophic Interactions in a
Synechococcus
Culture
Authors: Zheng Qiang , Wang Yu , Lu Jiayao , Lin Wenxin , Chen Feng , Jiao Nianzhi
Published: February 2020

The high complexity of
in situ
ecosystems renders it difficult to study marine microbial photoautotroph-heterotroph interactions. Two-member coculture systems of picocyanobacteria and single heterotrophic bacterial strains have been thoroughly investigated. However,
in situ
interactions comprise far more diverse heterotrophic bacterial associations with single photoautotrophic organisms. In the present study, combined metagenomic and metaproteomic data supplied the metabolic potentials and activities of uncultured dominant bacterial populations in the coculture system. The results of this study shed light on the nature of interactions between photoautotrophs and heterotrophs, improving our understanding of the complexity of
in situ
environments.
Draft Genome Sequences of 16 Halophilic Prokaryotes Isolated from Diverse Environments
Authors: Rodriguez-Medina Joel , Kim Hyunsoo G. , Castro Julia , Contreras Cameron M. , Glon Celine L. , Goyal Aditi , Guo Bonnie Y. , Knowles Sarai , Lin Jason C. , McGuiness Casey L. , Sorkin Eldar , Stefani Jordan , Yegireddi Sai J. , Chaganti Shyama , Cui Dante , Deck Samuel L. , Deokule Yashvi , Douglas Hallie , Kenaston Matthew , O’Brien Alana , Patterson Emily , Schoppa Nathan , Tran Vo Dean , Tran Kelly , Tran Thuy-Linh , Pérez-Irizarry Valeria , Carrasquillo-Nieves Krismarie , Montalvo-Rodriguez Rafael , Yao Andrew I. , Albeck John G. , Facciotti Marc T. , Nord Alex S. , Furrow Robert E.
Published: February 2020

Halophile-specific enzymes have wide-ranging industrial and commercial applications. Despite their importance, there is a paucity of available halophile whole-genome sequences. Here, we report the draft genome sequences of 16 diverse salt-tolerant strains of bacteria and archaea isolated from a variety of high-salt environments.
Outcomes of inflammatory bowel disease in patients with eosinophil-predominant colonic inflammation
Authors: Alhmoud Tarik , Gremida Anas , Colom Steele Diego , Fallahi Imaneh , Tuqan Wael , Nandy Nina , Ismail Mahmoud , Aburajab Altamimi Barakat , Xiong Meng-Jun , Kerwin Audra , Martin David
Published: February 2020

Background

Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear.

Methods

This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded.

Results

142 treatment-naïve IBD patients were included. Mean age was 39 years. 83% of patients had ulcerative colitis, and median follow-up was 3 years. 41% of patients had disease flare(s) and 24% required hospitalisation. Eosinophil count was not associated with risk of disease flare or hospitalisation. Patients with neutrophil-predominant inflammation (>70% neutrophils) had greater risk of disease flare(s): 27(55%) versus 24(36%) and 7(28%) in patients with mixed and eosinophil-predominant inflammation, respectively (p=0.04). Overall, patients with neutrophil-predominant inflammation were more likely to have a disease flare; HR: 2.49, 95% CI (1.0 to 5.6). Hospitalisation rate was higher in patients with neutrophil-predominant inflammation: 17(35%) compared to 17(19%) in patients with eosinophil-rich inflammation (p=0.04). Kaplan–Meier analysis showed higher flare-free survival in patients with eosinophil-predominant inflammation compared to mixed and neutrophil-predominant inflammation.

Conclusion

IBD patients with eosinophil-predominant inflammation phenotype might have reduced risk of disease flares and hospitalisation. Larger prospective studies to assess IBD outcomes in this subpopulation are warranted.
Laparoendoscopic single-site surgery compared with conventional laparoscopic surgery for benign ovarian masses: a systematic review and meta-analysis
Authors: Lin Yun , Liu Mubiao , Ye Haiyan , He Jianhui , Chen Jianguo
Published: February 2020

Objective

We aimed to evaluate the safety, efficiency and preferred indication for laparoendoscopic single-site surgery (LESS) compared with conventional laparoscopic (CL) surgery for benign ovarian masses.

Design

A systemic review and cumulative meta-analysis were performed in line with the criteria of Grading of Recommendations Assessment, Development and Evaluation: levels of evidence and grades of recommendation.

Data sources

We comprehensively searched the electronic databases including PubMed, Medline, Embase and the Cochrane Library in November 2018.

Eligibility criteria for selecting studies

We included all randomised controlled trials (RCTs) and retrospective studies published in recent 10 years, which investigated the performance of LESS versus CL in patients at all ages with benign ovarian masses.

Results

Four RCTs and nine retrospective studies published in recent decade including 1542 cases (744 cases for LESS and 798 cases for CL) were identified. Perioperative complication was consisted of intraoperative and postoperative complications, including ileus, wound infection or dehiscence and incisional hernia. Although LESS has less postoperative analgesic consumption (46.78% and 79.25%; OR: 0.49; 95% CI: 0.33 to 0.74, p<0.001) and shorter hospital stay (weighted mean difference (WMD): −0.24 days; 95% CI: −0.35 to −0.14; p<0.001), CL has less perioperative complications (6.59% and 2.85%; OR: 2.08; 95% CI: 1.05 to 4.11, p=0.04) and shorter operative time (WMD: 3.43 min; 95% CI: −0.03 to 6.88; p=0.05). Body mass index, history of previous abdominal surgery, size of adnexal mass, estimated blood loss and postoperative pain scores did not differ significantly between two techniques.

Conclusions

The indications of LESS for benign ovarian masses are similar to CL and it has better postoperative recovery. However, with less perioperative complications, CL surgery is safer than LESS.
Comparison between recent and long-term physical activity levels as predictors of cardiometabolic risk: a cohort study
Authors: Leskinen Tuija , Stenholm Sari , Pulakka Anna , Pentti Jaana , Kivimäki Mika , Vahtera Jussi
Published: February 2020

Objective

To compare recent and long-term physical activity levels as predictors of cardiometabolic risk in a risk factor-free adult population.

Design

A 12-year prospective cohort study.

Setting

The Finnish Public Sector study with surveys conducted in four waves at 4-year intervals.

Participants

19 230 participants (mean age 50.2 (SD 9.1) years, 84% women) with no prevalent cardiometabolic risk factors at wave 3 were included. Physical activity was assessed at waves 1, 2 and 3. The long-term physical activity level was determined as the mean of activity from wave 1 to 3 (over 8 years).

Outcome measure

4-year incidence of cardiometabolic risk factors (obesity, hypertension, dyslipidaemia and diabetes) after wave 3, measured individually and as a sum (accumulation of two or more risk factors vs none). Logistic and multinomial logistic regression analyses were used for the analysis.

Results

Graded associations between higher physical activity levels and lower odds of all risk factors were observed (p for trend <0.01). In comparison with the persistently vigorously active participants (≥60 metabolic equivalent (MET)-hours/week), those who were persistently inactive (<7 MET-hours/week) were about four times more likely to develop obesity (OR=4.24, 95% CI=2.83 to 6.36), two times more likely to develop hypertension (OR=2.02, 95% CI=1.45 to 2.82) and dyslipidaemia (OR=1.82, 95% CI=1.03 to 3.22) and eight times more likely to develop diabetes (OR=7.84, 95% CI=1.78 to 34.6). The corresponding OR for accumulating two or more risk factors was 5.24-fold (95% CI=2.39 to 11.47). For recently inactive versus recently vigorously active, the estimates were weaker (OR=2.36, 95% CI=1.71 to 3.25 for obesity; 1.78, 95% CI=1.35 to 2.35 for hypertension; 1.71, 95% CI=1.04 to 2.82 for dyslipidaemia; 3.56, 95% CI=1.06 to 11.96 for diabetes and 2.66, 95% CI=1.48 to 4.78 for ≥2 risk factors).

Conclusion

Cardiometabolic risk associated with physical inactivity is better captured by repeated measurements of physical activity than by a single measurement of the most recent activity level.
Asthma is associated with frailty among community-dwelling adults: the GAZEL cohort
Authors: Landré Benjamin , Nadif Rachel , Goldberg Marcel , Gourmelen Julie , Zins Marie , Ankri Joël , Herr Marie
Published: February 2020

Introduction

Early management of chronic respiratory diseases (CRDs) and frailty have been identified as key targets towards healthy ageing, but the association between CRDs and frailty has been poorly investigated. We studied the association between asthma and frailty in adults of the GAZEL cohort using different definitions of asthma over the 26 years of follow-up.

Methods

Current asthma definitions are based on yearly self-reports of symptoms or medication (in 2015, constant reports or at least one report between 1990 and 2015), or on a detailed respiratory symptoms questionnaire in 2002. Frailty definition is based on weakness, fatigue, unintentional weight loss, low physical activity and mobility in 2015. Frail participants had three criteria or more, pre-frail 1 or 2, and robust 0. Multinomial regression models adjusted for age, sex, body mass index, smoking, education, marital status and comorbidities were performed.

Results

In 2015, 12 345 adults (73% men, 61 to 77 years old) were included: 3% of them reported current asthma, 1.6% had constant reports during the follow-up and 9% reported current asthma at least once. In 2015, 6% were frail, 34% pre-frail and 13% of current asthmatics and 6% of non-asthmatics were frail (adjusted OR (aOR) 2.19 (1.44 to 3.34)). Significant associations were also found with the 2002 definition (aOR 2.24 (1.73 to 2.90)), constant reports (aOR 3.67 (1.70 to 7.93)) or at least once (aOR 1.50 (1.15 to 1.98)). Current asthma was also associated with pre-frailty with the 2002 definition (aOR 1.46 (1.26 to 1.68)).

Discussion

Participants with asthma had increased risk of frailty. A better understanding of their relationship could help to define and evaluate strategies for a better ageing of asthmatics.
Rapid recovery of postnivolumab vemurafenib-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome after tocilizumab and infliximab administration
Authors: Maximova Natalia , Maestro Alessandra , Zanon Davide , Marcuzzi Annalisa
Published: February 2020

Background

Immune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramatically altered the treatment outcomes of metastatic melanoma over the past few years. Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. Vemurafenib-related severe AEs with early onset are reported in patients who were previously treated with anti-programmed cell death-1 (anti PD-1) antibodies. A prolonged administration of systemic steroids is the first-line treatment of severe or life-threatening AEs. We report the case of a woman suffering from vemurafenib-related severe, rapidly worsening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, resolved in a few hours after single-dose administration of a combination of TNF-α antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab.

Case presentation

A 41-year-old woman treated with single-agent nivolumab presented with a melanoma progression. Biopsy samples were revised, revealing a BRAF V600E mutation. The patient was started on vemurafenib and cobimetinib treatment only 10 days after the last administration of nivolumab. On the third day of anti-BRAF therapy, profound lymphopenia was detected, and maculopapular eruption appeared afterward. Subsequently, the clinical conditions deteriorated further, and the woman was admitted on an emergency basis with high fever, respiratory and cardiocirculatory failure, diffuse rash, generalized edema, and lymphadenopathy. Diagnosis of DRESS syndrome with overexpressed capillary leakage was made. A single dose of tocilizumab was administered with an improvement of cardiocirculatory and renal function in a few hours. Because of worsening of liver function, skin lesions and mucositis, a single dose of infliximab was prescribed, and dramatic improvement was noted over the next 24 hours. Dabrafenib and trametinib were initiated, and coinciding with washout of infliximab from the patient’s blood, the drug toxicity recurred.

Conclusion

Anti-IL-6 and anti-TNF-α target treatment of very severe AEs may afford an immediate resolution of potentially life-threatening symptoms and reduce the duration and the costs of hospitalization. Maintenance of therapeutic infliximab blood concentrations permits an early switch to dabrafenib after vemurafenib-related AEs.
Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer
Authors: Lu Ye , Gentiluomo Manuel , Lorenzo-Bermejo Justo , Morelli Luca , Obazee Ofure , Campa Daniele , Canzian Federico
Published: February 2020

Background

Observational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC.

Objective

We sought to investigate the possible causal effects of established and putative factors on PDAC risk.

Methods

We conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses.

Results

We found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10−5). Fasting insulin (OR 2.84, 95% CI 1.23 to 6.56, p=0.01), low-density lipoprotein cholesterol (OR 1.16, 95% CI 1.02 to 1.32, p=0.03) and type 2 diabetes (OR 1.09, 95% CI 1.01 to 1.17, p=0.02) were also causally associated with PDAC risk. BMI showed both direct and fasting insulin-mediated causal effects.

Conclusion

We found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.
Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives
Authors: Carvalho Joana , Oliveira Patricia , Senz Janine , São José Celina , Hansford Samantha , Teles Sara Pinto , Ferreira Marta , Corso Giovanni , Pinheiro Hugo , Lemos Diana , Pascale Valeria , Roviello Franco , Huntsman David , Oliveira Carla
Published: February 2020

Background

Familial intestinal gastric cancer (FIGC) remains genetically unexplained and without testing/clinical criteria. Herein, we characterised the age of onset and disease spectrum of 50 FIGC families and searched for genetic causes potentially underlying a monogenic or an oligogenic/polygenic inheritance pattern.

Methods

Normal and tumour DNA from 50 FIGC probands were sequenced using Illumina custom panels on MiSeq, and their respective germline and somatic landscapes were compared with corresponding landscapes from sporadic intestinal gastric cancer (SIGC) and hereditary diffuse gastric cancer cohorts.

Results

The most prevalent phenotype in FIGC families was gastric cancer, detected in 138 of 208 patients (50 intestinal gastric cancer probands and 88 unknown gastric cancer histology relatives), followed by colorectal and breast cancers. After excluding benign and intronic variants lacking impact in splicing, 12 rare high-quality variants were found exclusively in 11 FIGC probands. Only two probands carried potentially deleterious variants, but lacked somatic second-hits, weakly supporting the monogenic hypothesis for FIGC. However, FIGC probands developed gastric cancer at least 10 years earlier and carried more TP53 germline common variants than SIGC (p=4.5E-03); FIGC and SIGC could be distinguished by specific germline and somatic variant profiles; there was an excess of FIGC tumours presenting microsatellite instability (38%); and FIGC tumours displayed significantly more somatic common variants than SIGC tumours (p=4.2E-06).

Conclusion

This study proposed the first data-driven testing criteria for FIGC families, and supported FIGC as a genetically determined, likely polygenic, gastric cancer-predisposing disease, with earlier onset and distinct from patients with SIGC at the germline and somatic levels.