bluuebunny/crossref_metadata_2025 huggingface dataset:
Younger Donor Tissue in Descemet Membrane Endothelial Keratoplasty Surgery: Clinical Outcomes
Authors: Hill Jordan R. , Chen Shin-Yi , Bauer Alex J. , Straiko Megan M. W. , Sanchez Philip James , Straiko Michael D. , Terry Mark A.
Published: December 2020

Purpose:

To determine whether using younger donor tissue for Descemet membrane endothelial keratoplasty (DMEK) surgery influences clinical outcomes.

Methods:

Scroll tightness, unscrolling time, rebubble rate, and preoperative and 3- and 6-month postoperative endothelial cell density (ECD) and endothelial cell loss (ECL) were compared for 661 DMEK grafts prepared from younger (aged younger than 50 yrs, n = 81) and older donors (aged 50 yrs or older, n = 580) with Student t test, χ2 test, or Mann–Whitney U test.

Results:

There was no difference in overall unscrolling time (younger donors: 3.1 ± 3.1 min, older donor: 2.9 ± 2.7 min, P = 0.503). Experienced faculty surgeons, compared with fellows, had a significantly lower unscrolling times for both younger donors (2.4 ± 2.3 vs. 4.6 ± 3.9 min, P = 0.002) and older donors (2.5 ± 2.1 vs. 3.7 ± 3.3 min, P <0.001). Rebubble rates were not statistically different between younger (12.3%) and older donors (15.0%, P = 0.527). Three-month ECD was higher in grafts from younger compared with that in those from older donors (2138 ± 442 vs. 1974 ± 470 cells/mm2, P = 0.024). Six-month ECD was similar for younger (1972 ± 509 cells/mm2) and older donors (1947 ± 460 cells/mm2, P = 0.585). There was no difference in 3- or 6-month ECL comparing younger (3-mo: 24.3% ± 13.4%; 6-mo: 31.1% ± 15.2%) with older donors (3-mo: 25.9% ± 15.5%, P = 0.489; 6-mo: 27.8% ± 15.1%, P = 0.231).

Conclusions:

DMEK grafts prepared from younger donors exhibited similar unscrolling times, rebubble rates, and 3- and 6-month ECL compared with older donors. Experienced surgeons might begin to accept DMEK grafts from younger donors with confidence.
Importance of Reviewing Antibiotic Courses by 48 Hours: Risk Factors for Third-Generation Cephalosporin Resistance Among AmpC Harboring Organisms in Urine and Respiratory Cultures
Authors: Stultz Jeremy S. , Bice Tabitha , Johnstone Kimberly , Stuart Connor M. , Shelton Chasity M. , Arnold Sandra R. , Bagga Bindiya , Lee Kelley R.
Published: December 2020

Background:

Citrobacter, Enterobacter, Morganella, and Serratia (AmpC organisms) species can exhibit third-generation cephalosporin (TGC) resistance after TGC exposure. We aimed to assess if institutional TGC utilization correlated with institutional AmpC organism susceptibility and if prior TGC exposure ≤48 hours were associated with TGC resistance in the first culture of a future infection episode caused by an AmpC organism.

Methods:

A 5-year retrospective cohort study was performed, including AmpC organisms isolated from pediatric urinary and respiratory tract cultures at an institution with TGC courses reviewed by the antimicrobial stewardship program at 48 hours. Correlations were assessed by Pearson’s correlation. Multivariable logistic regression identified factors independently associated with TGC resistance in a subcohort of infection episodes.

Results:

Among 654 cultures, AmpC organism TGC susceptibility increased from 74% in 2013 to 89.3% in 2017, and this correlated with a 26.1% decrease in TGC utilization (R = −0.906; P = 0.034). Among 275 AmpC organism infections, 21.1% were resistant. Resistance occurred in 13.6%, 17.4%, and 56.5% of infections with no exposure, ≤48 hours, and >48 hours of TGC exposure in the past 30 days, respectively. TGC exposure ≤48 hours was not associated with resistance (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.32–4.94; P = 0.74), whereas, TGC exposure >48 hours was (OR, 8.7; 95% CI, 3.67–20.6; P 
< 0.001). Infections in 2017 were less likely to be resistant (OR, 0.25; 95% CI, 0.08–0.8; P = 0.019).

Conclusions:

Decreased TGC utilization, likely related to antimicrobial stewardship, correlated with increased AmpC organism susceptibility. Limiting TGC exposure to ≤48 hours when possible may reduce AmpC organism resistance in future infections.
Development of Methods to Extract RNA From Archived Pediatric Needle Liver Biopsies to Produce Sequencing Data
Authors: Shin Emilia , Jones‐Brando Lorraine V. , Florea Liliana D. , Schwarz Kathleen B. , Yolken Robert H.
Published: December 2020

Genetic susceptibility has been proposed as etiopathogenic in several pediatric liver diseases including autoimmune hepatitis (AIH). High throughput sequencing (HTPS) has been applied to archived needle liver biopsies obtained from adults but rarely to pediatric biopsies. For conclusive diagnosis of AIH, most subjects have an initial formalin‐fixed paraffin embedded (FFPE) needle liver biopsy that is eventually archived and may be stored for decades.

Objective:

Our goal was to develop methods to utilize tissue from archived needle liver biopsies for extraction of RNA sufficient to produce HTPS data.

Methods:

We extracted total RNA from 45 FFPE needle liver biopsy samples (24 AIH type 1 patients and 21 controls [ages 15_11 and 19_10]; biopsy storage time 0.5–20 years) and constructed cDNA libraries that were then sequenced on an Illumina HiSeq2000 platform.

Results:

Forty (89%) of the libraries produced high‐quality sequences for further analyses. The average number of sequences obtained per library from HTPS was 55,136,519 (range 14,914,291–184,027,499). There was a significant inverse relationship between the number of human reads obtained and the age of the specimen (P < 2_10_7). It was possible to classify more than 90% of the reads as known genes in samples that had been stored for less than 10 years.

Conclusions:

Archived needle liver biopsies can be used for sequence based interrogation of the etiologic origins of complex liver diseases of young subjects, such as AIH.
Increased Cytoplasmic Yes-associated Protein (YAP) Expression in Mismatch Repair Protein-Proficient Colorectal Cancer With High-grade Tumor Budding and Reduced Autophagy Activity
Authors: Mikula Michael , Najjar Saleh , El Jabbour Tony , Dalvi Siddhartha , Umrau Kavita , Li Hua , Koo Brandon H. , Lee Hwajeong
Published: December 2020

Yes-associated protein (YAP) is a transcriptional coactivator regulated by autophagy that stimulates colorectal cancer (CRC) progression through activation of epithelial-mesenchymal transition (EMT), represented by tumor budding. The associations between these components in CRC are unknown. Archived surgically resected CRCs with known mismatch repair protein (MMR) status were retrieved (n=81; 2010 to 2016). Electronic medical records were reviewed for clinicopathologic variables including pathologic TNM stage and clinical stage. Tumor budding was graded according to consensus guidelines. Cytoplasmic and nuclear YAP and p62 (autophagy substrate) immunoreactivity were semiquantitatively scored within tumor samples. The Student t test, Fisher exact test, χ2 test, and Spearman correlation coefficient were performed with P<0.05 as a significance level. MMR proficiency (MMR-P) status correlated with high-grade tumor budding. The extent of cytoplasmic YAP staining and pathologic N stage was associated with tumor budding in multivariate analysis. Cytoplasmic YAP expression correlated with higher cytoplasmic p62 expression, suggesting an inverse correlation between autophagy activation and cytoplasmic YAP expression. Nuclear YAP expression correlated with pathologic N stage and clinical stage. A correlation between MMR-P status and tumor budding, combined with correlations between cytoplasmic YAP, tumor budding and p62 raise the possibility of 2 distinct neoplastic pathways concerning autophagy and YAP; one displaying relative activation of YAP and EMT, being commonly observed in MMR-P, and another with less active YAP and EMT, but active autophagy, being commonly seen in MMR-deficient CRC. Nuclear YAP staining could be useful in prognostication.
Morality and the Brain: The Right Hemisphere and Doing Right
Authors: Filley Christopher M. , Kletenik Isaiah , Churchland Patricia S.
Published: December 2020

Morality, the set of shared attitudes and practices that regulate individual behavior to facilitate cohesion and well-being, is a function of the brain, yet its localization is uncertain. Neuroscientific study of morality has been conducted by examining departures from moral conduct after neurologic insult and by functional neuroimaging of moral decision-making in cognitively intact individuals. These investigations have yielded conflicting results: Acquired sociopathy, a syndromic surrogate for acquired immorality, has been reported predominantly after right frontotemporal lesions, whereas functional neuroimaging during moral decision-making has demonstrated bilateral activation. Although morality is bilaterally represented, the right hemisphere is clinically more critical in light of focal lesion data suggesting that moral behavior is subserved by a network of right frontotemporal structures and their subcortical connections. Evolution may have endowed the brain with bilaterally represented but unilaterally right-dominant morality. The unilateral dominance of morality permits concentration of an essential social cognitive function to support the perceptual and executive operations of moral behavior within a single hemisphere; the bilateral representation of morality allows activation of reserve tissue in the contralateral hemisphere in the event of an acquired hemispheric injury. The observed preponderance of right hemisphere lesions in individuals with acquired immorality offers a plausible hypothesis that can be tested in clinical settings. Advances in the neuroscience of morality promise to yield potentially transformative clinical and societal benefits. A deeper understanding of morality would help clinicians address disordered conduct after acquired neurologic insults and guide society in bolstering public health efforts to prevent brain disease.
Loss of the glucocorticoid receptor causes accelerated ovarian ageing in zebrafish
Authors: Faught Erin , Santos Helio B. , Vijayan Mathilakath M.
Published: December 2020

Reproductive decline in mid-adult females is an established phenotype of the ageing process. Stress and the rise in glucocorticoids (GCs) accelerate reproductive ageing, but little is known about the mechanisms involved. During stress, GCs activate the glucocorticoid receptor (GR), a ubiquitously expressed, ligand-bound transcription factor, to elicit physiological changes for restoring homeostasis. Here, we tested the hypothesis that GC-GR signalling is essential for accelerating reproductive ageing. To test this, we used a ubiquitous GR knockout (GRKO) zebrafish, which is inherently hypercortisolemic, to delineate the role of high cortisol and GR signalling on reproductive ageing. The loss of GR led to premature ovarian ageing, including high frequency of typical and atypical follicular atresia in vitellogenic oocytes, yolk liquefaction and large inflammatory infiltrates. The reduction in oocyte quality was also associated with a decline in ovarian
tert
expression in the adult GRKO fish compared to the early adult GRKO and adult wild-type zebrafish. Accelerated ovarian ageing also impacted the progeny, including lower breeding success, fecundity, egg fertilization rate and delayed somitogenesis and embryo survival in the adult GRKO fish. We adduce that GR signalling is essential for prolonging the reproductive lifespan and improving the egg quality and embryo viability in zebrafish.
Cretaceous origins of the vibrotactile bill-tip organ in birds
Authors: du Toit C. J. , Chinsamy A. , Cunningham S. J.
Published: December 2020

Some probe-foraging birds locate their buried prey by detecting mechanical vibrations in the substrate using a specialized tactile bill-tip organ comprising mechanoreceptors embedded in densely clustered pits in the bone at the tip of their beak. This remarkable sensory modality is known as ‘remote touch’, and the associated bill-tip organ is found in probe-foraging taxa belonging to both the palaeognathous (in kiwi) and neognathous (in ibises and shorebirds) clades of modern birds. Intriguingly, a structurally similar bill-tip organ is also present in the beaks of extant, non-probing palaeognathous birds (e.g. emu and ostriches) that do not use remote touch. By comparison with our comprehensive sample representing all orders of extant modern birds (Neornithes), we provide evidence that the lithornithids (the most basal known palaeognathous birds which evolved in the Cretaceous period) had the ability to use remote touch. This finding suggests that the occurrence of the vestigial bony bill-tip organ in all modern non-probing palaeognathous birds represents a plesiomorphic condition. Furthermore, our results show that remote-touch probe foraging evolved very early among the Neornithes and it may even have predated the palaeognathous–neognathous divergence. We postulate that the tactile bony bill-tip organ in Neornithes may have originated from other snout tactile specializations of their non-avian theropod ancestors.
Plant carbohydrate content limits performance and lipid accumulation of an outbreaking herbivore
Authors: Talal Stav , Cease Arianne J. , Youngblood Jacob P. , Farington Ruth , Trumper Eduardo V. , Medina Hector E. , Rojas Julio E. , Fernando Copa A. , Harrison Jon F.
Published: December 2020

Locusts are major intermittent threats to food security and the ecological factors determining where and when these occur remain poorly understood. For many herbivores, obtaining adequate protein from plants is a key challenge. We tested how the dietary protein : non-structural carbohydrate ratio (p : c) affects the developmental and physiological performance of 4th-5th instar nymphs of the South American locust,
Schistocerca cancellata,
which has recently resurged in Argentina, Bolivia and Paraguay. Field marching locusts preferred to feed on high carbohydrate foods. Field-collected juveniles transferred to the laboratory selected artificial diets or local plants with low p : c. On single artificial diets, survival rate increased as foods became more carbohydrate-biased. On single local plants, growth only occurred on the plant with the lowest p : c. Most local plants had p : c ratios substantially higher than optimal, demonstrating that field marching locusts must search for adequate carbohydrate or their survival and growth will be carbohydrate-limited. Total body lipids increased as dietary p : c decreased on both artificial and plant diets, and the low lipid contents of field-collected nymphs suggest that obtaining adequate carbohydrate may pose a strong limitation on migration for
S. cancellata
. Anthropogenic influences such as conversions of forests to pastures, may increase carbohydrate availability and promote outbreaks and migration of some locusts.
Experimental evolution of post-ingestive nutritional compensation in response to a nutrient-poor diet
Authors: Cavigliasso Fanny , Dupuis Cindy , Savary Loriane , Spangenberg Jorge E. , Kawecki Tadeusz J.
Published: December 2020

The geometric framework of nutrition predicts that populations restricted to a single imbalanced diet should evolve post-ingestive nutritional compensation mechanisms bringing the blend of assimilated nutrients closer to physiological optimum. The evolution of such nutritional compensation is thought to be mainly driven by the ratios of major nutrients rather than overall nutritional content of the diet. We report experimental evolution of divergence in post-ingestive nutritional compensation in populations ofDrosophila melanogasteradapted to diets that contained identical imbalanced nutrient ratios but differed in total nutrient concentration. Larvae from ‘Selected’ populations maintained for over 200 generations on a nutrient-poor diet with a 1 : 13.5 protein : carbohydrate ratio showed enhanced assimilation of nitrogen from yeasts and reduced assimilation of carbon from sucrose than ‘Control’ populations evolved on a diet with the same nutrient ratio but fourfold greater nutrient concentration. Compared to the Controls, the Selected larvae also accumulated less triglycerides relative to protein. This implies that the Selected populations evolved a higher assimilation rate of amino acids from the poor imbalanced diet and a lower assimilation of carbohydrates than Controls. Thus, the evolution of nutritional compensation may be driven by changes in total nutrient abundance, even if the ratios of different nutrients remain unchanged.
Oricola thermophila sp. nov., a marine bacterium isolated from tidal flat sediment and emended description of the genus Oricola Hameed et al. 2015
Authors: Yang Sung-Hyun , Park Mi-Jeong , Kwon Kae Kyoung
Published: December 2020

A Gram-stain-negative, facultatively anaerobic, rod-shaped (1.8–4.4×0.5–0.7 µm) and motile marine bacterium, designated as MEBiC13590T, was isolated from tidal flat sediment sampled at Incheon City, on the west coast of the Republic of Korea. The 16S rRNA gene sequence analysis revealed that strain MEBiC13590T showed high similarity to

Oricola cellulosilytica

CC-AMH-0T (98.2 %), followed by

Oceaniradius stylonematis

StC1T (97.5 %); however, it clustered with

Oricola cellulosilytica

. The phylogenomic tree inferred by the up-to-date bacterial core gene set suggested that strain MEBiC13590T shared a phyletic line with

Oricola cellulosilytica

. Average nucleotide identity and digital DNA–DNA hybridization values (75.0 and 19.3 %, respectively) between strain MEBiC13590T and

Oricola cellulosilytica

CC-AMH-0T were below the respective species delineation cutoffs. Growth was observed at 22–50 °C (optimum, 45 °C), at pH 5–9 (optimum, pH 7) and with 1–6 % (optimum, 3 %) NaCl. The predominant cellular fatty acids were C16 : 0 (7.6 %), C18 : 0 (12.2 %), 11-methyl C18 : 1 ω7c (5.7 %), C19 : 0 cyclo ω6c and summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c; 38 %). The DNA G+C content was 63.5 mol%. The major respiratory quinone was Q-10. Several phenotypic characteristics such as growth temperature, oxygen requirement, enzyme activities of urease, gelatinase, lipase (C14), α-chymotrypsin, acid phosphatase, β-galactosidase, β-glucosidase etc. differentiate strain MEBiC13590T from

Oricola cellulosilytica

CC-AMH-0T. Based on this polyphasic taxonomic data, strain MEBiC13590T should be classified as representing a novel species in the genus

Oricola

for which the name Oricola thermophila sp. nov. is proposed . The type strain is MEBiC13590T (=KCCM 43313T=JCM 33661T).
Sulfurimonas indica sp. nov., a hydrogen- and sulfur-oxidizing chemolithoautotroph isolated from a hydrothermal sulfide chimney in the Northwest Indian Ocean
Authors: Hu Qitao , Wang Shasha , Lai Qiliang , Shao Zongze , Jiang Lijing
Published: December 2020

A novel mesophilic, hydrogen- and sulfur-oxidizing bacterium, designated strain NW8NT, was collected from a sulfide chimney at the deep-sea hydrothermal vent on the Carlsberg Ridge of the Northwest Indian Ocean. The cells were Gram-stain-negative, motile, short rods with a single polar flagellum. The temperature, pH and salinity ranges for growth of strain NW8NT were 4–40 °C (optimum, 33 °C), pH 4.5–7.5 (optimum, pH 5.5) and 340–680 mM NaCl (optimum, 510 mM). The isolate was an obligate chemolithoautotroph capable of growth using hydrogen, thiosulfate, sulfide or elemental sulphur as the sole energy source, carbon dioxide as the sole carbon source and molecular oxygen as the sole electron acceptor. The major cellular fatty acids of strain NW8NT were summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 0 and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c). The total size of its genome was 2 093 492 bp and the genomic DNA G+C content was 36.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences and core genes showed that the novel isolate belonged to the genus

Sulfurimonas

and was most closely related to

Sulfurimonas paralvinellae

GO25T (97.4 % sequence identity). The average nucleotide identity and DNA–DNAhybridization values between strain NW8NT and

S. paralvinellae

GO25T was 77.8 and 21.1 %, respectively. Based on the phylogenetic, genomic and phenotypic data presented here, strain NW8NT represents a novel species of the genus

Sulfurimonas

, for which the name Sulfurimonas indica sp. nov. is proposed, with the type strain NW8NT (=MCCC 1A13988T=KTCC 15780T).
Veillonella nakazawae sp. nov., an anaerobic Gram-negative coccus isolated from the oral cavity of Japanese children
Authors: Mashima Izumi , Theodorea Citra F. , Djais Ariadna A. , Kunihiro Tadao , Kawamura Yoshiaki , Otomo Maiko , Saitoh Masato , Tamai Riyoko , Kiyoura Yusuke
Published: December 2020

Two strains of previously unknown Gram-negative cocci, T1-7T and S6-16, were isolated from the oral cavity of healthy Japanese children. The two strains showed atypical phenotypic characteristics of members of the genus

Veillonella

, including catalase production. Sequencing of their 16S rRNA genes confirmed that they belong to genus

Veillonella

. Under anaerobic conditions, the two strains produced acetic acid and propionic acid as metabolic end-products in a trypticase–yeast extract–haemin medium containing 1 % (w/v) glucose, 1 % (w/v) fructose and 1 % (v/v) sodium lactate. Comparative analysis of the 16S rRNA, dnaK, rpoB and gltA gene sequences revealed that the two strains are phylogenetically homogeneous and comprise a distinct, novel lineage within the genus

Veillonella

. The sequences from the two strains shared the highest similarity, at 99.9, 95.8, 96.9 and 96.7 %, using the partial 16S rRNA, dnaK, rpoB and gltA gene sequences, respectively, with the type strains of the two most closely related species,

Veillonella dispar

ATCC 17748T and

Veillonella infantium

JCM 31738T. Furthermore, strain T1-7T shared the highest average nucleotide identity (ANI) value (94.06 %) with type strain of the most closely related species,

V. infantium

. At the same time, strain T1-7T showed the highest digital DNA–DNA hybridization (dDDH) value (55.5 %) with the type strain of

V. infantium

. The two strains reported in this study were distinguished from the previously reported species from the genus

Veillonella

based on catalase production, partial dnaK, rpoB and gltA sequences, average ANI and dDDH values. Based on these observations, the two strains represent a novel species, for which the name Veillonella nakazawae sp. nov. is proposed. The type strain is T1-7T (JCM 33966T=CCUG 74597T).
Protection of health care workers from exhaled air of patients operated under local, regional, spinal or epidural anaesthesia during COVID 19 pandemic
Authors: Atodaria Kuldeepsinh Pradipkumar , Singh Mayank , Prajapati Vimalkumar , Shah Kush Shaileshkumar , Atodaria Pradipkumar Raghuvirsinh
Published: December 2020

The SARS-CoV-2 (COVID-19) pandemic mandates the use of N-95/FFP-2 masks for healthcare workers, especially in operation room (OR) for surgical or aerosol producing procedures. During pandemic, surgical interventions such as limb trauma, limb amputations, and limb malignancies continued to flow into the hospitals and are normally performed under local, regional or spinal anaesthesia. N-95/FFP-2 masks normally do not prevent escape of exhaled air to surrounding and to avoid the escape of exhaled unfiltered air, sealing masks by taping its edges to face possibly serves the purpose, but causes significant discomfort to patients. HEPA filters, high vacuum suction apparatus, and negative pressure operating-room may protect partially against the-risk of infection if patient’s exhaled air is infected. In order to reduce risk of transmission from patients’ exhaled air to the healthcare workers, a technique has been designed to divert the patients’ exhaled air to outside the-OR using a suction machine. This technique is easy, simple and cost-effective and trial has been performed with four-volunteers to see feasibility to breathe through N-95 mask sealed by sticking its edges to face using tape. The trial reflected reduction in SpO2, causing increased respiratory-rate, tachycardia and hypertension, in-addition an un-acclimatized volunteers had difficulty in breathing through sealed N-95 masks, which was relieved by supplying oxygen to them. Attaching suction system to remove the-exhaled air aids to comfort levels. Treating exhaled-air with sodium-hypochlorite and diverting it externally to an open-space outside the-OR added to safety for the patients, surgical team and the hospital surroundings.
Distribution of SARS-CoV-2 RNA Signal in a Home with COVID-19 Positive Occupants
Authors: Maestre Juan P. , Jarma David , Yu Cesca , Siegel Jeff , Horner Sharon , Kinney Kerry A.
Published: December 2020

Although many COVID-19 patients quarantine and recover at home, the dispersal of SARS-CoV-2 onto surfaces and dust within the home environment remains poorly understood. To investigate the distribution and persistence of SARS-CoV-2 in a quarantine home, samples were collected from a household with two confirmed COVID-19 cases (one adult and one child). Home surface swab and dust samples were collected two months after symptom onset (and one month after symptom resolution) in the household. The strength of the SARS-CoV-2 molecular signal in fomites varied as a function of sample location, surface material and cleaning practices. Notably, the SARS-CoV-2 RNA signal was detected at several locations throughout the household although cleaning appears to have attenuated the signal on many surfaces. Of the 24 surfaces sampled, 46% were SARS-CoV-2 positive at the time of sampling. The SARS-CoV-2 concentrations in dust recovered from floor and HVAC filter samples ranged from 104-105 N2 gene copies/g dust. While detection of viral RNA does not imply infectivity, this study confirms that the SARS-CoV-2 RNA signal can be detected at several locations within a COVID-19 quarantine home and can persist after symptoms have resolved. In addition, the concentration of SARS-CoV-2 (normalized per unit mass of dust) recovered in home HVAC filters may prove useful for estimating SARS-CoV-2 airborne levels in homes.
A Net Benefit Approach for the Optimal Allocation of a COVID-19 Vaccine
Authors: Kirwin Erin , Rafferty Ellen , Harback Kate , Round Jeff , McCabe Christopher
Published: December 2020

OBJECTIVE

We implement a model-based approach to identify the optimal allocation of a COVID-19 vaccine in the province of Alberta, Canada.

METHODS

We develop an epidemiologic model to evaluate allocation strategies defined by age and risk target groups, coverage, effectiveness, and cost of vaccine. The model simulates hypothetical immunization scenarios within a dynamic context, capturing concurrent public health strategies and population behaviour changes.

RESULTS

In a scenario with 80% vaccine effectiveness, 40% population coverage, and prioritisation of those over the age of 60 at high-risk of poor outcomes, active cases are reduced by 17% and net monetary benefit increased by $263 million dollars, relative to no vaccine. Concurrent implementation of policies such as school closure and senior contact reductions have similar impacts on incremental net monetary benefit ($352 vs. 292 million, respectively) when there is no prioritisation given to any age or risk group. When older age groups are given priority, the relative benefit of school closures is much larger ($214 vs. 118 million). Results demonstrate that the rank ordering of different prioritisation options varies by prioritisation criteria, vaccine effectiveness and coverage, and concurrently implemented policies.

CONCLUSIONS

Our results have three implications: (i) optimal vaccine allocation will depend on the public health policies in place at the time of allocation and the impact of those policies on population behaviour; (ii) outcomes of vaccine allocation policies can be greatly supported with interventions targeting contact reduction in critical sub-populations; and (iii) identification of the optimal strategy depends on which outcomes are prioritised.
Dedifferentiation of memory-related brain function as a potential early biomarker of Alzheimer’s disease in asymptomatic older women: Results from the PREVENT-AD Cohort
Authors: Rabipour Sheida , Rajagopal Sricharana , Pasvanis Stamatoula ,   PREVENT-AD Research Group, Rajah M. Natasha
Published: December 2020

Late-onset Alzheimer’s disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether there are sex differences in episodic memory-related brain function in cognitively intact older adults at risk of developing AD. In the current study, we used task fMRI to test for sex differences in episodic memory-related brain activity and brain activity-behavior correlations in cognitively intact older adults with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03±3.78; Meducation=15.41±3.40). Importantly, we tested women and men who were matched in age, body mass index, years of education, and proximity to the age of parental AD onset. We used data-driven task-based multivariate partial least squares (PLS) analysis to identify sex differences in brain activity during the successful encoding and retrieval of objects and their associated spatial context. We used behavior PLS to examine sex differences in the correlations between brain activity and memory performance at encoding and retrieval. Our results suggested no significant sex differences in behavioral performance on the memory task. Yet, we observed sex differences in task-related brain activity and in brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Specifically, subsequent object-location associative retrieval associated with encoding related activation of caudate, cingulate, and middle occipital cortex in women and, additionally, of temporo-parietal regions in men. We also found male-specific activations in ventrolateral prefrontal cortex (PFC) and insula during associated with the encoding and retrieval of object-only information. Moreover, whereas activity in ventrolateral PFC, posterior cingulate, and inferior parietal regions during encoding supported subsequent performance in women, activity in these regions during retrieval supported object-location associative memory in men. Similarly, we found that activity in ventrolateral PFC, precuneus, parahippocampal, anterior cingulate, and occipital regions during retrieval supported general memory performance in women but object-only retrieval in men. Our findings suggest functional dedifferentiation of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development.
Hierarchical Morphogenesis of Swallowtail Butterfly Wing Scale Nanostructures
Authors: Seah Kwi Shan , Saranathan Vinodkumar
Published: December 2020

The study of color patterns in the animal integument is a fundamental question in biology, with many lepidopteran species being exemplary models in this endeavor due to their relative simplicity and elegance. While significant advances have been made in unravelling the cellular and molecular basis of lepidopteran pigmentary coloration, the morphogenesis of wing scale nanostructures involved in structural color production is not well understood. Contemporary research in this topic largely focuses on a few nymphalid model taxa (e.g.,Bicyclus,Heliconius), despite an overwhelming diversity in the hierarchical nanostructural organization of lepidopteran wing scales. Here, we present a time-resolved, comparative developmental study of hierarchical scale nanostructures inParides eurimedesand five other papilionid species. Our results uphold the putative conserved role of F-actin bundles in acting as spacers between developing ridges, as previously documented in several nymphalid species. Interestingly, while ridges are developing inP. eurimedes, plasma membrane manifests irregular mesh-like crossribs characteristic of Papilionidae, which delineate the accretion of cuticle into rows of planar disks in between ridges. Once the ridges have grown, disintegrating F-actin bundles appear to reorganize into a network that supports the invagination of plasma membrane underlying the disks, subsequently forming an extruded honeycomb lattice. Our results uncover a previously undocumented role for F-actin in the morphogenesis of complex wing scale nanostructures, likely specific to Papilionidae.
Dietary Monoterpenoids As a New Class of Allosteric Human Aryl Hydrocarbon Receptor Antagonists
Authors: Poulíková Karolína , Zůvalová Iveta , Vyhlídalová Barbora , Krasulová Kristýna , Jiskrová Eva , Vrzal Radim , Kortagere Sandhya , Kopečná Martina , Kopečný David , Šebela Marek , Rolfes Katharina Maria , Haarmann-Stemmann Thomas , Mani Sridhar , Dvořák Zdeněk
Published: December 2020

Carvones, the constituents of essential oils of dill, caraway, and spearmint, were reported to antagonize the human aryl hydrocarbon receptor (AhR); however, the exact molecular mechanism remains elusive. We show that carvones are non-competitive allosteric antagonists of the AhR that inhibit the induction of AhR target genes in a ligand-selective and cell type-specific manner. Carvones do not displace radiolabeled ligand from binding at the AhR, but they bind allosterically within the bHLH/PAS-A region of the AhR. Carvones did not influence a translocation of ligand-activated AhR into the nucleus. Carvones inhibited the heterodimerization of the AhR with its canonical partner ARNT and subsequent binding of the AhR to the promotor of CYP1A1. Interaction of carvones with potential off-targets, including ARNT and protein kinases, was refuted. This is the first report of a small dietary monoterpenoids as a new class of AhR non-competitive allosteric antagonists with the potential preventive and therapeutic application.
Dynamic cholinergic tone in the basal forebrain reflects reward-seeking and reinforcement during olfactory behavior
Authors: Hanson Elizabeth , Brandel-Ankrapp Katie L , Arenkiel Benjamin R
Published: December 2020

Sensory perception underlies how we internalize and interact with the external world. In order to adapt to changing circumstances and interpret signals in a variety of contexts, sensation needs to be reliable, but perception of sensory input needs to be flexible. An important mediator of this flexibility is top-down regulation from the cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers and gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This top-down control is necessary for sensory cue detection, learning, and memory, and is disproportionately disrupted in neurodegenerative diseases associated with cognitive decline. Intriguingly, cholinergic signaling acts locally within the basal forebrain to sculpt the activity of basal forebrain output neurons. To determine how local cholinergic signaling impacts basal forebrain output pathways that participate in top-down regulation, we sought to define the dynamics of cholinergic signaling within the basal forebrain during motivated behavior and learning. Towards this, we utilized fiber photometry and the genetically encoded acetylcholine indicator GAChR2.0 to define temporal patterns of cholinergic signaling in the basal forebrain during olfactory-guided, motivated behaviors and learning. We show that cholinergic signaling reliably increased during reward-seeking behaviors but was strongly suppressed by reward delivery in a go/no-go, olfactory-cued discrimination task. The observed transient reduction in cholinergic tone was mirrored by a suppression in basal forebrain GABAergic neuronal activity. Together, these findings suggest that cholinergic tone in the basal forebrain changes rapidly to reflect rewardseeking behavior and positive reinforcement to impact basal forebrain circuit activity.
Assessment by Matrix-Assisted Laser Desorption – Time of Flight Mass Spectrometry of the Diversity of Endophytes and Rhizobacteria Cultured from the Maize Microbiome
Authors: LaMontagne Michael G. , Tran Phi L. , Benavidez Alexander , Morano Lisa D.
Published: December 2020

Many endophytes and rhizobacteria associated with plants support the growth and health of their hosts. The vast majority of these potentially beneficial bacteria have yet to be cultured, in part because of the cost of identifying bacterial isolates. Matrix-assisted laser desorption – time of flight (MALDI-TOF) has enabled high throughput “culturomics” studies of host-associated microbiomes but analysis of mass spectra generated from plant-associated bacteria requires optimization. In this study, we aligned mass spectra generated from endophytes and rhizobacteria isolated from heritage and sweet varieties ofZea mays. Multiple iterations of alignment attempts identified a set of parameters that sorted 114 isolates into 60 coherent MALDI-TOF taxonomic units (MTUs). These MTUs corresponded to strains with practically identical (> 99%) 16S rRNA gene sequences. Mass spectra were used to successfully train a machine learning algorithm that perfectly classified isolates. The 60 MTUs provided > 70 % coverage of aerobic, heterotrophic bacteria readily cultured with nutrient rich media from the maize microbiome and allowed prediction of the total diversity recoverable with that particular cultivation method.Acidovoraxsp.,Pseudomonassp. andCellulosimicrobiumsp. dominated the library generated from the rhizoplane and the heritage variety contained a relatively high number of MTUs specific to that niche. This suggests a rapid, inexpensive method of describing the types of bacteria cultured from niches within maize microbiomes and the coverage achieved with a cultivation strategy.
Chlamydia gallinacea: genetically armed as a pathogen however a phenotypical commensal?
Authors: Heijne Marloes , Jelocnik Martina , Umanets Alexander , Brouwer Michael S.M. , Dinkla Annemieke , Harders Frank , van Keulen Lucien J.M. , Roest Hendrik Jan , Schaafsma Famke , Velkers Francisca C. , van der Goot Jeanet A. , Pannekoek Yvonne , Koets Ad P.
Published: December 2020

Chlamydia gallinaceais an obligate intracellular bacterium that has recently been added to the family ofChlamydiaceae.C. gallinaceais genetically diverse, widespread in poultry and a suspected cause of pneumonia in slaughterhouse workers. In poultry,C. gallinaceainfections appear asymptomatic, but studies about the pathogenic potential are limited. In this study two novel sequence types ofC. gallinaceawere isolated from apparently healthy chickens. Both isolates (NL_G47 and NL_F725) were closely related to each other and showed 99.1% DNA sequence identity toC. gallinaceaType strain 08-1274/3. To gain further insight in the pathogenic potential, infection experiments in embryonated chicken eggs and comparative genomics withChlamydia psittaciwere performed.C. psittaciis an ubiquitous zoonotic pathogen of birds and mammals, and infection in poultry can result in severe systemic illness. In experiments with embryonated chicken eggsC. gallinaceainduced mortality was observed, potentially strain dependent but lower compared toC. psittaciinduced mortality. Comparative analyses confirmed all currently availableC. gallinaceagenomes possess the hallmark genes coding for known and potential virulence factors as found inC. psittacialbeit to a reduced number of orthologues or paralogs. The presence of (potential) virulence factors and the observed mortality in embryonated eggs indicatesC. gallinaceashould rather be considered as a (conditional) pathogen than an innocuous commensal.

Importance

Chlamydiaceaeare a family of bacteria comprising human and animal pathogens including the recently recognizedChlamydia gallinacea. C. gallinaceais widespread in poultry without causing clinical signs, which raises questions about its pathogenic potential. To assess this potential, two novelC. gallinaceastrains were isolated, tested in infection experiments in embryonated chicken eggs and compared toC. psittaci. C. psittaciinfection in poultry can result in severe systemic illness, depending on the conditions, and infections can be transmitted to humans. In the experimentsC. gallinaceainfection induced mortality of the embryo, but to a lower extent than infection withC. psittaci. Subsequent genome comparisons confirmed bothC. gallinaceastrains possess potential virulence genes typical for chlamydia, but fewer thanC. psittaci. These results indicateC. gallinaceadoes have a pathogenic potential which warrants further research to elucidate its role as a poultry pathogen.
Balancing positive and negative selection:in vivoevolution ofCandida lusitaniae MRR1
Authors: Demers Elora G. , Stajich Jason , Ashare Alix , Occhipinti Patricia , Hogan Deborah A.
Published: December 2020

The evolution of pathogens in response to selective pressures present during chronic infections can influence persistence, virulence, and the outcomes of antimicrobial therapy. Because subpopulations within an infection can be spatially separated and the host environment can fluctuate, an appreciation of the pathways under selection may be most easily revealed through the analysis of numerous isolates from single infections. Here, we continued our analysis of a set of clonally-derivedClavispora (Candida) lusitaniaeisolates from a single chronic lung infection with a striking enrichment in the number of alleles ofMRR1. Genetic and genomic analyses found evidence for repeated acquisition of gain-of-function mutations that conferred constitutive Mrr1 activity. In the same population, there were multiple alleles with both gain-of-function mutations and secondary suppressor mutations that either attenuated or abolished the constitutive activity suggesting the presence of counteracting selective pressures. Our studies demonstrated tradeoffs between high Mrr1 activity, which confers resistance to the antifungal fluconazole, host factors, and bacterial products through its regulation ofMDR1, and resistance to hydrogen peroxide, a reactive oxygen species produced in the neutrophilic environment associated with this infection. This inverse correlation between high Mrr1 activity and hydrogen peroxide resistance was observed in multipleCandidaspecies and in serial analysis of populations from this individual collected over three years. These data lead us to propose that dynamic or variable selective pressures can be reflected in population genomics and that these dynamics can complicate the drug resistance profile of the population.

Importance

Understanding microbial evolution within patients is critical for managing chronic infections and understanding host-pathogen interactions. Here, our analysis of multipleMRR1alleles in isolates from a singleClavispora (Candida) lusitaniaeinfection revealed the selection for both high and low Mrr1 activity. Our studies reveal tradeoffs between high Mrr1 activity, which confers resistance to the commonly used antifungal fluconazole, host antimicrobial peptides and bacterial products, and resistance to hydrogen peroxide. This work suggests that spatial or temporal differences within chronic infections can support a large amount of dynamic and parallel evolution, and that Mrr1 activity is under both positive and negative selective pressure to balance different traits that are important for microbial survival.
Early detection of physiological deterioration in post-surgical patients using wearable technology combined with an integrated monitoring system: a pre- and post-interventional study
Authors: Watkinson Peter J , Pimentel Marco AF , Clifton Lei , Clifton David A , Vollam Sarah , Young Duncan , Tarassenko Lionel
Published: December 2020

Objectives

Late recognition of physiological deterioration is a frequent problem in hospital wards. We assessed whether ambulatory (wearable) physiological monitoring combined with a system that continuously merges physiological variables into a single “risk” score (VSI), changed care and outcome in patients after major surgery.

Design

Pre- and post-interventional study.

Setting

A single centre tertiary referral university hospital upper-gastrointestinal service.

Participants

Patients who underwent major upper-gastrointestinal surgery.

Interventions

Phase-I (pre-intervention phase): Patients received continuous wearable monitoring and standard care, but the VSI score was not available for clinical use. Phase-II (post-intervention phase): Patients received continuous wearable monitoring. In addition to standard care the VSI score was displayed for use in clinical practice.

Measurements and Main Results

200 participants were monitored in phase-I. 207 participants were monitored in phase-II. Participants were monitored (median, interquartile range, IQR) for 30.2% (13.8-49.2) of available time in phase-I and 58.2% (33.1-75.2) of available time in phase-II.

Clinical staff recorded observations more frequently in the 36 hours prior to a major adverse event (death, cardiac arrest or unplanned admission to intensive care) for phase-II participants (median, IQR, time between observations of 1.00, 0.50-2.08 hours) than phase-I participants (1.50, 0.75-2.50 hours, p<0.001). There was no difference in observation frequency between the two phases for participants who did not undergo an adverse event (p=0.129). 6/200 participants died before hospital discharge in phase-I, 1/207 participants died in hospital in phase-II. 20 (10.0%) patients in phase-I and 26 (12.6%) patients in phase-II had an unplanned admission to intensive care. Ward length-of-stay was unaltered (8.91, 6.71-14.02 days in phase-I, vs. 8.97, 5.99-13.85 days in phase-II, p=0.327).

Conclusion

The combination of the integrated monitoring system with ambulatory monitoring in high-risk post-surgical patients improved recognition and management of deteriorating patients without increasing the observation rate in those patients who did not deteriorate.
Correcting the Reproduction Number for Time-Varying Tests: a Proposal and an Application to COVID-19 in France*
Authors: Baunez Christelle , Degoulet Mickaël , Luchini Stéphane , Pintus Matteo L. , Pintus Patrick A. , Teschl Miriam
Published: December 2020

We provide a novel way to correct the effective reproduction number for the time-varying amount of tests, using the acceleration index (Baunez et al., 2021) as a simple measure of viral spread dynamics. Not correcting results in the reproduction number being a biased estimate of viral acceleration and we provide a formal decomposition of the resulting bias, involving the useful notions of test and infectivity intensities. When applied to French data for the COVID-19 pandemic (May 13, 2020 - October 26, 2022), our decomposition shows that the reproduction number, when considered alone, characteristically underestimates the resurgence of the pandemic, compared to the acceleration index which accounts for the time-varying volume of tests. Because the acceleration index aggregates all relevant information and captures in real time the sizable time variation featured by viral circulation, it is a more parsimonious indicator to track the dynamics of an infectious disease outbreak in real time, compared to the equivalent alternative which would combine the reproduction number with the test and infectivity intensities.

JEL Classification Numbers

I18; H12