bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular magnetic resonance determinants of ventricular arrhythmic events after myocardial infarction
Authors: Jáuregui Beatriz , Soto-Iglesias David , Penela Diego , Acosta Juan , Fernández-Armenta Juan , Linhart Markus , Ordóñez Augusto , San Antonio Rodolfo , Terés Cheryl , Chauca Alfredo , Carreño José M , Scherer Claudia , Falasconi Giulio , Prat-González Susana , Perea Rosario J , Mont Lluís , Bosch Xavier , Ortiz-Pérez José T , Berruezo Antonio
Published: October 2021

Aims

To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients.

Methods and results

A case–control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89–0.97); P < 0.001], with a significant increase in the AUC compared to other scar parameters (P < 0.001 for all pairwise comparisons). Adding BZC mass to LVEF allowed to reclassify 33.3% of the cases and 39.3% of the controls [net reclassification improvement = 0.73 (0.71–0.74)].

Conclusions

The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients.
Analysis of Sex Chromosome Evolution in the Clade Palaeognathae from Phased Genome Assembly
Authors: Okuno Miki , Mizushima Shusei , Kuroiwa Asato , Itoh Takehiko
Published: October 2021

Birds in the clade Palaeognathae, excluding Tinamiformes, have morphologically conserved karyotypes and less differentiated ZW sex chromosomes compared with those of other birds. In particular, the sex chromosomes of the ostrich and emu have exceptionally large recombining pseudoautosomal regions (PARs), whereas non-PARs are classified into two strata according to the date of their origins: stratum 0 and stratum 1 (S1). However, the construction and analysis of the genome sequences in these regions in the clade Palaeognathae can be challenging because assembling the S1 region is difficult owing to low sequence diversity between gametologs (Z-linked and W-linked sequences). We addressed this issue by applying the Platanus-allee assembler and successfully constructed the haplotype-resolved (phased) assembly for female emu, cassowary, and ostrich using only sequence read data derived from the Illumina platform. Comparative genomic and phylogenetic analyses based on assembled Z-linked and W-linked sequences confirmed that the S1 region of emu and cassowary formed in their common ancestor. Moreover, the interspersed repetitive sequence landscapes in the S1 regions of female emu showed an expansion of younger repetitive elements in the W-linked S1 region, suggesting an interruption in homologous recombination in the S1 region. These results provide novel insights into the trajectory of sex chromosome evolution in the clade Palaeognathae and suggest that the Illumina-based phased assembly method is an effective approach for elucidating the evolutionary process underlying the transition from homomorphic to differentiated sex chromosomes.
An efficient routing heuristic for a drone-assisted delivery problem
Authors: Kundu Abhishake , Escobar Ricardo Gatica , Matis Timothy I
Published: October 2021

In this paper, we present a routing heuristic for the Flying Sidekick Traveling Salesman Problem. This problem combines a single truck with a single drone. The drone may be launched from the truck from a customer location and can make a single package delivery before being recovered by the truck. While the drone is in flight, the truck can deliver packages independently. The problem is one of simultaneously assigning the customers to each vehicle and determining the synchronized routes for both vehicles to satisfy all customer demands in the shortest time possible. The problem is NP-hard. Our main contribution lies in developing a novel split algorithm that utilizes a shortest path approach for determining the optimal routing solution to a given order of customer locations. This split algorithm has polynomial complexity. We develop a heuristic solution to the problem by combining the split algorithm with local search techniques. This overall heuristic is shown to be accurate and computationally scalable to large, realistically sized problems applicable in last-mile logistics.
A discontinuous Galerkin coupling for nonlinear elasto-acoustics
Authors: Muhr Markus , Wohlmuth Barbara , Nikolić Vanja
Published: October 2021

Inspired by medical applications of high-intensity ultrasound we study a coupled elasto-acoustic problem with general acoustic nonlinearities of quadratic type as they arise, for example, in the Westervelt and Kuznetsov equations of nonlinear acoustics. We derive convergence rates in the energy norm of a finite element approximation to the coupled problem in a setting that involves different acoustic materials and hence jumps within material parameters. A subdomain-based discontinuous Galerkin approach realizes the acoustic-acoustic coupling of different materials. At the same time, elasto-acoustic interface conditions are used for a mutual exchange of forces between the different models. Numerical simulations back up the theoretical findings in a three-dimensional setting with academic test cases as well as in an application-oriented simulation, where the modeling of human tissue as an elastic versus an acoustic medium is compared.
The Biomedical Research Hub: a federated platform for patient research data
Authors: Barnes Craig , Bajracharya Binam , Cannalte Matthew , Gowani Zakir , Haley Will , Kass-Hout Taha , Hernandez Kyle , Ingram Michael , Juvvala Hara Prasad , Kuffel Gina , Martinov Plamen , Maxwell J Montgomery , McCann John , Malhotra Ankit , Metoki-Shlubsky Noah , Meyer Chris , Paredes Andre , Qureshi Jawad , Ritter Xenia , Schumm Philip , Shao Mingfei , Sheth Urvi , Simmons Trevar , VanTol Alexander , Zhang Zhenyu , Grossman Robert L
Published: October 2021

Objective

The objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).

Materials and Methods

The BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.

Results

The BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.

Discussion and conclusion

With the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.
Ubiquitin-dependent rapid degradation conceals a cell-protective function of cytoplasmic SIRT3 against oxidative stress
Authors: Hayashi Takashi , Matsushita Takashi , Hisahara Shin , Iwahara Naotoshi , Kuno Atsushi , Kunimoto Risa , Hosoda Ryusuke , Tanno Masaya , Shimohama Shun , Horio Yoshiyuki
Published: October 2021

SIRT3 is an NAD+-dependent protein deacetylase localized in mitochondria. Several studies reported localization of SIRT3 in the cytoplasm or nucleus, but data of these studies were not consistent. We detected expression of mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs in the mouse brain, and we also found SIRT3 immunostaining of mitochondria and cytoplasm in the brain and cultured neural cells. However, expression levels of SIRT3ct in COS cells transfected with SIRT3ct cDNA were much lower than those of SIRT3mt. We found that SIRT3ct but not SIRT3mt was promptly degraded by ubiquitin-dependent degradation, in which SIRT3ct degradation was mediated mainly by ubiquitination of NH2-terminal methionine and partly by that of lysine residues of SIRT3ct. SIRT3ct expression level was significantly enhanced by the treatment of cells with staurosporine or H2O2. H2O2 treatment promoted nuclear translocation of SIRT3ct and induced histone H3 deacetylation and superoxide dismutase 2 expression. Overexpression of SIRT3ct decreased cell death caused by H2O2 at levels similar to those achieved by overexpression of SIRT3mt. Knockdown of Sirt3 mRNA increased cell death caused by amyloid-β (Aβ), and overexpression of SIRT3ct suppressed the toxic function of Aβ in PC12 cells. These results indicate that SIRT3ct promotes cell survival under physiological and pathological conditions.
Influence of Abiotic Factors on Walking Behavior of Hunting Billbugs (Coleoptera: Curculionidae)
Authors: Gireesh Midhula , Joseph Shimat V
Published: October 2021

The hunting billbug, Sphenophorus venatus vestitus Chittenden, is an important insect pest of warm-season turfgrass. Larvae and adult S. venatus vestitus feed on turfgrass and affect normal grass growth and development. In sod farms and golf courses, management sprays are typically confined to affected areas because of the high insecticide and application costs. Understanding the walking behavior of S. venatus vestitus adults would help us to refine management tactics. Thus, the objective of this study was to determine the influence of abiotic factors on the walking behavior of adult S. venatus vestitus. A series of laboratory, semifield, and field assays were conducted in 2019 and 2020. For the laboratory assays, field-collected S. venatus vestitus adults were acclimated at 15, 18, 21, 28, and 32°C for 24 h, and the distances walked by these pre-acclimated adults were measured on sand and filter paper substrates using Noldus EthoVision XT software. For the semifield assays, the total and net distances walked by pre-acclimated adults were measured on a paved indoor surface. Sphenophorus venatus vestitus males and females moved farther when the temperature increased from 15 to 28°C in the laboratory and semifield assays. For the field assays, field-collected S. venatus vestitus adults were not acclimated. The total and net distances walked by the adults were documented on a paved surface. Increases in temperature and relative humidity did not affect the distance moved by adults, but an increase in wind speed reduced the distance moved.
A Potentially Known Confidential Settlement
Authors: Lee Frances Xu
Published: October 2021

This article studies the incentive to settle confidentially, openly, or to go to trial given that the existence of a confidential settlement might become publicly known. Depending on whether the defendant (D) or the plaintiff cares more about the Public’s inference from the litigation outcome, a confidential settlement may signal a more-culpable or less-culpable D. The informational disadvantage of confidentiality is weighed against the benefit of privacy, as well as the litigants’ relative desire for more visibility or less visibility. (JEL K41, K13).
Inhibition of 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE expression by brassinosteroid reduces carotenoid accumulation in Arabidopsis
Authors: Park Tae-Ki , Kang In-A , Park Chan-Ho , Roh Jeehee , Lee Se-Hwa , Kim Minjae , Jin EonSeon , Kim Seong-Ki , Kim Tae-Wuk
Published: October 2021

Unlike the indispensable function of the steroid hormone brassinosteroid (BR) in regulating plant growth and development, the metabolism of secondary metabolites regulated by BR is not well known. Here we show that BR reduces carotenoid accumulation in Arabidopsis seedlings. BR-deficient or BR-insensitive mutants accumulated higher content of carotenoids than wild-type plants, whereas BR treatment reduced carotenoid content. We demonstrated that BR transcriptionally suppresses 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE (HPPD) expression involved in carotenogenesis via plastoquinone production. We found that the expression of HPPD displays an oscillation pattern that is expressed more strongly in dark than in light conditions. Moreover, BR appeared to inhibit HPPD expression more strongly in darkness than in light, leading to suppression of a diurnal oscillation of HPPD expression. BR-responsive transcription factor BRASSINAZOLE RESISTANT 1 (BZR1) directly bound to the promoter of HPPD, and HPPD suppression by BR was increased in the bzr1-1D gain-of-function mutation. Interestingly, dark-induced HPPD expression did not cause carotenoid accumulation, due to down-regulation of other carotenoid biosynthetic genes in the dark. Our results suggest that BR regulates different physiological responses in dark and light through inhibition of HPPD expression.
Impact of bacterial volatiles on phytopathogenic fungi: anin vitrostudy on microbial competition and interaction
Authors: Das Piyali , Effmert Uta , Baermann Gunnar , Quella Manuel , Piechulla Birgit
Published: October 2021

Microorganisms in the rhizosphere are abundant and exist in very high taxonomic diversity. The major players are bacteria and fungi, and bacteria have evolved many strategies to prevail over fungi, among them harmful enzyme activities and noxious secondary metabolites. Interactions between plant growth promoting rhizobacteria and phytopathogenic fungi are potentially valuable since the plant would benefit from fungal growth repression. In this respect, the role of volatile bacterial metabolites in fungistasis has been demonstrated, but the mechanisms of action are less understood. We used three phytopathogenic fungal species (Sclerotinia sclerotiorum, Rhizoctonia solani, and Juxtiphoma eupyrena) as well as one non-phytopathogenic species (Neurospora crassa) and the plant growth promoting rhizobacterium Serratia plymuthica 4Rx13 in co-cultivation assays to investigate the influence of bacterial volatile metabolites on fungi on a cellular level. As a response to the treatment, we found elevated lipid peroxidation, which indirectly reflected the loss of fungal cell membrane integrity. An increase in superoxide dismutase, catalase, and laccase activities indicated oxidative stress. Acclimation to these adverse growth conditions completely restored fungal growth. One of the bioactive bacterial volatile compounds seemed to be ammonia, which was a component of the bacterial volatile mixture. Applied as a single compound in biogenic concentrations ammonia also caused an increase in lipid peroxidation and enzyme activities, but the extent and pattern did not fully match the effect of the entire bacterial volatile mixture.
An In Vitro Co-Culture System for Rapid Differential Response toFusarium oxysporumf. sp.vasinfectumRace 4 in Three Cotton Cultivars
Authors: Parris Stephen M. , Jeffers Steven N. , Olvey James M. , Olvey James M. , Adelberg Jeffrey W. , Wen Li , Udall Joshua A. , Coleman Jeffrey J. , Jones Don C. , Saski Christopher A.
Published: October 2021

Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4) is a devastating fungus pathogen that causes Fusarium wilt in both domesticated cotton species, Gossypium hirsutum (Upland) and G. barbadense (Pima). Greenhouse and field-based pathogenicity assays can be a challenge because of nonuniform inoculum levels, the presence of endophytes, and varying environmental factors. Therefore, an in vitro coculture system was designed to support the growth of both domesticated cotton species and FOV4 via an inert polyphenolic foam substrate with a liquid medium. A Fusarium wilt–susceptible Pima cotton cultivar, G. barbadense ‘GB1031’; a highly resistant Pima cotton cultivar, G. barbadense ‘DP348RF’; and a susceptible Upland cotton cultivar, G. hirsutum ‘TM-1’, were evaluated for 30 days during coculture with FOV4 in this foam-based system. Thirty days after inoculation, disease symptoms were more severe in both susceptible cultivars, which displayed higher percentages of foliar damage, and greater plant mortality than observed in ‘DP348RF’, the resistant Pima cotton cultivar. This foam-based in vitro system may be useful for screening cotton germplasm for resistance to a variety of fungus pathogens and may facilitate the study of biotic interactions in domesticated cotton species under controlled environmental conditions.
Celebrating Magnet® Nursing Excellence
Authors: Curto Christine
Published: October 2021

This month's Magnet® Perspectives column spotlights the recipients of the 2020 American Nurses Credentialing Center (ANCC) Magnet Program® National Magnet Nurse of the Year Awards and the ANCC Magnet Prize®, sponsored by Cerner, who were recognized during the ANCC National Awards virtual event on May 14, 2021.
Rethinking Resilience
Authors: Udod Sonia , MacPhee Maura , Baxter Pamela
Published: October 2021

Nurses and nurse leaders are working in unprecedented intense and demanding environments, and the COVID-19 pandemic continues to place strain on their mental well-being. If stressful work conditions remain at extraordinary high levels, nurses and leaders may ultimately leave their positions, creating even more uncertainty in the workforce. Enhancing individual resilience has become a superficial response in retaining nurses during a global nursing shortage. We argue that resilience is not solely an individual responsibility. Rather, resilience it is a mutual responsibility between the individual and the organization. In this article, we discuss how nurse leaders can foster organizational resilience while also enhancing their own individual resilience within the current pandemic environment, and as we transition to a post-COVID environment.
Creating a Statewide Nurse Residency
Authors: Cadmus Edna , Roberts Michele Livitch , Olson Evy
Published: October 2021

The Institute of Medicine recommends residency programs be implemented for new graduates across all settings, yet hospitals have not consistently hardwired this into their organizations. The value proposition is in recruitment, retention, and the conservation of resources. New Jersey's experiences using the US Department of Labor apprenticeship model for nurse residency programs provides a strategy that can be implemented on a statewide basis.
An Innovative Nurse Staffing Model
Authors: Woltz Patricia C. , Wheaton Sandra , Knight Dianna , Purdue Kimberly
Published: October 2021

OBJECTIVE

The aim of this study was to develop a flexible nurse reallocation solution.

BACKGROUND

Successful nurse reallocation supports appropriate staffing and may enhance workforce flexibility.

METHODS

An innovative program incentivizing regular nursing staff to volunteer for extra shifts systemwide was implemented at a large healthcare organization.

RESULTS

Nurses' perceptions of appropriate staffing improved, and nursing care quality was not compromised. The program primed the organization to respond to the pandemic.

CONCLUSIONS

The staffing model has been sustained for 3+ years.
Organizational Safety Climate and Job Enjoyment in Hospital Surgical Teams With and Without Crew Resource Management Training
Authors: Bacon Cynthia Thornton , McCoy Thomas P. , Henshaw Daryl S. , Stabel Cynthia L.
Published: October 2021

OBJECTIVE

The association between organizational safety climate (OSC) and job enjoyment (JE) for team members in surgical units in 2 hospitals was investigated. The treatment hospital received airline industry–based crew resource management (CRM) training, and the comparison hospital did not.

BACKGROUND

Strong OSC has been positively associated with healthy hospital work environments and was expected to also be associated with employee job enjoyment.

METHODS

Two hundred sixty-two surgical personnel responded to surveys about OSC and JE.

RESULTS

The effects of OSC on JE did not depend on having CRM training. However, OSC and JE scores were higher in the treatment hospital, and the main effect of OSC and JE scores in the treatment hospital was highly significant (P < 0.001), with higher safety climate scores associated with higher JE.

CONCLUSIONS

A strong OSC is important to employee job enjoyment. Nurse leaders should promote measures to strengthen the OSC in their surgical services departments.
Mapping a Danger Zone of the Dorsal Nerve of the Clitoris: Implications in Female Cosmetic Genital Surgery
Authors: Gordon Victoria , Rowe Joanna , Grubb Lauren , Lewis Adam , Johnson Kenneth , Segars Larry , Surek Christopher , McCumber Travis , Willet Gilbert M. , Olinger Anthony
Published: October 2021

Background:

The literature regarding the route of the dorsal nerve of the clitoris is sparse and lacks surgical focus. With an increasing number of procedures being performed on the labia, it is important to elucidate the route and note any variation from normal of the nerve.

Methods:

Fifty-one cadavers were dissected to yield 97 dorsal nerve of the clitoris samples. Measurements were taken from (1) the dorsal nerve of the clitoris penetration point of the perineal membrane to the urethra, (2) the nerve’s penetration point of the perineal membrane to the pubic bone, (3) the angle of the clitoris to the branch point of the dorsal nerve of the clitoris, and (4) the branch point of the nerve to the distalmost point of the glans clitoris. Any anomalous branching patterns of the dorsal nerve of the clitoris were recorded and classified.

Results:

The means and standard deviations of each measurement were used to create a surgical danger zone. The mean of each measurement was (1) 34.63 mm, (2) 5.74 mm, (3) −3.07 mm, and (4) 30.40 mm, respectively. In addition, six distinct branching patterns were observed, organized, and classified based on the location and number of branches observed.

Conclusions:

The dorsal nerve of the clitoris has multiple branching patterns and typically travels along the same course in most women. Further investigation of the course and three-dimensional position of the dorsal nerve of the clitoris is warranted to preserve sexual sensation as the frequency of procedures involving the female pudendum increases.
A Novel Injection Technique to the Lateral Pterygoid Muscle for Temporomandibular Disorders: A Cadaveric Study
Authors: Kucukguven Arda , Demiryurek Mehmet D. , Kucukguven Meric Bilgic , Vargel Ibrahim
Published: October 2021

Background:

Lateral pterygoid muscle activity is associated with the pathological mechanisms of some temporomandibular disorders. The authors aimed to define and demonstrate a novel, practical, and safe technique for botulinum toxin type A injection to the lateral pterygoid muscle based on their findings. Their secondary aims were to standardize the injection pattern according to the variations of the lateral pterygoid muscle and its surrounding anatomical structures, and to establish its advantages over intraoral injection.

Methods:

Twenty cadaver heads were dissected. The lateral pterygoid muscle and its surrounding structures were investigated for anatomical variations. Based on these findings, a standardized extraoral injection protocol was defined and compared with the intraoral technique for accuracy and safety.

Results:

The average depth of the lateral pterygoid plate from the skin surface was 49.9 ± 2.2 mm, and the mean width of the lateral pterygoid plate was 10.5 ± 3.9 mm. The extraoral injection approach based on the location of the maxillary tuberosity, tragus, and lateral pterygoid plate was consistent in all dissections for the accuracy of the intramuscular injection. In the intraoral approach, standardization of the entry point of the needle through the oral mucosa is difficult, which makes adjustment of the depth of the injection challenging while increasing the risk of neurovascular injury.

Conclusions:

The clinical significance of the lateral pterygoid muscle makes it worthwhile to implement minimally invasive treatments before considering more invasive options. The authors define a safe, accurate, and reliable approach with ease of administration in patients with temporomandibular disorders.
Molecular epidemiological characteristics of Mycobacterium abscessus complex in non-cystic fibrosis patients in Japan and Taiwan
Authors: Yoshida Mitsunori , Chien Jung-Yien , Morimoto Kozo , Kinjo Takeshi , Aono Akio , Murase Yoshiro , Fujiwara Keiji , Morishige Yuta , Nagano Hiroaki , Jou Ruwen , Hasegawa Naoki , Ato Manabu , Hoshino Yoshihiko , Hsueh Po-Ren , Mitarai Satoshi
Published: October 2021

Mycobacterium abscessus complex (MABC) is an emerging non-tuberculous mycobacterium (NTM). Specific MABC clones are reportedly spreading globally in cystic fibrosis (CF) patients, however, associated genomic epidemiology studies are lacking in East Asia. Analysis of whole-genome sequencing data for MABC isolates from 220 pre-treatment, non-CF patients in Japan and Taiwan revealed that 112/220, 105/220, and 3/220 were M. abscessus subsp. abscessus (ABS), M. abscessus subsp. massiliense (MAS), and M. abscessus subsp. bolletii (BOL), respectively. No significant differences in subspecies composition were noted based on location. Moreover, >50% of ABS and >70% of MAS were related to four predominant clones in the region. Known mutations conferring acquired macrolide resistance were rare (1.4%) and not enriched in the predominant clones. Conversely, the macrolide-susceptible erm(41) T28C mutation was significantly enriched in one predominant ABS clone. The most predominant ABS clone was genetically related to the dominant circulating clone (DCC). Hence, we have clarified the relationship between the predominant clones in Japan and Taiwan, and those reported in the international CF patient community. Our results provide insights regarding the genetic characteristics of globally dominant and area-specific strains isolated from patients with or without CF, as well as differences between globally spread and regionally-specific strains.
Performance of Valved Respirators to Reduce Respiratory Particles Generated by Speaking
Authors: Hazard Jessica M. , Cappa Christopher D.
Published: October 2021

Wearing of face coverings serves two purposes: reducing the concentration of ambient particles inhaled and reducing the emission of respiratory particles generated by the wearer. The efficiency of different face coverings depends on the material, design, and fit. Face coverings such as N95 respirators, when worn properly, are highly efficient at filtering ambient particles during inhalation. Some N95 respirators, as well as other face covering types, include a one-way valve to allow easier exhalation while still maintaining high filtration efficiency towards ambient particles. The extent to which these valves decrease filtration of emitted respiratory particles is, however, not well established. Here, we show that different valved N95s exhibit highly variable filtration efficiencies for exhaled respiratory particles. As such, valved N95s do not provide reliable source control of respired particles and their use should be discouraged in situations where such source control is needed.
Phylogenetic-based inference reveals distinct transmission dynamics of SARS-CoV-2 variant of concern Gamma and lineage P.2 in Brazil
Authors: Graf Tiago , Bello Gonzalo , Naveca Felipe Gomes , Gomes Marcelo , Oikawa Cardoso Vanessa Leiko , da Silva Alexandre Freitas , Dezordi Filipe Zimmer , dos Santos Mirleide Cordeiro , de Oliveira Santos Katia Correa , Rocha Batista Erika Lopes , alvares Magalhaes Alessandro Leonardo , Vinhal Fernando , Miyajima Fabio , Faoro Helisson , Khouri Ricardo , Wallau Gabriel Luz , Delatorre Edson , Siqueira Marilda Mendonca , Resende Paola Cristina
Published: October 2021

The COVID-19 epidemic in Brazil experienced two major country-wide lineage replacements, the first driven by the lineage P.2, formerly classified as variant of interest (VOI) Zeta in late 2020 and the second by the variant of concern (VOC) Gamma in early 2021. To better understand how these SARS-CoV-2 lineage turnovers occurred in Brazil, we analyzed 11,724 high-quality SARS-CoV-2 whole genomes of samples collected in different country regions between September 2020 and April 2021. Our findings indicate that the spatial dispersion of both variants in Brazil was driven by short and long-distance viral transmission. The lineage P.2 harboring Spike mutation E484K probably emerged around late July 2020 in the Rio de Janeiro (RJ) state, which contributed with most (∼50%) inter-state viral disseminations, and only became locally established in most Brazilian states by October 2020. The VOC Gamma probably arose in November 2020 in the Amazonas (AM) state, which was responsible for 60-70% of the inter-state viral dissemination, and the earliest timing of community transmission of this VOC in many Brazilian states was already traced to December 2020. We estimate that variant Gamma was 1.56-3.06 more transmissible than variant P.2 co-circulating in RJ and that the median effective reproductive number (Re) of Gamma in RJ and SP states (Re = 1.59-1.91) was lower than in AM (Re = 3.55). In summary, although the epicenter of the lineage P.2 dissemination in Brazil was the heavily interconnected Southeastern region, it displayed a slower rate of spatial spread than the VOC Gamma originated in the more isolated Northern Brazilian region. Our findings also support that the VOC Gamma was more transmissible than lineage P.2, although the viral Re of the VOC varied according to the geographic context.
Preliminary outcomes of combined treadmill and overground high-intensity interval training in ambulatory chronic stroke
Authors: Boyne Pierce , Doren Sarah , Scholl Victoria , Staggs Emily , Whitesel Dustyn , Carl Daniel , Shatz Rhonna , Sawyer Russel , Awosika Oluwole O. , Reisman Darcy S. , Billinger Sandra A. , Kissela Brett , Vannest Jennifer , Dunning Kari
Published: October 2021

Introduction

Locomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation that typically involves bursts of fast treadmill walking alternated with recovery periods. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and baseline response predictors are poorly understood. This pilot study aimed to guide future research by assessing preliminary outcomes of combined overground and treadmill HIIT.

Methods

Ten participants >6 months post stroke completed a multi-domain assessment battery before and after a 4-week no-intervention control phase, then again after a 4-week treatment phase involving 12 sessions of overground and treadmill HIIT. The primary analyses assessed relative changes in overground and treadmill walking speeds after HIIT, evaluated responsiveness of different outcome measures and estimated effects of baseline gait speed on treatment response.

Results

Overground and treadmill gait function both improved during the treatment phase relative to the control phase, with overground speed changes averaging 61% of treadmill speed changes (95% CI: 33-89%). Moderate or larger effect sizes were observed for measures of gait performance, balance, fitness, cognition, fatigue, perceived change and brain volume. Participants with baseline comfortable gait speed <0.4 m/s had less absolute improvement in walking capacity but similar proportional and perceived changes.

Discussion

Future locomotor HIIT studies should consider including: 1) both overground and treadmill training; 2) measures of cognition, fatigue and brain volume, to complement typical motor & fitness assessment; and 3) baseline gait speed as a covariate.
Prediction of recessive inheritance for missense variants in human disease
Authors: Petrazzini Ben O. , Balick Daniel J. , Forrest Iain S. , Cho Judy , Rocheleau Ghislain , Jordan Daniel M. , Do Ron
Published: October 2021

The prediction of pathogenic human missense variants has improved in recent years, but a more granular level of variant characterization is required. Further axes of information need to be incorporated in order to advance the genotype-to-phenotype map. Recent efforts have developed mode of inheritance prediction tools; however, these lack robust validation and their discrimination performance does not support clinical utility, with evidence of them being fundamentally insensitive to recessive acting diseases. Here, we present MOI-Pred, a three-way variant-level mode of inheritance prediction tool aimed at recessive identification for missense variants. MOI-Pred shows strong ability to discriminate missense variants causing autosomal recessive disease (area under the receiver operating characteristic (AUROC)=0.99 and sensitivity=0.85) in an external validation set. Additionally, we introduce an electronic health record (EHR)-based validation approach using real-world clinical data and show that our recessive predictions are enriched for recessive associations with human diseases, demonstrating utility of our method. Mode of inheritance predictions - pathogenic for autosomal recessive (AR) disease, pathogenic for autosomal dominant (AD) disease, or benign – for all possible missense variants in the human genome are available at https://github.com/rondolab/MOI-Pred/.
Role of Intraperitoneal Intraoperative Chemotherapy with Paclitaxel in the Surgical Treatment of Peritoneal Carcinomatosis from Ovarian Cancer. Hyperthermia versus Normothermia. A randomized controlled trial
Authors: Casado-Adam Angela , Rodríguez-Ortiz Lidia , Rufián-Peña Sebastián , Muñoz-Casares Francisco Cristobal , Caro-Cuenca Teresa , Ortega-Salas Rosa , Fernández-Peralbo María Auxiliadora , de Castro María Dolores Luque , Sánchez-Hidalgo Juan Manuel , Hervás-Martínez César , Romero Ruiz Antonio , Briceño-Delgado Javier , Arjona-Sanchez Alvaro
Published: October 2021

Background

The treatment of ovarian carcinomatosis with cytoreductive surgery and HIPEC is still controversial. The effect and pharmacokinetics of the chemotherapeutics used (specially taxanes) are under consideration at present.

Methods

A phase II, simple blind and randomized controlled trial (NTC02739698) was performed. Thirty-two patients with primary or recurrent ovarian carcinomatosis undergoing cytoreductive surgery (CRS) and intraoperative intraperitoneal chemotherapy with paclitaxel (PTX) were included; 16 in hyperthermic and 16 in normothermic conditions. Tissue, serum and plasma samples were taken in every patient before and after intraperitoneal chemotherapy to measure the concentration of PTX. To analyze the inmunohistochemical profile of p53, p27, p21, ki67, PCNA, caspasa-3 and the pathological response a scale of intensity and percentage of expression and a grouped Miller and Payne system were used, respectively. Perioperative characteristics and morbi-mortality were also analyzed.

Results

Main characteristics of patients, surgical morbidity, haematoxicity and nephrotoxicity were similar in both groups. The concentration of paclitaxel in the tissue was higher than that observed in plasma and serum, although no statistically significant differences were found between the two groups. No statistically significant association regarding pathological response and apoptosis (caspasa-3) between both groups was proved. Intraperitoneal PTX reduced the expression of p53, p27, p21, ki67 and PCNA more in hyperthermia group, but not significantly.

Conclusion

The use of intraperitoneal PTX has proven an adequate pharmacokinetics with reduction of cell cycle and proliferation markers globally without finding differences between its administration in hyperthermia versus normothermia conditions.
Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada
Authors: Skowronski Danuta M , Setayeshgar Solmaz , Febriani Yossi , Ouakki Manale , Zou Macy , Talbot Denis , Prystajecky Natalie , Tyson John R , Gilca Rodica , Brousseau Nicholas , Deceuninck Geneviève , Galanis Eleni , Fjell Chris D , Sbihi Hind , Fortin Elise , Barkati Sapha , Sauvageau Chantal , Naus Monika , Patrick David M , Henry Bonnie , Hoang Linda M N , De Wals Philippe , Garenc Christophe , Carignan Alex , Drolet Mélanie , Sadarangani Manish , Brisson Marc , Krajden Mel , De Serres Gaston
Published: October 2021

Background

The Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canada’s larger provinces.

Methods

Two-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults ≥18-years-old in British Columbia (BC) and Quebec, Canada.

Findings

In both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with ∼95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at ∼70% when both doses were ChAdOx1. Estimates were similar by age group (including adults ≥70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained ≥80%.

Interpretation

Two doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.
Phenotypic and genetic factors associated with differential consent to record linkage for prescription history in the Australian Genetics of Depression Study
Authors: Gomez Lina , Díaz-Torres Santiago , Colodro-Conde Lucía , Garcia-Marin Luis M. , Yap Chloe , Byrne Enda M. , Yengo Loic , Lind Penelope A. , Wray Naomi R. , Medland Sarah E. , Hickie Ian B. , Lupton Michelle K. , Rentería Miguel E. , Martin Nicholas G. , Campos Adrian I.
Published: October 2021

Samples can be prone to ascertainment and attrition biases.The Australian Genetics of Depression Study is a large publicly recruited cohort (n=20,689) established to increase the understanding of depression and antidepressant treatment response. As part of the recruitment, participants donated a saliva sample and were given the option to consent to linkage of prescription records for research purposes. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with a higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder and social anxiety disorder were associated with lower odds of donating a saliva sample whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was also associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia whereas there was no significant genetic effect for neuroticism. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not adjust, nor search, for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them.
Epidemiological, virological and serological investigation into a SARS-CoV-2 outbreak (Alpha variant) in a primary school: a prospective longitudinal study
Authors: Lorthe Elsa , Bellon Mathilde , Michielin Grégoire , Berthelot Julie , Zaballa María-Eugenia , Pennacchio Francesco , Bekliz Meriem , Laubscher Florian , Arefi Fatemeh , Perez-Saez Javier , Azman Andrew S , L’Huillier Arnaud G , Posfay-Barbe Klara M , Kaiser Laurent , Guessous Idris , Maerkl Sebastian , Eckerle Isabella , Stringhini Silvia
Published: October 2021

We report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school, as part of a longitudinal, prospective, primary school-based surveillance study. It involved repeated testing of pupils and teachers and household members of participants who tested positive, with rapid antigen tests and/or RT-PCR (Day 0-2 and Day 5-7), serologies on dried capillary blood samples (Day 0-2 and Day 30), contact tracing interviews and SARS-CoV-2 whole genome sequencing. This SARS-CoV-2 outbreak caused by the Alpha variant involved 20 children aged 4 to 6 years from 4 classes, 2 teachers and a total of 4 household members. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 classes, 22.2% among teachers and 0% among non-teaching staff. Secondary attack rate among household members was 15.4%. Symptoms were reported by 63% of infected children, 100% of teachers and 50% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests. This study confirmed child-to-child and child-to-adult transmission of the infection. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.
Adenovirus-α-defensin complexes induce NLRP3-associated maturation of human phagocytes via TLR4 engagement
Authors: Eichholz Karsten , Tran Tuan Hiep , Chéneau Coraline , Tran Thi Thu Phuong , Paris Océane , Pugniere Martine , Kremer Eric J
Published: October 2021

Intramuscular delivery of human adenovirus (HAdV)-based vaccines leads to rapid recruitment of neutrophils, which then release antimicrobial peptides/proteins (AMPs). How these AMPs influence vaccine efficacy over the subsequent 24 hr is poorly understood. In this study, we asked if human neutrophil protein 1 (HNP-1), an α-defensin that influences the direct and indirect innate immune responses to a range of pathogens, impacts the innate response of human phagocytes to three HAdV species/types (HAdV-C5, -D26, -B35). We show that HNP-1 binds to the capsids, redirects HAdV-C5, -D26, -B35 to Toll-like receptor 4 (TLR4), which leads to internalization, an NLRP3-mediated inflammasome response, and IL-1β release. Surprisingly, IL-1β release was not associated with notable disruption of plasma membrane integrity. These data further our understanding of HAdV innate immunogenicity and may provide pathways to extend HAdV-based vaccines efficacy.
Hepatitis C Virus Infects and Perturbs Liver Stem Cells
Authors: Meyers Nathan L , Ashuach Tal , Lyons Danielle E , Simoneau Camille R , Erickson Ann L , Bouhaddou Mehdi , Nguyen Thong T. , Khalid Mir M , Taha Taha Y , Natarajan Vaishaali , Baron Jody L , Neff Norma , Zanini Fabio , Mahmoud Tokameh , Quake Stephen R , Krogan Nevan J , Cooper Stewart , McDevitt Todd C , Yosef Nir , Ott Melanie
Published: October 2021

Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk beyond viral clearance remains unclear. We identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA-sequencing uncovered extensive transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data adds a pathogenesis factor – infection of liver stem cells – to the biology of HCV infection that explains persistent liver damage and enhanced cancer risk through an altered stem cell state.
Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly
Authors: Wong Siu-Shing , Wilmott Zachary M. , Saurya Saroj , Alvarez-Rodrigo Ines , Zhou Felix Y. , Chau Kwai-Yin , Goriely Alain , Raff Jordan W.
Published: October 2021

Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.