bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of compact massive quiescent and star-forming galaxies derived from the Re–Rh and Mstar–Mh relations
Authors: Zanisi L , Shankar F , Fu H , Rodriguez-Puebla A , Avila-Reese V , Faisst A , Daddi E , Boco L , Lapi A , Giavalisco M , Saracco P , Buitrago F , Huertas-Company M , Puglisi A , Dekel A
Published: May 2021

The mean size (effective radius Re) of massive galaxies (MGs; Mstar > 1011.2M⊙) is observed to increase steadily with cosmic time. It is still unclear whether this trend originates from the size growth of individual galaxies (via, e.g. mergers and/or AGN feedback) or from the inclusion of larger galaxies entering the selection at later epochs (progenitor bias). We here build a data-driven, flexible theoretical framework to probe the structural evolution of MGs. We assign galaxies to dark matter haloes via stellar mass–halo mass (SMHM) relations with varying high-mass slopes and scatters σSMHM in stellar mass at fixed halo mass, and assign sizes to galaxies using an empirically motivated, constant and linear relationship between Re and the host dark matter halo radius Rh. We find that (1) the fast mean size growth of MGs is well reproduced independently of the shape of the input SMHM relation; (2) the numbers of compact MGs grow steadily until z ≳ 2 and fall off at lower redshifts, suggesting a lesser role of progenitor bias at later epochs; (3) a time-independent scatter σSMHM is consistent with a scenario in which compact star-forming MGs transition into quiescent MGs in a few 108 yr with a negligible structural evolution during the compact phase, while a scatter increasing at high redshift implies significant size growth during the star-forming phase. A robust measurement of the size function of MGs at high redshift can set strong constraints on the scatter of the SMHM relation and, by extension, on models of galaxy evolution.
Genome editing in mammalian cells using the CRISPR type I-D nuclease
Authors: Osakabe Keishi , Wada Naoki , Murakami Emi , Miyashita Naoyuki , Osakabe Yuriko
Published: May 2021

Adoption of CRISPR–Cas systems, such as CRISPR–Cas9 and CRISPR–Cas12a, has revolutionized genome engineering in recent years; however, application of genome editing with CRISPR type I—the most abundant CRISPR system in bacteria—remains less developed. Type I systems, such as type I-E, and I-F, comprise the CRISPR-associated complex for antiviral defense (‘Cascade’: Cas5, Cas6, Cas7, Cas8 and the small subunit) and Cas3, which degrades the target DNA; in contrast, for the sub-type CRISPR–Cas type I-D, which lacks a typical Cas3 nuclease in its CRISPR locus, the mechanism of target DNA degradation remains unknown. Here, we found that Cas10d is a functional nuclease in the type I-D system, performing the role played by Cas3 in other CRISPR–Cas type I systems. The type I-D system can be used for targeted mutagenesis of genomic DNA in human cells, directing both bi-directional long-range deletions and short insertions/deletions. Our findings suggest the CRISPR–Cas type I-D system as a unique effector pathway in CRISPR that can be repurposed for genome engineering in eukaryotic cells.
B-CePs as cross-linking probes for the investigation of RNA higher-order structure
Authors: Sosic Alice , Göttlich Richard , Fabris Dan , Gatto Barbara
Published: May 2021

Elucidating the structure of RNA and RNA ensembles is essential to understand biological functions. In this work, we explored the previously uncharted reactivity of bis-chloropiperidines (B-CePs) towards RNA. We characterized at the molecular level the different adducts induced by the fast reacting compound B-CeP 1 with RNA. Following an approach based on solution thermal melting coupled with ESI mass spectrometry (STHEM-ESI), we proved the ability of B-CePs to induce inter-molecular cross-links between guanines in double stranded RNA. These results open the possibility of using B-CePs as structural probes for investigating higher-order structures, such as the kissing loop complex established by the dimerization initiation site (DIS) of the HIV-1 genome. We confirmed the potential of B-CePs to reveal the identity of RNA structures involved in long-range interactions, expecting to benefit the characterization of samples that are not readily amenable to traditional high-resolution techniques, and thus promoting the elucidation of pertinent RNA systems associated with old and new diseases.
The role of CTCF in the organization of the centromeric 11p15 imprinted domain interactome
Authors: Naveh Natali S Sobel , Deegan Daniel F , Huhn Jacklyn , Traxler Emily , Lan Yemin , Weksberg Rosanna , Ganguly Arupa , Engel Nora , Kalish Jennifer M
Published: May 2021

DNA methylation, chromatin-binding proteins, and DNA looping are common components regulating genomic imprinting which leads to parent-specific monoallelic gene expression. Loss of methylation (LOM) at the human imprinting center 2 (IC2) on chromosome 11p15 is the most common cause of the imprinting overgrowth disorder Beckwith-Wiedemann Syndrome (BWS). Here, we report a familial transmission of a 7.6 kB deletion that ablates the core promoter of KCNQ1. This structural alteration leads to IC2 LOM and causes recurrent BWS. We find that occupancy of the chromatin organizer CTCF is disrupted proximal to the deletion, which causes chromatin architecture changes both in cis and in trans. We also profile the chromatin architecture of IC2 in patients with sporadic BWS caused by isolated LOM to identify conserved features of IC2 regulatory disruption. A strong interaction between CTCF sites around KCNQ1 and CDKN1C likely drive their expression on the maternal allele, while a weaker interaction involving the imprinting control region element may impede this connection and mediate gene silencing on the paternal allele. We present an imprinting model in which KCNQ1 transcription is necessary for appropriate CTCF binding and a novel chromatin conformation to drive allele-specific gene expression.
Independent effects of secondary hyperparathyroidism and hyperphosphataemia on chronic kidney disease progression and cardiovascular events: an analysis from the NEFRONA cohort
Authors: Bozic Milica , Diaz-Tocados Juan M , Bermudez-Lopez Marcelino , Forné Carles , Martinez Cristina , Fernandez Elvira , Valdivielso José M
Published: May 2021

Background

Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers.

Methods

The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE.

Results

The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia.

Conclusions

We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.
A homolog of GuidedEntry of Tail-anchored proteins3 functions in membrane-specific protein targeting in chloroplasts of Arabidopsis
Authors: Anderson Stacy A. , Satyanarayan Manasa B. , Wessendorf Ryan L. , Lu Yan , Fernandez Donna E.
Published: May 2021

The chloroplasts and mitochondria of photosynthetic eukaryotes contain proteins that are closely related to cytosolic Guided Entry of Tail-anchored proteins3 (Get3). Get3 is a targeting factor that efficiently escorts tail-anchored (TA) proteins to the ER. Because other components of the cytosolic-targeting pathway appear to be absent in organelles, previous investigators have asserted that organellar Get3 homologs are unlikely to act as targeting factors. However, we show here both that the Arabidopsis thaliana chloroplast homolog designated as GET3B is structurally similar to cytosolic Get3 proteins and that it selectively binds a thylakoid-localized TA protein. Based on genetic interactions between a get3b mutation and mutations affecting the chloroplast signal recognition particle-targeting pathway, as well as changes in the abundance of photosynthesis-related proteins in mutant plants, we propose that GET3B acts primarily to direct proteins to the thylakoids. Furthermore, through molecular complementation experiments, we show that function of GET3B depends on its ability to hydrolyze ATP, and this is consistent with action as a targeting factor. We propose that GET3B and related organellar Get3 homologs play a role that is analogous to that of cytosolic Get3 proteins, and that GET3B acts as a targeting factor in the chloroplast stroma to deliver TA proteins in a membrane-specific manner.
A back-linked Fabry–Pérot interferometer for space-borne gravitational wave observations
Authors: Izumi Kiwamu , Fujimoto Masa-Katsu
Published: May 2021

Direct observations of gravitational waves at frequencies below 10 Hz will play a crucial role in fully exploiting the potential of gravitational wave astronomy. One approach to pursue this direction is the utilization of laser interferometers equipped with Fabry–Pérot optical cavities in space. However, there are a number of practical challenges in following this path. In particular, the implementation of precision control for cavity lengths and the suppression of laser phase noises may prevent a practical detector design. To circumvent such difficulties, we propose a new interferometer topology, called a back-linked Fabry–Pérot interferometer, where precision length controls are not required and an offline subtraction scheme for laser phase noises is readily applicable. This article presents the principle idea and the associated sensitivity analyses. Despite additional noises, a strain sensitivity of $$7\times10^{-23}\,\textrm{Hz}^{-1/2}$$ may be attainable in the decihertz band. Several technological developments must occur and studies must be carried out to pave the way for the implementation.
Using point-of-care ultrasound in nursing
Authors: Geer Brandon
Published: May 2021

In this article, the author examines the use of point-of-care ultrasound in nursing practice, including its benefits, clinical implications, and cost-effectiveness for nursing practice and healthcare systems in the long run.
Using COPD action plans to support outcomes after discharge
Authors: Conley Patricia
Published: May 2021

In 2017, the World Health Organization reported that chronic obstructive pulmonary disease (COPD) impacted 251 million individuals and was responsible for 3.17 million deaths globally. To educate hospitalized patients with COPD about self-management at home, nurses require an action plan to use as part of discharge instructions. This article discusses the benefits of COPD action plans revealed in the literature and describes the creation and use of such an action plan by the author.
Is Microthrombosis the Main Pathology in Coronavirus Disease 2019 Severity?—A Systematic Review of the Postmortem Pathologic Findings
Authors: Fahmy Omar H. , Daas Farah M. , Salunkhe Vidyulata , Petrey Jessica L. , Cosar Ediz F. , Ramirez Julio , Akca Ozan
Published: May 2021

Objectives:

This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019–associated thrombotic pathologies reported in the recent literature.

Data Sources:

PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020.

Study Selection:

Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019.

Data Extraction:

Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death.

Data Synthesis:

From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d-dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in nonsurvivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lung vasculature were the most common pathologic findings in the lungs and microthrombi in most of the assessed organ-tissue.

Conclusions:

Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Widespread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequent pulmonary and extrapulmonary microthrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specific hypercoagulability. Further discovery efforts in assessing the link between coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients is needed.
Surgical Treatment of Oromandibular Limb Hypogenesis Syndrome Type I A by Distraction Osteogenesis Combined With Orthodontic Rehabilitation
Authors: Sangwatanakul Jirayus , Song Shaohua , Zhou Nuo
Published: May 2021

Oromandibular limb hypogenesis syndrome is a rare developmental anomaly and only a few cases are reported with complete surgical and orthodontic rehabilitation. An adult male patient with isolated hypoglossia, micrognathism, hypodontia, (oromandibular limb hypogenesis syndrome type I A) was treated with a combination of distraction osteogenesis and orthodontic intervention. The patient was followed up for the duration of 6 years from his first visit to 4 years after the surgery. The combined procedure resulted in successful and satisfactory treatment of the patient by restoring facial aesthetics, occlusal balance, and functional harmony. However, there was not enough tongue enlargement due to late surgical intervention. The objective of this report is to describe the etiology of hypoglossia, the consequences for oral function, and to share our experience from the oral rehabilitation during the treatment procedure.
A Retrospective Study of Patients Undergoing Acute Electroconvulsive Therapy for Predominately Manic or Mixed Episodes With and Without Lithium in Singapore
Authors: Tang Kai Wen Aaron , Tan Xiao Wei , Tor Phern-Chern
Published: May 2021

Objective

The effect of lithium therapy during Electroconvulsive Therapy (ECT) on cognition and treatment effectiveness is unclear. In this study, we compare the cognitive and symptomatic outcomes of patients undergoing ECT with and without lithium in a large tertiary psychiatric institution.

Methods

Patients with predominantly manic or mixed episodes on lithium were propensity score matched with controls. Cognition was assessed using the Montreal Cognitive Assessment (MoCA), while severity of symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity Scale. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) and EuroQol Five Dimension (EQ-5D). Linear mixed-effects modeling and conditional logistic regression were conducted as appropriate.

Results

87 patients were included in the study. There was no significant difference in cognitive and symptomatic outcomes for patients receiving ECT with or without lithium after 6 sessions of ECT.

Conclusions

Concurrent lithium administration during the initial acute ECT course was not associated with differential cognitive or symptomatic outcomes. Lithium administration should not be a contraindication for appropriate acute ECT treatment in patients. Larger controlled studies to confirm these findings are warranted.
Surface and air contamination with SARS-CoV-2 from hospitalized COVID-19 patients in Toronto, Canada
Authors: Kotwa Jonathon D. , Jamal Alainna J. , Mbareche Hamza , Yip Lily , Aftanas Patryk , Barati Shiva , Bell Natalie G. , Bryce Elizabeth , Coomes Eric , Crowl Gloria , Duchaine Caroline , Faheem Amna , Farooqi Lubna , Hiebert Ryan , Katz Kevin , Khan Saman , Kozak Robert , Li Angel X. , Mistry Henna P. , Mozafarihashjin Mohammad , Nasir Jalees A. , Nirmalarajah Kuganya , Panousis Emily M. , Paterson Aimee , Plenderleith Simon , Powis Jeff , Prost Karren , Schryer Renée , Taylor Maureen , Veillette Marc , Wong Titus , Zhong Xi Zoe , McArthur Andrew G. , McGeer Allison J. , Mubareka Samira
Published: May 2021

Background

The aim of this prospective cohort study was to determine the burden of SARS-CoV-2 in air and on surfaces in rooms of patients hospitalized with COVID-19, and to identify patient characteristics associated with SARS-CoV-2 environmental contamination.

Methods

Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at six acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 viral RNA and cultured to determine potential infectivity. Whole viral genomes were sequenced from nasopharyngeal and surface samples. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated using a mixed-effects logistic regression model.

Findings

SARS-CoV-2 RNA was detected from surfaces (125/474 samples; 42/78 patients) and air (3/146 samples; 3/45 patients) in COVID-19 patient rooms; 17% (6/36) of surface samples from three patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient.

Multivariable analysis indicated hypoxia at admission, a PCR-positive nasopharyngeal swab with a cycle threshold of ≤30 on or after surface sampling date, higher Charlson co-morbidity score, and shorter time from onset of illness to sample date were significantly associated with detection of SARS-CoV-2 RNA in surface samples.

Interpretation

The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited. Surface contamination was greater when patients were earlier in their course of illness and in those with hypoxia, multiple co-morbidities, and higher SARS-CoV-2 RNA concentration in NP swabs. Our results suggest that air and surfaces may pose limited risk a few days after admission to acute care hospitals.
A model framework for projecting the prevalence and impact of Long-COVID in the UK
Authors: Martin Chris , Luteijn Michiel , Letton William , Robertson Josephine , McDonald Stuart
Published: May 2021

Background

The objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 in the UK population, including symptoms of ‘long-COVID’. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long COVID.

Methods

The prevalence of symptomatic COVID-19, encompassing acute symptoms and long-COVID symptoms, was modelled using a decay function. Permanent injury as a result of COVID-19 infection, was modelled as a fixed prevalence. Both parts are combined to calculate QALY loss due to COVID-19 symptoms.

Results

Assuming a 60% final attack rate for SARS-CoV-2 infection in the population, we modelled 299,719 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,754 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury). The UK Government willingness-to-pay to avoid these QALY losses would be £17.9 billion and £32.2 billion, respectively. Additionally, 90,143 people were subject to permanent injury from COVID-19 (0.14% of the population).

Conclusion

Given the ongoing development in information in this area, we present a model framework for calculating the health economic impacts of symptoms following SARS-CoV-2 infection. This model framework can aid in quantifying the adverse health impact of COVID-19, long COVID and permanent injury following COVID-19 in society and assist the proactive management of risk posed to health. Further research is needed using standardised measures of patient reported outcomes relevant to long COVID and applied at a population level.
Emergence and spread of the potential variant of interest (VOI) B.1.1.519 predominantly present in Mexico
Authors: Rodríguez-Maldonado Abril Paulina , Vázquez-Pérez Joel Armando , Cedro-Tanda Alberto , Taboada Blanca , Boukadida Celia , Wong-Arámbula Claudia , Nuñez-García Tatiana Ernestina , Cruz-Ortiz Natividad , Barrera-Badillo Gisela , Hernández-Rivas Lucía , López-Martínez Irma , Mendoza-Vargas Alfredo , Reyes-Grajeda Juan Pablo , Alcaraz Nicolas , Peñaloza-Figueroa Fernando , Gonzalez-Barrera Dulibeth , Rangel-DeLeon Daniel , Herrera-Montalvo Luis Alonso , Mejía-Nepomuceno Fidencio , Hernández-Terán Alejandra , Mújica-Sánchez Mario , Becerril-Vargas Eduardo , Martínez-Orozco José Arturo , Pérez-Padilla Rogelio , Salas-Hernández Jorge , Sanchez-Flores Alejandro , Isa Pavel , Matías-Florentino Margarita , Ávila-Ríos Santiago , Muñoz-Medina José Esteban , Grajales-Muñiz Concepción , Salas-Lais Angel Gustavo , Coy-Arechavaleta Andrea Santos , Hidalgo-Miranda Alfredo , Arias Carlos F. , Ramírez-González José Ernesto
Published: May 2021

SARS-CoV-2 variants have emerged in late 2020 and there are at least three variants of concern (B.1.1.7, B.1.351, P1) reported by WHO. These variants have several substitutions in the Spike protein that affect receptor binding; they present increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we are reporting the identification of a potential variant of interest harboring the mutations T478K, P681H, and T732A in the Spike protein, within the newly named lineage B.1.1.519, which rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.
Neutrophils cause critical illness in COVID-19 and reveal CDK6 inhibitors as potential treatment
Authors: Baukmann Hannes A. , Cope Justin L. , Ravarani Charles N. J. , Bannard Colin , Lamparter Margaretha R. J. , Schwinges Alexander R. E. C. , Klinger Joern E. , Schmidt Marco F.
Published: May 2021

Background

Despite recent development of vaccines and monoclonal antibodies to prevent SARS-CoV-2 infection, treatment of critically ill COVID-19 patients remains an important goal. In principle, genome-wide association studies (GWAS) could shortcut the clinical evidence needed to repurpose drugs - the use of an existing drug for a new indication. However, it has been shown that the genes found in GWA studies usually do not encode an established drug target and the causal role for disease, a key requirement for drug efficacy, is unclear. We report here an alternative method for finding and testing causal target candidates for drug repurposing.

Methods

Rather than focusing on the genetics of the disease, we looked for disease-causing traits by searching for significant differences in 33 blood cell types, 30 blood biochemistries, and body mass index between an infectious disease phenotype and healthy controls. We then matched critically ill COVID-19 cases with controls that exhibited mild or no symptoms after SARS-CoV-2 infection in order to identify disease-causing traits by applying causal inference methods.

Results

We found high neutrophil cell count as a causal trait for the immune overreaction in critical illness due to COVID-19. Based on these findings, we identified the enzyme CDK6 as a potential drug target to prevent the immune overreaction in critical illness due to COVID-19.

Conclusions

The genetics of disease-causing traits turns out to be a rich reservoir for the identification of known drug targets. This is due to the usually larger datasets of traits, as they also cover healthy ones. A clinical trial testing CDK6 inhibitor palbociclib in critically ill COVID-19 patients is currently ongoing (ClinicalTrials.gov Identifier: NCT05371275).
Can alcohol consumption in Germany be reduced by alcohol screening, brief intervention and referral to treatment in primary health care? Results of a simulation study
Authors: Manthey Jakob , Solovei Adriana , Anderson Peter , Carr Sinclair , Rehm Jürgen
Published: May 2021

Background

Screening, brief intervention and referral to treatment (SBIRT) is a programme to reduce alcohol consumption for drinkers with high alcohol consumption levels. Only 2.9% of patients in primary health care (PHC) are screened for their alcohol use in Germany, despite high levels of alcohol consumption and attributable harm. We developed an open-access simulation model to estimate the impact of higher SBIRT delivery rates in German PHC settings on population-level alcohol consumption.

Methods and findings

A hypothetical population of drinkers and non-drinkers was simulated by sex, age, and educational status for the year 2009 based on survey and sales data. Risky drinking persons receiving BI or RT were sampled from this population based on screening coverage and other parameters. Running the simulation model for a ten-year period, drinking levels and heavy episodic drinking (HED) status were changed based on effect sizes from meta-analyses.

In the baseline scenario of 2.9% screening coverage, 2.4% of the adult German population received a subsequent intervention between 2009 and 2018. If every second PHC patient would have been screened for alcohol use, 21% of adult residents in Germany would have received BI or RT by the end of the ten-year simulation period. In this scenario, population-level alcohol consumption would be 12% lower than it was in 2018, without any impact on HED prevalence. Screening coverage rates below 10% were not found to have a measurable effect on drinking levels.

Conclusions

Large-scale implementation of SBIRT in PHC settings can yield substantial reductions of alcohol consumption in Germany. As high screening coverage rates may only be achievable in the long run, other effective alcohol policies are required to achieve short-term reduction of alcohol use and attributable harm in Germany. There is large potential to apply this open-access simulation model to other settings and for other alcohol interventions.
Integrating Health Behavior Theories to Predict COVID-19 Vaccine Acceptance: Differences between Medical Students and Nursing Students
Authors: Rosental Hila , Shmueli Liora
Published: May 2021

Background

This study aimed to explore behavioral-related factors predicting the intention of getting a COVID-19 vaccine among medical and nursing students using an integrative model combining the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB).

Methods

A cross-sectional online survey was conducted among medical and nursing students aged > 18 years in their clinical years in Israel between 27 August and 28 September 2020. Hierarchical logistic regression was used to predict acceptance of a COVID-19 vaccine.

Results

A total number of 628 participants completed the survey. Medical students expressed higher intentions of getting vaccinated against COVID-19 than nursing students (88.1% vs. 76.2%, p < 0.01). The integrated model based on HBM and TPB was able to explain 66% of the variance (adjusted R2 = 0.66). Participants were more likely to be willing to get vaccinated if they reported higher levels of perceived susceptibility, benefits, barriers, cues to action, attitude, self-efficacy and anticipated regret. Two interaction effects revealed that male nurses had a higher intention of getting vaccinated than did female nurses and that susceptibility is a predictor of the intention of getting vaccinated only among nurses.

Conclusions

This study demonstrates that both models considered (i.e., HBM and TPB) are important for predicting the intention of getting a COVID-19 vaccine among medical and nursing students, and can help better guide intervention programs, based on components from both models. Our findings also highlight the importance of paying attention to a targeted group of female nurses, who expressed low vaccine acceptance.
In pursuit of a better broiler: A comparison of the inactivity, behavior, and enrichment use of fast- and slower-growing broiler chickens
Authors: Dawson Lauren C. , Widowski Tina M. , Liu Zhenzhen , Edwards A. Michelle , Torrey Stephanie
Published: May 2021

Selection for rapid growth has produced heavier, more efficient broiler chickens, but has also introduced health and welfare issues, which may cause or be caused by inactivity. Rapid growth may also limit the performance of motivated behaviors, whereas the provision of enrichment may increase these behaviors and general activity. This study aimed to evaluate the inactivity, behavior, and enrichment use of 2 fast- (CONV) and 12 slower-growing broiler strains [categorized as fastest (FAST), moderate (MOD) and slowest slow (SLOW), based on their growth rates]. To evaluate inactivity, one male and one female from 153 pens were outfitted with omni-directional accelerometers from day 21 until processing (14–24 birds/strain from 8-12 pens/strain). Additionally, to supplement inactivity data, five-minute continuous behavioral observations of four focal birds per pen (2 males, 2 females) were conducted on days 26, 42, and 56 (72–148 observations of 8–12 pens/strain) to quantify the duration and frequency of various behaviors; at the same time, 5–11 instantaneous scan samples were also performed for pen-based enrichment use. Inactivity peaked at 78-80% of the day for all strains; however, those with slower growth rates reached these levels at older ages. Compared to slower-growing strains at the same age, faster-growing strains were more inactive, spent more time sitting and feeding, spent less time standing and walking, and used enrichments less; these differences mostly occurred at younger ages. Generally, at the same age, strains with similar growth rates (within the same category) behaved similarly, with only a few exceptions. Results suggest that not all strains identified as ‘slow-growing’ broilers behave differently from fast-growing broilers, nor do they all behave similarly to each other. As such, results suggest that improved broiler welfare, particularly with respect to reduced inactivity, the performance of a wider range of normal, motivated behaviors, and/or increased enrichment use, is related to the broiler strain’s specific growth rate.
Multiframe Evolving Dynamic Functional Connectivity (EVOdFNC): A Method for Constructing and Investigating Functional Brain Motifs
Authors: Miller Robyn L. , Vergara Victor M. , Pearlson Godfrey , Calhoun Vince D.
Published: May 2021

The study of brain network connectivity as a time-varying property began relatively recently and to date has remained primarily concerned with capturing a handful of discrete static states that characterize connectivity as measured on a timescale shorter than that of the full scan. Capturing group-level representations of temporally evolving patterns of connectivity is a challenging and important next step in fully leveraging the information available in large resting state functional magnetic resonance imaging (rs-fMRI) studies. We introduce a flexible, extensible data-driven framework for the stable identification of group-level multiframe (movie-style) dynamic functional network connectivity (dFNC) states. Our approach employs uniform manifold approximation and embedding (UMAP) to produce a continuity-preserving planar embedding of high-dimensional time-varying measurements of whole-brain functional network connectivity. Planar linear exemplars summarizing dominant dynamic trends across the population are computed from local linear approximations to the 2D embedded trajectories. A high-dimensional representation of each 2D exemplar segment is obtained by averaging the dFNC observations corresponding to the n planar nearest neighbors of τ evenly spaced points along the 2D line segment representation (where n is the UMAP number-of-neighbors parameter and τ is the temporal duration of trajectory segments being approximated). Each of the 2D exemplars thus “lifts” to a multiframe high-dimensional dFNC trajectory of length τ. The collection of high-dimensional temporally evolving dFNC representations (EVOdFNCs) derived in this manner are employed as dynamic basis objects with which to characterize observed high-dimensional dFNC trajectories, which are then expressed as weighted combination of these basis objects. Our approach yields new insights into anomalous patterns of fluidly varying whole brain connectivity that are significantly associated with schizophrenia as a broad diagnosis as well as with certain symptoms of this serious disorder. Importantly, we show that relative to conventional hidden Markov modeling with single-frame unvarying dFNC summary states, EVOdFNCs are more sensitive to positive symptoms of schizophrenia including hallucinations and delusions, suggesting a more dynamic characterization is needed to help illuminate such a complex brain disorder.
A METHOD FOR INTEGRATIVE ANALYSIS OF LOCAL AND GLOBAL BRAIN DYNAMICS
Authors: Miller Robyn L. , Vergara Victor M. , Calhoun Vince D.
Published: May 2021

The most common pipelines for studying time-varying network connectivity in resting state functional magnetic resonance imaging (rs-fMRI) operate at the whole brain level, capturing a small discrete set of “states” that best represent time-resolved joint measures of connectivity over all network pairs in the brain. This whole-brain hidden Markov model (HMM) approach “uniformizes” the dynamics over what is typically more than 1000 pairs of networks, forcing each time-resolved high-dimensional observation into its best-matched high-dimensional state. While straightforward and convenient, this HMM simplification obscures functional and temporal nonstationarities that could reveal systematic, informative features of resting state brain dynamics at a more granular scale. We introduce a framework for studying functionally localized dynamics that intrinsically embeds them within a whole-brain HMM frame of reference. The approach is validated in a large rs-fMRI schizophrenia study where it identifies group differences in localized patterns of entropy and dynamics that help explain consistently observed differences between schizophrenia patients and controls in occupancy of whole-brain dFNC states more mechanistically.
Zika virus noncoding RNA cooperates with the viral protein NS5 to inhibit STAT1 phosphorylation and facilitate viral pathogenesis
Authors: Slonchak Andrii , Wang Xiaohui , Chaggar Harman , Aguado Julio , Freney Morgan , Yan Kexin , Torres Francisco J , Amarilla Alberto A , Balea Rickyle , Sng Julian D. J. , Setoh Yin Xiang , Peng Nias , Watterson Daniel , Wolvetang Ernst , Suhrbier Andreas , Khromykh Alexander A
Published: May 2021

Zika virus (ZIKV) is a re-emerging pathogenic flavivirus, which causes microcephaly in infants and poses a continuing threat to public health. ZIKV, like all other flaviviruses, produces highly abundant noncoding RNA known as subgenomic flaviviral RNA (sfRNA). Herein we utilized wild-type and mutant ZIKV defective in production of sfRNA to elucidate for the first time how production of sfRNA affects all aspects of ZIKV pathogenesis. We found that in mouse pregnancy model of infection sfRNA is required for trans-placental dissemination of ZIKV and subsequent infection of fetal brain. Using human brain organoids, we showed that sfRNA promotes apoptosis of neural progenitor cells leading to profound cytopathicity and disintegration of organoids. We also found by transcriptome profiling and gene network analysis that in infected human placental cells sfRNA inhibits multiple antiviral pathways and promotes apoptosis with STAT1 identified as a key shared factor linking these two interconnected sfRNA activities. We further showed for the first time that sfRNA inhibits phosphorylation and nuclear translocation of STAT1 by a novel mechanism which involves binding to and stabilizing viral protein NS5. This allows accumulation of NS5 at the levels required for efficient inhibition of STAT1 phosphorylation. Thus, we elucidated the molecular mechanism by which ZIKV sfRNA exerts its functions in vertebrate hosts and discovered a co-operation between viral noncoding RNA and a viral protein as a novel strategy employed by viruses to counteract antiviral responses.
Distinct effects of host and neighbour tree identity on arbuscular and ectomycorrhizal fungi along a tree diversity gradient
Authors: Ferlian Olga , Goldmann Kezia , Eisenhauer Nico , Tarkka Mika T. , Buscot François , Heintz-Buschart Anna
Published: May 2021

Plant diversity and plant-related ecosystem functions have been in focus in biodiversity-ecosystem functioning studies. However, in this context, biotic interactions with mycorrhizal fungi have been understudied although they are crucial for plant-resource acquisition. We investigated the effects of tree species richness, tree mycorrhizal type on arbuscular (AMF) and ectomycorrhizal fungal (EMF) communities. We aimed to understand how dissimilarities in taxa composition and beta-diversity are related to target trees and neighbours of the same/different mycorrhizal type. We sampled a tree experiment with saplings (∼7 years old), where tree species richness (monocultures, 2-species, and 4-species mixtures) and mycorrhizal type were manipulated. AMF and EMF richness significantly increased with increasing tree species richness. AMF richness of mixture plots resembled that of the sum of the respective monocultures, whereas EMF richness of mixture plots was lower compared to the sum of the respective monocultures. Specialisation scores revealed significantly more specialised AMF than EMF suggesting that, in contrast to previous studies, AMF were more specialised, whereas EMF were not. We further found that AMF communities were little driven by the surrounding trees, whereas EMF communities were. Our study revealed the drivers of mycorrhizal fungal communities and further highlights the distinct strategies of AMF and EMF.
Survival analysis of pathway activity as a prognostic determinant in breast cancer
Authors: Jeuken Gustavo S. , Tobin Nicholas P. , Käll Lukas
Published: May 2021

Most activities in a cell are dependent on sets of biomolecules, often referred to as pathways. Pathways are useful to study as their activities are frequently more directly related to the behavior of the cell than their components. Traditional pathway analysis gives significance to differences in the pathway components’ concentrations between sample groups. Here we instead advocate a singular value decomposition-based method for estimating individual samples’ pathway activities that allow us to investigate more advanced statistical models. Specifically, we investigate the pathway activities’ association with patients’ survival time based on the transcription profiles of the METABRIC dataset. Our implementation shows that pathway activities are better prognostic markers for survival time in METABRIC than the individual transcripts. We also demonstrate that we can regress out the effect of individual pathways on other pathways, which allows us to estimate the other pathways’ residual pathway activity on survival.
Phylogenomic analysis of the genus Pseudomonas and reclassification of P. humi, P. zeshuii, P. psychrotolerans, P. nitritireducens, P. pharmacofabricae and P. panacis are later heterotypic synonym of P. citronellolis Lang 2007, P. luteola, P. oryzihabitans, P. nitroreducens Lang 2007, P. fluvialis and P. marginalis (Brown 1918) Stevens 1925 (Approved Lists 1980), respectively
Authors: Archana Kujur Ritu Rani , Deb Sushanta , Das Subrata K
Published: May 2021

The present study described the comparative genomic analysis of the validly named species of the genus Pseudomonas to define the taxonomic assignment. Genomic information for 208 type strains was available in the NCBI genome database at the time of conducting this analysis. The ANI, AAI and in silico DNA DNA hybridization (isDDH) data were higher than the threshold values for the twelve strains with their closely related type species. Whole genome comparisons shared 97 - 99 % average nucleotide identity, 97.85 to 99.19 % average amino acid identity and 72.80 to 90.40 % digital DNA DNA hybridization values. Further, the phylogenomic analysis based on the core genome confirmed that P. humi CCA1 and P. citronellolis LMG 18378, P. zeshuii KACC 15471 and P. luteola NBRC 103146, P. oryzihabitans DSM 6835 and P. psychrotolerans DSM 15758, P. nitroreducens DSM 14399 and P. nitritireducens WZBFD3-5A2, P. fluvialis CCM 8778 and P. pharmacofabricae ZYSR67-Z, P. panacis DSM 18529 and P. marginalis DSM 13124 formed a monophyletic clade. Thus, we proposed six type species viz., P. humi CCA1, P. zeshuii KACC 15471, P. psychrotolerans DSM 15758, P. nitritireducens WZBFD3 5A2, P. pharmacofabricae ZYSR67 Z and P. panacis DSM 18529 are the later heterotypic synonym of P. citronellolis Lang 2007, P. luteola, P. oryzihabitans, P. nitroreducens Lang 2007, P. fluvialis and P. marginalis (Brown 1918) Stevens 1925 (Approved Lists 1980), respectively considering the priority date of publication.
Detection of Locomotion Deficit in a Post-Traumatic Syringomyelia Rat Model Using Automated Gait Analysis Technique
Authors: Pukale Dipak D. , Farrag Mahmoud , Leipzig Nic D.
Published: May 2021

Syringomyelia (SM) is a spinal cord disorder in which a cyst (syrinx) filled with fluid forms in the spinal cord post-injury/disease, in patients syrinx symptoms include loss of pain and temperature sensation or locomotion deficit. Currently, there are no small animal models and connected tools to help study the functional impacts of SM. The objective of this study was to determine the detectability of subtle locomotion deficits due to syrinx formation/expansion in post-traumatic syringomyelia (PTSM) rat model using the recently reported method of Gait Analysis Instrumentation, and Technology Optimized for Rodents (GAITOR) with Automated Gait Analysis Through Hues and Areas (AGATHA) technique. First videos of the rats were collected while walking in an arena (using GAITOR) followed by extracting meaningful locomotion information from collected videos (using AGATHA protocol. PTSM injured rats demonstrated detectable locomotion deficits in terms of duty factor imbalance, paw placement accuracy, step contact width, stride length, and phase dispersion parameters compared to uninjured rats due to SM. We concluded that this technique could detect mild and subtle locomotion deficits associated with PTSM injury, which also in future work could be used further to monitor locomotion responses after different treatment strategies for SM.
Buffered EGFR signaling regulated by spitz to argos expression ratio is critical for patterning the Drosophila eye
Authors: Pasnuri Nikhita , Jaiswal Manish , Ray Krishanu , Mazumder Aprotim
Published: May 2021

The Epidermal Growth Factor Receptor (EGFR) signaling pathway plays a critical role in regulating tissue patterning. Drosophila EGFR (DER) signaling achieves specificity through multiple ligands and feedback loops to finetune signaling spatiotemporally. The principal Drosophila EGF, cleaved Spitz, and the negative feedback molecule, Argos are diffusible and can act both in a cell autonomous and non-autonomous manner. The relative expression dose of Spitz and Argos early in development has been shown to be critical in patterning the Drosophila eye, but the exact identity of the cells expressing these genes in the larval eyedisc has been elusive. Using single molecule RNA Fluorescence in situ Hybridization (smFISH), we reveal an intriguing differential expression of spitz and argos in the Drosophila third instar eye imaginal disc indicative of directional DER signaling. By genetically tuning DER signaling, we show that rather than absolute levels of expression, the ratio of expression to be critical for determining the adult eye phenotype. Proper ommatidial patterning is robust to thresholds around a tightly maintained wildtype ratio, and breaks down beyond. This provides a powerful instance of developmental buffering.
Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology
Authors: Kolloli Afsal , Kumar Ranjeet , Singh Pooja , Narang Anshika , Kaplan Gilla , Sigal Alex , Subbian Selvakumar
Published: May 2021

Phagocytosis of Mycobacterium tuberculosis (Mtb) aggregates, rather than similar numbers of single bacilli, induces host macrophage death and favors bacterial growth. Here, we examined whether aggregation contributes to enhanced Mtb pathogenicity in vivo in rabbit lungs. Rabbits were exposed to infectious aerosols containing mainly Mtb-aggregates (Mtb-AG) or Mtb-single cells (Mtb-SC). The lung bacterial load, histology, and immune cell composition were investigated over time. Genome-wide transcriptome analysis, cellular and tissue-level assays, and immunofluorescent imaging were performed on lung tissue to define and compare differential immune activation and pathogenesis between Mtb-AG and Mtb-SC infection.

Lung bacillary loads, disease scores, lesion size, and structure were significantly higher in Mtb-AG than in Mtb-SC infected animals. A differential immune cell distribution and activation were noted in the lungs and spleen of the two groups of infected animals. Mtb-AG infected animals also showed early induction of inflammatory network genes associated with necrosis and reduced host cell viability. Consistently, larger lung granulomas with clumped Mtb, extensive necrotic foci, and elevated matrix metalloproteases expression were observed in Mtb-AG infected rabbits. Our findings suggest that bacillary aggregation increases Mtb fitness for improved growth and accelerated lung inflammation and cell death, thereby exacerbating disease pathology in the lungs.