bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase
Authors: Xia Zhen , Tang Min , Ma Jiayan , Zhang Hongyan , Gimple Ryan C , Prager Briana C , Tang Hongzhen , Sun Chongran , Liu Fuyi , Lin Peng , Mei Yutang , Du Ruoxin , Rich Jeremy N , Xie Qi
Published: June 2021

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.
Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Host Displaying Treatment Induced Viral Evolution
Authors: Monrad Ida , Sahlertz Signe Risgaard , Nielsen Stine Sofie Frank , Pedersen Louise Ørnskov , Petersen Mikkel Steen , Kobel Carl Mathias , Tarpgaard Irene Harder , Storgaard Merete , Mortensen Klaus Leth , Schleimann Mariane H , Tolstrup Martin , Vibholm Line K
Published: June 2021

We report a coronavirus disease 2019 case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisting beyond 333 days in an immunocompromised patient with chronic lymphocytic leukemia, asymptomatically carrying infectious SARS-CoV-2 at day 197 postdiagnosis. In addition, viral sequencing indicates major changes in the spike protein over time, temporally associated with convalescent plasma treatment.
Elevated Mortality Among People Experiencing Homelessness With COVID-19
Authors: Leifheit Kathryn M , Chaisson Lelia H , Medina Jesus A , Wahbi Rafik N , Shover Chelsea L
Published: June 2021

We reviewed publicly available data from major US health jurisdictions to compare severe acute respiratory syndrome coronavirus 2 case fatality rates in people experiencing homelessness with the general population. The case fatality rate among people experiencing homelessness was 1.3 times (95% CI, 1.1–1.5) that of the general population, suggesting that people experiencing homelessness should be prioritized for vaccination.
Relating gas dynamics to star formation in the central region of the barred spiral galaxy NGC 613
Authors: Sato Keisuke , Miyamoto Yusuke , Kuno Nario , Salak Dragan , Wagner Alexander Y , Seta Masumichi , Nakai Naomasa
Published: June 2021

The barred spiral galaxy NGC 613 has a star-forming ring in the center, and near-infrared observations have previously shown that the star formation activity on the eastern and western sides of the ring is asymmetric. We examined the dynamics and physical state of the molecular gas in the ring using high-resolution (∼15 pc) 12CO(1–0), 12CO(3–2), and 13CO(1–0) observations with ALMA. Using a dendrogram, we identified 111 molecular clouds in the bar and ring, and found that the virial parameter (αvir) gradually decreases (αvir < 2) toward the confluence of the northern bar and eastern ring, while the virial parameter is large (αvir > 2) around the corresponding confluence in the western side of the ring. A non-LTE analysis using RADEX showed that the temperature and density of the molecular gas increase downstream of the eastern point of confluence, whereas they change irregularly on the western side. The star formation efficiency is (1.7 ± 0.2) × 10−8 yr−1 in the eastern side of the ring, which is substantially higher than the (0.9 ± 0.3) × 10−8 yr−1 for the western side of the ring. Position–velocity diagrams show that the relative velocity of the gas between the bar and the ring is ∼70 km s−1 in the east, while it reaches ∼170 km s−1 in the west. We suggest that the star formation activity in the central region of NGC 613 depends strongly on the relative velocity of the gas between the bar and the ring.
Do Elections Keep the Compassionate out of the Candidate Pool?
Authors: Clifford Scott , Simas Elizabeth N , Kirkland Justin H
Published: June 2021

Political candidates must possess not only a desire for a position in government, but also a tolerance for the electoral process typically required to attain it. Recent works suggest that this latter requirement may keep certain types of people out of the potential candidate pool. We contend that individuals high in empathic concern are one such type. While compassion for others may make certain aspects of public service attractive, it should also make some of the more negative features of political campaigns repellant. We find support for this theory among two national samples. Those higher in empathic concern were more likely to express nascent ambition when considering a political position that was appointed rather than elected. This work further illustrates how exploring the interaction of psychological dispositions and political institutions can contribute to our understanding of the behavior of politicians and the quality of representation.
Artificial intelligence applications in psychoradiology
Authors: Li Fei , Sun Huaiqiang , Biswal Bharat B , Sweeney John A , Gong Qiyong
Published: June 2021

One important challenge in psychiatric research is to translate findings from brain imaging research studies that identified brain alterations in patient groups into an accurate diagnosis at an early stage of illness, prediction of prognosis before treatment, and guidance for selection of effective treatments that target patient-relevant pathophysiological features. This is the primary aim of the field of Psychoradiology. Using databases collected from large samples at multiple centers, sophisticated artificial intelligence (AI) algorithms may be used to develop clinically useful image analysis pipelines that can help physicians diagnose, predict, and make treatment decisions. In this review, we selectively summarize psychoradiological research using magnetic resonance imaging of the brain to explore the neural mechanism of psychiatric disorders, and outline progress and the path forward for the combination of psychoradiology and AI for complementing clinical examinations in patients with psychiatric disorders, as well as limitations in the application of AI that should be considered in future translational research.
Pion mass dependence of the electromagnetic form factors of singly heavy baryons
Authors: Kim June-Young , Kim Hyun-Chul
Published: June 2021

We study the electromagnetic form factors of the lowest-lying singly heavy baryons with spin 1/2 within the framework of the chiral quark–soliton model, focusing on the comparison with recent lattice data. To compare the present results quantitatively with the lattice data, it is essential to treat the pion mass as a variable parameter, i.e., to employ unphysical values of the pion mass, which are used in lattice calculations. While the results with a physical value of the pion mass fall off faster than those from the lattice calculations as the momentum transfer increases, the extrapolated results with larger pion masses get closer to the lattice data. This indicates that the pion mean-field approach describes the structures of both light and singly heavy baryons.
Physical Activity and Sedentary Behavior in Cardiac Rehabilitation: Does Body Mass Index Matter?
Authors: den Uijl Iris , ter Hoeve Nienke , Sunamura Madoka , Lenzen Mattie J , Braakhuis Hanneke E M , Stam Henk J , Boersma Eric , van den Berg-Emons Rita J G
Published: June 2021

Objective

The purpose of this study was to investigate the relationship between body mass index (BMI) class and physical activity and sedentary behavior in patients with acute coronary syndrome (ACS) during cardiac rehabilitation (CR).

Methods

This study was a secondary analysis of the OPTICARE trial. Physical activity and sedentary behavior were measured in participants with ACS (n = 359) using actigraphy at baseline, directly after completion of a multidisciplinary 12-week exercise-based CR program and 9 months thereafter. Outcome measures were step count and duration of time (percentage of wear time) spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior. Participants were classified as normal weight (BMI = 18.5–24.99 kg/m2; n = 82), overweight (BMI = 25.0–29.99 kg/m2; n = 182), or obese (BMI ≥ 30.0 kg/m2; n = 95). Linear mixed-effects models were applied to study the relationship between BMI class and physical activity and sedentary behavior.

Results

At the start of CR, compared with participants with normal weight, participants with obesity made on average 1.11 steps fewer per minute (952 steps/d), spent 2.9% (25 min/d) less time in light physical activity, and spent 3.31% (28 min/d) more time in sedentary behavior. Participants of all BMI classes improved their physical activity and sedentary behavior levels similarly during CR, and these improvements were maintained after completion of CR.

Conclusion

Participants with ACS who had obesity started CR with a less favorable physical activity and sedentary behavior profile than that of participants with normal weight. Because all BMI classes showed similar improvement during CR, this deficit was preserved.

Impact

This study indicates that reconsideration of the CR program in the Netherlands for patients with ACS and obesity is warranted, and development of more inclusive interventions for specific populations is needed. A new program for people with obesity should include added counseling on increasing physical activity and preventing sedentary behavior to facilitate weight loss and reduce mortality risk.

Lay Summary

People with ACS who have obesity are less active and sit more than individuals with normal weight, both during and after CR. This study suggests that CR needs to be changed to help individuals increase their physical activity to help them lose weight and reduce their risk of death.
OCCUPATIONAL DOSES TO RADIOGRAPHY INTERNSHIP STUDENTS IN SAUDI ARABIA USING OPTICALLY STIMULATED LUMINESCENCE DOSIMETRY
Authors: Alashban Yazeed , Shubayr Nasser , Alohaly Amani , Aloraini Sarah , Alamri Raziqi , Alghamdi Sami A
Published: June 2021

This study aimed to estimate a baseline for the effective doses received by radiography internship students in Saudi Arabia. A retrospective study was conducted from 2015 to 2018 to discern the effective dose measurements for a total of 206 students using optically stimulated luminescence dosemeters. Readings were performed using the OSLR-250 Automatic Reader. Data analysis was carried out on 813 readouts. The annual mean effective dose averaged over a period of 4 y was found to be 0.55 mSv, with a standard deviation of 0.34 mSv and a range of 0.14–1.58 mSv. The results show that 92% ($\frac{190}{206}$) of the students received annual effective doses of <1 mSv. No annual dose record exceeded the limits recommended by authorities (20 mSv/y). The study concluded that the applied radiation protection measures along with education and training help create a safe work environment for radiography internship students.
Present and future self in memory: the role of vmPFC in the self-reference effect
Authors: Stendardi Debora , Biscotto Francesca , Bertossi Elena , Ciaramelli Elisa
Published: June 2021

Self-related information is remembered better than other-related information (self-reference effect; SRE), a phenomenon that has been convincingly linked to the medial prefrontal cortex. It is not clear whether information related to our future self would also have a privileged status in memory, as medial prefrontal cortex (mPFC) regions respond less to the future than to the present self, as if it were an ‘other’. Here we ask whether the integrity of the ventral mPFC (vmPFC) is necessary for the emergence of the present and future SRE, if any. vmPFC patients and brain-damaged and healthy controls judged whether each of a series of trait adjectives was descriptive of their present self, future self, another person and that person in the future and later recognized studied traits among distractors. Information relevant to the present (vs future) was generally recognized better, across groups. However, whereas healthy and brain-damaged controls exhibited strong present and future SREs, these were absent in vmPFC patients, who concomitantly showed reduced certainty about their own present and anticipated traits compared to the control groups. These findings indicate that vmPFC is necessary to impart a special mnemonic status to self-related information, including our envisioned future self, possibly by instantiating the self-schema.
Under construction: Trusts, trust-like structures, foundations and beneficial owners registries in the European Union—The Czech perspective
Authors: Ronovská Kateřina , Pihera Vlastimil
Published: June 2021

Searching for a comprehensive EU policy on preventing money laundering, terrorist financing and abuse of the international financial system will be a hot topic in the EU for the next couple of years. Directive (EU) 2018/843, known as the 5th Anti-Money Laundering Directive, follows the trend set by the 4th AML Directive in 2015 and inter alia introduces new requirements concerning the extent to which trust structures must be registered in the beneficial ownership registries across the EU as well as the public accessibility of the information held in such registries. This article addresses the main problematic issues that have appeared in recent professional discussions in the Czech Republic in connection with the new UBO Registry Act, in effect from 1 June 2021.
Parasite species variation and impact of spatial displacement of the population on cutaneous leishmaniasis in Rio de Janeiro, Brazil
Authors: Salgueiro Mariza M , Pimentel Maria Inês F , Miranda Luciana F C , Cunha e Silva Rafael R , Oliveira Liliane F A , Lyra Marcelo R , Saheki Mauricio N , Valete-Rosalino Claudia M , Martins Ana Cristina C , Schubach Armando O , Marzochi Mauro C A , Bedoya-Pacheco Sandro J
Published: June 2021

Background

Cutaneous leishmaniasis results from complex interactions between human beings, vectors and the environment. Parasitic species differ in epidemiological and geographical contexts.

Methods

We studied a retrospective cohort of 696 patients with cutaneous leishmaniasis treated at a reference centre in the state of Rio de Janeiro, Brazil, between 2000 and 2015. We analysed displacements due to work, leisure and migrations with identification of Leishmania species.

Results

The geographic distribution of autochthonous cases showed that >95% of infections occurred in urban areas. In the state of Rio de Janeiro, most cases were concentrated in the cities surrounding forest parks and nature conservation areas. The same applies to the city of Rio de Janeiro, where these infections occurred in the neighbourhoods surrounding some mountain and forest areas. The non-displacement group included 575 (82.6%) patients and the displacement group included 121 (17.4%) patients. Leishmania (Viannia) braziliensis predominated in both groups. Other species were found in the displacement group.

Conclusions

The disordered urbanization of the state of Rio de Janeiro in recent decades has created conditions for the emergence of urban foci of transmission close to forest areas. Changes in the environment, movement of infected individuals and adaptation of sandflies may have contributed to this.
Climate influence the human leptospirosis cases in Brazil, 2007–2019: a time series analysis
Authors: Costa Anna Cecília Trolesi Reis Borges , Pereira Carine Rodrigues , Sáfadi Thelma , Heinemann Marcos Bryan , Dorneles Elaine Maria Seles
Published: June 2021

Background

Human leptospirosis is responsible for great losses and deaths, especially in developing countries, which can be mitigated by knowing the correct health indicators and climate influence on the disease.

Methods

Leptospirosis cases and deaths, population and precipitation were recovered from different databases (2007–2019). Annual incidence, mortality and case fatality rates (CFRs) of human leptospirosis and average precipitation were calculated for Brazil and its regions. Time series analysis using an moving average with external variable (ARMAX) model was used to analyse the monthly contribution and precipitation influence over leptospirosis cases for each Brazilian region and for the whole country. A forecast model to predict cases for 2020 was created for Brazil.

Results

Human leptospirosis exhibited heterogeneous distribution among Brazilian regions, with most cases occurring during the rainy season and precipitation influenced the disease occurrence in all regions but the South. The forecast model predicted 3276.99 cases for 2020 (mean absolute percentage error 14.680 and root mean square error 53.013). Considering the annual average for the period, the leptospirosis incidence was 1913 cases per 100 000 inhabitants, mortality was 0.168 deaths per 100 000 inhabitants and the CFR was 8.83%.

Conclusions

The models built can be useful for planning leptospirosis surveillance and control actions for the whole country and its regions and, together with the health indicators, revealed no uniform epidemiological situation of leptospirosis in Brazil.
Molecular phylogenetics and evolutionary analysis of a highly recombinant begomovirus, Cotton leaf curl Multan virus, and associated satellites
Authors: Farooq Tahir , Umar Muhammad , She Xiaoman , Tang Yafei , He Zifu
Published: June 2021

Cotton leaf curl Multan virus (CLCuMuV) and its associated satellites are a major part of the cotton leaf curl disease (CLCuD) caused by the begomovirus species complex. Despite the implementation of potential disease management strategies, the incessant resurgence of resistance-breaking variants of CLCuMuV imposes a continuous threat to cotton production. Here, we present a focused effort to map the geographical prevalence, genomic diversity, and molecular evolutionary endpoints that enhance disease complexity by facilitating the successful adaptation of CLCuMuV populations to the diversified ecosystems. Our results demonstrate that CLCuMuV populations are predominantly distributed in China, while the majority of alphasatellites and betasatellites exist in Pakistan. We demonstrate that together with frequent recombination, an uneven genetic variation mainly drives CLCuMuV and its satellite’s virulence and evolvability. However, the pattern and distribution of recombination breakpoints greatly vary among viral and satellite sequences. The CLCuMuV, Cotton leaf curl Multan alphasatellite, and Cotton leaf curl Multan betasatellite populations arising from distinct regions exhibit high mutation rates. Although evolutionarily linked, these populations are independently evolving under strong purifying selection. These findings will facilitate to comprehensively understand the standing genetic variability and evolutionary patterns existing among CLCuMuV populations across major cotton-producing regions of the world.
A Problem of Classification: 2 Cases of Epstein–Barr Virus + Primary Cutaneous Plasmacytoma Arising in Immunocompetent Elderly Patients
Authors: Robson Alistair , Kempf Werner , Kolm Isabel , Kutzner Heinz , Willsmore Zena , Moonim Mufaddal
Published: June 2021

Primary extramedullary plasmacytoma is rare monoclonal proliferation of plasma cells, which arise in various nonosseous anatomic locations without detectable underlying systemic disease. Historically, cutaneous infiltrates rich in mature neoplastic plasma cells have fallen into one of the following categories, plasmacytoma, lymphoplasmacytic lymphoma, and marginal zone lymphoma, which included immunocytoma. Since 2005, each of these was subsumed under the marginal zone lymphoma umbrella, largely on the basis of acknowledged diagnostic difficulties in some of these cases. We describe 2 cases in which the cutaneous infiltrates consisted of a pure population of light chain–restricted mature plasma cells in the absence of any other evidence for a marginal zone proliferation, or evidence of extracutaneous involvement, including a paraprotein. We propose that primary cutaneous plasmacytoma is the accurate diagnosis and is consistent with wider nomenclature. The unusual observation of widespread Epstein–Barr virus expression in both tumors is also discussed.
Scurvy and Tinea Corporis Simulating Leukocytoclastic Vasculitis
Authors: Heibel Haley D. , Ibad Sidra , Chao Yusuf , Patel Komal K. , Hutto Jake , Redd Lucas E. , Nussenzveig Daniel R. , Laborde Kimberly H. , Cockerell Clay J. , Shwin Kyawt
Published: June 2021

Leukocytoclastic vasculitis (LCV) is a small vessel inflammatory condition considered to be caused by circulating immune complexes and often occurs after an acute infection or exposure to a new medication, although it may be associated with an underlying systemic disease or be idiopathic in nature. It is important to determine the etiology, identify the extent of the disease for early intervention and appropriate management, and treat and/or eliminate the underlying cause. Here, we report cases of scurvy and tinea corporis that presented with histopathologic features of LCV and had significant clinical improvement with treatment of the underlying etiologies. These cases emphasize that histopathologic features of early evolving LCV may be seen in other settings including scurvy and tinea corporis. Appropriate treatment of the underlying condition is important for optimized patient management.
Doubly Misdiagnosed: Exophiala Masquerading as Squamous Cell Carcinoma and Chromoblastomycosis
Authors: Guerra Ricardo , Guffey Darren , Russell Mark
Published: June 2021

Deep cutaneous fungal infections (DCFI) can arise in the setting of skin trauma and immunosuppression. DCFI may be secondary to chromoblastomycosis, which is typically characterized by pseudoepitheliomatous hyperplasia histologically and can be mistaken for squamous cell carcinoma. In addition, “copper penny” spore–like pigmented yeast forms on Grocott's methenamine silver stain can suggest chromoblastomycosis, but this finding is not specific. By contrast, phaeohyphomycosis characteristically exhibits circumscribed pseudocyst or abscess on histopathology, and both yeast and hyphae can be seen. Our case reports a DCFI with pseudoepitheliomatous hyperplasia and “copper penny” yeast forms, ultimately diagnosed as phaeohyphomycosis after isolating Exophiala spinifera on fungal culture.
Research in Sickle Cell Disease: From Bedside to Bench to Bedside
Authors: Salinas Cisneros Gabriel , Thein Swee Lay
Published: June 2021

Sickle cell disease (SCD) is an exemplar of bidirectional translational research, starting with a remarkable astute observation of the abnormally shaped red blood cells that motivated decades of bench research that have now translated into new drugs and genetic therapies. Introduction of hydroxyurea (HU) therapy, the only SCD-modifying treatment for >30 years and now standard care, was initiated through another clinical observation by a pediatrician. While the clinical efficacy of HU is primarily due to its fetal hemoglobin (HbF) induction, the exact mechanism of how it increases HbF remains not fully understood. Unraveling of the molecular mechanism of how HU increases HbF has provided insights on the development of new HbF-reactivating agents in the pipeline. HU has other salutary effects, reduction of cellular adhesion to the vascular endothelium and inflammation, and dissecting these mechanisms has informed bench—both cellular and animal—research for development of the 3 recently approved agents: endari, voxelotor, and crizanlizumab; truly, a bidirectional bench to bedside translation. Decades of research to understand the mechanisms of fetal to adult hemoglobin have also culminated in promising anti-sickling genetic therapies and the first-in-human studies of reactivating an endogenous (γ-globin) gene HBG utilizing innovative genomic approaches.
Onclarity Performance in Human Papillomavirus DNA Detection in Formalin-Fixed Paraffin-Embedded Cervical Samples
Authors: Bottari Fabio , Passerini Rita , Renne Giuseppe , Guerrieri Maria Elena , Sandri Maria Teresa , Li Aojun , Orlandini Anna , Iacobone Anna Daniela
Published: June 2021

Objectives

Diagnosis of HPV infection is usually performed from cervical liquid-based cytology specimens (LBC), but these often contain a large amount of human papillomavirus (HPV) genotypes, most of which might cause transient infections. The aim of the study was to evaluate the performance of BD Onclarity HPV test genotyping method on formalin-fixed, paraffin-embedded (FFPE) cervical specimens compared with genotyping results from LBC.

Materials and Methods

Formalin-fixed, paraffin-embedded specimens from women surgically treated for cervical intraepithelial lesions (CINs) at the European Institute of Oncology, Milan, from September 2012 to June 2013 were retrieved from the archives of the Department of Pathology of the European Institute of Oncology. The FFPE and LBC specimens were genotyped using the same extended genotyping Onclarity assay.

Results

We collected 99 samples (26 CIN 1, 30 CIN 2, and 43 CIN 3+), but 15 were excluded from the analysis: these 84 samples show an overall agreement of 89% for HPV status between FFPE Onclarity samples versus LBC samples. The FFPE and LBC samples showed identical genotype in 75% samples, compatible genotype (at least 1 of the genotypes detected in LBC sample was found in the tissue sample) in 14% specimens, and discrepant genotype in 11% samples.

Conclusions

Our data demonstrate a very good concordance between HPV genotypes found in cytological and tissue samples, suggesting that the Onclarity method could also be used to detect HPV in tissue samples and that the HPV genotype detected in FFPE samples is one of the HPV detected in cytological samples, supporting the thesis that one lesion is caused by one HPV genotype.
Predictors and outcomes of acute recoil after ultrathin bioresorbable polymer sirolimus-eluting stents implantation: an intravascular ultrasound in native coronary arteries
Authors: Sato Takao , Goto Sonoka , Yuasa Sho , Akazawa Kohei , Aizawa Yoshifusa
Published: June 2021

Background

Ultrathin bioresorbable polymer sirolimus-eluting stents (BP-SESs) may easily lead to acute recoil. This study investigated acute recoil after BP-SES implantation on the basis of intravascular ultrasound (IVUS).

Methods

We enrolled 40 consecutive stents. Absolute acute recoil by quantitative coronary angiography was defined as the difference between the mean diameter of the last inflated balloon (X) and mean lumen diameter of the BP-SES immediately after balloon deflation (Y). Percent (%) acute recoil was defined as (X−Y)×100/X. IVUS was performed within the culprit lesion. Plaque eccentricity, % plaque burden and calcification grade score were assessed using IVUS. Calcification grade was scored on the basis of quadrants. On the basis of the median acute recoil value of 5.0%, the stents were divided into two groups: low (LAR, n = 20) and high % acute recoil (HAR, n = 20).

Results

Mean % acute recoil was 5.8 ± 5.3%. Plaque eccentricity, % plaque burden and stent/artery ratio were significantly higher in the HAR group than in the LAR group. Significant differences in % acute recoil were not observed regarding the types of stent diameter. In multivariate logistic regression and multiple linear regression analysis, plaque eccentricity and % plaque burden in the culprit plaque were significant positive predictors for the occurrence of % acute recoil. No significant differences, including clinical outcomes, were found between both groups at follow-up.

Conclusion

Acute recoil of BP-SESs may be influenced by an eccentric plaque with a large burden, which did not affect long-term outcomes. However, the present study might suggest the proper strategy (e.g. a more exhaustive plaque preparation) before BP-SES implantation in a case with these IVUS characteristics.
Considering Domain-Specific Experiential Learning: Self-Efficacy in Pediatric Physical Therapy Education
Authors: Scott Kimberley , Wissinger Jennifer , Hand Brittany , Heathcock Jill
Published: June 2021

Background:

Variability exists in pediatric training in physical therapy programs. Little is known about educator implementation of curriculum recommendations. Few options exist for evaluating student outcomes following pediatric instruction.

Purpose:

The purposes of this study are to describe the pediatric curriculum of a physical therapy program, quantify changes in self-efficacy following pediatric instruction, and define relationships between self-efficacy, prior experience, and interest in future pediatric practice.

Methods:

A prospective cohort study included 48 students. Measures were pediatric content hours, the Pediatric Communication and Handling Self-Efficacy Scale, prior experience, and self-reported interest in future pediatric practice.

Results:

Pediatric content hours followed published recommendations. There was a significant increase in self-efficacy after pediatric instruction. Prior experience and interest in future pediatric practice were significantly related to self-efficacy.

Conclusions:

Our results indicate that physical therapy programs reaching the recommended content hours for pediatric instruction support growth in student communication and handling self-efficacy.
Experiential Learning in Pediatric Physical Therapist Education: Faculty and Student Perceptions
Authors: Fiss Alyssa LaForme , Rapport Mary Jane , Gagnon Kendra , Wynarczuk Kimberly , Kendall Eydie , Schreiber Joseph
Published: June 2021

This study aimed to describe use of experiential learning (EL) with children in entry-level doctor of physical therapy programs. Experiential learning is a recommended educational strategy for building physical therapy knowledge and skills.

Subjects:

Faculty teaching pediatric content in accredited doctor of physical therapy programs was recruited; 106 responded. Students representing 20 participating programs were also invited to participate; 23 responded.

Methods:

Participants received an online questionnaire including closed- and open-ended questions regarding EL with children. Descriptive statistics were used to describe responses. Responses to open-ended questions were compiled and reviewed.

Results:

Respondents reported an average of 12.4 hours of EL with children in required courses. Satisfaction with quality was stronger than with amount of EL. Several perceived barriers and facilitators were reported.

Conclusions:

Use of and satisfaction with EL with children in physical therapists' education vary. Continued research on this variation and potential effects to educational outcomes is needed.
Pediatric Physical Therapy Telehealth and COVID-19: Factors, Facilitators, and Barriers Influencing Effectiveness—a Survey Study
Authors: Hall Jamie B. , Woods Morgan L. , Luechtefeld Jessica T.
Published: June 2021

Purpose:

The purpose of this study was to identify the important factors, facilitators, and barriers for telehealth effectiveness as described by pediatric physical therapists, transitioning from in-person to telehealth during the COVID-19 pandemic.

Methods:

Pediatric physical therapists' responses to 3 open-ended questions and 1 multipart Likert Scale question from an anonymous survey were collected and analyzed using thematic analysis and descriptive statistics.

Results:

Three overarching themes (Caregiver Engagement, Technology, and Resilience) were identified and accompanied by 3 subthemes (Personal Attributes, Equity, and COVID-Specific Considerations). Themes were supported by the Likert Scale question with Child/Caregiver Interaction, Internet Connection, and Family Factors identified as the most important factors related to telehealth effectiveness.

Conclusions:

High caregiver engagement and access to stable technology were most important for telehealth effectiveness. The telehealth service model met a need during the pandemic; however, emerging evidence suggests that it could be considered as an effective service delivery mode postpandemic.
Parental Satisfaction With Autonomous Pediatric Ambulatory Surgery Units
Authors: Poves-Álvarez Rodrigo , Gómez-Sánchez Esther , Martínez-Rafael Beatriz , Bartolomé Cecilia , Alvarez-Fuente Elisa , Muñoz-Moreno María Fe , Eiros José María , Tamayo Eduardo , Gómez-Pesquera Estefanía
Published: June 2021

Background and Objectives:

Ambulatory surgery is much favored in children, as they are usually healthy with no major comorbidities. Obvious benefits are minimization of health costs, optimal utilization of resources, decreased exposure to infections, and psychological and emotional advantages of avoiding admission of the patient, especially for the family. Parental satisfaction is a challenge in pediatric surgery processes. The objective of this study was to compare satisfaction in parents whose children underwent surgery without overnight stays with parents whose children were operated on in an autonomous major ambulatory surgery unit (hospital isolated).

Methods:

This was a prospective observational study of 200 children who received surgery on an outpatient basis (133 were included in an outpatient unit and 67 in a hospital setting). Different variables were collected, including sex, age, type of surgery, and length of stay in the hospital and location, and a telephone perception survey was conducted (questionnaire of satisfaction of 14 questions with possible answers from 1 to 4 on a Likert scale and a 15th question on global satisfaction, with an answer from 0 to 10).

Results:

Overall satisfaction during the hospital stay was higher in the group operated on in the autonomous major surgery unit (3.54 ± 0.57 vs 3.28 ± 0.64, P = .004). Whether parents respond as being very satisfied with the hospital stay is influenced by several factors, among which are: being treated at major ambulatory surgery units (odds ratio [OR] = 2.16), good or very good information received prior to surgery (OR = 2.03), and good or very good information received at discharge (OR = 2.48).

Conclusions:

Parents of children who received surgery on an outpatient basis were more satisfied if the procedure was performed in an autonomous major ambulatory surgery unit compared with hospitalization, even if it was not overnight. The information received during the care process influenced the parents' satisfaction. These findings suggest that efforts should be devoted to the creation of autonomous units for ambulatory surgery and to the improvement of perioperative information.
ICTV Virus Taxonomy Profile: Portogloboviridae
Authors: Prangishvili David , Liu Ying , Krupovic Mart ,   ICTV Report Consortium
Published: June 2021

Portogloboviridae is a family of viruses with circular, double-stranded DNA genomes of about 20 kbp. Their icosahedral virions have a diameter of 87 nm, and consist of an outer protein shell, an inner lipid layer and a nucleoprotein core wound up into a spherical coil. Portogloboviruses infect hyperthermophilic archaea of the genus

Saccharolobus

, order Sulfolobales and are presumably nonlytic. Portogloboviruses encode mini-CRISPR arrays which they use to compete against other co-infecting viruses. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Portogloboviridae, which is available at ictv.global/report/portogloboviridae.
High throughput SARS-CoV-2 variant analysis using molecular barcodes coupled with Next Generation Sequencing
Authors: Cohen-Aharonov Lyora A. , Rebibo-Sabbah Annie , Yaacov Adar , Granit Roy Z. , Strauss Merav , Colodner Raul , Cheshin Ori , Rosenberg Shai , Eavri Ronen
Published: June 2021

The identification of SARS-CoV-2 variants across the globe and their implications on the outspread of the pandemic, infection potential and resistance to vaccination, requires modification of the current diagnostic methods to map out viral mutations rapidly and reliably. Here, we demonstrate that integrating DNA barcoding technology, sample pooling and Next Generation Sequencing (NGS) provide an applicable solution for large-population viral screening combined with specific variant analysis.

Our solution allows high throughput testing by barcoding each sample, followed by pooling of test samples using a multi-step procedure. First, patient-specific barcodes are added to the primers used in a one-step RT-PCR reaction, amplifying three different viral genes and one human housekeeping gene (as internal control). Then, samples are pooled, purified and finally, the generated sequences are read using an Illumina NGS system to identify the positive samples with a sensitivity of 82.5% and a specificity of 97.3%. Using this solution, we were able to identify six known and one unknown SARS-CoV-2 variants in a screen of 960 samples out of which 258 (27%) were positive for the virus.

Thus, our diagnostic solution integrates the benefits of large population and epidemiological screening together with sensitive and specific identification of positive samples including variant analysis at a single nucleotide resolution.
Chronic SARS-CoV-2 infection and viral evolution in a hypogammaglobulinaemic individual
Authors: Williamson Maia Kavanagh , Hamilton Fergus , Hutchings Stephanie , Pymont Hannah M. , Hackett Mark , Arnold David , Maskell Nick A , MacGowan Alasdair , Albur Mahableshwar , Jenkins Megan , Heys Izak , Knapper Francesca , Elsayed Mustafa , Milligan Rachel ,   The COVID-19 Genomics UK (COG-UK) Consortium, Muir Peter , Vipond Barry , Matthews David A , Moran Ed , Davidson Andrew D.
Published: June 2021

There is widespread interest in the capacity for SARS-CoV-2 evolution in the face of selective pressures from host immunity, either naturally acquired post-exposure or from vaccine acquired immunity. Allied to this is the potential for long perm persistent infections within immune compromised individuals to allow a broader range of viral evolution in the face of sub-optimal immune driven selective pressure. Here we report on an immunocompromised individual who is hypogammaglobulinaemic and was persistently infected with SARS-CoV-2 for over 290 days, the longest persistent infection recorded in the literature to date. During this time, nine samples of viral nucleic acid were obtained and analysed by next-generation sequencing. Initially only a single mutation (L179I) was detected in the spike protein relative to the prototypic SARS-CoV-2 Wuhan-Hu-1 isolate, with no further changes identified at day 58. However, by day 155 the spike protein had acquired a further four amino acid changes, namely S255F, S477N, H655Y and D1620A and a two amino acid deletion (ΔH69/ΔV70). Infectious virus was cultured from a nasopharyngeal sample taken on day 155 and next-generation sequencing confirmed that the mutations in the virus mirrored those identified by sequencing of the corresponding swab sample. The isolated virus was susceptible to remdesivirin vitro, however a 17-day course of remdesivir started on day 213 had no effect on the viral RT-PCR cycle threshold (Ct) value. On day 265 the patient was treated with the combination of casirivimab and imdevimab. The patient experienced progressive resolution of all symptoms over the next 8 weeks and by day 311 the virus was no longer detectable by RT-PCR. The ΔH69/ΔV70 deletion in the N-terminus of the spike protein which arose in our patient is also present in the B.1.1.7 variant of concern and has been associated with viral escape mutagenesis after treatment of another immunocompromised patient with convalescent plasma. Our data confirms the significance of this deletion in immunocompromised patients but illustrates it can arise independently of passive antibody transfer, suggesting the deletion may be an enabling mutation that compensates for distant changes in the spike protein that arise under selective pressure.
CHST6-related macular corneal dystrophy: a matter of endothelium
Authors: Zhang Bi Ning , Qi Benxiang , Wang Xin , Dong Chunxiao , Cheng Jun , Li Dewei , Li Suxia , Chen Min , Zhang Bin , Zhou Qingjun , Xie Lixin
Published: June 2021

Macular corneal dystrophy (MCD) is classified as corneal stromal dystrophy. In this study, we retrospectively reviewed the surgical outcomes of 118 MCD patients receiving surgical treatment in the past 30 years and found patients receiving penetrating keratoplasty had the lowest recurrence rate 13.75%, compared with 40.91% patients receiving deep anterior lamellar keratoplasty and 25% receiving phototherapeutic keratectomy. Transcriptomic analysis in human corneal single-cell sequencing atlas found the MCD pathogenic gene CHST6 was abundant in corneal endothelium rather than other cell types. CHST6 protein showed a similar expression pattern to its mRNA. The mouse homologous gene Chst5 was 120-fold higher in corneal endothelium than in the epithelial and stromal layers. Mice with specifically Chst5 knockdown in the endothelial layer by microinjection of the adeno-associated virus serotype 9 - shRNA plasmids into the anterior chamber, rather than Chst5 knockdown into the stroma, showed MCD-like phenotypes. Corneal opacification and abnormally larger collagen fibrils were observed in the endothelial Chst5 knockdown mice. The same corneal characteristics were observed after overexpressing human CHST6 mutant R50H in the mouse endothelium. These observations indicating the pathogenesis of MCD is more related to the corneal endothelium rather than the stroma.

Significance Statement

Our study gave evidence that corneal endothelium contributing more to the macular corneal dystrophy (MCD) development, rather than other cell types in the cornea. We proposed penetrating keratoplasty might serve as a more proper surgical treatment for MCD according to the recurrence rate analysis. We also provided a novel method to construct MCD mouse model.
Wastewater Based Epidemiology Enabled Surveillance of Antibiotic Resistance
Authors: Riquelme M.V. , Garner E. , Gupta S. , Metch J. , Zhu N. , Blair M.F. , Arango-Argoty G. , Maile-Moskowitz A. , Li A. , Flach C-F , Aga D.S. , Nambi I. , Larsson D.G.J. , Bürgmann H. , Zhang T. , Pruden A. , Vikesland P.J.
Published: June 2021

Wastewater-based epidemiology (WBE) for disease monitoring is highly promising, but requires consistent methodologies that incorporate predetermined objectives, targets, and metrics. We demonstrate a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage, enabling assessment of: 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends including antibiotic concentrations in sewage. Across an internationally-sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Sales data were not predictive of antibiotics measured in sewage, emphasizing need for direct measurements. The WBE approach defined herein demonstrates multi-site comparability and sensitivity to local/regional factors.
Mutations in emerging variant of concern lineages disrupt genomic sequencing of SARS-CoV-2 clinical specimens
Authors: Kuchinski Kevin S. , Nguyen Jason , Lee Tracy D. , Hickman Rebecca , Jassem Agatha N. , Hoang Linda M. N. , Prystajecky Natalie A. , Tyson John R.
Published: June 2021

Mutations in emerging SARS-CoV-2 lineages can interfere with the laboratory methods used to generate high-quality genome sequences for COVID-19 surveillance. Here, we identify 46 mutations in current variant of concern lineages affecting the widely used laboratory protocols for SARS-CoV-2 genomic sequencing by Freed et al. and the ARTIC network. We provide laboratory data showing how three of these mutations disrupted sequencing of P.1 lineage specimens during a recent outbreak in British Columbia, Canada, and we also demonstrate how we modified the Freed et al. protocol to restore performance.
Human genetic factors associated with pneumonia susceptibility, a cue for COVID-19 mortality
Authors: Guin Debleena , Yadav Saroj , Singh Priyanka , Singh Pooja , Thakran Sarita , Kukal Samiksha , Kanojia Neha , Paul Priyanka Rani , Pattnaik Bijay , Sardana Viren , Grover Sandeep , Hasija Yasha ,   Indian Genome Variation Consortium, Agrawal Anurag , Kukreti Ritushree
Published: June 2021

The risk for community acquired pneumonia (CAP) is partially driven by genetics. To identify the CAP-associated genetic risk loci, we performed a meta-analysis of clinically diagnosed CAP (3,310 individuals) with 2,655 healthy controls. The findings revealed CYP1A1 variants (rs2606345, rs4646903, rs1048943) associated with pneumonia. We observed rs2606345 [G vs T; OR=1.49(1.29-1.69); p=0.0001; I2= 15.5%], and rs1048943 [T vs G; OR= 1.31(0.90-1.71); p=0.002; I2=19.3%] as risk markers and rs4646903 [T vs C; OR= 0.79(0.62-0.96); p=0.03; I2=0%] as a protective marker for susceptibility to CAP, when compared with healthy controls. Our meta-analysis showed the presence of CYP1A1 SNP alleles contributing significant risk toward pneumonia susceptibility. Interestingly, we observed a striking difference of allele frequency for rs2606345 (CYP1A1) among Europeans, Africans and Asians which may provide a possible link for observed variations in death due to coronavirus disease 2019 (COVID-19), a viral pneumonia. We report, for the first time, a significant positive correlation for the risk allele (T or A) of rs2606345, with a higher COVID-19 mortality rate worldwide and within a genetically heterogeneous nation like India. Mechanistically, the risk allele ‘A’ (rs2606345) is associated with lower expression of CYP1A1 and presumably leads to reduced capacity for xenobiotic detoxification. We note that ambient air pollution, a powerful inducer of CYP1A1 gene expression, is globally associated with lower, not higher mortality, as would normally be predicted. In conclusion, we find that CYP1A1 alleles are associated with CAP mortality, presumably via altered xenobiotic metabolism. We speculate that gene-environment interactions governing CYP1A1 expression may influence COVID-19 mortality.