bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Intra-Party Democracy: An Exploratory Analysis of Podemos and the Labour Party
Authors: García Lupato Fabio , Meloni Marco
Published: February 2021

The role of technology is growing in intra-party democracy (IPD) processes. This article presents a proposal for analysing digital IPD, by applying empirical democratic theory dimensions. To test our methodology, we analyse two different types of parties, a new digital one, Pos, and a traditional one undergoing reform, the Labour Party. Our analysis shows, first, that the application of technology is not neutral, with a differential impact depending on the specific democratic dimension considered and, secondly, that—due to convergent developments—new and established parties are closer in their digital IPD than expected. These results point out the relevance, for the ongoing debate on the quality of IPD, of considering the impact of digital on different democratic dimensions and its evolution over time.
An epigenetic pathway in rice connects genetic variation to anaerobic germination and seedling establishment
Authors: Castano-Duque Lina , Ghosal Sharmistha , Quilloy Fergie A , Mitchell-Olds Thomas , Dixit Shalabh
Published: February 2021

Rice production is shifting from transplanting seedlings to direct sowing of seeds. Following heavy rains, directly sown seeds may need to germinate under anaerobic environments, but most rice (Oryza sativa) genotypes cannot survive these conditions. To identify the genetic architecture of complex traits, we quantified percentage anaerobic germination (AG) in 2,700 (wet-season) and 1,500 (dry-season) sequenced rice genotypes and performed genome-wide association studies (GWAS) using 693,502 single nucleotide polymorphisms. This was followed by post-GWAS analysis with a generalized SNP-to-gene set analysis, meta-analysis, and network analysis. We determined that percentage AG is intermediate-to-high among indica subpopulations, and AG is a polygenic trait associated with transcription factors linked to ethylene responses or genes involved in metabolic processes that are known to be associated with AG. Our post-GWAS analysis identified several genes involved in a wide variety of metabolic processes. We subsequently performed functional analysis focused on the small RNA and methylation pathways. We selected CLASSY 1 (CLSY1), a gene involved in the RNA-directed DNA methylation (RdDm) pathway, for further analyses under AG and found several lines of evidence that CLSY1 influences AG. We propose that the RdDm pathway plays a role in rice responses to water status during germination and seedling establishment developmental stages.
Prevention of necrosis caused by transient expression in Nicotiana benthamiana by application of ascorbic acid
Authors: Nosaki Shohei , Kaneko Mika K , Tsuruta Fuminori , Yoshida Hideki , Kato Yukinari , Miura Kenji
Published: February 2021

Application of high concentrations of sodium ascorbate suppresses necrosis caused by the expression of recombinant proteins in Nicotiana benthamiana, resulting in an increase in protein accumulation.
A year of COVID-19 and the spiritual well-being of the people
Authors: Rosales Renniel Jayson Jacinto
Published: February 2021

The global impact of the coronavirus disease 2019 pandemic has caused innumerable damages to the total well-being of the people. In previous studies, spirituality has shown positive effect to the well-being of the people. As the Catholic Church continuously provide religious and spiritual nourishment through online or virtual celebration of the liturgy, the ideal and lived experience of the select Catholic faithful shows no dissonance. The online and virtual celebrations give hope and to the people post-pandemic, as we enter to the new normal.
COVID-19: vaccination in a developing country
Authors: Gutiérrez-Zevallos Juan Diego , Espíritu-Martínez Libertad Beatriz
Published: February 2021

The common good and public service are important to gain public trust especially in the midst of a pandemic of misinformation about vaccines and miracle therapies being spread on social media. Controversies in the government of a developing country do not help to control the SARS-COV-2 pandemic. Is it only the government’s responsibility or can doctors and medical students promote the truth with appropriate communication strategies to decrease COVID-19 vaccine hesitancy?
Embedding Learning in a Learning Health Care System to Improve Clinical Practice
Authors: McEvoy Matthew D. , Dear Mary Lynn , Buie Reagan , Fowler Leslie C. , Miller Bonnie , Fleming Geoffrey M. , Moore Don , Rice Todd W. , Bernard Gordon R. , Lindsell Christopher J. ,   for the Vanderbilt Learning Healthcare System Investigators
Published: February 2021

Problem

In an ideal learning health care system (LHS), clinicians learn from what they do and do what they learn, closing the evidence-to-practice gap. In operationalizing an LHS, great strides have been made in knowledge generation. Yet, considerable challenges remain to the broad uptake of identified best practices. To bridge the gap from generating actionable knowledge to applying that knowledge in clinical practice, and ultimately to improving outcomes, new information must be disseminated to and implemented by frontline clinicians. To date, the dissemination of this knowledge through traditional avenues has not achieved meaningful practice change quickly.

Approach

Vanderbilt University Medical Center (VUMC) developed QuizTime, a smartphone application learning platform, to provide a mechanism for embedding workplace-based clinician learning in the LHS. QuizTime leverages spaced education and retrieval-based practice to facilitate practice change. Beginning in January 2020, clinician–researchers and educators at VUMC designed a randomized, controlled trial to test whether the QuizTime learning system influenced clinician behavior in the context of recent evidence supporting the use of balanced crystalloids rather than saline for intravenous fluid management and new regulations around opioid prescribing.

Outcomes

Whether spaced education and retrieval-based practice influence clinician behavior and patient outcomes at the VUMC system level will be tested using the data currently being collected.

Next Steps

These findings will inform future directions for developing and deploying learning approaches at scale in an LHS, with the goal of closing the evidence-to-practice gap.
Pregnancy and Parenting in Medical School: Highlighting the Need for Data and Support
Authors: Durfey Shayla N.M. , White Jordan , Adashi Eli Y.
Published: February 2021

More than 7% of medical students graduate from medical school with at least 1 nonspouse dependent, the majority of whom are likely children. However, there are no national studies on medical students who are parents, and very little is known about what medical schools are doing to support them. A growing literature on the experiences of residents and attending physicians who are parents has neglected to include those of medical students who are parents. It is possible that focusing on research and policy change for residents and attending physicians who are parents without considering medical students may bring about improvements that come too late for many. Further data are needed both on the available policies for students who are parents and on the experiences and needs of these students. Leading national organizations in medical education can help guide medical schools by leveraging their national networks to highlight existing best practices and to foster discussions about how best to support medical students who are parents.
We Burn Out, We Break, We Die: Medical Schools Must Change Their Culture to Preserve Medical Student Mental Health
Authors: Veal Christopher Thomas
Published: February 2021

The author explores medical student depression and suicide through the lens of the author’s personal struggle during the first 2 years of medical school. While the author’s story is unique, other medical students have also faced challenges that have led them to consider a permanent solution to a temporary problem. Although resources are available, stigma represents a significant barrier for students as they decide whether to seek help. Students fear that showing the slightest hint of vulnerability or imperfection will be used against them in an advancement committee, a course evaluation, or the dean’s letter for residency applications. This difficulty asking for help and the subsequent suppression of feelings can lead to burnout and ultimately to increased risk of suicide.

The author calls for medical schools to make changes to their culture to preserve medical student mental health. These include committing to helping students who are struggling academically or psychologically, implementing an institution-wide program to screen for individuals at risk for suicide, educating members of the institution’s community about depression to destigmatize seeking help for mental health, and ensuring confidential mental health services are readily available to those who need them. But, most importantly, medical schools must create a culture that normalizes the need for self-care and includes vulnerability as part of training in professionalism.
Association Between Medicaid Status, Social Determinants of Health, and Bariatric Surgery Outcomes
Authors: Liu Natalie , Venkatesh Manasa , Hanlon Bret M. , Muraveva Anna , Johnson Morgan K. , Hanrahan Lawrence P. , Funk Luke M.
Published: February 2021

Objective:

To compare outcomes after bariatric surgery between Medicaid and non-Medicaid patients and assess whether differences in social determinants of health were associated with postoperative weight loss.

Background:

The literature remains mixed on weight loss outcomes and healthcare utilization for Medicaid patients after bariatric surgery. It is unclear if social determinants of health geocoded at the neighborhood level are associated with outcomes.

Methods:

Patients who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2008 to 2017 and had ≥1 year of follow-up within a large health system were included. Baseline characteristics, 90-day and 1-year outcomes, and weight loss were compared between Medicaid and non-Medicaid patients. Area deprivation index (ADI), urbanicity, and walkability were analyzed at the neighborhood level. Median regression with percent total body weight (TBW) loss as the outcome was used to assess predictors of weight loss after surgery.

Results:

Six hundred forty-seven patients met study criteria (191 Medicaid and 456 non-Medicaid). Medicaid patients had a higher 90-day readmission rate compared to non-Medicaid patients (19.9% vs 12.3%, P < 0.016). Weight loss was similar between Medicaid and non-Medicaid patients (23.1% vs 21.9% TBW loss, respectively; P = 0.266) at a median follow-up of 3.1 years. In adjusted analyses, Medicaid status, ADI, urbanicity, and walkability were not associated with weight loss outcomes.

Conclusions:

Medicaid status and social determinants of health at the neighborhood level were not associated with weight loss outcomes after bariatric surgery. These findings suggest that if Medicaid patients are appropriately selected for bariatric surgery, they can achieve equivalent outcomes as non-Medicaid patients.
Oncological Impact of Gross Proximal Margin Length in Distal Gastrectomy for Gastric Cancer: Is the Japanese Recommendation Valid?
Authors: Hayami Masaru , Ohashi Manabu , Ishizuka Naoki , Hiki Naoki , Kumagai Koshi , Ida Satoshi , Sano Takeshi , Nunobe Souya
Published: February 2021

Objective:

To identify an oncological impact of gross proximal margin (PM) length in distal gastrectomy for cancer.

Summary background data:

In Japan, to obtain pathologically negative PMs in gastrectomy for cancer, the Gastric Cancer Treatment Guidelines (GCTGs) recommend maintaining the PM length to at least 2 cm for cT1, 3 cm for the expansive growth type (Exp), and 5 cm for the infiltrative growth type (Inf) of cT2–4. The GCTGs also recommend confirming pathologically negative PMs by intraoperative frozen section analyses when the gross PMs are shorter than the recommendations. However, whether they are valid is unknown.

Methods:

Patients who intended to undergo curative distal gastrectomy were included. They were divided into groups A (adherence to the GCTGs) and NA (nonadherence) according to the PM length. The incidence of pathologically positive PMs and survival outcomes were compared between the groups. Propensity scores (PSs) were used in comparisons of survival outcomes to eliminate potential confounders.

Results:

A total of 1036 patients were eligible. Pathologically positive PMs were identified in group NA with cT1 and Inf, and the incidence was 1.6% and 3.1%, respectively. Adjusted analysis using the PSs showed comparable survival outcomes between the groups. However, the hazard ratios according to the PSs presented a possible survival advantage in maintaining the recommended gross PM lengths except for cT1 and Exp located in the lower stomach.

Conclusion:

Surgeons should maintain the gross PM lengths recommended in the GCTGs to both obtain pathologically negative PMs and avoid survival disadvantages.
Surgical Patients’ Hospital Experience Scores: Neighborhood Context Conceptual Framework
Authors: Kranjac Ashley Wendell , Kranjac Dinko , Fortier Michelle A. , Patton Pat , Giafaglione Brad , Kain Zeev N.
Published: February 2021

Objective:

Through geocoding the physical residential address included in the electronic medical record to the census tract level, we present a novel model for concomitant examination of individual patient-related and residential context-related factors that are associated with patient-reported experience scores.

Summary Background Data:

When assessing patient experience in the surgical setting, researchers need to examine the potential influence of neighborhood-level characteristics on patient experience-of-care ratings.

Methods:

We geocoded the residential address included in the electronic medical record (EMR) from a tertiary care facility to the census tract level of Orange County, CA. We then linked each individual record to the matching census tract and use hierarchical regression analyses to test the impact of distinct neighborhood conditions on patient experience. This approach allows us to estimate how each neighborhood characteristic uniquely influences Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores.

Results:

Individuals residing in communities characterized by high levels of socioeconomic disadvantage have the highest experience ratings. Accounting for individual patient’s characteristics such as age, gender, race/ethnicity, primary language spoken at home, length of stay, and average pain levels during their hospital stay, neighborhood-level characteristics such as proportions of people receiving public assistance influence the ratings of hospital experience (0.01, P < 0.05) independent of, and beyond, these individual-level factors.

Conclusions:

This manuscript is an example of how geocoding could be used to analyze surgical patient experience scores. In this analysis, we have shown that neighborhood-level characteristics influence the ratings of hospital experience independent of, and beyond, individual-level factors
Adoption and Usage of Video Telehealth in a Large, Academic Department of Surgery
Authors: Lazar Andrew N. , Nemeth Samantha K. , Kurlansky Paul A. , Patel Virendra I. , Homma Shunichi , Morrissey Nicholas J.
Published: February 2021

Objectives:

To understand the impact that video telehealth has on outpatient visit volume and reimbursement as a method of maintaining care.

Background:

As the coronavirus disease 2019 (COVID-19) spread across the United States starting in 2020, it caused numerous areas of medicine and healthcare to reexamine how we provide care to patients across all disciplines. One method clinicians used to rapidly adapt to these transformed settings was video telehealth, which was previously rarely used.

Methods:

This retrospective review examined outpatient volume and reimbursement data of a large, academic department of surgery. The study reviewed data during 2 time periods: pre-COVID-19 (February 1, 2020, to March 15, 2020) and COVID-19 (March 16, 2020, to April 30, 2020).

Results:

During the period of February 1 to April 30, 13,193 outpatient visits were analyzed. The pre-COVID-19 group contained 9041 (68.5%) visits, whereas the COVID-19 group contained 4152 (31.4%) visits. All divisions noted a drop in visit volume from pre-COVID-19 compared with COVID-19. There was rapid adoption of video telehealth during COVID-19, which made up most patient visits during that time (61.3%). We also found that video telehealth led to significant reimbursements while also allowing patients in numerous states to receive care.

Conclusions:

Previously, video telehealth was used by clinicians in a small portion of outpatient visits. However, safety concerns surrounding COVID-19 forced multiple changes to the way care is provided. Although outpatient volume at our center was less than that before the pandemic, video telehealth was rapidly adopted by providers and allowed for safe and effective outpatient care to patients in a high number of states while still being reimbursed at a high rate.
Is Surgical Training Prepared for the “Second Wave” of COVID-19? A Collaborative Perspective
Authors: Rajgor Harshadkumar Dhirajlal , Rajgor Amarkumar Dhirajlal , Sidhu Manpreet Singh , Khan Shehzaad Aziz , Hossain Fahad , Moores Thomas Steven
Published: February 2021

Restructuring of surgical services during the ‘first wave’ of the coronavirus-disease 2019 pandemic led to significant disruption in surgical learning opportunities provided to junior surgeons. Recent challenges faced by trainees have never been faced before. These include disruption to surgical opportunities available, completing assessments and attending educational events. With a ‘second wave’ now upon the United Kingdom it is vitally important we reflect upon the ‘first wave’ to ensure junior surgeons are able to achieve appropriate surgical case numbers, complete assessments and progress to the next stage of training. Alternate assessment methods in the United Kingdom need to be considered should the pandemic continue and clear information should be provided to surgical trainees regarding career progression. These are difficult times for surgical training and we need to endeavor that trainees are provided with opportunities similar to their predecessors albeit in difficult circumstances. This is to ensure the future standard of surgical patient care remains of the highest standard.
The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness
Authors: Coopersmith Craig M. , Antonelli Massimo , Bauer Seth R. , Deutschman Clifford S. , Evans Laura E. , Ferrer Ricard , Hellman Judith , Jog Sameer , Kesecioglu Jozef , Kissoon Niranjan , Martin-Loeches Ignacio , Nunnally Mark E. , Prescott Hallie C. , Rhodes Andrew , Talmor Daniel , Tissieres Pierre , De Backer Daniel
Published: February 2021

OBJECTIVES:

To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients.

DESIGN:

The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document.

METHODS:

Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research.

RESULTS:

The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given?

CONCLUSIONS:

Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.
Development of a medical device compatible with MRI/CT to measure ankle joint laxity: the Porto Ankle Testing Device
Authors: Andrade Renato , Pereira Rogério , Leal Ana , Pereira Bruno , Vilas Boas João Paulo , van Dijk C. Niek , Espregueira-Mendes João
Published: February 2021

Ankle sprains are common and often develop into chronic ankle instability. Ankle laxity is usually assessed by manual testing followed by magnetic resonance imaging to confirm the diagnosis. Manual testing however provides a subjective measure and is limited to the assessor sensibility. Current available technologies incorporate arthrometers to objectively measuring ankle laxity, but are not capable to assess the structural integrity of the capsuloligamentous structures. To overcome these limitations, we developed a novel medical device to assist in the diagnosis of ankle ligament injuries—the Porto Ankle Testing Device. With this device, it is possible to combine and correlate the assessment of the capsuloligamentous’ structural integrity with the joint functional competence (ie, joint multiplanar laxity). The main purpose of this work is to present the fundamental aspects and step-by-step development of the Porto Ankle Testing Device. We discuss the design specifications and technical requirements with the purpose to design and develop this medical device, described the features of the different components and explained the mechanical systems that are incorporated emulate manual testing and to measure the multiplanar ankle laxity. The preliminary findings are presented with the purpose to display the assessment protocol, the method of laxity measurement and the obtained results. We propose a unique and reliable medical device to safety and effectively assess ankle ligament injuries and contribute to enhance diagnosis, refine treatment indications and allow objective measurement of ligament laxity before and/or after stabilization surgery.
Revisiting the clinical usefulness of C-reactive protein in the set of cancer cachexia
Authors: Tavares Patrícia , Gonçalves Daniel Moreira , Santos Lúcio Lara , Ferreira Rita
Published: February 2021

Cancer cachexia is a highly complex multifactorial disorder that is often misdiagnosed, leading to suboptimal health outcomes. Indeed, cachexia is a concern in cancer, typifying lower response to treatment and risk of death. Thus, efforts have been made to better understand the molecular basis of this syndrome, envisioning to improve its diagnosis and management.

C-reactive protein (CRP) has been reported to be consistently increased in the circulation of patients with body wasting associated to chronic diseases. However, the role of CRP in the pathogenesis of cachexia remains elusive. Several hypotheses have been advanced but most of experimental findings support an indirect effect on the activation of muscle proteolysis, mostly through its interplay with pro-inflammatory cytokines. Herein, we overview the contribution of CRP to body wasting and its putative biomarker value for the diagnosis and follow-up of the therapeutic management of cachexia.
A systematic review and meta-analysis on the prevalence of vancomycin-resistant enterococci (VRE) among Nigerians
Authors: Orababa Oluwatosin Qawiyy , Soriwei Jeffry Difiye , Akinsuyi Samuel Oluwamayowa , Essiet Utibeima Udo , Solesi Olusola Michael
Published: February 2021

Background:

Enterococci are opportunistic pathogens and are one of the most important bacteria in hospital-acquired infections. Their resistance to antibiotics such as vancomycin has led to life-threatening and difficult-to-treat nosocomial infections. The true prevalence in clinical settings in Nigeria is not well known due to the lack of a comprehensive antibiotic surveillance system. This study aims to estimate the prevalence of vancomycin-resistant enterococci (VRE) in clinical infections in Nigeria.

Methods:

Databases (PubMed, African Journal Online, and Google scholar) were searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2015 statements for articles reporting VRE prevalence, and were published before August 5, 2020. Data from the studies were extracted and analyzed using Microsoft Excel and Comprehensive Meta-Analysis (CMA 3.0), respectively. The pooled prevalence of VRE was estimated with the random-effects model and the 95% confidence interval (CI). The heterogeneity level was assessed using Cochran Q and I
2 tests.

Results:

A total of 35 articles were scanned for eligibility, among which 7 were included in the study after fulfilling the eligibility criteria. The studies analyzed a total of 832 enterococci isolates and 90 VRE strains. The prevalence of Enterococcus faecium and E faecalis in this study are 361 (59.3%) and 248 (40.7%), respectively, among which 41 (63.1%) of the E faecium and 24 (36.9%) of the E faecalis were vancomycin resistant. The pooled prevalence of VRE was estimated at (95% CI; 10.0–53.9%; I
2 = 93.50%; P < .001). The highest prevalence of VRE was reported from western Nigeria, 14.6% (95% CI; I
2 = 97.27; P < .001).

Conclusion:

The prevalence of VRE in Nigeria according to the reports from this study is relatively high. The report of this study should help policymakers to put in place measures that will help curb the spread of VRE and associated resistant genes to other important clinical pathogens like Staphylococcus aureus.
Long lasting complete response with immunotherapy in a metastatic bladder carcinoma: a case report
Authors: Magalhães Denise S.T. , Magalhães Helena M. , Mesquita Alexandra S.A.
Published: February 2021

At diagnosis, approximately 25% of urothelial carcinoma are invasive and only 15% of stage IV are alive at 5-years. We report a case of a 69-year-old woman with oligometastatic bladder cancer, treated with Atezolizumab in first-line, achieving a complete response after 4 cycles. Presently, the patient has an overall survival and progression free survival of 26 months with an improvement in her quality of life. Therefore, immunotherapy seems to be a promising treatment in advanced urothelial carcinoma. The previously performed radiotherapy, in association with a good performance status and oligometastatic disease, might have contributed to this admirable outcome.
Embryonic Stem Cell-like Population in Hypertrophic Port-wine Stain
Authors: Williams Jazmean , Brasch Helen Dian , Bockett Nicholas , Patel Josie , Paterson Erin , Davis Paul Frank , Tan Swee Thong
Published: February 2021

Objective:

To identify and characterize an embryonic stem cell (ESC)-like population within hypertrophic port-wine stain (HPWS).

Methods:

HPWS tissue samples from 15 patients underwent immunohistochemical staining for induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC. Immunofluorescence staining was performed on 2 of these tissue samples to investigate colocalization of these markers. In situ hybridization and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were performed on 6 of the HPWS samples to investigate transcript expression of these iPSC markers. Western blotting and RT-qPCR were performed on 3 HPWS-derived primary cell lines, to determine protein and transcript expression of these markers, respectively.

Results:

Immunohistochemical staining demonstrated expression of OCT4, SOX2, KLF4, and c-MYC but not NANOG on the endothelium and media of lesional vessels and on cells within the stroma in all 15 HPWS tissue samples. Immunofluorescence staining showed the presence of an OCT4+/SOX2+/NANOG-/KLF4+/c-MYC+ ESC-like subpopulation within the endothelium and media of the lesional vessels, and cells within the stroma of HPWS. In situ hybridization detected OCT4, SOX2, KLF4, and c-MYC transcripts in all 6 HPWS tissue samples. RT-qPCR demonstrated transcripts of all 5 iPSC markers in the HPWS tissue samples and in the HPWS-derived primary cell lines, which expressed OCT4, SOX2, KLF4, and c-MYC but not NANOG proteins by Western blotting.

Conclusion:

This study demonstrated an OCT4+/SOX2+/NANOG-/KLF4+/c-MYC+ ESC-like population within the endothelium and media of the lesional vessels and the cells within the stroma of HPWS.
Psychological distress among patients with lymphoma: the association with personality and coping strategies
Authors: Arts Lindy P.J. , Oerlemans Simone , Schoormans Dounya , Sanders Arnate L.T.M. , Stevens Wendy B.C. , Posthuma Eduardus F.M. , Tick Lidwine W. , van de Poll-Franse Lonneke V.
Published: February 2021

Background:

Up to one-quarter of patients with lymphoma experience persisting levels of psychological distress. This study aims to examine the extent to which personality traits and coping strategies, separately and together, are associated with psychological distress among patients with lymphoma, controlling for sociodemographic and clinical characteristics.

Methods:

A population-based sample of patients with lymphoma, selected from the Netherlands Cancer Registry (NCR), was invited to complete a questionnaire about psychological distress, personality, and coping strategies (Mental Adjustment to Cancer). Sociodemographic and clinical data were retrieved from the NCR. Multivariable linear regression models were constructed to assess the unique variance in psychological distress explained by personality traits and coping strategies separately and together.

Results:

A total of 456 patients completed the questionnaire (51%), the average age was 65 years, 64% were male, and 17% reported psychological distress. Of sociodemographic and clinical characteristics, comorbidity (β = .14, P < .001) and age (β = −.10, P = .03) were independently associated with psychological distress. In addition, of personality traits, only neuroticism was related to psychological distress (neuroticism, β = .43, P < .001). Furthermore, the coping styles anxious preoccupation (β = .12, P = .01) and helplessness/hopelessness (β = .30, P < .001) were associated with more psychological distress, whereas avoidance was associated to less psychological distress (β = −.09, P = .01).

Conclusions:

In conclusion, besides comorbidity and age, personality traits—in particular neuroticism—and the coping strategies helplessness/hopelessness, anxious preoccupation, and avoidance were significantly independently associated with psychological distress. Unlike personality, coping strategies are considered to be changeable and could be targeted by interventions such as cognitive behavioral therapy.
How signalling games explain mimicry at many levels: from viral epidemiology to human sociology
Authors: Casey William , Massey Steven E , Mishra Bud
Published: February 2021

Mimicry is exhibited in multiple scales, ranging from molecular, to organismal, and then to human society. ‘Batesian’-type mimicry entails a conflict of interest between sender and receiver, reflected in a deceptive mimic signal. ‘Müllerian’-type mimicry occurs when there is perfect common interest between sender and receiver in a particular type of encounter, manifested by an honest co-mimic signal. Using a signalling games approach, simulations show that invasion by Batesian mimics will make Müllerian mimicry unstable, in a coevolutionary chase. We use these results to better understand the deceptive strategies of SARS-CoV-2 and their key role in the COVID-19 pandemic. At the biomolecular level, we explain how cellularization promotes Müllerian molecular mimicry, and discourages Batesian molecular mimicry. A wide range of processes analogous to cellularization are presented; these might represent a manner of reducing oscillatory instabilities. Lastly, we identify examples of mimicry in human society that might be addressed using a signalling game approach.
An early Sox2-dependent gene expression programme required for hippocampal dentate gyrus development
Authors: Mercurio Sara , Alberti Chiara , Serra Linda , Meneghini Simone , Berico Pietro , Bertolini Jessica , Becchetti Andrea , Nicolis Silvia K.
Published: February 2021

The hippocampus is a brain area central for cognition. Mutations in the human SOX2 transcription factor cause neurodevelopmental defects, leading to intellectual disability and seizures, together with hippocampal dysplasia. We generated an allelic series of Sox2 conditional mutations in mouse, deleting Sox2 at different developmental stages. Late Sox2 deletion (from E11.5, via Nestin-Cre) affects only postnatal hippocampal development; earlier deletion (from E10.5, Emx1-Cre) significantly reduces the dentate gyrus (DG), and the earliest deletion (from E9.5, FoxG1-Cre) causes drastic abnormalities, with almost complete absence of the DG. We identify a set of functionally interconnected genes (Gli3, Wnt3a, Cxcr4, p73 and Tbr2), known to play essential roles in hippocampal embryogenesis, which are downregulated in early Sox2 mutants, and (Gli3 and Cxcr4) directly controlled by SOX2; their downregulation provides plausible molecular mechanisms contributing to the defect. Electrophysiological studies of the Emx1-Cre mouse model reveal altered excitatory transmission in CA1 and CA3 regions.
A visual atlas of meiotic protein dynamics in living fission yeast
Authors: Escorcia Wilber , Tripathi Vishnu P. , Yuan Ji-Ping , Forsburg Susan L.
Published: February 2021

Meiosis is a carefully choreographed dynamic process that re-purposes proteins from somatic/vegetative cell division, as well as meiosis-specific factors, to carry out the differentiation and recombination pathway common to sexually reproducing eukaryotes. Studies of individual proteins from a variety of different experimental protocols can make it difficult to compare details between them. Using a consistent protocol in otherwise wild-type fission yeast cells, this report provides an atlas of dynamic protein behaviour of representative proteins at different stages during normal zygotic meiosis in fission yeast. This establishes common landmarks to facilitate comparison of different proteins and shows that initiation of S phase likely occurs prior to nuclear fusion/karyogamy.
Spatial sampling heterogeneity limits the detectability of deep time latitudinal biodiversity gradients
Authors: Jones Lewis A. , Dean Christopher D. , Mannion Philip D. , Farnsworth Alexander , Allison Peter A.
Published: February 2021

The latitudinal biodiversity gradient (LBG), in which species richness decreases from tropical to polar regions, is a pervasive pattern of the modern biosphere. Although the distribution of fossil occurrences suggests this pattern has varied through deep time, the recognition of palaeobiogeographic patterns is hampered by geological and anthropogenic biases. In particular, spatial sampling heterogeneity has the capacity to impact upon the reconstruction of deep time LBGs. Here we use a simulation framework to test the detectability of three different types of LBG (flat, unimodal and bimodal) over the last 300 Myr. We show that heterogeneity in spatial sampling significantly impacts upon the detectability of genuine LBGs, with known biodiversity patterns regularly obscured after applying the spatial sampling window of fossil collections. Sampling-standardization aids the reconstruction of relative biodiversity gradients, but cannot account for artefactual absences introduced by geological and anthropogenic biases. Therefore, we argue that some previous studies might have failed to recover the ‘true’ LBG type owing to incomplete and heterogeneous sampling, particularly between 200 and 20 Ma. Furthermore, these issues also have the potential to bias global estimates of past biodiversity, as well as inhibit the recognition of extinction and radiation events.
Conservation and turnover of miRNAs and their highly complementary targets in early branching animals
Authors: Praher Daniela , Zimmermann Bob , Dnyansagar Rohit , Miller David J. , Moya Aurelie , Modepalli Vengamanaidu , Fridrich Arie , Sher Daniel , Friis-Møller Lene , Sundberg Per , Fôret Sylvain , Ashby Regan , Moran Yehu , Technau Ulrich
Published: February 2021

MicroRNAs (miRNAs) are crucial post-transcriptional regulators that have been extensively studied in Bilateria, a group comprising the majority of extant animals, where more than 30 conserved miRNA families have been identified. By contrast, bilaterian miRNA targets are largely not conserved. Cnidaria is the sister group to Bilateria and thus provides a unique opportunity for comparative studies. Strikingly, like their plant counterparts, cnidarian miRNAs have been shown to predominantly have highly complementary targets leading to transcript cleavage by Argonaute proteins. Here, we assess the conservation of miRNAs and their targets by small RNA sequencing followed by miRNA target prediction in eight species of Anthozoa (sea anemones and corals), the earliest-branching cnidarian class. We uncover dozens of novel miRNAs but only a few conserved ones. Further, given their high complementarity, we were able to computationally identify miRNA targets in each species. Besides evidence for conservation of specific miRNA target sites, which are maintained between sea anemones and stony corals across 500 Myr of evolution, we also find indications for convergent evolution of target regulation by different miRNAs. Our data indicate that cnidarians have only few conserved miRNAs and corresponding targets, despite their high complementarity, suggesting a high evolutionary turnover.
Fiber1, but not fiber2, is the essential fiber gene for fowl adenovirus 4 (FAdV-4)
Authors: Zou Xiaohui , Rong Yejing , Guo Xiaojuan , Hou Wenzhe , Yan Bingyu , Hung Tao , Lu Zhuozhuang
Published: February 2021

Fibre is the viral protein that mediates the attachment and infection of adenovirus to the host cell. Fowl adenovirus 4 (FAdV-4) possesses two different fibre trimers on each penton capsomere, and roles of the separate fibres remain elusive. Here, we attempted to investigate the function of FAdV-4 fibres by using reverse genetics approaches. Adenoviral plasmids carrying fiber1 or fiber2 mutant genes were constructed and used to transfect chicken LMH cells. Fiber1-mutated recombinant virus could not be rescued. Such defective phenotype was complemented when a fiber1-bearing helper plasmid was included for co-transfection. The infection of fiber-intact FAdV-4 (FAdV4-GFP) to LMH cells could be blocked with purified fiber1 knob protein in a dose-dependent manner, while purifed fiber2 knob had no such function. On the contrary, fiber2-mutated FAdV-4, FAdV4XF2-GFP, was successfully rescued. The results of one-step growth curves showed that proliferative capacity of FAdV4XF2-GFP was 10 times lower than that of the control FAdV4-GFP. FAdV4XF2-GFP also caused fewer deaths of infected chicken embryos than FAdV4-GFP did, which resulted from poorer virus replication in vivo. These data illustrated that fiber1 mediated virus adsorption and was essential for FAdV-4, while fiber2 was dispensable although it significantly contributed to the virulence.
Disease burden of bloodstream infections caused by antimicrobial-resistant bacteria: a population-level study—Japan, 2015-2018
Authors: Tsuzuki Shinya , Matsunaga Nobuaki , Yahara Koji , Shibayama Keigo , Sugai Motoyuki , Ohmagari Norio
Published: February 2021

Background

Antimicrobial resistance (AMR) is a global health problem. However, quantitative evaluation of its disease burden is challenging. This study aimed to estimate the disease burden of bloodstream infections (BSIs) caused by major antimicrobial-resistant bacteria in Japan between 2015 and 2018 in terms of disability-adjusted life-years (DALYs).

Methods

We estimated the DALYs of BSIs caused by the six major antimicrobial-resistant bacteria in Japan by utilising comprehensive national surveillance data of all routine bacteriological test results from more than 1,400 hospitals between 2015 and 2018. We modified the methodology of a previous study by Cassini and colleagues to enable comparison of our results with those in other countries.

Results

We estimated that 135.8 (95% uncertainty interval [UI] 128.6-142.9) DALYs per 100,000 population was attributable to BSIs caused by the six antimicrobial-resistant bacteria in 2018. Staphylococcus aureus (MRSA), fluoroquinolone-resistant Escherichia coli (FQREC), and third-generation cephalosporin-resistant E. coli (3GREC) accounted for 88.6% of the total. The burden did not decrease during the study period and was highest in people aged 65 years or older.

Conclusion

Our results revealed for the first time the disease burden of BSIs caused by six major antimicrobial-resistant bacteria in Japan. The estimated disease burden associated with AMR in Japan is substantial and has not begun to decrease. Notably, the burden from FQREC and 3GREC has increased steadily and that from MRSA is larger than EU/EEA area, whereas that from other bacteria was comparatively small. Our results are expected to provide useful information for healthcare policymakers for prioritising interventions for AMR.

Funding

Ministry of Health, Labour and Welfare research grant (20HA2003); Japan Agency for Medical Research and Development Research Program on Emerging and Re-emerging Infectious Diseases (JP19fk0108061)
SARS CoV-2 escape variants exhibit differential infectivity and neutralization sensitivity to convalescent or post-vaccination sera
Authors: Kuzmina Alona , Khalaila Yara , Voloshin Olga , Keren-Naus Ayelet , Bohehm Liora , Raviv Yael , Shemer-Avni Yonat , Rosenberg Elli , Taube Ran
Published: February 2021

Towards eradicating COVID19, developing vaccines that induce high levels of neutralizing antibodies is a main goal. As counter measurements, viral escape mutants rapidly emerge and potentially compromise vaccine efficiency. Herein we monitored ability of convalescent or Pfizer-BTN162b2 post-vaccination sera to neutralize wide-type SARS-CoV2 or its UK-B.1.1.7 and SA-B.1.351 variants. Relative to convalescent sera, post-vaccination sera exhibited higher levels of neutralizing antibodies against wild-type or mutated viruses. However, while SARS-CoV2 wild-type and UK-N501Y were similarly neutralized by tested sera, the SA-N501Y/K417N/E484K variant moderately escaped neutralization. Significant contribution to infectivity and sensitivity to neutralization was attributed to each of the variants and their single or combined mutations, highlighting alternative mechanisms by which prevalent variants with either N501Y or E484K/K417N mutations spread. Our study validates the clinical significance of currently administered vaccines, but emphasizes that their efficacy may be compromised by circulated variants, urging the development of new ones with broader neutralization functions.
SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a that limit immune suppression
Authors: Nemudryi Artem , Nemudraia Anna , Wiegand Tanner , Nichols Joseph , Snyder Deann T , Hedges Jodi F , Cicha Calvin , Lee Helen , Vanderwood Karl K , Bimczok Diane , Jutila Mark , Wiedenheft Blake
Published: February 2021

Over 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral chal-lenge experiments to demonstrate that Δ115 mutation results in a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon stimulated gene expression. Collectively, this work indicates that ORF7a mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response.

Highlights

ORF7a mutations are found in SARS-CoV-2 genomes isolated from around the globe.

ORF7a mutation results in a replication defect.

An ORF7a mutation limits viral suppression of the interferon response.
COVID-19 in New York state: Effects of demographics and air quality on infection and fatality
Authors: Mondal Sumona , Chaipitakporn Chaya , Kumar Vijay , Wangler Bridget , Gurajala Supraja , Dhaniyala Suresh , Sur Shantanu
Published: February 2021

The coronavirus disease 2019 (COVID-19) has had a global impact that has been unevenly distributed amongst and, even within countries. Multiple demographic and environmental factors have been associated with the risk of COVID-19 spread and fatality, including age, gender, ethnicity, poverty, and air quality among others. However, specific contributions of these factors are yet to be understood. Here, we attempted to explain the variability in infection, death, and fatality rates by understanding the contributions of a few selected factors. We compared the incidence of COVID-19 in New York State (NYS) counties during the first wave of infection and analyzed how different demographic and environmental variables associate with the variation observed across the counties. We observed that the two important COVID-19 metrics of infection rates and death rates to be well correlated, and both metrics being highest in counties located near New York City, considered one of the epicenters of the infection in the US. In contrast, disease fatality was found to be highest in a different set of counties despite registering a low infection rate. To investigate this apparent discrepancy, we divided the counties into three clusters based on COVID-19 infection, death rate, or fatality, and compared the differences in the demographic and environmental variables such as ethnicity, age, population density, poverty, temperature, and air quality in each of these clusters. Furthermore, a regression model built on this data reveals PM2.5 and distance from the epicenter are significant risk factors for high infection rate, while disease fatality has a strong association with age and PM2.5. Our results demonstrate, for the NYS, distinct contributions of old age, PM2.5, ethnicity these factors to the overall COVID-19 burden and highlight the detrimental impact of poor air quality. These results could help design and direct location-specific control and mitigation strategies.