bluuebunny/crossref_metadata_2025 huggingface dataset:
In-hospital day-by-day systolic blood pressure variability during rehabilitation: a marker of adverse outcome in secondary prevention after myocardial revascularization
Authors: Lazzeroni Davide , Camaiora Umberto , Castiglioni Paolo , Bini Matteo , Garibaldi Silvia , Geroldi Simone , Moderato Luca , Brambilla Lorenzo , Brambilla Valerio , Parati Gianfranco , Coruzzi Paolo
Published: June 2020

Objective:

Although it is known that increased visit-to-visit or home day-by-day variability of blood pressure (BP), independently of its average value, results in an increased risk of cardiovascular events, the prognostic value of in-hospital day-by-day BP variability in secondary cardiovascular prevention has not yet been established.

Methods:

We studied 1440 consecutive cardiac patients during a cardiovascular rehabilitation program of about 12 days after coronary artery bypass graft (CABG) and/or valve surgery. We measured auscultatory BP at the patient bed in each rehabilitation day twice, in the morning and the afternoon. We correlated SBP variability assessed as standard deviation (SBP-SD) and coefficient of variation (SBP-CoV) of the daily measures with overall mortality, cardiovascular mortality and major adverse cardiocerebrovascular events (MACCEs) after a mean follow-up of 49 months by Cox hazard analysis.

Results:

In our patients (age 68 ± 11years, 61% hypertensive patients) the ranges of SBP-SD tertiles were: 4.1–9.1, 9.2–11.5 and 11.6–24.5 mmHg. Fifty-five percent of the patients underwent CABG, 33% underwent valve surgery, 12% both CABG and valve surgery. In CABG patients, the highest SBP-SD tertile showed the highest overall mortality, cardiovascular mortality and MACCEs (P < 0.01). Results remained significant after multivariate analysis adjusting for age, sex, mean SBP, BMI, hypertension, hyperlipidaemia, and diabetes. No association between SBP-SD and mortality or MACCEs was found in valve surgery patients.

Conclusion:

In-hospital day-by-day SBP variability predicts mortality and MACCEs in CABG patients, possibly representing a target during rehabilitation and treatment in secondary cardiovascular prevention.
Extrapulmonary Manifestations of SARS-CoV-2
Authors: Osorio María F. , Vaca Richard G.
Published: June 2020

On December 30, 2019, the first reports of a group of patients with unknown etiology pneumonia appeared in Wuhan city, Hubei province, China. Taking into consideration the large amount of similar nucleotide sequences between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the past epidemic coronavirus, it will be appropriate to expect that such pathogens share the same cell line tropism and systemic pathology. Although several studies have, so far, identified the clinical characteristics of COVID-19 cases, there is very little knowledge on the extrapulmonary affection of SARS-CoV-2.

In this review, we summarize reports of the main affected organs besides the pulmonary system such as the liver and kidneys, as well as the cardiovascular and nervous system. The mechanisms of lesion remain largely unclear. The approach of this investigation is to suggest multisystemic work-up in patients with SARS-CoV-2 infection, aside from its respiratory management.
Storytelling Through Music to Improve Well-being in Oncology Nurses
Authors: Phillips Carolyn S. , Volker Deborah L. , Becker Heather , Davidson Kristin L.
Published: June 2020

Background

Professional grief is one cause of psychosocial stress that, if not attended to, may contribute to burnout and compassion fatigue. Oncology nurses often avoid their emotions and learn to cope with professional grief in isolation. Interventions aimed at professional grief are limited.

Objectives

To determine the feasibility of implementing a multidimensional intervention, Storytelling Through Music, with oncology nurses.

Intervention/Methods

This was a 2-group, quasi-experimental design utilizing both qualitative and quantitative methods. The 6-week intervention combined storytelling, reflective writing, music, and psychoeducation. Descriptive statistics and conventional content analysis were used to analyze the feasibility data.

Results

Most participants (n = 43) were female, white, working full-time in the outpatient oncology setting, with an average 8.5 years (range, 2–36 years) of oncology experience. Ninety-eight percent of the intervention was completed, and 98% of participants were retained. Analysis indicates that the intervention was acceptable, the participants learned they were not alone in their feelings, and they were supported by the group.

Conclusions

Results indicate that Storytelling Through Music is a feasible and acceptable intervention to address work-related emotions and psychosocial stress in this group of oncology nurses.

Implications for Practice

In 2017, the National Academy of Medicine stated clinician well-being must be a priority. Participation in this study was independently sought out by the oncology nurses and completed during their personal time. A future policy recommendation is to make participation in wellness interventions part of the mandatory competency training required by accrediting bodies so that institutions ensure the well-being of clinicians as a priority.
Recommendations to Leverage the Palliative Nursing Role During COVID-19 and Future Public Health Crises
Authors: Rosa William E. , Gray Tamryn F. , Chow Kimberly , Davidson Patricia M. , Dionne-Odom J. Nicholas , Karanja Viola , Khanyola Judy , Kpoeh Julius D. N. , Lusaka Joseph , Matula Samuel T. , Mazanec Polly , Moreland Patricia J. , Pandey Shila , de Campos Amisha Parekh , Meghani Salimah H.
Published: June 2020

With the daily number of confirmed COVID-19 cases and associated deaths rising exponentially, social fabrics on a global scale are being worn by panic, uncertainty, fear, and other consequences of the health care crisis. Comprising more than half of the global health care workforce and the highest proportion of direct patient care time than any other health professional, nurses are at the forefront of this crisis. Throughout the evolving COVID-19 pandemic, palliative nurses will increasingly exercise their expertise in symptom management, ethics, communication, and end-of-life care, among other crucial skills. The literature addressing the palliative care response to COVID-19 has surged, and yet, there is a critical gap regarding the unique contributions of palliative nurses and their essential role in mitigating the sequelae of this crisis. Thus, the primary aim herein is to provide recommendations for palliative nurses and other health care stakeholders to ensure their optimal value is realized and to promote their well-being and resilience during COVID-19 and, by extension, in anticipation of future public health crises.
Comparing the Efficacy of Resuscitation Educational Modalities
Authors: Walker Mandi D. , Nuxoll Bridget , Niner Sherle , Hagan Thomas L.
Published: June 2020

This study evaluated the efficacy of online versus instructor-led advanced cardiac life support for first-time registered nurse participants. Participants were randomized into online or instructor-led courses, with learning outcomes measured in the cognitive, psychomotor, and affective domains. The instructor-led group showed statistically significant better performance during simulated megacode. Further analysis identified key areas where instructor-led participants out-performed the online group, enabling educators to articulate risk and benefit of the two learning modalities.
Nursing Students' Mindsets and Choice of Learning Strategies
Authors: Williams Cheryl
Published: June 2020

Background

Nursing students may not use the most effective learning strategies. Offering students an academic success model such as Dweck's mindset model may improve student learning. The influence of nursing students' mindsets on study strategies has not been explored.

Purpose

This study examined nursing students' mindset proclivity and choice of learning strategies.

Methods

This descriptive, cross-sectional quantitative pilot study used a web-based survey to examine a national sample of 151 nursing students' mindsets and learning habits.

Results

Students with a growth mindset demonstrated the use of more effective learning strategies than their fixed mindset peers.

Conclusions

Nurse educators need to assess student learning because half of the students in this study had never had anyone teach them how to learn effectively. Early evidence is emerging that the growth mindset model may hold promise as an academic success model for nursing education.
Joining Datasets Without Identifiers: Probabilistic Linkage of Virtual Pediatric Systems and PEDSnet*
Authors: Dziorny Adam C. , Lindell Robert B. , Bennett Tellen D. , Bailey L. Charles
Published: June 2020

Objectives:

To 1) probabilistically link two important pediatric data sources, Virtual Pediatric Systems and PEDSnet, 2) evaluate linkage accuracy overall and in patients with severe sepsis or septic shock, and 3) identify variables important to linkage accuracy.

Design:

Retrospective linkage of prospectively collected datasets from Virtual Pediatrics Systems, Inc (Los Angeles, CA) and the PEDSnet consortium.

Setting:

Single-center academic PICU.

Patients:

All PICU encounters between January 1, 2012, and December 31, 2017, that were deterministically matched between the two datasets.

Interventions:

None.

Measurements and Main Results:

We abstracted records from Virtual Pediatric Systems and PEDSnet corresponding to PICU encounters and probabilistically linked using 44 features shared by the two datasets. We generated a gold standard deterministic linkage using protected health information elements, which were then removed from datasets. We then calculated candidate pair log-likelihood ratios for all pairs of subjects and selected optimal pairs in a two-stage algorithm. A total of 22,051 gold standard PICU encounter pairs were identified over the study period. The optimal linkage model demonstrated excellent discrimination (area under the receiver operating characteristic curve > 0.99); 19,801 cases (89.9%) were matched with 13 false positives. The addition of two protected health information dates (admission month, birth day-of-year) increased to 20,189 (91.6%) the cases matched, with three false positives. Restricting to patients with Virtual Pediatric Systems diagnosis of severe sepsis or septic shock (n = 1,340 [6.1%]) matched 1,250 cases (93.2%) with zero false positives. Increased number of laboratory values present in the first 12 hours of admission significantly increased log-likelihood ratios, suggesting stronger candidate pair matching.

Conclusions:

We demonstrated the use of probabilistic linkage to accurately join two complementary pediatric critical care datasets at a single academic PICU in the absence of protected health information. Combining datasets with curated diagnoses and granular measurements can validate patient acuity metrics and facilitate multicenter machine learning algorithms. We anticipate these methods will generalize to other common PICU diagnoses.
Predictors of Long-term Outcomes in Patients With Connective Tissue Disease Associated With Pulmonary Arterial Hypertension
Authors: Nakayama Kazuhiko , Nakajima Yasuo , Tanaka Rika , Hirata Ken-ichi , Emoto Noriaki
Published: June 2020

Background/Objective

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance that can lead to right-sided heart failure. Connective tissue disease–associated PAH (CTD-PAH) often has poorer outcomes than idiopathic or hereditary PAH, suggesting the presence of non-PAH factors that could affect the prognoses. This cohort study aimed to identify prognostic factors for CTD-PAH management.

Methods

Medical records from April 1999 to November 2014 were reviewed to determine the time from treatment initiation to the occurrence of a clinically worsening event and the time elapsed until death. Data at baseline and the final assessment were used to identify prognostic factors associated with events using univariate and multivariate analyses by the stepwise Cox regression method.

Results

In 36 patients with CTD-PAH analyzed, the proportions with no clinically worsening events at 1, 2, and 3 years after treatment initiation were 62%, 52%, and 45%, respectively, with survival rates of 88%, 77%, and 77%, respectively. The regression model showed that reduced hemoglobin at baseline, reduced qR pattern in electrocardiogram lead V1, increased 60-minute erythrocyte sedimentation rate, and increased mean pulmonary arterial pressure at the final assessment were risk factors that were significantly associated with clinical worsening. For survival, no prognostic factor was identifiable.

Conclusions

Hemodynamic and non-PAH factors, such as anemia, nutritional status, and inflammatory activity of the underlying CTD, which are not listed in the risk assessment table of PAH guidelines, should be strictly controlled to improve the prognosis of patients with CTD-PAH. A more multifactorial treatment strategy should be developed.
COVID-19 and Its Potential Effect on Patients With Rheumatic Diseases in Latin America
Authors: Elera-Fitzcarrald Claudia , Ugarte-Gil Manuel F. , Alarcón Graciela S.
Published: June 2020

The COVID-19 (coronavirus disease 2019) pandemic has dramatically affected the entire world. Because of significant disparity levels in Latin American countries with deficient health care access and significant poverty, their population may end up among the most severely impacted. Patients with chronic conditions such as rheumatic diseases are quite vulnerable because of their high flaring risks and subsequent poor outcomes. Additionally, an overuse of antimalarials for the treatment of COVID-19 could lead to shortages in our region. Telemedicine, personal protective equipment use by patients and providers, web conferences, and comprehensive care are tools that will contribute to reduce the risk of infections and other complications in rheumatic disease patients, as well as to improve the knowledge and experience of rheumatologists at a global level.
A Systematic Review of Minimally Invasive Trans-thoracic Liver Resection to Examine Intervention Description, Governance, and Outcome Reporting of an Innovative Technique
Authors: Pathak Samir , Main Barry G. , Blencowe Natalie S. , Rees Jonathan R. E. , Robertson Harry F. , Abbadi Reyad A. G. , Blazeby Jane M.
Published: June 2020

Introduction:

The number of laparoscopic liver resections undertaken has increased. However, lesions located postero-superiorly are difficult to access. This may be overcome by the novel use of trans-thoracic port(s). Methods for the safe and transparent introduction of new and modified surgical procedures are limited and a summary of these issues, for minimally invasive trans-thoracic liver resections (MITTLR), is lacking. This study aims to understand and summarize technique description, governance procedures, and reporting of outcomes for MITTLR.

Methods:

A systematic literature search to identify primary studies of all designs describing MITTLR was undertaken. How patients were selected for the new technique was examined. The technical components of MITTLR were identified and summarized to understand technique development over time. Governance arrangements (eg, Institutional Review Board approval) and steps taken to mitigate harm were recorded. Finally, specific outcomes reported across studies were documented.

Results:

Of 2067 screened articles, 16 were included reporting data from 145 patients and 6 countries. Selection criteria for patients was explicitly stated in 2 papers. No studies fully described the technique. Five papers reported ethical approval and 3 gave details of patient consent. No study reported on steps taken to mitigate harm.

Technical outcomes were commonly reported, for example, blood loss (15/16 studies), operative time (15/16), and margin status (11/16). Information on patient-reported outcomes and costs were lacking.

Conclusions:

Technical details and governance procedures were poorly described. Outcomes focussed on short term details alone. Transparency is needed for reporting the introduction of new surgical techniques to allow their safe dissemination.
LekCheck: A Prospective Study to Identify Perioperative Modifiable Risk Factors for Anastomotic Leakage in Colorectal Surgery
Authors: Huisman Daitlin E. , Reudink Muriël , van Rooijen Stefanus J. , Bootsma Boukje T. , van de Brug Tim , Stens Jurre , Bleeker Wim , Stassen Laurents P. S. , Jongen Audrey , Feo Carlo V. , Targa Simone , Komen Niels , Kroon Hidde M. , Sammour Tarik , Lagae Emmanuel A. G. L. , Talsma Aalbert K. , Wegdam Johannes A. , de Vries Reilingh Tammo S. , van Wely Bob , van Hoogstraten Marie J. , Sonneveld Dirk J. A. , Veltkamp Sanne C. , Verdaasdonk Emiel G. G. , Roumen Rudi M. H. , Slooter Gerrit D. , Daams Freek
Published: June 2020

Objective:

To assess potentially modifiable perioperative risk factors for anastomotic leakage in adult patients undergoing colorectal surgery.

Summary Background Data:

Colorectal anastomotic leakage (CAL) is the single most important denominator of postoperative outcome after colorectal surgery. To lower the risk of CAL, the current research focused on the association of potentially modifiable risk factors, both surgical and anesthesiological.

Methods:

A consecutive series of adult patients undergoing colorectal surgery with primary anastomosis was enrolled from January 2016 to December 2018. Fourteen hospitals in Europe and Australia prospectively collected perioperative data by carrying out the LekCheck, a short checklist carried out in the operating theater as a time-out procedure just prior to the creation of the anastomosis to check perioperative values on 1) general condition 2) local perfusion and oxygenation, 3) contamination, and 4) surgery related factors. Univariate and multivariate logistic regression analysis were performed to identify perioperative potentially modifiable risk factors for CAL.

Results:

There were 1562 patients included in this study. CAL was reported in 132 (8.5%) patients. Low preoperative hemoglobin (OR 5.40, P < 0.001), contamination of the operative field (OR 2.98, P < 0.001), hyperglycemia (OR 2.80, P = 0.003), duration of surgery of more than 3 hours (OR 1.86, P = 0.010), administration of vasopressors (OR 1.80, P = 0.010), inadequate timing of preoperative antibiotic prophylaxis (OR 1.62, P = 0.047), and application of epidural analgesia (OR, 1.81, P = 0. 014) were all associated with CAL.

Conclusions:

This study identified 7 perioperative potentially modifiable risk factors for CAL. The results enable the development of a multimodal and multidisciplinary strategy to create an optimal perioperative condition to finally lower CAL rates.
Development and Evaluation of a Novel Instrument to Measure Severity of Intraoperative Events Using Video Data
Authors: Jung James J. , Jüni Peter , Gee Denise W. , Zak Yulia , Cheverie Joslin , Yoo Jin S. , Morton John M. , Grantcharov Teodor
Published: June 2020

Objective:

To develop and evaluate a novel instrument to measure SEVERE processes using video data.

Background:

Surgical video data can serve an important role in understanding the relationship between intraoperative events and postoperative outcomes. However, a standard tool to measure severity of intraoperative events is not yet available.

Methods:

Items to be included in the instrument were identified through literature and video reviews. A committee of experts guided item reduction, including pilot tests and revisions, and determined weighted scores. Content validity was evaluated using a validated sensibility questionnaire. Inter-rater reliability was assessed by calculating intraclass correlation coefficient. Construct validity was evaluated on a sample of 120 patients who underwent laparoscopic Roux-en-Y gastric bypass procedure, in which comprehensive video data was obtained.

Results:

SEVERE index measures severity of 5 event types using ordinal scales. Each intraoperative event is given a weighted score out of 10. Inter-rater reliability was excellent [0.87 (95%-confidence interval, 0.77–0.92)]. In a sample of consecutive 120 patients undergoing gastric bypass procedures, a median of 12 events [interquartile range (IQR) 9–18] occurred per patient and bleeding was the most frequent type (median 10, IQR 7–14). The median SEVERE score per case was 11.3 (IQR 8.3–16.9). In risk-adjusted multivariable regression models, history of previous abdominal surgery (P = 0.02) and body mass index (P = 0.005) were associated with SEVERE scores, demonstrating construct validity evidence.

Conclusion:

The SEVERE index may prove to be a useful instrument in identifying patients with high risk of developing postoperative complications.
Rayleigh–Taylor and Kelvin–Helmholtz instability studied in the frame of a dimension-reduced model
Authors: Bestehorn Michael
Published: June 2020

Introducing an extension of a recently derived dimension-reduced model for an infinitely deep inviscid and irrotational layer, a two-layer system is examined in the present paper. A second thin viscous layer is added on top of the original one-layer system. The set-up is a combination of a long-wave approximation (upper layer) and a deep-water approximation (lower layer). Linear stability analysis shows the emergency of Rayleigh–Taylor and Kelvin–Helmholtz instabilities. Finally, numerical solutions of the model reveal spatial and temporal pattern formation in the weakly nonlinear regime of both instabilities.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Sir George Gabriel Stokes in Skreen: how a childhood by the sea influenced a giant in fluid dynamics
Authors: Kearins Aoife
Published: June 2020

George Gabriel Stokes spent most of his life at the University of Cambridge, where he undertook his undergraduate degree and later became Lucasian Professor of Mathematics and Master of Pembroke College. However, he spent the first 13 years of his life in Skreen, County Sligo, Ireland, a rural area right by the coastline, overlooking the Atlantic Ocean. As this paper will discuss, the time he spent there was short but its influence on him and his research was long reaching, with his childhood activities of walking by and bathing in the sea being credited for first piquing Stokes' interest in ocean waves, which he would go on to write papers about. More generally, it marked the beginning of an interest in fluid dynamics and a curious nature regarding natural phenomena in his surroundings. Stokes held a special affinity for the ocean for the rest of his life, constantly drawing inspiration for it in his mathematical and physical studies and referencing it in his correspondences. This commentary was written to celebrate Stokes' 200th birthday as part of the theme issue of
Philosophical Transactions A
.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Stokes: Victorian Britain's most important religious scientist?
Authors: Mathieson Stuart
Published: June 2020

Sir George Gabriel Stokes is justly recognized for his substantial contributions to mathematics and physics, particularly optics and hydrodynamics. Yet Stokes also had a particularly noteworthy involvement in the religious life of Victorian Britain, and especially in the relationship between science and religion. As an outspoken evangelical, a prominent religious scientist, a lecturer on natural theology, and a lay writer on widely-debated theological topics such as eternal punishment, Stokes made contributions unsurpassed by any of his contemporaries. However, these have often been overlooked. This article redresses this situation, by explaining Stokes's religious life, his influence on debates over science and religion, his natural theology, and his promotion of the doctrine of conditional immortality.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Stokes layers in oscillatory flows of viscoelastic fluids
Authors: Ortín Jordi
Published: June 2020

Oscillatory flows of viscoelastic fluids are studied from the perspective of Stokes viscoelastic layers. We identify the governing dimensionless variables, and study the flows in a general way for fluids with linear rheology. Nonlinearities can be treated perturbatively to account for reported flow instabilities.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Sir George Gabriel Stokes, Bart (1819–1903): his impact on science and scientists
Authors: Ranford Paul
Published: June 2020

Lucasian Professor Sir George Gabriel Stokes was appointed joint-Secretary of the Royal Society in 1854, a post he held for the unprecedented period of 31 years, relinquishing the role when he succeeded T.H. Huxley as President in 1885. An eminent scientist of the Victorian era, Stokes explained fluorescence (he also coined the word) and his hydrodynamical formulae (the ‘Navier–Stokes equations’) remain ubiquitous today in the physics of any phenomenon involving fluid flows, from pipelines to glaciers to large-scale atmospheric perturbations. He also made seminal advances in optics and mathematics, and formulae that bear his name remain widely used today. The historiography however appears to understate Stokes's significant impact on science as unacknowledged collaborator on a wide range of scientific developments. His scientific peers regarded him as a mentor, advisor, designer of crucial experiments and, as editor of the Royal Society's scientific journals, arbiter of the standards of excellence in scientific communication to be attained before publication would be considered. Three brief case studies on Stokes's correspondence with Lord Kelvin, Sir William Crookes and the chemist Arthur Smithells exemplify how his impact was conveyed through the work of other scientists. This paper also begins consideration of why the character and worldview of Stokes led him to eschew personal reputation and profit for the sake of science and the Royal Society, and of how the development of the discipline of history of science has impacted on historiography relating to Stokes and others.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Stokes, Tyndall, Ruskin and the nineteenth-century beginnings of climate science
Authors: Cardoso Silvana S. S. , Cartwright Julyan H. E. , Huppert Herbert E.
Published: June 2020

Although we humans have known since the first smokey campfires of prehistory that our activities might alter our local surroundings, the nineteenth century saw the first indications that humankind might alter the global environment; what we currently know as anthropogenic climate change. We are now celebrating the bicentenaries of three figures with a hand in the birth of climate science. George Stokes, John Tyndall and John Ruskin were born in August 1819, August 1820 and February 1819, respectively. We look back from the perspective of two centuries following their births. We outline their contributions to climate science: understanding the equations of fluid motion and the recognition of the need to collect global weather data together with comprehending the role in regulating terrestrial temperature played by gases in the atmosphere. This knowledge was accompanied by fears of the Earth’s regression to another ice age, together with others that industrialization was ruining humankind’s health, morals and creativity. The former fears of global cooling were justified but seem strange now that the balance has tipped so far the other way towards global warming; the latter, on the other hand, today seem very prescient.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Heat Shock Protein 27 versus Estrogen Therapy for Post-Menopausal Atherosclerosis: Rethinking Mechanisms of Cholesterol Lowering
Authors: Maarouf Nadia , Chen Yong-Xiang , Shi Chunhua , Deng Jingti , Diao Catherine , Rosin Matthew , Shrivastava Vipul , Batulan Zarah , Liu Jingwen , O’Brien Edward R.
Published: June 2020

Aims

The estrogen-inducible protein Heat Shock Protein 27 (HSP27) as well as anti-HSP27 antibodies are elevated in healthy subjects compared to cardiovascular disease patients. Vaccination ofApoE-/-mice with recombinant HSP25 (rHSP25, the murine ortholog), boosts anti-HSP25 levels and attenuates atherogenesis. As estrogens promote HSP27 synthesis, cellular release and blood levels, we hypothesize that menopause will result in loss of HSP27 atheroprotection. Hence, we now compare the efficacy of rHSP25 vaccinationvs. estradiol (E2) therapy for the prevention of post-menopausal atherogenesis.

Methods and Results

ApoE-/-mice subjected to ovariectomy (OVX) showed a 65% increase atherosclerotic burden compared to sham mice after 5 weeks of a high fat diet. Relative to vaccination with rC1, a truncated HSP27 control peptide, atherogenesis was reduced by 5-weekly rHSP25 vaccinations (−43%), a subcutaneous E2 slow release pellet (−52%) or a combination thereof (−82%). Plasma cholesterol levels declined in parallel with the reductions in atherogenesis, but relative to rC1/OVX mice plasma PCSK9 levels were 52% higher in E2/OVX and 41% lower in rHSP25/OVX mice (p<0.0001 for both). Hepatic LDLR mRNA levels did not change with E2 treatment but increased markedly with rHSP25 vaccination. Conversely, hepatic PCSK9 mRNA increased 148% with E2 treatmentvs. rC1/OVX but did not change with rHSP25 vaccination. In human HepG2 hepatocytes E2 increased PCSK9 promoter activity 303%, while the combination of [rHSP27 + PAb] decreased PCSK9 promoter activity by 64%.

Conclusion

The reduction in post-OVX atherogenesis and cholesterol levels with rHSP25 vaccination is associated with increased LDLR but not PCSK9 expression. Surprisingly, E2 therapy attenuates atherogenesis and cholesterol levels post-OVX without altering LDLR but increases PCSK9 expression and promoter activity. This is the first documentation of increased PCSK9 expression with E2 therapy and raises questions about balancing physiological estrogenic / PCSK9 homeostasis and targeting PCSK9 in women – are there effects beyond cholesterol?
Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV
Authors: Mahé Dominique , Matusali Giulia , Deleage Claire , Alvarenga Raquel L. L. S. , Satie Anne-Pascale , Pagliuzza Amélie , Mathieu Romain , Lavoué Sylvain , Jégou Bernard , de França Luiz R. , Chomont Nicolas , Houzet Laurent , Rolland Antoine D. , Dejucq-Rainsford Nathalie
Published: June 2020

Viruses have colonized the germ line of our ancestors at several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few non-retroviruses. Among the recently emerged viruses infecting humans, several target the testis (eg HIV, Zika and Ebola viruses). Here we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCsin vitro. Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and SIV DNA were detected within a few TGCs in the testis from one infected patient, one rhesus macaque and one African Green monkeyin vivo. Molecular landscape analysis revealed that early TGCs were enriched in HIV early co-factors up to integration and had overall low antiviral defenses when compared with testicular macrophages and Sertoli cells. In conclusion, our study reveals that TGCs can support the entry and integration of HIV upon cell-associated infection. This could represent a way for this contemporary virus to integrate our germline and become endogenous in the future, as happened during human evolution for a number of viruses.

Importance

Viruses have colonized the host germ line at many occasions during evolution to eventually become endogenous. Here we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCsin vitro. Our results indicate that isolated primary TGCs express alternative HIV-1 receptors allowing virions binding but not entry. However, HIV-1 entered and integrated in TGCs upon cell-associated infection, and produced low level of viral proteins.In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication including integration, suggesting potential for endogenization in the future generations.
Case Study: Using Facebook Data to Monitor Adherence to Stay-at-home Orders in Colorado and Utah
Authors: Layer Ryan , Fosdick Baily , Bradshaw Michael , Larremore Dan , Doherty Paul
Published: June 2020

In the absence of effective treatments, social distancing has been the only public health measure available to combat the COVID-19 pandemic. In the US, implementing this response has been left to state, county, and city officials, and many localities have issued some form of a stay-at-home order. Without existing tools and with limited resources, localities struggled to understand how their orders changed behavior. In response, several technology companies opened access to their users’ location data. As part of the COVID-19 Data Mobility Network, we obtained access to Facebook User data and developed four key metrics and visualizations to monitor various aspects of adherence to stay at home orders. These metrics were carefully incorporated into static and interactive visualizations for dissemination to local officials.

All code is open source and freely available at https://github.com/ryanlayer/COvid19
Heart Disease Deaths during the Covid-19 Pandemic
Authors: Faust Jeremy S. , Lin Zhenqiu , Krumholz Harlan M.
Published: June 2020

The SARS-CoV-2 pandemic is associated with a reduction in hospitalization for an acute cardiovascular conditions. In a major health system in Massachusetts, there was a 43% reduction in these types of hospitalizations in March 2020 compared with March 2019.4 Whether mortality rates from heart disease have changed over this period is unknown.

We assembled information from the National Center for Health Statistics (Centers for Disease Control and Prevention) for 118,356,533 person-weeks from Week 1 (ending January 4) through Week 17 (ending April 25) of 2020 for the state of Massachusetts. We found that heart disease deaths are unchanged during the Covid-19 pandemic period as compared to the corresponding period of 2019. This is despite reports that admissions for acute myocardial infarction have fallen during this time.
COVID-19 and HIV co-infection: a living systematic evidence map of current research
Authors: Masukume Gwinyai , Mapanga Witness , van Zyl Doreen S
Published: June 2020

The world currently faces two ongoing devastating pandemics. These are the new severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 (SARS-CoV-2/COVID-19) and the prior human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) pandemics. The literature regarding the confluence of these global plagues expands at pace. A systematic search of the literature considering COVID-19 and HIV co-infection was performed.

After five months, from the beginning of the COVID-19 pandemic, there were at least thirty-five studies reported from thirteen countries. These ranged from individual case reports and series to cohort studies. Based on studies that could be extrapolated to the general population, co-infected individuals with suppressed HIV viral loads did not have disproportionate COVID-19 sickness and death. At least four patients, newly diagnosed with HIV recovered from COVID-19. Current evidence suggests that co-infected patients should be treated like the general population.

This ongoing living systematic evidence map of contemporary primary SARS-CoV-2 and HIV co-infection research provides a platform for researchers, policy makers, clinicians and others to more quickly discover and build relevant insights.
A rapid systematic review and case study on test, contact tracing, testing, and isolation policies for Covid-19 prevention and control
Authors: Chung Sheng-Chia , Marlow Sushila , Tobias Nicholas , Alogna Ivano , Alogna Alessio , You San-Lin
Published: June 2020

Objectives

To conduct a rapid review on the efficacy and policy of contact tracing, testing, and isolation (TTI) in Covid-19 prevention and control, including a case study for their delivery.

Method

Research articles and reviews on the use of contact tracing, testing, self-isolation and quarantine for Covid-19 management published in English within 1 year (2019 to 28th May, 2020) were eligible to the review. We searched MEDLINE (PubMed), Cochrane Library, SCOPUS and JSTOR with search terms included “contact tracing” or “testing” or “self-isolation” or “quarantine” in the title in combination with “Covid-19” or “COVID-19” or “coronavirus” in the title or abstract. Studies not associated with TTI or Covid-19 or being solely commentary were excluded. A narrative synthesis with a tabulation system was used to analyse studies for their diverse research designs, methods, and implications. Data for the case study were obtained from the Ministry of Health and Welfare and Centers for Disease Control Taiwan.

Results

Among the 160 initial publications, 48 eligible studies are included in the review. Included studies applied various designs: experiments, clinical studies, Government Documents, systematic reviews, observational studies, surveys, practice guidelines, technical reports. A case study on TTI delivery is summarised based on policy and procedures in Taiwan.

Conclusions

The information included in the review may inform the TTI program in the UK.
MCL1 dependence across MDS subtypes and dual inhibition of MCL1 and BCL2 in MISTRG6 mice
Authors: Fischer Melissa A. , Song Yuanbin , Gbyli Rana , Arrate Maria P. , Villaume Matthew T. , Childress Merrida A. , Smith Brianna N. , Stricker Thomas P. , Halene Stephanie , Savona Michael R.
Published: June 2020

Treatment for myelodysplastic syndromes (MDS) remains insufficient due to clonal heterogeneity and clinical complexity. Dysregulation of apoptosis is observed across MDS subtypes regardless of mutations and represents an attractive therapeutic opportunity. Venetoclax (VEN), a selective inhibitor of anti-apoptotic protein B-cell lymphoma-2 (BCL2), has yielded impressive responses in older patients with acute myeloid leukemia (AML). BCL2 family anti-apoptotic proteins BCL-XLand induced myeloid cell leukemia 1 (MCL1) are implicated in leukemia survival, and upregulation of MCL1 is seen in VEN-resistant AML and MDS. Here, we determined thein vitrosensitivity of MDS patient samples to selective inhibitors of BCL2, BCL-XLand MCL1. While VEN response positively correlated with increasing blast counts, all MDS subtypes responded to the MCL1 inhibitor, S63845. Treatment with combined VEN+S63845 was synergistic in all MDS subtypes and reduced MDS engraftment in MISTRG6 mice supporting the pursuit of clinical trials with combined BCL2+MCL1 inhibition in MDS.
How prior pair-bonding experience affects future bonding behavior in monogamous prairie voles
Authors: Harbert Kelsey J. , Pellegrini Matteo , Gordon Katelyn M. , Donaldson Zoe R.
Published: June 2020

Monogamous prairie voles (Microtus ochrogaster) form mating-based pair bonds. Although wild prairie voles rarely re-pair following loss of a partner, laboratory studies have shown that previous pairing and mating does not negate the ability to form a new partner preference. However, little is known about how prior bond experience may alter the trajectory and display of a new pair bond. In the present study, we disrupted an initial pair bond by separating partners and then varied the amount of time before a new partner was introduced. We assessed how separation time affected the stability of partner preference over time and influenced decision-making in male voles performing a head-to-head partner preference test in which they chose between the first and second partner. We found that the ability to consistently display a preference for the second partner, supplanting the initial pair bond, depended on how long the test animal was separated from their first partner. Prior bonding experience also shaped the subsequent effects of mating on partner preference. Partner preference strength was sensitive to latency to mate with the second partner but not the first partner, irrespective of separation time. These results suggest that the ability to form a consistent, strong preference for a new partner after an initial pair bond depends upon the amount of time that has passed since separation from the first partner. These results provide valuable insight into how social bonds are dynamically shaped by prior social experience and identify variables that contribute to recovery from partner loss and the ability to form a new pair bond.
Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis
Authors: Garzón-Tituaña Marcela , Sierra-Monzón José L , Comas Laura , Santiago Llipsy , Khaliulina-Ushakova Tatiana , Uranga-Murillo Iratxe , Ramirez-Labrada Ariel , Tapia Elena , Morte-Romea Elena , Algarate Sonia , Couty Ludovic , Camerer Eric , Bird Phillip I , Seral Cristina , Luque Pilar , Paño-Pardo José R , Galvez Eva M , Pardo Julián , Arias Maykel
Published: June 2020

Sepsis is a serious syndrome characterised by a dysregulated systemic inflammatory response. Here we have analysed the role and the therapeutic potential of Granzyme A (GzmA) in the pathogenesis of peritoneal sepsis using the Cecal Ligation and Puncture (CLP) polymicrobial sepsis model and samples from humans undergoing abdominal sepsis.

Elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen indicating that GzmA has no role in bacterial control. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα.

Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis, and suggest that it could be targeted for treatment of this severe pathology.
Explicit integration of dispersal-related metrics improves predictions of SDM in predatory arthropods
Authors: Jérémy Monsimet , Olivier Devineau , Julien Pétillon , Denis Lafage
Published: June 2020

Fishing spiders (Dolomedes spp.) make an interesting model to predict the impact of global changes because they are generalist, opportunistic predators, whose distribution is driven mostly by abiotic factors. Yet, the two European species are expected to react differently to forthcoming environmental changes, because of habitat specialization and initial range. We used an original combination of habitat and dispersal data to revisit these predictions under various climatic scenarios. We used the future range of suitable habitat, predicted with habitat variables only, as a base layer to further predict the range or reachable habitat by accounting for both dispersal ability and landscape connectivity. Our results confirm the northward shift in range and indicate that the area of co-occurrences should also increase. However, reachable habitat should expand less than suitable habitat, especially when accounting for landscape connectivity. In addition, the potential range expansion was further limited for the red-listedD. plantarius, which is more habitat-specialist and has a lower ability to disperse. This study highlights the importance of looking beyond habitat variables to produce more accurate predictions for the future of arthropods populations.
Local sleep during mind-wandering enhances processes of spatial attention allocation
Authors: Wienke Christian , Bartsch Mandy V. , Vogelgesang Lena , Reichert Christoph , Hinrichs Hermann , Heinze Hans-Jochen , Dürschmid Stefan
Published: June 2020

Mind wandering (MW) is a subjective, cognitive phenomenon, in which thoughts move away from the task towards an internal train of thoughts, possibly during phases of neuronal sleep-like activity (local sleep, LS). MW decreases cortical processing of external stimuli and is assumed to decouple attention from the external world. Here, we directly tested how indicators of LS, cortical processing and attentional selection change in a pop-out visual search task during phases of MW. Participants brain activity was recorded using magnetoencephalography, MW was assessed via self-report using randomly interspersed probes. As expected, MW worsened performance being accompanied by a decrease in high frequency activity (HFA, 80-150Hz) and an increase in slow wave activity (SWA, 1-6Hz), consistent with the occurrence of LS. In contrast, visual attentional selection as indexed by the N2pc component was enhanced during MW with the N2pc amplitude being directly linked to participants’ performance. This observation clearly contradicts accounts of attentional decoupling predicting a decrease in attention-related responses to external stimuli during MW. Together our results suggest that MW occurs during phases of LS with processes of attentional target selection being upregulated, potentially to compensate for the mental distraction during MW.
Diacylglycerol kinase ζ deficiency triggers early signs of aplastic anemia in mice
Authors: Martín-Salgado M , Andrada E , Liébana R , López-Santalla M Mercedes , Merida I
Published: June 2020

Acquired aplastic anemia (AA) is a rare blood disorder that results from immune-mediated destruction of bone marrow (BM) progenitor cells. Improved understanding of the mechanisms that favor T cell attack in BM could help to improve early diagnosis and disease treatment. Diacylglycerol kinase ζ (DGKζ) limits T cell responses through phosphorylation of diacylglycerol into phosphatidic acid. This reaction attenuates diacylglycerol-dependent activation of the Ras/ERK/CD69 and PKCθ/NFκB pathways in response to antigen. Here we show that, in contrast to the lack of basal activation observed in peripheral lymphoid organs, DGKζ-/-mice showed increased numbers of activated T cells in BM, together with a significant increase in IFNγ as well as perforin and granzyme B and C levels. The enhanced presence of T cells in DGKζ-/-mouse BM correlates with reduced BM cellularity, impaired hematopoiesis, and lower frequency of circulating red cells, granulocytes, and platelets. Our studies coincide with the recent characterization of lower DGKζ expression in T cells isolated from the BM of patients with acquired AA, and suggest that limited DGKζ expression and/or functions predispose to T cell-mediated BM destruction. This study identifies the BM as a niche particularly sensitive to DGKζ deficiency and indicates that this mouse model could be of interest for studying the mechanism that contributes to AA development.

Key points

DGKζ-deficiency in mice results in larger numbers of CD69-positive T cells in bone marrow, with enhanced expression of IFNγ and lytic enzymes.

DGKζ loss recapitulates many clinical aspects of human aplastic anemia, identifying a critical hub for immune system-dependent bone marrow failure.

Visual abstract