bluuebunny/crossref_metadata_2025 huggingface dataset:
Very long-chain saturated fatty acids and diabetes and cardiovascular disease
Authors: Lemaitre Rozenn N. , King Irena B.
Published: December 2021

Purpose of review

In contrast to other saturated fatty acids, very long-chain saturated fatty acids (VLSFAs) have received limited attention The purpose of this review is to summarize the associations of VLSFAs, including arachidic acid, behenic acid, and lignoceric acid, with cardiovascular disease outcomes and type 2 diabetes; to discuss the findings implications; and to call for future studies of the VLSFAs.

Recent findings

Increased levels of circulating VLSFAs have been found associated with lower risks of incident heart failure, atrial fibrillation, coronary heart disease, mortality, sudden cardiac arrest, type 2 diabetes, and with better aging. The VLSFA associations are paralleled by associations of plasma ceramide and sphingomyelin species carrying a VLSFA with lower risks of heart failure, atrial fibrillation, and mortality, suggesting VLSFAs affect the biological activity of ceramides and sphingomyelins thereby impacting health. For diabetes, there is no such parallel and the associations of VLSFAs with diabetes may be confounded or mediated by triglyceride and circulating palmitic acid, possible biomarkers of de novo lipogenesis.

In many ways, the epidemiology has preceded our knowledge of VLSFAs biology. We hope this review will spur interest from the research community in further studying these potentially beneficial fatty acids.
Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula
Authors: Björmsjö Maria , Hernell Olle , Lönnerdal Bo , Berglund Staffan K.
Published: December 2021

Objectives:

Compared to formula‐fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti‐infective and anti‐inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.

Methods:

In a double‐blind controlled trial, term formula‐fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low‐iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low‐iron formula with no added lactoferrin (Lf−; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.

Results:

No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF‐β)1, TGF‐β2, tumor necrosis factor alfa (TNF‐α) or interleukin2 (IL‐2) at 4, 6, or 12 months, except of higher TGF‐β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.

Conclusions:

Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well‐nourished and healthy population.
Confronting the Workforce Tsunami
Authors: Boston-Fleischhauer Carol
Published: December 2021

The sobering facts are clear: hospitals and health systems are facing a severe nursing shortage, with safe inpatient staffing approaching near-crisis levels. Safely staffing inpatient care is challenging. Stopping the exodus of nurses from acute care must be prioritized by the entire C-suite, with the chief nurse executive at the center of all decisions. Beyond aggressive retention strategies, different in-kind solutions to address the practice environment are nonnegotiable and help address nursing concerns about continued hospital employment.
Beyond the Pandemic
Authors: Kapu April
Published: December 2021

This month's column highlights health system priorities for advanced practice leaders and advanced practice infrastructure and support.
Fellow Designations of Interest to Nurse Leaders
Authors: Herrin-Griffith Donna , Waxman KT
Published: December 2021

Achieving fellow designation is commonly a career goal for nurse leaders. The path to achievement can be confusing, and once a goal is set, choosing the right designation is important. This column outlines the background of fellow designation, clarifies differences between fellow designation and other career advancement options, and presents ideas for consideration by nurse leaders as they pursue career advancement through fellow designation.
Establishment of Nurse Manager Leadership Competencies to Support Clinicians in Evidence-Based Practice
Authors: Caramanica Laura , Gallagher-Ford Lynn , Idelman Lynda , Mindrila Diana , Richter Sally , Thomas Bindu Koshy
Published: December 2021

OBJECTIVE

This 2-part study was conducted to validate nurse manager (NM) leadership competencies that support clinicians in using evidence-based practice (EBP).

BACKGROUND

Numerous studies validate the critical need for NM support among clinicians seeking to engage in EBP.

METHODS

In phase 1, a Delphi study was conducted to establish the validity of a set of NM leadership competencies that support EBP. In phase 2, descriptive analyses, tests of significance, and reliability coefficients were used to assess reliability.

RESULTS

An expert panel achieved consensus on a set of 22 NM leadership competencies that constitute effective support for EBP. Further quantitative analyses demonstrated excellent levels of internal consistency and overall consistent outcomes across time.

CONCLUSION

A valid set of 22 NM leadership competencies with evidence of reliability that successfully support clinicians to engage in EBP in clinical settings was established.
Comparison of the Clinicopathologic Features and T-Cell Infiltration of B7-H3 and B7-H4 Expression in Triple-negative Breast Cancer Subtypes
Authors: Kim Nah Ihm , Park Min Ho , Cho NamKi , Lee Ji Shin
Published: December 2021

Previously we revealed an upregulated expression of B7-H3 and B7-H4 mRNA and protein in breast cancer, including triple-negative breast cancer (TNBC). However, little is known regarding the clinical impact and value of B7-H3 and B7-H4 in TNBC subtypes. Thus, this study evaluated the clinicopathologic effects of B7-H3 and B7-H4 mRNA and protein expression according to the TNBC subtypes. RNAscope in situ hybridization and immunohistochemistry of B7-H3 and B7-H4 was done for 186 TNBC samples using tissue microarray. Immunohistochemistry was also performed for TNBC molecular subtype-surrogate markers, CD3, and CD8. TNBCs were classified into basal-like (BL) (64.5%), luminal androgen receptor (10.8%), and unclassifiable (24.7%) subtypes. Tumor B7-H4 mRNA expression was associated with younger age at the initial diagnosis and with molecular TNBC subtypes. Expression of B7-H3 mRNA and protein in the tumor cells was negatively correlated with CD3+ and CD8+ T-cell infiltration density in the tumor and/or stromal region of TNBCs and their subtypes. High stromal B7-H3 mRNA expression was associated with poor disease-free and overall survival in the TNBCs and with overall survival in the unclassifiable subtype. Stromal B7-H3 mRNA expression was independently associated with overall survival and disease-free survival in the TNBCs and BL subtype, respectively. Our results indicate the importance of the stromal expression of B7-H3 mRNA as a prognostic factor in the TNBCs and BL subtype. The inverse relationship between B7-H3 expression and CD3+ and CD8+ T-lymphocyte infiltration represents a promising target for immunotherapy for the TNBCs, especially the BL subtype.
Quality Improvement Initiative to Improve Hand Hygiene Compliance in Indian Special Newborn Care Unit
Authors: Rai Reena , Sethi Amanpreet , Kaur Amarpreet , Kaur Gurmeet , Vardhan Gupta Harsh , Kaur Sumandeep , Singh Parihar Man , Paul Singh Satwinder
Published: December 2021

Introduction:

Pilot data on Hand hygiene (HH) compliance using a standard World Health Organisation checklist for 1-week suggested only 20% compliance. So, we planned a Quality Improvement study to improve HH compliance among health care providers in our Special Newborn Care Unit from 20% to 60% over 12 months.

Methods:

We did this study in 3 phases: Baseline phase (2 months), Intervention phase (8 months), and Postintervention phase (2 months). A multidisciplinary Quality Improvement team composed of doctors, nursing staff, and ward attendants was constituted. The team analyzed potential barriers to HH by Fishbone analysis. Three trained observers randomly selected two target Special Newborn Care Unit patients daily and collected data on HH compliance unobtrusively during the three 8-h shifts over 24 h. In addition, we tested a range of interventions using multiple Plan Do Study Act cycles: Staff education; Displaying posters; Round the clock availability of soap and hand rub; Staff felicitation; Group performance feedback. We also collected data on healthcare-associated infections in all three phases.

Results:

The total observations for HH during the baseline, intervention, and postintervention phase were 1488, 5808, and 1464, respectively. The HH compliance improved from 27.2% to 57.1% in the postintervention phase. There was no difference in the healthcare-associated infections among the three phases.

Conclusions:

The HH compliance rates improved significantly but not to the desired extent. So, we planned to increase our workforce, and improve our training program and infrastructure.
A Quality Improvement Approach to Early Patient Discharge
Authors: Stansbury Nicholas , Marlow Taylor Richard , Wueste Beth
Published: December 2021

Introduction:

Lack of bed availability is a common problem in our pediatric unit, as in many hospitals. To address this issue, we instituted a quality improvement (QI) initiative involving collaborative nurse–physician rounding. This intervention has been shown to expedite discharge, improve patient care, and increase bed availability in other settings.

Methods:

By utilizing PDCA (Plan, Do, Check, Act) processes, we created two improvement initiatives, “Increasing Patient Discharge Before 12 pm” and “Midnight Rounds with Discharge Focus.” Senior resident and faculty physicians rounded on discharge-ready patients before teaching rounds, and by 10 am, placed discharge orders to allow for a 12 pm discharge. A night team consisting of senior residents and nurses conducted “Midnight Rounds” and identified potential discharges for the morning team. The project aimed to increase patient discharges before 12 pm from a June–November 2018 baseline of 15%–20% by June 2019.

Results:

Patient discharge percentage before 12 pm increased from 15% to 21% (P < 0.01) by June 2019, and as a result, bed availability increased by 16% (P < 0.01).

Conclusions:

QI methodology clarified the root causes of limited bed availability. Understanding the existing discharge process allowed for QI initiatives to develop a consistent and sustainable discharge process. Patient discharge percentages before 12 pm increased by 40%, and bed availability increased by 16% after QI implementations.
Increasing Adherence to Acute Otitis Media Treatment Duration Guidelines using a Quality Improvement Approach
Authors: Uhl Bethany D. , Boutzoukas Angelique , Gallup Nathaniel , Patrick Michael , Stultz Jerry , Porter Courtney , Watson Joshua R.
Published: December 2021

Introduction:

This quality improvement initiative aimed to improve American Academy of Pediatrics acute otitis media (AOM) guideline adherence in pediatric urgent care sites by increasing the percentage of patients 2 years and older with AOM who received a short duration (7 days or fewer) of antibiotics from a baseline of 7% to a goal of 50%.

Methods:

This quality improvement initiative was conducted in a network of seven urgent care sites affiliated with a large academic children’s hospital. The interventions focused on clinician and family education, clinical decision support, and a discharge template that defaulted to a 7-day duration of antibiotics for patients 2 years and older diagnosed with AOM. The outcome measure was the percentage of patients receiving 7 days or fewer of antibiotics. The process measure was the percentage of prescriptions originating from the new discharge template. A repeat visit for AOM within 30 days from the initial visit was the balancing measure.

Results:

The percentage of patients diagnosed with AOM receiving a short antibiotic course increased from a baseline of 7% to a new centerline mean of 67%, which exceeded the goal. This project resulted in 10,138 antibiotic days being avoided. Eighty-two percent of short-course prescriptions originated from the discharge template. Repeat visits for AOM within 1 month of the initial visit did not increase.

Conclusions:

A quality improvement initiative combining education and clinical decision support improved adherence to AOM treatment duration guidelines and avoided unnecessary antibiotic exposure in a pediatric urgent care network without increasing treatment failures.
Clinical Specialty Setting as Determinant of Management of Psoriatic Arthritis
Authors: da Silva Souza Cacilda , Goldenstein-Schainberg Cláudia , Alvarenga Anti Loduca Lima Sonia Maria , Spelling Gormezano Natali , Ferreira Magalhães Renata , Ranza Roberto
Published: December 2021

Objective

The aim of this study was to examine the effect of clinical specialty setting on the management of psoriatic arthritis (PsA) as well as disease activity/burden in Brazil.

Methods

This study is a post hoc analysis of the Brazilian population in a cross-sectional, observational study conducted in 17 countries. Patients were 18 years or older with suspected or confirmed PsA attending routine visits at participating sites. Primary end points were time from symptom onset to PsA diagnosis, from diagnosis to first conventional systemic disease-modifying antirheumatic drug (DMARD) or first biologic DMARD, and from first conventional systemic DMARD to first biologic DMARD. Potential associations were assessed using the Student t test or the Mann-Whitney U nonparametric test. Normality was tested using the Shapiro-Wilk and Kolmogorov-Smirnov tests. For qualitative variables, the χ2 test was adopted.

Results

Patients (n = 130) visited dermatology (n = 75) or rheumatology (n = 55) sites. All primary end points were similar between the 2 settings; however, dermatology patients had significantly greater enthesitis counts (2.1 vs 0.6; p = 0.002), absenteeism at work (Work Productivity and Activity Impairment, 19.7% vs 5.2%; p = 0.03), and pain (Health Assessment Questionnaire–Disability Index pain scale, 1.39 vs 1.01; p = 0.032), as well as worse quality of life related to psoriasis (Dermatology Life Quality Index total score, 8.5 vs 5.0; p = 0.019) and mental health (12-item Short-Form Health Survey, version 2.0 subscale, 42.4 vs 47.4; p = 0.029).

Conclusions

In Brazil, PsA disease burden and disease activity were influenced by clinical specialty. Irrespective of setting, patients experienced a delay in being diagnosed with PsA, reinforcing the need for collaborative management of PsA by rheumatologists and dermatologists for better outcomes in these patients.
Comparison Between Radial Forearm Free Flap and Pectora is Major Myocutaneous Flap for Reconstruction in Oral Cavity Cancer Patients: Assessment of the Quality of Life
Authors: Zhang Cheng-Feng , Liu Xiang-Jun , Liu Dong-Wei , Zhang Xu
Published: December 2021

We aimed to evaluate the quality of life of Chinese patients after immediate reconstruction surgery on individuals with oral cavity cancer. In addition, we compared the differences between radial forearm free flap and pectoralis major myocuta- neous flap. Using the University of Washington quality of life v4 questionnaire, 1:1 matched research was performed on patients received PMM or RFF flap. Chi-square test was used to analyze the variables. One hundred twenty four of 179 questionnaires were returned (69.3%). Age, N stage, and postoperative radiotherapy were similar for both groups. However, there were significant differences between two groups in gender, T stage, operation duration, and complication rate. Oral cavity cancer patients reconstructed with radial forearm free flap had better shoulder and speech functions but worse appearance domains. The results of our research provide important information for patients and physicians during their discussion of treatment programs for oral cavity cancers.
Heparin Binding Protein for the Early Diagnosis and Prognosis of Sepsis in the Emergency Department: The Prompt Multicenter Study
Authors: Katsaros Konstantinos , Renieris Georgios , Safarika Asimina , Adami Evangelia-Maria , Gkavogianni Theologia , Giannikopoulos George , Solomonidi Nicky , Halvatzis Stamatios , Koutelidakis Ioannis M. , Tsokos Nikolaos , Tritzali Maroula , Koutoukas Pantelis , Avgoustou Cristina , Vasishta Anil , Giamarellos-Bourboulis Evangelos J.
Published: December 2021

Background:

The validation of new biomarkers for the diagnosis and risk stratification of patients with sepsis at an early point is essential for successful treatment. Recent publications prompted us to investigate of heparin binding protein (HBP) for the emergency department (ED) admissions.

Materials and Methods:

In this multicenter, cross-sectional study, HBP and procalcitonin (PCT) were measured within the first hour upon admission to the ED in plasma samples of 371 patients with signs of infection. Patients were classified into non-sepsis and sepsis by the Sepsis-3 definitions and were followed up for outcome.

Results:

HBP was significantly higher in patients with sepsis and was positively correlated to PCT and C-reactive protein, absolute neutrophil and monocyte counts, creatinine, bilirubin and lactate. Sensitivity, specificity, positive predictive value, and negative predictive value of HBP more than 19.8 ng/mL for the diagnosis of sepsis was 66.3%, 44.9%, 49.3%, and 62.2%, respectively; and for prediction of early death was 100%, 41.0%, 4.5%, and 100%, respectively. Single HBP and PCT could not predict 28-day mortality; this was performed with sensitivity, specificity, positive predictive value, and negative predictive value 44.8%, 81.8%, 17.3%, and 94.6% when used in combination.

Conclusion:

Admission HBP can be used as a tool for the early diagnosis of sepsis and for the risk of early death in the ED.
NRF2 Inhibits Cardiomyocyte Pyroptosis Via Regulating CTRP1 in Sepsis-Induced Myocardial Injury
Authors: Teng Yan , Li Ningjun , Wang Yi , Sun Shuling , Hou Junxia , Chen Yahui , Pan Haiyan
Published: December 2021

C1q/tumor necrosis factor-related protein 1 (CTRP1) has been demonstrated as a crucial regulator in myocardial injury (MI). The present study aims to evaluate the mechanism of CTRP1 in sepsis-induced MI. The septic mouse model was established via cecal ligation and puncture and the in vitro cell model was established via lipopolysaccharide treatment. The mouse survival rate within 96 h was recorded. Morphologic changes of cardiomyocytes were observed and cell viability and cardiac functions were detected. CTRP1 and nuclear factor erythroid 2-related factor (Nrf2) expressions, creatine troponin-T, and creatine phosphokinase isoenzyme levels, and expressions of pyroptotic markers were determined. The binding relationship between Nrf2 and the CTRP1 promotor was predicted and verified. Rescue experiments were designed to confirm the role of CTRP1. CTRP1 was poorly expressed in septic mice. CTRP1 overexpression inhibited cardiomyocyte pyroptosis and improved cardiac functions, MI, and survival rate in septic mice. Nrf2was decreased in cecal ligation and puncture -treated mice. Nrf2 overexpression promoted CTRP1 expression via binding to the CTRP1 promotor and suppressed cardiomyocyte pyroptosis. CTRP1 downregulation abolished the inhibitory effect of Nrf2 overexpression on cardiomyocyte pyroptosis. Overall, Nrf2 promoted CTRP1 expression via binding to the CTRP1 promotor to inhibit cardiomyocyte pyroptosis, thereby alleviating MI in septic mice.
Patient and Clinician Perceptions of Informed Consent and Decision Making About Accepting KDPI > 85 Kidneys
Authors: Schantz Karolina , Gordon Elisa J. , Lee Unsun , Rocha Maria , Friedewald John , Ladner Daniela P. , Becker Yolanda , Formica Richard , Reese Peter P. , Kaufman Dixon , Barah Masoud , Walker Marissa , Mehrotra Om , Viveros Dania , Mehrotra Sanjay
Published: December 2021

Background.

Although the impact of the kidney donor profile index (KDPI) on kidney discard is well researched, less is known about how patients make decisions about whether to give consent for KDPI > 85 kidney offers.

Methods.

We conducted in-depth, semistructured interviews with 16 transplant recipients, 15 transplant candidates, and 23 clinicians (transplant surgeons, nephrologists, and nurse coordinators) to assess and compare perceptions of transplant education, informed consent for KDPI > 85 kidneys‚ and the decision-making process for accepting kidney offers. Thematic analysis was used to analyze qualitative data.

Results.

Four themes emerged: (1) patients reported uncertainty about the meaning of KDPI or could not recall information about KDPI; (2) patients reported uncertainty about their KDPI > 85 consent status and a limited role in KDPI > 85 consent decision making; (3) patients’ reported willingness to consider KDPI > 85 kidneys depended on their age, health status, and experiences with dialysis, and thus it changed over time; (4) patients’ underestimated the survival benefit of transplantation compared with dialysis, which could affect their KDPI > 85 consent decision making.

Conclusions.

To better support patients’ informed decision making about accepting KDPI > 85 kidneys, centers must ensure that all patients receive education about the trade-offs between accepting a KDPI > 85 kidney and remaining on dialysis. Additionally, education about KDPI and discussions about informed consent for KDPI > 85 kidneys must be repeated at multiple time points while patients are on the waiting list.
Antidepressant efficacy is correlated with plasma levels: mega-analysis and further evidence
Authors: Cellini Lorenzo , De Donatis Domenico , Zernig Gerald , De Ronchi Diana , Giupponi Giancarlo , Serretti Alessandro , Xenia Hart , Conca Andreas , Florio Vincenzo
Published: December 2021

The debate around optimal target dose for first-line antidepressants (ADs) is still ongoing. Along this line, therapeutic drug monitoring (TDM) represents one of the most promising tools to improve clinical outcome. Nevertheless, a few data exist regarding the concentration-effect relationship of first-line ADs which limits TDM implementation in routine clinical practice. We conducted the first patient-level concentration-response mega-analysis including data acquired by us previously and explored the concentration dependency of first-line AD (206 subjects). Further, new data on mirtazapine are reported (18 subjects). Hamilton Depression Rating Scale-21 administered at baseline, at month 1 and month 3 was used as the measure of efficacy to assess antidepressant response (AR). When pooling all four first-line ADs together, normalized plasma levels and AR significantly fit a bell-shaped quadratic function with a progressive increase of AR up to around the upper normalized limit of the therapeutic reference range with a decrease of AR at higher serum levels. Our results complement the available evidence on the issue and the recent insights gained from dose-response studies. A concentration-dependent clinical efficacy, such as previously demonstrated for tricyclic compounds, also emerge for first-line ADs. Our study supports a role for TDM as a tool to optimize AD treatment to obtain maximum benefit.
Deciphering early-warning signals of SARS-CoV-2 elimination and resurgence from limited data at multiple scales
Authors: Parag Kris V. , Cowling Benjamin J. , Donnelly Christl A.
Published: December 2021

Inferring the transmission potential of an infectious disease during low-incidence periods following epidemic waves is crucial for preparedness. In such periods, scarce data may hinder existing inference methods, blurring early-warning signals essential for discriminating between the likelihoods of resurgence versus elimination. Advanced insight into whether elevating caseloads (requiring swift community-wide interventions) or local elimination (allowing controls to be relaxed or refocussed on case-importation) might occur can separate decisive from ineffective policy. By generalizing and fusing recent approaches, we propose a novel early-warning framework that maximizes the information extracted from low-incidence data to robustly infer the chances of sustained local transmission or elimination in real time, at any scale of investigation (assuming sufficiently good surveillance). Applying this framework, we decipher hidden disease-transmission signals in prolonged low-incidence COVID-19 data from New Zealand, Hong Kong and Victoria, Australia. We uncover how timely interventions associate with averting resurgent waves, support official elimination declarations and evidence the effectiveness of the rapid, adaptive COVID-19 responses employed in these regions.
Realistic computer modelling of stent retriever thrombectomy: a hybrid finite-element analysis-smoothed particle hydrodynamics model
Authors: Mousavi J. S. S. Mostafa , Faghihi Danial , Sommer Kelsey , Bhurwani Mohammad M. S. , Patel Tatsat R. , Santo Briana , Waqas Muhammad , Ionita Ciprian , Levy Elad I. , Siddiqui Adnan H. , Tutino Vincent M.
Published: December 2021

Stent retriever thrombectomy is a pre-eminent treatment modality for large vessel ischaemic stroke. Simulation of thrombectomy could help understand stent and clot mechanics in failed cases and provide a digital testbed for the development of new, safer devices. Here, we present a novel,in silicothrombectomy method using a hybrid finite-element analysis (FEA) and smoothed particle hydrodynamics (SPH). Inspired by its biological structure and components, the blood clot was modelled with the hybrid FEA–SPH method. The Solitaire self-expanding stent was parametrically reconstructed from micro-CT imaging and was modelled as three-dimensional finite beam elements. Our simulation encompassed all steps of mechanical thrombectomy, including stent packaging, delivery and self-expansion into the clot, and clot extraction. To test the feasibility of our method, we simulated clot extraction in simple straight vessels. This was compared againstin vitrothrombectomies using the same stent, vessel geometry, and clot size and composition. Comparisons with benchtop tests indicated that our model was able to accurately simulate clot deflection and penetration of stent wires into the clot, the relative movement of the clot and stent during extraction, and clot fragmentation/embolus formation. In this study, we demonstrated that coupling FEA and SPH techniques could realistically model stent retriever thrombectomy.
‘Your very obliging correspondence’: the Royal Society and the provincial Republic of Letters in Georgian Lincolnshire
Authors: Sims Liam
Published: December 2021

It has been said that the Royal Society of the eighteenth century was in decline. The ground-breaking experimentation of the Restoration period was long gone, to be followed by talk rather than action, and the pages of
Philosophical Transactions
were filled with papers by provincial clergymen on natural curiosities and antiquities. But the links between the Royal Society and the Spalding Gentlemen's Society (SGS)—founded in 1712 and still in existence as the country's longest-lived provincial learned society—show a connection not just between city and country, but between scientific and antiquarian research, fields that had not yet assumed their distinct modern forms. A fruitful correspondence existed between the two societies for several decades in the first half of the century, and a number of Fellows (including Newton) became honorary members of the SGS. In this article, I show that the SGS did not simply rely on its metropolitan connections for intellectual sustenance, but rather, that this joint association allowed it to flourish as a dynamic society that cultivated international networks.
A Carboniferous synapsid with caniniform teeth and a reappraisal of mandibular size-shape heterodonty in the origin of mammals
Authors: Huttenlocker Adam K. , Singh Suresh A. , Henrici Amy C. , Sumida Stuart S.
Published: December 2021

Heterodonty is a hallmark of early mammal evolution that originated among the non-mammalian therapsids by the Middle Permian. Nonetheless, the early evolution of heterodonty in basal synapsids is poorly understood, especially in the mandibular dentition. Here, we describe a new synapsid,Shashajaia bermanigen. et sp. nov., based on a well-preserved dentary and jaw fragments from the Carboniferous–Permian Halgaito Formation of southern Utah.Shashajaiashares with some sphenacodontids enlarged (canine-like) anterior dentary teeth, a dorsoventrally deep symphysis and low-crowned, subthecodont postcanines having festooned plicidentine. A phylogenetic analysis of 20 taxa and 154 characters placesShashajaianear the evolutionary divergence of Sphenacodontidae and Therapsida (Sphenacodontoidea). To investigate the ecomorphological context of Palaeozoic sphenacodontoid dentitions, we performed a principal component analysis based on two-dimensional geometric morphometrics of the mandibular dentition in 65 synapsids. Results emphasize the increasing terrestrialization of predator–prey interactions as a driver of synapsid heterodonty; enhanced raptorial biting (puncture/gripping) aided prey capture, but this behaviour was probably an evolutionary antecedent to more complex processing (shearing/tearing) of larger herbivore prey by the late Early to Middle Permian. The record ofShashajaiasupports the notion that the predatory feeding ecology of sphenacodontoids emerged in palaeotropical western Pangea by late Carboniferous times.
Travelling-wave analysis of a model of tumour invasion with degenerate, cross-dependent diffusion
Authors: Colson Chloé , Sánchez-Garduño Faustino , Byrne Helen M. , Maini Philip K. , Lorenzi Tommaso
Published: December 2021

In this paper, we carry out a travelling-wave analysis of a model of tumour invasion with degenerate, cross-dependent diffusion. We consider two types of invasive fronts of tumour tissue into extracellular matrix (ECM), which represents healthy tissue. These types differ according to whether the density of ECM far ahead of the wave front is maximal or not. In the former case, we use a shooting argument to prove that there exists a unique travelling-wave solution for any positive propagation speed. In the latter case, we further develop this argument to prove that there exists a unique travelling-wave solution for any propagation speed greater than or equal to a strictly positive minimal wave speed. Using a combination of analytical and numerical results, we conjecture that the minimal wave speed depends monotonically on the degradation rate of ECM by tumour cells and the ECM density far ahead of the front.
Area, isolation and climate explain the diversity of mammals on islands worldwide
Authors: Barreto Elisa , Rangel Thiago F. , Pellissier Loïc , Graham Catherine H.
Published: December 2021

Insular biodiversity is expected to be regulated differently than continental biota, but their determinants remain to be quantified at a global scale. We evaluated the importance of physical, environmental and historical factors on mammal richness and endemism across 5592 islands worldwide. We fitted generalized linear and mixed models to accommodate variation among biogeographic realms and performed analyses separately for bats and non-volants. Richness on islands ranged from one to 234 species, with up to 177 single island endemics. Diversity patterns were most consistently influenced by the islands’ physical characteristics. Area positively affected mammal diversity, in particular the number of non-volant endemics. Island isolation, both current and past, was associated with lower richness but greater endemism. Flight capacity modified the relative importance of past versus current isolation, with bats responding more strongly to current and non-volant mammals to past isolation. Biodiversity relationships with environmental factors were idiosyncratic, with a tendency for greater effects sizes with endemism than richness. The historical climatic change was positively associated with endemism. In line with theory, we found that area and isolation were among the strongest drivers of mammalian biodiversity. Our results support the importance of past conditions on current patterns, particularly of non-volant species.
Complex axial growth patterns in an early Cambrian trilobite from South Australia
Authors: Holmes James D. , Paterson John R. , García-Bellido Diego C.
Published: December 2021

The exceptional fossil record of trilobites provides our best window on developmental processes in early euarthropods, but data on growth dynamics are limited. Here, we analyse post-embryonic axial growth in the Cambrian trilobite
Estaingia bilobata
from the Emu Bay Shale, South Australia. Using threshold models, we show that abrupt changes in growth trajectories of different body sections occurred in two phases, closely associated with the anamorphic/epimorphic and meraspid/holaspid transitions. These changes are similar to the progression to sexual maturity seen in certain extant euarthropods and suggest that the onset of maturity coincided with the commencement of the holaspid period. We also conduct hypothesis testing to reveal the likely controls of observed axial growth gradients and suggest that size may better explain growth patterns than moult stage. The two phases of allometric change in
E. bilobata
, as well as probable differing growth regulation in the earliest post-embryonic stages, suggest that observed body segmentation patterns in this trilobite were the result of a complex series of changing growth controls that characterized different ontogenetic intervals. This indicates that trilobite development is more complex than previously thought, even in early members of the clade.
The ChpR transcriptional regulator of Sinorhizobium meliloti senses 3,5,6-trichloropyridinol, a degradation product of the organophosphate pesticide chlorpyrifos
Authors: McDonald Nathan D. , Love Courtney E. , Gibbons Henry S.
Published: December 2021

The global use of organophosphate insecticides (OPPs) and the growing concern of off-target side effects due to OPP exposure has prompted the need for sensitive and economical detection methods. Here we set out to engineer a previously identified OPP responsive transcription factor, ChpR, from Sinorhizobium melilotii to respond to alternative OPPs and generate a repertoire of whole-cell biosensors for OPPs. The ChpR transcription factor and cognate promoter P
chpA, have been shown to activate transcription in the presence of the OPP chlorpyrifos (CPF). Utilizing a GFP reporter regulated by ChpR in a whole-cell biosensor we found that the system responds significantly better to 3,5,6-trichloro-2-pyridinol (TCP), the main degradation product of CPF, compared to CPF itself. This biosensor was able to respond to TCP at 390 nM within 4 h compared to 50 µM of CPF in 7 h. The ChpR-P
chpA
, and the activating ligand TCP, were able to regulate expression of a kanamycin resistance/sucrose sensitivity (kan/sacB) selection/counterselection module suitable for high throughput mutagenesis screening studies. The ability to control both GFP and the kan/sacB module demonstrates the utility of this reporter for the detection of CPF affected areas. The ChpR-P
chpA
system serves as an additional positive regulator switch to add to the growing repertoire of controllers available within synthetic biology.
Investigation of the polyamine biosynthetic and transport capability of Streptococcus agalactiae: the non-essential PotABCD transporter
Authors: Khazaal Sarah , Al Safadi Rim , Osman Dani , Hiron Aurélia , Gilot Philippe
Published: December 2021

Polyamines constitute a group of organic polycations positively charged at physiological pH. They are involved in a large variety of biological processes, including the protection against physiological stress. In this study, we show that the genome of

Streptococcus agalactiae

, a commensal bacterium of the intestine and the vagina and one of the most common agents responsible of neonate infections, does not encode proteins homologous to the specific enzymes involved in the known polyamine synthetic pathways. This lack of biosynthetic capability was verified experimentally by TLC analysis of the intracellular content of

S. agalactiae

grown in the absence of polyamines. However, similar analyses showed that the polyamines spermidine, spermine and putrescine can be imported from the growth media into the bacteria. We found that all strains of

S. agalactiae

possess the genes encoding the polyamine ABC transporter PotABCD. We demonstrated that these genes form an operon with folK, a gene involved in folate biosynthesis, murB, a gene involved in peptidoglycan biosynthesis, and with clc, a gene encoding a Cl−/H+ antiporter involved in resistance to acid stress in

Escherichia coli

. Transcription of the potABCD operon is induced by peroxide-induced oxidative stress but not by acidic stress. Spermidine and spermine were found to be inducers of potABCD transcription at pH 7.4 whereas putrescine induces this expression only during peroxide-induced oxidative stress. Using a deletion mutant of potABCD, we were nevertheless unable to associate phenotypic traits to the PotABCD transporter, probably due to the existence of one or more as yet identified transporters with a redundant action.
The role of ecosystem engineers in shaping the diversity and function of arid soil bacterial communities
Authors: Baubin Capucine , Farrell Arielle M. , Šťovíček Adam , Ghazaryan Lusine , Giladi Itamar , Gillor Osnat
Published: December 2021

Ecosystem engineers (EEs) are present in every environment and are known to strongly influence ecological processes and thus shape the distribution of species and resources. In this study, we assessed the direct and indirect effect of two EEs (perennial shrubs and ant nests), individually and combined, on the composition and function of arid soil bacterial communities. To that end, top soil samples were collected in the Negev Desert Highlands during the dry season from four patch types: (1) barren soil; (2) under shrubs; (3) near ant nests; or (4) near ant nests situated under shrubs. The bacterial composition was evaluated in the soil samples (fourteen replicates per patch type) using 16S rRNA gene amplicon sequencing, together with physico-chemical measures of the soil, and the potential functions of the community. We have found that the EEs differently affected the community composition. Indeed, barren patches supported a soil microbiome, dominated byRubrobacterandProteobacteria, while in EE patches theDeinococcus-Thermusphylum was dominating. The presence of the EEs similarly enhanced the abundance of phototrophic, nitrogen cycle and stress- related genes. In addition, only when both EEs were combined, were the soil characteristics altered. Our results imply that arid landscapes foster unique communities selected by each EE(s), solo or in combination, yet these communities have similar potential biological traits to persist under the harsh arid conditions. Environments with multiple EEs are complicated to study due to the possibility of non-additive effects of EEs and thus further research should be done.

IMPORTANCE

Ecosystem engineers are organisms that can create, modify, or maintain their habitat. They are present in various environments but are particularly conspicuous in desert ecosystems, where their presence is tightly linked to vital resources like water or nutrients. Despite their key role in structuring and controlling desert ecosystems, joint engineering, and their effect on soil function, are unknown. Our study explores the contributions of key ecosystem engineers to the diversity and function of their soil microbiome allowing better understanding of their role in shaping habitats and engineering their activity
Stiffness of fluid and gel phase lipid nanovesicles: weighting the contributions of membrane bending modulus and luminal pressurization
Authors: Ridolfi Andrea , Caselli Lucrezia , Baldoni Matteo , Montis Costanza , Mercuri Francesco , Berti Debora , Valle Francesco , Brucale Marco
Published: December 2021

The mechanical properties of biogenic membranous compartments are thought to be relevant in numerous biological processes; however, their quantitative measurement remains challenging for most of the already available Force Spectroscopy (FS)-based techniques. In particular, the debate on the mechanics of lipid nanovesicles and on the interpretation of their mechanical response to an applied force is still open. This is mostly due to the current lack of a unified model being able to describe the mechanical response of gel and fluid phase lipid vesicles and to disentangle the contributions of membrane rigidity and luminal pressure. In this framework, we herein propose a simple model in which the contributions of membrane rigidity and luminal pressure to the overall vesicle stiffness are described as a series of springs; this approach allows estimating the two contributions for both gel and fluid phase liposomes. Atomic Force Microscopy-based FS (AFM-FS), performed on both vesicles and Supported Lipid Bilayers (SLBs), is exploited for obtaining all the parameters involved in the model. Moreover, the use of coarse-grained full-scale molecular dynamics simulations allowed for better understanding the differences in the mechanical responses of gel and fluid phase bilayers and supported the experimental findings. Results suggest that the pressure contribution is similar among all the probed vesicle types; however, it plays a dominant role in the mechanical response of lipid nanovesicles presenting a fluid phase membrane, while its contribution becomes comparable to the one of membrane rigidity in nanovesicles with a gel phase lipid membrane. The herein presented results offer a simple way to quantify two of the most important parameters in vesicular nanomechanics, and as such represent a first step towards a currently unavailable, unified model for the mechanical response of gel and fluid phase lipid nanovesicles.
Safety and immunogenicity of a heterologous booster of protein subunit vaccine MVC-COV1901 after two doses of adenoviral vector vaccine AZD1222
Authors: Cheng Shu-Hsing , Lin Yi-Chun , Chen Cheng-Pin , Cheng Chien-Yu
Published: December 2021

We report the interim safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 or 24 weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers were 14- and 8.6-fold increased, respectively, when compared to the titer levels on the day of the booster dose. We also observed 5.2- and 5.6-fold increases in neutralizing titer levels against wildtype and Omicron variant pseudovirus after the booster dose, respectively. These interim results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222.
MULTITRAIT ANALYSIS EXPANDS GENETIC RISK FACTORS IN CARDIOEMBOLIC STROKE
Authors: Cárcel-Márquez Jara , Muiño Elena , Gallego-Fabrega Cristina , Cullell Natalia , Lledós Miquel , Llucià-Carol Laia , Sobrino Tomás , Campos Francisco , Castillo José , Freijo Marimar , Arenillas Juan Francisco , Obach Victor , Álvarez-Sabín José , Molina Carlos A. , Ribó Marc , Jiménez-Conde Jordi , Roquer Jaume , Muñoz-Narbona Lucia , Lopez-Cancio Elena , Millán Mònica , Diaz-Navarro Rosa , Vives-Bauza Cristòfol , Serrano-Heras Gemma , Segura Tomás , Ibañez Laura , Heitsch Laura , Delgado Pilar , Dhar Rajat , Krupinski Jerzy , Delgado-Mederos Raquel , Prats-Sánchez Luis , Camps-Renom Pol , Blay Natalia , Sumoy Lauro , de Cid Rafael , Montaner Joan , Cruchaga Carlos , Lee Jin-Moo , Martí-Fàbregas Joan , Férnandez-Cadenas Israel
Published: December 2021

Background and Purpose

The genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data.

Methods

For the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS).

Results

MTAG-CES analysis revealed 40 novel and significant loci (p-value<5×10−8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-value<0.05 in the CES vs controls independent analysis. KIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses.

Conclusions

We found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.