bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical treatment of vulvodynia, dyspareunia and pudendal neuralgia: A single clinic audit of amitriptyline and oestriol in organogel
Authors: Ruoss Chantelle M. , Howard Elizabeth A. , Chan Karen , Stevenson Paul G. , Vancaillie Thierry
Published: January 2021

Background

Vulvodynia and pudendal neuralgia comprise significant contributors to vulvar‐related pain and its impact on daily life.

Aim

A retrospective clinical audit was conducted at the Women’s Health & Research Institute of Australia, Sydney, to determine the pattern of use and the efficacy of the application of topical amitriptyline 0.5% plus oestriol 0.03% in organogel (AOO), to the vulvar vestibule in reducing the impact of pain on daily life.

Materials and Methods

There were 1174 patients who received a script from May 2017 until February 2020: 1054 patients agreed to be contacted and had a valid email address.

Results

There were 376 (35.7%) patients who replied. Pain with intercourse was the main indication for use. Treatment was rated effective by 51.2% (95% CI: 35.4–66.8%) of patients less than 30 years of age, 66.7% (95% CI: 57.3–74.9%) of patients 30–50 years of age, and 58.3% (95% CI: 50.9–65.4%) in patients over 50. Stinging at the site of application was the most commonly reported side effect.

Conclusion

Topical AOO is an effective and well‐tolerated treatment for vulvar pain.
Contemporary training methods in regional anaesthesia: fundamentals and innovations
Authors: Ramlogan R. R. , Chuan A. , Mariano E. R.
Published: January 2021

Over the past two decades, regional anaesthesia and medical education as a whole have undergone a renaissance. Significant changes in our teaching methods and clinical practice have been influenced by improvements in our theoretical understanding as well as by technological innovations. More recently, there has been a focus on using foundational education principles to teach regional anaesthesia, and the evidence on how to best teach and assess trainees is growing. This narrative review will discuss fundamentals and innovations in regional anaesthesia training. We present the fundamentals in regional anaesthesia training, specifically the current state of simulation‐based education, deliberate practice and curriculum design based on competency‐based progression. Moving into the future, we present the latest innovations in web‐based learning, emerging technologies for teaching and assessment and new developments in alternate reality learning systems.
Defining success in regional anaesthesia
Authors: Johnston D. F. , Turbitt L. R.
Published: January 2021

Utilisation of regional anaesthesia is increasing globally; however, it remains challenging to determine the overall benefit of individual regional anaesthesia procedures. Like any peri‐operative intervention, the benefit to the patient and healthcare system must outweigh any patient risk or resource implications. This review aims to identify markers of success in regional anaesthesia, categorise these into an objective framework and rationalise suggestions on how measuring outcomes in regional anaesthesia can be used to develop the widespread performance of this evolving subspecialty. This framework of measuring success of regional anaesthesia contains four pillars: patient‐centred, population‐centred, healthcare‐centred and training‐centred outcomes. Each pillar of success contains several outcomes which provide a structure for the measurement and development of regional anaesthesia success on a global scale.
A pilot study on the use of prednisolone‐encapsulated liposomes for the treatment of moderate‐to‐severe Graves’ orbitopathy with reduced systemic steroid exposure
Authors: Detiger Sanne E. , Kremer Tessa M. , A.S.H. Dalm Virgil , de Keizer Ronald O.B. , Wubbels Rene J. , Metselaar J.M. , van Hagen P. Martin , Peeters Robin P. , Paridaens Dion
Published: January 2021

Purpose

To demonstrate that long‐circulating PEGylated liposomal prednisolone is a safe and effective therapy in patients with active moderate‐to‐severe Graves’ orbitopathy.

Methods

Open‐label, proof‐of‐concept, multicentre pilot study. Ten patients with moderate‐to‐severe Graves’s orbitopathy, who were euthyroid for at least three months. Long‐circulating PEGylated liposomal prednisolone 150 mg was administered intravenously twice, with 2‐week interval. Total follow‐up was 12 months, with visits at baseline, week 2, 6, 13, 26 and 52. Physical, laboratory and ophthalmological examinations were performed. Response to treatment was defined as a reduction in Clinical Activity Score by ≥2 points; palpebral aperture by ≥3 mm; soft tissue signs by ≥2 grades; exophthalmos by ≥2 mm; and motility by >8 degrees or improvement in diplopia score. A response was sustained when equally observed at weeks 6 and 13.

Results

One patient achieved a sustained response according to the predetermined definition. All patients showed a decrease in Clinical Activity Score after one infusion, with a mean decrease of two points. The Clinical Activity Score was ≤1 at week 52 for all patients. Improvement was also observed in the soft tissue signs. Most of the adverse events were mild and of a transient nature. Two patients required further treatment with intravenous methylprednisolone.

Conclusion

This pilot study showed a positive effect of long‐circulating PEGylated liposomal prednisolone on the Clinical Activity Score in patients with moderate‐to‐severe Graves’s orbitopathy, resulting in fewer hospital visits and possibly less glucocorticoid‐related side‐effects.
Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)
Authors: Lim Seng Gee , Phyo Wah Wah , Ling Joanna Zhi Jie , Cloherty Gavin , Butler Emily K. , Kuhns Mary C. , McNamara Anne L. , Holzmayer Vera , Gersch Jeffrey , Yang Wei Lyn , Ngu Jing Hieng , Chang Jason , Tan Jessica , Ahmed Taufique , Dan Yock Young , Lee Yin Mei , Lee Guan Huei , Tan Poh Seng , Huang Daniel Q. , Khine Htet Toe Wai , Lee Chris , Tay Amy , Chan Edwin
Published: January 2021

Background

Biomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core‐related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy.

Aim(s)

Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss.

Methods

CHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg‐negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR).

Results

HBsAg loss occurred in 15/114(13%) HBeAg‐negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound.

Conclusions

On‐treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.
Developing patient resources to enable the exchange of healthy lifestyle information between clinicians and families of children with complex heart problems
Authors: Saxena Shikha , Vo Jennifer , Millage Jamie , Wong Derek , Bélanger Priscilla , Fournier Amelie , Bodiam Lorene , Allison Archie , Longmuir Patricia E.
Published: January 2021

Background

Healthy active lifestyles are critically important for children with complex heart problems (CHP) that affect heart structure, rhythm or function. They are at increased risk for morbidities such as atherosclerosis, obesity, anxiety and depression. Educating children with CHP and their families about the relevance of healthy lifestyles is an important part of clinical care.

Design

This study used a collaborative approach among six patients/family members and 22 health professionals to develop a series of knowledge‐to‐action tools suitable for counselling children with CHP and their families about their healthy lifestyle needs.

Methods

After development of the knowledge‐to‐action tools had been completed, one cardiologist and one research assistant implemented one or more of these new resources during each clinic visit as appropriate for each patient. Thirty‐nine parents and eight children completed post‐clinic interviews to explore their perceptions of the new resources. The nine resources developed included brochures and websites addressing physical activity with a heart condition, body contact restrictions, exercise test results, emotional health, finding community resources, encouragement for asking healthy lifestyle questions and a brief, in‐clinic healthy lifestyle assessment.

Results

Families found the resources useful and helpful for clarifying their specific concerns. They also provided suggestions to improve the content and delivery of the resources so that they would be suitable for a variety of settings—schools, community and sports.

Conclusion

Future research is required to evaluate the effectiveness of these resources for raising awareness and knowledge about healthy active lifestyles among children with CHP and the impact of these resources for changing healthy lifestyle behaviours.
Human liver model systems in a dish
Authors: Thompson Wendy L. , Takebe Takanori
Published: January 2021

The human adult liver has a multi‐cellular structure consisting of large lobes subdivided into lobules containing portal triads and hepatic cords lined by specialized blood vessels. Vital hepatic functions include filtering blood, metabolizing drugs, and production of bile and blood plasma proteins like albumin, among many other functions, which are generally dependent on the location or zone in which the hepatocyte resides in the liver. Due to the liver's intricate structure, there are many challenges to design differentiation protocols to generate more mature functional hepatocytes from human stem cells and maintain the long‐term viability and functionality of primary hepatocytes. To this end, recent advancements in three‐dimensional (3D) stem cell culture have accelerated the generation of a human miniature liver system, also known as liver organoids, with polarized epithelial cells, supportive cell types and extra‐cellular matrix deposition by translating knowledge gained in studies of animal organogenesis and regeneration. To facilitate the efforts to study human development and disease using in vitro hepatic models, a thorough understanding of state‐of‐art protocols and underlying rationales is essential. Here, we review rapidly evolving 3D liver models, mainly focusing on organoid models differentiated from human cells.
Obesity of politicians and corruption in Ukraine in 2000–2020– Reply
Authors: Blavatskyy Pavlo R.
Published: January 2021

We collected 469 frontal face images of Ukrainian cabinet ministers who were in office in 2000–2020. For each image, the minister's body mass index was estimated using a computer vision algorithm. The time series of median estimated body mass index of cabinet ministers co‐moves over time with two existing measures of corruption – World Bank worldwide governance indicator Control of Corruption, and the discrepancy between the quantity of luxury wristwatches exported from Switzerland to Ukraine (reported by Swiss statistics) and the corresponding quantity imported by Ukraine from Switzerland (reported by Ukrainian statistics).
The youth online training and employment system: Study protocol for a randomized controlled trial of an online vocational intervention for young people with mental ill health
Authors: Simmons Magenta B. , Nicholas Jennifer , Chinnery Gina , O'Sullivan Shaunagh , D'Alfonso Simon , Bendall Sarah , Cagliarini Daniela , Hamilton Matthew , Gleeson John , Killackey Eóin , Alvarez‐Jimenez Mario
Published: January 2021

Aim

People diagnosed with mental disorders experience higher rates of unemployment than those without. Career adaptability, defined as the ability to respond flexibly and make informed career decisions in work and throughout career transitions, is becoming increasingly important as the nature of work changes rapidly. Early vocational intervention may ameliorate poor education and employment outcomes experienced by young people with mental ill‐health and promote transferable skills and adaptability. Online‐based career support allows for ongoing access throughout different career stages. The current study combines mental health‐informed digital career and peer motivation, to create a Youth Online Training and Employment System (YOTES) that supports young people with mental ill‐health obtain and remain in education or employment.

Methods

This study is an unblinded randomized controlled trial for young people with mental ill‐health, aged 16–25, who are seeking vocational support. Participants will be randomized to receive either YOTES, a moderated, online intervention with vocational, social, and peer motivation, or a control intervention, the headspace Digital Work and Study Service. Both groups will have access to in‐person career support if seeking employment. The primary outcome will be career adaptability compared between the YOTES and control groups at 6‐months post baseline. Secondary outcomes include number of hours worked in the past 7 days, hope, career confidence, psychological distress and health economic outcomes at 6‐ and 12‐months post baseline.

Conclusion

Results will demonstrate whether an online career intervention moderated by career practitioners with peer motivation can result in improved career adaptability in young people with mental ill‐health.
Boldness and exploration vary between shell morphs but not environmental contexts in the snail Cepaea nemoralis
Authors: Dahirel Maxime , Gaudu Valentin , Ansart Armelle
Published: January 2021

Understanding the maintenance of among‐individual behavioral variation in populations and predicting its consequences are key challenges in behavioral ecology. Studying the association between repeatable behaviors and other traits under selection may shed light on the underlying selective pressures. We used the model snail Cepaea nemoralis to examine whether individual behavior is associated with shell morph, a key trait that has been extensively studied in the context of thermal tolerance and predator avoidance, and which is known to be under strict genetic control in this species. We quantified proxies of boldness and exploration in snails of three morphs coming from two habitats with different thermal contexts. We show that both behaviors were repeatable at the among‐individual level (within‐state Rboldness = 0.22 [95% credible interval: 0.15; 0.29]; Rexploration = 0.20 [0.15; 0.25]). Behavior was associated with shell morph, with the darker morph (five‐banded) being consistently shyer and slower to explore. There was no evidence that thermal environment of origin influenced behavior. Snails became faster when test temperature increased; we found no evidence morphs differed in their thermal response. Boldness and exploration were correlated among individuals, forming a syndrome (r = 0.28 [0.10; 0.46]). The link we find between morph and boldness is compatible with visual selection by avian predators, assuming a positive association between boldness and morphological defense (phenotypic compensation hypothesis). The fact morph‐behaviors associations are consistent across environments, despite selection on morph, hint to a possible underlying genetic origin. Finally, we discuss how our findings combined with decades of evolutionary research make C. nemoralis a very valuable model to study the evolution of behavior in response to environmental changes.
The Quilombola Movement: Sensing Futures in Afroindigenous Amazonia
Authors: Arregui Aníbal G.
Published: January 2021

The “quilombola movement” is a political current that supports the legal emancipation and territorial autonomy of the descendants of runaway African slaves, called quilombolas in Brazil. As an alternative ethnographic approach, this essay accompanies Amazonian quilombolas through their “movement” in a literal‐kinematic sense of the word, and as their characteristic ways of moving are “sensed” and imagined to exist in the future. Local body techniques and their related kinesthetic sensations have an important role in scaffolding present practices and in orienting subjects in unfolding ecological and economic events. Drawing on an ethnography of daily practices—hunting, horticulture, fishing, and leisure—this essay shifts the focus from ethnohistoric representations towards an embodied account of quilombola collective identification, political struggles, and projects. In dialogue with cultural phenomenology and the broadening field of the anthropology of time, this analytical avenue seeks to show how corporeal ethnographies may be reframed as future‐oriented forms of inquiry.
A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin's possible mode of action against SARS‐CoV‐2
Authors: Kinobe Robert T. , Owens Leigh
Published: January 2021

Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS‐CoV‐2 regarding efficacy, mechanisms and selective toxicity. The SARS‐CoV‐2 genome was mined to determine potential nuclear location signals for ivermectin and meta‐analyses forin vivostudies included all comparators over time, dose range and viral replication in multiple organs. Ivermectin inhibited the replication of many viruses including those inFlaviviridae,CircoviridaeandCoronaviridaefamiliesin vitro. Real and mock nuclear location signals were identified in SARS‐CoV‐2, a potential target for ivermectin and predicting a sequestration bait for importin β, stopping infected cells from reaching a virus‐resistant state. While pharmacokinetic evaluations indicate that ivermectin could be toxic if applied based onin vitrostudies, inhibition of viral replicationin vivowas shown for Porcine circovirus in piglets and Suid herpesvirus in mice. Overall standardized mean differences and 95% confidence intervals for ivermectin versus controls were −4.43 (−5.81, −3.04),p < 0.00001. Based on current results, the potential for repurposing ivermectin as an antiviral agent is promising. However, further work is needed to reconcilein vitrostudies with clinical efficacy. Developing ivermectin as an additional antiviral agent should be pursued with an emphasis on pre‐clinical trials in validated models of infection.
Static strength of brittle materials under multiaxial nonuniform stress states: A novel statistical model for assessing size effects
Authors: Pagnoncelli Ana Paula , Tridello Andrea , Paolino Davide Salvatore
Published: January 2021

In this paper, a model for the assessment of size effects on quasi‐static strength of brittle materials subjected to applied load inducing a nonuniform stress distribution within the material volume is proposed. An equivalent stress computed through finite element analysis is introduced in the model to account for the effect of the stress gradient within the loaded volume. The defect size distribution is modelled, differently from the literature, with the largest extreme value distribution. The proposed model has been validated with datasets available in the literature and obtained through bending tests on concrete specimens. For each type of test, the model permits to properly assess size effects. Due to its general formulation, a model for the strength variation with respect to the loaded volume, regardless of the testing type, was also obtained, further proving its effectiveness.
Determination of Stress–Strain Behaviour of Magnesium Alloy AZ31 under Variable Thermomechanical Loading
Authors: Šeruga Domen , Bešter Tomaž , Nagode Marko , Klemenc Jernej
Published: January 2021

Growing environmental demands and higher fuel efficiency encourage the use of new light‐weight load‐bearing materials even for operation under rougher environmental conditions. Consequently, as the materials used in the vital load‐bearing components of the chassis, brake system or exhaust system are subjected to thermomechanical fatigue during the operation due to variable mechanical and thermal loads, it is crucial for design engineers and CAE analysts to understand the cyclic behaviour of new materials under such conditions. Here we have analysed the stress–strain behaviour of magnesium alloy AZ31 and the influence of variable thermomechanical loads. A uniaxially loaded flat specimen has been first mechanically loaded at −25°C. The temperature was then increased to 150°C whilst the variable mechanical loading remained unchanged. The tests have been strain‐controlled using a video extensometer. The stress–strain behaviour of the magnesium alloy AZ31 has been then investigated considering both variable temperature and variable mechanical load.
Review: Helicobacter pylori infection in children
Authors: Seo Ji‐Hyun , Bortolin Kristen , Jones Nicola L.
Published: January 2021

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy‐based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post‐eradication follow‐up, was supported by the current literature.
Humorous or occasioned instructions: Learning the “shoulder check” in theoretical and practical driving lessons
Authors: Helmer Henrike
Published: January 2021

This study investigates how driving school instructors adapt their instructions to constraints and affordances of different activity types. Adopting a Conversation Analytic approach and building on a comparative corpus of theoretical and practical driving lessons in German, it compares sequences of instructions of the execution of the “shoulder check” (i.e., checking the blind spot) in stationary theoretical versus mobile practical driving lessons. In theoretical lessons, the instructor uses vivid and humorous embodied instructions. In practical driving lessons, the instructor orients to the complex multi‐activity and delivers instructions in a succinct manner, considering the students’ previous knowledge and the embeddedness into the global tasks. The paper shows how instructional practices are sensitive to contextual contingencies which they reflect and treat by their situated design.
Epistemics in post‐match interviews: A focus on questioning turn design
Authors: Wilton Antje
Published: January 2021

This contribution reports on a study of questioning turns in German and English football post‐match interviews (PMIs). Previous research on PMIs suggests that their main aim is to provide room for a delivery of the player's perspective of the match, thereby foregrounding his expertise and experience. The study uses a conversation analytic approach to focus on how interviewers design their turns in order to achieve this foregrounding. It is shown that participants employ means to systematically maintain an epistemic balance that reflects the player's epistemic access to the match as more authoritative. Furthermore, while both German and English interviewers perform similar actions in their turns, there are significant differences in the use of overtly marked questions, revealing different overall strategies of foregrounding.
International environmental agreements under an evolutionary mechanism of imitation and asymmetric countries
Authors: Chen Hsiao‐Chi , Chow Yunshyong , Liu Shi‐Miin
Published: January 2021

Under an often employed imitation mechanism, we investigate whether countries with different emission abatement benefits and costs can achieve an international environmental agreement. When the abatement efficiencies, ancillary benefits of abatement, and/or the numbers of countries are large, an international environmental agreement with full participation is the unique long‐run equilibrium. For the remaining situations, either no agreement is the unique equilibrium or both equilibria above can emerge with positive probability. These results hold whatever the function forms of countries' abatement costs are, whether the transboundary pollution of emissions is considered, and whether the mutation rates depend on abatement costs and time.
CBAC4C: conflict‐based VM isolation control for cloud computing
Authors: Dlamini M.T. , Eloff J.H.P. , Venter H.S. , Eloff M.M.
Published: January 2021

For businesses to benefit from the many opportunities of cloud computing, they must first address a number of security challenges, such as the potential leakage of confidential data to unintended third parties. An inter‐VM (where VM is virtual machine) attack, also known as cross‐VM attack, is one threat through which cloud‐hosted confidential data could be leaked to unintended third parties. An inter‐VM attack exploits vulnerabilities between co‐resident guest VMs that share the same cloud infrastructure. In an attempt to stop such an attack, this paper uses the principles of logical analysis to model a solution that provides physical separation of VMs belonging to conflicting tenants based on their levels of conflict. The derived mathematical model is founded on scientific principles and implemented using four conflict‐aware VM placement algorithms. The resultant algorithms consider a tenant's risk appetite and cost implications. The model offers guidance to VM placement and is validated using a proof of concept. A cloud simulation tool was used to test and evaluate the effectiveness and efficiency of the model. The findings reflect that the introduction of the proposed model introduced a time lag in the time it took to place VM instances. On top of this, it was also discovered that the number and size of the VM instances has an effect on the VM placement performance. The findings further illustrate that the conflict tolerance level of a VM has a direct impact on the time it took to place.
Flash sintering of yttria‐stabilized zirconia powders coated with nanoscale films of alumina by atomic layer deposition
Authors: O’Toole Rebecca J. , Yoon Bola , Gump Christopher J. , Raj Rishi , Weimer Alan W.
Published: January 2021

The addition of small quantities of aluminum oxide (Al2O3) to 8 mol% yttria‐stabilized zirconia (8YSZ) benefits conventional sintering by acting as a sintering aid and altering grain growth behavior. However, it is uncertain if these benefits observed during conventional sintering extend to flash sintering. In this work, nanoscale films of Al2O3 are deposited on 8YSZ powders by particle atomic layer deposition (ALD). The ALD‐coated powders were flash sintered using voltage‐to‐current control and current rate experiments. The sintering behavior, microstructural evolution, and ionic conductivities were characterized. The addition of Al2O3 films changed the conductivity of the starting powder, effectively moving the flash onset temperature. The grain size of the samples flashed with current rate experiments was ~65% smaller than that of conventionally sintered samples. Measurement of grain size and estimates of sample density as a function of temperature during flash sintering showed that small quantities of Al2O3 can enhance grain growth and sintering of 8YSZ. This suggests that Al2O3 dissolves into the 8YSZ grain boundaries during flash sintering to form complexions that enhance the diffusion of species controlling these processes.
The toughening of pyrochlore La2Zr2O7 by a ferroelastic NdAlO3 second phase for potential thermal barrier coating applications
Authors: Wang Yanfei , Han Jing , Du Jingping , Liu Rongjun , Wan Fan
Published: January 2021

The poor fracture toughness of La2Zr2O7 severely limits its application as a high temperature thermal barrier coating topcoat material. To toughen it, a ferroelastic second phase, NdAlO3, with a Curie temperature of 1367°C has been introduced to form x NdAlO3/(1‐x) La2Zr2O7 composite ceramics by a spark plasma sintering technique, where x = 10, 20, 30, 40, and 50 mol%. The fracture toughness of sintered composite ceramic compacts is measured at both room temperature and 1200°C, respectively, by a single‐edge‐notch beam test method. The results show that, at room temperature, the residual compressive stress in the La2Zr2O7 matrix plays an important role in the toughening of composite ceramics. By eliminating this factor, the remaining toughening effects agree with the measured fracture toughness at 1200°C, suggesting that the other toughening is probably ferroelastic domain switching toughening and that it is still valid at high temperature. Furthermore, the toughening effect arising from ferroelastic domain switching is governed by the overall domain switching zone, which is determined by both individual domain switching zone width and the “concentration” of ferroelastic phases. A relatively high coercive stress of NdAlO3 and relatively low residual tensile stress in NdAlO3 second phases contribute to negligible influence of residual tensile stress on domain switching zone width, leading to the continuous increase of fracture toughness of composite ceramics with more NdAlO3 added at room temperature.
Leadless pacemaker implant with concomitant atrioventricular node ablation: Experience with the Micra transcatheter pacemaker
Authors: El‐Chami Mikhael F. , Shinn Timothy , Bansal Sundeep , Martinez‐Sande Jose L. , Clementy Nicolas , Augostini Ralph , Ravindran Bipin , Sagi Venkata , Ramanna Hemanth , Garweg Christophe , Roberts Paul R. , Soejima Kyoko , Stromberg Kurt , Fagan Dedra H. , Zuniga Nicky , Piccini Jonathan P.
Published: January 2021

Background

The feasibility and outcomes of concomitant atrioventricular node ablation (AVNA) and leadless pacemaker implant are not well studied. We report outcomes in patients undergoing Micra implant with concomitant AVNA.

Methods

Patients undergoing AVNA at the time of Micra implant from the Micra Transcatheter Pacing (IDE) Study, Continued Access (CA) study, and Post‐Approval Registry (PAR) were included in the analysis and compared to Micra patients without AVNA. Baseline characteristics, acute and follow‐up outcomes, and electrical performance were compared between patients with and without AVNA during the follow‐up period.

Results

A total of 192 patients (mean age 77.4 ± 8.9 years, 72% female) underwent AVNA at the time of Micra implant and were followed for 20.4 ± 15.6 months. AVNA patients were older, more frequently female, and tended to have more co‐morbid conditions compared with non‐AVNA patients (N = 2616). Implant was successful in 191 of 192 patients (99.5%). The mean pacing threshold at implant was 0.58 ± 0.35 V and remained stable during follow‐up. Major complications within 30 days occurred more frequently in AVNA patients than non‐AVNA patients (7.3% vs. 2.0%, p < .001). The risk of major complications through 36‐months was higher in AVNA patients (hazard ratio: 3.81, 95% confidence interval: 2.33–6.23, p < .001). Intermittent loss of capture occurred in three AVNA patients (1.6%), all were within 30 days of implant and required system revision. There were no device macrodislodgements or unexpected device malfunctions.

Conclusion

Concomitant AVN ablation and leadless pacemaker implant is feasible. Pacing thresholds are stable over time. However, patient comorbidities and the risk of major complications are higher in patients undergoing AVNA.
Spatiotemporal differences in precordial electrocardiographic amplitude before and after flecainide provocation are associated with a history of unstable ventricular arrhythmia in Brugada syndrome
Authors: Chen Chun‐Chao , Chung Fa‐Po , Lin Yenn‐Jiang , Chang Shih‐Lin , Lo Li‐Wei , Hu Yu‐Feng , Tuan Ta‐Chuan , Chao Tze‐Fan , Liao Jo‐Nan , Lin Chin‐Yu , Chang Ting‐Yung , Wu Cheng‐I , Liu Chih‐Min , Chin Chye‐Gen , Liu Shin‐Huei , Cheng Wen‐Han , Chou Ching‐Yao , Lugtu Isaiah C. , Chen Shih‐Ann
Published: January 2021

Introduction

A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of electrocardiography (ECG) features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown.

Methods

Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0–51.0] years; 25 men), including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada‐like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12‐lead ECGs recorded from the second, third, and fourth intercostal spaces (ICS) before and at 1, 6, 12, 18, and 24 h after DPT (oral flecainide 400 mg) were analyzed.

Results

The total amplitude of V1 at the third ICS 18 and 24 h after DPT was significantly lower in patients with a history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the second ICS 12 h after DPT than in those without unstable VAs (0.28 [0.18–0.41] mV vs. 0.08 [0.01–0.15] mV, p = .01). A multivariate analysis revealed that the amplitude of V1 at the third ICS 18 and 24 h after DPT and the ∆ amplitude of V1 at the second ICS 12 h after DPT were associated with a history of unstable VA.

Conclusion

Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification.
Visit‑to‑visit blood pressure variability is associated with arterial stiffness in Chinese adults: A prospective analysis
Authors: Zhang Yuwen , Bie Lizhan , Li Mian , Wang Tiange , Xu Min , Lu Jieli , Wang Shuangyuan , Zhang Jie , Bi Yufang , Wang Weiqing , Ning Guang , Chen Yuhong , Xu Yu
Published: January 2021

Blood pressure (BP) variability may have its effect on the development of vascular disease. The authors aimed to examine the association between the visit‐to‐visit variability (VVV) of BP and arterial stiffness in Chinese adults. The authors included 1407 participants from a prospective cohort study of community residents who were ≥40 years, without a history of myocardial infarction or stroke, and with data at the baseline, the second and the third visits in 2008, 2009, and 2013. The VVV of BP was defined as the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV), and the variability independent of the mean (VIM) in BP levels at the 3 visits. Arterial stiffness was measured by brachial‐ankle pulse wave velocity (ba‐PWV) at the 2nd and the 3rd visits. Levels of ba‐PWV change and the occurrence of an elevated ba‐PWV increased significantly in the highest tertile of VVV measures of systolic BP (SBP) and pulse pressure (PP) compared with the lowest tertile, respectively. The multivariable regression analysis revealed that VVV measures of SBP and PP were significantly associated with levels of ba‐PWV change and the risks of developing an elevated ba‐PWV. The odds ratios (ORs) and 95% confidence intervals (CIs) for the risk were 2.12 (1.57–3.12) and 1.92 (1.38–2.68) in participants with the highest versus the lowest tertile of SBP‐SD and PP‐SD, respectively. No significant association was found for diastolic BP variability measures. The increased long‐term variabilities of SBP and PP were associated with an increased risk of arterial stiffness.
Identification of key candidate biomarkers for severe influenza infection by integrated bioinformatical analysis and initial clinical validation
Authors: Liu Shuai , Huang Zhisheng , Deng Xiaoyan , Zou Xiaohui , Li Hui , Mu Shengrui , Cao Bin
Published: January 2021

One of the key barriers for early identification and intervention of severe influenza cases is a lack of reliable immunologic indicators. In this study, we utilized differentially expressed genes screening incorporating weighted gene co‐expression network analysis in one eligible influenza GEO data set (GSE111368) to identify hub genes associated with clinical severity. A total of 10 genes (PBI, MMP8, TCN1, RETN, OLFM4, ELANE, LTF, LCN2, DEFA4 and HP) were identified. Gene set enrichment analysis (GSEA) for single hub gene revealed that these genes had a close association with antimicrobial response and neutrophils activity. To further evaluate these genes' ability for diagnosis/prognosis of disease developments, we adopted double validation with (a) another new independent data set (GSE101702); and (b) plasma samples collected from hospitalized influenza patients. We found that 10 hub genes presented highly correlation with disease severity. In particular, BPI and MMP8 encoding proteins in plasma achieved higher expression in severe and dead cases, which indicated an adverse disease development and suggested a frustrating prognosis. These findings provide new insight into severe influenza pathogenesis and identify two significant candidate genes that were superior to the conventional clinical indicators. These candidate genes or encoding proteins could be biomarker for clinical diagnosis and therapeutic targets for severe influenza infection.
A novel Cytochrome P450 26A1 expressing NK cell subset at the mouse maternal‐foetal interface
Authors: Wei Dan‐Ping , Li Dan‐Dan , Gu Ai‐Qin , Ji Wen‐Heng , Yang Ying , Peng Jing‐Pian
Published: January 2021

Cyp26a1 had important roles in mouse embryo implantation and was highly expressed in some of NK cells at the human maternal‐foetal interface in early pregnancy. However, the regulatory effect of Cyp26a1 on NK cells remains poorly understood. Through qPCR and flow cytometric assays, we found that Cyp26a1 was expressed by mouse uterine NK cells but not spleen NK cells during the peri‐implantation period and there was a group of NK cells that highly expressed Cyp26a1, that is Cyp26a1+NK cell subset. single cell‐population transcriptome sequencing on Cyp26a1+NK and Cyp26a1−NK cell subsets was performed. We found that there were 3957 differentially expressed genes in the Cyp26a1+NK cell subset with a cut‐off of fold change ≥2 and FDR < 0.01, 2509 genes were up‐regulated and 1448 genes were down‐regulated in Cyp26a1+NK cell subset. Moreover, cytokine‐cytokine receptor interaction signalling pathway and natural killer cell–mediated cytotoxicity signalling pathway were enriched according to KEGG pathway enrichment analysis. We further found that the expression of Gzma and Klrg1 was significantly increased and Fcgr4 was significantly decreased when inhibiting Cyp26a1. Our experimental results show that there is a novel NK cell subset of Cyp26a1+NK cells in mouse uterus and Cyp26a1 can regulate the gene expression of Gzma, Klrg1 and Fcgr4 in the Cyp26a1+NK cells.
Saccharomycomorphapsychra n. g., n. sp., a Novel Member of Glissmonadida (Cercozoa) Isolated from Arctic and Antarctica
Authors: Feng Jian‐Ju , He Chen‐Yang , Jiang Shu‐Hua , Zhang Tao , Yu Li‐Yan
Published: January 2021

A novel genus and species within the order Glissmonadida (Cercozoa, Rhizaria), Saccharomycomorpha psychra n. g., n. sp., is described from lichen in the Ny‐Ålesund region (High Arctic) and moss in the Fildes peninsula of King George Island (Maritime Antarctica). Cells were spherical and did not appear to present flagella in organic‐rich Potato Dextrose Agar medium where they were able to feed osmotrophically. Molecular phylogenetic analyses based on 18S rRNA gene sequence demonstrated that Saccharomycomorpha psychra belong to “clade T” within the order Glissmonadida (Cercozoa, Rhizaria). All three investigated strains could grow at 4 °C and had an optimum growth temperature of 12 °C, 20 °C, and 20 °C, while a maximum growth temperature of 20 °C, 20 °C, and 25 °C, respectively. In conclusion, we established the phenotypic identity of “clade T,” which until now was exclusively detected by environmental sequences, and erect a new family Saccharomycomorphidae for “clade T.” Nomenclatural, morphological and ecological aspects of this novel species are discussed.
When destruction comes first: Two new species of Hypostomus Lacépède, 1803 (Siluriformes: Loricariidae) from a deeply‐impacted river in the Rio São Francisco basin in Brazil
Authors: Penido Iago S. , Pessali Tiago C. , Zawadzki Cláudio H.
Published: January 2021

Environmental disasters affecting Brazilian rivers have been frequent recently, especially involving mining activities. Two recent dam‐rupture events suddenly released millions of cubic meters of iron tailings downstream into two major Brazilian watersheds. These events generated major losses to the environment and human life. Additionally, the biodiversity in both watersheds was still incompletely known. Two new species of the armoured catfish genus Hypostomus were discovered in the Rio Paraopeba and surrounding rivers of the Rio São Francisco Basin. The species share some main characteristics including a depressed body, large dark spots on a clearer background and the absence of keels on flanks. However, while one species (Hypostomus freirei sp. n.) has a large mandibular ramus and numerous slender teeth, the other (Hypostomus guajupia sp. n.) has a shorter mandibular ramus and few robust teeth. The discovery of these two new mid‐sized fish species emphasizes the presumption that the effects of major environmental disasters cannot be fully estimated as local biodiversity is not completely known. This discovery in a recently devastated area also shows that tough environmental laws for the protection, supervision and mitigation of major impacts are urgently needed in developing countries.
Comment on: Predicting In‐Hospital Mortality in COVID‐19 Older Patients with Specifically Developed Scores
Authors: Odille Geoffrey , Girard Noémie , Sanchez Stephane , Lelarge Sarah , Mignot Alexandre , Putot Sophie , Larosa Fabrice , Vovelle Jeremie , Nuss Valentine , Da Silva Sofia , Barben Jeremy , Manckoundia Patrick , Putot Alain
Published: January 2021

See the Reply by De Matteis et al.
Maize endosperm development
Authors: Dai Dawei , Ma Zeyang , Song Rentao
Published: January 2021

Recent breakthroughs in transcriptome analysis and gene characterization have provided valuable resources and information about the maize endosperm developmental program. The high temporal‐resolution transcriptome analysis has yielded unprecedented access to information about the genetic control of seed development. Detailed spatial transcriptome analysis using laser‐capture microdissection has revealed the expression patterns of specific populations of genes in the four major endosperm compartments: the basal endosperm transfer layer (BETL), aleurone layer (AL), starchy endosperm (SE), and embryo‐surrounding region (ESR). Although the overall picture of the transcriptional regulatory network of endosperm development remains fragmentary, there have been some exciting advances, such as the identification of OPAQUE11 (O11) as a central hub of the maize endosperm regulatory network connecting endosperm development, nutrient metabolism, and stress responses, and the discovery that the endosperm adjacent to scutellum (EAS) serves as a dynamic interface for endosperm‐embryo crosstalk. In addition, several genes that function in BETL development, AL differentiation, and the endosperm cell cycle have been identified, such as ZmSWEET4c, Thk1, and Dek15, respectively. Here, we focus on current advances in understanding the molecular factors involved in BETL, AL, SE, ESR, and EAS development, including the specific transcriptional regulatory networks that function in each compartment during endosperm development.
Generations and Change in Central America: An Introduction
Authors: Burrell Jennifer L. , Moodie Ellen
Published: January 2021

In this introduction we consider generation and change in Central America as part of the celebration of the twenty‐fifth anniversary of this journal. We reflect on meanings of generation, starting with Salvador Allende's 1972 declaration: “To be young and not revolutionary may even be a biological contradiction.” Karl Mannheim's theorization of generation as a cohort sharing formative experiences in particular historical moments, often requiring “wholly new minds,” becomes crucial in our understanding of the concept. To follow Mannheim's claim, we trace histories of Central American political generations in the past half‐century. While our collection uncovers many moments of generational difference and tension—particularly in Nicaragua, Honduras, and El Salvador—we also find that conflicts can be opportunities for dialogue, for forms of mutual engagement, as cases in Costa Rica and Guatemala demonstrate.
Electrophysiological investigation of motor axonal excitability in a mouse model of nerve constriction injury
Authors: Makker Preet G. S. , Keating Brooke A. , Lees Justin G. , Burke David , Howells James , Moalem‐Taylor Gila
Published: January 2021

Peripheral nerve injuries caused by focal constriction are characterised by local nerve ischaemia, axonal degeneration, demyelination, and neuroinflammation. The aim of this study was to understand temporal changes in the excitability properties of injured motor axons in a mouse model of nerve constriction injury (NCI). The excitability of motor axons following unilateral sciatic NCI was studied in male C57BL/6J mice distal to the site of injury at the acute (6 hours‐1 week) and chronic (up to 20 weeks) phases of injury, using threshold tracking. Multiple measures of nerve excitability, including strength‐duration properties, threshold electrotonus, current‐threshold relationship, and recovery cycle were examined using the automated nerve excitability protocol (TRONDNF). Acutely, injured motor axons developed a pattern of excitability characteristic of ischemic depolarisation. In most cases, the sciatic nerve became transiently inexcitable. When a liminal compound muscle action potential could again be recorded, it had an increase in threshold and latency, compared to both pre‐injury baseline and sham‐injured groups. These axons showed a greater threshold change in response to hyperpolarising threshold electrotonus and a significant upward shift in the recovery cycle. Mathematical modelling suggested that the changes seen in chronically injured axons involve shortened internodes, reduced myelination, and exposed juxtaparanodal fast K+ conductances. The findings of this study demonstrate long‐term changes in motor excitability following NCI (involving alterations in axonal properties and ion channel activity) and are important for understanding the mechanisms of neurapraxic injuries and traumatic mononeuropathies.