bluuebunny/crossref_metadata_2025 huggingface dataset:
Description of neurodevelopmental phenotypes associated with 10 genetic neurodevelopmental disorders: A scoping review
Authors: Hanly Ciara , Shah Harshil , Au Ping Yee Billie , Murias Kara
Published: November 2020

Neurodevelopmental disorders (NDDs) are a heterogeneous group of conditions including intellectual disability, global developmental delay, autism spectrum disorder, and attention deficit hyperactivity disorder. Advances in genetic diagnostic technology have led to the identification of a number of NDD‐associated genes, but reports of cognitive and developmental outcomes in affected individuals have been variable. The objective of this scoping review is to synthesize available information pertaining to the developmental outcomes of individuals with pathogenic variants in ten emerging recurrent NDD‐associated genes identified from large scale sequencing studies; ADNP, ANKRD11, ARID1B, CHD2, CHD8, CTNNB1, DDX3X, DYRK1A, SCN2A, and SYNGAP1. After a comprehensive search, 260 articles were selected that reported on neurodevelopmental measures or diagnoses. We identify the spectrum of developmental outcomes for each genetic NDD, including prevalence of intellectual disability, frequency of co‐morbid NDDs such as ADHD and autism, and commonly reported medical issues that can help inform diagnosis and treatment. There are significant gaps in our understanding of the natural history of these conditions. Future research focusing on barriers to assessment, the development of modified assessment tools appropriate for long‐term outcomes in genetic NDD, and collection of longitudinal data will increase understanding of prognosis in these conditions and inform evaluations of treatment.
CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
Authors: Cai Shuang , Ye Qianhong , Zeng Xiangzhou , Yang Guangxin , Ye Changchuan , Chen Meixia , Yu Haitao , Wang Yuming , Wang Gang , Huang Shuo , Quan Shuang , Zeng Xiangfang , Qiao Shiyan
Published: November 2020

Objectives

Early pregnancy loss is a major clinical concern in animal and human reproduction, which is largely influenced by embryo implantation. The importance of methionine for embryo implantation is widely neglected.

Materials and methods

We performed a series of experiments with primiparous rats fed diets containing different levels of methionine during early pregnancy to investigate the role of methionine in embryonic implantation and pregnancy outcomes, and used them to perform in vivo metabolic assessments and in vitro uterine explant culture. In addition, through transcriptome analysis and silencing the expression of cystathionine β‐synthase (CBS, the key enzyme in transsulfuration pathway) and cell adhesion assay, we measured signalling within Ishikawa, pTr and JAR cells.

Results

We determined the relevance and underlying mechanism of methionine on embryo implantation. We showed that methionine deprivation sharply decreased embryo implantation sites, expression of CBS and transsulfuration pathway end products, which were reversed by maternal methionine supplementation during early pregnancy. Moreover, we found CBS improved methionine‐mediated cell proliferation and DNA synthesis by CBS inhibition or interference. In addition, transcriptome analysis also revealed that CBS influenced the signalling pathway‐associated cell proliferation and DNA synthesis, as well as a correlation between CBS and methionine adenosyltransferase 2A (MAT2A), implying that MAT2A was possibly involved in cell proliferation and DNA synthesis. Further analysis revealed that MAT2A influenced S‐adenosylmethionine receptor SAMTOR expression, and SAMTOR activated mTORC1 and its downstream S6K1 and CAD, ultimately enhancing DNA synthesis in the embryo and uterus.

Conclusions

Taken together, these studies demonstrate that CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation.
Faunal responses to fire in Australian tropical savannas: Insights from field experiments and their lessons for conservation management
Authors: Andersen Alan N.
Published: November 2020

Aim

Fire is particularly frequent, complex and contentious in the vast tropical savannas of northern Australia, where declines in many threatened species are associated with fire, and substantial areas are under fire management for greenhouse gas abatement. Controlled field experiments are crucial for understanding biodiversity responses, and here I present key insights into faunal responses to fire that have been revealed by them, along with their lessons for fire management.

Location

Australian monsoonal tropics.

Methods

Results are synthesized from six replicated fire experiments that have been conducted in Australian savannas and include multispecies assessments of fauna. The synthesis also draws on other fire studies and is presented in the form of five key insights into faunal responses.

Results

The key insights are as follows: (a) most faunal groups are extremely resilient to fire, with highly contrasting fire regimes often having little or no detectable impact on species abundances, at least in the medium term; (b) the most important effects of fire are typically indirect through habitat modification, even when there is substantial direct mortality; (c) fire intensity is not as important a factor as is widely thought; rather, fire frequency is particularly important; (d) there will always be winners and losers with any fire; and (e) fire is required for the maintenance of diversity.

Main conclusions

These insights have important implications for conservation management in Australian savannas: management needs to focus on fire‐induced changes to habitat suitability, and to consider faunal outcomes at the landscape scale; a combination of frequently (every 2–3 years) and less frequently (every ≥5 years) burned habitat may adequately conserve the great majority of animal species without a need for complex fire mosaics; special management attention is required for frequent‐fire losers because of an extremely low representation of longer‐unburnt habitat; and fire needs to be actively managed to promote diversity, not excluded. The insights are widely applicable to tropical grassy ecosystems more generally, and some appear to be universal to fire‐prone biomes.
Visit‐to‐visit variability of clinical risk markers in relation to long‐term complications in type 1 diabetes
Authors: Rotbain Curovic Viktor , Theilade Simone , Winther Signe Abitz , Tofte Nete , Tarnow Lise , Jorsal Anders , Parving Hans‐Henrik , Persson Frederik , Hansen Tine Willum , Rossing Peter
Published: November 2020

Background

Clinical characteristics such as HbA1c, systolic blood pressure (SBP), albuminuria and estimated glomerular filtration rate (eGFR) are important when treating type 1 diabetes. We investigated the variability in these measures as risk markers for micro‐ and macrovascular complications.

Methods

This prospective study included 1062 individuals with type 1 diabetes. Visit‐to‐visit variability of HbA1c, SBP, albuminuria and eGFR was calculated as the SD of the residuals in individual linear regression models using all available measures in a specified period of 3 years (VV). Endpoints included were as follows: cardiovascular events (CVE) defined as myocardial infarction, non‐fatal stroke, or coronary or peripheral arterial intervention; end‐stage kidney disease (ESKD) defined as eGFR <15 ml/min/1.73 m2, chronic dialysis or kidney transplantation; eGFR decline ≥30%; and mortality. Adjustment included age, sex, cholesterol, HbA1c, SBP, body mass index, smoking, albuminuria, eGFR, and mean, intercept, slope of respective exposure variables and regression models.

Results

SBP VV was significantly associated with CVE (adjusted hazard ratio per 50% increase, (CI 95%); p: 1.21 [1.05–1.39]; p = 0.008), ESKD (1.51 [1.16–1.96]; p = 0.002) and mortality (1.25 [1.09–1.44]; p = 0.002). HbA1c VV was significantly associated with mortality (1.51 [1.30–1.75]; p < 0.001); albuminuria VV with eGFR decline (1.14 [1.08–1.20]; p = 0.024) and ESKD (1.14 [1.02–1.27]; p < 0.001), but neither CVE nor mortality. Adjusted eGFR VV was not associated with endpoints.

Conclusion

In type 1 diabetes, higher variability of basic clinical risk markers adds important risk stratification information for the development of micro‐ and macrovascular complications.
Spontaneous homeotic mutants and genetic control of floral organ identity in a ranunculid
Authors: Martínez‐Gómez Jesús , Galimba Kelsey D. , Coté Erin Y. , Sullivan Alessandra M. , Di Stilio Verónica S.
Published: November 2020

The regulation of floral organ identity was investigated using a forward genetic approach in five floral homeotic mutants of Thalictrum, a noncore eudicot. We hypothesized that these mutants carry defects in the floral patterning genes. Mutant characterization comprised comparative floral morphology and organ identity gene expression at early and late developmental stages, followed by sequence analysis of coding and intronic regions to identify transcription factor binding sites and protein–protein interaction (PPI) motifs. Mutants exhibited altered expression of floral MADS‐box genes, which further informed the function of paralogs arising from gene duplications not found in reference model systems. The ensuing modified BCE models for the mutants supported instances of neofunctionalization (e.g., B‐class genes expressed ectopically in sepals), partial redundancy (E‐class), or subfunctionalization (C‐class) of paralogs. A lack of deleterious mutations in the coding regions of candidate floral MADS‐box genes suggested that cis‐regulatory or trans‐acting mutations are at play. Consistent with this hypothesis, double‐flower mutants had transposon insertions or showed signs of transposon activity in the regulatory intron of AGAMOUS (AG) orthologs. Single amino acid substitutions were also found, yet they did not fall on any of the identified DNA binding or PPI motifs. In conclusion, we present evidence suggesting that transposon activity and regulatory mutations in floral homeotic genes likely underlie the striking phenotypes of these Thalictrum floral homeotic mutants.
Oral health and healthy chewing for healthy cognitive ageing: A comprehensive narrative review
Authors: Lopez‐Chaichio Lucia , Padial‐Molina Miguel , O’Valle Francisco , Gil‐Montoya Jose Antonio , Catena Andres , Galindo‐Moreno Pablo
Published: November 2020

Introduction

Ageing leads to physiological cognitive decline that it is worsened in people with neurodegenerative diseases such as Alzheimer's disease. Despite the ongoing search for a solution to this cognitive decline, no effective remedies have been established. It has been determined that modifiable external factors, such as oral health and occlusal function, prevent cognitive decline.

Objective

To analyse the primary interactions between occlusal function and cognitive functions.

Main findings

Masticatory function is related to cognitive functions. In particular, current evidence, from both animal and human studies, suggests that the activation of masticatory muscles and proper mastication, with natural teeth or dental prosthesis, induces the release of several mediators and the activation of specific brain areas. Together, they result in higher neuronal activity, neurotrophic support, blood flow and the prevention of amyloid‐beta plaque formation. Thus, all the components of the masticatory system must work together in order to preserve cognitive function.

Conclusions

Available evidence suggests that oral and cognitive health are more interconnected than previously thought. Therefore, maintenance and adequate restoration of the whole masticatory system are important for the prevention of cognitive decline. In summary, oral and chewing health lead to healthy cognitive ageing.
Reversion From Chronic Migraine to Episodic Migraine in Patients Treated With Fremanezumab: Post Hoc Analysis From HALO CM Study
Authors: Lipton Richard B. , Cohen Joshua M. , Bibeau Kristen , Galic Maja , Seminerio Michael J. , Ramirez Campos Verena , Halker Singh Rashmi B. , Ailani Jessica
Published: November 2020

Background

Migraine preventive medications are used to reduce headache frequency, severity, and duration. In patients with chronic migraine (CM), reversion to episodic migraine (EM) is an important treatment goal.

Objective

To evaluate the effect of fremanezumab on the rate of reversion from CM to EM.

Methods

This phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group trial included a 28‐day pretreatment period and a 3‐month treatment period. Patients with CM received subcutaneous fremanezumab quarterly (675 mg at baseline) or monthly (675 mg at baseline; 225 mg at Weeks 4 and 8), or placebo. Post hoc analyses evaluated the proportion of patients who reverted from CM to EM, defined as either a reduction to an average of <15 headache days per month during the 3‐month treatment period or a reduction to <15 headache days per month in all 3 months of the treatment period.

Results

This analysis included data from 1088 CM patients (quarterly, n = 366; monthly, n = 365; placebo, n = 357). More fremanezumab‐treated patients with CM reverted to EM using either the monthly average number of headache days criteria for reversion (quarterly: 50.5% [185/366], P = .108; monthly: 53.7% [196/365], P = .012; vs placebo: 44.5% [159/357]) or the monthly headache day count at Months 1, 2, and 3 criteria for reversion (quarterly: 31.2% [114/366], P = .008; monthly: 33.7% [123/365], P = .001; vs placebo: 22.4% [80/357]). Patients with CM who reported previous topiramate or onabotulinumtoxinA use, concomitant preventive medication use, or medication overuse were less likely to revert to EM.

Conclusions

Fremanezumab may offer the benefit of reversion from CM to EM, based on a reduction in the number of headache days over 3 months of treatment.
Developing one corpus‐based grammar textbook about irregular multi‐verb sequences in English
Authors: Matsumoto Noriko
Published: November 2020

This article addresses the development of a corpus‐based grammar textbook on four types of irregular multi‐verb sequences in English— V‐V, V‐and‐V, V‐to‐V, and V‐Ving. Since many current grammar textbooks have seldom treated these four types of irregular multi‐verb sequences, this article empirically demonstrates the need to develop corpus‐based grammar textbooks. Our framework to develop the corpus‐based grammar textbook adopted in this article relies on two things: a combination of corpora and descriptions of English grammar proposed by linguists working in the field of theoretical linguistics. The corpus‐based grammar textbook in this article is a pilot scheme that can be extended to other grammatical areas. This article thus claims that the development of corpus‐based grammar textbooks clearly makes a positive contribution to grammatical instruction.
Occurrence of persistent atrial fibrillation during pacing for sinus node disease: The influence of His bundle pacing versus managed ventricular pacing
Authors: Pastore Gianni , Marcantoni Lina , Lanza Daniela , Maines Massimiliano , Noventa Franco , Corbucci Giorgio , Rigatelli Gianluca , Baracca Enrico , Roncon Loris , Zanon Francesco
Published: November 2020

Introduction

In patients with sinus node disease (SND), the dual‐chamber pacemaker (PM) is programmed in DDDR mode with an algorithm to avoid unnecessary right ventricular (RV) pacing. This pacing mode may prolong PR interval with consequently atrioventricular (AV) asynchrony which is associated with a higher risk of atrial fibrillation (AF). We evaluate whether preserving AV synchrony by setting a fixed AV delay during physiological RV pacing, that is, His bundle pacing (HBP), could reduce the risk of AF occurrence in comparison with a standard pacing mode with an algorithm to avoid unnecessary RV pacing (DDD‐VPA).

Methods and Results

We collected retrospective data from 313 consecutive patients who had undergone PM for SND. The first occurrence of persistent AF (>7 consecutive days) as a function of the pacing mode was evaluated. HBP and DDD‐VPA were implemented in 82 and 231 patients, respectively. Persistent AF occurred in 128 (40.9%) patients over a median follow‐up of 70 months (67–105). The DDD‐VPA pacing mode was significantly correlated with the occurrence of persistent AF only when the basal PR was long (>180 ms). The risk of persistent AF was significantly lower in patients on HBP than in those on DDD‐VPA, adjusted HR = .57 (95% CI, .36– .89, p=.014). Other independent predictors of persistent AF occurrence were: A history of AF (HR = 3.91; 95% CI, 2.48–6.19, p = .001), age, and long PR interval (HR = 2.98; 95% CI, 2.00–4.43, p=.001).

Conclusion

In SND patients and long basal PR interval, the HBP may reduce the risk of persistent AF in comparison with the DDD‐VPA.
Focal and pseudo/rotational activations in human atrial fibrillation defined with automated periodicity mapping
Authors: Nayyar Sachin , Ha Andrew C. T. , Timmerman Nicholas , Suszko Adrian , Ragot Don , Chauhan Vijay S.
Published: November 2020

Introduction

Defining atrial fibrillation (AF) wave propagation is challenging unless local signal features are discrete or periodic. Periodic focal or rotational activity may identify AF drivers. Our objective was to characterize AF propagation at sites with periodic activation to evaluate the prevalence and relationship between focal and rotational activation.

Methods

We included 80 patients (61 ± 10 years, persistent AF 49%) from the FaST randomized trial that compared the efficacy of adjunctive focal site ablation versus pulmonary vein isolation. Patients underwent left atrial (LA) activation mapping with a 20‐pole circular catheter during spontaneous or induced AF. Five‐second bipolar and unipolar electrograms in AF were analyzed. Periodic sites were identified by spectral analysis of the bipolar electrogram. Activation maps of periodic sites were constructed using an automated, validated tracking algorithm, and classified into three patterns: focal sites (FS), rotation (RO), or pseudo‐rotation (pRO).

Results

The most common propagation pattern at periodic sites was FS for 5‐s in all patients (4.9 ± 1.9 per patient). RO and pRO were observed in two and seven patients, respectively, but were all transient (3–5 cycles). Activation from a FS evolved into transient RO/pRO in five patients. No patient had autonomous RO/pRO activations. Patients with RO/pRO had greater LA surface area with periodicity (78 ± 7 vs. 63 ± 16%, p = .0002) and shorter LA periodicity CL (166 ± 10 vs. 190±28 ms, p = .0001) than the rest.

Conclusion

Using automated, regional AF periodicity mapping, FS is more prevalent and temporally stable than RO/pRO. Most RO/pRO evolve from neighboring FS. These findings and their implications for AF maintenance require verification with global, panoramic mapping.
Multifactorial analysis of optical properties, sorption, and solubility of sculptable universal composites for enamel layering upon staining in colored beverages
Authors: Miletic Vesna , Stasic Jovana N. , Komlenic Vojislav , Petrovic Renata
Published: November 2020

Objective

To analyze the effects of factors 'composite,' 'medium,' and 'time' on color, translucency, and sorption/solubility of sculptable universal composites for enamel layering upon immersion in colored beverages.

Materials and methods

Disk‐shaped specimens, 10 mm in diameter and 2 mm thick (n = 5/group), of ultrafine, hybrid composite Essentia (GC), microhybrid Gaenial Anterior (GC), nanofilled Filtek Ultimate Enamel and Body ( 3M ESPE) were immersed in red wine, coffee, or distilled water for 15 days. CIELab color coordinates were measured and CIEDE2000 (∆E00) and Translucency Parameter differences (∆TP00) were calculated. Sorption and solubility were determined according to ISO 4049:2009. Data were analyzed using the analyses of variance and Tukey's post‐hoc test (α = 0.05).

Results

Essentia and Gaenial exhibited the lowest and the highest staining‐dependent color differences, with mean ∆E00 range of 1.7–6.1 and 5.1–11.3, respectively (p < 0.05). ∆TP00 was more pronounced in wine than in coffee (p < 0.05). Sorption and solubility varied between 9.8 and 15.3 μg/mm3 and −1.6 and −5.4 μg/mm3, respectively, with positive correlation between ∆TP00 and sorption (p = 0.005).

Conclusions

Total color and translucency differences of sculptable composites for enamel layering were material‐, time‐ and medium‐dependent. Translucency differences positively correlated with sorption. Overall, the ultrafine, hybrid composite exhibited the best results in terms of color stability, sorption and solubility.

Clinical significance

Clinicians should be aware of differences in color stability of sculptable composites for enamel layering as these are directly exposed to discoloration in the oral environment and are directly related to patients' long‐term satisfaction and restoration longevity. Ultrafine, hybrid composite may be preferred due to better color stability, lower sorption and solubility compared to nanofilled and microhybrid composites evaluated in this study.
Artificial intelligence in colonoscopy ‐ Now on the market. What's next?
Authors: Mori Yuichi , Neumann Helmut , Misawa Masashi , Kudo Shin‐ei , Bretthauer Michael
Published: November 2020

Adoption of artificial intelligence (AI) in clinical medicine is revolutionizing daily practice. In the field of colonoscopy, major endoscopy manufacturers have already launched their own AI products on the market with regulatory approval in Europe and Asia. This commercialization is strongly supported by positive evidence that has been recently established through rigorously designed prospective trials and randomized controlled trials. According to some of the trials, AI tools possibly increase the adenoma detection rate by roughly 50% and contribute to a 7–20% reduction of colonoscopy‐related costs. Given that reliable evidence is emerging, together with active commercialization, this seems to be a good time for us to review and discuss the current status of AI in colonoscopy from a clinical perspective. In this review, we introduce the advantages and possible drawbacks of AI tools and explore their future potential including the possibility of obtaining reimbursement.
Nothing Much Has Changed: COVID‐19 Nursing Home Cases and Deaths Follow Fall Surges
Authors: Konetzka R. Tamara , Gorges Rebecca J.
Published: November 2020

This letter comments on the article by Storer et al.
Delegation of Regulation*
Authors: Kundu Tapas , Nilssen Tore
Published: November 2020

We discuss a government’s incentives to delegate regulation to bureaucrats. The government faces a trade‐off in its delegation decision: bureaucrats have knowledge of the firms in the industry that the government does not have, but at the same time, they have other preferences than the government. The preference bias and the private information interact to affect the incentives to delegate regulation. Allowing for constrained delegation, we introduce the concepts of weak and strict delegation. We find that bureaucratic discretion reduces with bureaucratic drift, while the effect of increased uncertainty about the firm’s technology depends on how that uncertainty changes.
Integrative Approach Helps Clarify Confusing Taxonomy of the Pseudopediastrum boryanum Species Complex (Chlorophyceae), Including Recognition of five Distinct Species
Authors: Lenarczyk Joanna , Saługa Marta , Piątek Jolanta
Published: November 2020

Sixteen monoclonal strains classified into six morphotypes typical of, or close to, intraspecific taxa of Pseudopediastum boryanum, including P. alternans (ALT), P. boryanum var. boryanum (BOR), P. boryanum var. cornutum (COR), P. boryanum var. forcipatum (FOR), P. boryanum var. longicorne (LON), and P. boryanum var. perforatum (PER), were simultaneously subjected to phylogenetic (26S rDNA and rbcL cpDNA) and morphometric analyses. Marginal cell shape, coenobium and cell size, and granule density on the cell surface were analyzed statistically. The shapes of some morphotypes (BOR, COR, FOR, and PER) were also compared to the shapes of corresponding type illustrations. Pseudopediastrum boryanum var. boryanum, without any reliable morphological and phylogenetic data, appeared to be a questionable taxon that needs a neotype. The variety longicorne proved to be a complex taxon that should be split after morphometric data of more strains and of the corresponding lectotype are included in the statistical analysis. A new species, Pseudopediastrum oblongum, was described, and four varieties were elevated to the species level, which resulted in establishing new combinations, P. cornutum, P. forcipatum, P. perforatum, and P. subgranulatum. Reference sequences for the new species and combinations were obtained. The paleoecological value of P. boryanum sensu lato appeared to be limited by the relatively low percentage of marginal cells typical of particular varieties and a high risk of their misidentification in the light microscope. The shape of marginal cells seemed to be the best diagnostic feature. Granule density could be helpful to discriminate between certain taxa.
Adverse event rates in the retrospective cohort study of safety of paediatric soft contact lens wear: the ReCSS study
Authors: Chalmers Robin L , McNally John J , Chamberlain Paul , Keay Lisa
Published: November 2020

Purpose

To ascertain the safety of soft contact lens (SCL) wear in children through a retrospective chart review including real‐world clinical practice settings.

Methods

The study reviewed clinical charts from 963 children: 782 patients in 7 US eye care clinics and 181 subjects from 2 international randomised clinical trials (RCTs). Subjects were first fitted while 8–12 years old with various SCL designs, prescriptions and replacement schedules, and observed through to age 16. Clinical records from visits with potential adverse events (AEs) were electronically scanned and reviewed to consensus by an Adjudication Panel.

Results

The study encompassed 2713 years‐of‐wear and 4611 contact lens visits. The cohort was 46% male, 60% were first fitted with daily disposable SCLs, the average age at first fitting was 10.5 years old, with a mean of 2.8 ± 1.5 years‐of‐wear of follow‐up observed. There were 122 potential ocular AEs observed from 118/963 (12.2%) subjects; the annualised rate of non‐infectious inflammatory AEs was 0.66%/year (95% CI 0.39–1.05) and 0.48%/year (0.25–0.82) for contact lens papillary conjunctivitis. After adjudication, two presumed or probable microbial keratitis (MK) cases were identified, a rate of 7.4/10 000 years‐of‐wear (95% CI 1.8–29.6). Both were in teenage boys and one resulted in a small scar without loss of visual acuity.

Conclusion

This study estimated the MK rate and the rate of other inflammatory AEs in a cohort of SCL wearers from 8 through to 16 years of age. Both rates are comparable to established rates among adults wearing SCLs.
The association between body temperature and electrocardiographic parameters in normothermic healthy volunteers
Authors: Fienieg Bart , Hassing Gerardus J. , van der Wall Hein E. C. , van Westen Gerard J. P. , Kemme Michiel J. B. , Adiyaman Ahmet , Elvan Arif , Burggraaf Jacobus , Gal Pim
Published: November 2020

Background

Previous studies reported that hypo‐ and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis’ objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers.

Methods

Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5‐37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable.

Results

Mean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = −0.255, P < .001), female gender (SC = +0.209, P < .001), heart rate (SC = +0.231, P < .001), P‐wave axis (SC = −0.051, P < .001), J‐point elevation in lead V4 (SC = −0.121, P < .001), and QTcF duration (SC = −0.061, P = .002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = −0.121, P < .001) was independently associated with body temperature.

Conclusion

Body temperature in normothermic healthy volunteers was associated with heart rate, P‐wave axis, J‐point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration.
An ethical analysis of obesity as a determinant of pediatric heart transplant candidacy
Authors: Berkman Emily , Wightman Aaron , Friedland‐Little Joshua M. , Albers Erin L. , Diekema Douglas , Lewis‐Newby Mithya
Published: November 2020

Background

Inclusion of BMI as criterion in the determination of heart transplant candidacy in children is a clinical and ethical challenge. Childhood obesity is increasing and children with heart disease are not spared. Currently, many adult heart transplant centers consider class II obesity and higher (BMI > 35 kg/m2) to be a relative contraindication for transplantation due to risk of poor outcome after transplant. No national guidelines exist regarding consideration of BMI in pediatric heart transplant and outcomes data are limited. This leaves decisions about transplant candidacy in obese pediatric patients to individual institutions or on a case‐by‐case basis, allowing for bias and inequity.

Methods

We review (a) the prevalence of childhood obesity, including among heart transplant candidates, (b) the lack of existing BMI guidelines, and (c) relevant literature on BMI and pediatric heart transplant outcomes. We discuss the ethical considerations of using obesity as a criterion using the principles of utility, justice, and respect for persons.

Results

Existing transplant outcomes data do not show that obese children have different or poor enough outcomes compared to non‐obese children to warrant exclusion. Moreover, obesity in the United States is unequally distributed by race and socioeconomic status. Children already suffering from health disparities are therefore doubly penalized if obesity denies them access to life‐saving transplant.

Conclusion

Insufficient data exist to support using any BMI cutoff as an absolute contraindication for heart transplant in children. Attention should be paid to health equity issues when considering excluding a patient for transplant based on obesity.
Transcription factors as key molecular target to strengthen the drought stress tolerance in plants
Authors: Manna Mrinalini , Thakur Tanika , Chirom Oceania , Mandlik Rushil , Deshmukh Rupesh , Salvi Prafull
Published: November 2020

Amid apprehension of global climate change, crop plants are inevitably confronted with a myriad of abiotic stress factors during their growth that inflicts a serious threat to their development and overall productivity. These abiotic stresses comprise extreme temperature, pH, high saline soil, and drought stress. Among different abiotic stresses, drought is considered the most calamitous stressor with its serious impact on the crops' yield stability. The development of climate‐resilient crops that withstands reduced water availability is a major focus of the scientific fraternity to ensure the food security of the sharply increasing population. Numerous studies aim to recognize the key regulators of molecular and biochemical processes associated with drought stress tolerance response. A few potential candidates are now considered as promising targets for crop improvement. Transcription factors act as a key regulatory switch controlling the gene expression of diverse biological processes and, eventually, the metabolic processes. Understanding the role and regulation of the transcription factors will facilitate the crop improvement strategies intending to develop and deliver agronomically‐superior crops. Therefore, in this review, we have emphasized the molecular avenues of the transcription factors that can be exploited to engineer drought tolerance potential in crop plants. We have discussed the molecular role of several transcription factors, such as basic leucine zipper (bZIP), dehydration responsive element binding (DREB), DNA binding with one finger (DOF), heat shock factor (HSF), MYB, NAC, TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP), and WRKY. We have also highlighted candidate transcription factors that can be used for the development of drought‐tolerant crops.
The impact of water deficit and heat stress combination on the molecular response, physiology, and seed production of soybean
Authors: Cohen Itay , Zandalinas Sara I , Fritschi Felix B. , Sengupta Soham , Fichman Yosef , Azad Rajeev K. , Mittler Ron
Published: November 2020

A combination of drought and heat stress, occurring at the vegetative or reproductive growth phase of many different crops can have a devastating impact on yield. In soybean (Glycine max), a considerable effort has been made to develop genotypes with enhanced yield production under conditions of drought or heat stress. However, how these genotypes perform in terms of growth, physiological responses, and most importantly seed production, under conditions of drought and heat combination is mostly unknown. Here, we studied the impact of water deficit and heat stress combination on the physiology, seed production, and yield per plant of two soybean genotypes, Magellan and Plant Introduction (PI) 548313, that differ in their reproductive responses to heat stress. Our findings reveal that although PI 548313 produced more seeds than Magellan under conditions of heat stress, under conditions of water deficit, and heat stress combination its seed production decreased. Because the number of flowers and pollen germination of PI 548313 remained high under heat or water deficit and heat combination, the reduced seed production exhibited by PI 548313 under the stress combination could be a result of processes that occur at the stigma, ovaries and/or other parts of the flower following pollen germination.
Negative impact of long‐term exposure of salinity and drought stress on native Tetraena mandavillei L.
Authors: Alam Hasnain , Khattak Jabar Z. K. , Ksiksi Taoufik S. , Saleem Muhammad H. , Fahad Shah , Sohail Hamza , Ali Qasim , Zamin Muhammad , El‐Esawi Mohamed A. , Saud Shah , Jiang Xue , Alwahibi Mona S. , Alkahtani Jawaher
Published: November 2020

Tetraena mandavillei L. is a perennial shrub native to the Middle Eastern countries of Asia, which is extensively regarded as a drought‐tolerant plant. However, the plant reduces growth and biomass when grown in high concentrations of sodium chloride in the soil. We conducted a pot experiment to influence the negative impact of different levels of salinity (0, 10, and 20 dSm−1) and drought stress (100, 80, 60, and 40% water field capacity), to study different growth‐related parameters, physiological alterations and ion uptake by T. mandavillei. Both salinity and drought stress caused a negative impact by affecting several attributes of T. mandavillei, but the plants showed some resistance against drought stress conditions in terms of growth and biomass. In addition to that, we noticed that a combinatorial and individual impact of drought and salinity stress decreased photosynthetic pigments and gas exchange parameters in T. mandavillei. Results also depicted that the combination of the abiotic stress conditions drought and salinity induced reactive oxygen species (ROS), indicating that the plants undergo oxidative damaged. However, due to the active plant defense system, the plant enhanced its performance under abiotic stress conditions, but due to the severe drought condition (40% water field capacity), a significant (P < 0.05) decrease in the activities of antioxidant compounds was caused. Furthermore, osmolytes also increased under both salinity and drought stress conditions in this study. Our results also showed that increased salinity and drought stress in the soil caused a significant increase in sodium (Na+) and chloride (Cl−) ions in roots and shoots of T. mandavillei. In contrast to that, the contents of Calcium (Ca2+) and potassium (K+) were decreased in all organs of the plants with increasing levels of salinity and drought stress. Taken together, T. mandavillei can be classified as a facultative halophyte with the ability to tolerate drought stress and using salt accumulation mechanisms to tolerate salinity stress.
Correcting Misclassification Errors in Crowdsourced Ecological Data: A Bayesian Perspective
Authors: Santos-Fernandez Edgar , Peterson Erin E. , Vercelloni Julie , Rushworth Em , Mengersen Kerrie
Published: November 2020

Many research domains use data elicited from ‘citizen scientists’ when a direct measure of a process is expensive or infeasible. However, participants may report incorrect estimates or classifications due to their lack of skill. We demonstrate how Bayesian hierarchical models can be used to learn about latent variables of interest, while accounting for the participants’ abilities. The model is described in the context of an ecological application that involves crowdsourced classifications of georeferenced coral-reef images from the Great Barrier Reef, Australia. The latent variable of interest is the proportion of coral cover, which is a common indicator of coral reef health. The participants’ abilities are expressed in terms of sensitivity and specificity of a correctly classified set of points on the images. The model also incorporates a spatial component, which allows prediction of the latent variable in locations that have not been surveyed. We show that the model outperforms traditional weighted-regression approaches used to account for uncertainty in citizen science data. Our approach produces more accurate regression coefficients and provides a better characterisation of the latent process of interest. This new method is implemented in the probabilistic programming language Stan and can be applied to a wide number of problems that rely on uncertain citizen science data.
Accuracy from the slot: Evaluating draft selections in the National Hockey League
Authors: Farah Lou , Baker Joseph
Published: November 2020

The National Hockey League (NHL) entry draft is a process wherein teams make sequential selections from a pool of eligible players. Given the young age of prospects, drafting requires long‐term forecasting of future performance under a high level of uncertainty. This study assessed the selection accuracy across all seven rounds of the draft, as well as between lottery and non‐lottery picks within the first round. NHL performance data were collected for all forwards (N = 956) and defensemen (N = 558) drafted between 2007 and 2014. In both groups, Kruskal‐Wallis H tests conducted between draft rounds revealed a significant, relatively strong, overall effect of draft order on future performance. However, Mann‐Whitney U post‐hoc tests showed projecting future performance of forwards was only accurate in the first two rounds, while for defensemen, selection was only accurate in the first round. Moreover, forwards selected with lottery picks in the first round outperformed their non‐lottery peers offensively but not defensively. As for defensemen, those selected with lottery picks did not differ from their non‐lottery peers in offensive or defensive performance. Our findings highlight substantial inaccuracies in the NHL draft, particularly past the first two rounds of selection. We offer multiple possible explanations driving such inaccuracies that could form the basis for further work in this area.
Association of HLA‐B22 serotype with SARS‐CoV‐2 susceptibility in Hong Kong Chinese patients
Authors: Yung Yuk‐Lin , Cheng Chi‐Keung , Chan Hoi‐Yun , Xia Jenny T. , Lau Kin‐Mang , Wong Raymond S. M. , Wu Alan K. L. , Chu Raymond W. , Wong Alice C. C. , Chow Eudora Y. D. , Yip Sze‐Fai , Leung Jennifer N. S. , Lee Cheuk‐Kwong , Ng Margaret H. L.
Published: November 2020

The coronavirus disease 2019 (COVID‐19) is a highly infectious disease caused by SARS‐CoV‐2. Since its first report in December 2019, COVID‐19 has evolved into a global pandemic causing massive healthcare and socioeconomic challenges. HLA system is critical in mediating anti‐viral immunity and recent studies have suggested preferential involvement of HLA‐B in COVID‐19 susceptibility. Here, by investigating the HLA‐B genotypes in 190 unrelated Chinese patients with confirmed COVID‐19, we identified a significant positive association between the B22 serotype and SARS‐CoV‐2 infection (p = 0.002, Bonferroni‐corrected p = 0.032). Notably, the B22 serotype has been consistently linked to susceptibility to other viral infections. These data not only shed new insights into SARS‐CoV‐2 pathogenesis and vaccine development but also guide better infection prevention/control.
Resource allocation strategies among vegetative growth, sexual reproduction, asexual reproduction and defense during growing season of Aconitum kusnezoffii Reichb.
Authors: Tang Mingze , Zhao Wei , Xing Ming , Zhao Jiaxin , Jiang Zhang , You Jian , Ni Biao , Ni Yuanbo , Liu Chengbai , Li Jiangnan , Chen Xia
Published: November 2020

Natural plants must actively allocate their limited resources for survival and reproduction. Although vegetative growth, sexual reproduction, asexual reproduction and defense are all basic processes in the life cycle of plants, the strategies used to allocate resources between these processes are poorly understood. These processes are conspicuous in naturally grown Aconitum kusnezoffii Reichb., which makes it a suitable study subject. Here, the morphology, dry matter, total organic carbon, total nitrogen and aconitum alkaloid levels of shoot, principal root (PR) and lateral roots were measured throughout the growing season. Then, transcriptome and metabolite content analyses were performed. We found that vegetative growth began first. After vegetative growth ceased, sexual development began. Flower organ development was accompanied by increased photosynthesis and the PR consumed temporarily stored resources after flower formation. Asexual propagule development initiated earlier than sexual reproduction and kept accumulating resources after that. Development was slow before flower formation, mainly manifesting as increasing length; then, after flower formation it accelerated via enhanced material transport and accumulation. Defense compounds were maintained at low levels before flowering. In particular, the turnover of defense compounds was enhanced before and after flower bud emergence, providing resources for other processes. After flower formation, defense compounds were accumulated. The pattern found herein provides a vivid example for further studies on resource allocation strategies. The exciting finding that the PR, as a more direct storage site for photosynthate, is a buffer unit for resources, and that defense compounds can be reused for other processes, suggests a need to explore potential mechanisms.
Sex differences in diaphragmatic fatigue: Effects of hypoxia during inspiratory loading
Authors: Archiza Bruno , Reinhard Paige A. , Welch Joseph F. , Sheel A. William
Published: November 2020

Key points

Under normoxic conditions, both healthy female and male diaphragms fatigue at a similar degree when matched for absolute diaphragmatic work during inspiratory loading.

We investigated whether similarities in diaphragm fatigability persist under acute hypoxic conditions.

We found that, in acute hypoxia, fatigue of the diaphragm is greater in women compared to men, whereas the magnitude of fatigue in normoxia did not differ between sexes.

When matched for maximal diaphragm strength, women and men had a similar pressor response to work‐matched inspiratory loading, independent of oxygen availability.

In normoxia, women and men display a comparable magnitude of diaphragmatic fatigue (DF) after work‐matched inspiratory loading. Whether these sex similarities are maintained under acute hypoxic conditions is unknown. We investigated the influence of acute hypoxia during work‐matched inspiratory pressure‐threshold loading (PTL) on DF in healthy women (n = 8) and men (n = 8). Two 5 min isocapnic PTL tasks targeting a transdiaphragmatic pressure (Pdi) of 92 cmH2O in normoxia and hypoxia (8% O2) were performed on separate days (≥48 h). DF was quantified by twitch Pdi (Pdi,tw) via cervical magnetic stimulation post‐PTL. Women and men had similar maximal Pdi (Pdi,max; women: 171 ± 16, men: 178 ± 20 cmH2O) and relative target workload (women: 54 ± 5%, men: 53 ± 6% Pdi,max). The absolute cumulative diaphragmatic work did not differ between sexes in normoxia (women: 12,653 ± 1796 cmH2O s−1, men: 13,717 ± 1231 cmH2O s−1; P = 0.202) or hypoxia (women: 11,624 ± 1860 cmH2O s−1, men: 12 722 ± 1502 cmH2O s−1; P = 0.189). In normoxia, the magnitude of reduction in Pdi,tw post‐PTL was similar between sexes (women: –21.1 ± 8.4%, men: –22.5 ± 4.9 %; P = 0.193); however, a higher degree of DF was observed in women compared to men following PTL in acute hypoxia (women: −27.6 ± 7.7%, men: −23.4 ± 9.6%, P = 0.019). We conclude that the female diaphragm is more susceptible to fatigue after inspiratory loading under acute hypoxic conditions. This finding may be related to sex differences in diaphragm muscle metabolism, such as fibre type composition, contractile properties, substrate utilisation and blood perfusion.
Enhancing host cell infection by SARS-CoV-2
Authors: Kielian Margaret
Published: November 2020

Neuropilin-1 binds the furin-processed spike protein of SARS-CoV-2 to promote virus entry
fosM
, a New Family of Fosfomycin Resistance Genes Identified in Bacterial Species Isolated from Human Microbiota
Authors: Khabthani Sami , Hamel Mouna , Baron Sophie Alexandra , Diene Seydina M. , Rolain Jean-Marc , Merhej Vicky
Published: November 2020

Fosfomycin is a decades-old antibiotic, currently reused because of its activity against multidrug-resistant bacteria. Here, we used a combined
in vitro/in silico
approach to search for fosfomycin resistance determinants in 25 new bacterial species isolated from the human microbiota.
Supplemental Material: The role of megacontinents in the supercontinent cycle
Authors: Wang Chong , Mitchell Ross , al. et
Published: November 2020

Supplemental Figure S1 and references providing the distance of continents from their Euler poles of rotation in the assembly of Eurasia.
Supplemental Material: Mechanical twinning of monazite expels radiogenic lead
Authors: Fougerouse Denis , al. et
Published: November 2020

Figure S1 (atom probe tomography data of specimens 3 and 4), and Figure S2 (bright field TEM image and EDS data).