bluuebunny/crossref_metadata_2025 huggingface dataset:
Two intronic cis‐acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia
Authors: Fellner Avi , Lossos Alexander , Kogan Elena , Argov Zohar , Gonzaga‐Jauregui Claudia , Shuldiner Alan R. , Darawshe Malak , Bazak Lily , Lidzbarsky Gabriel , Shomron Noam , Basel‐Salmon Lina , Goldberg Yael
Published: January 2021

POLR3A encodes the largest subunit of the DNA‐dependent RNA polymerase III. Pathogenic variants in this gene are associated with dysregulation of tRNA production and other non‐coding RNAs. POLR3A‐related disorders include variable phenotypes. The genotype–phenotype correlation is still unclear. Phenotypic analysis and exome sequencing were performed in four affected siblings diagnosed clinically with hereditary spastic ataxia, two healthy siblings and their unaffected mother. All four affected siblings (ages 46–55) had similar clinical features of early childhood‐onset hypodontia and adolescent‐onset progressive spastic ataxia. None had progeria, gonadal dysfunction or dysmorphism. All affected individuals had biallelic POLR3A pathogenic variants composed by two cis‐acting intronic splicing‐altering variants, c.1909 + 22G > A and c.3337–11 T > C. The two healthy siblings had wild‐type alleles. The mother and another unaffected sibling were heterozygous for the allele containing both variants. This is the first report addressing the clinical consequence associated with homozygosity for a unique pathogenic intronic allele in the POLR3A gene. This allele was previously reported in compound heterozygous combinations in patients with Wiedemann‐Rautenstrauch syndrome, a severe progeroid POLR3A‐associated phenotype. We show that homozygosity for this allele is associated with spastic ataxia with hypodontia, and not with progeroid features. These findings contribute to the characterization of genotype–phenotype correlation in POLR3A‐related disorders.
Construct validity of the brief physical activity assessment tool for clinical use in COPD
Authors: Cruz Joana , Jácome Cristina , Oliveira Ana , Paixão Cátia , Rebelo Patrícia , Flora Sofia , Januário Filipa , Valente Carla , Andrade Lília , Marques Alda
Published: January 2021

Introduction

Low physical activity (PA) levels are associated with poor health‐related outcomes in Chronic Obstructive Pulmonary Disease (COPD). Thus, PA should be routinely assessed in clinical practice.

Objectives

This study assessed the construct validity of the Brief Physical Activity Assessment Tool (BPAAT) for clinical use in COPD and explored differences in age, sex and COPD grades.

Methods

After linguistic adaptation of the tool to Portuguese, 110 patients (66.4 ± 9.6yrs, 72.7% male, FEV1 = 59.3 ± 25.5%predicted) completed the BPAAT and received an accelerometer. The BPAAT includes two questions assessing the weekly frequency and duration of vigorous‐ and moderate‐intensity PA/walking, classifying individuals as insufficiently or sufficiently active. The BPAAT was correlated with accelerometry (moderate PA, MPA = 1952‐5724 counts‐per‐min [CPM]); vigorous PA, VPA = 5725‐∞CPM; moderate‐to‐vigorous PA, MVPA = 1952‐∞CPM; daily steps), through: Spearman’s correlations (ρ) for continuous data; %agreement, Kappa, sensitivity and specificity, positive and negative predictive values (PPV, NPV) for categorical data.

Results

The BPAAT identified 73.6% patients as “insufficiently active” and 26.4% as “sufficiently active”. The BPAAT was weakly to moderately correlated with accelerometry (0.394 ≤ ρ ≤ 0.435, P < 0.05), except for VPA (P = 0.440). This was also observed in age (<65/≥65yrs), COPD grades (GOLD 1–2/3–4) and in male patients (0.363 ≤ ρ ≤ 0.518, P < 0.05 except for VPA). No significant correlations were found in female patients (P > 0.05). Agreement was fair to moderate (0.36 ≤ κ ≤ 0.43; 73.6% ≤ %agreement ≤ 74.5%; 0.50 ≤ sensitivity ≤ 0.52; 0.84 ≤ specificity ≤ 0.91, 0.55 ≤ PPV ≤ 0.79, 0.72 ≤ NPV ≤ 0.82).

Conclusion

The BPAAT may be useful to screen patients’ PA, independently of age and COPD grade, and identify male patients who are insufficiently active. Care should be taken when using this tool to assess vigorous PA or female patients.
Does Security of Land Operational Rights Matter for the Improvement of Agricultural Production Efficiency under the Collective Ownership in China?
Authors: Ji Xianqing , Liu Shouying , Yan Jianan , Li Youyi
Published: January 2021

Under the “separation of three rights” policy, the impact of security of land operational rights on agricultural production efficiency has attracted much attention in recent years. Data envelopment analysis and mediation effect analysis were applied to 888 family farms run by new‐type agricultural operators from Songjiang to identify the mechanism of the effect of land operational rights security on agricultural production efficiency through long‐term investment. The results show that greater security of land operational rights generally increased agricultural production efficiency. Approximately 37.94 percent of the impact could be explained by long‐term investment. The results also indicate that significant heterogeneity exists in the effect of land operational rights security on agricultural production efficiency at various levels of the family farms’ efficiency distributions. It is suggested that government should legalize land operational rights and give them a status equal to those of households’ contractual rights and land ownership rights in China's future land tenure reform.
Self‐awareness in children with developmental disorders: challenging the normal
Authors: Zebracki Kathy
Published: January 2021

This commentary is on the invited review by Rochat on pages 382–386 of this issue.
Drug adulteration of sexual enhancement supplements: a worldwide insidious public health threat
Authors: Yéléhé‐Okouma Mélissa , Pape Elise , Humbertjean Lisa , Evrard Marion , El Osta Rabih , Petitpain Nadine , Gillet Pierre , El Balkhi Souleiman , Scala‐Bertola Julien
Published: January 2021

Worldwide, the consumption of dietary supplements for the enhancement of sexual performance is common. Consumers are generally fond of these products because they often want to avoid drugs, preferring “natural” than “chemical” solutions. This is challenging, as many of these supplements labelled “herbal” or “natural” are actually adulterated with drugs, mainly phosphodiesterase‐5 inhibitors. This phenomenon is facilitated by fewer demanding regulations for marketing supplements. Thus, consumers may be widely exposed to serious adverse events, such as acute liver injury, kidney failure, pulmonary embolism, stroke or even death. We aim to warn physicians about this issue. This multidisciplinary review simultaneously deals with clinical consequences of this phenomenon, analytical toxicology and regulation. Indeed, after outlining this worldwide issue and highlighting that a drug‐adulterated dietary supplement is actually a falsified drug, we discuss its main contributing factors. Then, we describe some examples of adverse events of which a case of sildenafil–tadalafil‐induced ischaemic stroke that benefited medical care in our hospital. Furthermore, we present some means to avoid adulteration and discuss their limitations that may be explained by the heterogeneity of the regulation of dietary supplements between countries. Doing so, we point out the requirement of a global harmonization of this regulation for an efficient eradication of this public health threat. Meanwhile, dietary supplements should be considered adulterated until proven otherwise. Thus, we encourage physicians to investigate these products in the drug histories of their patients, especially when clinical conditions cannot be explained by classical aetiologies.
Tumor‐associated macrophages in immunotherapy
Authors: Yan Shijia , Wan Guohui
Published: January 2021

Tumor‐associated macrophages (TAMs) are essential components of the tumor microenvironment involved in the progression and metastasis of cancer. They are intimately involved in angiogenesis and immunosuppression in normal and malignant tissues, as well as pro‐fibrotic activities. With the development of immunotherapy, eradication of cancer cells through activation of the innate immune system has achieved inspiring results, whereas only a handful of patients show a durable response. The tumor‐suppressive environment has been investigated with respect to playing a vital role in cancer relapse. In this review, we uncover the heterogeneity of the origin of TAMs, as well as the functions of TAMs in tumor progression associated with intricate regulatory networks in the tumor microenvironment, aiming to inspire therapeutic insight for tumor immunotherapy.
The role of eutherian‐specific RTL1 in the nervous system and its implications for the Kagami‐Ogata and Temple syndromes
Authors: Kitazawa Moe , Sutani Akito , Kaneko‐Ishino Tomoko , Ishino Fumitoshi
Published: January 2021

RTL1 (also termed paternal expressed 11 (PEG11)) is considered the major imprinted gene responsible for the placental and fetal/neonatal muscle defects that occur in the Kagami–Ogata and Temple syndromes (KOS14 and TS14, respectively). However, it remains elusive whether RTL1 is also involved in their neurological symptoms, such as behavioral and developmental delay/intellectual disability, feeding difficulties, motor delay, and delayed speech. Here, we demonstrate that the mouse RTL1 protein is widely expressed in the central nervous system (CNS), including the limbic system. Importantly, two disease model mice with over‐ and under‐expression of Rtl1 exhibited reduced locomotor activity, increased anxiety, and impaired amygdala‐dependent cued fear, demonstrating that Rtl1 also plays an important role in the CNS. These results indicate that the KOS14 and TS14 are neuromuscular as well as neuropsychiatric diseases caused by irregular CNS RTL1 expression, presumably leading to impaired innervation of motor neurons to skeletal muscles as well as malfunction of the hippocampus‐amygdala complex. It is of considerable interest that eutherian‐specific RTL1 is expressed in mammalian‐ and eutherian‐specific brain structures, that is, the corticospinal tract and corpus callosum, respectively, suggesting that RTL1 might have contributed to the acquisition of both these structures themselves and fine motor skill in eutherian brain evolution.
Psychometric validation and meaningful within‐patient change of the Migraine‐Specific Quality of Life questionnaire version 2.1 electronic patient‐reported outcome in patients with episodic and chronic migraine
Authors: Speck Rebecca M. , Yu Ren , Ford Janet H. , Ayer David W. , Bhandari Rohit , Wyrwich Kathleen W.
Published: January 2021

Objective

To evaluate the measurement properties of all three domains of the Migraine‐Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) electronic patient‐reported outcome (ePRO) to assess the functional impact of migraine in patients with episodic or chronic migraine (CM); and identify meaningful within‐patient change thresholds for the Role Function‐Restrictive (RFR), Role Function‐Preventive (RFP), and Emotional Function (EF) domains.

Methods

Data were drawn from three double‐blind, placebo‐controlled, and randomized Phase 3 clinical studies (episodic migraine [EM]: EVOLVE‐1 and EVOLVE‐2; CM: REGAIN). The psychometric properties of the MSQ v2.1 ePRO domains were demonstrated by evaluating reliability (internal consistency and test–retest), construct validity (convergent and known groups), and responsiveness. Meaningful within‐patient change thresholds for domains were estimated using anchor‐based approaches, supplemented by empirical cumulative distribution function curves and probability density function plots to enable interpretation of meaningful change over 3 months. The Patient Global Impression of Severity (PGI‐S) and Patient Global Impression of Improvement served as anchors.

Results

A total of 2,850 patients with either EM (EVOLVE‐1: 851; EVOLVE‐2: 909) or CM (REGAIN: 1,090) were included. The Cronbach's alpha estimates of internal consistency exceeded the recommended threshold of ≥0.70 for all domains from the three studies, indicating adequate internal consistency. Test–retest reliability intraclass correlation coefficients were ≥0.80 for all domains across all three studies, demonstrating almost perfect agreement. Convergent validity was supported by moderate‐to‐strong correlation (r ≥ 0.30) between all domains of MSQ v2.1 ePRO and studied anchors (Migraine Disability Assessment Score and PGI‐S scores) across all three studies. Known group validity was established between all domains and subgroups of patients stratified by baseline PGI‐S scores and baseline number of monthly migraine headache days for all three studies. The 3‐month meaningful within‐patient change thresholds were the same for EM and CM for RFP: 20.00 and EF: 26.67; and for RFR: 25.71.

Conclusions

These findings demonstrate that all three domains of the MSQ v2.1 ePRO have sufficient reliability, validity, responsiveness, and appropriate interpretation standards. Our results suggest that MSQ v2.1 ePRO is a well‐defined and reliable patient‐reported outcome instrument that is suitable for use in clinical studies for evaluating the impact of migraine on patient functioning in episodic and CM.
Mismatched response predicts behavioral speech discrimination outcomes in infants with hearing loss and normal hearing
Authors: Uhler Kristin , Hunter Sharon , Gilley Phillip M.
Published: January 2021

Children with hearing loss (HL) remain at risk for poorer language abilities than normal hearing (NH) children despite targeted interventions; reasons for these differences remain unclear. In NH children, research suggests speech discrimination is related to language outcomes, yet we know little about it in children with HL under the age of 2 years. We utilized a vowel contrast, /a‐i/, and a consonant‐vowel contrast, /ba‐da/, to examine speech discrimination in 47 NH infants and 40 infants with HL. At Mean age =3 months, EEG recorded from 11 scalp electrodes was used to compute the time‐frequency mismatched response (TF‐MMRSE) to the contrasts; at Mean age =9 months, behavioral discrimination was assessed using a head turn task. A machine learning (ML) classifier was used to predict behavioral discrimination when given an arbitrary TF‐MMRSE as input, achieving accuracies of 73% for exact classification and 92% for classification within a distance of one class. Linear fits revealed a robust relationship regardless of hearing status or speech contrast. TF‐MMRSE responses in the delta (1–3.5 Hz), theta (3.5–8 Hz), and alpha (8–12 Hz) bands explained the most variance in behavioral task performance. Our findings demonstrate the feasibility of using TF‐MMRSE to predict later behavioral speech discrimination.
Epidemiology and seasonality of human parainfluenza serotypes 1‐3 in Australian children
Authors: Greiff Daniel R. L. , Patterson‐Robert Alice , Blyth Christopher C. , Glass Kathryn , Moore Hannah C.
Published: January 2021

Background

Parainfluenza viruses are significant contributors to childhood respiratory illness worldwide, although detailed epidemiological studies are lacking. Few recent Australian studies have investigated serotype‐specific PIV epidemiology, and there is a paucity of southern hemisphere PIV reports. We report age‐stratified PIV hospitalisation rates and a mathematical model of PIV seasonality and dynamics in Western Australia (WA).

Methods

We used linked perinatal, hospital admission and laboratory diagnostic data of 469 589 children born in WA between 1996 and 2012. Age‐specific rates of viral testing and PIV detection in hospitalised children were determined using person time‐at‐risk analysis. PIV seasonality was modelled using a compartmental SEIRS model and complex demodulation methods.

Results

From 2000 to 2012, 9% (n = 43 627) of hospitalised children underwent PIV testing, of which 5% (n = 2218) were positive for PIV‐1, 2 or 3. The highest incidence was in children aged 1‐5 months (PIV‐1:62.6 per 100 000 child‐years, PIV‐2:26.3/100 000, PIV‐3:256/100 000), and hospitalisation rates were three times higher for Aboriginal children compared with non‐Aboriginal children overall (IRR: 2.93). PIV‐1 peaked in the autumn of even‐numbered years, and PIV‐3 annually in the spring, whereas PIV‐2 had inconsistent peak timing. Fitting models to the higher incidence serotypes estimated reproduction numbers of 1.24 (PIV‐1) and 1.72 (PIV‐3).

Conclusion

PIV‐1 and 3 are significant contributors towards infant respiratory hospitalisations. Interventions should prioritise children in the first 6 months of life, with respect to the observed autumn PIV‐1 and spring PIV‐3 activity peaks. Continued surveillance of all serotypes and investigation into PIV‐1 and 3 interventions should be prioritised.
Absence of association between 2019‐20 influenza vaccination and COVID‐19: Results of the European I‐MOVE‐COVID‐19 primary care project, March‐August 2020
Authors: Kissling Esther , Hooiveld Mariëtte , Brytting Mia , Vilcu Ana‐Maria , de Lange Marit , Martínez‐Baz Iván , Sigerson Debbie , Enkirch Theresa , Belhillil Sylvie , Meijer Adam , Castilla Jesus , William Naoma , Carnahan AnnaSara , Falchi Alessandra , Hendriksen Janneke , Casado Itziar , Murray Josie , Enouf Vincent , Dijkstra Frederika , Marques Diogo F. P. , Valenciano Marta
Published: January 2021

Background

Claims of influenza vaccination increasing COVID‐19 risk are circulating. Within the I‐MOVE‐COVID‐19 primary care multicentre study, we measured the association between 2019‐20 influenza vaccination and COVID‐19.

Methods

We conducted a multicentre test‐negative case‐control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019‐20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with <15% of missing influenza vaccination. In secondary analyses, we included five countries, using multiple imputation with chained equations to account for missing data.

Results

We included 257 COVID‐19 cases and 1631 controls in the main analysis (three countries). The overall aOR between influenza vaccination and COVID‐19 was 0.93 (95% CI: 0.66‐1.32). The aOR was 0.92 (95% CI: 0.58‐1.46) and 0.92 (95% CI: 0.51‐1.67) among those aged 20‐59 and ≥60 years, respectively. In secondary analyses, we included 6457 cases and 69 272 controls. The imputed aOR was 0.87 (95% CI: 0.79‐0.95) among all ages and any delay between swab and symptom onset.

Conclusions

There was no evidence that COVID‐19 cases were more likely to be vaccinated against influenza than controls. Influenza vaccination should be encouraged among target groups for vaccination. I‐MOVE‐COVID‐19 will continue documenting influenza vaccination status in 2020‐21, in order to learn about effects of recent influenza vaccination.
‘It's been adapted rather than impacted’: A qualitative evaluation of the impact of Covid‐19 restrictions on the positive behavioural support of people with an intellectual disability and/or autism
Authors: McKenzie Karen , Murray George C. , Martin Rachel
Published: January 2021

Background

We used a qualitative approach to explore the experiences of social care staff regarding the provision of positive behavioural support (PBS) to people with an intellectual disability at the height of the Covid‐19 restrictions.

Method

We conducted semi‐structured interviews with 19 staff who had recently completed a PBS workforce development programme. Data were analysed using thematic analysis.

Results

Three themes were identified in the context of the restrictions: The challenges to maintaining quality of life and PBS of the people being supported and staff attempts to overcome these; the ways in which PBS and behaviour support plans were implemented and the impact on behaviours that challenge; the ways in which PBS principles were applied at organisational levels to help to understand and address staff stress and distress.

Conclusions

Overall, the staff identified many unexpected benefits of the restrictions. The results are discussed in the context of the study limitations.
Friendship and romance across the U.S. political divide: Hindrance or help for outgroup political attitudes?
Authors: Buliga Elena , MacInnis Cara C. , Hodson Gordon , Biamonte Julia
Published: January 2021

Consistent with the intergroup contact literature, cross‐political relationships (e.g., friendships or romantic relationships between different partisans) may help reduce inter‐political group prejudice. Given that unfavorable attitudes based on the political group membership are particularly heightened at present in the United States, we explored whether having cross‐political friendships (Study 1) or romantic relationships (Study 2) predict more positive interpersonal or intergroup attitudes among American Democrats and Republicans. In Study 1, using a social network measure (N = 301), where participants reported on their closest friends, cross‐political (versus same‐political) friendship was associated with less positive interpersonal attitudes when this relationship was unsatisfying. Having any (versus no) or more (versus less) cross‐political group friendships was not associated with holding more positive intergroup attitudes. In Study 2, cross‐political romantic relationships were examined (N = 392). Having a cross‐ (versus same‐) political romantic relationship was associated with relatively less positive attitudes toward the political outgroup via lower empathy when relationship satisfaction was low. Study findings highlight the potential limitations of the beneficial effects of intergroup contact.
Effects of a major Amazonian river confluence on the distribution of floodplain forest avifauna
Authors: Laranjeiras Thiago Orsi , Naka Luciano Nicolas , Leite Gabriel Augusto , Cohn‐Haft Mario
Published: January 2021

Aim

Although ‘river color’ or water type is an important determinant of Amazonian floodplain biodiversity, the relevance of mixing distinct water types at river confluences to the distribution of terrestrial floodplain fauna has been largely overlooked. We investigated how the influx of a sediment‐rich whitewater tributary affects the floodplain forest avifauna along the world's largest blackwater river.

Location

Northwestern Brazilian Amazon.

Taxon

Birds.

Methods

We sampled floodplain avifauna and retrieved estimates of sediment concentration in the water (the main parameter in river‐water classification) at 52 sites, along the Negro (blackwater) and Branco (whitewater) rivers, above and below their confluence. We compared species richness and composition using analyses of variance, ordinations, generalized linear models and indicator species analyses.

Results

Bird species composition on the lower Rio Negro (below the confluence) was distinct from both the upper Negro (above the confluence) and the Branco, and species richness on the Negro increased below the confluence. Typical whitewater bird species occurring on the Branco were found exclusively or predominantly along the left side of the lower Rio Negro, where the Branco's muddy waters seem to be channelled. Overall avian compositional variation among sites was correlated with sediment concentration in the water, a determinant of floodplain forest structure.

Main conclusions

The influx of the muddy waters of the Rio Branco into the Rio Negro promotes the co‐occurrence of bird species that are segregated by river type upstream, increasing species richness at the landscape scale. Rather than just representing a potential blackwater barrier between whitewater systems, the lower Rio Negro comprises a unique biogeographical transition zone, with a mixed avifauna occurring in a mosaic of varied floodplain forest types. Our results suggest that confluences of large rivers of distinct water types represent a significant factor determining species distributional boundaries and geographic patterns of Amazonian floodplain biodiversity.
Phylogenetic structure of European forest vegetation
Authors: Padullés Cubino Josep , Lososová Zdeňka , Bonari Gianmaria , Agrillo Emiliano , Attorre Fabio , Bergmeier Erwin , Biurrun Idoia , Campos Juan A. , Čarni Andraž , Ćuk Mirjana , De Sanctis Michele , Indreica Adrian , Jiménez‐Alfaro Borja , Khanina Larisa , Knollová Ilona , Lenoir Jonathan , Pielech Remigiusz , Rašomavičius Valerijus , Škvorc Željko , Svenning Jens‐Christian , Vassilev Kiril , Willner Wolfgang , Chytrý Milan
Published: January 2021

Aims

(a) To determine the contribution of current macro‐environmental factors in explaining the phylogenetic structure of European forest vegetation, (b) to map and describe spatial patterns in their phylogenetic structure and (c) to examine which lineages are the most important contributors to phylogenetic clustering and whether their contribution varies across forest types and regions.

Location

Europe.

Taxon

Angiosperms.

Methods

We analysed the phylogenetic structure of 61,816 georeferenced forest vegetation plots across Europe considering alternative metrics either sensitive to basal (ancient evolutionary dynamics) or terminal (recent dynamics) branching in the phylogeny. We used boosted regression trees to model metrics of the phylogenetic structure as a function of current macro‐environmental factors. We also identified clades encompassing significantly more taxa than under random expectation in phylogenetically clustered plots.

Results

Phylogenetic clustering was driven by climatic stress and instability and was strong in the areas glaciated during the Pleistocene, likely reflecting limited postglacial migration, and to a lower extent in areas of northern‐central Europe and in summer‐dry Mediterranean regions. Phylogenetic overdispersion was frequent in the hemiboreal zone in Russia, in some areas around the Mediterranean Basin, and along the Atlantic seaboard of the Iberian Peninsula. The families Ericaceae, Poaceae and Fagaceae were overrepresented in clustered plots in different regions of Europe.

Main conclusions

We provide the first maps and analyses on the phylogenetic structure of European forest vegetation at the plot level. Our results highlight the role of environmental filtering, postglacial dispersal limitation and spatial transitions between major biomes in determining the distribution of plant lineages in Europe.
Expository multimedia comprehension in E‐learning: Presentation format, verbal ability and working memory capacity
Authors: Burin Debora I. , González Federico M. , Martínez Magali , Marrujo Jonathan G.
Published: January 2021

Most of the studies establishing factors affecting digital text and multimedia comprehension have been conducted in controlled conditions. The present study sought to test and extend the modality and seductive details effects, and the role of verbal ability and working memory capacity, to a remote, self‐paced, E‐learning scenario. Two hundred and thirteen first‐year undergraduates read or watched videos about scientific expository content in three formats: digital text (written expository texts, navigated in seven screens), presentation video (audio explanation, with written keywords), and presentation video with dynamic decorative images (audio explanation, written keywords, and dynamic decorative and irrelevant images). In a face‐to‐face session, they completed working memory and verbal ability tests. Comprehension performance was similar for the three conditions. For the multimedia videos with dynamic decorative irrelevant images, comprehension depended on working memory capacity. Verbal ability was relevant for both expository text and videos.
Factors associated with hypertension among stroke‐free indigenous Africans: Findings from the SIREN study
Authors: Akpa Onoja M. , Okekunle Akinkunmi P. , Ovbiagele Bruce , Sarfo Fred S. , Akinyemi Rufus O. , Akpalu Albert , Wahab Kolawole W. , Komolafe Morenikeji , Obiako Reginald , Owolabi Lukman F. , Ogbole Godwin , Fawale Bimbo , Fakunle Adekunle , Asaleye Christianah M. , Akisanya Cynthia O. , Hamisu Dambatta A. , Ogunjimi Luqman , Adeoye Abiodun , Ogah Okechukwu , Lackland Dan , Uvere Ezinne O. , Faniyan Moyinoluwalogo M. , Asowata Osahon J. , Adeleye Osimhiarherhuo , Aridegbe Mayowa , Olunuga Taiwo , Yahaya Isah S. , Olaleye Adeniji , Calys‐Tagoe Benedict , Owolabi Mayowa O. ,   the SIREN Study as part of the H3Africa Consortium
Published: January 2021

Hypertension is one of the most important risk factors for stroke and cardiovascular diseases (CVD) globally. Understanding risk factors for hypertension among individuals with matching characteristics with stroke patients may inform primordial/primary prevention of hypertension and stroke among them. This study identified the risk factors for hypertension among community‐dwelling stroke‐free population in Ghana and Nigeria. Data for 4267 community‐dwelling stroke‐free controls subjects in the Stroke Investigative Research and Education Network (SIREN) study in Nigeria and Ghana were used. Participants were comprehensively assessed for sociodemographic, lifestyle and metabolic factors using standard methods. Hypertension was defined as a previous diagnosis by a health professional or use of an anti‐hypertensive drug or mean systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Logistic regression analysis was used to estimate adjusted odds ratios (aOR) of hypertension and their 95% confidence intervals (CI) at p < .05. Overall, 56.7% of the participants were hypertensive with a higher proportion among respondents aged ≥60 years (53.0%). Factors including physical inactivity (aOR: 9.09; 95% CI: 4.03 to 20.53, p < .0001), diabetes (aOR: 2.70; CI: 1.91 to 3.82, p < .0001), being ≥60 years (aOR: 2.22; 95% CI: 1.78 to 2.77, p < .0001), and family history of CVD (aOR 2.02; CI: 1.59 to 2.56, p < .0001) were associated with increased aOR of hypertension. Lifestyle factors were associated with hypertension in the current population of community‐dwelling stroke‐free controls in west Africa. Community‐oriented interventions to address sedentary lifestyles may benefit this population and reduce/prevent hypertension and stroke among them.
Sex‐specific associations between life‐history traits and a novel reproductive polymorphism in the Pacific field cricket
Authors: Richardson Jon , Heinen‐Kay Justa L. , Zuk Marlene
Published: January 2021

Associations between heritable polymorphisms and life‐history traits, such as development time or reproductive investment, may play an underappreciated role in maintaining polymorphic systems. This is because selection acting on a particular morph could be bolstered or disrupted by correlated changes in life history or vice versa. In a Hawaiian population of the Pacific field cricket (Teleogryllus oceanicus), a novel mutation (flatwing) on the X‐chromosome is responsible for a heritable polymorphism in male wing structure. We used laboratory cricket colonies fixed for male wing morph to investigate whether males and females bearing the flatwing or normal‐wing (wild‐type) allele differed in their life‐history traits. We found that flatwing males developed faster and had heavier testes than normal‐wings, whereas flatwing homozygous females developed slower and had lighter reproductive tissues than normal‐wing homozygous females. Our results advance our understanding of the evolution of polymorphisms by demonstrating that the genetic change responsible for a reproductive polymorphism can also have consequences for fundamental life‐history traits in both males and females.
Oxidative and radiation stress induces transposable element transcription in Drosophila melanogaster
Authors: de Oliveira Daniel Siqueira , Rosa Marcos Trindade , Vieira Cristina , Loreto Elgion L. S.
Published: January 2021

It has been shown that stressors are capable of activating transposable elements (TEs). Currently, there is a hypothesis that stress activation of TEs may be involved in adaptive evolution, favouring the increase in genetic variability when the population is under adverse conditions. However, TE activation under stress is still poorly understood. In the present study, we estimated the fraction of differentially expressed TEs (DETEs) under ionizing radiation (144, 360 and 864 Gy) and oxidative stress (dioxin, formaldehyde and toluene) treatments. The stress intensity of each treatment was estimated by measuring the number of differentially expressed genes, and we show that several TEs families are activated by stress whereas others are repressed. The proportion of DETEs was positively related to stress intensity. However, even under the strongest stress, only a small fraction of TE families were activated (9.28%) and 17.72% were repressed. Considering all treatments together, the activated proportion was 19.83%. Nevertheless, as several TEs are incomplete or degenerated, only 10.55% of D. melanogaster mobilome is, at same time, activated by the stressors and able to transpose or at least code a protein. Thus, our study points out that although stress activates TEs, it is not a generalized activation process, and for some families, the stress induces repression.
Using gradient Forest to predict climate response and adaptation in Cork oak
Authors: Vanhove Mathieu , Pina‐Martins Francisco , Coelho Ana Cristina , Branquinho Cristina , Costa Augusta , Batista Dora , Príncipe Adriana , Sousa Paulo , Henriques André , Marques Isabel , Belkadi Bouchra , Knowles L. Lacey , Paulo Octávio S.
Published: January 2021

Climate change is impacting locally adapted species such as the keystone tree species cork oak (Quercus suber L.). Quantifying the importance of environmental variables in explaining the species distribution can help build resilient populations in restoration projects and design forest management strategies. Using landscape genomics, we investigated the population structure and ecological adaptation of this tree species across the Mediterranean Basin. We applied genotyping by sequencing and derived 2,583 single nucleotide polymorphism markers genotyped from 81 individuals across 17 sites in the studied region. We implemented an approach based on the nearest neighbour haplotype ‘coancestry’ and uncovered a weak population structure along an east–west climatic gradient across the Mediterranean region. We identified genomic regions potentially involved in local adaptation and predicted differences in the genetic composition across the landscape under current and future climates. Variants associated with temperature and precipitation variables were detected, and we applied a nonlinear multivariate association method, gradient forest, to project these gene–environment relationships across space. The model allowed the identification of geographic areas within the western Mediterranean region most sensitive to climate change: south‐western Iberia and northern Morocco. Our findings provide a preliminary assessment towards a potential management strategy for the conservation of cork oak in the Mediterranean Basin.
Evidence of a rapid and adaptive response of hemipteran mouthparts to a physical barrier
Authors: Allen Pablo E. , Cui Quentin , Miller Christine W.
Published: January 2021

Animals have encountered novel foods at points throughout history, due to factors such as range expansions and niche shifts driven by competition. One of the first challenges presented by novel foods is how to eat them. Mouthpart morphology is thus critical during the process of host shifts. Developmental plasticity in mouthparts is one potential mechanism that may allow animals to tolerate new foods and eventually to thrive upon them. Here, we investigated the extent to which insect mouthparts from two geographically distant populations can converge in morphology when feeding on common resources. We conducted a common garden/reciprocal transplant experiment using two populations of the cactus bug, Narnia femorata, that differ in mouthpart length. This insect uses straw‐like mouthparts (hereafter ‘beak’) to get through the cactus fruit wall to reach the pulp inside. Our experimental results revealed clear developmental plasticity in beak length. Insects from both populations grew longer beaks when they fed on the cactus fruit with the thicker walls, and they grew shorter beaks when they fed on the cactus fruit with the thinner walls. Thus, insects from distant populations exhibited immediate developmental responses to a new food, and in the predicted directions. These results suggest that some fauna may be able to respond more rapidly than predicted when they encounter novel plants.
Flagellum Malfunctions Trigger Metaboly as an Escape Strategy in Euglena gracilis
Authors: Chen Yong‐Jun , Huang Guo‐Bin
Published: January 2021

Euglenoids present the ability to alter the shape of their bodies, a process referred to as metaboly. Metaboly is usually used by phagotrophic cells to engulf their prey. However, Euglena gracilis is osmotrophic and photosynthetic. Though metaboly was discovered centuries ago, it remains unclear why E. gracilis undergo metaboly and what causes them to deform, and some consider metaboly to be a functionless ancestral vestige. Here, we discover that flagellum malfunctions trigger metaboly and metaboly is a smart escape strategy adopted by E. gracilis when the proper rotation and beating of the flagellum are hindered by restrictions including surface obstruction, sticking, resistance, or limited space. Metaboly facilitates escape in five ways: (i) detaching the body from the surface; (ii) enlarging the space between flagellum and the restricting surface which restores beating and rotation of the flagellum; (iii) decreasing the torque of viscous resistance for rotation of the body; (iv) decreasing the length of the body; and (v) crawling backwards on a surface or swimming backwards if the flagellum completely malfunctions or has broken off. Our findings suggest that metaboly plays a key role in enabling E. gracilis to escape from harmful conditions when flagellar functions are impaired or absent.
Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice
Authors: Wolf Leslie E. , Patel Mayank J. , Tarver Brett A. Williams , Austin Jeffrey L. , Dame Lauren A. , Beskow Laura M.
Published: January 2021

Answering important public health questions often requires collection of sensitive information about individuals. For example, our understanding of how HIV is transmitted and how to prevent it only came about with people's willingness to share information about their sexual and drug-using behaviors. Given the scientific need for sensitive, personal information, researchers have a corresponding ethical and legal obligation to maintain the confidentiality of data they collect and typically promise in consent forms to restrict access to it and not to publish identifying data.

The interests of others, however, can threaten researchers' promises of confidentiality when legal demands are made to access research data (e.g., through subpoena). In some cases, the subject of the litigation is tightly connected to the research questions, and litigants' interest in the data is not surprising. Researchers conducting studies on tobacco or occupational or other chemical exposures, for example, are relatively frequent targets of subpoenas.
Conflict Resolution in the Clinical Setting: A Story Beyond Bioethics Mediation
Authors: Morreim Haavi
Published: January 2021

Rarely do ethics consults focus on genuine moral puzzlement in which people collectively wonder what is the right thing to do. Far more often, consults are about conflict. Each side knows quite well what is “right.” The problem is that the other side is too blind or stubborn to recognize it. And so the ethics consultant is called, perhaps in the hope that s/he will throw the weight of ethics toward one side and end the controversy so everyone can get on with other business.

Perhaps the greater problem in these scenarios is that even if one side “wins” by gaining the power to dictate what happens next, the toxicity permeating the relationships often markedly worsens and other conflicts erupt, major and minor.
Legal Innovations to Advance a Culture of Health
Authors: Hodge James G. , Weidenaar Kim , Baker-White Andy , Barraza Leila , Bauerly Brittney Crock , Corbett Alicia , Davis Corey , Frey Leslie T. , Griest Megan M. , Healy Colleen , Krueger Jill , Lowrey Kerri McGowan , Tilburg William
Published: January 2021

Since its inception in 2010, the Network for Public Health Law (Network) has aligned with federal, state, tribal, and local public health practitioners to assess how law can promote and protect the public’s health. In 2013, Network authors illustrated major trends in public health laws and policies emanating from an internal assessment of thousands of requests for technical assistance nationally. More recently, the Robert Wood Johnson Foundation (RWJF) has invited the Network and other partners to consider new ideas and strategies toward building a “culture of health.” Per Figure 1, RWJF’s conception of a culture of health emphasizes key action areas essential to the promotion of health across all sectors and diverse populations.
Effects of ML351 and tissue plasminogen activator combination therapy in a rat model of focal embolic stroke
Authors: Cheng Guangsen , Zhao Wei , Xin Yongjie , Huang Guomin , Liu Yongkang , Li Zhongliang , Zhan Meixiao , Li Yong , Lu Ligong , van Leyen Klaus , Liu Yu
Published: January 2021

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by risks of hemorrhagic transformation (HT). We have reported that a new 12/15‐lipoxygenase (12/15‐LOX) inhibitor ML351 reduced tPA related HT in mice subjected to experimental stroke under anticoagulation. In this study, we asked whether ML351 can ameliorate tPA induced HT in an embolic stroke model. Rats were subjected to embolic middle cerebral artery occlusion with 2 or 3 hr ischemia and tPA infusion, with or without ML351. Regional cerebral blood flow was monitored 2 hr after ischemia and continuously monitored for 1 hr after treatment for determining reperfusion. Hemoglobin was determined in brain homogenates and infarct volume was quantified at 24 hr after stroke.12/15‐LOX, cluster of differentiation 68(CD68), immunoglobulin G (IgG), and tight junction proteins expression was detected by immunohistochemistry. ML351 significantly reduced tPA related hemorrhage after stroke without affecting its thrombolytic efficacy. ML351 also reduced blood–brain barrier disruption and improved preservation of junction proteins. ML351 and tPA combination improved neurological deficit of rats even though ML351 did not further reduce the infarct volume compared to tPA alone treated animals. Pro‐inflammatory cytokines were suppressed by ML351 both in vivo and in vitro experiments. We further showed that ML351 suppressed the expression of c‐Jun‐N‐terminal kinase (JNK) in brains and microglia cultures, whereas exogenous 12‐HETE attenuated this effect in vitro. In conclusion, ML351 and tPA combination therapy is beneficial in ameliorating HT after ischemic stroke. This protective effect is probably because of 12/15‐LOX inhibition and suppression of JNK‐mediated microglia/macrophage activation.

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Efficacy of topical calcipotriol betamethasone dipropionate as a new adjuvant therapy to follicular unit extraction technique in treatment of stable vitiligo: clinical, dermoscopic and immunohistological study
Authors: Abd Elazim Nagwa E. , Kamal Ahmed , Abdel Gaber Reham M. , Fathy Eman , EL‐Deek Heba E. M.
Published: January 2021

Background

Follicular unit extraction (FUE) grafting is a surgical procedure which provides the vitiliginous patches with undifferentiated stem cells of the hair follicles. It has been postulated that adjuvant therapy enhances the results. This is the first study to assess two different adjuvant therapies vs FUE alone.

Aims

To study the efficiency of FUE alone or combined with either topical calcipotriol betamethasone dipropionate (CBD) or NB‐UVB phototherapy in cases of nonsegmental stable vitiligo. To assess the role of dermoscopy in monitoring the pattern and degree of repigmentation.

Patients/ Methods

53 patients with 94 lesions with stable nonsegmental vitiligo were divided into three groups. Group 1 (n = 16) with 30 lesions received FUE alone. Group 2 (n = 18) with 32 lesions received FUE plus topical CBD. Group 3 (n = 19) with 32 lesions received FUE plus NB‐UVB phototherapy. Assessment was done by grades of repigmentation, color match, percent of size reduction, and immunohistochemical evaluation of perilesional CD8+T lymphocytes.

Results

The fastest onset of repigmentation was observed in both groups 2 and 3 in the second week (16.7%, 10.5%, respectively).Group 2 achieved the best response by all methods of assessment. Perifollicular diffuse repigmentation was the commonest dermoscopic pattern in 60 lesions (63.8%). There was a statistically significant decrease in perilesional CD8+T lymphocytes after 4 months.

Conclusion

FUE is an effective method of surgical treatment of stable vitiligo, and topical CBD as a new adjuvant therapy is successful in targeting the immunological background of vitiligo. Dermoscopy has an essential role in monitoring the repigmentation response.
Does the addition of clonidine to opioid therapy improve outcomes in infants with Neonatal Abstinence Syndrome?
Authors: D'Abaco Elise
Published: January 2021

To undertake a literature search and critical appraisal of best available evidence to answer the clinical question: Does the addition of clonidine (I) to standard treatment with an opioid (C) improve outcomes (O) in infants with Neonatal Abstinence Syndrome? A search of both comprehensive (MedLine and Embase) and pre‐filtered databases (Dynamed, UpToDate and TRIP), utilising Boolean Operators to combine search terms appropriately. Three relevant studies were identified. One paper describing the outcomes of a randomised controlled trial by Agthe et al. (2009) most accurately answered the clinical question posed. This paper was critically appraised, and evidence applied to the clinical scenario. The use of clonidine as an adjunct to opioid in the management of infants with NAS reduces the total number of treatment days and dose of opioid required to control symptoms. However, there is a higher risk of rebound in symptoms post‐cessation of opioid and clinicians need to account for this in their discharge planning. More large scale, multi‐centre high‐quality research is needed to clarify the role of clonidine in the treatment of NAS: as monotherapy versus adjunct, the optimal dose and longer‐term impact on neurodevelopment.