bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-targeting B-RAF and PTEN enables sensory axons to regenerate across and beyond the spinal cord injury
Authors: Noristani Harun N. , Kim Hyukmin , Pang Shuhuan , Zhong Jian , Son Young-Jin
Published: March 2022

Primary sensory axons in adult mammals fail to regenerate after spinal cord injury (SCI), in part due to insufficient intrinsic growth potential. Robustly boosting their growth potential continues to be a challenge. Previously, we showed that constitutive activation of B-RAF (rapidly accelerated fibrosarcoma kinase) markedly promotes axon regeneration after dorsal root and optic nerve injuries. The regrowth is further augmented by supplemental deletion of PTEN (phosphatase and tensin homolog). Here, we examined whether concurrent B-RAF activation and PTEN deletion promotes dorsal column axon regeneration after SCI. Remarkably, genetically targeting B-RAF and PTEN selectively in DRG neurons of adult mice enables many DC axons to enter, cross, and grow beyond the lesion site after SCI; some axons reach ~2 mm rostral to the lesion by 3 weeks post-injury. Co-targeting B-RAF and PTEN promotes more robust DC regeneration than a pre-conditioning lesion, which additively enhances the regeneration triggered by B-RAF/PTEN. We also found that post-injury targeting of B-RAF and PTEN enhances DC axon regeneration. These results demonstrate that co-targeting B-RAF and PTEN effectively enhances the intrinsic growth potential of DC axons after SCI and therefore may help to develop a novel strategy to promote robust long-distance regeneration of primary sensory axons.
E. coli Leucine-responsive regulatory protein bridges DNA in vivo and tunably dissociates in the presence of exogenous leucine
Authors: Ziegler Christine A. , Freddolino Peter L.
Published: March 2022

Feast-Famine Response Proteins are a widely conserved class of global regulators in prokaryotes, the most highly studied of which is the E. coli leucine-responsive regulatory protein (Lrp). Lrp senses environmental nutrition status and subsequently regulates up to one-third of the genes in E. coli, either directly or indirectly. Lrp exists predominantly as octamers and hexadecamers (16mers), where leucine is believed to shift the equilibrium towards the octameric state. In this study, we analyzed the effects of three oligomerization state mutants of Lrp in terms of their ability to bind to DNA and regulate gene expression in response to exogenous leucine. We find that oligomerization beyond dimers is required for Lrp’s regulatory activity, and that contrary to prior speculation, exogenous leucine modulates Lrp activity at its target promoters exclusively by inhibiting Lrp binding to DNA. We also find evidence that Lrp binding bridges DNA over length scales of multiple kilobases, revealing a new range of mechanisms for Lrp-mediated transcriptional regulation.
What drives bank lending? A closer look at bank lending types in Africa
Authors: Ayagre Philip , Dzeha Gloria , Kriese Maryam , Kusi Baah
Published: March 2022

Purpose

In this study, the authors present unique evidence on bank lending types by paying particular attention to the factors that drive the different types of bank lending in Africa using bank level data.

Design/methodology/approach

In presenting such evidence, the study employs a robust fixed effect panel data with year and technological controls comprising 57 banks from 29 African economies between 2006 and 2015.

Findings

The results show that different factors affect different bank lending types differently in Africa. Specifically, while the authors find that total or aggregate bank lending is positively driven by bank capitalization and spread but negatively driven by bank size, corporate and commercial bank lending is positively driven by bank size, spread, inflation, elections and extent of business disclosure but negatively driven by bank capitalization, loan loss reserves, operational cost and gross domestic product per capita. Moreover, interbank lending is both negatively and positively driven by bank capitalization and size, respectively, while other bank lending type is driven positively by financial crisis but negatively driven by bank size, inflation and extent of business disclosure. Finally, retail and consumer lending is positively driven by bank capitalization, loan loss reserves and spread while negatively driven by bank size and inflation.

Practical implications

These imply that bank managers, regulators, policymakers and researchers must begin to see each bank lending category separately and independently since varying factors influence the different categories of bank lending differently.

Originality/value

The study presents new insights into how different factors determine different lending types in Africa for the first time to the best of the authors’ knowledge.
How does training boost employees' intention to implement environmental activities? An empirical study in Vietnam
Authors: Pham Nhat Tan , Jabbour Charbel Jose Chiappetta , Usman Muhammad , Ali Moazzam , Phan Hoang-Long
Published: March 2022

Purpose

Drawing on the conservation of resources theory, this study aims to apply a mixed-method to enrich the literature by investigating interrelationships among training, environmental triggers (environmental knowledge, awareness and concern) and employees' intention to carry out environmental activities.

Design/methodology/approach

This research applied a mixed-method carried out in Vietnam. By using the time-lagged data, Study 1 (quantitative research) was employed to test hypotheses. With Study 2 (qualitative research), four in-depth interviews were conducted to gain insight into a few unexpected findings from Study 1.

Findings

Study 1 indicates that environmental training is critical to directly boost not only the three environmental triggers but also employees' intention to engage in environmental activities. The findings further point out that environmental concern and awareness mediate the relationship between environmental training and employees' intention to engage in environmental activities. Unexpectedly, connections from environmental concern and awareness to employees' intentions were not moderated by environmental knowledge. The findings of Study 2 shed light on the role of environmental knowledge.

Originality/value

Based on the conservation of resources and social exchange theories, the research contributes to the existing literature by providing a better understanding of how environmental training stimulates employees' intention to implement environmental activities. The findings may be helpful for managers to encourage employees to contribute to organizations' green objectives.
Compulsory Licensing of Pharmaceuticals in High‐Income Countries: A Comparative Analysis
Authors: QUNAJ LINDOR , KALTENBOECK ANNA , BACH PETER B.
Published: March 2022

Policy Points

Pharmaceutical trade organizations and media outlets in the United States regularly point to compulsory licensing—or even its threat—as the mechanism that peer countries use to control the price of prescription drugs.

Our comparative analysis shows that compulsory licensing is not frequently employed in high‐income countries outside the United States as a direct response to drug prices. When its use is threatened, a license is rarely issued and even less often does it lead to a price discount. Accordingly, compulsory licensing is unlikely to contribute to price discrepancies between the United States and other developed nations.

In fact, of the 21 compulsory licensing petitions we identified outside the United States, over one‐third were made by pharmaceutical companies themselves and only three were threatened by a government authority.

Context

Compulsory licensing is a practice whereby national authorities can license a third party to produce a patented product, such as a pharmaceutical drug, effectively enabling the production of a generic before the original patent expires. The policy was designed—and has historically been used—to improve access to essential medicines in low‐income countries and during public health crises. Although it was not intended to impact drug prices directly, the threat of compulsory licensing may indeed contribute to lower drug prices in high‐income countries outside the United States. Our study sought to determine the plausibility of this claim.

Methods

We compiled a comprehensive database of compulsory licensing episodes in the United States and 17 comparator nations over the 20 years following the 2001 Doha Declaration, and we recorded the motivation and outcome of each instance. Our search began with publicly available reports compiled by organizations specializing in pharmaceutical intellectual property, expanded to a query of legal proceedings in Westlaw, and concluded with a comprehensive literature review on PubMed.

Findings

This strategy yielded 45 unique episodes of compulsory licensing, 24 in the United States and 21 outside. A minority (24%) of petitions outside the United States were motivated by high prices, and in all countries, only three cases were clearly associated with a price discount.

Conclusions

We found no evidence to suggest that compulsory licensing is either frequently threatened or successfully implemented by countries outside the United States to secure price discounts for the most expensive pharmaceuticals, those that are newly patented and just entering the market.
‘My Blood Was All Turning to Water’: Testimonial Advertisements and the Creation of a Menstrual Network in the U.S., 1870s–1910s
Authors: Davey Frances
Published: March 2022

This article explores the nexus of two phenomena – the mass production of consumer goods and the maelstrom of medical theorising on the female reproductive system – through testimonial advertisements produced by the Lydia E. Pinkham Medicine Company (LEPMC). This article argues that a wide‐ranging, self‐regenerating group of predominantly white, middle‐class American women formed a network rooted in LEPMC advertisements to negotiate power over the practice and meaning of their own reproductive lives. By publicly testifying to the efficacy of Pinkham products, these women used the tools of mass advertising and their collective understanding of modern medicine to campaign for empowered womanhood. They created a narrative in which they played long‐suffering protagonists who challenged physicians’ authority, claimed ownership over reproductive knowledge and prioritised female consumers. By forefronting the female consumers who engaged directly with the LEPMC advertising department and indirectly with each other, this article situates the Pinkham network in a complex discourse on women's reproductive agency.
Nutritional potassium limitation impact on serum potassium change, and death in chronic kidney disease: A meta‐analysis
Authors: Gong Zhumei , Chen Taiai
Published: March 2022

Introduction

We performed a meta‐analysis to evaluate the impact of nutritional potassium limitation on serum potassium change, and death in chronic kidney disease.

Methods

A systematic literature search up to October 2021 was carried out and eight studies included 92 558 subjects with chronic kidney disease at the start of the study; 41 474 of them were provided with nutritional potassium limitation and 510 084 were nonrestricted diet.

Results

Nutritional potassium limitation had significantly lower serum potassium change (MD, −0.33; 95% CI, −0.58 to −0.07; p = 0.01) compared to nonrestricted diet in subjects with chronic kidney disease. However, nutritional potassium limitation had no significant impact on the death (OR, 0.80; 95% CI, 0.58–1.10; p = 0.17) compared to nonrestricted diet in subjects with chronic kidney disease.

Conclusion

Nutritional potassium limitation had significantly lower serum potassium change compared to nonrestricted diet in subjects with chronic kidney disease. Further studies are required to validate these findings.
Reducing pesticide use through optimal reallocation at different spatial scales: The case of French arable farming
Authors: Kahindo Salomé , Blancard Stéphane
Published: March 2022

Reduction of pesticide use is one of the major challenges in the agricultural sector. Several methods, including efficiency analysis, have been proposed to address this issue. In general, efficiency analysis in the use of pesticides is conducted at the individual level (e.g., farm). We here propose to extend this analysis from farm level to aggregate (or district) level. In addition to the potential pesticide reduction by eliminating individual inefficiency, we measure the reduction due to the reallocation of productive activity across farms, within increasingly large spatial units. Results show that pesticides could be reduced by more than 50% in a sample of farms in the French Department of Meuse during 2014–2016, after eliminating individual technical inefficiency and reallocating activities across farms at the largest spatial unit, while producing at least the same output. Therefore, the reallocation associated with inefficiency elimination can help achieve the pesticide reduction targets set by several countries.
Altitude and temperature drive anuran community assembly in a Neotropical mountain region
Authors: Matavelli Rodrigo , Oliveira Juliano Machado , Soininen Janne , Ribeiro Milton Cezar , Bertoluci Jaime
Published: March 2022

Understanding the spatial variation in species richness and the mechanisms that limit species range sizes along geographical gradients belong to the central research issues in macroecology. Here, we aim to test the topographic and climatic effects on anuran species richness and community composition in mountainous regions in the Brazilian Atlantic Forest biome. We used Individual‐Based Rarefaction Curve (interpolation and extrapolation), Generalized Additive Model (GAM), Midpoint method and Principal Coordinates Analysis (PCoA) to analyze the topographic and climatic effects on anuran community composition, richness, and range sizes in a global biodiversity hotspot. Our results showed that altitude and annual mean temperature and temperature seasonality were the main drivers of species altitudinal range sizes and community assembly in mountainous regions. In conclusion, Anuran community richness peaked at intermediate altitudes following thus a hump‐shaped pattern and corroborated the Rapoport's altitudinal rule as range sizes increased with altitude in mountainous regions from the Atlantic Forest biome. This study revealed new insights into the patterns and drivers of Neotropical anuran communities.

Abstract in Portuguese is available with online material.
Economic costs of invasive bivalves in freshwater ecosystems
Authors: Haubrock Phillip J. , Cuthbert Ross N. , Ricciardi Anthony , Diagne Christophe , Courchamp Franck
Published: March 2022

Aim

To assess spatio‐temporal and taxonomic patterns of available information on the costs of invasive freshwater bivalves, as well as to identify knowledge gaps.

Location

Global.

Time period

1980–2020.

Taxon studied

Bivalvia.

Methods

We synthesize published global economic costs of impacts from freshwater bivalves using the InvaCost database and associated R package, explicitly considering the reliability of estimation methodologies, cost types, economic sectors and impacted regions.

Results

Cumulative total global costs of invasive macrofouling bivalves were $ 63.7 billion (2017 US$) across all regions and socio‐economic sectors between 1980 and 2020. Costs were heavily biased taxonomically and spatially, dominated by two families, Dreissenidae and Cyrenidae (Corbiculidae), and largely reported in North America. The greatest share of reported costs ($ 31.5 billion) did not make the distinction between damage and management. However, of those that did, damages and resource losses were one order of magnitude higher ($ 30.5 billion) than control or preventative measures ($ 1.7 billion). Moreover, although many impacted socio‐economic sectors lacked specification, the largest shares of costs were incurred by authorities and stakeholders ($ 27.7 billion, e.g., public and private sector interventions) and through impacts on public and social welfare ($ 10.1 billion, e.g., via power/drinking water plant and irrigation system damage) in North America. Average cost estimates over the entire period amounted to approximately $ 1.6 billion per year, most of which was incurred in North America.

Main conclusions

Our results highlight the burgeoning economic threat caused by invasive freshwater bivalves, offering a strong economic incentive to invest in preventative management such as biosecurity and rapid response eradications. Even if the damages and resource losses are severely understated because economic impacts are lacking for most invaded countries and invasive bivalve species, these impacts are substantial and likely growing.
The moral relevance of social categories: Analysing the case of childhood
Authors: Brando Nico
Published: March 2022

What makes the categorisation of a human collective morally relevant? How does the categorisation of individuals into groups affect their social status and treatment? This article provides an account of the moral relevance of social categories and assesses the status of “childhood” within this framework. It distinguishes morally relevant social categories (labelled as social groups) through three conditions: first, individuals are externally ascribed to the social category; second, the properties of the social category are reified through the social construction of its definition; and, third, the social category predetermines the normative treatment owed to the individuals ascribed. The existence of these three characteristics in the construction of a social category entails that the individuals ascribed may be affected by unjust constraints and restrictions on their lives and choices, thus, requiring a re‐evaluation of how their social grouping frames their status and treatment. The article claims that the “childhood” social category complies with the three conditions (ascription, reification, and normativisation). This implies that individuals categorised as “children” may suffer from unjust constraints and restrictions based on their social categorisation.
Positivity bias in higher education research
Authors: Tight Malcolm
Published: March 2022

Many forms of bias have been identified in higher education research, and in educational and social research in general. This article identifies a further form of bias, positivity bias, and places it in this broader context. Positivity bias is the tendency, in some forms of published higher education research, to only or chiefly report examples of initiatives or innovations that worked and received positive evaluations. Empirical evidence of positivity bias, in the form of an analysis of a sample of published articles from selected higher education journals, is presented and discussed. Suggestions as to the causes of positivity bias and how it might be handled are presented.
Effect of substance use on premature mortality among severely hypertensive African Americans
Authors: Varadarajan Vinithra , Ibe Chidinma A. , Young J. Hunter
Published: March 2022

Low‐income African Americans residing in impoverished neighborhoods confront myriad barriers to adhering to antihypertensive regimens. Substance use may thwart medication adherence and lifestyle modification efforts, which has implications for excess cardiovascular disease mortality. The Inner‐City Hypertension and Body Organ Damage (ICHABOD) Study was a longitudinal cohort study that evaluated causes of mortality among African Americans who lived in urban areas, had severe, poorly controlled hypertension, and were admitted to a local hospital between 1999–2001 and 2002–2004. The authors employed Cox proportional hazards models to assess mortality associated with illicit substance use, including use of heroin and cocaine, as well as by use of tobacco and alcohol. Among192 participants with poorly controlled hypertension, 30% were active illicit substance users (specifically, 22.7% heroin users, 19.8% were cocaine users, and 30.7% were both cocaine and heroin users). The mean age among substance non‐users was 52.3 years versus 48.7 years among those reporting current use. Mortality over 7.6 years of follow‐up was 52.5% among substance users and 33.8% among nonusers (p‐value, 0.01). After adjusting for potential confounders, the hazard ratio (HR) for cocaine use was 2.52 (95% confidence interval (CI) 1.38–4.59), while the HR for heroin use was 2.47 (95% CI 1.42–4.28) and the HR for both was 2.75 (95% CI 1.60–4.73). Substance use was associated with increased mortality among urban black Americans with poorly controlled hypertension. These data suggest the need for targeted interventions to support African Americans who have poorly controlled hypertension and use illicit substances, as a means of reducing excess mortality.
Influence of Metal Guide Sleeves on the Accuracy and Precision of Dental Implant Placement Using Guided Implant Surgery: An In Vitro Study
Authors: Adams Coleman R. , Ammoun Rami , Deeb George R. , Bencharit Sompop
Published: March 2022

Purpose

Metal sleeves are commonly used in implant guides for guided surgery. Cost and sleeve specification limit the applications. This in vitro study examined the differences in the implant position deviations produced by a digitally designed surgical guide with no metal sleeve in comparison to a conventional one with a metal sleeve.

Materials and Methods

The experiment was conducted in two steps for each step: n = 20 casts total, 10 casts each group; Step 1 to examine one guide from each group with ten implant placements in a dental cast, and Step 2 to examine one guide to one cast. Implant placement was performed using a guided surgical protocol. Postoperative cone‐beam computed tomography images were made and were superimposed onto the treatment‐planning images. The implant horizontal and angulation deviations from the planned position were measured and analyzed using t‐test and F‐test (p = 0.05).

Results

For Step 1 and 2, respectively, implant deviations for the surgical guide with sleeve were –0.3 ±0.17 mm and 0.15 ±0.23 mm mesially, 0.60 ±1.69 mm, and –1.50 ±0.99 mm buccolingual at the apex, 0.20 ±0.47 mm and –0.60 ±0.27 mm buccolingual at the cervical, and 2.73° ±4.80° and –1.49° ±2.91° in the buccolingual angulation. For Step 1 and 2, respectively, the implant deviations for the surgical guide without sleeve were –0.17 ±0.14 mm and –0.06 ±0.07 mm mesially, 0.35 ±1.04 mm and –1.619 ±1.03 mm buccolingual at the apex, 0.10 ±0.27 mm and –0.62 ±0.27 mm buccolingual at the cervical, and 1.73° ±3.66° and –1.64° ±2.26° in the buccolingual angulation. No statistically significant differences were found in any group except for mesial deviation of the Step 2 group (F‐test, p < 0.001).

Conclusions

A digitally designed surgical guide with no metal sleeve demonstrates similar accuracy but higher precision compared to a surgical guide with a metal sleeve. Metal sleeves may not be required for guided surgery.
Effect of dietary licorice flavonoids powder on performance, intestinal immunity and health of weaned piglets
Authors: You Ting , Tang Jiayong , Yin Shenggang , Jia Gang , Liu Guangmang , Tian Gang , Chen Xiaoling , Cai Jingyi , Kang Bo , Zhao Hua
Published: March 2022

Licorice flavonoids, a bioactive substance derived from glycyrrhiza, have been reported for many pharmacological properties and are beneficial to animal health. This study aimed to explore the effects of licorice flavonoids powder (LFP) on growth performance and intestinal health of piglets. A total of 96 weaned piglets were randomly assigned into four treatments and supplemented with 0, 50, 150 and 250 mg/kg LFP for 5 weeks. Dietary LFP supplementation tended to increase (p = 0.068) average daily gain (ADG) and reduce (p = 0.089) the feed intake/body gain (F/G) of piglets than that of the control group during 15–35 days; and concentrations of LFP supplementation reduced (p < 0.01) diarrhoea index during 14–35 days and 0–35 days. Piglets fed on diets supplied with LFP had a lower (p < 0.05) pH in caecum and colon. Dietary LFP supplementation increased (p < 0.01) the villi height and the ratio of villi height/crypt depth in duodenum, and reduced (p < 0.05) crypt depth in duodenum. Compared with the control group, 250 mg/kg LFP supplementation up‐regulated (p < 0.05) the mRNA level of occludin (OCLN) in ileum. Meanwhile, dietary LFP supplementation down‐regulated (p < 0.05) mRNA abundance of Interleukin (IL)‐1β, IL‐8 and induced nitrogen monoxide synthase (INOS) in duodenum. Dietary 150 mg/kg LFP supplementation down‐regulated (p < 0.05) mRNA abundance of IL‐1β and 250 mg/kg LFP up‐regulated (p < 0.05) the expression of IL‐10 in ileum. In summary, dietary LFP supplementation has a trend to improve the performance of weaning piglets, those improvements are accompanied by reduction in diarrhoea, enhancement of intestinal morphological structure, barrier function, immune function, and development. In general, 150 mg/kg LFP supplementation is more effective.
Stability of dilutions of methadone alone, and in combination with lidocaine and ketamine
Authors: Gomez A. , Al‐Tannak N. , Auckburally A. , Watson D. , Flaherty D.
Published: March 2022

Objectives

To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions.

Materials and Methods

Solutions of methadone diluted in 0.9% NaCl, and methadone–lidocaine–ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4°C and protected from light, were maintained over 10 days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240 hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time.

Results

There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone–lidocaine–ketamine with Hartmann's solution at 4°C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone–lidocaine–ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone–lidocaine–ketamine components retained acceptable stability (<10% degradation) for at least 48 hours following preparation, irrespective of diluent or storage conditions.

Clinical Significance

Regardless of the diluent or storage method, methadone–lidocaine–ketamine solutions degrade over time, but this only becomes clinically significant after 48 hours. Solutions of 1 mg/ml methadone in 0.9% NaCl are stable for at least 10 days under storage conditions likely to be encountered in general practice.
Examining the psychometric properties of brief screening measures of depression and anxiety in chronic pain: The Patient Health Questionnaire 2‐item and Generalized Anxiety Disorder 2‐item
Authors: Bisby Madelyne A. , Karin Eyal , Scott Amelia J. , Dudeney Joanne , Fisher Alana , Gandy Milena , Hathway Taylor , Heriseanu Andreea I. , Staples Lauren , Titov Nickolai , Dear Blake F.
Published: March 2022

Objective

Individuals with chronic pain experience anxiety and depressive symptoms at rates higher than the general population. The Patient Health Questionnaire 2‐item (PHQ‐2) and Generalized Anxiety Disorder 2‐item (GAD‐2) are brief screening measures of depression and anxiety, respectively. These brief scales are well‐suited for use in routine care due to their brevity and ease of administration, yet their psychometric properties have not been established in heterogeneous chronic pain samples when administered over the Internet.

Materials and Methods

Using existing data from randomized controlled trials of an established Internet‐delivered pain management program (n = 1333), we assessed the reliability, validity, diagnostic accuracy, and responsiveness to treatment change in the PHQ‐2 and GAD‐2, as well as the long‐form counterparts. Exploratory analyses were conducted to obtain cutoff scores using those participants with diagnostic data (n = 62).

Results

The PHQ‐2 and GAD‐2 demonstrated appropriate reliability (eg, Cronbach'sα = 0.79–0.84), validity (eg, higher scores in individuals with a diagnosis;p < 0.001), and responsiveness to treatment change (eg, pre‐ to post‐treatment scores,p < 0.001). The psychometric properties of the short forms compared well with the longer forms. Cutoff scores on the short forms were consistent with general population samples, while cutoff scores on the long forms were higher than previously observed using general population samples. All four scales favored specificity over sensitivity.

Conclusions

The PHQ‐2 and GAD‐2 demonstrated acceptable psychometric properties in the current sample, as did the long forms. Based on our findings, the PHQ‐2 and GAD‐2 can be used as screening tools with chronic pain samples when administered over the Internet.
Transposon insertions regulate genome‐wide allele‐specific expression and underpin flower colour variations in apple (Malus spp.)
Authors: Tian Yi , Thrimawithana Amali , Ding Tiyu , Guo Jian , Gleave Andrew , Chagné David , Ampomah‐Dwamena Charles , Ireland Hilary S. , Schaffer Robert J. , Luo Zhiwei , Wang Meili , An Xiuhong , Wang Dajiang , Gao Yuan , Wang Kun , Zhang Hengtao , Zhang Ruiping , Zhou Zhe , Yan Zhenli , Zhang Liyi , Zhang Caixia , Cong Peihua , Deng Cecilia H. , Yao Jia‐Long
Published: March 2022

Allele‐specific expression (ASE) can lead to phenotypic diversity and evolution. However, the mechanisms regulating ASE are not well understood, particularly in woody perennial plants. In this study, we investigated ASE genes in the apple cultivar ‘Royal Gala’ (RG). A high quality chromosome‐level genome was assembled using a homozygous tetra‐haploid RG plant, derived from anther cultures. Using RNA‐sequencing (RNA‐seq) data from RG flower and fruit tissues, we identified 2091 ASE genes. Compared with the haploid genome of ‘Golden Delicious’ (GD), a parent of RG, we distinguished the genomic sequences between the two alleles of 817 ASE genes, and further identified allele‐specific presence of a transposable element (TE) in the upstream region of 354 ASE genes. These included MYB110a that encodes a transcription factor regulating anthocyanin biosynthesis. Interestingly, another ASE gene, MYB10 also showed an allele‐specific TE insertion and was identified using genome data of other apple cultivars. The presence of the TE insertion in both MYB genes was positively associated with ASE and anthocyanin accumulation in apple petals through analysis of 231 apple accessions, and thus underpins apple flower colour evolution. Our study demonstrated the importance of TEs in regulating ASE on a genome‐wide scale and presents a novel method for rapid identification of ASE genes and their regulatory elements in plants.
Effects of melatonin implants on reproductive performance of dairy sheep and dairy goats
Authors: Tölü Cemil , Yazgan Nazif , Akbağ Hande Işıl , Yurtman İsmail Yaman , Savaş Türker
Published: March 2022

Contents

This study investigated the effects of melatonin implants in the female and male animals before the breeding season on the reproductive performance of Tahirova sheep and Turkish Saanen goats. Seventy‐five sheep and 53 goats (including 6 rams and 4 bucks) were used in the research. Melatonin implants (18 mg) were applied to half of the female and male animals, one to female animals and three to male animals. The rate of oestrus was determined as 100% in the melatonin (M) and control (C) groups. The non‐return rate, conception rate and lambing rate were close in both groups of ewes and rams groups (p > .05). The rate of oestrus was 100% in the melatonin and control groups of does and bucks groups in Turkish Saanen goats. The non‐return rate in does was 75.0 ± 9.02% in M group and 92.0 ± 5.53% in C group (p = .0101), the non‐return rate was 83.3 ± 6.92% in group M and 84.2 ± 8.59% in group C for bucks (p = .5570). For ewes, the duration from ram introduction to first oestrus, conception and lambing was significantly lower in group M than in group C (p ≤ .05). Litter size of M in ewe and ram groups were 1.70 ± 0.08 and 1.59 ± 0.09, respectively, whereas it was 1.62 ± 0.10 and 1.74 ± 0.10 in C group, respectively. Birth weight significantly differed between ewe groups (p = .0017). For goats, the duration from buck introduction to first oestrus, conception and lambing was similar in the groups of does and bucks (p > .05). Litter size of M in doe and buck groups were 1.57 ± 0.11 and 1.53 ± 0.12, respectively, and 1.46 ± 0.11and 1.50 ± 0.09 in C group, respectively (p > .05). While the live weight and body condition score (BCS) of ewes were significantly affected by melatonin implants (p ≤ .05), the live weight and BCS of does were not affected. In conclusion, it might be said that melatonin implants obtained better results for reproduction in Tahirova sheep than Turkish Saanen goats.
Can optimism solve the entrepreneurial earnings puzzle?*
Authors: Dell'Era Michele , Opromolla Luca David , Santos‐Pinto Luís
Published: March 2022

In this paper, we apply a general equilibrium occupational choice model to the study of the impact of optimism on the earnings of entrepreneurs and workers. We extend the work of Lucas (1978 Bell Journal of Economics 9, 508–523) by assuming a fraction of individuals are optimistic about their ability as entrepreneurs. The model shows that optimism leads to a misallocation of talent and inputs, which raises input prices and lowers output. The model is calibrated to match salient features of the UK economy and the British Household Panel Survey. The calibration shows that optimism can account for more than half of the size of the entrepreneurial earnings puzzle in the UK.
Comparative effects of latanoprost and latanoprostene bunod on intraocular pressure and pupil size in ophthalmologically normal Beagle dogs
Authors: Desai Sujata J. , Pumphrey Stephanie A. , Koethe Benjamin
Published: March 2022

Objective

To compare effects of latanoprost, a topical prostaglandin analogue (PGA) commonly used to treat glaucoma and lens instability in dogs, and latanoprostene bunod, a novel PGA with a nitric oxide‐donating moiety, on intraocular pressure (IOP) and pupil diameter (PD).

Animals studied

Ten ophthalmologically normal Beagle dogs.

Procedures

Dogs were treated twice a day for 5 days in a randomly selected eye with either latanoprost or latanoprostene bunod. After a 6‐week washout period, dogs were treated with the opposite drug. IOP and PD were measured at treatment times, at midday on days 1 and 5, and for 6 days post‐treatment.

Results

Both drugs significantly decreased IOP and PD. At midday on day 5 of treatment, mean IOP in eyes treated with latanoprost was 4.5 mmHg lower than the fellow eye and 3.0 mmHg lower than the same eye at baseline, while mean IOP in eyes treated with latanoprostene bunod was 5.5 mmHg lower than the fellow eye and 3.6 mmHg lower than baseline. Mean PD was 0.94 mm in eyes treated with latanoprost and 0.76 mmHg in eyes treated with latanoprostene bunod. There was no significant difference between the two drugs for either parameter at that time point (p = .372 and .619, respectively, for IOP relative to control and to baseline; p = .076 for PD) or when analyzed longitudinally. Significant diurnal variation in PD was noted and may have implications for treatment of lens' instability.

Conclusions

Latanoprost and latanoprostene bunod produce similar IOP reduction and miosis in normal canine eyes.
Entanglement generation in a quantum network with finite quantum memory lifetime
Authors: Semenenko Vyacheslav , Hu Xuedong , Figueroa Eden , Perebeinos Vasili
Published: March 2022

We simulate entanglement sharing between two end-nodes of a linear chain quantum network using SeQUeNCe, an open-source simulation package for quantum networks. Our focus is on the rate of entanglement generation between the end-nodes with many repeaters with a finite quantum memory lifetime. Numerical and analytical simulations show limits of connection performance for a given number of repeaters involved, memory lifetimes, the distance between the end-nodes, and an entanglement management protocol. Our findings demonstrate that the performance of quantum connection depends highly on the entanglement management protocol, which schedules entanglement generation and swapping, resulting in the final end-to-end entanglement.
Biomechanical and organisational constraints of pregnant women at work: definition of exposure levels using a consensus method (Delphi)
Authors: Certenais Thomas , Teysseire Raphaëlle , Garlantezec Ronan , Brochard Patrick , Manangama Guyguy , Delva Fleur
Published: March 2022

Objectives

To identify the biomechanical and organisational constraints that influence pregnancy outcomes and define the exposure levels at which the risks for pregnancy become significant.

Setting and participants

We applied a consensus method (Delphi) consisting of a literature review followed by expert opinions on exposure levels. The group of experts was made up of 12 people from different medical specialities and working in various structures in France.

Outcome measures

The studied variables were: (1) exposure: night work/shift work, weekly hours at work, lifting of heavy loads, prolonged standing and multiple exposure and (2) pregnancy outcomes: prematurity, low birth weight and spontaneous miscarriages.

Results

The consensus method resulted in the following recommendations. The time spent working must not exceed 40 hours/week; in the absence of a consensus on the level of exposure, night and/or shift work must be avoided; prolonged standing must not exceed 3 hours/day; lifting must be limited to carrying loads <11 kg, with a daily load <100 kg; multiple exposure must be avoided, in particular: vibration, night work/shift work, time spent working exceeding 40 hours/week, prolonged standing and lifting of heavy loads.

Conclusions

These results could help the occupational physician to address the question of whether an exposed employee should remain at work, considering her individual characteristics (medical history, family situation, socioeconomic level, etc) in consultation with pregnancy specialists (obstetricians, midwives).
Public acceptability of non-pharmaceutical interventions to control a pandemic in the UK: a discrete choice experiment
Authors: Loría-Rebolledo Luis Enrique , Ryan Mandy , Watson Verity , Genie Mesfin G , Sakowsky Ruben Andreas , Powell Daniel , Paranjothy Shantini
Published: March 2022

Objective

To understand how individuals trade off between features of non-pharmaceutical interventions (eg, lockdowns) to control a pandemic across the four nations of the UK.

Design

A survey that included a discrete choice experiment. The survey design was informed using policy documents, social media analysis and input from remote think-aloud interviews with members of the public (n=23).

Setting

A nationwide survey across the four nations of the UK using an online panel between 29 October and 12 December 2020.

Participants

Individuals who are over 18 years old. A total of 4120 adults completed the survey (1112 in England, 848 in Northern Ireland, 1143 in Scotland and 1098 in Wales).

Primary outcome measure

Adult’s preferences for, and trade-offs between, type of lockdown restrictions, length of lockdown, postponement of routine healthcare, excess deaths, impact on the ability to buy things and unemployment.

Results

The majority of adults are willing to accept higher excess deaths if this means lockdowns that are less strict, shorter and do not postpone routine healthcare. On average, respondents in England were willing to accept a higher increase in excess deaths to have less strict lockdown restrictions introduced compared with Scotland, Northern Ireland and Wales, respectively. In all four countries, one out of five respondents were willing to reduce excess deaths at all costs.

Conclusions

The majority of the UK population is willing to accept the increase in excess deaths associated with introducing less strict lockdown restrictions. The acceptability of different restriction scenarios varies according to the features of the lockdown and across countries. Governments can use information about trade-off preferences to inform the introduction of different lockdown restriction levels and design compensation policies that maximise societal welfare.
Neuroimmune responses following joint mobilisation and manipulation in people with persistent neck pain: a protocol for a randomised placebo-controlled trial
Authors: Lutke Schipholt Ivo J , Scholten-Peeters Gwendolyne , Bontkes Hetty , Coppieters Michel W
Published: March 2022

Introduction

Joint mobilisation and manipulation often results in immediate pain relief in people with neck pain. However, the biological mechanisms behind pain relief are largely unknown. There is preliminary evidence that joint mobilisation and manipulation lessens the upregulated neuroimmune responses in people with persistent neck pain.

Methods and analysis

This study protocol describes a randomised placebo-controlled trial to investigate whether joint mobilisation and manipulation influence neuroimmune responses in people with persistent neck pain. People with persistent neck pain (N=100) will be allocated, in a randomised and concealed manner, to the experimental or control group (ratio 3:1). Short-term (ie, baseline, immediately after and 2 hours after the intervention) neuroimmune responses will be assessed, such as inflammatory marker concentration following in vitro stimulation of whole blood cells, systemic inflammatory marker concentrations directly from blood samples, phenotypic analysis of peripheral blood mononuclear cells and serum cortisol. Participants assigned to the experimental group (N=75) will receive cervical mobilisations targeting the painful and/or restricted cervical segments and a distraction manipulation of the cervicothoracic junction. Participants assigned to the control group (N=25) will receive a placebo mobilisation and placebo manipulation. Using linear mixed models, the short-term neuroimmune responses will be compared (1) between people in the experimental and control group and (2) within the experimental group, between people who experience a good outcome and those with a poor outcome. Furthermore, the association between the short-term neuroimmune responses and pain relief following joint mobilisation and manipulation will be tested in the experimental group.

Ethics and dissemination

This trial is approved by the Medical Ethics Committee of Amsterdam University Medical Centre, location VUmc (Approval number: 2018.181).

Trial registration number

NL6575 (trialregister.nl
Status migrainosus inpatient treatment with eptinezumab (SMITE): study protocol for a randomised controlled trial
Authors: Ray Jason Charles , Chen Zhibin , Ramsay Georgia , Germaine Jack , Hutton Elspeth J
Published: March 2022

Introduction

Status migrainosus is a disabling complication of migraine, which frequently results in hospitalisation. For patients who fail to respond to simple analgesia, triptans and intravenous prochlorperazine or chlorpromazine, there are limited treatment options, and a paucity of high-quality evidence to guide clinical practice. Eptinezumab, an intravenous monoclonal antibody specific for the calcitonin gene-related peptide ligand which achieves maximal plasma concentration immediately following administration and may improve migraines from day one. Intravenous lignocaine is an anaesthetic medication used in treatment of status migrainosus, often requiring prolonged admissions and with potential cardiac adverse events. The aim of this study is to assess the efficacy and safety of eptinezumab in the treatment of status migrainosus in comparison to intravenous lidocaine.

Methods and analysis

Status migrainosus inpatient treatment with eptinezumab is a randomised, controlled, single-centre clinical trial conducted in a parallel design with an active comparator conducted in Melbourne, Australia. This study randomises forty patients (1:1) to receive either eptinezumab or an infusion of intravenous lignocaine for up to 5 days. It will assess the effect of eptinezumab compared with intravenous lignocaine in aborting status migrainosus, with the primary outcome of time from infusion until resolution of pain. It will explore several secondary measures including change in health resource utilisation, effect on patient reported outcomes of migraine disability and the safety and tolerability of each medication.

Ethics and dissemination

This study has been reviewed and approved by the Human Research Ethics Committee of Alfred Health, local reference number 443/21, and all participants will provide informed consent for participation in the trial and dissemination of results.

Trial registration number

The trial registration number is ACTRN12621001616864. The results of this study will be disseminated through peer-reviewed journals, conference presentations and social media.
Visual outcomes and complications in infantile cataract surgery: a real - world scenario
Authors: Chattannavar Goura , Badakere Akshay , Mohamed Ashik , Kekunnaya Ramesh
Published: March 2022

Objective

To evaluate visual outcomes and complications of infantile cataract surgery through a 1-year follow-up period in a real world scenario.

Methods and analysis

Prospective observational study evaluating infants with cataract undergoing surgery.

Results

We analysed 173 eyes of 97 infants (76 bilateral); median age 18.7 weeks, (IQR: 11–33.9 weeks). Toxoplasmosis, rubella, cytomegalovirus and herpes infection was the most common aetiology in both unilateral 10 (47.6%) and bilateral 43 (55.1%) cases, followed by familial and syndromic cases. Fifty-four eyes (29.5%) received primary intraocular lens (IOL) implantation.

Seventy-five infants (76%) were less than 6 months of age. At 1-year follow-up, mean log MAR best-corrected visual acuity was 1.00±0.08 and 1.21±0.03 in unilateral and bilateral cases respectively (p=0.012), which was not statistically significant. At 1-year follow-up, pseudophakic(1.09±0.05) eyes had a better mean log MAR visual acuity comparing aphakes(1.24±0.04) clinically but was not statistically significant after the application of Bonferroni correction (p=0.012). The mean myopic shift of −2.9 D±0.39 and −4.53 D±0.55 over 1 year was noted in aphakes and pseudophakes, respectively (p=0.016). Visual axis opacification and glaucoma were the most common complications noted in pseudophakes and aphakes, respectively.

Conclusion

Primary IOL implantation in selected cases of infantile cataract is a feasible option, particularly in cases when optimal aftercare and refractive rehabilitation of aphakia are not possible.