bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo CRISPR-Cas9 screens reveal drivers of aging in neural stem cells of the brain
Authors: Ruetz Tyson J. , Kashiwagi Chloe M. , Morton Bhek , Yeo Robin W. , Leeman Dena S. , Morgens David W. , Tsui C. Kimberly , Li Amy , Bassik Michael C. , Brunet Anne
Published: November 2021

Aging impairs the ability of neural stem cells to transition from quiescence to activation (proliferation) in the adult mammalian brain. Neural stem cell (NSC) functional decline results in decreased production of new neurons and defective regeneration upon injury during aging1–9, and this is exacerbated in Alzheimer’s disease10. Many genes are upregulated with age in NSCs3, 11–13, and the knockout of some of these boosts old NSC activation and rejuvenates aspects of old brain function14–18. But systematic functional testing of genes in old NSCs – and more generally in old cells – has not been done. This has been a major limiting factor in identifying the most promising rejuvenation interventions. Here we develop in vitro and in vivo high-throughput CRISPR-Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screening pipeline in primary cultures of young and old NSCs identifies over 300 gene knockouts that specifically restore old NSC activation. Interestingly, the top gene knockouts are involved in glucose import, cilium organization and ribonucleoprotein structures. To determine which gene knockouts have a rejuvenating effect for the aging brain, we establish a scalable CRISPR-Cas9 screening platform in vivo in old mice. Of the 50 gene knockouts we tested in vivo, 23 boost old NSC activation and production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes for the GLUT4 glucose transporter, is a top rejuvenating intervention for old NSCs. GLUT4 protein expression increases in the stem cell niche during aging, and we show that old NSCs indeed uptake ∼2-fold more glucose than their young counterparts. Transient glucose starvation increases the ability of old NSCs to activate, which is not further improved by knockout of Slc2a4/GLUT4. Together, these results indicate that a shift in glucose uptake contributes to the decline in NSC activation with age, but that it can be reversed by genetic or external interventions. Importantly, our work provides scalable platforms to systematically identify genetic interventions that boost old NSC function, including in vivo in old brains, with important implications for regenerative and cognitive decline during aging.
A chemical method to sequence 5-formylcytosine on RNA
Authors: Li Ang , Sun Xuemeng , Arguello A. Emilia , Kleiner Ralph E.
Published: November 2021

Epitranscriptomic RNA modifications can regulate biological processes, but there remains a major gap in our ability to identify and measure individual modifications at nucleotide resolution. Here we present Mal-Seq, a chemical method to sequence 5-formylcytosine (f5C) modifications on RNA based upon selective and efficient malononitrile-mediated labeling of f5C residues to generate adducts that are read as C-to-T mutations upon reverse transcription and PCR amplification. We apply Mal-Seq to characterize the prevalence of f5C at the wobble position of mt-tRNA(Met) in different organisms and tissue types and find that high-level f5C modification is present in mammals but lacking in lower eukaryotes. Our work sheds light on mitochondrial tRNA modifications throughout eukaryotic evolution and provides a general platform for characterizing the f5C epitranscriptome.
SELENOT deficiency alters projection neuron migration during corticogenesis in mice
Authors: Carpentier Emmanuelle , Falluel-Morel Anthony , Brunet Lisa , Bénard Magalie , Godefroy David , Boukhzar Loubna , Arabo Arnaud , Anouar Youssef
Published: November 2021

During corticogenesis, projection neurons migrate along the radial glial axis to form cortical layers, the alteration of which is associated with functional deficits in adulthood. As byproducts of cell metabolism, reactive oxygen species act as second messengers to contribute to neurodevelopment; however, free radical excess may impede this process. SELENOT is a thioredoxin-like enzyme of the endoplasmic reticulum abundantly expressed during embryogenesis whose gene disruption in the brain leads to neuroblast cell demise due to increased free radical levels. To determine the potential contribution of SELENOT to the establishment of cortical networks, we analyzed first its expression profile in the neocortex at different stages of development. These studies revealed the widespread expression of SELENOT in all cortical layers, and its continous increase throughout mouse lifespan. In addition, we disrupted the SELENOT gene in the cortex using in utero electroporation and Nes-Cre/lox knockout. SELENOT deficiency altered neuroblast migration polarity, at the level of radial scaffolding, and projection neuron positionning. These results indicate that SELENOT plays a crucial role during neurodevelopment by sustaining projection neuron migration.
Distinct histone H3–H4 binding modes of sNASP reveal the basis for cooperation and competition of histone chaperones
Authors: Liu Chao-Pei , Jin Wenxing , Hu Jie , Wang Mingzhu , Chen Jingjing , Li Guohong , Xu Rui-Ming
Published: November 2021

Chromosomal duplication requires de novo assembly of nucleosomes from newly synthesized histones, and the process involves a dynamic network of interactions between histones and histone chaperones. sNASP and ASF1 are two major histone H3–H4 chaperones found in distinct and common complexes, yet how sNASP binds H3–H4 in the presence and absence of ASF1 remains unclear. Here we show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded Nα region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3–H4 complex. Our study also implicates a critical role of the C-terminal tail of H4 in the transfer of H3–H4 between sNASP and ASF1 and the coiled-coil domain of sNASP in nucleosome assembly. These findings provide mechanistic insights into coordinated histone binding and transfer by histone chaperones.
Hi-C detects genomic structural variants in peripheral blood of pediatric leukemia patients
Authors: Mallard Claire , Johnston Michael J. , Bobyn Anna , Nikolic Ana , Argiropoulos Bob , Chan Jennifer A. , Guilcher Gregory M.T. , Gallo Marco
Published: November 2021

B-cell acute lymphoblastic leukemia (B-ALL) is often driven by chromosome translocations that result in recurrent and well-studied gene fusions. Currently, fluorescent in situ hybridization probes are used to detect candidate translocations in bone marrow samples from B-ALL patients. Recently Hi-C, a sequencing-based technique originally designed to reconstruct the three-dimensional architecture of the nuclear genome, was shown to effectively recognize structural variants. Here, we demonstrate that Hi-C can be used as a genome-wide assay to detect translocations and other structural variants of potential clinical interest. Structural variants were identified in both bone marrow and peripheral blood samples, including anETV6–RUNX1translocation present in one pediatric B-ALL patient. Our report provides proof of principle that Hi-C could be an effective strategy to globally detect driver structural variants in B-ALL peripheral blood specimens, reducing the need for invasive bone marrow biopsies and candidate-based clinical tests.
New thermal-hydraulic correlations for printed circuit heat exchangers (PCHEs) with zigzag channels under high Reynolds numbers
Authors: Naveira-Cotta Carolina P. , Su Jian , Lucena Kreppel Paes Paulo , Egmont Philippe R. , Moreira Rodrigo P.M. , Silva Gabriel Caetano G.R. da , Monteiro André Sampaio
Published: November 2021

Purpose

The purpose of this paper is to investigate the impact of semi-circular zigzag-channel printed circuit heat exchanger (PCHE) design parameters on heat transfer and pressure drop of flows under high Reynolds numbers and provide new thermal-hydraulic correlations relevant to conditions encountered in natural gas processing plants.

Design/methodology/approach

The correlations were developed using three-dimensional steady-state computational fluid dynamics simulations with varying semicircular channel diameter (from 1 to 5 mm), zigzag angle (from 15° to 45°) and Reynolds number (from 40,000 to 100,000). The simulation results were validated by comparison with experimental results and existing correlations.

Findings

The results revealed that the thermal-hydraulic performance was mostly affected by the zigzag angle, followed by the ratio of the zigzag channel length to the hydraulic diameter. Overall, smaller zigzag angles favored heat transfer intensification while keeping reasonably low pressure drops.

Originality/value

This study is, to date, the only one providing thermal-hydraulic correlations for PCHEs with zigzag channels under high Reynolds numbers. Besides, the broad range of parameters considered makes the proposed correlations valuable PCHE design tools.
“Is it all just lip service?”: on Instagram and the normalisation of the cosmetic servicescape
Authors: Rodner Victoria , Goode Amy , Burns Zara
Published: November 2021

Purpose

To better understand the uptake of cosmetic procedures in the wake of Instagram, this study aims to unravel how the aesthetic labour of influencers acts as the packaging of the cosmetic servicescape. In doing so, the authors contribute to theorising of aesthetic and emotional labour within the services marketing literature, fleshing out the bodywork of influential others not as employees but endorsers, who act like the “walking billboards” (Zeithaml and Bitner, 2003) for the cosmetic service industry.

Design/methodology/approach

This study adopts a dual qualitative approach to data collection, coupling netnographic material from Instagram posts with 16 in-depth interviews with female Instagram users who have undergone or hope to undergo cosmetic surgery. Using mediated discourse analysis, the authors weave their visual and discursive data together for a richer account of the commoditisation of cosmetic surgery.

Findings

Adopting a postfeminist neoliberal lens, where women are viewed as aesthetic entrepreneurs who are constantly working on the body and the self, the findings of the study reveal how influencers’ aesthetic and emotional labour help package, propagate and demystify the cosmetic servicescape. Through their visual storytelling, we see how influencers help endorse (local) cosmetic services; commoditise cosmetic procedures through the conspicuous display of their ongoing body projects whilst masking the labour and pain involved; and how face-filters that use augmented reality (AR) technology foster new forms of (digitised) body dysmorphia.

Originality/value

The authors shed light on the darker side of social media and body-enhancing technologies, where tales of body transformation trivialise cosmetic intervention and AR technology induces a digitised body dysmorphia.
Rewiring practice: community mental health professionals’ attitudes towards and knowledge of electroconvulsive therapy in the context of advance decision-making
Authors: Dunlop Rebecca , Cetrano Gaia
Published: November 2021

Purpose

In England, electroconvulsive therapy (ECT) cannot be administered to service users who make an advance decision to refuse the treatment, unless in life-threatening circumstances. In a sector where person-centred practice is revered, no prior research has investigated whether community mental health practitioners (CMHPs) encourage service users to make advance decisions about ECT. This study aims to explore whether CMHPs have supported advance decision-making about ECT and whether their profession, attitudes towards and knowledge of the treatment affect this.

Design/methodology/approach

A quantitative online survey was completed by n = 120 CMHPs (nurses, social workers and occupational therapists). The validated Questionnaire on Attitudes and Knowledge of ECT was used.

Findings

In total, 93% of participants knew service users who had undergone ECT, yet only 12% had supported a service user to make an advance decision about ECT. Compared to those who had not supported advance decision-making, those who had shown significantly higher knowledge and a more positive attitude. Nurses and those who had worked in the mental health field for over 10 years had significantly higher knowledge of ECT.

Originality/value

CMHPs are well placed to support advance decision-making about ECT. Increased knowledge about advance decisions and ECT may bolster the uptake of advance decision-making, thus greater training is recommended.
Multi-physics properties of thermoplastic polyurethane at various fused filament fabrication parameters
Authors: Kasmi Samir , Ginoux Geoffrey , Labbé Eric , Alix Sébastien
Published: November 2021

Purpose

The purpose of this study is to test a flexible polymer with different characteristics compared to other classical polymers mostly used in the additive manufacturing process, and to improve its mechanical properties and microstructure, by modifying different printing parameters, to make it more suitable for various industrial applications.

Design/methodology/approach

Seven parameters were tested, namely, nozzle temperature, bed temperature, layer thickness, printing speed, flow rate, printing time gap between two successive printed layers and raster orientation. Rheological characterizations were conducted to evaluate the influence of nozzle temperature on the melt viscosity of thermoplastic polyurethane (TPU). The effect of thermal printing parameters on the crystallinity behavior was explored. Tomographic characterizations were realized to measure the porosity and evaluate the internal structure quality of printed specimens.

Findings

Increases of the nozzle temperature, bed temperature, layer thickness and flow rate had a positive influence on the tensile strength properties of TPU with a reduction of porosity. Higher printing speeds created defects and negatively influenced the strength properties of TPU. An increase in the printing time gap between layers led to poor interlayer adhesion and decreased the tensile strength. Specimens with layers all oriented parallel to the loading direction exhibited superior mechanical properties compared to other raster orientations.

Originality/value

Thermoplastic elastomers are a unique class of polymers characterized by the combined thermal, chemical and mechanical properties of their elastomer and thermoplastic parts. TPU elastomer, as one of the elastomer families, has found an important position in the bioengineering and three-dimensional printing industry. This study reports a comprehensive study of the impact of additive manufacturing parameters on the properties of TPU.
Resident interactions when affirming and correcting peers in a therapeutic community for women
Authors: Warren Keith Leverett , Doogan Nathan , Wernekinck Uwe , Doherty Fiona Claire
Published: November 2021

Purpose

While recent years have seen a number of studies of social networks in therapeutic communities (TCs) and other residential settings, these have primarily focused on male residents. This paper aims to conduct a longitudinal social network analysis of interpersonal interactions in a TC for women.

Design/methodology/approach

The data consists of a longitudinal directed social network of instances of feedback between 56 residents of a 16 bed TC for women over a period of 611 days. Mean age of the participants was 33.1 years, mean length of stay was 133.9 days and 91% of the participants were female. Feedback consisted of written affirmations for prosocial behavior and written corrections for contravening TC norms. Data was analyzed using a latent factor longitudinal social network model.

Findings

Residents react to peer intervention in complex ways. Residents reciprocated affirmations (B = 0.14, 95% confidence interval = 0.10, 0.18) and corrections (B = 0.20, 95% CI = 0.13, 0.25). Controlling for reciprocity, participants who received affirmations were more likely to affirm and correct peers (B = 0.10, 95% CI = 0.06, 0.15; B = 0.17, 95% CI = 0.10, 0.23), suggesting that the encouragement offered by affirmations leads to increased activity. Homophily by admission time occurred in both affirmations and corrections (B = 0.23, 95% CI = 0.10, 0.37; B = 0.51, 95% CI = 0.29, 0.74).

Originality/value

While affirmations and corrections serve as vehicles for behavioral reinforcement and social learning, they also allow residents to interact in ways that strengthen social bonds.
Cyanobacterial persistence and influence on microbial community dynamics over 15 years in induced biocrusts
Authors: Lan Shubin , Wu Li , Adessi Alessandra , Hu Chunxiang
Published: November 2021

Biocrusts provide numerous ecological functions in drylands. Recovering biocrusts via cyanobacterial inoculation recently gathered interest for ecological restoration, yet it still lacks long‐term experiments to unravel biocrust community dynamics. To examine how cyanobacterial inoculants influenced local microbial community and biocrust development, we observed a 2 km2 (Qubqi Desert, China) inoculation experiment after 10 and 15 years, following biocrust formation. Our results revealed that biocrust development was in line with ecological regime shift, providing evidence for biocrust community succession, from cyanobacteria‐ to moss‐dominated types. Associated with biocrust development, microbial communities differed significantly with less specialists compared to shifting sands. Cyanobacterial community analysis showed that Microcoleus vaginatus and Scytonema javanicum are an ideal inoculating model, as they were still dominating the community after 15 years since inoculation, while other nitrogen‐fixing cyanobacteria occurred profusely with biocrust development. Biocrust community composition combined with thickness, Chl‐a and exopolysaccharide measurements revealed the large variation of cyanobacterial ecological functions along biocrust development, suggesting a main function shift: from carbon fixation associated with exopolysaccharide secretion in bare sandy soils to nitrogen fixation in developed biocrusts. This large‐scale field study verifies that cyanobacterial inoculation accelerates biocrust development and forwards succession, shaping the biocrust community composition over a long time.
Austerity Redux: The Post‐pandemic Wave of Budget Cuts and the Future of Global Public Health
Authors: Kentikelenis Alexander , Stubbs Thomas
Published: November 2021

The convergence of health, economic and social crises over the past 1.5 years has posed profound questions over the direction of travel for the world after COVID‐19. The narrative emerging out of major international organizations like the International Monetary Fund stresses avoiding a ‘divergent recovery’, whereby some countries steam ahead with high growth rates underpinned by robust government interventions and others fall further behind. In this account, crisis aftermath should not witness budget cuts, but investment in employment and human capital formation. So, is austerity a thing of the past? In this article, we review available evidence, focusing on public spending projections by the IMF and the precise content of IMF lending arrangements. Overall, we find that abandonment of the austerity argument is partially true right now, and questionable in the medium‐term. Our analysis of public expenditure projections reveals that by 2023, 83 out of 189 countries will face contractions in government spending compared to their 2010s average, thereby exposing a cumulative total of 2.3 billion people to the socio‐economic consequences of budget cuts. Most of the contracting countries will be middle‐income, while public spending in low‐income countries is expected to stagnate at low levels. Further, the IMF's lending arrangements reveal the return of extensive austerity measures and structural reforms, reminiscent of the organization's past policy advice. Drawing on these findings, we elaborate on how this will likely impact global public health.
Gambling and homelessness in older adults: a qualitative investigation
Authors: Vandenberg Brian , Livingstone Charles , Carter Adrian , O'Brien Kerry
Published: November 2021

Background and Aims

Homelessness is one of the most significant harms associated with gambling and appears to affect older adults disproportionately, but the relationship has received little research attention. This exploratory study investigated how gambling and homelessness is linked in older adults.

Methods

Using qualitative research methods, we undertook in‐depth semi structured face‐to‐face individual and group interviews to gather data from a purposive sample (n = 48) of key informants working in service provision for older adults (aged 50+ years) experiencing gambling‐related harm and/or homelessness in Victoria, Australia. Thematic analysis of data focused on evaluating mechanisms and identifying contextual conditions that activate pathways between gambling and homelessness.

Results

The relationship between gambling and homelessness in older adults is often indirect and non‐linear, and can represent a reflexive cycle. Experiencing periods of homelessness into older age can contribute to gambling, often because the adverse impacts of homelessness on older adults’ mental and material wellbeing increase the appeal of gambling. Additionally, comorbidities (e.g. substance use, mental illness, past trauma) and structural conditions (e.g. gambling accessibility, poverty, housing insecurity) can activate gambling. Furthermore, because gambling in the older homeless adult population is frequently hidden and regularly overlooked by service providers, it often continues unabated. Gambling in older adults can also contribute to the onset of first‐time homelessness. Large and rapid losses from high‐intensity gambling frequently characterize this route to homelessness. Such gambling is often triggered by major life events and changes (e.g. bereavement, job loss, relationship difficulties), and the outcomes are often worsened by the conduct of gambling operators and creditors.

Conclusions

The link between gambling and homelessness in older adults is complex, with connecting mechanisms often contingent upon individual, interpersonal and structural conditions and contexts. There is potential for preventative and ameliorative action given many of the underlying conditions appear modifiable through policy intervention.
Opioid and sedative requirements in extracorporeal membrane oxygenation patients on hydromorphone versus fentanyl
Authors: Browder Kelsey , Wanek Matthew , Wang Lu , Hohlfelder Benjamin
Published: November 2021

Background

The extracorporeal membrane oxygenation (ECMO) circuit causes pharmacokinetic alterations of medications which impact drug selection and dosing. Although hydromorphone has a favorable pharmacokinetic profile, it is unclear whether hydromorphone provides better patient‐centered benefits compared to fentanyl. The objective of this study is to compare opioid and sedative requirements in ECMO patients started on a fentanyl‐ versus hydromorphone‐based analgesia regimen.

Methods

This was a non‐interventional retrospective cohort study. It was conducted at a single center in the cardiovascular intensive care units and cardiac intensive care units. We included venovenous (VV) or venoarterial ECMO patients. Patients who were started on a fentanyl continuous infusion within 24 h of cannulation were compared to patients started on a hydromorphone continuous infusion.

Results

A linear mixed effects model was performed to compare doses of opioid, sedative, and propofol between groups over time. We included 28 hydromorphone patients and 53 fentanyl patients, with 85% on VV ECMO. There were no differences between hydromorphone and fentanyl groups in opioid or sedative (including propofol and benzodiazepine) doses for any ECMO day (p value for interaction .63 and .83, respectively). Propofol doses alone, however, were significantly higher in the fentanyl group on ECMO days three, four, and five.

Conclusions

There appear to be no major differences in opioid or sedative requirements whether ECMO patients are initiated on a hydromorphone‐ or fentanyl‐based regimen.
Clinical characteristics and comorbidities associated with testosterone prescribing in men
Authors: Sharma Aditi , Ul‐Haq Zia , Sindi Emad , Al‐Sharefi Ahmed , Kamalati Tahereh , Dhillo Waljit S. , Minhas Suks , Jayasena Channa N.
Published: November 2021

Objective

Testosterone replacement therapy (TRT) is recommended for the treatment of symptomatic hypogonadism in men. Data on prescription behaviours are, however, limited and conflicting. The objective of this study was to investigate clinical characteristics associated with the likelihood of being prescribed TRT by general practitioners (GP) in North‐West London (NWL).

Design

Retrospective cohort study using Discover database of GP‐registered patients in NWL between 2015 and 2019.

Patients

We identified 20,299 men aged ≥18 years with serum total testosterone measurement (TT) and without prior TRT prescription records.

Measurements

We determined whether TRT was subsequently commenced, while analysing clinical characteristics related to hypogonadism.

Results

Of all men having TT measurement, 19,583 (96.4%) were not commenced on TRT (Group A) and 716 (3.5%) men were commenced on TRT (Group B). Men prescribed TRT (Group B) had higher mean age, body mass index (BMI) and higher risks of hypertension, depression type 2 diabetes and ischaemic heart disease; conversely, men in Group B had lower mean pretreatment TT and were less likely to have prostate cancer. Four‐hundred and thirty‐six men (24.3%) with TT < 8 nmol/L and symptoms of low libido were not prescribed TRT.

Conclusions

Our study highlights several factors which may influence the decisions made by clinicians when initiating TRT in primary care. Clearer guidance for clinicians may help to improve the consistency of treatment of men with hypogonadism.
Identification of a novel mutant allele of LIM homeobox transcription factor 1 alpha (dreher) in mice
Authors: Suto Jun‐ichi
Published: November 2021

A male mouse exhibiting bidirectional circling behavior was identified in a Y‐chromosome consomic strain known as DH‐Chr YRR. The putative mutation responsible for the circling behavior was inherited in an autosomal recessive manner and was termed circ. To identify its causative gene, we performed exome sequencing; of the 34 candidates discovered, we found a novel nonsynonymous single nucleotide variation in LIM homeobox transcription factor 1 alpha (Lmx1a) (c.394G > C, p.Gly132Arg). The genetic linkage between Lmx1a and circ was confirmed in (♀BALB/cA × ♂DH‐Chr YRR‐circ/circ) F2 and (♀C57BL/6J × ♂DH‐Chr YRR‐circ/circ) F2 mice. The Lmx1a mutation led to many abnormalities that affected growth, pigmentation, reproduction, and cerebellar morphology. We showed that (♀BALB/cA × ♂DH‐Chr YRR‐circ/circ) F2‐circ/circ mice demonstrated significantly lower body mass than the F2‐+/? mice. Unlike the F2‐+/? mice, few (♀C57BL/6J × ♂DH‐Chr YRR‐circ/circ) F2‐circ/circ mice exhibited a belly spot. The circ/circ females were also invariably sterile, probably because of an underdeveloped uterus. Moreover, the circ/circ mice presented fewer cerebellar granule cells with lower density than the F2‐+/? mice. Although non‐complementation between circ and the known Lmx1a mutant alleles remains unconfirmed, the coisogenic nature of circ strongly suggests that it is a novel variant of Lmx1a, previously known as dreher. Therefore, we have assigned the gene symbol Lmx1adr‐circ to circ. In addition to Lmx1adr‐J and Lmx1adr‐kjmi, Lmx1adr‐circ is the third allele that causes a missense mutation within LIM domains. Identification of missense mutations is necessary to specify the critical residues for abrogating the in vivo functions of LMX1A.
Outcomes of hybrid closed‐loop insulin delivery activated 24/7 versus evening and night in free‐living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial
Authors: Renard Eric , Tubiana‐Rufi Nadia , Bonnemaison Elisabeth , Coutant Régis , Dalla‐Vale Fabienne , Bismuth Elise , Faure Nathalie , Bouhours‐Nouet Natacha , Farret Anne , Storey Caroline , Donzeau Aurélie , Poidvin Amélie , Amsellem‐Jager Jessica , Place Jérôme , Breton Marc D. ,   Free‐life Kid AP Study Group
Published: November 2021

Aim

To assess the safety and efficacy of hybrid closed‐loop (HCL) insulin delivery 24/7 versus only evening and night (E/N), and on extended 24/7 use, in free‐living children with type 1 diabetes.

Materials and Methods

Prepubertal children (n = 122; 49 females/73 males; age, 8.6 ± 1.6 years; diabetes duration, 5.2 ± 2.3 years; insulin pump use, 4.6 ± 2.5 years; HbA1c 7.7% ± 0.7%/61 ± 5 mmol/mol) from four centres were randomized for 24/7 versus E/N activation of the Tandem Control‐IQ system for 18 weeks. Afterwards, all children used the activated system 24/7 for 18 more weeks. The primary outcome was the percentage of time spent in the 70‐180 mg/dL glucose range (TIR).

Results

HCL was active 94.1% and 51.1% of the time in the 24/7 and E/N modes, respectively. TIR from baseline increased more in the 24/7 versus the E/N mode (52.9% ± 9.5% to 67.3% ± 5.6% [+14.4%, 95% CI 12.4%‐16.7%] vs. 55.1% ± 10.8% to 64.7% ± 7.0% [+9.6%, 95% CI 7.4%‐11.6%]; P = .001). Mean percentage time below range was similarly reduced, from 4.2% and 4.6% to 2.7%, and the mean percentage time above range decreased more in the 24/7 mode (41.9% to 30.0% [–11.9%, 95% CI 9.7%‐14.6%] vs. 39.8% to 32.6% [–7.2%, 95% CI 5.0%‐9.9%]; P = .007). TIR increased through the whole range of baseline levels and always more with 24/7 use. The results were maintained during the extension phase in those initially on 24/7 use and improved in those with initial E/N use up to those with 24/7 use. Neither ketoacidosis nor severe hypoglycaemia occurred.

Conclusions

The current study shows the safety and efficacy of the Tandem Control‐IQ system in free‐living children with type 1 diabetes for both E/N and 24/7 use; 24/7 use shows better outcomes, sustained for up to 36 weeks with no safety issues.
Do anxiety and depression symptoms moderate the effect of motivational enhancement therapy as a pretreatment to dialectical behaviour therapy skills training? A follow‐up analysis of a pilot randomised controlled trial for youth
Authors: Colvin Eamon , Tobon Juliana I. , Zipursky Robert B. , Streiner David L. , Ouimet Allison J.
Published: November 2021

Aim

We conducted a follow‐up analysis of a pilot randomised controlled trial to examine whether baseline depression and anxiety symptoms moderated the impact of a motivational enhancement therapy (MET) pretreatment to dialectical behaviour therapy skill training (DBT‐ST) for EA experiencing emotion dysregulation.

Methods

All participants completed a 12‐week DBT‐ST group intervention and participants in the MET/DBT‐ST condition also completed a 4‐week group MET pretreatment. Nineteen MET/DBT‐ST participants and 26 DBT‐ST only participants completed the treatment as per protocol.

Results

Baseline anxiety and depression symptoms moderated the impact of the MET pretreatment for participants' reductions in emotion dysregulation and psychological distress, respectively, at a 3‐month follow‐up: participants with more severe baseline symptoms benefited more from the pretreatment. However, baseline symptoms did not moderate the effect of MET immediately after treatment.

Conclusions

These results identified for whom MET is most effective as a pretreatment for DBT‐ST amongst a heterogenous sample of EA in a real‐world setting.
How is working length determination taught? A survey to assess what is recommended in undergraduate Schools of Dentistry in Brazil
Authors: Rech Luara Cristina , Montagner Francisco , Luisi Simone Bonato , Melo Tiago André Fontoura de
Published: November 2021

Introduction

To analyse what are the methods for working length (WLD) determination taught for undergraduate students in Brazilian Dental Schools and the perception of professors about the use of electronic WL determination in the clinical practice.

Methods

An online questionnaire with eighteen closed questions was sent to 209 Schools of Dentistry in Brazil using the Google Forms Platform. The questionnaire was structured to analyse the perception of professors in the department of endodontics about the method of working length determination taught in undergraduate courses in Dentistry. The data collected in the questionnaires were transferred to an Excel® spreadsheet and analysed using absolute and relative frequencies. The non‐parametric Mann‐Whitney test was used to compare groups.

Results

Of the 209 schools contacted, 41 (19.61%) returned answers to the questionnaire. According to professors, electronic working length (WL) determination had a shorter length of time to perform it (p < .001), WL measurement accuracy (p < .001) and ease of performance (p < .001). Professors felt safer when maintaining patency when using electronic WL determination (p = .0020).

Conclusions

Both radiographic and electronic methods of WL determination are taught in Brazilian Schools of Dentistry. The electronic method was used more frequently, especially in undergraduate clinical courses.
Studying the in vivo application of a liquid dermal scaffold in promoting wound healing in a mouse model
Authors: Pakyari Mohammadreza (Sam) , Jalili Reza B. , Kilani Ruhangiz Taghi , Amiri Nafise , Brown Erin , Ghahary Aziz
Published: November 2021

Lack of matrix deposition is one of the main factors that complicates the healing process of wounds. The aim of this study was to test the efficacy and safety of a liquid dermal scaffold, referred to as MeshFill (MF) that can fill the complex network of tunnels and cavities which are usually found in chronic wounds and hence improve the healing process. We evaluated in vitro and in vivo properties of a novel liquid dermal scaffold in a delayed murine full‐thickness wound model. We also compared this scaffold with two commercially available granular collagen‐based products (GCBP). Liquid dermal scaffold accelerated wound closure significantly compared with no‐treated control and collagen‐based injectable composites in a delayed splinted wound model. When we compared cellular composition and count between MF, no treatment and GCBP at the histology level, it was found that MF was the most analogous and consistent with the normal anatomy of the skin. These findings were matched with the clinical outcome observation. The flowable in situ forming scaffold is liquid at cold temperature and gels after application to the wound site. Therefore, it would conform to the topography of the wound when liquid and provides adequate tensile strength when solidified. This patient‐ready gelling dermal scaffold also contains the nutritional ingredients and therefore supports cell growth. Applying an injectable liquid scaffold that can fill wound gaps and generate a matrix to promote keratinocytes and fibroblasts migration, can result in improvement of the healing process of complex wounds.
Area‐based management of blue water fisheries: Current knowledge and research needs
Authors: Hilborn Ray , Agostini Vera N. , Chaloupka Milani , Garcia Serge M. , Gerber Leah R. , Gilman Eric , Hanich Quentin , Himes‐Cornell Amber , Hobday Alistair J. , Itano David , Kaiser Michel J. , Murua Hilario , Ovando Daniel , Pilling Graham M. , Rice Jake C. , Sharma Rishi , Schaefer Kurt M. , Severance Craig J. , Taylor Nathan G. , Fitchett Mark
Published: November 2021

The pelagic fisheries beyond the continental shelves are currently managed with a range of tools largely based on regulating effort or target catch. These tools comprise both static and dynamic area‐based approaches to include gear limitations, closed areas and bycatch limits. There are increasing calls for additional area‐based interventions, particularly expansion of marine protected areas, with many now advocating closing 30% of the oceans to fishing. In this paper, we review the objectives, methods and successes of area‐based management of blue water fisheries across objectives related to food production and environmental, social and economic impacts. We also consider the methods used to evaluate the performance of area‐based regulations and provide a summary of the relative quality of evidence from alternative evaluation approaches. We found that few area‐based approaches have been rigorously evaluated, and that it is often difficult to obtain requisite observational data to define a counterfactual to infer any causal effect for such evaluation. Management agencies have been relatively successful at maintaining important commercial species at or near their target abundance, but success at meeting ecological or social goals is less clear. The high mobility of both target and bycatch species generally reduces the effectiveness of area‐based management, and shifting distributions due to climate change suggest that adaptive rather than static approaches will be preferred. We prioritize research and management actions that would make area‐based management more effective.
Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K‐dependent carboxylation
Authors: Chen Xuejie , Furukawa Natsuko , Jin Da‐Yun , Liu Yizhou , Stafford Darrel W. , Williams Craig M. , Suhara Yoshitomo , Tie Jian‐Ke
Published: November 2021

UbiA prenyltransferase domain‐containing protein‐1 (UBIAD1) is responsible for the biosynthesis of menaquinone‐4 (MK‐4), a cofactor for extrahepatic carboxylation of vitamin K‐dependent (VKD) proteins. Genetic variations of UBIAD1 are mainly associated with Schnyder corneal dystrophy (SCD), a disease characterized by abnormal accumulation of cholesterol in the cornea. Results from in vitro studies demonstrate that SCD‐associated UBIAD1 mutations are defective in MK‐4 biosynthesis. However, SCD patients do not exhibit typical phenotypes associated with defects of MK‐4 or VKD carboxylation. Here, we coupled UBIAD1’s biosynthetic activity of MK‐4 with VKD carboxylation in HEK293 cells that stably express a chimeric VKD reporter protein. The endogenous Ubiad1 gene in these cells was knocked out by CRISPR‐Cas9‐mediated genome editing. The effect of UBIAD1 mutations on MK‐4 biosynthesis and VKD carboxylation was evaluated in Ubiad1‐deficient reporter cells by determining the production of MK‐4 or by measuring the efficiency of reporter‐protein carboxylation. Our results show that the hot‐spot mutation N102S has a moderate impact on MK‐4 biosynthesis (retained ˜ 82% activity) but does not affect VKD carboxylation. However, the G186R mutation significantly affected both MK‐4 biosynthesis and VKD carboxylation. Other mutations exhibit varying degrees of effects on MK‐4 biosynthesis and VKD carboxylation. These results are consistent with in vivo results obtained from gene knock‐in mice and SCD patients. Our findings suggest that UBIAD1’s MK‐4 biosynthetic activity does not directly correlate with the phenotypes of SCD patients. The established cell‐based assays in this study provide a powerful tool for the functional studies of UBIAD1 in a cellular milieu.
Herbage allowance and stocking method effect on grazing systems: Results of a long‐term experiment
Authors: Moojen Fernanda G. , Bremm Carolina , Laca Emilio A. , Machado Débora R. , Savian Jean V. , Carvalho Paulo C. de F.
Published: November 2021

Sward management is critical for animal performance in pastoral environments. We evaluated the performance of sheep grazing Italian ryegrass pastures under factorial combinations of two stocking methods (SM) (continuous and rotational) and two herbage allowances (HA) (10% and 20% of LWT) over 9 years. Average daily gain (ADG) was greater in continuous than in rotational stocking (p < .001) and in HA‐20% when compared with HA‐10% (p = .002). Weight gain per hectare was greater in HA‐10% than HA‐20% (p < .001). HA and total herbage production were the most important factors determining live weight (LW) gain per hectare, whilst sheep ADG relies upon sward parameters (i.e., sward height). Moreover, to increase sheep LW production per hectare in grazing systems, the amount of herbage production and its availability to animals is more important than the SM. These outcomes provide the basis to build sound grazing systems through the optimization of sward management.
Femtosecond laser micromachining of integrated glass devices for high‐order harmonic generation
Authors: Martínez Vázquez Rebeca , Ciriolo Anna G. , Crippa Gabriele , Tosa Valer , Sala Federico , Devetta Michele , Vozzi Caterina , Stagira Salvatore , Osellame Roberto
Published: November 2021

Femtosecond laser micromachining is a versatile technique that is broadly used for the fabrication of integrated optics and microfluidic devices. In this work, we present the fabrication and demonstration of a microfluidic device used for high‐order harmonic generation in a hollow waveguide filled with helium. We found a higher generation yield and a harmonic spectrum reshaping (at gas baking pressures over 400 mbar) in the hollow waveguide with a smoother surface. We believe that, thanks to the high versatility and three‐dimensional capability of this microstructuring technique, in the next future it will be possible to integrate more functionalities in the same glass chip thus paving the way to strong laser field physics in a lab‐on‐chip.
Natural ingredient paeoniflorin could be a lead compound against white spot syndrome virus infection in Litopenaeus vannamei
Authors: Hu Yang , Liu Lei , Shan Li‐peng , Chen Jiong
Published: November 2021

White spot syndrome virus (WSSV) is an important pathogen causing high mortality in the shrimp industry in aquaculture, yet there is no treatment available to date. In order to find a treatment against WSSV infection, this study examined the anti‐WSSV activity of eight natural compounds using shrimp larvae as a model. Among the eight compounds, paeoniflorin showed the most obvious anti‐WSSV effect, with a maximum protection efficiency of WSSV‐infected shrimp >60% at 100 μM. Furthermore, pretreatment and post‐treatment experiments revealed that paeoniflorin could prevent and treat WSSV infection in shrimp. The antiviral activity of paeoniflorin in aquaculture water decreased rapidly with time, and the results showed that the stable anti‐WSSV activity of paeoniflorin could only remain in water for 1 day. Thus, the dosing pattern of continuous medication changes was evaluated. Obviously, in the model of continuous change of paeoniflorin, WSSV copy numbers in the virus‐treated shrimp group still progressively increased, while the virus content in WSSVpaeoniflorin‐treated group continued to decrease. Interestingly, paeoniflorin inhibited horizontal transmission of WSSV to a certain extent. Notably, paeoniflorin significantly increased the expression of antimicrobial peptides of shrimp to resist WSSV. In conclusion, paeoniflorin has the potential to protect shrimp against WSSV.
Neuronal membrane glycoprotein (nmgp‐1) gene deficiency affects chemosensation‐related behaviors, dauer exit and egg‐laying in Caenorhabditis elegans
Authors: Fernández Eliana M. , Cutraro Yamila B. , Adams Jessica , Monteleone Melisa C. , Hughes Kiley J. , Frasch Alberto C. , Vidal‐Gadea Andrés G. , Brocco Marcela A.
Published: November 2021

The nervous system monitors the environment to maintain homeostasis, which can be affected by stressful conditions. Using mammalian models of chronic stress, we previously observed altered brain levels of GPM6A, a protein involved in neuronal morphology. However, GPM6A's role in systemic stress responses remains unresolved. The nematode Caenorhabditis elegans expresses a GPM6A ortholog, the neuronal membrane glycoprotein 1 (NMGP‐1). Because of the shared features between nematode and mammalian nervous systems and the vast genetic tools available in C. elegans, we used the worm to elucidate the role of GPM6A in the stress response. We first identified nmgp‐1 expression in different amphid and phasmid neurons. To understand the nmgp‐1 role, we characterized the behavior of nmgp‐1(RNAi) animals and two nmgp‐1 mutant alleles. Compared to control animals, mutant and RNAi‐treated worms exhibited increased recovery time from the stress‐resistant dauer stage, altered SDS chemosensation and reduced egg‐laying rate resulting in egg retention (bag‐of‐worms phenotype). Silencing of nmgp‐1 expression induced morphological abnormalities in the ASJ sensory neurons, partly responsible for dauer exit. These results indicate that nmgp‐1 is required for neuronal morphology and for behaviors associated with chemosensation. Finally, we propose nmgp‐1 mutants as a tool to screen drugs for human nervous system pathologies.

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‘We can bear it!’ Unpacking barriers to hepatocellular carcinoma screening among patients with hepatitis B: A qualitative study
Authors: Li Caixia , Lu Xiling , Xiao Jinnan , Chan Carmen W. H.
Published: November 2021

Aims and objectives

To explore barriers to hepatocellular carcinoma screening among patients with hepatitis B.

Background

Hepatitis B‐related hepatocellular carcinoma is a major cause of cancer‐related mortality globally. A preventive strategy for screening is needed to improve early tumour detection and overall survival. However, utilisation remains suboptimal and barriers are understudied and largely focused on clinical factors.

Design

A qualitative study based on the preventive health model using phenomenological hermeneutical approach.

Methods

Face‐to‐face semi‐structured interviews were conducted with 23 hepatitis B patients from November 2020 to February 2021. Interpretative phenomenological analysis was used. The COREQ checklist was followed.

Results

Four themes were identified: (i) miscognition, (ii) cultural stigma and taboo, (iii) social norms of enduring hardship and (iv) social barriers at the community, health system and policy levels. Patients had misconceptions about inactive carriers, asymptomatic nature of chronic hepatitis B, hepatocellular carcinoma risks and screening recommendations. Influenced by the taboo of hepatocellular carcinoma, stigma against hepatitis B and enduring hardship norms, they perceived screening as divination, avoided utilisation to hide disease status and endured symptoms until they were intolerable. Insufficient community support, a lack of shared decision‐making in health systems, and inadequate rural reimbursement policy and hepatocellular carcinoma detection capacity further precluded utilisation.

Conclusions

Cognitive and sociocultural barriers precluded individuals’ intention, utilisation and persistence of hepatocellular carcinoma screening. The results highlight intervention targets for miscognition, stigma, taboo and social norms; propose family‐focused, community‐based education programs; suggest health systems to introduce decision aids; and inform policymaking and upskilling of physicians in rural areas.

Relevance to clinical practice

Collaborative efforts are needed to improve real‐world hepatocellular carcinoma screening, including education to address knowledge deficiencies, psychological counselling to reduce stigma and taboo beliefs, support for shared decision‐making and reimbursement policies.