bluuebunny/crossref_metadata_2025 huggingface dataset:
Early consequences of the phospholamban mutation PLN‐R14del+/− in a transgenic mouse model
Authors: Maniezzi Claudia , Eskandr Marem , Florindi Chiara , Ferrandi Mara , Barassi Paolo , Sacco Elena , Pasquale Valentina , Maione Angela S. , Pompilio Giulio , Teixeira Vivian Oliveira Nunes , de Boer Rudolf A. , Silljé Herman H. W. , Lodola Francesco , Zaza Antonio
Published: January 2024

Aims

The heterozygous phospholamban (PLN) mutation R14del (PLN R14del+/−) is associated with a severe arrhythmogenic cardiomyopathy (ACM) developing in the adult. “Superinhibition” of SERCA2a by PLN R14del is widely assumed to underlie the pathogenesis, but alternative mechanisms such abnormal energy metabolism have also been reported. This work aims to (1) to evaluate Ca2+ dynamics and energy metabolism in a transgenic (TG) mouse model of the mutation prior to cardiomyopathy development; (2) to test whether they are causally connected.

Methods

Ca2+ dynamics, energy metabolism parameters, reporters of mitochondrial integrity, energy, and redox homeostasis were measured in ventricular myocytes of 8–12 weeks‐old, phenotypically silent, TG mice. Mutation effects were compared to pharmacological PLN antagonism and analyzed during modulation of sarcoplasmic reticulum (SR) and cytosolic Ca2+ compartments. Transcripts and proteins of relevant signaling pathways were evaluated.

Results

The mutation was characterized by hyperdynamic Ca2+ handling, compatible with a loss of SERCA2a inhibition by PLN. All components of energy metabolism were depressed; myocyte energy charge was preserved under quiescence but reduced during stimulation. Cytosolic Ca2+ buffering or SERCA2a blockade reduced O2 consumption with larger effect in the mutant. Signaling changes suggest cellular adaptation to perturbed Ca2+ dynamics and response to stress.

Conclusions

(1) PLN R14del+/− loses its ability to inhibit SERCA2a, which argues against SERCA2a superinhibition as a pathogenetic mechanism; (2) depressed energy metabolism, its enhanced dependency on Ca2+ and activation of signaling responses point to an early involvement of metabolic stress in the pathogenesis of this ACM model.
Calcineurin inhibition, cardiovascular consequences, vascular resistance, and potential responses
Authors: Luft Friedrich C.
Published: January 2024

Aim

To place the consequences of calcineurin inhibition in a cardiovascular context.

Methods

Literature review coupled with personal encounters.

Results

Calcineurin is a calcium‐binding and calmodulin‐binding protein that is conserved across evolution from yeast to mammals. The enzyme functions as a calcium‐dependent, calmodulin‐stimulated protein phosphatase. Its role in regulating physiology has largely been elucidated by observing calcineurin inhibition. Calcineurin inhibition transformed organ transplantation from an experiment into a therapy and made much of general immunotherapy possible. The function of this phosphatase and how its inhibition leads to toxicity concern us to this date. Initial research from patients and animal models implicated a panoply of factors contributing to hypertension and vasculopathy. Subsequently, the role of calcineurin in regulating the effective fluid volume, sodium reabsorption, and potassium and hydrogen ion excretion was elucidated by investigating calcineurin inhibition. Understanding the regulatory effects of calcineurin on endothelial and vascular smooth muscle cell function has also made substantial progress. However, precisely how the increase in systemic vascular resistance arises requires further mechanistic research.

Conclusion

Calcineurin inhibition continues to save lives; however, options to counteract the negative effects of calcineurin inhibition should be vigorously pursued.
FilmArray (BCID2) provides essential and timely results in bloodstream infections in small acute care hospitals without conventional microbiology services
Authors: Harboe‐Sjåvik Hege , Endresen Kristoffer Hammer , Åsheim Sandra , Sundsfjord Arnfinn
Published: January 2024

We have evaluated the performance of FilmArray BCID2 in reactive blood cultures in a small acute care hospital compared to conventional diagnostics at a regional microbiological laboratory. This is a retrospective observational study of BactAlert reactive blood cultures (n = 160) from Helgeland Hospital, July–December 2021, analysed by BCID2 locally and conventional culture at a regional laboratory. The overall clinical and analytic sensitivity with BCID2 were 87.2% and 97.8%, respectively. The false‐negative BCID2 rate was low (n = 4; 2.9%). No false‐positive BCID2 results were observed. The BCID2 data were available on average 1.88 days earlier than culture‐based results, due to long transport time to the regional laboratory. The BCID2 provided results to support a significantly earlier optimized targeted antibiotic treatment in 27% of the cases according to national guidelines for empirical treatment of BSI. The high clinical and analytical sensitivity, and specificity support the use of BCID2 as a robust supplement to traditional cultivation of positive blood cultures. The significant time gain to microbial identification and detection of resistance determinants suggests a great clinical importance of BCID2 in small acute care hospitals with long transport time to conventional clinical microbiology services.
Fieldnotes as never really ‘raw’ data: Analysing the social life of public space on London's South Bank
Authors: Jones Alasdair
Published: January 2024

Unlike for other forms of qualitative data, examples of how fieldnotes are analysed are rarely provided in the literature. Using fieldnotes from my ethnographic study of the production of public space on London's South Bank as a starting point, this paper considers why this might be the case. In particular, the paper argues that for fieldnote‐based research, analysis is a feature of note‐taking, rather than a discrete phase of activity conducted using our fieldnotes once they have been collected. In this vein, the paper encourages researchers to be aware of the analytical in their fieldnotes, and to be open to the ways that analysis inside the notebook can help us identify salient objects of enquiry in our work.
The outcomes for women planning aVBACat a private hospital in Australia
Authors: Chu Julieanne , Keedle Hazel , Sutcliffe Kerry , Blumenthal Norman , Levett Kate
Published: January 2024

Background

Rates of cesarean birth (CBs) are steadily increasing and account for 36.7% of all births in New South Wales (NSW), with primary cesareans driving the increase. NSW Health guidelines recommend women attempt a vaginal birth after a previous CB (VBAC); however, rates of VBAC are decreasing, particularly within the private hospital setting. This study aimed to determine the rates of adverse outcomes for women who planned a VBAC (pVBAC) compared with women who planned an elective repeat CB (pERCB) at one private hospital in Sydney, Australia.

Method

This retrospective data review evaluated patient records over a 10‐year period (2010–2019). Records (n = 2039) were divided into four groups: pVBAC, pVBAC + EMCB, labor + ERCB (lab + ERCB), and pERCB. The incidence of adverse maternal and neonatal outcomes is reported as counts and percentages. Regression and chi‐squared tests were used to compare groups. Significance was determined at ap‐value of <0.05.

Results

Overall, very low rates (N = 148, 7.3%) of women had a VBAC compared with a repeat CB at this private hospital over the 10‐year period. The incidence of adverse outcomes was low regardless of study group. Outcomes differed significantly between groups for postpartum hemorrhage (pERCB seven times less likely than VBAC group) and special care nursery admission (pVBAC + EMCB is 4.6 times more likely than in the VBAC group).

Conclusion

Overall, it is safe to attempt a VBAC at this private hospital, and labor after a cesarean should be recommended, yet very few women had a VBAC at the study site. The incidence of adverse outcomes was low compared with other published research.
Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate
Authors: Calanchini Matilde , Bradley‐Watson James , McMillan Fiona , Myerson Saul , Fabbri Andrea , Turner Helen E. , Orchard Elizabeth
Published: January 2024

Objective

The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS‐related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement.

Methods

151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts.

Results

70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS‐related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac‐alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post‐operatively.

Conclusions

Mean aortic growth in our TS population was increased compared to non‐TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.
Recent advances in the use of optical coherence tomography in neuro‐ophthalmology: A review
Authors: Ge Jasmine Yaowei , Teo Zhen Ling , Loo Jing Liang
Published: January 2024

Optical coherence tomography (OCT) is an in vivo imaging modality that provides non‐invasive, high resolution and fast cross‐sectional images of the optic nerve head, retina and choroid. OCT angiography (OCTA) is an emerging tool. It is a non‐invasive, dye‐free imaging approach of visualising the microvasculature of the retina and choroid by employing motion contrast imaging for blood flow detection and is gradually receiving attention for its potential roles in various neuro‐ophthalmic and retinal conditions. We will review the clinical utility of the OCT in the management of various common neuro‐ophthalmic and neurological disorders. We also review some of the OCTA research findings in these conditions. Finally, we will discuss the limitations of OCT as well as introduce other emerging technologies.
Tracing the barriers to decarbonising ophthalmology: A review
Authors: Lam Lydia , Bradbrook Darren , Gale Jesse
Published: January 2024

As climate change demands increasingly urgent mitigation of greenhouse gas emissions, the health sector needs to do its part to decarbonise. Ophthalmologists share concerns about climate change and seek opportunities to reduce their environmental impact. When measuring the footprint of ophthalmology, major contributions are from patient travel to clinics, and from the large amounts of single‐use disposable materials that are consumed during surgeries and sterile procedures. Ophthalmic services in India have already demonstrated systems that consume far fewer of these products through efficient throughput of patients and the safe reuse of many items, while maintaining equivalent safety and quality outcomes. Choosing these low‐cost low‐emission options would seem obvious, but many ophthalmologists experience barriers that prevent them operating as Indian surgeons do. Understanding these barriers to change is a crucial step in the decarbonisation of ophthalmology and the health sector more broadly.
Multi‐Level Linguistic Alignment in a Dynamic Collaborative Problem‐Solving Task
Authors: Duran Nicholas D. , Paige Amie , D'Mello Sidney K.
Published: January 2024

Cocreating meaning in collaboration is challenging. Success is often determined by people's abilities to coordinate their language to converge upon shared mental representations. Here we explore one set of low‐level linguistic behaviors, linguistic alignment, that both emerges from, and facilitates, outcomes of high‐level convergence. Linguistic alignment captures the ways people reuse, that is, “align to,” the lexical, syntactic, and semantic forms of others' utterances. Our focus is on the temporal change of multi‐level linguistic alignment, as well as how alignment is related to communicative outcomes within a unique collaborative problem‐solving paradigm. The primary task, situated within a virtual educational video game, requires creative thinking between three people where the paths for possible solutions are highly variable. We find that over time interactions are marked by decreasing lexical and syntactic alignment, with a trade‐off of increasing semantic alignment. However, greater semantic alignment does not translate into better team performance. Overall, these findings provide greater clarity on the role of linguistic coordination within complex and dynamic collaborative problem‐solving tasks.
SIRT1 activation promotes bone repair by enhancing the coupling of type H vessel formation and osteogenesis
Authors: Liu Zhikai , Liu Hanghang , Liu Shibo , Li Bolun , Liu Yao , Luo En
Published: January 2024

Bone repair is intricately correlated with vascular regeneration, especially of type H vessels. Sirtuin 1 (SIRT1) expression is closely associated with endothelial function and vascular regeneration; however, the role of SIRT1 in enhancing the coupling of type H vessel formation with osteogenesis to promote bone repair needs to be investigated. A co‐culture system combining human umbilical vein endothelial cells and osteoblasts was constructed, and a SIRT1 agonist was used to evaluate the effects of SIRT1 activity. The angiogenic and osteogenic capacities of the co‐culture system were examined using short interfering RNA. Mouse models with bone defects in the femur or mandible were established to explore changes in type H vessel formation and bone repair following modulated SIRT1 activity. SIRT1 activation augmented the angiogenic and osteogenic capacities of the co‐culture system by activating the PI3K/AKT/FOXO1 signalling pathway and did not significantly regulate osteoblast differentiation. Inhibition of the PI3K/AKT/FOXO1 pathway attenuated SIRT1‐mediated effects. The SIRT1 activity in bone defects was positively correlated with the formation of type H vessels and bone repair in vivo, whereas SIRT1 inhibition substantially weakened vascular and bone formation. Thus, SIRT1 is crucial to the coupling of type H vessels with osteogenesis during bone repair.
A novel gelatinized barium sulfate injection method for assessment of bronchoalveolar lavage parameters
Authors: Gross Alexander R. , Kehinde Temitope , Morais Lindsey , Hutchison Marshall , Grise Joy , Mohamed Nada , Badami Varun , Ahmed Haroon , Zdilla Matthew J. , Vos Jeffrey A. , Gross Austin G. , Leonard Rachel
Published: January 2024

Introduction

Bronchoalveolar lavage (BAL) is frequently used in pulmonary medicine though it requires further optimization. Practical obstacles such as patient safety and procedural limitation have to date precluded large, controlled trials aimed at standardization of BAL procedure. Indeed, BAL guidelines are based on observational data. Innovative research methods are necessary to advance the clinical practice of BAL.

Methods

In our study, we evaluated the effect of injecting a gelatinized barium solution into different lobes and segments of cadaveric lungs. As the technique requires an irreversible injection into lung airspaces, it is not suitable for in vivo purposes. We measured the volume returned from BAL as well as the distribution of BAL injection via dissection. Segmental anatomic orientation was compared to a radiologist's impression of plain film radiographs taken of injected lungs.

Results

Mean injected volume distributions were greatest in the upper lobes and lowest in the lower lobes; mean ratios of injected volume distribution to lung lobe volume also followed this trend. Cannulated bronchi orders favored lower branches in the upper lobe and higher branches in the lower lobes. Segmental anatomy varied by the lung lobe injected and was most varied in the lower lobes.

Conclusion

This novel gelatinized‐barium injection technique provides a minimally complex method to yield clinically meaningful feedback on the performance of BAL. The technique is also adaptable to study of procedural parameters in the context of variable lung anatomies and pathologies.
Safety and utility of panniculectomy in renal transplant candidates and end stage renal disease patients
Authors: Laspro Matteo , Stead Thor S. , Barrow Brooke , Brydges Hilliard T. , Onuh Ogechukwu C. , Gelb Bruce E. , Chiu Ernest S.
Published: January 2024

Background

As the obesity crisis in the United States continues, some renal transplantation centers have liberalized their BMI criteria necessary for transplant eligibility. More individuals with larger body‐habitus related comorbidities with End‐Stage Renal Disease (ESRD) now qualify for renal transplantation (RT). Surgical modalities from other fields also interact with this patient population.

Methods

In order to assess surgical outcomes of panniculectomy in the context of renal transplantation and ESRD, the authors performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta‐Analyses (PRISMA) 2020 guidelines. Due to a paucity of existing primary studies, we retrospectively collected data on patients with ESRD undergoing panniculectomy from the American College of Surgeons’ National Surgical Quality Improvement Program (NSQIP) to evaluate outcomes of body contouring in this patient population.

Results

From the systematic review, a total of 783 ESRD patients underwent panniculectomy among the studies identified. Of these, 91 patients underwent panniculectomy simultaneously to RT while 692 had their pannus resected prior to kidney transplant. The most common complication was hematoma followed by wound dehiscence. From the NSQIP database, 24 868 patients met the inclusion criteria for analysis. In the setting of renal transplant status, patients with diabetes, hypertension requiring medication, and requiring dialysis were more likely to suffer postoperative complications (OR 1.31, 1.15, and 2.2, respectively). However, upon sub‐analysis of specific types of complications, the only retained association was between diabetes and wound complication.

Conclusion

Preliminary data show that panniculectomy in ESRD patients appears to be safe, though with a nominal increased risk for complications. Pannus resection does not appear to impact post‐transplantation outcomes, including long‐term allograft survival. Larger, higher powered, randomized studies are needed to confirm the safety, utility, and medical benefit of panniculectomy in the context of renal transplantation.
Endotheliale und tumor‐intrinsische Mechanismen der hepatischen Melanommetastasierung
Authors: Wohlfeil Sebastian A. , Géraud Cyrill
Published: January 2024

Die Behandlung des metastasierten kutanen Melanoms wurde durch die Entdeckung und Zulassung von Immuncheckpoint‐Inhibitoren (ICI) wie Anti‐PD‐1‐ und Anti‐CTLA‐4‐Antikörpern sowie der zielgerichteten Therapie mit BRAF‐ und MEK‐Inhibition grundlegend verbessert. Allerdings entwickeln viele Patienten Rezidive aufgrund von Resistenzmechanismen, die zum Teil durch Metastasierung in bestimmte Organe verursacht werden. Insbesondere Hirn‐ und Lebermetastasen sind negative prädiktive Faktoren für beide Behandlungsmodalitäten. Bislang gibt es nur begrenzte Möglichkeiten, organspezifische Metastasierung aufzuhalten oder zu behandeln. Daher muss sich die experimentelle Forschung unter anderem Mechanismen der hepatischen Metastasierung des Melanoms widmen, um diesen Prozess besser zu verstehen und therapeutische Ziele ausfindig zu machen.
The personal epistemology of parents predicts the development of scientific reasoning in children aged 6–10 years
Authors: Osterhaus Christopher , Koerber Susanne
Published: January 2024

The influence of the epistemological beliefs of parents on the development of comprehensive scientific reasoning abilities was investigated in a five‐wave longitudinal study from kindergarten to elementary school. The 161 German 5–10‐year‐olds (89 girls, 72 boys) were assessed yearly on their scientific reasoning abilities using comprehensive measures for experimentation and data‐interpretation skills, as well as understanding of the nature of science. The children were also tested on their language abilities and intelligence. Their parents completed a sociodemographics questionnaire and answered ten questions about their epistemological beliefs regarding (1) the interpretive nature of science, (2) the tentative nature of knowledge, and (3) the role of scientific framework theories. The personal epistemology of the parents significantly predicted the scientific reasoning development of their children regardless of the parents’ education level and the children's general cognitive abilities. However, the effect of the epistemology of parents on their children's scientific reasoning was limited to the intercepts, suggesting that the epistemic understanding of parents affects how scientific reasoning develops in their children, but not the development speed. Although parental epistemology exerts substantial effects on scientific reasoning of their children, it did not affect their reading ability, suggesting an involvement of science‐specific mechanisms rather than generalized family‐based influences. These findings highlight the importance of family as a variable in the development of scientific reasoning, which is an area lacking in research, and it suggests that early interventions targeted at the epistemic understanding of caregivers can provide useful ways for promoting the reasoning of children.

Research Highlights

A five‐year longitudinal study shows significant development of scientific reasoning from kindergarten to elementary school.

Caregivers’ personal epistemology predicted scientific reasoning development—independent of children's general cognitive abilities and caregivers’ level of education.

The effect was most‐pronounced for caregivers’ understanding that social framework theories determine which aspects of science are accepted and how they are conducted.

Caregivers’ personal epistemology did not predict children's reading abilities, suggesting that the effect of the caregivers’ epistemology on children's scientific reasoning is domain‐specific.
Influence of pore water pressure on concrete creep and a creep model considering the effect of cohesion and internal friction angle
Authors: Liu Wenbo , Zhang Shuguang
Published: January 2024

A new nonlinear viscoplastic body considering cohesion and internal friction coefficient versus time is proposed by considering cohesion and internal friction angle. A new creep model for concrete considering cohesion and internal friction angle is obtained by interlocking it with the conventional model. The results show that the creep model can properly reflect the creep development of soft‐cut concrete at the pile head by comparing the creep model with the three‐dimensional creep test data trends under various levels of loading. The model can well describe the whole process of creep deformation and also better compensate for the shortcomings of the traditional creep model that cannot describe the characteristics of accelerated creep deformation.
Connecting through clicks: A longitudinal examination of internet use and depressive symptoms among middle‐ and old‐aged Chinese
Authors: Mu Aruhan , Hong Ziying , Wu Xiang
Published: January 2024

Aim

While prior investigations into the influence of internet engagement on depressive symptoms in middle‐aged and older individuals have largely been favorable, concerns persist. Some research posits that internet use may detract from direct interpersonal interactions, elevating depression risks. Here, we scrutinize these contrasting views, endeavoring to delineate the relationship between internet use, social participation, and the ensuing depressive manifestations.

Methods

We analyzed nationally representative data from three consecutive waves (2013‐T1, 2015‐T2, 2018‐T3) of the China Health and Retirement Longitudinal Study survey. Measures of social participation encompassed formal social participation (i.e., attending clubs for mahjong, chess, sports, or other activities; participation in community organizations, volunteering, or enrolling in training courses) and informal social participation (i.e., interactions with friends or extending assistance to relatives, friends, or neighbors). Structural equation modeling was used to evaluate a focused longitudinal mediation model.

Results

Our dataset comprised 13 671 individuals aged 45 years or older. Baseline internet use was associated with a decrease in depressive symptoms by T3 ( = −0.143, SE = 0.055). The longitudinal association between internet use and the alleviation of depressive symptoms was partially mediated by enhanced formal social participation (indirect effect  = −0.023, SE = 0.011).

Conclusions

For developing nations such as China, grappling with a rapidly aging demographic and scarce mental health infrastructure, pioneering initiatives that merge digital and formal social participation might be a valuable component in a multifaceted approach to alleviate late‐life depression. Geriatr Gerontol Int 2024; 24: 218–224.
Improving the mechanical property of the castables bonded with hydratable magnesium carboxylate by incorporating MgO fumes
Authors: Chen Jianjun , Xiao Guoqing , Ding Donghai , Sun Luyan , Zang Yunfei , Yin Chaofan , Feng Haixia , Dong Binbin , Wang Qingfeng , Qian Yuejin
Published: January 2024

Previous studies have indicated that hydratable magnesium carboxylate (HMC) exhibits potential as an MgO‐based binder, but its limited medium‐temperature strength has hindered its widespread industrial application. In this study, the incorporation of MgO fumes into castables is intended to react with microsilica to form magnesium–silicate–hydrate (M–S–H), and the synergistic effect of HMC and M–S–H is anticipated to improve the mechanical properties of castables at intermediate temperatures. The effects of MgO fumes on the properties of HMC‐bonded castables were comprehensively investigated. The results demonstrate that incorporating MgO fumes into castable serves multiple functions. The ionized MgOH+ from MgO fumes hinders the hydration process of HMC, prolonging the final setting time from 13 to 98 min and improving the workability of castables. The incorporation of MC‐1100 enhanced mechanical properties at medium temperature due to the synergistic effects of brucite, HMC, and M–S–H. Specifically, the CMOR increased 20% after sintering at 800°C. Furthermore, adding MC‐1100 increases the residual strength rate of castable by 10% compared to those without MgO fumes. This can be attributed to enhanced spinel formation resulting from adding MgO fumes that improves elastic modulus and reduces elastic strain energy generation during thermal shock, thus increasing crack propagation resistance.
Transitioning patients from intravenous to subcutaneous infliximab and vedolizumab for inflammatory bowel disease: what is the opportunity cost of improving access to healthcare?
Authors: Hilley Patrick , Wong Darren , Ma Ronald , Peterson Adam , De Cruz Peter
Published: January 2024

Background

Biologic drugs are highly effective for inflammatory bowel disease (IBD) management but are key drivers of costs of care especially when administered intravenously (i.v.). Availability of subcutaneous (SC) formulations has increased convenience for patients and improved access to care, but at the cost of revenue to health services.

Aims

To evaluate the economic impact of transitioning a tertiary centre IBD cohort from i.v. to SC biologic administration and assess the implications for key stakeholders.

Methods

A retrospective analysis of all patients who received i.v. infliximab or vedolizumab in the outpatient infusion centre of a tertiary IBD centre between July 2019 and June 2021 was undertaken. Data were collated from electronic medical records, pharmacy dispensing systems and the hospital business intelligence unit. An economic analysis and theoretical financial/capacity impact analysis of a transition to an SC model were estimated under two scenarios using a random 10% and 30% of the patient cohort.

Results

Transitioning our IBD cohort from i.v. to SC administration would result in a loss to our health service of AU$2 732 123.75, composed of AU$1 463 003.75 in Weighted Inlier Equivalent Separation (WIES) and AU$1 269 120 in drug procurement revenue. However, it would ease capacity in the infusion centre by up to 5256 h.

Conclusions

Transitioning patients to SC administration results in improved access to infusion centres and substantial savings to state governments; however, switching results in a loss of i.v. biologic‐generated WIES to health services. Alternative funding models are required to achieve sustainability in IBD care and reduce reliance on i.v. biologic‐generated income.
Acceleration of optimizing the dielectric properties of (Ca0.7Nd0.2)1−x(Li0.5Nd0.5)xTi1−y(Mg1/3Nb2/3)yO3 with the aid of machine learning
Authors: Ni Ziqi , Wang Fenglin , Guan Yeqing , Hu Kaijia , Zhao Fengyuan , Chen Xingyu , Ye Yicong , Zhang Weijun , Bai Shuxin
Published: January 2024

The three key properties required for microwave dielectric ceramics are suitable dielectric constant (εr), high quality factor (Q × f), and near‐zero temperature coefficient of resonant frequency (τf). Due to the intricate coupling relationship among these three properties, regulating one often leads to the deterioration of the remaining two. In this study, the synergetic regulation of dielectric properties of Ca0.7Nd0.2TiO3 was investigated to reduce τf to near‐zero while maintaining its high εr by A‐ and B‐site substitutions. To avoid the seesaw effect and improve the efficiency of composition optimization, machine learning method was introduced in this study. First, the models for predicting dielectric properties were fitted based on a small amount of high‐quality data gathered via a uniform experimental design. Then the dielectric properties of 1037 compositions of (Ca0.7Nd0.2)1−x(Li0.5Nd0.5)xTi1−y(Mg1/3Nb2/3)yO3 were predicted, from which 69 microwave dielectric ceramics with near‐zero τf and adjustable εr of 95–125 were quickly picked out, and 5 of them were proved by experiments with very high prediction accuracy. This work was finished within a period of 1 month, which proves the obvious acceleration of composition designing process of microwave dielectric ceramics with the aid of machine learning.
Revitalizing the skin: Exploring the role of barrier repair moisturizers
Authors: Madnani Nina , Deo Jyotsna , Dalal Krunal , Benjamin Brian , Murthy Vidya V. , Hegde Rashmi , Shetty Tanvi
Published: January 2024

Background

Moisturizers are designed to maintain skin health and treat dermatological conditions associated with impaired skin barrier function. However, differences in their composition account for the differences in their effect.

Aims

This narrative review aims to discuss the role of barrier repair moisturizers, highlight the role of different components in a moisturizer and their role in impaired skin conditions (e.g., dry, itchy, inflamed, sensitive skin, atopic eczema), and thereby empower dermatologists and pediatricians in selecting the right moisturizer.

Methods

PubMed, Embase, and Scopus electronic databases were searched from January 2000 to June 2023 for publications on skin barrier repair and use of barrier repair moisturizers for the treatment of dry, itchy, inflamed, sensitive skin, or atopic eczema. Studies conducted in humans, published in English for which full texts were freely available were included.

Results

The structure and composition of lipid lamellae within the stratum corneum play an important role in maintaining an effective skin barrier and protecting the body from various external assaults. Endocannabinoid mediators play an active role in maintaining skin barrier function. Moisturizers containing physiological lipids and functional ingredients (e.g., endocannabinoids such as palmitoylethanolamide [PEA]) and based on the principles of biomimic technology are demonstrated to be beneficial for the management of conditions associated with a disrupted skin barrier.

Conclusions

Moisturizer based on the innovative biomimic formulation has good cosmetic efficacy and is generally well tolerated, and the addition of PEA might represent a new generation of compounds that may be beneficial for long‐term management of impaired skin conditions.
N1‐Acetyl‐5‐methoxykynuramine, which decreases in the hippocampus with aging, improves long‐term memory via CaMKII/CREB phosphorylation
Authors: Watanabe Kazuki , Maruyama Yusuke , Iwashita Hikaru , Kato Haruyasu , Hirayama Jun , Hattori Atsuhiko
Published: January 2024

Melatonin is a molecule ubiquitous in nature and involved in several physiological functions. In the brain, melatonin is converted to N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and then to N1‐acetyl‐5‐methoxykynuramine (AMK), which has been reported to strongly enhance long‐term object memory formation. However, the synthesis of AMK in brain tissues and the underlying mechanisms regarding memory formation remain largely unknown. In the present study, young and old individuals from a melatonin‐producing strain, C3H/He mice, were employed. The amount of AMK in the pineal gland and plasma was very low compared with those of melatonin at night; conversely, in the hippocampus, the amount of AMK was higher than that of melatonin. Indoleamine 2, 3‐dioxygenase (Ido) mRNA was expressed in multiple brain tissues, whereas tryptophan 2,3‐dioxygenase (Tdo) mRNA was expressed only in the hippocampus, and its lysate had melatonin to AFMK conversion activity, which was blocked by the TDO inhibitor. The expression levels of phosphorylated cAMP response element binding protein (CREB) and PSD‐95 in whole hippocampal tissue were significantly increased with AMK treatment. Before increasing in the whole tissue, CREB phosphorylation was significantly enhanced in the nuclear fraction. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that downregulated genes in hippocampus of old C3H/He mice were more enriched for long‐term potentiation (LTP) pathway. Gene set enrichment analysis showed that LTP and neuroactive receptor interaction gene sets were enriched in hippocampus of old mice. In addition, Ido1 and Tdo mRNA expression was significantly decreased in the hippocampus of old mice compared with young mice, and the decrease in Tdo mRNA was more pronounced than Ido1. Furthermore, there was a higher decrease in AMK levels, which was less than 1/10 that of young mice, than in melatonin levels in the hippocampus of old mice. In conclusion, we first demonstrated the Tdo‐related melatonin to AMK metabolism in the hippocampus and suggest a novel mechanism of AMK involved in LTP and memory formation. These results support AMK as a potential therapeutic agent to prevent memory decline.
Beyond age‐structured single‐species management: Optimal harvest selectivity in the face of predator–prey interactions
Authors: Bang Rasmus Noss , Steinshamn Stein Ivar
Published: January 2024

In the single‐species literature, it is widely acknowledged that conserving young fish for future harvesting is beneficial. This finding holds great significance in fisheries economics and has garnered substantial attention over the years. In this study, a full‐blown age‐structured predator–prey model is developed and used to demonstrate that multispecies considerations may shift the optimal selection of predators towards smaller individuals, providing valuable counteractive insights. These new results offer a fresh perspective highly relevant to regulation and choice of selectivity patterns.
A Non‐parametric Estimation of Productivity with Idiosyncratic and Aggregate Shocks: The Role of Research and Development (R&D) and Corporate Tax
Authors: Bournakis Ioannis , Tsionas Mike
Published: January 2024

We develop a non‐parametric technique framework for estimating firm‐level Total Factor Productivity (TFP). Our paper has two major novelties: first, we propose a modelling of productivity with both firm‐idiosyncratic factors and aggregate shocks. Second, we apply the Bayesian Markov Chain Monte Carlo (MCMC) technique that offers a numerical integration of productivity outside the posterior overcoming the restrictive assumptions about the relationship between productivity and variable production inputs. We implement our methodology in a group of 4,286 manufacturing firms from France, Germany, Italy, and the UK (2001–14). The results show that: (i) aggregate shocks matter for firm TFP evolution. The global financial crisis of 2008 caused severe, albeit short, adverse effects on TFP; (ii) there is substantial heterogeneity across countries in the way firms react to changes in R&D and taxation. German and UK firms are more sensitive to fiscal changes than R&D, while the opposite is true for Italian firms. R&D and taxation effects are symmetrical for French firms; (iii) the UK productivity handicap continues for years after the financial crisis; and (iv) there are substantial knowledge spillovers among German and Italian firms.
How Does the Slump Sitting Radiograph Increase Proportion of Segmental Instability and Kyphotic Alignment of Lumbar Degenerative Spondylolisthesis?
Authors: Zhou Qingshuang , Sun Xu , Wang Bin , Zhu Zezhang , Qiu Yong
Published: January 2024

Objective

Clinical and radiographic degenerative spondylolisthesis (CARDS) classification was proposed to differentiate homogenous lumbar degenerative spondylolisthesis (LDS) subgroups. The sitting radiograph exhibited lumbar malalignment with maximum lumbar kyphosis, intervertebral kyphosis, and spondylolisthesis.This study aimed to assess the sitting radiograph for distribution of clinical and radiographic degenerative spondylolisthesis classification, and to elucidate its significance for exhibiting kyphotic alignment (CARDS type D) and segmental instability.

Methods

A cohort of 101 patients with symptomatic lumbar degenerative spondylolisthesis (LDS) between September 2018 and December 2020 were recruited. The distribution and relibility of CARDS classification with or without sitting radiograph was assessed. The translational and angular range of motion and segmental instability was also evaluated. Univariate analysis of variance was used for multiple groups, and the least significant difference for two groups. Kappa consistency test of intrarater and interrater was evaluated for CARDS classification with or without sitting radiograph. Chi‐square test was used to compare paried categorical data.

Results

Utility of sitting radiographs for CARDS classification revealed higher percentage of type D than that without the sitting radiograph (p < 0.001). The sitting radiograph revealed a larger slip distance than the flexion radiograph (p = 0.003), as well as a lower slip angle than flexion radiograph (p < 0.001). The sitting‐supine modality demonstrated the largest translational range of motion compared to the sitting‐extension (p < 0.001) and flexion‐extension modalities (p < 0.001). The sitting‐supine modality showed larger angular range of motion than the flexion‐extension modality (p < 0.001). The percentage of flexion, extension, upright, supine, and sitting radiograph to identify translational instability was higher than that without sitting radiograph (p < 0.001), as well as taking angular motion ≥10° as an additional criterion for segmental instability (p < 0.001).

Conclusion

The CARDS classification was reliable for LDS. The sitting radiograph showed maximal slip distance and kyphotic slip angle. Application of the sitting radiograph was necessary for evaluating segmental instability and kyphotic alignment of LDS.
Editing of ORF138 restores fertility of Ogura cytoplasmic male sterile broccoli via mitoTALENs
Authors: Xu Fengyuan , Su Tongbing , Zhang Xiaochen , Qiu Lei , Yang Xiaodong , Koizuka Nobuya , Arimura Shin‐ichi , Hu Zhongyuan , Zhang Mingfang , Yang Jinghua
Published: January 2024

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator‐like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re‐sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold‐sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost‐effective toolkit to accelerate the life cycle of fertile lines from CMS‐derived broccoli hybrids. By applying the k‐mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold‐sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature‐responsive ability are regulated by the mitochondria.
Identification of transcriptional modules linked to the drought response of Brassica napus during seed development and their mitigation by early biotic stress
Authors: Bianchetti Grégoire , Clouet Vanessa , Legeai Fabrice , Baron Cécile , Gazengel Kévin , Vu Benoit Ly , Baud Sébastien , To Alexandra , Manzanares‐Dauleux Maria J. , Buitink Julia , Nesi Nathalie
Published: January 2024

In order to capture the drought impacts on seed quality acquisition in Brassica napus and its potential interaction with early biotic stress, seeds of the ‘Express’ genotype of oilseed rape were characterized from late embryogenesis to full maturity from plants submitted to reduced watering (WS) with or without pre‐occurring inoculation by the telluric pathogen Plasmodiophora brassicae (Pb + WS or Pb, respectively), and compared to control conditions (C). Drought as a single constraint led to significantly lower accumulation of lipids, higher protein content and reduced longevity of the WS‐treated seeds. In contrast, when water shortage was preceded by clubroot infection, these phenotypic differences were completely abolished despite the upregulation of the drought sensor RD20. A weighted gene co‐expression network of seed development in oilseed rape was generated using 72 transcriptomes from developing seeds from the four treatments and identified 33 modules. Module 29 was highly enriched in heat shock proteins and chaperones that showed a stronger upregulation in Pb + WS compared to the WS condition, pointing to a possible priming effect by the early P. brassicae infection on seed quality acquisition. Module 13 was enriched with genes encoding 12S and 2S seed storage proteins, with the latter being strongly upregulated under WS conditions. Cis‐element promotor enrichment identified PEI1/TZF6, FUS3 and bZIP68 as putative regulators significantly upregulated upon WS compared to Pb + WS. Our results provide a temporal co‐expression atlas of seed development in oilseed rape and will serve as a resource to characterize the plant response towards combinations of biotic and abiotic stresses.
The 8 billion milestone: Risk perceptions of global population growth among UK and US residents
Authors: Dawson Ian G. J. , Zhang Danni
Published: January 2024

In November 2022, the global human population reached 8 billion and is projected to reach 10 billion by 2060. Theories, models, and evidence indicate that global population growth (GPG) increases the likelihood of many adverse outcomes, such as biodiversity loss, climate change, mass migrations, wars, and resource shortages. A small body of research indicates that many individuals are concerned about the effects of GPG, and these concerns are strongly related to the willingness to engage in mitigative and preventative actions. However, scientific understanding of the factors that influence GPG risk perceptions remains limited. To help address this research gap, we conducted a study of the perceived risk of GPG among UK and US residents (N = 1029) shortly after the “8 billion milestone.” Our results confirmed that GPG is perceived as a moderate‐to‐high risk and these perceptions have a strong positive relationship with the willingness to engage in and support risk management actions. Our participants believed that the worst effects of GPG were yet to come but would largely be geographically and socially remote. Despite their willingness to engage in risk management actions, our participants reported low self‐efficacy and that governments (cf. individuals and communities) have the greatest capacity to influence GPG. Risk perceptions were strongly predicted by worldviews and were higher among our UK (cf. US) participants. We also found that the perceived benefits of GPG were low and found no evidence to suggest that risk perceptions were affected by exposure to media coverage of the 8 billion milestone.
Refining vanadium hyper‐enrichment in black shales of the Late Devonian–Early Mississippian Bakken Formation (USA)
Authors: Wang Yunfeng
Published: January 2024

Vanadium hyper‐enrichment (V ≥ 500 μg g−1) is widespread in ancient marine organic‐rich sedimentary rocks and is controlled by its source and accumulation. To understand how V source and accumulation control V hyper‐enrichment, the V hyper‐enriched organic‐rich black shales of the Late Devonian–Early Mississippian Bakken Formation (USA) were investigated here. The results imply that V in the Bakken Formation black shales is mainly derived from detritus and open ocean. Its hyper‐enrichment was always related to the complexation of V(IV) species by organic matter and/or fine clay mineral adsorption, though extremely reducing (i.e. euxinic) depositional conditions sometimes assisted in accumulating V through forming V(IV)–sulphur structure and/or V(III). Vanadium is a frequently used seawater redox indicator, but its hyper‐enrichment in marine sediments/sedimentary rocks does not always need to be redox driven. This study, thus, reminds us to be more careful when reconstructing palaeoceanographic redox states using V‐involved proxies.
Design and Testing of a New LARMbot Torso
Authors: Gao Wenshuo , Russo Matteo , Ceccarelli Marco
Published: January 2024

Developing a robotic torso mechanism is crucial in replicating human mobility in humanoid robots. Previous research has presented the LARMbot humanoid's torso as a potential solution, which has now been improved with a novel design proposed in this paper. We conduct a kinematic analysis on the proposed LARMbot torso design, which is developed through an analysis of the human spine's structure. A kinematic model of the novel design is proposed using piecewise constant curvature to capture the relationship between input and output parameters and to represent the workspace. A prototype is utilized for conducting experiments to test the human-like movements of the novel mechanism. The outcomes show that the proposed LARMbot torso architecture can enhance performance. The generated humanoid torso prototype has the capacity to bend approximately 30 deg, and as such, it can be expected to make humanoid robots achieve human-like motion and tasks.