bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the potential of social prescribing in individual-level type 2 diabetes prevention: a mixed-methods realist evaluation
Authors: Calderón-Larrañaga Sara , Greenhalgh Trish , Clinch Megan , Robson John , Dostal Isabel , Eto Fabiola , Finer Sarah
Published: March 2023

Background

Social prescribing (SP) usually involves linking patients in primary care with services provided by the voluntary and community sector. Preliminary evidence suggests that SP may offer a means of connecting patients with community-based health promotion activities, potentially contributing to the prevention of long-term conditions, such as type 2 diabetes (T2D).

Methods

Using mixed-methods realist evaluation, we explored the possible contribution of SP to individual-level prevention of T2D in a multi-ethnic, socio-economically deprived population in London, UK. We made comparisons with an existing prevention programme (NHS Diabetes Prevention Programme (NDPP)) where relevant and possible. Anonymised primary care electronic health record data of 447,360 people 18+ with an active GP registration between December 2016 and February 2022 were analysed using quantitative methods. Qualitative data (interviews with 11 primary care clinicians, 11 social prescribers, 13 community organisations and 8 SP users at high risk of T2D; 36 hours of ethnographic observations of SP and NDPP sessions; and relevant documents) were analysed thematically. Data were integrated using visual means and realist methods.

Results

People at high risk of T2D were four times more likely to be referred into SP than the eligible general population (RR 4.31 (95% CI 4.17–4.46)), with adjustment for socio-demographic variables resulting in attenuation (RR 1.33 (95% CI 1.27–1.39)). More people at risk of T2D were referred to SP than to NDPP, which could be explained by the broad referral criteria for SP and highly supportive (proactive, welcoming) environments. Holistic and sustained SP allowed acknowledgement of patients’ wider socio-economic constraints and provision of long-term personalised care. The fact that SP was embedded within the local community and primary care infrastructure facilitated the timely exchange of information and cross-referrals across providers, resulting in enhanced service responsiveness.

Conclusions

Our study suggests that SP may offer an opportunity for individual-level T2D prevention to shift away from standardised, targeted and short-term strategies to approaches that are increasingly personalised, inclusive and long-term. Primary care-based SP seems most ideally placed to deliver such approaches where practitioners, providers and commissioners work collectively to achieve holistic, accessible, sustained and integrated services.
Circ-Ntrk2 acts as a miR-296-5p sponge to activate the TGF-β1/p38 MAPK pathway and promote pulmonary hypertension and vascular remodelling
Authors: Su Lihuang , Li Xiuchun , Mao Xulong , Xu Tingting , Zhang Yiying , Li Shini , Zhu Xiayan , Wang Liangxing , Yao Dan , Wang Jian , Huang Xiaoying
Published: March 2023

Background

Circular RNAs (circRNAs), a novel class of non-coding RNAs, play an important regulatory role in pulmonary arterial hypertension (PAH); however, the specific mechanism is rarely studied. In this study, we aimed to discover functional circRNAs and investigate their effects and mechanisms in hypoxia-induced pulmonary vascular remodelling, a core pathological change in PAH.

Methods

RNA sequencing was used to illustrate the expression profile of circRNAs in hypoxic PAH. Bioinformatics, Sanger sequencing, and quantitative real-time PCR were used to identify the ring-forming characteristics of RNA and analyse its expression. Then, we established a hypoxia-induced PAH mouse model to evaluate circRNA function in PAH by echocardiography and hemodynamic measurements. Moreover, microRNA target gene database screening, fluorescence in situ hybridisation, luciferase reporter gene detection, and western blotting were used to explore the mechanism of circRNAs.

Results

RNA sequencing identified 432 differentially expressed circRNAs in mouse hypoxic lung tissues. Our results indicated that circ-Ntrk2 is a stable cytoplasmic circRNA derived from Ntrk2 mRNA and frequently upregulated in hypoxic lung tissue. We further found that circ-Ntrk2 sponges miR-296-5p and miR-296-5p can bind to the 3′-untranslated region of transforming growth factor-β1 (TGF-β1) mRNA, thereby attenuating TGF-β1 translation. Through gene knockout or exogenous expression, we demonstrated that circ-Ntrk2 could promote PAH and vascular remodelling. Moreover, we verified that miR-296-5p overexpression alleviated pulmonary vascular remodelling and improved PAH through the TGF-β1/p38 MAPK pathway.

Conclusions

We identified a new circRNA (circ-Ntrk2) and explored its function and mechanism in PAH, thereby establishing potential targets for the diagnosis and treatment of PAH. Furthermore, our study contributes to the understanding of circRNA in relation to PAH.
Understanding school food systems to support the development and implementation of food based policies and interventions
Authors: Bryant Maria , Burton Wendy , O’Kane Niamh , Woodside Jayne V. , Ahern Sara , Garnett Phillip , Spence Suzanne , Sharif Amir , Rutter Harry , Baker Tim , Evans Charlotte E. L.
Published: March 2023

Background

Schools provide opportunities to improve the quality of children's diet, whilst reducing inequalities in childhood diet and health. Evidence supports whole school approaches, including consistency in food quality, eating culture and food education. However, such approaches are often poorly implemented due to the highly complex environments in which schools operate. We aimed to develop a school food systems map using a systems thinking approach to help identify the key factors influencing primary school children’s dietary choice.

Methods

Eight workshops were conducted with 80 children (from schools from varying locations (region of England/UK; urban/rural), deprivation levels and prioritisation of school food policies)) and 11 workshops were held with 82 adult stakeholders across the UK (principals, teachers, caterers, school governors, parents, and local and voluntary sector organisations) to identify factors that influence food choice in children across a school day and their inter-relationships. Initial exploratory workshops started with a ‘blank canvas’ using a group model building approach. Later workshops consolidated findings and supported a wider discussion of factors, relationships and influences within the systems map. Strengths of the relationship between factors/nodes were agreed by stakeholders and individually depicted on the map. We facilitated an additional eight interactive, in-person workshops with children to map their activities across a whole school day to enable the production of a journey map which was shared with stakeholders in workshops to facilitate discussion.

Results

The final ‘CONNECTS-Food’ systems map included 202 factors that were grouped into 27 nodes. Thematic analysis identified four key themes: leadership and curriculum; child food preference; home environment; and school food environment. Network analysis highlighted key factors that influence child diet across a school day, which were largely in keeping with the thematic analysis; including: 'available funds/resources', 'awareness of initiatives and resources', 'child food preference and intake', 'eligibility of free school meals', 'family circumstances and eating behaviours', 'peer/social norms', 'priorities of head teachers and senior leaders'.

Conclusions

Our systems map demonstrates the need to consider factors external to schools and their food environments. The map supports the identification of potential actions, interventions and policies to facilitate a systems-wide positive impact on children’s diets.
Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis
Authors: Razzaghi Khamesi Pooya , Charitatos Vasileios , Heerfordt Eva K. , MacAulay Nanna , Kurtcuoglu Vartan
Published: March 2023

Background

The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested.

Methods

To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data.

Results

Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production.

Conclusions

The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production.
Participation in leisure activities and quality of life of people with psychosis in England: a multi-site cross-sectional study
Authors: Ngamaba Kayonda Hubert , Webber Martin , Xanthopoulou Penny , Chevalier Agnes , Giacco Domenico
Published: March 2023

Background

Leisure activities can improve quality of life in the general population. For people with psychosis, negative symptoms (e.g. being unmotivated, difficulty in sticking with activities) are often a barrier to engaging in social leisure activities. However, we do not know if participation in leisure activities is associated with quality of life in this group and, whether psychosocial interventions should aim to increase leisure activities.

Aim

This study investigates participation in social leisure activities of people with psychosis and whether their participation is associated with better quality of life.

Methods

A cross-sectional survey was conducted in 6 NHS mental health trusts. Adults aged 18–65 (N = 533) with a diagnosis of a psychosis-related condition (ICD-10 F20-29) were recruited from outpatient secondary mental health services. Several measures were used including an adapted version of the Time Use Survey (TUS), the Social contacts assessment (SCA) and Manchester Short Assessment of Quality of Life (MANSA). A Structural Equation Model (SEM) was used to explore the relationships between participation in leisure activities and quality of life, and whether social contacts mediated the link.

Results

Participants attended an average of 2.42 (SD = 1.47) leisure activities in the last 7 days. Their quality of life increased with the number of leisure activities they attended. Participation in leisure activities was positively associated with quality of life in people with psychosis (B = 0.104, SE = 0.051, p = 0.042, 95% CI [0.003 to 0.204]). Leisure activities predicted social contacts, but the link between social contacts and the quality of life was not significant. After controlling for sociodemographic factors, being female and unemployed were negatively linked with quality of life (B = − 0.101, SE = 0.048, p = 0.036, 95% CI [− 0.196 to − 0.006; B = − 0.207, SE = 0.050, p = 0.001, 95% CI [− 0.305 to − 0.108, respectively].

Conclusion

People with psychosis who attend more leisure activities have a higher quality of life. Quality of life was lower amongst female and unemployed participants who attended leisure activities. Intervention which helps improve participation in leisure activities may be beneficial for people with psychosis.

Trial registration number ISRCTN15815862.
Comparison of diagnosis and treatment of MSSA and MRSA osteomyelitis in children: a case–control study of 64 patients
Authors: Wen Yuwei , Wang Chunhua , Jia Haiting , Liu Tao , Yu Jiazhi , Zhang Mengyuan
Published: March 2023

Background

We aimed to compare the clinical characteristics of acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) in children.

Methods

We retrospectively analyzed the data of 64 children treated between September 2017 and June 2021. Based on the bacterial culture results, they were divided into MRSA and MSSA infection groups. Both groups were treated with debridement and vacuum-assisted closure for negative pressure drainage. Parameters including clinical manifestations, number of operations, length of hospital stay, inflammatory indicators, and concurrent arthritis were compared between the two groups.

Results

In the MRSA infection group, there was one case each of residual joint stiffness and pathological fracture. Conversely, the MSSA group had two cases of residual joint stiffness. The MRSA infection group was more prone to high fever (t = 3.61, P = 0.001), white blood cell count elevation (t = 2.41, P = 0.022), arthritis (X2 = 7.48, P = 0.013), metastatic abscess (X2 = 4.78, P = 0.042), and a shorter length of progression from onset to admission (t = − 2.04, P = 0.046); however, it required more surgeries (t = 2.68, P = 0.009) and longer hospital stay (t = 2.04, P = 0.045).

Conclusions

Pediatric acute osteomyelitis caused by MRSA is more prone to cause high fever and markedly elevated of white blood cell count, and is often accompanied with suppurative infection of adjacent joints and metastatic abscesses, thus requiring more surgeries and longer hospital stay.
Strategies of pretreatment of feedstocks for optimized bioethanol production: distinct and integrated approaches
Authors: Shukla Akanksha , Kumar Deepak , Girdhar Madhuri , Kumar Anil , Goyal Abhineet , Malik Tabarak , Mohan Anand
Published: March 2023

Bioethanol is recognized as a valuable substitute for renewable energy sources to meet the fuel and energy demand of the nation, considered an environmentally friendly resource obtained from agricultural residues such as sugarcane bagasse, rice straw, husk, wheat straw and corn stover. The energy demand is sustained using lignocellulosic biomass to produce bioethanol. Lignocellulosic biomass (LCBs) is the point of attention in replacing the dependence on fossil fuels. The recalcitrant structure of the lignocellulosic biomass is disrupted using effective pretreatment techniques that separate complex interlinked structures among cellulose, hemicellulose, and lignin. Pretreatment of biomass involves various physical, chemical, biological, and physiochemical protocols which are of importance, dependent upon their individual or combined dissolution effect. Physical pretreatment involves a reduction in the size of the biomass using mechanical, extrusion, irradiation, and sonification methods while chemical pretreatment involves the breaking of various bonds present in the LCB structure. This can be obtained by using an acidic, alkaline, ionic liquid, and organosolvent methods. Biological pretreatment is considered an environment-friendly and safe process involving various bacterial and fungal microorganisms. Distinct pretreatment methods, when combined and utilized in synchronization lead to more effective disruption of LCB, making biomass more accessible for further processing. These could be utilized in terms of their effectiveness for a particular type of cellulosic fiber and are namely steam explosion, liquid hot water, ammonia fibre explosion, CO2 explosion, and wet air oxidation methods. The present review encircles various distinct and integrated pretreatment processes developed till now and their advancement according to the current trend and future aspects to make lignocellulosic biomass available for further hydrolysis and fermentation.
A variability in response of osteoclasts to zoledronic acid is mediated by smoking-associated modification in the DNA methylome
Authors: Tan Qihua , Møller Anaïs Marie Julie , Qiu Chuan , Madsen Jonna Skov , Shen Hui , Bechmann Troels , Delaisse Jean-Marie , Kristensen Bjarne Winther , Deng Hong-Wen , Karasik David , Søe Kent
Published: March 2023

Background

Clinical trials have shown zoledronic acid as a potent bisphosphonate in preventing bone loss, but with varying potency between patients. Human osteoclasts ex vivo reportedly displayed a variable sensitivity to zoledronic acid > 200-fold, determined by the half-maximal inhibitory concentration (IC50), with cigarette smoking as one of the reported contributors to this variation. To reveal the molecular basis of the smoking-mediated variation on treatment sensitivity, we performed a DNA methylome profiling on whole blood cells from 34 healthy female blood donors. Multiple regression models were fitted to associate DNA methylation with ex vivo determined IC50 values, smoking, and their interaction adjusting for age and cell compositions.

Results

We identified 59 CpGs displaying genome-wide significance (p < 1e−08) with a false discovery rate (FDR) < 0.05 for the smoking-dependent association with IC50. Among them, 3 CpGs have p < 1e−08 and FDR < 2e−03. By comparing with genome-wide association studies, 15 significant CpGs were locally enriched (within < 50,000 bp) by SNPs associated with bone and body size measures. Furthermore, through a replication analysis using data from a published multi-omics association study on bone mineral density (BMD), we could validate that 29 out of the 59 CpGs were in close vicinity of genomic sites significantly associated with BMD. Gene Ontology (GO) analysis on genes linked to the 59 CpGs displaying smoking-dependent association with IC50, detected 18 significant GO terms including cation:cation antiporter activity, extracellular matrix conferring tensile strength, ligand–gated ion channel activity, etc.

Conclusions

Our results suggest that smoking mediates individual sensitivity to zoledronic acid treatment through epigenetic regulation. Our novel findings could have important clinical implications since DNA methylation analysis may enable personalized zoledronic acid treatment.
[18F]Fluoride uptake in various bone types and soft tissues in rat
Authors: Savisto Nina , Grönroos Tove J. , Oikonen Vesa , Rajander Johan , Löyttyniemi Eliisa , Bergman Jörgen , Forsback Sarita , Solin Olof , Haaparanta-Solin Merja
Published: March 2023

Background

In the development of new 18F-labelled tracers, it is important to assess the amount of released [18F]fluoride taken up in the bones of experimental animals because all 18F-labelled PET-tracers are prone, to lesser or higher degree, to undergo defluorination, with subsequent release of [18F]fluoride during scanning. However, the pharmacokinetics of [18F]fluoride in bones and other organs of healthy rats have not been well documented in a comprehensive manner. We aimed to study pharmacokinetics of [18F]NaF in rats in order to increase our understanding of the biodistribution of [18F]fluoride originating from defluorination of 18F-labelled tracers. We studied [18F]fluoride uptake in Sprague Dawley rat bones, including the epiphyseal parts of the tibia and radius, the mandible, ilium, lumbar vertebrae, costochondral joints, tibia, radius, and ribs, with 60-min in vivo PET/CT imaging. Kinetic parameters, K1, Ki, Ki/K1, and k3 were calculated with a three-compartment model. In addition, separate groups of male and female rats were studied with ex vivo bone and soft tissue harvesting and gamma counting over a 6-h period.

Results

[18F]fluoride perfusion and uptake varied among the different bones. [18F]fluoride uptake was higher in trabecular bones, due to high perfusion and osteoblastic activity, compared to cortical bones. In soft tissues, the organ-to-blood uptake ratios increased over time in the eyes, lungs, brain, testes, and ovaries during the 6 h study period.

Conclusion

Understanding the pharmacokinetics of [18F]fluoride in various bones and soft tissues is highly useful for assessing 18F-labelled radiotracers that release [18F]fluoride.
Exosomal USP13 derived from microvascular endothelial cells regulates immune microenvironment and improves functional recovery after spinal cord injury by stabilizing IκBα
Authors: Ge Xuhui , Zhou Zheng , Yang Siting , Ye Wu , Wang Zhuanghui , Wang Jiaxing , Xiao Chenyu , Cui Min , Zhou Jiawen , Zhu Yufeng , Wang Rixiao , Gao Yu , Wang Haofan , Tang Pengyu , Zhou Xuhui , Wang Ce , Cai Weihua
Published: March 2023

Spinal cord injury (SCI) can result in irreversible sensory and motor disability with no effective treatment currently. After SCI, infiltrated macrophages accumulate in epicenter through destructed blood-spinal cord barrier (BSCB). Further, great majority of macrophages are preferentially polarized to M1 phenotype, with only a few transient M2 phenotype. The purpose of this study was to explore roles of vascular endothelial cells in microglia/macrophages polarization and the underlying mechanism. Lipopolysaccharide (LPS) was used to pretreat BV2 microglia and RAW264.7 macrophages followed by administration of conditioned medium from microvascular endothelial cell line bEnd.3 cells (ECM). Analyses were then performed to determine the effects of exosomes on microglia/macrophages polarization and mitochondrial function. The findings demonstrated that administration of ECM shifted microglia/macrophages towards M2 polarization, ameliorated mitochondrial impairment, and reduced reactive oxygen species (ROS) production in vitro. Notably, administration of GW4869, an exosomal secretion inhibitor, significantly reversed these observed benefits. Further results revealed that exosomes derived from bEnd.3 cells (Exos) promote motor rehabilitation and M2 polarization of microglia/macrophages in vivo. Ubiquitin-specific protease 13 (USP13) was shown to be significantly enriched in BV2 microglia treated with Exos. USP13 binds to, deubiquitinates and stabilizes the NF-κB inhibitor alpha (IκBα), thus regulating microglia/macrophages polarization. Administration of the selective IκBα inhibitor betulinic acid (BA) inhibited the beneficial effect of Exos in vivo. These findings uncovered the potential mechanism underlying the communications between vascular endothelial cells and microglia/macrophages after SCI. In addition, this study indicates exosomes might be a promising therapeutic strategy for SCI treatment.
Impact of different nutritional approaches on sarcopenia: a protocol for systematic review and network meta-analysis
Authors: Kim Jung-Hyun , Kim Sung-Min , Kim Yong-Chan , Seo Byung-Kwan
Published: March 2023

Although it is known that proper nutrition is effective in managing sarcopenia, the most powerful nutrients have not yet been determined. This study is designed to investigate the effects of various nutritional approaches on muscle mass, muscle strength, and sarcopenia prevention in systematic reviews. In study design, network and pairwise meta-analyses of randomized clinical trials were considered. Clinical studies regarding the nutritional effects associated with the physiological activity of skeletal muscle and management of sarcopenia will be covered. The main outcomes will cover the following five elements: anti-fatigue impact with skeletal muscle, muscle atrophy prevention, differentiation level with skeletal muscular cell, anti-inflammatory effect, and muscle injury prevention. Authors will conduct the study selection, extracting data process, and methodological quality investigation.

Systematic review registration

OSF registry (ethical approval number:https://osf.io/ye4q7).
Digital entrepreneurial acceptance: an examination of technology acceptance model and do-it-yourself behavior
Authors: Ilyas Muhammad , ud din Arif , Haleem Muhammad , Ahmad Irshad
Published: March 2023

The study extended the existing literature on digital entrepreneurship, do-it-yourself and technology acceptance models with the help of empirical data. It further aimed to identify the factors associated with the e-entrepreneurial acceptance by examining the integration of do-it-yourself and technology acceptance models. A data sample consisting of 200 questionnaires were collected from small–medium enterprise using the digital platforms for their business activities. Structural equation modeling was applied for testing the association of the models. A robust theoretical framework adopted to validate to use digital entrepreneurship as a standalone or along with the traditional entrepreneurial. The study was only limited to the small–medium enterprises working in the context of Pakistan. A total of 200 respondents were visited to collect the data using convenience sampling technique. The findings of this study concluded that all the variables of technology acceptance model are significantly related to the digital entrepreneurial acceptance. Similarly, factors associated with do-it-yourself behavior had a substantial influence, with the exception of perceived lack of product quality as well as perceived lack of product availability variables, which had no significant impact on digital entrepreneurial acceptance.
The approaching pilot for One Health governance index
Authors: Li Odel Y. , Wang XiangCheng , Yang Kelly , Liu DongMei , Shi HuaChen
Published: March 2023

Background

One Health approach advocates realizing the best health and harmonious symbiosis of human, animal and natural environment through cross-border, multi-sectoral and interdisciplinary cooperation. The good governance model is the leading factor for the performance of One Health governance. In order to tackle the complex problems in the One Health governance at the global level, the variation of One Health governance in different countries was analyzed by a set of indicators within the One Health system.

Method

The capacity of One Health governance was assessed after establishment of a set of indicators for the One Health governance index (OHGI) following the methodology of the global One Health index. The data to calculate OHGI was collected from various database sources, including the Food and Agriculture Organization, the World Health Organization, the World Organization for Animal Health, and official health-related institutions of various countries. Eight indicators (including 19 sub-indicators) were employed in the OHGI system to comprehensively evaluate the capacity of One Health governance in 146 countries of the world.

Results

Among the 146 countries scored in the OHGI system, the average score was 34.11, with a median score of 31.49, ranged from 8.50 to 70.28. Most countries with higher OHGI scores come from Europe and Central Asia, East Asia and the Pacific and North America, while countries with the lower OHGI scores are almost from sub-Saharan Africa. Six countries scored more than 65 points, including Australia, Sweden, Germany, Netherlands, the United States of America and Finland, indicating that these countries are relatively mature in most aspects of One Health governance. However, there were some developing countries with OHGI scored lower than 15. Therefore, the gap between countries with higher OHGI scores and those with lower OHGI scores is more than 60.

Conclusions

Good governance on One Health is an important indicator to measure One Health’s governance capacity. The political stability, the level of rule of law and economic conditions in different regions are significantly correlated with the One Health governance capacity. Actions need to be taken urgently to close the gap of One Health governance between different regions.
The determinants of a resilient food system for Finland in the 2020s—three opinion polls for improvements based on a Delphi study among food system experts
Authors: Rikkonen Pasi , Rimhanen Karoliina , Aro Kalle , Aakkula Jyrki
Published: March 2023

Sudden shocks, disturbances, and changes in today’s and the future’s operating environment call for a more resilient food system. COVID-19 and Russia’s latest war in Ukraine have revealed that rapid shocks and disturbances in global social-ecological systems can affect societies and pose various risks to food security. The discussion of food security and especially food supply security under uncertain changes has therefore been highlighted. In this study, food system resilience and the driving forces and current trends affecting it were evaluated in an expert panel study. We used the Delphi technique for the data collection, which included several rounds of iterative evaluation of future food system development up to 2030. We analysed the results using cluster analysis. Based on the results, three clusters were identified which weigh different points within the development foci of food system resilience, namely: (1) the lack of efficient and consensual global crisis preparedness, (2) looking after domestic food production, and (3) trusting the current good efforts in resilience building. The key resilience determinants in each cluster and their importance analysis are presented. We also present enablers and barriers from techno-economic, politico-institutional, and socio-cognitive perspectives that hinder or support resilience building.
Living and leaving a life of coercion: a qualitative interview study of patients with anorexia nervosa and multiple involuntary treatment events
Authors: Mac Donald Benjamin , Gustafsson Sanna A. , Bulik Cynthia M. , Clausen Loa
Published: March 2023

Background

A small but significant group of patients with anorexia nervosa (AN) undergo multiple involuntary treatment (IT) events. To enhance our understanding of IT and potentially inform treatment, we explored experiences and perspectives on IT of these patients.

Methods

We designed a qualitative semi-structured interview study and used reflexive thematic analysis. Participants were at least 18 years of age, had multiple past IT events (≥ 5) related to AN over a period of at least one month of which the last IT event happened within the preceding five years. Participants had no current IT, intellectual disability, acute psychosis, or severe developmental disorder. We adopted an inductive approach and constructed meaning-based themes.

Results

We interviewed seven participants. The data portrayed a process of living and leaving a life of coercion with a timeline covering three broad themes: living with internal coercion, coercive treatment, and leaving coercion; and five subthemes: helping an internal battle, augmenting suffering, feeling trapped, a lasting imprint, and changing perspectives. We highlighted that patients with AN and multiple IT events usually experienced internal coercion from the AN prior to external coercion from the health care system. IT evoked significant negative affect when experienced, and often left an adverse imprint. Moreover, IT could help an internal battle against AN and perspectives on IT could change over time.

Conclusions

Our study suggests that feeling internally coerced by AN itself sets the stage for IT. Clinicians should be conscious of the potential iatrogenic effects of IT, and reserve IT for potentially life-threatening situations.
Covid-19 vaccine acceptance among individuals incarcerated in Connecticut state jails
Authors: Lind Margaret L. , Kennedy Byron S. , Nieto Murilo Dorion , Houde Amy J. , Sosensky Peri , Borg Ryan , Cummings Derek A. T. , Ko Albert I. , Richeson Robert P.
Published: March 2023

Background

Vaccine hesitancy is common among incarcerated populations and, despite vaccination programs, vaccine acceptance within residents remains low, especially within jails. With the goal of assessing the Connecticut DOC’s COVID-19 vaccine program within jails we examined if residents of DOC operated jails were more likely to become vaccinated following incarceration than in the community. Specifically, we conducted a retrospective cohort analysis among people who spent at least one night in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination.

Results

During the study period, 3,716 people spent at least one night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 479 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% Confidence Intervals: 10.2–15.3).

Conclusions

We found that residents were more likely to become vaccinated in jail than in the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.
Beyond diagnosis: is there a role for radiomics in prostate cancer management?
Authors: Stanzione Arnaldo , Ponsiglione Andrea , Alessandrino Francesco , Brembilla Giorgio , Imbriaco Massimo
Published: March 2023

The role of imaging in pretreatment staging and management of prostate cancer (PCa) is constantly evolving. In the last decade, there has been an ever-growing interest in radiomics as an image analysis approach able to extract objective quantitative features that are missed by human eye. However, most of PCa radiomics studies have been focused on cancer detection and characterisation. With this narrative review we aimed to provide a synopsis of the recently proposed potential applications of radiomics for PCa with a management-based approach, focusing on primary treatments with curative intent and active surveillance as well as highlighting on recurrent disease after primary treatment. Current evidence is encouraging, with radiomics and artificial intelligence appearing as feasible tools to aid physicians in planning PCa management. However, the lack of external independent datasets for validation and prospectively designed studies casts a shadow on the reliability and generalisability of radiomics models, delaying their translation into clinical practice.

Key points

• Artificial intelligence solutions have been proposed to streamline prostate cancer radiotherapy planning.

• Radiomics models could improve risk assessment for radical prostatectomy patient selection.

• Delta-radiomics appears promising for the management of patients under active surveillance.

• Radiomics might outperform current nomograms for prostate cancer recurrence risk assessment.

• Reproducibility of results, methodological and ethical issues must still be faced before clinical implementation.
Effects of parasitism by the braconid wasp, Bracon hebetor (Hymenoptera: Braconidae), on the host hemolymph and phenoloxidase activation of the rice moth, Corcyra cephalonica larvae (Lepidoptera: Pyralidae)
Authors: Fathy Reham , Zohdy Nawal , Abd-El-Samie Emtithal M. , Abou-Elfadl Hazem , Moamen Shaimaa , Younes Aly
Published: March 2023

Background

Biological control of insect pests is an economic, eco-friendly and harmless approach to integrated pest management strategies. Bracon hebetor (Say) (Hymenoptera: Braconidae) considers a polyphagous ectoparasitoid of various pests of the order Lepidoptera. The parasitized host insects' defense mechanisms are triggered as a result of the parasitic wasps' injury and penetration. Thus, induce the host cellular and humoral immune responses through a blend of secretions injected into the host body. The present study was designed to evaluate the efficacy of B. hebetor on the immune response of the parasitized full grown larval instar of the rice moth, Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae) under natural envenomation.

Results

On cellular level, the ultrastructure examination of the hemocytes displayed a considerable structural deformation in hemocyte morphology of the detected types of the hemocytes. Moreover, the effects of parasitism on both differential hemocyte counts (DHCs) and total hemocyte counts (THCs) were investigated. The number of prohemocytes (PR) (40.33 ± 5.61, 43 ± 8.33 and 26 ± 2.31) was statistically differed after (24, 48 and 72 h) of parasitism, respectively, compared to unparasitized (31.33 ± 6.49) larvae. Similar observations were recorded in plasmatocytes (PL) before and after the parasitism. However, Spherulocytes (SP) and Oenocytoids (OE) were recorded in the hemolymph with little abundance. On the other side, the quantitative analysis of total hemolymph proteins (THP) provoked a significant effect of considering parasitized and non-parasitized larvae. As the Phenoloxidase (PO) cascade plays a critical role in immune defenses, so the substantial activation of PO in the host's hemolymph following successive hours of parasitism compared to unparasitized larvae using L-DOPA as a substrate indicated the induction of larval immune system. The parasitized larvae showed a gradual increase in the PO activity (0.442 ± 0.103) after 24 h reached up to (1.482 ± 0.272) at the end of parasitism (72 h) in comparable to unparasitized larvae (0.177 ± 0.0.044).

Conclusion

The present investigations clarified the efficacy of B. hebetor parasitism on the host immune mechanism, which will enable the progress of sustainable stored product protection approaches for the control of an important pest rice moth C. cephalonica.
Surgery in Early Metastatic Seminoma: A Phase II Trial of Retroperitoneal Lymph Node Dissection for Testicular Seminoma With Limited Retroperitoneal Lymphadenopathy
Authors: Daneshmand Siamak , Cary Clint , Masterson Timothy , Einhorn Lawrence , Adra Nabil , Boorjian Stephen A. , Kollmannsberger Christian , Schuckman Anne , So Alan , Black Peter , Bagrodia Aditya , Skinner Eila , Alemozaffar Mehrdad , Brand Timothy , Eggener Scott , Pierorazio Phillip , Stratton Kelly , Nappi Lucia , Nichols Craig , Luo Chunqiao , Li Ming , Hu Brian
Published: March 2023

PURPOSE

The long-term toxicities of chemotherapy and radiotherapy can represent a significant burden to testicular cancer survivors. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors with minimal late morbidity although little data exist on its efficacy in early metastatic seminoma. Surgery in early metastatic seminoma is a prospective phase II single-arm, multi-institutional trial of RPLND as first-line treatment for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy.

PATIENTS AND METHODS

Twelve sites in the United States and Canada prospectively enrolled adult patients with testicular seminoma and isolated retroperitoneal lymphadenopathy (1-3 cm). Open RPLND was performed by certified surgeons with a primary end point of 2-year recurrence-free survival (RFS). Complication rates, pathologic up/downstaging, recurrence patterns, adjuvant therapies, and treatment-free survival were assessed.

RESULTS

A total of 55 patients were enrolled, with a median (IQR) largest clinical lymph node size of 1.6 cm (1.3-1.9). RPLND pathology demonstrated a median (IQR) largest lymph node size of 2.3 cm (0.9-3.5); nine patients (16%) were pN0, 12 (22%) pN1, 31 (56%) pN2, and 3 (5%) pN3. One patient received adjuvant chemotherapy. With a median (IQR) follow-up of 33 months (12.0-61.6), 12 patients experienced recurrence, with a 2-year RFS of 81% and a recurrence rate of 22%. Of the patients who experienced recurrence, 10 were treated with chemotherapy and two underwent additional surgery. At last follow-up, all patients who experienced a recurrence were disease-free and the 2-year overall survival was 100%. Four patients (7%) experienced short-term complications, and four patients experienced long-term complications including incisional hernia (1) and anejaculation (3).

CONCLUSION

RPLND is a treatment option for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy and is associated with low long-term morbidity.
Peripodial adherens junctions regulate Ajuba-Yorkie signaling to preserve fly eye morphology
Authors: DeSantis Dana F. , Neal Scott J. , Zhou Qingxiang , Pignoni Francesca
Published: March 2023

The Drosophila eye develops from the larval eye disc, a flattened vesicle comprised of continuous retinal and peripodial epithelia (PE). The PE is an epithelium that plays a supporting role in retinal neurogenesis, but gives rise to cuticle in the adult. We report here that the PE is also necessary to preserve the morphology of the retinal epithelium. Depletion of the adherens junction (AJ) components β-Catenin (β-Cat), DE-Cadherin or α-Catenin from the PE leads to altered disc morphology, characterized by retinal displacement (RDis); so too does loss of the Ajuba protein Jub, an AJ-associated regulator of the transcriptional coactivator Yorkie (Yki). Restoring AJs or overexpressing Yki in β-Cat deficient PE results in suppression of RDis. Additional suppressors of AJ-dependent RDis include knockdown of Rho kinase (Rok) and Dystrophin (Dys). Furthermore, knockdown of βPS integrin (Mys) from the PE results in RDis, while overexpression of Mys can suppress RDis induced by the loss of β-Cat. We thus propose that AJ-Jub-Yki signaling in PE cells regulates PE cell contractile properties and/or attachment to the extracellular matrix to promote normal eye disc morphology.
Differential effects of Mendelian GDAP1 clinical variants on mitochondria-lysosome membrane contacts sites
Authors: Cantarero Lara , García-Vargas Gisela , Hoenicka Janet , Palau Francesc
Published: March 2023

GDAP1 pathogenic variants cause Charcot-Marie-Tooth (CMT) disease, the most common hereditary motor and sensory neuropathy. CMT-GDAP1 can be axonal or demyelinating, with autosomal dominant or recessive inheritance, leading to phenotypic heterogeneity. Recessive GDAP1 variants cause a severe phenotype, whereas dominant variants are associated with a milder disease course. GDAP1 is an outer mitochondrial membrane protein involved in mitochondrial membrane contact sites (MCSs) with the plasmatic membrane, the endoplasmic reticulum (ER), and lysosomes. In GDAP1-deficient models, the pathophysiology includes morphological defects in mitochondrial network and ER, impaired Ca2+ homeostasis, oxidative stress, and mitochondrial MCSs defects. Nevertheless, the underlying pathophysiology of dominant variants is less understood.

Here, we study the effect upon mitochondria–lysosome MCSs of two GDAP1 clinical variants located in the α-loop interaction domain of the protein. p.Thr157Pro dominant variant causes the increase in these MCSs that correlates with a hyper-fissioned mitochondrial network. In contrast, p.Arg161His recessive variant, which is predicted to significantly change the contact surface of GDAP1, causes decreased contacts with more elongated mitochondria.

Given that mitochondria–lysosome MCSs regulate Ca2+ transfer from the lysosome to mitochondria, our results support that GDAP1 clinical variants have different consequences for Ca2+ handling and that could be primary insults determining differences in severity between dominant and recessive forms of the disease.
Hox genes are crucial regulators of periosteal stem cell identity
Authors: Leclerc Kevin , Remark Lindsey H. , Ramsukh Malissa , Josephson Anne Marie , Palma Laura , Parente Paulo E. L. , Sambon Margaux , Lee Sooyeon , Lopez Emma Muiños , Morgani Sophie M. , Leucht Philipp
Published: March 2023

Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function. Hox genes are transcriptionally enriched in periosteal stem cells and their overexpression in more committed progenitors drives reprogramming to a naïve, self-renewing stem cell-like state. Crucially, individual Hox family members are expressed in a location-specific manner and their stem cell-promoting activity is only observed when the Hox gene is matched to the anatomical origin of the PSPC, demonstrating a role for the embryonic Hox code in adult stem cells. Finally, we demonstrate that Hoxa10 overexpression partially restores the age-related decline in fracture repair. Together, our data highlight the importance of Hox genes as key regulators of PSPC identity in skeletal homeostasis and repair.
Artificial intelligence and digital twins in power systems: Trends, synergies and opportunities
Authors: Shen Zhiwei , Arraño-Vargas Felipe , Konstantinou Georgios
Published: March 2023

Artificial Intelligence (AI) promises solutions to the challenges raised by the digitalization of power grids and their assets. Decision-making, forecasting and even operational optimization of grids and assets are just some of the solutions that AI algorithms can provide to operators, utilities and vendors. Nevertheless, barriers such as access to quality datasets, interpretability, repeatability, and availability of computational resources currently limit the extent of practical AI implementations. At the same time, Digital Twins (DTs) are foreseen as platforms that can overcome these barriers, and also provide a new environment for the development of enhanced and more intelligent applications. In this manuscript, we review the published literature to determine the existing capabilities and implementation challenges of AI algorithms in power systems, and classify AI-based applications based on their time scale to reveal their temporal sensitivity. Furthermore, DT-based technologies are discussed, identifying the potentials to tackle current limitations of real-world AI applications as well as exploring the synergies between DTs and AI. By combining AI and DT, we outline multiple prospective use cases for AI-enhanced power grid and power asset DTs. Our review also identifies that the combination of AI-based solutions and DTs leverages new applications with the potential to fundamentally change multiple aspects of the power industry.