bluuebunny/crossref_metadata_2025 huggingface dataset:
Global prevalence of advanced fibrosis in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis
Authors: Wongtrakul Wasit , Niltwat Sorachat , Charatcharoenwitthaya Natthinee , Karaketklang Khemajira , Charatcharoenwitthaya Phunchai
Published: June 2024

Background and Aim

Patients with type 2 diabetes mellitus (T2DM) face a heightened susceptibility to advanced fibrosis, a condition linked to adverse clinical outcomes. However, reported data on liver fibrosis severity among individuals with T2DM vary significantly across studies with diverse characteristics. This meta‐analysis aimed to estimate the global prevalence of advanced fibrosis among T2DM patients.

Methods

A comprehensive systematic search of the EMBASE and MEDLINE databases from inception to November 2022 was conducted to identify studies assessing advanced fibrosis in individuals with T2DM. Random‐effects models were utilized to calculate point estimates of prevalence, accompanied by 95% confidence interval (CI). Meta‐regression with subgroup analysis was employed to address heterogeneity.

Results

We identified 113 eligible studies involving 244,858 individuals from 29 countries. Globally, the prevalence of advanced fibrosis among T2DM patients was 19.5% (95% CI 16.8–22.4%). Regionally, the prevalence rates were as follows: 60.5% in West Asia (95% CI 50.3–70.4%), 24.4% in South Asia (95% CI 16.2–33.7%), 20.1% in East Asia (95% CI 14.7–26.1%), 20.0% in Europe (95% CI 15.8–24.6%), 15.8% in North America (95% CI 11.0–21.3%), and 11.3% in South America (95% CI 6.2–17.5%). The prevalence of advanced fibrosis varied notably based on the study setting and diagnostic methodology employed. Meta‐regression models highlighted that 45.13% of the observed heterogeneity could be attributed to combined diagnostic modality and study setting.

Conclusions

Globally, approximately one fifth of the T2DM population presents advanced fibrosis, with prevalence differing across geographical regions. Our findings underscore the need for effective strategies to alleviate its global burden.
Network energy use not directly proportional to data volume: The power model approach for more reliable network energy consumption calculations
Authors: Mytton David , Lundén Dag , Malmodin Jens
Published: June 2024

It is commonly assumed that data volume and network energy consumption are directly proportional, a notion perpetuated by numerous studies and media coverage. This paper challenges this assumption, offering a comprehensive examination of network operations to explain why the relationship between energy consumption and data volume is nonlinear. The power model approach is explored as an alternative methodology for calculating network energy consumption providing a more reliable representation of network energy use. The power model demonstrates that simple energy intensity calculations, expressed as kilowatt hours per gigabyte of data, are insufficient for accurately estimating real‐world network energy consumption.
Midkine is upregulated in the hippocampus following both spatial and olfactory reward association learning and enhances memory
Authors: Abdulmalek Sarah , Connole Laura M. , O'Sullivan Niamh C. , Beyna Mercedes , Pangalos Menelas N. , von Schack David , Ring Robert H. , Murphy Keith J.
Published: June 2024

Hippocampal neuronal plasticity is a fundamental process underpinning learning and memory formation and requiring elaborate molecular mechanisms that result in the dynamic remodelling of synaptic connectivity. The neurotrophic properties of midkine (Mdk) have been implicated in the development and repair of the nervous system, while Mdk knockout resulted in deficits in the formation of certain types of memory. The role of Mdk in the process of memory‐associated neuronal plasticity, however, remains poorly understood. We investigated the learning‐induced regulation of Mdk in spatial navigation and association learning using the water maze and the odour reward association learning paradigms, characterising a temporal profile of Mdk protein expression post‐learning. Both learning events revealed similar patterns of upregulation of expression of the protein in the rat hippocampal dentate gyrus, which were rapid and transient. Moreover, administration of recombinant Mdk during the endogenous Mdk upregulation following learning enhanced memory in the water maze task revealing a pro‐cognitive action of Mdk. We further show that, within the adult hippocampus, Mdk mRNA is predominantly expressed in granular and pyramidal neurons and that hippocampal neuronal Mdk expression is regulated by the canonical plasticity‐associated neurotransmitter glutamate. Finally, we confirm that the positive action of Mdk on neurite outgrowth previously noted in cortical and cerebellar neurons extends to hippocampal neurons. Together, our findings suggest a role for Mdk in glutamate‐mediated hippocampal neuronal plasticity important for long‐term memory consolidation.

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20S constitutive proteasome, 20S immunoproteasome, and cathepsin S are high‐sensitivity and independent markers of immunological activity in relapsing‐remitting type of multiple sclerosis
Authors: Górska Ewelina , Tylicka Marzena , Kamińska Joanna , Hermanowicz Adam , Matuszczak Ewa , Ołdak Łukasz , Gorodkiewicz Ewa , Karpińska Elżbieta , Socha Katarzyna , Kochanowicz Jan , Jakoniuk Marta , Homšak Evgenija , Koper‐Lenkiewicz Olga Martyna
Published: June 2024

Research on the markers of autoimmune response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations as potential biomarkers of a relapsing‐remitting type of MS (RRMS). Surface plasmon resonance imaging (SPRI) biosensors were used for the evaluation of protein concentrations. Plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations were significantly higher in RRMS patients compared to the control group. All three parameters were characterized by excellent usefulness in differentiating MS patients from healthy individuals (AUC equal to or close to 1.000). The plasma concentration of analyzed parameters was not correlated with severity of disability in the course of RRMS (EDSS value), the number of years from the first MS symptoms, the number of years from MS diagnosis, or the number of relapses within the 24‐month observational period. Our study has shown that plasma concentrations of 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S have promising potential in differentiating RRMS patients from healthy individuals. All of the analyzed parameters were found to be independent of the time of MS relapse and the severity of neurological symptoms. Hence, their potential as highly sensitive and independent circulating markers of RRMS suggests a stronger association with immunological activity (inflammatory processes) than with the severity of the disease.

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Health outcomes in children with prenatal opioid exposure with and without neonatal abstinence syndrome in the first seven years of life: An observational cohort study
Authors: Lambert Joshua , Arter Sara , Duah Henry , Xavier Teenu , Sprague Jon E.
Published: June 2024

Introduction

Prenatal opioid exposure (POE) is a major public health consequence of the opioid epidemic. Long‐term health outcomes associated with POE remain unclear, especially for children with POE without a diagnosis of neonatal abstinence syndrome (NAS). Here, we aimed to describe the health outcomes of children with POE and with POE and NAS compared to unexposed children during the first 7 years of life.

Design

In this retrospective observational cohort study, children born between 2015 and 2022 were identified from the Maternal and Infant Data Hub (MIDH), a data repository that continuously integrates maternal, neonatal, and pediatric records from two academic medical centers and one pediatric hospital system in the Midwest, USA.

Methods

International Classification of Diseases, 10th Revision, Clinical Modification (ICD‐10 CM) chapters A00‐N99 served as outcomes of interest. Annual incidence and crude incidence rate ratios were calculated to explore descriptive differences between the exposed and unexposed groups.

Results

The study included 22,002 children, 20,130 (91.5%) of whom were unexposed and 1872 (8.5%) were exposed. Of the 1872 exposed children, 371 (19.8%) received a diagnosis of NAS (POE + NAS) and 1501 were in the POE‐NAS group. Across all 7 years, exposed children had a higher incidence of diagnoses in most ICD‐10 CM chapters compared to unexposed children. A consistently higher incidence rate ratio of diagnosis was observed in both POE‐NAS and POE + NAS groups (vs. unexposed) related to mental and behavioral disorders, eye diagnoses, and diseases of the musculoskeletal system and gastrointestinal systems.

Conclusions

POE is associated with an increased risk of diagnoses in a number of ICD‐10 CM chapters throughout childhood. These findings underscore the need for early screening and targeted interventions to support exposed children and improve their well‐being. Further research is required to explore underlying mechanisms and develop preventive measures for at‐risk populations.

Clinical Relevance

Understanding the conditions more often diagnosed in children with prenatal opioid exposure will help to improve care provided to this population. As a result of study findings, nurses who provide care to children with prenatal opioid exposure can prioritize their assessments and allocate time, resources, and education toward areas more likely to be affected.
How do older employees achieve successful ageing at work through generativity in the digital workplace? A self‐affirmation perspective
Authors: Wang Changyu , Zhang Yimeng , Feng Jiaojiao
Published: June 2024

The necessity of helping older employees achieve career success in the digital workplace has drastically increased. Drawing on self‐affirmation theory, we postulate that using enterprise social media (ESM) to conduct intergenerational knowledge sharing (IGKS) is a generativity and self‐affirmation behaviour in the digital workplace, and investigate how it would help older employees enhance job performance and thus achieve successful ageing at work. Study 1 (a three‐wave time‐lagged survey study with 262 older employees over 40 years old) demonstrates that, older employees' IGKS in ESM positively affects their job performance via personal needs‐job supplies fit. Perceived younger colleagues' knowledge disseminative capacity can weaken, but perceived younger colleagues' knowledge absorptive capacity can strengthen the above indirect effect. We replicated the first study's findings in Study 2 using a two‐wave survey with 161 older employees over 50 years old. Additionally, we found that older employees' IGKS in ESM positively influences their job performance via a serial mediation of organization‐based self‐esteem and needs‐supplies fit. Perceived younger colleagues' knowledge disseminative capacity can weaken, but knowledge absorptive capacity can strengthen the serial mediation relationship. These findings contribute to integrating IGKS and ESM literature to improve the theoretical framework of successful ageing at work.
Emergency department mental health presentations in young children: a retrospective chart review
Authors: Bourke Elyssia M , Say Daniela F , Carison Anna , O'Donnell Sinead M , Babl Franz E ,   the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network
Published: June 2024

Aim

To characterise key features of young people presenting to the emergency department (ED) with a mental health complaint when comparing children (aged 7 to 12 years) and teenagers (13 years and greater).

Methods

Retrospective review of all ED mental health presentations in children aged 7–17 years presenting over a 12‐month period in 2018 to a tertiary children's hospital in Victoria, Australia. Univariate analyses were carried out to examine the relationship between children and teenagers and a number of key presentation variables. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were calculated for ED management outcomes.

Results

There were 1691 ED mental health presentations in 2018. Of these presentations, 407 (24%) were children aged 12 years or less. The remaining 76% (1284) were teenagers. The younger aged cohort were more likely to be male (OR 2.43, CI 1.92–3.08) and have a past history of autism spectrum disorder (OR 1.92, CI 1.45–1.84). They were more likely to have a presenting complaint of acute behavioural disturbance (OR 2.03, CI 1.59–2.60), be physically restrained (OR 2.01, CI 1.18–3.37) and have sedative medication provided (OR 2.87, CI 1.63–5.04). The older aged cohort were more likely to have a past history of depression (OR 0.19, CI 0.12–0.29) and a presenting complaint of intentional self‐poisoning (OR 0.33, CI 0.15–0.65).

Conclusions

Children aged 12 years or less represent one‐quarter of all young people presenting to the ED with a mental health concern. They experience high rates of acute behavioural disturbance and are more likely to require restrictive interventions during their presentation.
Factors influencing the prioritisation of access to medicines in trade‐related intellectual property policymaking in Thailand
Authors: Tenni Brigitte , Lexchin Joel , Akaleephan Chutima , Kittitrakul Chalermsak , Townsend Belinda , Gleeson Deborah
Published: June 2024

Thailand is facing ongoing trade‐related challenges that threaten access to an affordable and sustainable supply of medicines. Despite Thailand's history of balancing trade pressures and public health priorities, little is known about the factors that enable or constrain a focus on access to medicines in trade‐related intellectual property (IP) decision making. Using document analysis and qualitative interviews, and drawing on Kingdon's Multiple Streams Framework, this qualitative study examines the factors that have enabled or constrained Thailand from focusing on access to medicines in three case studies of trade‐related IP policy: Thailand's patent law and its amendments; its issuance of compulsory licences; and its decision‐making about TRIPS‐plus trade agreements including potential membership of the Comprehensive and Progressive Agreement for Trans‐Pacific Partnership. The degree to which access to medicines has been prioritised in Thailand's trade‐related IP policymaking has varied across different types of policymaking and over time. Integral to its successes has been the involvement of the Ministry of Health and sustained advocacy by access to medicines coalitions which exert political pressure, generate evidence, and provide technical assistance to support evidence‐based policy reform. In addition, Thailand's compulsory licencing was made possible by a policy entrepreneur with the motivation and authority to implement policy change. Constraints to Thailand's focus on access to medicines have included its trade dependence on the United States (US), ongoing US trade pressure to implement TRIPS‐plus measures, and intense lobbying from Pharmaceutical Research and Manufacturers of America, the organisation representing US‐based major pharmaceutical companies, to increase IP protection for pharmaceuticals in Thailand. Through the use of Kingdon's framework, this study's focus on three different types of trade‐related IP policymaking has provided a detailed picture of the factors that have influenced the prioritisation of access to medicines and how these have played out in Thailand. Thailand's mixed history with regard to the prioritisation of access to medicines could provide lessons for other low‐ and middle‐income countries facing similar challenges to access to medicines by ensuring that the conditions are right in each of the three streams for windows of opportunity to emerge.
NPCC4: Concepts and tools for envisioning New York City's futures
Authors: Balk Deborah , McPhearson Timon , Cook Elizabeth M. , Knowlton Kim , Maher Nicole , Marcotullio Peter , Matte Thomas , Moss Richard , Ortiz Luis , Towers Joel , Ventrella Jennifer , Wagner Gernot
Published: June 2024

This chapter of the New York City Panel on Climate Change 4 (NPCC4) report discusses the many intersecting social, ecological, and technological‐infrastructure dimensions of New York City (NYC) and their interactions that are critical to address in order to transition to and secure a climate‐adapted future for all New Yorkers. The authors provide an assessment of current approaches to “future visioning and scenarios” across community and city‐level initiatives and examine diverse dimensions of the NYC urban system to reduce risk and vulnerability and enable a future‐adapted NYC. Methods for the integration of community and stakeholder ideas about what would make NYC thrive with scientific and technical information on the possibilities presented by different policies and actions are discussed. This chapter synthesizes the state of knowledge on how different communities of scholarship or practice envision futures and provides brief descriptions of the social‐demographic and housing, transportation, energy, nature‐based, and health futures and many other subsystems of the complex system of NYC that will all interact to determine NYC futures.
Isochrony as ancestral condition to call and song in a primate
Authors: De Gregorio Chiara , Maiolini Marco , Raimondi Teresa , Carugati Filippo , Miaretsoa Longondraza , Valente Daria , Torti Valeria , Giacoma Cristina , Ravignani Andrea , Gamba Marco
Published: June 2024

Animal songs differ from calls in function and structure, and have comparative and translational value, showing similarities to human music. Rhythm in music is often distributed in quantized classes of intervals known as rhythmic categories. These classes have been found in the songs of a few nonhuman species but never in their calls. Are rhythmic categories song‐specific, as in human music, or can they transcend the song–call boundary? We analyze the vocal displays of one of the few mammals producing both songs and call sequences: Indri indri. We test whether rhythmic categories (a) are conserved across songs produced in different contexts, (b) exist in call sequences, and (c) differ between songs and call sequences. We show that rhythmic categories occur across vocal displays. Vocalization type and function modulate deployment of categories. We find isochrony (1:1 ratio, like the rhythm of a ticking clock) in all song types, but only advertisement songs show three rhythmic categories (1:1, 1:2, 2:1 ratios). Like songs, some call types are also isochronous. Isochrony is the backbone of most indri vocalizations, unlike human speech, where it is rare. In indri, isochrony underlies both songs and hierarchy‐less call sequences and might be ancestral to both.
Kinematics and coordination of moth flies walking on smooth and rough surfaces
Authors: Brandt Erin E. , Manyama Maria R. , Nirody Jasmine A.
Published: June 2024

The moth fly, Clogmia albipunctata, is a common synanthropic insect with a worldwide range that lives in nearly any area with moist, decaying organic matter. These habitats comprise both smooth, slippery substrates (e.g., bathroom drains) and heterogeneous, bumpy ground (e.g., soil in plant pots). By using terrain of varying levels of roughness, we focus specifically on how substrate roughness at the approximate size scale of the organism affects kinematics and coordination in adult moth flies. Finally, we compare and contrast our characterizations of locomotion in C. albipunctata with previous work of insect walking in naturalistic environments.
Tooth movement analysis of maxillary dentition distalization using clear aligners with buccal and palatal mini‐screw anchorages: A finite element study
Authors: Guo Runzhi , Li Linwei , Lam Xiang Yao , Qin Qianyi , Zheng Yunfei , Huang Yiping , Lin Yifan , Li Weiran
Published: June 2024

Objective

To assess the tooth movement trends during the three stages of maxillary dentition distalization with clear aligners (CA) and to compare the efficacy of different mini‐screw anchorage systems.

Materials and Methods

Three‐dimensional (3D) finite element models of three anchorage systems (A, control group; B, buccal mini‐screw anchorage group; C, palatal mini‐screw anchorage group) were established. Three stages of simulating maxillary dentition distalization with CA included maxillary molar distalization (stage 1), maxillary premolar distalization (stage 2) and maxillary anterior teeth retraction (stage 3). Therefore, a total of nine models were constructed to analyse the 3D displacement of maxillary teeth during the distalization process.

Results

The displacement pattern of maxillary dentition during distalization was similar across the three groups, but with varying magnitudes. During stage 1, groups B and C exhibited greater amounts of molar distalization compared to group A. Group C also demonstrated the least amount of labial movement of the maxillary central incisor compared to the other two groups. During stage 2, the mesial displacement of the maxillary first molar was less significant in groups B and C than in group A. In the final stage, group C exhibited a greater amount of maxillary anterior retraction compared to groups A and B.

Conclusion

The palatal mini‐screw anchorage system was effective in reducing anchorage loss and improving the efficacy of maxillary dentition distalization with CA.
Power‐dependent study of the photothermal response of several alcoholic media with femtosecond laser‐induced thermal lens
Authors: Rawat Ashwini Kumar , Chakraborty Subhajit , Mishra Amit Kumar , Goswami Debabrata
Published: June 2024

We explore the photothermal response of methanol, ethylene glycol, and glycerol using the femtosecond laser‐induced thermal lens spectroscopy (FTLS) technique. A mode mismatched pump–probe spectroscopic technique was utilized to analyze the influence of localized thermal heating on the photothermal response of solvents. The findings revealed a strong dependence on both the input pump power and the molecular characteristics of the solvents. At significantly high pump power, the excess heat load deposited to the solvent is found to be responsible for the induction of the convection currents in the heat transfer mechanisms. Our results highlight that the influence of pump power on photothermal and thermal lens characteristics is intricately linked to the natural drifting and heat transfer mechanisms of solvent molecules. The molecular motion and existing connective processes were correlated with the molecular characteristics of the samples. The present finding reveals that FTLS is a sensitive probe for comprehending the impact of input laser power, molecular structure, and intermolecular H bonding on the photothermal characteristics and thermo‐optical properties of the alcoholic medium.
Enhanced drought resistance in tomato via reduced auxin sensitivity: delayed dehydration and improved leaf resistance to embolism
Authors: Andrade Moab T. , Cardoso Amanda A. , Oliveira Leonardo A. , Pereira Talitha S. , Haverroth Eduardo J. , Souza Genaina A. , DaMatta Fábio M. , Zsögön Agustín , Martins Samuel C. V.
Published: June 2024

Auxins are master regulators of plant development and auxin perception mutants display smaller leaves, lower transpiration, and narrower xylem vessels than their corresponding wild types. Here, we evaluated whether the leaf embolism resistance and overall plant resistance to drought are altered in the auxin perception mutant diageotropica (dgt). Our assessments demonstrate that the dgt mutants in tomato exhibit considerably smaller xylem vessels in stems (‐24%), leaf petioles (‐43%), and leaf midribs (‐34%) than the wild type. Alongside narrower vessels, dgt mutants exhibited greater xylem cell wall thickness‐to‐conduit diameter and greater leaf embolism resistance than the wild type. The water potential at 50% cumulative leaf embolism (P50) of dgt and wild type was ‐1.39 and ‐1.14 MPa, respectively. Plants of dgt also exhibited higher stomatal safety margin (water potential difference between stomatal closure and P50), needed a longer time to reach their P50 in a dry‐down experiment, and showed a faster recovery in leaf gas exchange upon rehydration than the wild type. The impaired auxin signaling resulted in lower canopy area and stomatal conductance, which likely contributed to delaying the time for plants to reach hydraulic damage during drought. These findings demonstrate a clear association between structural and physiological changes and improved resistance against drought‐induced hydraulic dysfunction in the dgt tomato mutant.
The effect of stress on the antibody response after vaccination in children aged 0–18 years: A systematic review
Authors: Svensson Rikke , Malon Michelle , Stensballe Lone G. , Thorsen Steffen U. , Svensson Jannet
Published: June 2024

Stress has been associated with less effective vaccine responses in adults. This review aims to investigate the evidence for a similar association in children. A systematic review search was conducted in January 2021 in three databases: Medline, Embase and PsycInfo. An updated search of the Medline database was systematically conducted until the most recent update on September 25th, 2023, to ensure the inclusion of the most current research available. Keywords related to stress, vaccines and children were used, and a total of 7263 (+1528) studies were screened by two independent investigators. Six studies met the inclusion criteria for data extraction and analysis. For quality assessment of the studies, the risk of bias in non‐randomized studies—of interventions (ROBINS‐I) tool was applied. Most of the studies suggest a negative role of stress on vaccine responses. However, the scarcity of studies, lack of confirmatory studies, risk of bias and heterogeneity according to age, type of vaccine, measures of stress and vaccine responses prevent a clear conclusion. Future studies should emphasize the use of as strict study designs as possible, including well‐defined stress metrics and thorough examination of both pre‐ and post‐vaccination responses. Systematic review registration: Prospero CRD42021230490.
The role of hsa‐miR‐193a‐5p as an important factor for control of inositol in alopecia areata
Authors: AbdElneam Ahmed Ibrahim , Al‐Dhubaibi Mohammed Saleh , Bahaj Saleh Salem , Mohammed Ghada Farouk , Atef Lina Mohammed
Published: June 2024

Background

MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen‐stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA.

Aim

The significance and function of hsa‐miR‐193a‐5p as a genetic marker for AA and its potential influence on the advancement of the disease.

Subjects and methods

A case‐control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR‐200c‐3p in both groups, the real‐time PCR technique was utilized. The prediction of suitable genes for hsa‐miR‐193a‐5p, as well as the identification of pathways and gene‐gene interactions, were carried out using bioinformatic tools.

Results

The levels of hsa‐miR‐193a‐5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa‐miR‐193a‐5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene.

Conclusion

For the first time, our study demonstrates the significant over‐expression of a new miRNA, hsa‐miR‐193a‐5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa‐miR‐193a‐5p in AA.
High‐frequency ultrasound evaluation of morphea: Retrospective analytical study
Authors: Yazdanparast Taraneh , Mohseni Alireza , Dehghan Kobra Soltan , Delavar Shohreh , Firooz Alireza
Published: June 2024

Background

To date, there are no accepted outcome measures to monitor morphea, and consensus on specific monitoring criteria for morphea remains elusive.

A few studies have assessed the criterion validity of skin ultrasound in morphea. So, in this study, we approach ultrasound findings in morphea lesions.

Material and methods

This was a retrospective‐analytical study conducted between December 2021 and May 2023. Patients were clinically evaluated at a dermatology outpatient clinic and then referred for high‐frequency ultrasound (HF‐US) evaluation and were selected to be included in this study. The lesions were confirmed by histopathology as well. Sonographic evaluations were performed on the lesion site and the symmetrical uninvolved other side. Dermal thickness and dermal echogenicities were recorded. Statistical analysis of group differences was performed by using the 2‐tailed Student t‐test. A p‐value of less than 0.05 was considered statistically significant.

Results

Forty‐one morphea lesions in the inflammatory phase of 27 patients were included in the study. The mean dermal thickness of morphea lesions was 1107.97 ± 414.3 and the mean dermal thickness of the control side was 1094.65 ± 331.06, The difference between these two variables was not statistically significant. The mean dermal density of lesions was 49.13 ± 18.97 and the mean dermal density of the control side was 52.22 ± 25.33. The difference between these two variables was not statistically significant.

Conclusion

This study shows that HF‐US indicated increasing dermal thickness and reducing the dermal density of the morphea lesions in the inflammatory phase confirmed with the histopathology.
Four glycosyltransferase genes are responsible for synthesis and accumulation of different flavonol glycosides in apple tissues
Authors: Zhu Xiaoping , Chen Ying , Jiao Ju , Zhao Shanshan , Yan Yanfang , Ma Fengwang , Yao Jia‐Long , Li Pengmin
Published: June 2024

Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP‐dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3‐O‐galactosyltransferase (UGT78T6), flavonol 3‐O‐glucosyltransferase (UGT78S1), flavonol 3‐O‐xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3‐O‐rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3‐O‐glycosyltransferases of other plant species.
Prevalence of presumed endplate junction failure at the lumbosacral intervertebral junction in dogs on computed tomography
Authors: Tellegen Anna R. , Beukers Martijn , Meij Björn P. , Tryfonidou Marianna A. , Veraa Stefanie
Published: June 2024

Lumbosacral intervertebral disc herniation (IVDH) is a common cause of lower back pain in dogs and humans. In humans, the vertebral endplate to annulus fibrosus (AF) attachment was implicated as an alternative failure site besides rupture through the dorsal AF (AFF). Endplate junction failure (EPJF) is characterized by IVDH, accompanied by endplate irregularities (type A), rim avulsions (type B), or larger bony avulsions on one (type C) or both endplates (type D), associated with an adjacent endplate defect. This retrospective study reports the CT prevalence of presumed EPJF in dogs and its associations with signalment and other lumbosacral CT abnormalities. CT scans, including the lumbosacral spine of dogs obtained at two institutions, were assessed, yielding 324 scans. Presumed EPJF was found in 69 dogs (21%) and AFF in 68 dogs (21%), commonly at the caudal endplate of the last lumbar vertebra (71%). The remaining 187 dogs did not show presumed EPJF or AFF. Presumed EPJF type A occurred in 49/69, type B in 19/69, and type C in 1/69 dogs. Univariable logistic regression showed that presumed EPJF was associated with significantly higher IVDH grades than AFF. In the multiple regression model, presumed EPJF and AFF remained associated with increasing age and spondylosis deformans. Presumed EPJF was associated with vertebral endplate sclerosis and AFF with zygapophyseal joint osteoarthritis. In conclusion, presumed EPJF was observed on CT in 21% of dogs with lumbosacral IVDH. Prospective studies correlating EPJF on CT with clinical, surgical, and histopathological findings are needed for a better understanding of the underlying pathology and clinical relevance.
Molecular characterization of rabies virus from wild and domestic animals in the Sultanate of Oman
Authors: Ali Haytham , Ali Ahmed , Al Mawly Julanda , Tohamy Hossam G. , El‐Neweshy Mahmoud S.
Published: June 2024

Aims

Rabies virus (RV) is endemic in some Arabian countries. However, it is difficult to control RV without understanding the epidemiological evolution of endemic RV isolates. The current study aimed to characterize RV from domestic and wild animal clinical cases in Oman.

Methods and Results

Twelve brain samples from domestic (Five camels, three goats and one cattle) and wild animals (Two foxes and one honey badger) were investigated from different locations in Oman between 2017 and 2020. All samples were confirmed by RV nucleoprotein (N) gene‐specific primers. Seven out of the 12 amplified samples were successfully sequenced and subjected to sequence and phylogenetic analysis. The detected RVs shared an in‐between 96.8%–98.7% and 96.9%–99% nucleotide and amino acid identities, respectively. However, the wild animal RVs shared only 92.6%–93.9% and 95.9% nucleotide and amino acid identities with the domestic animal RVs, respectively. Negri bodies were detected histologically in six brain samples from camels (n = 3), goats (n = 1) and foxes (n = 2). The RVs from domestic animals shared 97%–98.7% and 98%–100% nucleotide and amino acid identities with the previously published fox RVs from Oman and Gulf countries. Phylogenetic analysis suggested that all RV sequences belong to a distinct clade confined to the previously reported clade V within the Middle Eastern Cluster.

Conclusions

As indicated by the analysis of RVs from different locations between 2017 and 2020, a genetic variant isolated to the Gulf region may exist within the Middle East clade. Moreover, it appears that new RV lineages are emerging rapidly within this region. Therefore, a comprehensive genomic and phylogenetic analysis of the circulating RV is important for the development of future prevention and control strategies.
Health net-outcome objectives and approaches for spatial planning and development: a scoping review protocol
Authors: Stewart-Evans James , Wilson Emma , Langley Tessa , Hands Angela , Leonardi-Bee Jo
Published: June 2024

Objective:

The objective of this scoping review is to review the body of knowledge on net gain and no net loss (net-outcome) objectives and approaches applicable to health in spatial planning and development policies and practice.

Introduction:

There is an established body of academic and gray literature addressing environmental net-outcome objectives, such as biodiversity net gain, in spatial planning policies and practice. A “health net gain” objective has recently been proposed as a driver for health protection and the realization of health. Such an objective and approach are yet to be scoped and defined.

Inclusion criteria:

This review will consider sources in the scientific and gray literature that describe health net-outcome objectives that can be implemented in spatial planning and development policies and practice. Source contexts will not be limited to specific countries, geographical areas, or settings. All types of evidence will be considered.

Methods:

This review will follow the JBI methodology for scoping reviews. Databases to be searched include PsycINFO, Embase, HMIC Health Management Information Consortium, MEDLINE (Ovid), Scopus, and selected databases from the ProQuest Social Science Premium Collection. Sources of gray literature to be searched include ProQuest Dissertations and Theses, TRIP Pro, and BASE. No language or date restrictions will be applied. Two independent reviewers will retrieve and review full-text studies and extract data. The results will be presented in tabular or diagrammatic format with a narrative summary.

Review registration:

Open Science Framework https://osf.io/4dbcm
Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1‐G93A mice
Authors: Deutsch Andrew J. , Elbasiouny Sherif M.
Published: June 2024

Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)‐G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild‐type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age‐matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK‐mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age‐based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS.

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Key points

Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature.

Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild‐type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells.

The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS.

Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.
Right-sided Morgagni diaphragmatic hernia presenting as isolated left shoulder pain
Authors: Kemerling Morgan K , Okekumata Isimenmen , Alasadi Rusul , Cedeno-Rodriguez Alex R , Nuckton Thomas J
Published: June 2024

A woman in her 60s presented to the emergency department with excruciating, deep left shoulder pain and was found to have a right-sided Morgagni hernia, a rare type of congenital diaphragmatic hernia (CDH). She did not have chest pain, palpitations, shortness of breath, cough, abdominal pain, constipation, diarrhoea, nausea, vomiting or other symptoms classically associated with CDHs in adults. Laparoscopic robotic-assisted repair with mesh placement was performed, and the patient’s recovery was uncomplicated, with no recurrence of shoulder pain. Our patient’s presentation was unusual due to the absence of symptoms typically seen with CDHs in adults, and the presence of contralateral, left-sided shoulder pain with a right-sided Morgagni hernia.
Post-infectious hydrocephalus complicating Listeria meningitis in a healthy newborn
Authors: D'Sa Saskia , Saleh Ezzeldin , Chaudhary Subhash , Rodriguez Marcela
Published: June 2024

Listeria monocytogenesis a relatively uncommon cause of foodborne infection in the general population. Most cases of Listeriosis occur among newborns, pregnant women, the elderly and those with impairment of cellular immunity. Neonatal Listeria meningitis is rare. We present a case of Listeria meningitis at the age of 15 days in a previously healthy neonate who presented with acute onset of fever, poor feeding and lethargy. Sepsis workup revealedL. monocytogenesidentified in cerebrospinal fluid PCR and culture. The infant’s course was complicated by transient syndrome of inappropriate antidiuretic hormone and subsequent hydrocephalus that required a ventriculoperitoneal shunt placement. Though rare, neonatal infections due to Listeria can present with meningitis leading to serious and devastating complications. Our case emphasises the importance of considering Listeria in cases of neonatal meningitis and the value of close follow-up of such cases through early detection and management of acute and long-term complications.
Intracardiac diffuse large B-cell lymphoma: an unexpected diagnosis
Authors: Alattar Komeil , Dodhia Sagar , Huang Chieh-Yin , Neves Joana Briosa , Haris Arafat
Published: June 2024

Intracardiac lymphomas are exceedingly rare accounting for only 1% of all primary cardiac tumours. Historically, due to their insidious development and non-specific clinical presentation, the diagnosis has been challenging with most cases being confirmed on post-mortem examination. Our case report details the experience of a previously fit and active woman in her 60s who presented with gradual onset exertional dyspnoea. Through a series of multimodal imaging tools (including echocardiogram, cardiac MRI, CT and positron emission tomography-CT) and biopsy, we confirmed the diagnosis of intracardiac diffuse large B-cell lymphoma. Our patient was managed with chemotherapy and went on to demonstrate excellent radiological response with near-complete resolution of the intracardiac mass. Subjectively, our patient reported significant improvement in exercise tolerance within weeks of commencing treatment.
Views of emergency care providers in providing healthcare for asylum seekers and refugees
Authors: Doherty Cal , Quinn Joanna , Lowe David John , Khanolkar Amal R
Published: June 2024

Background

The number of asylum seekers awaiting decisions on their claims in the UK has more than tripled since 2014. How we meet international obligations to provide appropriate healthcare to asylum seekers and refugees (ASRs) is therefore an increasingly important issue. The views of frontline healthcare workers are vital to ensure the development of sustainable and effective health policy when it comes to caring for this group.

Method

A single-centre qualitative study in the form of semistructured interviews was conducted at the Queen Elizabeth University Hospital ED in Glasgow, Scotland, between January and March 2023. Volunteering ED care providers (EDCPs)—doctors and nurses—working in the ED were interviewed and the data analysed and presented through a thematic analytical framework.

Results

12 semistructured interviews were conducted—6 doctors and 6 nurses. Analysis revealed four themes: (1) ‘staff attitudes’ highlighted in particular the positive views of the participants in providing care for ASRs; (2) ‘presentation patterns’ revealed significant variations in opinion, with one-third of participants, for example, believing there was no difference in presentations compared with the general population; (3) ‘challenges to optimal care’ outlines multiple subthemes which impact care including the unique challenge of the ED triage system; and (4) ‘transition in care’ discusses participant concerns regarding arranging safe and appropriate follow-up for ASR patients. Ethical dilemmas in providing care, as highlighted in previous studies, did not feature heavily in discussions in this study.

Conclusion

This study provides an insight into the views of EDCPs in providing care to ASRs in the ED. Study findings can potentially contribute to the development of ED-specific guidelines as well as inform wider health policy and provide a focus and direction for further research.
Protein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy
Authors: Li Qianyu , Guo Wenyun , Qian Yifei , Li Songling , Li Linfeng , Zhu Zijun , Wang Fan , Tong Yu , Xia Qiang , Liu Yanfeng
Published: June 2024

Background and aims

The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.

Methods

De novoMYC/Trp53−/−liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion.

Results

We identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53−/−mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies.

Conclusions

Our findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.