bluuebunny/crossref_metadata_2025 huggingface dataset:
P20 Characterizing monoamine signalling in human dermal fibroblasts and keratinocytes
Authors: Andriuskevicius Tomas , Parke Brenna , Rhodes Anna , Knight Leigh , Hashemi Parastoo , Higgins Claire A
Published: May 2024

Introduction and aims

Our mental health depends upon a fine balance of monoamines in the brain. Interestingly, there is ample evidence indicating that mental health disorders such as stress or anxiety have an impact on skin condition and appearance. For example, stress induces neurogenic inflammation, which in turn leads to mast cell degranulation in the skin and increases local histamine levels. This increased histamine within the skin exacerbates skin conditions such as eczema and psoriasis, while impacting the skin barrier. In this study, we first sought to investigate monoamine signalling in both skin keratinocytes and fibroblasts, with a specific focus on histamine and serotonin modulation. Next, we investigated mechanisms of release via pharmacological intervention to block corresponding receptors, informed by using single-cell RNA sequencing from existing datasets.

Methods

We adapted a powerful electrochemical technique, fast-scan cyclic voltammetry (FSCV) to codetect monoamine signalling in real-time in vitro. Employing the advanced capabilities of our artificial neural network models, we analysed extensive FSCV colour plot data in real-time to establish neurotransmitter release patterns and understand their characteristics.

Results

Our Results show that both keratinocytes and fibroblasts are capable of releasing serotonin and histamine without external intervention. After administering diphenhydramine, an H1 receptor inhibitor, to the cells, we observed a rise in the frequency and amplitude of both serotonin and histamine signalling compared with the cells that received no treatment. However, bafilomycin, a vacuolar H+ ATPase inhibitor, reduced the signalling frequency significantly. This suggests a potential autoregulation mechanism and interdependency between the two monoamines.

Conclusions

Overall, using analytical Methods, our work shows that skin-resident fibroblasts and keratinocytes can release monoamines including serotonin and histamine. This finding provides an opportunity to examine interventions that facilitate serotonin release, to decrease histamine levels, and improve the skin function and general mental wellbeing.
P21 Advancing dermatological care: a comprehensive evaluation of the steroid-free GL-1 formulation
Authors: Sharma Pragya
Published: May 2024

Introduction and aims

The prolonged use of topical steroids introduces notable dermatological risks, including the onset of permanent stretch marks, bruising, discoloration and vascular abnormalities. This study presents an innovative strategy by formulating GL-1, a steroid-free treatment amalgamating seaweed bioactives, sesame oil and naturally occurring salts and minerals. The objective of this study was to address the limitations of conventional topical steroids and introduce pioneering solutions to dermatological care.

Methods

To assess the safety and efficacy of GL-1 (product 1), a comprehensive battery of in vitro tests was employed. The skin corrosion test (OECD 431) established the noncorrosive nature of GL-1, validating its safety on reconstructed human epidermis. The skin irritation test (OECD 439) demonstrated the nonirritating attributes of GL-1, aligning with the United Nations Globally Harmonized System of Classification and Labelling guidelines. Additionally, the bovine corneal opacity and permeability test (OECD 437) affirmed the noninducing nature of GL-1 in relation to eye irritation or serious eye damage.

Results

Preliminary outcomes from dermal clinical trials indicate promising Results for GL-1. In vitro experiments on HaCaT and human dermal fibroblasts, adult (HDFa) cell lines highlighted the noncytotoxicity of GL-1, contrasting with the ‘Cortopin’, which exhibited cytotoxicity. GL-1 exhibited a proliferative effect in HDFa cells, signifying its potential for regenerative applications. Furthermore, both GL-1 and ‘Cortopin’ displayed antioxidant activity in HaCaT cells, underscoring the additional merits of our formulation.

Conclusions

Our steroid-free formulation, GL-1, demonstrates exceptional safety and efficacy through a meticulous series of in vitro assessments and initial clinical trials. These findings position GL-1 as a promising candidate for diverse dermal applications, offering a secure alternative to traditional topical steroids. The potential impact of GL-1 transcends its therapeutic efficacy, emphasizing its robust safety profile validated through multiple in vitro evaluations.
P25 Identification of early changes in extracellular microRNA biomarkers of scleroderma for point-of-care diagnosis
Authors: Teenan Oliver , Kenaan Ahmad , Delgaldo Francesco , Malaktou Christina , Strid Jessica , Daniels Connor , Ladame Sylvain , Higgins Claire
Published: May 2024

Introduction and aims

Scleroderma is a rare autoimmune disease, characterized by excessive extracellular matrix deposition leading to chronic inflammation and fibrosis. As a progressive disease initially affecting the skin, it presents similarly to Raynaud phenomenon, which delays diagnosis and treatment. Clinical diagnostic tests lack sensitivity, therefore novel Methods of detection and sensitive biomarkers are required to improve diagnosis rates. MicroRNAs are short, stable, noncoding RNAs, often present in the extracellular space, and can be sampled from interstitial skin fluid (ISF) through the employment of hydrogel microneedles. We aim to use this technique to improve upon current clinical gold standards of diagnosing scleroderma, at earlier stages of the disease.

Methods

In this study, we performed next-generation small-RNA sequencing on ISF from healthy individuals, patients prior to a clinical diagnosis of scleroderma [termed very early detection of systemic sclerosis (VEDOSS)], and patients with scleroderma classified as low and high skin score, identifying a panel of microRNA biomarkers for scleroderma diagnosis. Swellable hydrogel microneedles were manufactured in house, applied to excised human tissue and preclinical mouse models to demonstrate the ability to access and quantify extracellular microRNAs in ISF.

Results

Patients who received a VEDOSS diagnosis have increased ISF abundance of miR-379-5p and miR-125a-5p and decreased miR-30e-3p compared with healthy patients. miR-379-5p, miR-363-3p and miR-221-3p are sensitive to the progression of scleroderma and could be used to track the disease with improved sensitivity to autoantibodies in blood or where clinical practices usually require a skin biopsy. Using preclinical models of skin disease, we could differentiate between conditions, with higher sensitivity than blood sampling using our microneedle technology.

Conclusions

By identifying extracellular mircoRNAs, we have shown the potential use of these sensitive biomarkers in a liquid biopsy that can be applied at point-of-care. Peptide nucleic acids complementary to our microRNA biomarkers, will be used to provide real-time on-the-chip readouts of these ­biomarkers.
P26 The effect of interleukin-23 stimulation on gene expression in CD4+ Jurkat cells
Authors: Shellard Elan
Published: May 2024

Introduction and aims

There is now robust evidence that genetic changes along the interleukin (IL)-23 axis increase the risk of developing psoriasis, with CD4+ T cells likely to be pivotal in the disease pathway. Here, we stimulated Jurkat CD4+ T-cell lines that expressed either the risk or protective version of IL23R, identified through genetic studies in psoriasis, and measured the effect in whole-genome expression at different timepoints poststimulation, with the aim of characterizing the downstream effect on the IL-23 pathway.

Methods

The transformed Jurkat CD4+IL12Rβ1+ IL23Rwt/IL23Rmut-R381Q T cells were stimulated with IL-23 protein (10 ng mL−1) for 0, 2, 4, 16 and 24 h, with triplicates used for each timepoint. RNA sequencing was performed by Novogene, and statistical analyses was performed using negative binomial generalized linear models and then a likelihood-ratio test to remove condition-specific differences over time.

Results

Of the identified significantly expressed genes (Padj > 10−5), five are also implicated as psoriasis risk genes, i.e. HLA-B, SOCS1, MARS, HLA-C and RUNX3. Specifically, a significant increase in RUNX3 expression in wildtype (WT) vs. mutant (MuT) at 16–24 h, and in suppressor of cytokine signalling (SOCS)-1 at 2–24 h was observed, with runt-related transcription factor (RUNX)3 expression peaking at 4 h and SOCS1 showing consistently high expression beyond 0 h. Decreased expression of SOCS1 disrupts IL-23 production and signalling, whereas increased expression of RUNX3 increases T helper (Th)17 and Th22 levels, key cells downstream of IL-23 signalling

Conclusions

Here, we show that carriage of the WT vs. MuT IL23R has downstream effects on expression of HLA-B, SOCS1, MARS, HLA-C and RUNX3, implicating these genes in the IL-23 pathway. This is important as defining pathways that are perturbed in patients has great potential within stratified medicine, with the possibility for better annotation of personalized genetic risk scores.
P34 Evaluating the adaptation of the amputee skin owing to prosthesis use: a study using in vivo Raman spectroscopy
Authors: Hayes Jack , Andrews Jennifer , Andriuskevicius Tomas , Abdelwahab Omar , Briggs Tom , Worsley Peter , Higgins Claire , Masen Marc
Published: May 2024

Introduction and aims

Lower limb prosthesis has proven to be an extremely successful intervention for amputees. However, to achieve adequate function, the device places significant friction and load on the skin, which leads to substantial skin breakdown. Current rehabilitation practices require skin to be ‘trained’ to perform a load-bearing role. Despite this, there are very high injury statistics for skin on the residual limb in the literature, we hypothesize that rehabilitation practices to adapt amputee skin are limited.

Methods

To interrogate this, we used in vivo Raman spectroscopy to evaluate the lower limbs of 13 unilateral lower limb amputees. This enabled us to assess how key constituents of the stratum corneum (SC) such as natural moisturizing factor (NMF), water and lipid content vary with depth. We also analysed sebum content to quantify cytokines present and performed mechanical characterization of the lower limb to investigate stiffness and friction.

Results

We found that the Raman spectra of the amputated limb show reduced NMF, lipid content and water content at the top of the SC when compared with the intact limb (P < 0.05). In addition, we found that amputee skin contains higher levels of inflammatory cytokines compared with control skin. We also recorded that skin on the residuum is four times softer than the intact limb, while friction is much higher at 0.5 on the residuum skin, compared with 0.3 on the intact limb.

Conclusions

Here, we show the adaptations of amputee skin in response to rehabilitation to be minimal. Contrary to the dogma that rehabilitation trains skin to bear load, we found that skin barrier function in amputee skin is impaired, as indicated by altered water and lipid profile in addition to higher baseline inflammation.
Comparative plasma biochemistry analyte data in nesting leatherback (Dermochelys coriacea), foraging green (Chelonia mydas) and foraging and nesting hawksbill (Eretmochelys imbricata) sea turtles in Grenada, West Indies
Authors: Kucinick Madison , Charles Kate E , Carter Kenrith , Edwards Jonnel , Costlow Catherine , Wilkerson Melinda , Seddon Dawn , Marancik David
Published: May 2024

Blood biochemistry represents a minimally invasive tool for monitoring sea turtle health, assessing injured sea turtles and supporting conservation strategies. In Grenada, West Indies, plasma biochemical variables were examined in 33 nesting leatherback (Dermochelys coriacea), 49 foraging green (Chelonia mydas), 49 foraging hawksbill (Eretmochelys imbricata) and 12 nesting hawksbill sea turtles sampled between 2017 and 2022. Plasma biochemistry reference intervals are described herein except for nesting hawksbills, which are represented by descriptive statistics due to the low sample size. Select analyte concentrations were positively correlated with curved carapace length in leatherbacks (chloride), green turtles (total protein, albumin and globulin) and foraging hawksbills (total protein, albumin and phosphorus). Cholesterol (7.8 mmol/l ± 1.6 SD) and triglyceride (6.9 mmol/l ± 1.9 SD) concentrations were significantly higher in leatherbacks compared to foraging green turtles, foraging hawksbills and nesting hawksbills (P < 0.001 for all). Cholesterol was significantly higher in nesting hawksbills compared to foraging green turtles (P = 0.050) and foraging hawksbills (P = 0.050). Foraging hawksbills demonstrated significantly higher aspartate transaminase activities than leatherbacks (P = 0.002), green turtles (P = 0.009) and nesting hawksbills (P < 0.001). Biochemical results provide baseline population health data and support guidance for treatments during clinical sea turtle rehabilitation efforts. They also provide insight into species-specific physiologic differences and preludes further studies to better characterize the impacts of life-stage class on biochemistry reference intervals to better support wild sea turtle populations in Grenada.
Associations Between Brain Morphology, Inflammatory Markers, and Symptoms of Fatigue, Depression, or Anxiety in Active and Remitted Crohn’s Disease
Authors: Thomann Anne K , Schmitgen Mike M , Stephan Jule C , Ebert Matthias P , Thomann Philipp A , Szabo Kristina , Reindl Wolfgang , Wolf R Christian
Published: May 2024

Background

Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn’s disease [CD] in different disease states.

Methods

In this prospective observational study, n = 109 participants [n = 67 persons with CD, n = 42 healthy controls] underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin, and completed questionnaires to assess symptoms of fatigue, depression, and anxiety. We analysed differences in grey matter volume [GMV] between patients and controls, and associations between regional GMV alterations, neuropsychiatric symptoms, and faecal calprotectin.

Results

Symptoms of fatigue, depression, and anxiety were increased in patients with CD compared with controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV associations for fatigue in remitted but not in active CD, whereas fatigue was positively associated with faecal calprotectin in active but not in remitted disease.

Conclusion

Our findings support disturbed brain-gut interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches.
Excess mortality in Denmark, Finland, Norway and Sweden during the COVID-19 pandemic 2020–2022
Authors: Forthun Ingeborg , Madsen Christian , Emilsson Louise , Nilsson Anton , Kepp Kasper P , Björk Jonas , Vollset Stein Emil , Lallukka Tea , Skrindo Knudsen Ann Kristin
Published: May 2024

Background

The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020–2022.

Methods

Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010–2019 used as reference period. We then compared excess mortality across the countries in 2020–2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses.

Results

While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29–122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14–90), 130 (83–177) and 88 (48–128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022.

Conclusion

Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates—arguably the most accurate available for any region in capturing pandemic-related excess deaths—may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic.
Evaluation of ERCP-related perforation: a single-center retrospective study
Authors: Zhou Feng , Zhan Xiaoyun , Hu Dan , Wu Nanzhen , Hong Junbo , Li Guohua , Chen Youxiang , Zhou Xiaojiang
Published: May 2024

Background

Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is a rare and serious adverse event. The aim of our study was to evaluate the risk factors and management of ERCP-related perforation, and to further determine the predictive factors associated with perforation outcome.

Methods

A total of 27,018 ERCP procedures performed at the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 2007 and March 2022 were included in the investigation of ERCP-related perforation. Medical records and endoscopic data were extracted to analyse the risk factors, management, and clinical outcome of ERCP-related perforation.

Results

Seventy-six patients (0.28%) were identified as having experienced perforation following ERCP. Advanced age, Billroth II anatomy, precut sphincterotomy, and papillary balloon dilatation were significantly associated with ERCP-related perforation. Most patients with perforation (n = 65) were recognized immediately during ERCP whereas 11 were recognized later on. The delay in recognition primarily resulted from stent migration (n = 9). In addition, 12 patients experienced poor clinical outcome including death or hospice discharge (n = 3), ICU admission for >3 days (n = 6), and prolonged hospital stay for >1 month due to perforation (n = 3). Cancer and systemic inflammatory response syndrome (SIRS) are associated with a higher risk of poor outcome.

Conclusions

Advanced age, Billroth II anatomy, precut sphincterotomy, and balloon dilation increase the risk of ERCP-related perforation whereas cancer and SIRS independently predicted poor clinical outcome.
Cropland Microclimate and Leaf-nesting Behavior Shape the Growth of Caterpillar under Future Warming
Authors: Wang Ling , Xing Shuang , Chang Xinyue , Ma Liang , Wenda Cheng
Published: May 2024

Synopsis

Predicting performance responses of insects to climate change is crucial for biodiversity conservation and pest management. While most projections on insects’ performance under climate change have used macro-scale weather station data, few incorporated the microclimates within vegetation that insects inhabit and their feeding behaviors (e.g., leaf-nesting: building leaf nests or feeding inside). Here, taking advantage of relatively homogenous vegetation structures in agricultural fields, we built microclimate models to examine fine-scale air temperatures within two important crop systems (maize and rice) and compared microclimate air temperatures to temperatures from weather stations. We deployed physical models of caterpillars and quantified effects of leaf-nesting behavior on operative temperatures of two Lepidoptera pests: Ostrinia furnacalis (Pyralidae) and Cnaphalocrocis medinalis (Crambidae). We built temperature-growth rate curves and predicted the growth rate of caterpillars with and without leaf-nesting behavior based on downscaled microclimate changes under different climate change scenarios. We identified widespread differences between microclimates in our crop systems and air temperatures reported by local weather stations. Leaf-nesting individuals in general had much lower body temperatures compared to non-leaf-nesting individuals. When considering microclimates, we predicted leaf-nesting individuals grow slower compared to non-leaf-nesting individuals with rising temperature. Our findings highlight the importance of considering microclimate and habitat-modifying behavior in predicting performance responses to climate change. Understanding the thermal biology of pests and other insects would allow us to make more accurate projections on crop yields and biodiversity responses to environmental changes.
Fisheries independent surveys in a new era of offshore wind energy development
Authors: Lipsky Andy , Silva Angela , Gilmour Fiona , Arjona Yolanda , Hogan Fiona , Lloret Josep , Bolser Derek , Haase Stefanie , Oesterwind Daniel , ten Brink Talya , Roach Michael , Ford Kathryn
Published: May 2024

Fisheries independent surveys require rethinking because of increasing spatial restrictions and interactions with offshore wind energy development (OWD). Fisheries, protected species, and environmental data collections have been conducted by scientific institutions to meet societal demands for food security, conservation, and other marine uses. These data collections provide information on key resource measures, essential for fisheries, protected species, and ecosystem management. With the increase in pace and magnitude of OWD's industrialization of marine waters, disruptions in these long-term time series can be expected. These disruptions will impact the ability to support current and future management goals and objectives. This paper presents an expert survey on the perceptions of OWD interactions with common survey designs and survey methodologies in Europe and the U.S., along with a selected sample of 75 fisheries independent surveys in the U.S. and Europe providing an initial assessment and description of potential impacts from OWD. About 72% of the surveys sampled record interactions with operational, planned or future OWD. Four case studies demonstrate efforts to address these interactions within European regions that have operational OWD and the U.S. where development has just begun. Finally, we make recommendations for future research important to continue meaningful scientific-based management advice.
Global epidemiology and antimicrobial resistance of Enterobacterales harbouring genes encoding OXA-48-like carbapenemases: insights from the results of the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme 2018–2021
Authors: Lee Yu-Lin , Wang Wei-Yao , Ko Wen-Chien , Hsueh Po-Ren
Published: May 2024

Objectives

The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes.

Methods

Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018–2021. Comprehensive antimicrobial susceptibility testing and β-lactamase gene detection were also conducted, along with statistical analysis of the collected data.

Results

Among the 72 244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (P < 0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018–2021.

Conclusions

This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens.
A multi-task learning network based on the Transformer network for airborne electromagnetic detection imaging and denoising
Authors: Liu Yajie , Zhang Yan , Guo Cheng , Zhang Song , Kang Houqin , Zhao Qing
Published: May 2024

As an emerging geophysical exploration technology in recent years, airborne electromagnetic exploration has the advantages of adapting to diverse terrains, wide coverage, and providing a large amount of electromagnetic data, and can be applied to the rapid collection of large amounts of data. Scenarios are often used in fields such as deep geological structures, mineral resource exploration, and environmental engineering research. However, traditional airborne electromagnetic data inversion technology usually takes a long time to process a large amount of airborne electromagnetic data, and it is difficult to remove the noise in the later signals. Therefore, this paper proposes a multi-task learning network structure based on Transformer. By constraining the two network branches of imaging and denoising, a sub-network with simultaneous denoising and imaging is established to process aeronautical electromagnetic data. The noise test set is introduced for testing. This model achieved a 582.61% signal-to-noise ratio improvement in smooth Gaussian noise denoising, and a 129.69% and 112.74% signal-to-noise ratio improvement in non-smooth Gaussian noise and random impulse noise denoising, respectively. The method proposed in this article overcomes the shortcomings of traditional inversion imaging such as slow speed and low resolution, and at the same time eliminates the influence of noise in airborne electromagnetic data. This is of great significance for the application of deep learning in the field of geophysical exploration.
Source code obfuscation with genetic algorithms using LLVM code optimizations
Authors: de la Torre Juan Carlos , Jareño Javier , Aragón-Jurado José Miguel , Varrette Sébastien , Dorronsoro Bernabé
Published: May 2024

With the advent of the cloud computing model allowing a shared access to massive computing facilities, a surging demand emerges for the protection of the intellectual property tied to the programs executed on these uncontrolled systems. If novel paradigm as confidential computing aims at protecting the data manipulated during the execution, obfuscating techniques (in particular at the source code level) remain a popular solution to conceal the purpose of a program or its logic without altering its functionality, thus preventing reverse-engineering on the program even with the help of computing resources. The many advantages of code obfuscation, together with its low cost, makes it a popular technique. This paper proposes a novel methodology for source code obfuscation that can be used together with other traditional obfuscation techniques, making the code more robust against reverse engineering attacks. Three program complexity metrics are used to define three different single-objective combinatorial optimization versions of the problem, which are solved and analysed. Additionally, three multi-objective problems are defined, those considering each of the selected metrics together with the program execution time, in order to avoid strong obfuscations penalizing the performance. The goal of the defined problems is to find sequences of LLVM optimizations that lead to highly obfuscated versions of the original code. These transformations are applied to the back-end pseudo-assembly code (i.e., LLVM Intermediate Representation), thus avoiding any further optimizations by the compiler. Classical genetic algorithms (GAs) are used to solve the studied problems, namely a basic cellular GA for the single-objective problems and the popular NSGA-II for the multi-objective ones. The promising results show the potential of the proposed technique.
Records of fleas (Siphonaptera) from Delaware
Authors: Kennedy Ashley C , Winter Wil S , Gardner Alfred L , Woodman Neal , Shifflett Scarlet A , Redus Sierra , Newcomer Jeffrey R , Eckerlin Ralph P
Published: May 2024

We present an annotated checklist of fleas (Siphonaptera) known to occur in the state of Delaware based on an examination of Siphonaptera collections at the University of Delaware and the Carnegie Museum of Natural History, as well as new specimens of fleas we collected from wildlife, other hosts, and tick flags. We review published records and compile them herein with our new records, which include 3 species previously unreported from Delaware. With these additions, there are now 18 flea species from 19 avian and mammalian hosts documented from Delaware.
Cost-Effectiveness of Pediatric Conjunctivitis Management and Return to Childcare and School Strategies: A Comparative Study
Authors: Frost Holly M , Stein Amy B , Keith Amy , Jenkins Timothy C
Published: May 2024

Background

Infectious conjunctivitis affects 1 in 8 children annually, resulting in high ophthalmic antibiotic prescribing and absenteeism from childcare and school. We aimed to quantify the cost-effectiveness and annual savings of 3 evidence-based approaches to conjunctivitis management and return to childcare and school compared to usual care.

Methods

Using a decision analytic model from a societal perspective over a 1-year time horizon, we conducted a cost-effectiveness analysis of 3 management strategies for children aged 6 months to 17 years with non-severe conjunctivitis compared to usual care in the United States. Strategies accounted for rate of transmission. Strategies included (1) refraining from prescribing ophthalmic antibiotics for non-severe conjunctivitis, (2) allowing children without systemic symptoms to attend childcare and school, (3) and the combined approach of refraining from prescribing ophthalmic antibiotics and allowing children without systemic symptoms to attend childcare and school.

Results

The estimated annual expenditure for pediatric conjunctivitis was $1.95 billion. Usual care was the most expensive ($212.73/episode), followed by refraining from ophthalmic antibiotic prescribing ($199.92) and allowing children without systemic symptoms to attend childcare and school ($140.18). The combined approach was the least costly ($127.38). Disutility was similar between approaches (quality-adjusted life days 0.271 vs 0.274). Refraining from antibiotic prescribing and the combination approach were dominant compared to usual care. The combined approach resulted in an estimated $783 million annual savings and 1.6 million ophthalmic antibiotic courses averted.

Conclusions

Conjunctivitis poses an economic burden that could be reduced by refraining from ophthalmic antibiotic use and allowing children without systemic symptoms to remain at school or childcare.
Similar chilling response of dormant buds in potato tuber and woody perennials
Authors: Roitman Marina , Eshel Dani
Published: May 2024

Bud dormancy is a survival strategy that plants have developed in their native habitats. It helps them endure harsh seasonal changes by temporarily halting growth and activity until conditions become more favorable. Research has primarily focused on bud dormancy in tree species and the ability to halt growth in vegetative tissues, particularly in meristems. Various plant species, such as potato, have developed specialized storage organs, enabling them to become dormant during their yearly growth cycle. Deciduous trees and potato tubers exhibit a similar type of bud endodormancy, where the bud meristem will not initiate growth, even under favorable environmental conditions. Chilling accumulation activates C-repeat/dehydration responsive element binding (DREB) factors (CBFs) transcription factors that modify the expression of dormancy-associated genes. Chilling conditions shorten the duration of endodormancy by influencing plant hormones and sugar metabolism, which affect the timing and rate of bud growth. Sugar metabolism and signaling pathways can interact with abscisic acid, affecting the symplastic connection of dormant buds. This review explores how chilling affects endodormancy duration and explores the similarity of the chilling response of dormant buds in potato tubers and woody perennials.
Exploring Schizophrenia Classification Through Multimodal MRI and Deep Graph Neural Networks: Unveiling Brain Region-Specific Weight Discrepancies and Their Association With Cell-Type Specific Transcriptomic Features
Authors: Gao Jingjing , Qian Maomin , Wang Zhengning , Li Yanling , Luo Na , Xie Sangma , Shi Weiyang , Li Peng , Chen Jun , Chen Yunchun , Wang Huaning , Liu Wenming , Li Zhigang , Yang Yongfeng , Guo Hua , Wan Ping , Lv Luxian , Lu Lin , Yan Jun , Song Yuqing , Wang Huiling , Zhang Hongxing , Wu Huawang , Ning Yuping , Du Yuhui , Cheng Yuqi , Xu Jian , Xu Xiufeng , Zhang Dai , Jiang Tianzai
Published: May 2024

Background and Hypothesis

Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification.

Study Design

Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions.

Study Results

Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research.

Conclusions

Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI’s superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.
On the last European giraffe, Palaeotragus inexspectatus (Mammalia: Giraffidae); new remains from the Early Pleistocene of Greece and a review of the species
Authors: Laskos Kostantis , Kostopoulos Dimitris S
Published: May 2024

Eurasian Giraffidae went through a drastic biodiversity decline after the Miocene–Pliocene boundary; scanty palaeotragine populations are likely to have survived in Central Asia, providing the necessary stock for a Late Pliocene–Early Pleistocene expansion from Central Asia to Spain and from the Mediterranean to southern Russia. Here, we describe new giraffid findings from the Greek middle Villafranchian faunas of Dafnero-3 and Volax and from the late Villafranchian faunas of Tsiotra Vryssi and Krimni-3, and we revise previous material from Dafnero-1. Our results support the synonymy of almost all the Villafranchian Eurasian giraffids under a single species of Palaeotragus, i.e. Palaeotragus inexspectatus, and allow us to improve its diagnosis. The orientation of the ossicones and the relative shortening of the lower premolar row might indicate affinities to some Late Miocene–Pliocene Palaeotragus from China. Our study suggests that P. inexspectatus was equally abundant at MNQ17 and MNQ18 in the Eastern Mediterranean and that its extinction after MNQ19 was probably attributable to the combination of the climatic and environmental turnover at the Villafranchian–Epivillafranchian boundary, along with the competition with emerging ruminant groups, such as giant cervids. A preliminary analysis of its palaeoecology suggests a giraffid more involved in grazing than its Late Miocene relatives.
Isolates of Corynespora cassiicola, Causal Agent of Target Spot of Soybean, in Kentucky Contain the G143A Mutation Conferring Resistance to Quinone Outside Inhibitor Fungicides
Authors: Neves Danilo L. , Bradley Carl A.
Published: May 2024

Target spot, caused by Corynespora cassiicola, is a soybean disease of increasing importance in the southern United States. Recently, isolates of C. cassiicola with resistance to quinone outside inhibitor (QoI) fungicides have been confirmed with the G143A mutation in multiple southern states, including Alabama, Arkansas, Mississippi, and Tennessee. From 2017 to 2019, a total of 84 isolates of C. cassiicola were recovered from soybean fields in 12 counties in Kentucky. DNA sequencing of the cytochrome b gene of these isolates revealed that 15.5% of the isolates had the G143A mutation that confers resistance to QoI fungicides and were in 50% of the counties in which isolates originated. This represents the first report of QoI fungicide resistance in C. cassiicola isolates from Kentucky soybean fields. Considering these findings, Kentucky soybean growers should adopt target spot management practices that include rotating to nonhost crops, planting resistant soybean cultivars, and applying fungicides from different fungicide classes.
Cardiopulmonary exercise testing, computed tomography-derived body composition, systemic inflammation and survival after elective abdominal aortic aneurysm repair
Authors: Bradley Nicholas A. , McGovern Josh , Beecroft Christina , Roxburgh Campbell S.D. , McMillan Donald C. , Guthrie Graeme J.K.
Published: May 2024

BACKGROUND

Cardio-pulmonary exercise testing (CPEX) is selectively used before intervention for abdominal aortic aneurysm (AAA). Sarcopenia, a chronic condition defined by reduced skeletal muscle function and volume, can be assessed radiologically by computed tomography (CT)-derived body composition analysis (CT-BC), and is associated with systemic inflammation.

OBJECTIVE

The aim was to describe the association between CT-BC, CPEX, inflammation and survival in patients undergoing elective intervention for AAA.

SETTING

Patients were recruited retrospectively from a single, secondary-care centre-operative database. Cases undergoing elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR) between 31 March 2015 and 25 June 2020 were included.

PATIENTS

There were 176 patients (130 EVAR, 46 OSR) available for analysis in the final study; median (interquartile range [IQR]) follow-up was 60.5 [27] months, and all completed a minimum of 2 years follow-up.

MAIN OUTCOME MEASURES

Preoperative CPEX tests were recorded. CT sarcopenia score [CT-SS, range 0 to 2, calculated based on normal/low SMI (0/1) and normal/low SMD (0/1)] assessed radiological sarcopenia. Preoperative modified Glasgow Prognostic score (mGPS) was used to assess systemic inflammation.

RESULTS

Mean [95% confidence interval (CI) survival in the CT-SS 0 vs. CT-SS 1 vs. CT-SS 2 subgroups was 80.1 (73.6 to 86.6) months vs. 70.3 (63.5 to 77.1) months vs. 63.8 (53.4 to 74.2) months] (P = 0.01). CT-SS was not associated with CPEX results (P > 0.05). Elevated CT-SS [hazard ratio (HR) 1.83, 95% CI, 1.16 to 2.89, P < 0.01] was independently associated with increased hazard of long-term mortality; however, CPEX results were not (P > 0.05).

CONCLUSION

CPEX test results were not consistently associated with body composition and did not have significant prognostic value in patients undergoing elective treatment for AAA.
Perspectives on sustainable practices in the use of nitrous oxide for labour analgesia
Authors: McGarrigle Conor , Hartigan Sean , Duffy Oscar , Tan Terry
Published: May 2024

BACKGROUND

Climate change has emerged as the single biggest global health threat of the twenty-first century. Nitrous oxide accounts for the largest carbon footprint amongst our use of anaesthetic gas. It is a potent greenhouse gas possessing a global warming potential of approximately 265 times that of carbon dioxide. Despite recent curtailment of its use, it remains extensively employed as an analgesic for women in labour.

OBJECTIVES

Assessment of the opinions of post-natal women and staff on nitrous oxide use and to investigate whether knowledge of its environmental harm would influence their choice of labour analgesia.

DESIGN

Postnatal women and healthcare staff were invited to participate in a survey of nitrous oxide use as a labour analgesic and knowledge of its effect of the environment.

SETTING

A single-centre study in a major obstetric tertiary referral centre in Ireland in 2021.

MAIN OUTCOME MEASURES

To evaluate the awareness and perceptions of postnatal women and staff regarding the environmental impact of nitrous oxide and if it would affect their decision to use it in the future.

RESULTS

One hundred postnatal women and 50 healthcare staff completed the survey. One hundred and six post-natal women were invited to complete the survey, resulting in a response rate of 94%. Knowledge of nitrous oxide's environmental impact was low. After receiving information, 46% of patients were more inclined to seek epidural or request it earlier (54%) to limit their nitrous oxide use, while 51% would choose an alternative analgesia to avoid nitrous oxide altogether. Overwhelmingly, 99% believed they had the right to know about these harmful effects when choosing an analgesic option.

CONCLUSIONS

Patients should be informed of the environmental impact of nitrous oxide antenatally, empowering them to make informed decision on a climate friendly analgesic option if they wish.
Food Insecurity and Family Dynamics
Authors: Krishnamurthy Sudarshan , Chait Joshua S. , Reddy Menaka N. , Galli Lucas D. , Skelton Joseph A.
Published: May 2024

Background:

Undernutrition is related to numerous childhood outcomes. However, little research has investigated the relationship between food insecurity and family dynamics. This systematic review seeks to validate the evidence for a relationship between these 2 factors.

Methods:

A systematic literature review was conducted in Embase, PubMed, and Scopus. Inclusion criteria include peer-reviewed research articles published during or after 1996 in English, using standardized measures of family function and food insecurity. Exclusion criteria include measurement of parent or child characteristics without assessing household or family characteristics or demographics. Two reviewers independently voted using Covidence, and Alpha agreement was determined at each phase.

Results:

A total of 15 studies were included for data extraction after the initial search being completed in April 2022. All included studies were found to be appropriate in numerous categories for quality assessment. Primary findings from these studies show a potential relationship exists between food insecurity and family dynamics.

Discussion:

The findings in this review suggest that effects of food insecurity expand to various aspects of healthy family functioning. Unhealthy family dynamics in childhood can also expose children to trauma and lead to increased physical and mental health disorders in the future.
Permanent Peripheral Nerve Stimulator for Complex Regional Pain Syndrome of the Forearm and Hand
Authors: Chappell Ava G. , Kalainov David M. , Samworth Alexander , Yuksel Selcen S. , Rangwani Sean , Nader Antoun
Published: May 2024

A 51-year-old woman with diabetes and depression was referred to the anesthesia pain clinic with a 15-year history of complex regional pain syndrome type I of the right forearm and hand in the radial sensory nerve distribution. There was no recognized antecedent trauma and she had failed both medical treatment and radial sensory nerve decompression surgery. An ultrasound-guided local anesthetic block of the radial nerve in the upper arm resulted in partial and temporary improvement in pain. She subsequently underwent trial of a peripheral nerve stimulator (PNS) followed by permanent PNS implant placement over the radial nerve proper proximal to the elbow. Within the first month of use, she endorsed substantially improved pain and strength in her right hand. These improvements were sustained for more than 1 year. Applications of PNS technology for treatment of extremity complex regional pain syndrome and neuropathic extremity pain in general are reviewed.
The Lymphedematous Limb as a Donor Site for Breast Fat Grafting
Authors: Ahmed Shahnur , Mohan Ganesh , Hulsman Luci , Greene Arin K. , Shaheen Muhammad , Sinha Mithun , Hassanein Aladdin H.
Published: May 2024

Breast cancer–related lymphedema results in chronic upper limb swelling with subcutaneous deposition of fluid and fibroadipose tissue. Morbidity includes psychosocial distress, infection, and difficulty using the extremity. Operative management includes excisional procedures such as suction-assisted lipectomy to reduce abnormal subcutaneous fibroadipose tissue to improve limb volume. Patients who have had postmastectomy breast reconstruction often benefit from fat grafting. This report introduces the concept of fat grafting the breast using the lymphedematous arm as a donor site. This technique improves the volume of the limb by removing the excess subcutaneous adipose, and at the same time reconstructs the breast without adding a donor site not related to the breast cancer–related lymphedema.