bluuebunny/crossref_metadata_2025_split huggingface dataset:
P22 Fibrosis in delayed wound healing in diabetes: the role of insulin-like growth factor binding proteins
Authors: Were Sharlene , Wilson Taryn , Martin Patricia , Wright Catherine 
Published: July 2023

Abstract
Skin fibrosis is thought to be a factor in delayed wound healing in people with diabetes. Insulin-like growth factor binding protein 5 (IGFBP-5), which is fibrotic in other organs, is augmented in the skin of people with diabetes. We examined the effects of IGFBP-5, connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 on skin fibrosis and wound-healing capacity in human primary dermal fibroblasts from people with and without diabetes. In vitro scrape wound closure in diabetic dermal fibroblasts was delayed in diabetic fibroblasts. IGFBP-5 treatment further retarded scrape-wound closure rates above that seen with diabetic fibroblasts. Diabetic fibroblasts were more adhesive to substrates than normal fibroblasts in adhesion assays, reducing their migratory capacity, and normal fibroblasts treated with IGFBP-5 and TGF-β1 showed increased adhesion over controls. Diabetic fibroblasts also had reduced cell viability. Fibronectin and collagen production by fibroblasts were increased with IGFBP-5 in cultures; thus upregulated IGFBP-5 in diabetic skin may increase extracellular matrix (ECM) deposition. IGFBP-5 and α-smooth muscle actin protein was overexpressed in diabetic fibroblasts by Western blotting, so IGFBP-5 induces fibroblast to myofibroblast transition. Gene expression of matrix metalloproteinase (MMP)-1, MMP-9, CTGF and tissue inhibitor of metalloproteinase 1 (TIMP-1) was raised in diabetic fibroblasts; MMP-9, MMP-1 and TIMP-1 expression levels were increased with IGFBP-5 treatment. Elevated levels of IGFBP-5 and CGTF in the dermis may contribute to retarded wound healing and ulceration in people with diabetes (despite increases in fibroblast MMPs), causing fibroblasts to lay down more ECM, contributing to fibrosis and compromising the wound bed. Diabetic dermal fibroblasts are compromised in viability and migratory capacity, and are more adhesive and stiffer, making it more difficult for them to populate granulation tissue. They are thus less able to close wounds and hyperproliferate around wound edges. IGFBP-5 and CTGF could be novel therapeutic targets to mitigate diabetic skin fibrosis and improve wound healing.
P25 Hsa-miR-6727-5p contributes to the impact of high-density lipoprotein on fibroblast wound healing in vitro
Authors: Bastaki Khaled , Tarlton Jamie , Lightbody Richard , Martin Patricia , Graham Annette 
Published: July 2023

Abstract
There is a clear unmet clinical need to develop effective strategies to improve chronic nonhealing wound closure rates, with distinct skin cell populations responding to potential therapies in different ways. Recent evidence suggests that high-density lipoproteins (HDL) can enhance wound closure rates, but, owing to the complexity, heterogeneity and relative instability of this lipoprotein fraction, developing a translational rationale to explore this observation is challenging. In the present work we explored the ability of primary human neonatal keratinocytes (HKn) and fibroblasts (HDFn), and adult dermal fibroblasts (HDFa), to respond to HDL by monitoring cholesterol efflux and scratch wound assays. Global changes in expression of small noncoding microRNA sequences (miRs), following the exposure of HDFn and HDFa to HDL, was determined by microchip array, validated by independent quantitative polymerase chain reaction, and the impact of a selected miRNA mimic on scrape wound closure assessed. All experiments were performed in triplicate. The data revealed that all cell types respond to HDL in terms of cholesterol efflux, confirming the functionality of this lipoprotein, but promotion of wound healing only occurs in HDFn and HDFa cells, with no response in HKn. Exposure of both HDFn and HDFa cells to HDL induces multiple changes in the expression of miR sequences, including hsa-miR-6727-5p. Levels of this miR increased in HDFn, but decreased in HDFa cells, following HDL exposure. Delivery of a hsa-miR6727-5p mimic repressed the expression of different target genes in HDFn (ZNF584) and HDFa (EDEM3, KRAS), while rates of wound closure were enhanced in the presence of a hsa-6727-5p mimic in HDFn cells and an inhibitor in HDFa cells. Intriguingly, analysis of the microarray data also revealed distinct expression landscapes in neonatal and adult fibroblasts, providing insight into the epigenetic evolution of these cells during the wound healing process. Thus, exposure to HDL has distinct impacts on the expression of the miR hsa-mir-6727-5p in neonatal and adult fibroblasts, which play differential roles in wound healing. We identify a range of pathways influenced by this miR but note that this miR alone cannot replicate the myriad effects of HDL. Future work will explore the impact of (dys)functional HDL and hsa-miR-6727-5p on wound closure rates in fibroblasts isolated from diabetic patients. Moreover, this study offers opportunities to expand knowledge of how profound changes in epigenetic profile can influence wound healing during ageing.
Funding sources: K.B. was supported by a PhD scholarship provided by the Kuwaiti government; human fibroblasts were provided by the GCU Research Tissue Bank (NHS REC Ref 16/E0069).
P29 Manuka honey downregulates IL-4-induced CCL26 via activation of the aryl hydrocarbon receptor
Authors: Alangari Abdullah A , Ashoori Matin Dokht , Alwan Wisam , Stockinger Brigitta , Barker Jonathan N   , Wincent Emma , Di Meglio Paola  
Published: July 2023

Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that regulates skin homeostasis. AHR activation by physiological ligands (e.g. indoles originated from host or microbial metabolism of tryptophan) leads to the expression of cytochrome P450 (CYP) enzymes, such as CYP1A1 and has anti-inflammatory effects in animal models and clinical samples of psoriasis and atopic dermatitis. Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH downregulates interleukin (IL)-4-induced CCL26 expression in immortalized keratinocytes. Recent studies suggest that MH contains potential AhR ligands, including indoles. Thus, we hypothesize that its anti-inflammatory effect may be mediated, at least partially, via AhR activation. Here, we treated HaCaT keratinocytes, either stably transfected with an empty vector (EV-HaCaT) or in which AhR had been stably silenced (AhR-silenced HaCaT), or primary normal human epithelial keratinocytes (NHEK) with 2% MH for 24 h and measured gene expression by reverse transcriptase quantitative polymerase chain reaction. We detected a 15.4-fold upregulation of CYP1A1 in EV-HaCaTs, which was significantly reduced (P ≤ 0.001) in AhR-silenced cells. Pretreatment with the AhR antagonist CH223191 significantly (P ≤ 0.0001) abrogated this effect. Similar findings were observed in NHEKs. In vivo epicutaneous treatment of Cyp1a1Cre × R26ReYFP reporter mice with pure MH significantly (P &lt; 0.0001) induced CYP1A1 expression compared with Vaseline. Treatment of HaCaT with 2% MH significantly decreased (P &lt; 0.0001) baseline CYP1A1 enzymatic activity at 3 and 6 h but increased it after 12 h, suggesting that MH may activate the AhR through both direct and indirect means. Importantly, MH downregulation of IL-4-induced CCL26 mRNA and protein was abrogated in AhR-silenced HaCaTs and by pretreatment with CH223191. Finally, MH significantly (P &lt; 0.0001) upregulated filaggrin (FLG) expression in NHEKs in an AhR-dependent manner. In conclusion, MH activates AhR, both in vitro and in vivo, thereby providing a mechanism of its IL-4-induced CCL26 downregulation and upregulation of FLG expression. Taken together, our data show that the AhR-activating properties of MH could have broader clinical implications in a range of skin inflammatory conditions.
P32 Restoring the ageing skin barrier in vitro
Authors: Garcha Priya , Jones Eleri , Shelley Jennifer , Caley Matthew 
Published: July 2023

Abstract
The skin provides an essential barrier to the body. As we age, the make-up of this barrier changes, with a reduction of stratum corneum lipids. This loss of lipids as we age can lead to the formation of dry and easily damaged skin, allowing for water loss from the skin surface. One mechanism for this reduction in stratum corneum lipids is dysfunctional lipid transport. To investigate lipid transport within the skin we have developed a two-dimensional high-throughput cholesterol transport assay. Using this assay we have screened 200 naturally occurring compounds and 800 plant extracts to determine their ability to improve cholesterol transport. We identified seven compounds that were able to increase cholesterol transport with no cellular toxicity. Three compounds were selected for further testing in three-dimensional (3D) organotypic skin models with or without defects in cholesterol transport and stratum corneum lipids. Three-dimensional organotypic skin models were grown for 7 days before daily treatment with either dimethyl sulfoxide or 1 µmol L–1 of the selected compound for an additional 7 days. Immunofluorescent staining was conducted to assess skin differentiation (K14, K10, TGM1), proliferation (Ki67), basement membrane (laminin α3) and stratum corneum lipids (Nile red). We have developed a 2D screening and 3D testing platform to assess compounds and drugs for their effect on cholesterol transport. Compounds that can target cholesterol transport within keratinocytes could be a beneficial treatment to help improve the ageing skin barrier, improving dry and damaged skin.
Eocene palynoflora from the La Marcelina Formation, Patagonia, Argentina
Authors: Noetinger Sol , Aramendía Inés , Pujana Roberto R , García Massini Juan L , Barreda Viviana D 
Published: July 2023

Abstract
Southern Patagonia contains several Eocene fossiliferous deposits that have only been superficially explored and studied. One of these corresponds to the La Marcelina Formation with outcrops in the south-western slope of the Deseado Massif, Santa Cruz Province, Argentina. No detailed palynological studies have been performed so far in this unit. Here we estimate the age, palaeoenvironment, and climatic conditions based on the analysis of terrestrially derived spores, algae cysts, and pollen grains. The recovered association supports an Eocene age and concurs with a mixed flora, including Gondwanan and Neotropical elements, dominated by Podocarpaceae, Nothofagaceae, and Proteaceae, and that probably developed under a temperate and humid climate. Overall, these results expand our understanding of the composition of Eocene floras from the highest latitudes of South America, as well as provide new evidence of past paleoclimates for the area.
New insights into risk variables associated with gas embolism in loggerhead sea turtles (Caretta caretta) caught in trawls and gillnets
Authors: Garcia-Parraga Daniel , Crespo-Picazo Jose Luis , Sterba-Boatwright Blair , Marco Vicente , Muñoz-Baquero Marta , Robinson Nathan J , Stacy Brian , Fahlman Andreas 
Published: July 2023

Abstract
Tissue and blood gas embolism (GE) associated with fisheries bycatch are likely a widespread, yet underestimated, cause of sea turtle mortality. Here, we evaluated risk factors associated with tissue and blood GE in loggerhead turtles caught incidentally by trawl and gillnet fisheries on the Valencian coastline of Spain. Of 413 turtles (303 caught by trawl, 110 by gillnet fisheries), 54% (n = 222) exhibited GE. For sea turtles caught in trawls, the probability and severity of GE increased with trawl depth and turtle body mass. In addition, trawl depth and the GE score together explained the probability of mortality (P[mortality]) following recompression therapy. Specifically, a turtle with a GE score of 3 caught in a trawl deployed at 110 m had a P[mortality] of ~50%. For turtles caught in gillnets, no risk variables were significantly correlated with either the P[GE] or GE score. However, gillnet depth or GE score, separately, explained P[mortality], and a turtle caught at 45 m or with a GE score between 3 and 4 had a P[mortality] of 50%. Differences in the fishery characteristics precluded direct comparison of GE risk and mortality between these gear types. Although P[mortality] is expected to be significantly higher in untreated turtles released at sea, our findings can improve estimates of sea turtle mortality associated with trawls and gillnets, and help guide associate conservation efforts.
Imaging for implementation of heart failure guidelines
Authors: Nagueh Sherif F , Nabi Faisal , Chang Su Min , Al-Mallah Mouaz , Shah Dipan J , Bhimaraj Arvind 
Published: July 2023

Abstract
The classification of heart failure with implications for pharmacological therapeutic interventions rests on defining ejection fraction (EF) which is an imaging parameter. Imaging can provide diagnostic clues as to aetiology of heart failure; it can also guide and help assess response to treatment. Echocardiography, CMR, cardiac computed tomography, positron emission tomography, and Tc 99 m pyrophosphate scanning provide information about the aetiology of heart failure. Further, echocardiography plays the primary role in the evaluation of LV diastolic function and the estimation of left ventricular (LV) filling pressures both at rest and with exercise during diastolic stress testing. Heart failure guidelines recognize four stages (A, B, C, and D) for heart failure. Cardiac imaging along with risk factors and clinical status is needed for identifying these stages. There are joint societal echocardiographic guidelines by American Society of Echocardiography (ASE) of Echocardiography and European Association of Cardiovascular Imaging that are applicable to the imaging of heart failure patients. There are also separate guidelines for the evaluation of patients being considered for LV assist device implantation and for multimodality imaging of patients with heart failure and preserved EF. Cardiac catheterization is needed in patients whose haemodynamic status is uncertain after clinical and echocardiographic evaluation and to evaluate for coronary artery disease. Myocardial biopsy can identify the presence of myocarditis or specific infiltrative diseases when the findings by non-invasive imaging are not conclusive.
Case report of culture-negative endocarditis in lupus nephritis
Authors: Khandait Harshwardhan , Ong Cheng Ken , Javaid Ayesha , Sandhu Rav 
Published: July 2023

Abstract

Background
Cardiovascular involvement is frequent in systemic lupus erythematosus (SLE). Valvular abnormalities are increasingly being recognized with the advent of echocardiography.

Case summary
We present a case of a 46-year-old lady who presented to the emergency department with upper limb ischaemia. On examination, she had poor dentition and a short systolic murmur on auscultation. A blood workup revealed a diagnosis of SLE. Further investigations showed vegetations on the mitral valve. Initially, an infective endocarditis (IE) diagnosis was made, which was treated with antibiotics. High-dose steroids and immunosuppressants were initiated due to her clinical deterioration and biopsy-proven lupus nephritis. She improved clinically before being discharged home.

Discussion
It can be difficult to distinguish between IE and Libman–Sacks endocarditis (LSE), especially in the setting of risk factors for both. Antibiotics and immunosuppressants might be started simultaneously in these cases. A multidisciplinary team is required to manage challenging cases of culture-negative endocarditis. Procalcitonin may have a role in differentiating bacterial endocarditis and LSE.
Drivers and consequences of bacteriophage host range
Authors: Holtappels Dominique , Alfenas-Zerbini Poliane , Koskella Britt 
Published: July 2023

Abstract
Bacteriophages are obligate parasites of bacteria characterized by the breadth of hosts that they can infect. This “host range” depends on the genotypes and morphologies of the phage and the bacterial host, but also on the environment in which they are interacting. Understanding phage host range is critical to predicting the impacts of these parasites in their natural host communities and their utility as therapeutic agents, but is also key to predicting how phages evolve and in doing so drive evolutionary change in their host populations, including through movement of genes among unrelated bacterial genomes. Here, we explore the drivers of phage infection and host range from the molecular underpinnings of the phage–host interaction to the ecological context in which they occur. We further evaluate the importance of intrinsic, transient, and environmental drivers shaping phage infection and replication, and discuss how each influences host range over evolutionary time. The host range of phages has great consequences in phage-based application strategies, as well as natural community dynamics, and we therefore highlight both recent developments and key open questions in the field as phage-based therapeutics come back into focus.
Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
Authors: Bell Avery Davis , Chou Han Ting , Valencia Francisco , Paaby Annalise B 
Published: July 2023

Abstract
Though natural systems harbor genetic and phenotypic variation, research in model organisms is often restricted to a reference strain. Focusing on a reference strain yields a great depth of knowledge but potentially at the cost of breadth of understanding. Furthermore, tools developed in the reference context may introduce bias when applied to other strains, posing challenges to defining the scope of variation within model systems. Here, we evaluate how genetic differences among 5 wild Caenorhabditis elegans strains affect gene expression and its quantification, in general and after induction of the RNA interference (RNAi) response. Across strains, 34% of genes were differentially expressed in the control condition, including 411 genes that were not expressed at all in at least 1 strain; 49 of these were unexpressed in reference strain N2. Reference genome mapping bias caused limited concern: despite hyperdiverse hotspots throughout the genome, 92% of variably expressed genes were robust to mapping issues. The transcriptional response to RNAi was highly strain- and target-gene-specific and did not correlate with RNAi efficiency, as the 2 RNAi-insensitive strains showed more differentially expressed genes following RNAi treatment than the RNAi-sensitive reference strain. We conclude that gene expression, generally and in response to RNAi, differs across C. elegans strains such that the choice of strain may meaningfully influence scientific inferences. Finally, we introduce a resource for querying gene expression variation in this dataset at https://wildworm.biosci.gatech.edu/rnai/.
An Open-Source Photogrammetry Workflow for Reconstructing 3D Models
Authors: Zhang C , Maga A M 
Published: July 2023

SynopsisAcquiring accurate 3D biological models efficiently and economically is important for morphological data collection and analysis in organismal biology. In recent years, structure-from-motion (SFM) photogrammetry has become increasingly popular in biological research due to its flexibility and being relatively low cost. SFM photogrammetry registers 2D images for reconstructing camera positions as the basis for 3D modeling and texturing. However, most studies of organismal biology still relied on commercial software to reconstruct the 3D model from photographs, which impeded the adoption of this workflow in our field due the blocking issues such as cost and affordability. Also, prior investigations in photogrammetry did not sufficiently assess the geometric accuracy of the models reconstructed. Consequently, this study has two goals. First, we presented an affordable and highly flexible SFM photogrammetry pipeline based on the open-source package OpenDroneMap (ODM) and its user interface WebODM. Second, we assessed the geometric accuracy of the photogrammetric models acquired from the ODM pipeline by comparing them to the models acquired via microCT scanning, the de facto method to image skeleton. Our sample comprised 15 Aplodontia rufa (mountain beaver) skulls. Using models derived from microCT scans of the samples as reference, our results showed that the geometry of the models derived from ODM was sufficiently accurate for gross metric and morphometric analysis as the measurement errors are usually around or below 2%, and morphometric analysis captured consistent patterns of shape variations in both modalities. However, subtle but distinct differences between the photogrammetric and microCT-derived 3D models could affect the landmark placement, which in return affected the downstream shape analysis, especially when the variance within a sample is relatively small. At the minimum, we strongly advise not combining 3D models derived from these two modalities for geometric morphometric analysis. Our findings can be indictive of similar issues in other SFM photogrammetry tools since the underlying pipelines are similar. We recommend that users run a pilot test of geometric accuracy before using photogrammetric models for morphometric analysis. For the research community, we provide detailed guidance on using our pipeline for building 3D models from photographs.
Identifying contributors to disparities in patient access of online medical records: examining the role of clinician encouragement
Authors: Sisk Bryan A , Lin Sunny , Balls-Berry Joyce (Joy) E , Servin Argentina E , Mack Jennifer W 
Published: July 2023

Abstract

Objective
The aim of this study was to understand the influence of clinician encouragement and sociodemographic factors on whether patients access online electronic medical records (EMR).

Materials and Methods
We analyzed 3279 responses from the Health Information National Trends Survey 5 cycle 4 survey, a cross-sectional, nationally representative survey administered by the National Cancer Institute. Frequencies and weighted proportions were calculated to compare clinical encouragement and access to their online EMR. Using multivariate logistic regression, we identified factors associated with online EMR use and clinician encouragement.

Results
In 2020, an estimated 42% of US adults accessed their online EMR and 51% were encouraged by clinicians to access their online EMR. In multivariate regression, respondents who accessed EMR were more likely to have received clinician encouragement (odds ratio [OR], 10.3; 95% confidence interval [CI], 7.7–14.0), college education or higher (OR, 1.9; 95% CI, 1.4–2.7), history of cancer (OR, 1.5; 95% CI, 1.0–2.3), and history of chronic disease (OR, 2.3; 95% CI, 1.7–3.2). Male and Hispanic respondents were less likely to have accessed EMR than female and non-Hispanic White respondents (OR, 0.6; 95% CI, 0.5–0.8, and OR, 0.5; 95% CI, 0.3–0.8, respectively). Respondents receiving encouragement from clinicians were more likely to be female (OR, 1.7; 95% CI, 1.3–2.3), have college education (OR, 1.5; 95% CI, 1.1–2.0), history of cancer (OR, 1.8; 95% CI, 1.3–2.5), and greater income levels (OR, 1.8–3.6).

Discussion
Clinician encouragement of patient EMR use is strongly associated with patients accessing EMR, and there are disparities in who receives clinician encouragement related to education, income, sex, and ethnicity.

Conclusions
Clinicians have an important role to ensure that all patients benefit from online EMR use.