bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical and biological characterization of Melaleuca subulata (Cheel) Craven leaves’ volatile constituents supported by chemometric analysis and molecular docking
Authors: Elsayed Heba E. , Ayoub Iriny M. , Mady Mohamed S. , Moharram Fatma A. 
Published: February 2024

Abstract
Background
The genus Melaleuca (Myrtaceae) comprises dozens of essential oil (EO)-rich species that are appreciated worldwide for their various medicinal values. Additionally, they are renowned in traditional medicine for their antimicrobial, antifungal, and other skin-related activities. The current study investigated the chemical profile and skin-related activities of volatile constituents derived from M. subulata (Cheel) Craven (Synonym Callistemon subulatus) leaves cultivated in Egypt for the first time.

Methods
The volatile components were extracted using hydrodistillation (HD), headspace (HS), and supercritical fluid (SF). GC/MS and Kovat’s retention indices were implemented to identify the volatile compounds, while the variations among the components were assessed using Principal Component Analysis and Hierarchical Cluster Analysis. The radical scavenging activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and β-carotene assays. Moreover, the anti-aging effect was evaluated using anti-elastase, and anti-collagenase, while the antimicrobial potential was deduced from the agar diffusion and broth microdilution assays. Lastly, the molecular docking study was executed using C-docker protocol in Discovery Studio 4.5 to rationalize the binding affinity with targeted enzymes.

Results
The SF extraction approach offered the highest EO yield, being 0.75%. According to the GC/MS analysis, monoterpene hydrocarbons were the most abundant volatile class in the HD oil sample (54.95%), with α-pinene being the most copious component (35.17%). On the contrary, the HS and SF volatile constituents were pioneered with oxygenated monoterpenes (72.01 and 36.41%) with eucalyptol and isopulegone being the most recognized components, representing 67.75 and 23.46%, respectively. The chemometric analysis showed segregate clustering of the three extraction methods with α-pinene, eucalyptol, and isopulegone serving as the main discriminating phytomarkers. Concerning the bioactivity context, both SF and HD-EOs exhibited antioxidant effects in terms of ORAC and β-carotene bleaching. The HD-EO displayed potent anti-tyrosinase activity, whereas the SF-EO exhibited significant anti-elastase properties. Moreover, SF-EO shows selective activity against gram-positive skin pathogens, especially S. aureus. Ultimately, molecular docking revealed binding scores for the volatile constituents; analogous to those of the docked reference drugs.

Conclusions
M. subulata leaves constitute bioactive volatile components that may be indorsed as bioactive hits for managing skin aging and infection, though further in vivo studies are recommended.
Machine learning based biomarker discovery for chronic kidney disease–mineral and bone disorder (CKD-MBD)
Authors: Li Yuting , Lou Yukuan , Liu Man , Chen Siyi , Tan Peng , Li Xiang , Sun Huaixin , Kong Weixin , Zhang Suhua , Shao Xiang 
Published: February 2024

Abstract
Introduction
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and some other complications. Although there are diagnostic criteria for CKD-MBD, in situations when conducting target feature examining are unavailable, there is a need to investigate and discover alternative biochemical criteria that are easy to obtain. Moreover, studying the correlations between the newly discovered biomarkers and the existing ones may provide insights into the underlying molecular mechanisms of CKD-MBD.

Methods
We collected a cohort of 116 individuals, consisting of three subtypes of CKD-MBD: calcium abnormality, phosphorus abnormality, and PTH abnormality. To identify the best biomarker panel for discrimination, we conducted six machine learning prediction methods and employed a sequential forward feature selection approach for each subtype. Additionally, we collected a separate prospective cohort of 114 samples to validate the discriminative power of the trained prediction models.

Results
Using machine learning under cross validation setting, the feature selection method selected a concise biomarker panel for each CKD-MBD subtype as well as for the general one. Using the consensus of these features, best area under ROC curve reached up to 0.95 for the training dataset and 0.74 for the perspective dataset, respectively.

Discussion/Conclusion
For the first time, we utilized machine learning methods to analyze biochemical criteria associated with CKD-MBD. Our aim was to identify alternative biomarkers that could serve not only as early detection indicators for CKD-MBD, but also as potential candidates for studying the underlying molecular mechanisms of the condition.
Impacts of the COVID-19 public health emergency on healthcare professional delivery of opportunistic behaviour change interventions: a retrospective cohort study
Authors: Keyworth Chris , Conner Mark , Johnson Judith , Epton Tracy , Vogt Katharina S. , Armitage Christopher J. 
Published: February 2024

Abstract
Background
The public health policy “Making Every Contact Count” (MECC) compels healthcare professionals to deliver health behaviour change interventions during routine consultations. As healthcare systems continue their recovery from the impacts of the COVID-19 public health emergency, supporting people to modify health behaviours is more important now than when the policy was introduced. The present study aims to: (a) examine changes in healthcare professionals’ awareness of, and engagement with the policy over a five-year period, (b) examine the psychosocial drivers associated with delivering behaviour change interventions, and (c) identify targets to increase healthcare professionals’ delivery of interventions.

Methods
Comparison of data from two independent representative surveys of NHS healthcare professionals working in the UK. In both surveys (July-September 2017; N = 1387, and February-March 2022; N = 1008), participants were asked to report: (1) awareness of the MECC policy, (2) the prevalence of MECC-related practice (perceived patient benefit, how often interventions were delivered, and time spent delivering interventions), and (3) perceptions of capabilities, opportunities and motivations to deliver behaviour change interventions. T- tests (independent-samples), MANOVA, multiple linear regression, and chi-square analyses were used to generate comparisons between the surveys.

Results
Awareness of the policy increased from 2017 (31.4%) to 2022 (52.0%). However, in 2022 compared with 2017, healthcare professionals reported (a) fewer patients would benefit from behaviour change interventions (49.1% versus 55.9%), (b) they delivered behaviour change interventions to a lower proportion of patients (38.0% versus 50.0%), and (c) they spent a lower proportion of the consultation time delivering interventions (26.5% versus 35.3%). Further, in 2022, compared with 2017, healthcare professionals reported fewer physical opportunities, fewer social opportunities, and fewer psychological capabilities to deliver behaviour change interventions. In the 2022 survey, perceptions of patient benefit and delivery of interventions was associated with greater perceptions of opportunities and motivations.

Conclusions
Health behaviour change interventions remain an important part of routine healthcare in the continued recovery from COVID-19 public health emergency, however reported engagement with MECC-related practices appears to have reduced over time. Future research should consider how healthcare professionals identify patients who might benefit from opportunistic behaviour change interventions, and to increase capabilities, opportunities, and motivations to deliver interventions during routine consultations.
Genome-wide methylome stability and parental effects in the worldwide distributed Lombardy poplar
Authors: Vanden Broeck An , Meese Tim , Verschelde Pieter , Cox Karen , Heinze Berthold , Deforce Dieter , De Meester Ellen , Van Nieuwerburgh Filip 
Published: February 2024

Abstract
Background
Despite the increasing number of epigenomic studies in plants, little is known about the forces that shape the methylome in long-lived woody perennials. The Lombardy poplar offers an ideal opportunity to investigate the impact of the individual environmental history of trees on the methylome.

Results
We present the results of three interconnected experiments on Lombardy poplar. In the first experiment, we investigated methylome variability during a growing season and across vegetatively reproduced generations. We found that ramets collected over Europe and raised in common conditions have stable methylomes in symmetrical CG-contexts. In contrast, seasonal dynamics occurred in methylation patterns in CHH context. In the second experiment, we investigated whether methylome patterns of plants grown in a non-parental environment correlate with the parental climate. We did not observe a biological relevant pattern that significantly correlates with the parental climate. Finally, we investigated whether the parental environment has persistent carry-over effects on the vegetative offspring’s phenotype. We combined new bud set observations of three consecutive growing seasons with former published bud set data. Using a linear mixed effects analysis, we found a statistically significant but weak short-term, parental carry-over effect on the timing of bud set. However, this effect was negligible compared to the direct effects of the offspring environment.

Conclusions
Genome-wide cytosine methylation patterns in symmetrical CG-context are stable in Lombardy poplar and appear to be mainly the result of random processes. In this widespread poplar clone, methylation patterns in CG-context can be used as biomarkers to infer a common ancestor and thus to investigate the recent environmental history of a specific Lombardy poplar. The Lombardy poplar shows high phenotypic plasticity in a novel environment which enabled this clonal tree to adapt and survive all over the temperate regions of the world.
Ethnicity-specific blood pressure thresholds based on cardiovascular and renal complications: a prospective study in the UK Biobank
Authors: Su Donghan , Yang Huanhuan , Chen Zekun , Kong Yuhao , Na Xiaona , Lin Queran , Zhao Ai , Zheng Yan , Ma Yanan , Li Xiaoyu , Li Zhihui 
Published: February 2024

Abstract
Background
The appropriateness of hypertension thresholds for triggering action to prevent cardiovascular and renal complications among non-White populations in the UK is subject to question. Our objective was to establish ethnicity-specific systolic blood pressure (SBP) cutoffs for ethnic minority populations and assess the efficacy of these ethnicity-specific cutoffs in predicting adverse outcomes.

Methods
We analyzed data from UK Biobank, which included 444,418 participants from White, South Asian, Black Caribbean, and Black African populations with no history of cardiorenal complications. We fitted Poisson regression models with continuous SBP and ethnic groups, using Whites as the referent category, for the composite outcome of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. We determined ethnicity-specific thresholds equivalent to the risks observed in Whites at SBP levels of 120, 130, and 140 mm Hg. We adjusted models for clinical characteristics, sociodemographic factors, and behavioral factors. The performance of ethnicity-specific thresholds for predicting adverse outcomes and associated population-attributable fraction (PAF) was assessed in ethnic minority groups.

Results
After a median follow-up of 12.5 years (interquartile range, 11.7–13.2), 32,662 (7.4%) participants had incident composite outcomes. At any given SBP, the predicted incidence rate of the composite outcome was the highest for South Asians, followed by White, Black Caribbean, and Black African. For an equivalent risk of outcomes observed in the White population at an SBP level of 140 mm Hg, the SBP threshold was lower for South Asians (123 mm Hg) and higher for Black Caribbean (156 mm Hg) and Black African (165 mm Hg). Furthermore, hypertension defined by ethnicity-specific thresholds was a stronger predictor and resulted in a larger PAF for composite outcomes in South Asians (21.5% [95% CI, 2.4,36.9] vs. 11.3% [95% CI, 2.6,19.1]) and Black Africans (7.1% [95% CI, 0.2,14.0] vs. 5.7 [95% CI, -16.2,23.5]) compared to hypertension defined by guideline-recommended thresholds.

Conclusions
Guideline-recommended blood pressure thresholds may overestimate risks for the Black population and underestimate risks for South Asians. Using ethnicity-specific SBP thresholds may improve risk estimation and optimize hypertension management toward the goal of eliminating ethnic disparities in cardiorenal complications.
A systematic analysis of deep learning in genomics and histopathology for precision oncology
Authors: Unger Michaela , Kather Jakob Nikolas 
Published: February 2024

Abstract
Background
Digitized histopathological tissue slides and genomics profiling data are available for many patients with solid tumors. In the last 5 years, Deep Learning (DL) has been broadly used to extract clinically actionable information and biological knowledge from pathology slides and genomic data in cancer. In addition, a number of recent studies have introduced multimodal DL models designed to simultaneously process both images from pathology slides and genomic data as inputs. By comparing patterns from one data modality with those in another, multimodal DL models are capable of achieving higher performance compared to their unimodal counterparts. However, the application of these methodologies across various tumor entities and clinical scenarios lacks consistency.

Methods
Here, we present a systematic survey of the academic literature from 2010 to November 2023, aiming to quantify the application of DL for pathology, genomics, and the combined use of both data types. After filtering 3048 publications, our search identified 534 relevant articles which then were evaluated by basic (diagnosis, grading, subtyping) and advanced (mutation, drug response and survival prediction) application types, publication year and addressed cancer tissue.

Results
Our analysis reveals a predominant application of DL in pathology compared to genomics. However, there is a notable surge in DL incorporation within both domains. Furthermore, while DL applied to pathology primarily targets the identification of histology-specific patterns in individual tissues, DL in genomics is more commonly used in a pan-cancer context. Multimodal DL, on the contrary, remains a niche topic, evidenced by a limited number of publications, primarily focusing on prognosis predictions.

Conclusion
In summary, our quantitative analysis indicates that DL not only has a well-established role in histopathology but is also being successfully integrated into both genomic and multimodal applications. In addition, there is considerable potential in multimodal DL for harnessing further advanced tasks, such as predicting drug response. Nevertheless, this review also underlines the need for further research to bridge the existing gaps in these fields.
HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing
Authors: Zhang Qin , Yan Liming , Lu Ye , Liu Xiaodong , Yin Yan , Wang Qiuyue , Gu Xiu , Zhou Xiaoming 
Published: February 2024

Abstract
Background
Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD.

Methods
Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603.

Results
HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-β1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-β1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-β1 induced cell migration.

Conclusions
These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-β1/Smad2/3 signalling pathway.
In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system
Authors: Mercier Clément , Pourchez Jérémie , Leclerc Lara , Forest Valérie 
Published: February 2024

Abstract
Background
Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface.

Methods
Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure.

Results
PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm².

Conclusion
Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid.
The ethical foundations of patient-centered care in aesthetic medicine
Authors: da Prato Editta Buttura , Cartier Hugues , Margara Andrea , Molina Beatriz , Tateo Antonello , Grimolizzi Franco , Spagnolo Antonio Gioacchino 
Published: February 2024

AbstractThis article addresses some critical aspects of the relationship between aesthetic medicine (AM) and ethics and proposes a possible deontological ethical line to pursue based on current practices. The role of AM has always been controversial and suffers from unclear practical and moral boundaries, even within academic settings, since it aims to improve the appearance of individuals, not to cure a disease. Today, it is essential and pertinent to discuss these issues, as AM specialists are dealing with a growing and increasingly demanding patient population that has undergone profound evolution in recent years. Current challenges within the field of AM include a lack of global uniformity concerning the education of AM specialists, an increasing number of physicians practicing AM with diverse training backgrounds, the spread of AM being practiced outside of medical practice or hospital settings, and the influence of social media where the success is modelled and dictated by the identification of a youthful appearance). By the field of action enriched by technologies that aim not only at enhancement per se but also at the preservation and regeneration of tissues, it is necessary to establish an active multidisciplinary discussion on the definition of shared ethical limits. This discussion would allow AM to fully reclaim its identity as a specialty that aims to improve patient well-being whilst maintaining respect for patient aesthetic harmony, the expertise of specialists who practice AM, the essential role of safety, and awareness of the importance of a confidential doctor−patient relationship.