bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of dual IQOS and cigarette smoke exposure on airway epithelial cells: implications for lung health and respiratory disease pathogenesis
Authors: Saha Pritam , Jain Siddhi , Mukherjee Ipsita , Panda Samir R. , Zeki Amir A. , Naidu V.G.M. , Sharma Pawan 
Published: February 2023

BackgroundCigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone.MethodsHuman airway epithelial cells (BEAS-2B) were exposed to either CS, IQOS or their dual combination (CS+IQOS) at concentrations of 0.1%, 1.0%, 2.5% and 5.0%. Cytotoxicity, oxidative stress, mitochondrial homeostasis, mitophagy and effects on epithelial–mesenchymal transition (EMT) signalling were assessed.ResultsBoth CS and IQOS alone significantly induced loss of cell viability in a concentration-dependent manner which was further enhanced by dual exposure compared with IQOS alone (p<0.01). Dual exposure significantly increased oxidative stress and perturbed mitochondrial homeostasis when compared with CS or IQOS alone (p<0.05). Additionally, dual exposure induced EMT signalling as shown by increased mesenchymal (α-smooth muscle actin and N-cadherin) and decreased epithelial (E-cadherin) markers when compared with CS or IQOS alone (p<0.05).ConclusionCollectively, our study demonstrates that dual CS+IQOS exposure enhances pathogenic signalling mediated by oxidative stress and mitochondrial dysfunction leading to EMT activation, which is an important regulator of small airway fibrosis in obstructive lung diseases.
Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review
Authors: Dumbuya John Sieh , Li Siqi , Liang Lili , Zeng Qiyi 
Published: February 2023

AbstractSepsis-associated encephalopathy (SAE) is one of the most common types of organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae, its mortality in patients diagnosed with sepsis, progressing to SAE, is 9% to 76%. The pathophysiology of SAE is still unknown, but its mechanisms are well elaborated, including oxidative stress, increased cytokines and proinflammatory factors levels, disturbances in the cerebral circulation, changes in blood–brain barrier permeability, injury to the brain’s vascular endothelium, altered levels of neurotransmitters, changes in amino acid levels, dysfunction of cerebral microvascular cells, mitochondria dysfunction, activation of microglia and astrocytes, and neuronal death. The diagnosis of SAE involves excluding direct CNS infection or other types of encephalopathies, which might hinder its early detection and appropriate implementation of management protocols, especially in paediatric patients where only a few cases have been reported in the literature. The most commonly applied diagnostic tools include electroencephalography, neurological imaging, and biomarker detection. SAE treatment mainly focuses on managing underlying conditions and using antibiotics and supportive therapy. In contrast, sedative medication is used judiciously to treat those showing features such as agitation. The most widely used medication is dexmedetomidine which is neuroprotective by inhibiting neuronal apoptosis and reducing a sepsis-associated inflammatory response, resulting in improved short-term mortality and shorter time on a ventilator. Other agents, such as dexamethasone, melatonin, and magnesium, are also being explored in vivo and ex vivo with encouraging results. Managing modifiable factors associated with SAE is crucial in improving generalised neurological outcomes. From those mentioned above, there are still only a few experimentation models of paediatric SAE and its treatment strategies. Extrapolation of adult SAE models is challenging because of the evolving brain and technical complexity of the model being investigated. Here, we reviewed the current understanding of paediatric SAE, its pathophysiological mechanisms, diagnostic methods, therapeutic interventions, and potential emerging neuroprotective agents.
A study of hydrogen plasma-induced charging effect in EUV lithography systems
Authors: Huang Yao-Hung , Lin Chrong Jung , King Ya-Chin 
Published: February 2023

AbstractIn the extreme ultraviolet lithography system, EUV-induced hydrogen plasma charging effect is observed by in situ embedded micro-detector array. The 4k-pixel on-wafer array can detect and store the distributions of H2 plasma in each in-pixel floating gate for non-destructive off-line read. The local uniformity of H2 plasma intensity extracted by the threshold voltages on an array and its distributions across a wafer by the average bit cell current of MDAs provide insights into the detailed conditions inside advanced EUV lithography chambers.
A 3D human co-culture to model neuron-astrocyte interactions in tauopathies
Authors: Batenburg Kevin L. , Sestito Claudia , Cornelissen-Steijger Paulien , van Weering Jan R. T. , Price Leo S. , Heine Vivi M. , Scheper Wiep 
Published: February 2023

Abstract
Background
Intraneuronal tau aggregation is the major pathological hallmark of neurodegenerative tauopathies. It is now generally acknowledged that tau aggregation also affects astrocytes in a cell non-autonomous manner. However, mechanisms involved are unclear, partly because of the lack of models that reflect the situation in the human tauopathy brain. To accurately model neuron-astrocyte interaction in tauopathies, there is a need for a model that contains both human neurons and human astrocytes, intraneuronal tau pathology and mimics the three-dimensional architecture of the brain.

Results
Here we established a novel 100–200 µm thick 3D human neuron/astrocyte co-culture model of tau pathology, comprising homogenous populations of hiPSC-derived neurons and primary human astrocytes in microwell format. Using confocal, electron and live microscopy, we validate the procedures by showing that neurons in the 3D co-culture form pre- and postsynapses and display spontaneous calcium transients within 4 weeks. Astrocytes in the 3D co-culture display bipolar and stellate morphologies with extensive processes that ensheath neuronal somas, spatially align with axons and dendrites and can be found perisynaptically. The complex morphology of astrocytes and the interaction with neurons in the 3D co-culture mirrors that in the human brain, indicating the model’s potential to study physiological and pathological neuron-astrocyte interaction in vitro. Finally, we successfully implemented a methodology to introduce seed-independent intraneuronal tau aggregation in the 3D co-culture, enabling study of neuron-astrocyte interaction in early tau pathogenesis.

Conclusions
Altogether, these data provide proof-of-concept for the utility of this rapid, miniaturized, and standardized 3D model for cell type-specific manipulations, such as the intraneuronal pathology that is associated with neurodegenerative disorders.
Targeted magnetochemotherapy modified by 5-Fu-loaded thermally on/off switching nanoheaters for the eradication of CT26 murine colon cancer by inducing apoptotic and autophagic cell death
Authors: Shirvalilou Sakine , Khoee Sepideh , Khoei Samideh , Karimi Mohammad Reza , Sadri Elaheh , Shirvaliloo Milad 
Published: February 2023

AbstractDespite significant breakthroughs in diagnosis and treatment of colorectal cancer (CRC), the extent of morbidity and mortality secondary to CRC is still concerning. In this study, we evaluated the efficacy of our new tumor-selective nanoplatforms at induction of apoptosis and autophagy, which was tested using active 5-fluorouracil (5-Fu)-based targeting of tumor cells in a BALB/c murine model of CRC combined with magnetic thermal therapy. Nanoparticles were synthesized and characterized by zeta sizer, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cytotoxicity and tissue uptake of 5-Fu-loaded folic acid (Fa)-modified magnetic nanoparticles (5-Fu/MNPs-Fa) was assessed using MTT, ICP-OES, and HPLC. The rate of apoptosis and autophagy, as two major indicators of antitumor activity, was measured based on protein expression of Bax, Bcl2, Caspase 3, mTOR, P-mTOR, Beclin-1, and LC3B in CT-26 murine CRC, along with tumor volume and survival time. The spherical 5-Fu/MNPs-Fa exhibited sustained thermal on/off switching drug release and higher therapeutic index compared to free 5-Fu. Our de novo synthetized magnetic nanoheaters successfully delivered the therapeutic agent to the tumor site, enhanced the conversion of radio frequency energy to heat in tumor cells, exhibited higher antitumor efficiency based on Bax/Bcl2 ratio and overexpression of Beclin-1 and LC3B, increased the survival time, and decreased the tumor volume (P < 0.05). Our findings indicated that magnetochemotherapy (MHC) was substantially more effective than hyperthermia and/or chemotherapy alone. From a translational standpoint, the 5-Fu/MNPs-Fa would be a promising candidate sustained drug targeting system that could improve cancer cell therapy via inducing apoptosis and autophagy.
Graphical Abstract
Adjusted fence height: an improved phenotype for the genetic evaluation of show jumping performance in Warmblood horses
Authors: Chapard Léa , Van Thillo Anna , Meyermans Roel , Gorssen Wim , Buys Nadine , Janssens Steven 
Published: February 2023

Abstract
Background
Show jumping is one of the most popular disciplines in the horse sector, which makes success in show jumping competitions an important breeding goal for many studbooks. Therefore, the genetic evaluation of show jumping performance is of major interest and this is the case for two Belgian Warmblood studbooks: the Belgian Warmblood horse and Zangersheide. In this study, first an improved phenotype for show jumping performance was developed, i.e. adjusted fence height based on a new non-arbitrary method to scale ranking and competition level, which are two major components of success in competitions. Second, we assessed the importance of including a rider effect in genetic models for show jumping performance, this effect being under debate in sport horse breeding. Third, genetic models based on elementary performances and one model based on a summarized performance were compared in terms of model fit, heritabilities and the stability of estimated breeding values to define the most suitable one for the genetic evaluation of show jumping performance.

Results
In this study, more than 600,000 Belgian competition records and almost 81,000 horses were used. Genetic evaluations were developed based on elementary performances (Blom-transformed ranking and adjusted fence height) and on a summarized performance (highest level achieved). Estimated heritabilities of Blom-transformed ranking, adjusted fence height and highest level achieved were 0.09, 0.12 and 0.39, respectively. Including a rider effect improved the models for genetic evaluations. Estimated genetic correlations between the studied models were moderate to high (rg = 0.60–0.99). With the best fit model, the accuracy of the estimated breeding value (EBV) for adjusted fence height reached 0.70 for a larger number of stallions and for stallions that tended to be younger.

Conclusions
We recommend breeders to implement this new phenotype ‘adjusted fence height’ in breeding programs. It is moderately to highly correlated with Blom-transformed ranking and highest level achieved, a proxy for lifetime success, and is available for selection candidates from an early age onwards.
Sperm capacitation and transcripts levels are altered by in vitro THC exposure
Authors: Truong Vivien B. , Davis Ola S. , Gracey Jade , Neal Michael S. , Khokhar Jibran Y. , Favetta Laura A. 
Published: February 2023

Abstract
Background
Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment.

Results
Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p < 0.05) compared to control and vehicle group sperm. Transcriptome analysis revealed that 39 genes were found to be differentially expressed by 0.032µM THC exposure, 196 genes were differentially expressed by 0.32µM THC exposure, and 33 genes were differentially expressed by 3.2µM THC. Secondary analysis reveals pathways involving development, nucleosomes, ribosomes and translation, and cellular metabolism to be significantly enriched.

Conclusion
Phytocannabinoid exposure to sperm may adversely affect sperm function by stimulating premature capacitation. These findings also show for the first time that spermatozoal transcripts may be altered by THC exposure. These results add to previous research demonstrating the molecular effects of cannabinoids on sperm and warrant further research into the effects of cannabis on male fertility.
Oak stands along an elevation gradient have different molecular strategies for regulating bud phenology
Authors: Le Provost Gregoire , Lalanne Céline , Lesur Isabelle , Louvet Jean-Marc , Delzon Sylvain , Kremer Antoine , Labadie Karine , Aury Jean-Marc , Da Silva Corinne , Moritz Thomas , Plomion Christophe 
Published: February 2023

Abstract
Background
Global warming raises serious concerns about the persistence of species and populations locally adapted to their environment, simply because of the shift it produces in their adaptive landscape. For instance, the phenological cycle of tree species may be strongly affected by higher winter temperatures and late frost in spring. Given the variety of ecosystem services they provide, the question of forest tree adaptation has received increasing attention in the scientific community and catalyzed research efforts in ecology, evolutionary biology and functional genomics to study their adaptive capacity to respond to such perturbations.

Results
In the present study, we used an elevation gradient in the Pyrenees Mountains to explore the gene expression network underlying dormancy regulation in natural populations of sessile oak stands sampled along an elevation cline and potentially adapted to different climatic conditions mainly driven by temperature. By performing analyses of gene expression in terminal buds we identified genes displaying significant dormancy, elevation or dormancy-by-elevation interaction effects. Our Results highlighted that low- and high-altitude populations have evolved different molecular strategies for minimizing late frost damage and maximizing the growth period, thereby increasing potentially their respective fitness in these contrasting environmental conditions. More particularly, population from high elevation overexpressed genes involved in the inhibition of cell elongation and delaying flowering time while genes involved in cell division and flowering, enabling buds to flush earlier were identified in population from low elevation.

Conclusion
Our study made it possible to identify key dormancy-by-elevation responsive genes revealing that the stands analyzed in this study have evolved distinct molecular strategies to adapt their bud phenology in response to temperature.
Sporogenesis, gametophyte development and embryogenesis in Glehnia littoralis
Authors: Zhou Chunxia , An Kang , Zhang Xin , Tong Boqiang , Liu Dan , Kong Dongrui , Bian Fuhua 
Published: February 2023

Abstract
Background
Glehnia littoralis is an economic herb with both medicinal and edible uses. It also has important ecological value and special phylogenetic status as it is a monotypic genus species distributing around beach. Little information on its reproductive biology has been reported so far, which has hindered conservation and application of this species. In this study, we observed morphological changes from buds emergence to seeds formation and internal changes during sporogenesis, gametophyte development and embryo and endosperm development of G. littoralis using paraffin-embedded-sectioning and stereo microscope.

Results
The results showed that the stages of internal development events of G. littoralis corresponded to obvious external morphological changes, most of developmental features were consistent with other Apiaceae species. The development of male and female gametophytes was not synchronized in the same flower, however, exhibited temporal overlap. From mid-late April to mid-May, the anther primordial and ovule primordial developed into the trinucleate pollen grain and eight-nuclear embryo sac, respectively. From late-May to mid-July, the zygote developed into mature embryo. In addition, some defects in gynoecium or ovule development and abnormal embryo and endosperm development were found. We induced that the possible causes of abortion in G. littoralis were as follows: nutrient limitation, poor pollination and fertilization, and bad weather.

Conclusions
This study revealed the whole process and morphological characteristics of the development of reproductive organ in G. littoralis, which not only provided important data for the study of systematic and conservation biology, but also provided a theoretical basis for cross breeding.
Physiological, biochemical and molecular responses associated with drought tolerance in grafted grapevine
Authors: Jiao Shuzhen , Zeng Fanwei , Huang Yaping , Zhang Libing , Mao Juan , Chen Baihong 
Published: February 2023

Abstract
Background
Grafting is one of the promising techniques for improving abiotic stress tolerance in horticultural crops, but the underlying regulatory mechanisms of drought on grafted grapevine are largely unexplored.

Results
Herein, we investigated the phenotypic, physiologic, biochemical, and drought related genes change of self-rooted 1103P (1103 Paulsen), SM (Shine Muscat) and grafted SM/1103P (SM shoot/1103P root) under drought stress condition. The results indicated that grafted grapevine effectively alleviated drought damage in grape leaves by higher RWC, water potential and free water content. Drought stress led to the alterations of chlorophyll, carotenoid, photosynthetic parameters and chlorophyll fluorescence in grapevine leaves after drought treatment indicated grafted plants improved the photosystem response to drought stress. Moreover, grafted plants under drought stress exhibited higher levels of abscisic acid (ABA), indoleacetic acid (IAA) and soluble protein, but less contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) both in leaves and roots. Drought stress also increased the activities of antioxidant enzymes (SOD, POD and CAT) and activated the transcript expression of VvCu/ZnSOD, VvPOD4 and VvCAT1) in both leaves and roots. Further expression analysis by real-time PCR indicated that the expression levels of ABA-dependent and ABA-independent related genes could be activated in grafted grape after drought treatment.

Conclusions
Taken together, our findings demonstrated that grafting onto 1103P enhanced tolerance against drought stress in grape by improving water content, photosynthesis and antioxidant defense capacity, which provided a valuable information for understanding the mechanisms of drought tolerance regulated by grafting plants.
IMpleMenting Effective infection prevention and control in ReSidential aged carE (IMMERSE): protocol for a multi-level mixed methods implementation study
Authors: Tropea Joanne , Peters Sanne , Francis Jill J. , Bennett Noleen , Fetherstonhaugh Deirdre , Buising Kirsty , Lim Lyn-li , Marshall Caroline , Flynn Madelaine , Murray Michael , Yates Paul , Aboltins Craig , Johnson Douglas , Kwong Jason , Long Karrie , McCahon Judy , Lim Wen K. 
Published: February 2023

Abstract
Background
Older people living in residential aged care facilities are at high risk of acquiring infections such as influenza, gastroenteritis, and more recently COVID-19. These infections are a major cause of morbidity and mortality among this cohort. Quality infection prevention and control practice in residential aged care is therefore imperative. Although appointment of a dedicated infection prevention and control (IPC) lead in every Australian residential aged care facility is now mandated, all people working in this setting have a role to play in IPC. The COVID-19 pandemic revealed inadequacies in IPC in this sector and highlighted the need for interventions to improve implementation of best practice.

Methods
Using mixed methods, this four-phase implementation study will use theory-informed approaches to: (1) assess residential aged care facilities’ readiness for IPC practice change, (2) explore current practice using scenario-based assessments, (3) investigate barriers to best practice IPC, and (4) determine and evaluate feasible and locally tailored solutions to overcome the identified barriers. IPC leads will be upskilled and supported to operationalise the selected solutions. Staff working in residential aged care facilities, residents and their families will be recruited for participation in surveys and semi-structured interviews. Data will be analysed and triangulated at each phase, with findings informing the subsequent phases. Stakeholder groups at each facility and the IMMERSE project’s Reference Group will contribute to the interpretation of findings at each phase of the project.

Discussion
This multi-site study will comprehensively explore infection prevention and control practices in residential aged care. It will inform and support locally appropriate evidence-based strategies for enhancing infection prevention and control practice.