bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated exposure to the synthetic cannabinoid JWH-018 induces enduring immune and glial alterations in the rat brain
Authors: Pintori Nicholas , Mostallino Rafaela , Orrù Valeria , Piras Maria Grazia , Castelli M. Paola , Luca Maria Antonietta 
Published: October 2023

Abstract
Background
The misuse of synthetic cannabinoid receptor agonists (SCRAs) poses major psychiatric risks. We previously showed that repeated exposure to the prototypical SCRA JWH-018 induces alterations in dopamine (DA) transmission, abnormalities in the emotional state, and glial cell activation in the mesocorticolimbic DA circuits of rats. Despite growing evidence suggesting the relationship between drugs of abuse and neuroinflammation, little is known about the impact of SCRA on the neuroimmune system. Here, we investigated whether repeated JWH-018 exposure altered neuroimmune signaling, which could be correlated with previously reported central effects.
Methods
Adult male Sprague‒Dawley rats were exposed to JWH-018 (0.25 mg/kg, i.p.) for fourteen consecutive days, and the expression of cytokines, chemokines, and growth factors was measured seven days after treatment discontinuation in the striatum, cortex, and hippocampus. Moreover, microglial (ionized calcium binding adaptor molecule 1, IBA-1) and astrocyte (glial fibrillary acidic protein, GFAP) activation markers were evaluated in the caudate-putamen (CPu).
Results
Repeated JWH-018 exposure induces a perturbation of neuroimmune signaling specifically in the striatum, as shown by increased levels of cytokines [interleukins (IL) -2, -4, -12p70, -13, interferon (IFN) γ], chemokines [macrophage inflammatory protein (MIP) -1α, -3α], and growth factors [macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF)], together with increased IBA-1 and GFAP expression in the CPu.
Conclusions
JWH-018 exposure induces enduring brain region-specific immune alterations, which may contribute to the behavioral and neurochemical dysregulations in striatal areas that play a role in reward and reward-related processes, such as addictive behaviors.
Detection of low expression of molecular subtype HER2 in breast cancer using ultrasound-based radiomics
Authors: Zhang Xueling , Wu Shaoyou , Zu Xiao , Li Xiaojing , Zhang Qing , Ren Yongzhen , Tong Shan , Li Hongbo 
Published: October 2023

Abstract
Purpose: HER2-low expression breast cancer (BC) accounts for nearly half of all breast cancers which may benefit from new antibody-drug conjugates targeted treatments. HER2-low BC is gradually being recognized as a distinct subtype. Therefore, we aimed to use ultrasound-based radiomics（USR）to develop an efficient evaluation approach of HER2-low status.
Methods: 222 patients with a histologically diagnosis of BC were retrospectively analyzed and randomly divided into training and test cohort. Radiomics features were extracted from the preoperative ultrasound images, followed by Lasso regression for dimension reduction.Based on the selected features, the optimal machine learning classifier was selected to construct a USR model to predict HER2-low expression. Multivariable logistic regression was used to identify independent clinical risk factors.Finally, a clinical-USR model incorporating the radiomics features and the clinical risk factors was constructed. Model performance was assessed using receiver operating characteristic curve and decision curve analysis.
Results: The USR model and clinical-USR model had good predictive ability in the training cohort ( AUC 0.91; 0.86 , respectively) and test cohort ( AUC 0.83; 0.78 , respectively).Both of them outperformed the clinical model (p < 0.05, DeLong test).Decision curve analysis confirmed that the model had clinical utility.
Conclusion: The machine learning model based on ultrasound images had high prediction value for HER2-low BC.
Comparison of Cas12a and Cas9- mediated mutagenesis in tomato cells
Authors: Slaman Ellen , Kottenhagen Lisanne , de Martines William , Angenent Gerco C. , de Maagd Ruud A. 
Published: October 2023

Abstract
Cas12a is a promising addition to the CRISPR toolbox, offering versatility due to its TTTV-protospacer adjacent motif (PAM) and the fact that it induces double-stranded breaks (DSBs) with single-stranded overhangs. We characterized Cas12a-mediated genome editing in tomato using high-throughput amplicon sequencing on protoplasts. Of the three tested variants, Lachnospiraceae (Lb) Cas12a was the most efficient. Additionally, we developed an easy and effective Golden-Gate-based system for crRNA cloning. We compared LbCas12a to SpCas9 by investigating on-target efficacy and specificity at 35 overlapping target sites and 57 (LbCas12a) or 100 (SpCas9) predicted off-target sites. We found LbCas12a an efficient, robust addition to SpCas9, with similar overall though target-dependent efficiencies. LbCas12a induced more and larger deletions than SpCas9, which can be advantageous for specific genome editing applications. Off-target activity for LbCas12a was found at 10 out of 57 investigated sites. One or two mismatches were present distal from the PAM in all cases. We conclude that Cas12a-mediated genome editing is generally precise as long as such off-target sites can be avoided. In conclusion, we have determined the mutation pattern and efficacy of Cas12a-mediated CRISPR mutagenesis in tomato and developed a cloning system for the routine application of Cas12a for tomato genome editing.
Fractured Guidewire in Calcified Chronic Total Occlusion: Is Rotational Atherectomy Contraindicated?
Authors: Hong Xu-Lin , Zhu Jun-hui , Fu Guo-Sheng , Zhang Wen-Bin 
Published: October 2023

Abstract
Guidewires fracture may occur in severely calcified coronary chronic total occlusion (CTO). Rotational atherectomy (RA) is safe if the broken guidewire is firmly entrapped in the lesion. We present a case of using RA to open the calcified CTO and meanwhile grind the entrapped wire.
Association between systemic immune-inflammation index and insulin resistance and mortality: Evidence from NHANES 2011–2016
Authors: Deng xiaoqi , Liu Dichuan , Li Miao , He Jie , Fu Yufan 
Published: October 2023

Abstract
The role of inflammation in disease promotion is significant, yet the precise association between a newly identified inflammatory biomarker and insulin resistance (IR) and mortality remains uncertain. We aim to explore the potential correlation between systemic immune-inflammation index (SII) and these factors. We used data from 2011–2016 of National Health and Nutrition Examination Surve, and multivariate logistic regression and restricted cubic spline were employed. Subgroup and interaction analysis were conducted to recognize the consistency of the results. The association between SII and mortality was described by survival analysis. 6734 participants were enrolled, of whom 49.3% (3318) exhibited IR and 7.02% experienced mortality. Multivariate logistic regression revealed that individuals in the highest quartile (Q4) of SII had a significantly increased risk of IR compared to those in the lowest quartile (Q1). We then identified a linear association between SII and IR with an inflection point of 407, but may be influenced by gender. Similarly, compared to Q1, people whose SII at Q4 showed a higher all-cause and cardiovascular mortality. It showed a significant association between SII and both all-cause and cardiovascular mortality, but the results need to be interpreted with caution.
Causal effects between negative moods and cardiovascular diseases: a Mendelian randomization study
Authors: Yu Shuyang , Chen Songzan , Tao Tingting , Liu Xianglan , Fu Guosheng , Shen Zhida , Huang He 
Published: October 2023

Abstract
Background.
Previous observational studies have found that negative moods are associated with cardiovascular diseases (CVDs). However, their causal association remains unclear. We aim to evaluate the causal associations of genetically determined negative moods with CVDs including coronary artery disease (CAD), myocardial infarction (MI), stroke, and subtypes of stroke using Mendelian randomization study.
Methods.
Summary statistics for negative moods were extracted from the UK Biobank and a large genome-wide association study including 366,726 subjects. Six negative moods, tiredness, depressed mood, tenseness, unenthusiasm, anxiety, and anger, were included. Genetic associations with CVDs were extracted from the CardiogramplusC4D consortium and MEGASTROKE consortium: CAD (n = 184,305), MI (n = 171,875), stroke (n = 446,696), and subtypes of stroke. Causal effects were inferred between related traits by univariable, reverse and multivariable Mendelian randomization (MR) method.
Results.
Univariable MR analyses found that tiredness was genetically correlated with CAD (OR 1.91; 95% CI 1.23–2.97; P = 0.004) and MI (OR 2.12; 95% CI 1.29–3.47; P = 0.003). Besides, we found that the genetic liability to depressed mood was associated with higher risks of CAD (OR 2.97; 95%CI: 1.25–7.09; P = 0.014) and MI (OR 2.81; 95%CI: 1.06–7.42; P = 0.037). No causal relationship between negative moods and stroke was found. Bidirectional MR analysis failed to find any significant causal effect of CVDs on the risk of negative moods. Multivariable MR analyses revealed compelling evidence of tiredness on the risk of CAD and MI. However, after adjusting for other cardiovascular risk traits, the causal relationship between depressed mood and CVDs disappeared.
Conclusions.
This MR study found that genetic predisposition to tiredness may have a causal effect on the risk of CAD and MI. Early diagnosis and prevention of tiredness may be helpful in the management of CAD and MI.
Dihydroartemisinin inhibits EMT progression in medullary thyroid carcinoma through Hippo signaling pathway regulated by IL-6
Authors: Li Ruicong , Zhang Xinyu , Ge Yanan , Zhao Zhen , Feng Liangliang , Li Xiaoming 
Published: October 2023

Abstract
Dihydroartemisinin, an artemisinin derivative, has the ability to influence both the inflammatory response and the growth of certain malignancies. In this study, we used the CCK-8 and Transwell assays to show that DHA had a suppressive effect on the growth, migration, and invasion of medullary thyroid cancer cells. Furthermore, we used Elisa, Western blot, and immunofluorescence assays to confirm the expression of transcriptional co-activators YAP/TAZ downstream of the Hippo pathway, as well as changes in the expression of EMT process markers E-cadherin and N-cadherin.The results demonstrated that DHA effectively reduced the expression of IL-6 in medullary thyroid carcinoma cells and hindered their EMT process by regulating the Hippo pathway. This regulation was achieved through the promotion of YAP phosphorylation and the inhibition of YAP/TAZ protein expression.Following additional activation of the Hippo pathway with GA-017, the inhibitory effect of DHA on IL-6 was alleviated. Subsequently, the Hippo pathway was activated, leading to an increase in the expression of E-cadherin, a marker associated with the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that DHA can regulate the Hippo pathway by inhibiting IL-6 secretion, leading to the inhibition of the EMT process in medullary thyroid carcinoma. These findings provide a theoretical foundation for further exploring the anticancer mechanism of DHA. Additionally, this study offers valuable insights for the potential clinical application of DHA as a combination drug.
Changes of inflammatory mediator’s expression in the rat medial prefrontal cortex (mPFC) after minocycline treatment in lipopolysaccharide induced neuroinflammation rat model
Authors: Qaid Entesar Yaseen Abdo , Abdullah Zuraidah , Zakaria Rahimah , Long Idris 
Published: October 2023

Abstract
Introduction:
Minocycline has been showed can ameliorates neuroinflammation that was encountered in many neurodegenerative diseases. This study aims to investigate the expression of inflammatory mediators in the rat medial prefrontal cortex (mPFC) after minocycline treatment in lipopolysaccharide (LPS) induced neuroinflammation rat model.
Methods
Adult male Sprague Dawley (SD) rats (N = 50) were divided into 5 groups: 1) control, 2) LPS (5 mg/kg), 3) LPS + minocycline (25 mg/kg), 4) LPS + minocycline (50 mg/kg) and 5) LPS + memantine (10 mg/kg). Intraperitoneal minocycline and memantine were given daily for 14 days, while LPS injection was given once on 5th day. Western blot and immunohistochemistry were used to assess density and expression of TLR-4, nuclear factor kappa-B (NF-kB), tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in the medial prefrontal cortex (mPFC) of rats.
Results
Findings displayed that minocycline significantly decreased expression and density of TLR-4, NF-kB, TNF-α and COX-2 proteins that were comparable to memantine in mPFC of SD rat injected with single intraperitoneal LPS. Interestingly, the anti-inflammatory effects of minocycline 50 mg/kg were significantly more than minocycline 25 mg/kg.
Conclusion
This study suggested that minocycline can modulated LPS-induced neuroinflammation in dose-dependent manner in the mPFC area. Thus, it is suggested that minocycline can be used as potential preventive-therapeutic drug for neuroinflammatory diseases such as depression and anxiety.
A dopamine D1-like receptor-specific agonist improves the survival of septic mice while suppressing neuroinflammation
Authors: Tanaka Koichi , Choudhury Mohammed , Kikuchi Satoshi , Umakoshi Kensuke , Miyaue Noriyuki , Takenaga Ayane , Shinabe Rintaro , Mikami Kanta , Matsumoto Hironori , Yano Hajime , Nagai Masahiro , Takeba Jun , Tanaka Junya 
Published: October 2023

Abstract
Background
Sepsis is a leading cause of mortality in intensive-care units worldwide. It is accompanied by dysregulated systemic immune reactions, which lead to multiple organ failure. In addition to the peripheral organs, the brain is often affected by sepsis. Sepsis-induced brain dysfunction is termed sepsis-associated encephalopathy (SAE) and displays severity ranging from mild delirium to deep coma. SAE is known to increase the mortality of sepsis cases.
Methods
A murine sepsis model was prepared using the cecum ligation and puncture (CLP) technique. The expression of dopamine (DA) receptors (DRs) was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) was used to decrease intracerebral DA levels. The blood-brain barrier (BBB)-permeable DA D1-like receptor selective agonist SKF-81297 (SKF), the BBB-impermeable D1R agonist fenoldopam, and DA were intraperitoneally administered shortly after CLP. CLP-induced changes in body temperature and mortality were then monitored every 12 h. Systemic and brain inflammation were investigated using flow cytometry, quantitative RT-PCR, and an enzyme-linked immunosorbent assay. SAE-like symptoms were evaluated using behavioral tests and electroencephalogram (EEG)/electromyogram (EMG) recordings.
Results
D1-like receptors were significantly expressed in the brain but not in the lung. MPTP aggravated mortality in septic mice. SKF, but not fenoldopam, prevented CLP-induced death of septic mice. SKF ameliorated acute lung injury-like pathology and inhibited leukocyte accumulation in the lung and in the brain. SKF suppressed the expression of TNFα and IL-1β in the periphery and brain. The Morris water maze and Y-maze tests revealed that CLP-induced cognitive dysfunction was ameliorated by SKF, and EEG/EMGs showed that SKF increased sleep duration after CLP.
Conclusion
These data suggest that endogenous DA prevents sepsis-induced neuroinflammation through D1-like receptors, and BBB-permeable D1-like receptor agonists can be novel drugs for treating sepsis. Neuroinflammation that causes SAE may be a critical cause of sepsis-induced death.
Distribution of Staphylococcus species and Bacillus species in environment of dairy farm located at sewerage site, river Ravi and urban area, Lahore, Pakistan
Authors: Khan Tanveer Ali , Afzal Hanan , Noreen Amara , Ali Zulfiqar , Mustafa Ghulam 
Published: October 2023

Abstract
Bioaerosol contains many pathogenic species of bacteria. The workers of dairy farms are continuously exposed to the farm environment so they are more prone and susceptible to airborne infections. In the current study, different samples from the dairy farm of three regions viz sewerage site, river Ravi and urban areas were collected. The bacterial load was accessed and also some pathogenic bacteria were isolated. The 16S rRNA gene characterization analysis followed by the phylogenetic tree analysis showed 98–99% similarities with the staphylococcus sciuri, bacillus toyogensis and bacillus pulmis. The overall microbial load was higher in open and sewerage site farms as compared to the open farm of river Ravi and urban area farm. Similar trend was observed in closed farms. The 16s rRNA gene characterization and phylogenetic analysis not only help to identify species level identification but also genetic relatedness with other species. So, farm’s worker’s health is more at risk at open and sewerage site farm than river Ravi and urban area farms.
Complex Interplay of Psychiatry Disorders, Fractures, and Osteoporosis: A Mendelian Randomization Study
Authors: wu xueqiang , Li zefang , li hanzheng , bi cong , zhang can , sun yiqing , Yan Zhaojun 
Published: October 2023

Abstract
Background
Neurodevelopmental disorders, such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on psychological, social, and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, considering factors like self-harm and the impact of psychotropic medications.
Methods
Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions.
Results
The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. These results provide a genetic perspective on the complex relationships between neurodevelopmental disorders and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare.
Conclusion
This research sheds new light on the intricate connections between neurodevelopmental disorders and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both psychological and physical well-being. Early diagnosis, pharmacological interventions, and diligent monitoring of bone health are essential components of improved healthcare strategies for individuals with ADHD and ASD.
Seasonal and ecological determinants of wild boar rooting on priority protected grasslands
Authors: Calosi Martina , Gabbrielli Chiara , Lazzeri Lorenzo , Fattorini Niccolò , Cesaretti Gloria , Burrini Lucia , Petrillo Ottavio , Ferretti Francesco 
Published: October 2023

Abstract
Wild ungulates can influence various trophic levels, regulating carnivore abundance as well as affecting habitat structure. Conservation problems can arise when high ungulate densities threaten species or habitats with conservation concern. Assessing factors influencing the intensity of their impact is important to identify appropriate measures enhancing the conservation of protected habitats. We assessed seasonal and ecological factors influencing wild boar Sus scrofa pressure on EU priority grasslands in three protected areas of central Italy, by modelling the effects of habitat/topography-related variables, as well as wild boar population density, on indices of rooting activity. We seasonally surveyed 136 sampling plots from spring 2019 to spring 2021 to estimate rooting, and we used faecal counts to estimate wild boar densities in summer. Estimates of density and rooting varied from 3.5 to 22.2 individuals/km2 and from 1.5 to 22.2% of rooted ground, respectively. We detected a clear seasonal trend in rooting activity, that peaked in autumn and winter. We also found a positive correlation between spring-summer rooting and summer density, across sites. Rooting intensity was negatively related to the local extent of rock cover and increased with the size of the grassland patch and with the percentage of forest around each plot. These results emphasise the wild boar tendency to exploit feeding sites in ecotonal areas, i.e., at the interface between forest and meadows, which maximises security and ease of finding food resources. Actions aiming at the protection of focal plants in grassland habitats, as well as reducing wild boar densities, are supported.
Myopia Progression during COVID-19 Home Quarantine in Indonesia: A Retrospective Multicenter Cohort Study
Authors: Sitorus Rita S , Caesarya Sesy , Karfiati Feti , Manurung Florence M , Ekowati Liana , Sumual Vera , Loebis Rozalina , Darusman Kianti Raisa , Surasmiati Ni made Ayu , Sayuti Kemala , Aldy Fithria , Wulandari Lely Retno , Rahmah Marlyanti Nur , Estu Dian , Barliana Julie Dewi , Prabaniswara Marcelius Patria , Sutandi Nathania , Widyahening Indah Suci 
Published: October 2023

Abstract
Purpose: To evaluate the impact of home quarantine on myopia progression in Indonesian children during COVID-19 pandemic.
Methods: This multicenter retrospective cohort study included children aged 8-17 years old from 20 hospitals across 9 provinces in Indonesia. Medical records of children diagnosed with myopia and/or astigmatism were obtained and grouped to pre-pandemic (September 2019-March 2020) and pandemic periods (September 2021-May 2022). Patient demographics and spherical equivalents of refraction (SER) were collected. Direct or phone interviews were conducted with questions regarding the child’s screen time, outdoor activity time, break time in between gadget use, and sleep duration.
Results: In total, 607 children were enrolled. There was a significant increase in SER progression (-0.97 ± 1.04 D, p<0.001). SER progression in Java-Bali was higher compared to others (-1.3± 1.18 D vs 0.57± 0.67 D, p<0.001). A total of 262 patients were interviewed. Younger age (OR: 2.52, 95% CI:[1.42-5.03], p = 0.004), female gender (OR: 2.16, 95% CI:[1.18-3.83], p = 0.011), screen time of ≥4 hours daily for leisure activities (OR: 1.95, 95% CI:[1.07-3.54], p = 0.028), ≤1 hour of time spent outdoor daily (OR: 1.89, 95% CI:[1.03-3.47], p = 0.047, and sleep duration of >8 hours (OR: 2.7, 95% CI:[1.46-4.99], p = 0.002) were significantly associated with fast myopia progression.
Conclusion: Myopia progression was accelerated during COVID-19 home quarantine, especially in more urban area. Collaborative efforts should be made to address this current issue.