bluuebunny/crossref_metadata_2025_split huggingface dataset:
The “Gateway” hypothesis: evaluation of evidence and alternative explanations
Authors: Selya Arielle 
Published: June 2024

Abstract
Background
Electronic nicotine delivery systems (ENDS) offer a substantial harm reduction opportunity for adults who smoke and are unlikely to quit. However, a major concern about ENDS is their use by non-smoking youth, and particularly whether ENDS are acting as a “gateway” that leads youth to later start smoking cigarettes. However, evidence for the gateway hypothesis can be interpreted in alternative ways, e.g. that youth who have certain characteristics were already predisposed to use both ENDS and cigarettes (“common liability” explanation).

Aims
This commentary provides an evaluation of the gateway hypothesis that is accessible by a lay audience. This paper first reviews and evaluates the evidence interpreted as supporting the gateway hypothesis. Important alternative explanations (i.e., common liability) are discussed, as are different types of evidence (i.e., population-level trends) that can help differentiate between these competing explanations.

Overview
Evidence for the gateway hypothesis is based on the finding that youth who use ENDS are more likely to also smoke cigarettes. However, this evidence suffers from an important flaw: these studies fail to fully account for some youths’ pre-existing tendency to use products containing nicotine, and inappropriately interpret the results as ENDS use causing some youth to smoke. Common liability studies suggest that ENDS use does not, in and of itself, directly cause youth to later smoke cigarettes, beyond their pre-existing tendency to use products containing nicotine. Population-level trends show that youth cigarette smoking declined faster after ENDS use became common, which contradicts the central prediction of the gateway hypothesis (i.e. that youth smoking would be more common following ENDS uptake, than otherwise be expected).

Conclusion
Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking.
Connecting the dots: the role of fatigue in female infertility
Authors: Li Wenzhu , Huang Xiaoyan , Wei Yiqiu , Yin Tailang , Diao Lianghui 
Published: June 2024

AbstractFatigue, an increasingly acknowledged symptom in various chronic diseases, has garnered heightened attention, during the medical era of bio-psycho-social model. Its persistence not only significantly compromises an individual’s quality of life but also correlates with chronic organ damage. Surprisingly, the intricate relationship between fatigue and female reproductive health, specifically infertility, remains largely unexplored. Our exploration into the existing body of evidence establishes a compelling link between fatigue with uterine and ovarian diseases, as well as conditions associated with infertility, such as rheumatism. This observation suggests a potentially pivotal role of fatigue in influencing overall female fertility. Furthermore, we propose a hypothetical mechanism elucidating the impact of fatigue on infertility from multiple perspectives, postulating that neuroendocrine, neurotransmitter, inflammatory immune, and mitochondrial dysfunction resulting from fatigue and its co-factors may further contribute to endocrine disorders, menstrual irregularities, and sexual dysfunction, ultimately leading to infertility. In addition to providing this comprehensive theoretical framework, we summarize anti-fatigue strategies and accentuate current knowledge gaps. By doing so, our aim is to offer novel insights, stimulate further research, and advance our understanding of the crucial interplay between fatigue and female reproductive health.
The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia
Authors: Zheng Renren , Wei Wei , Liu Suotian , Zeng Dachuan , Yang Zesong , Tang Jie , Tan Jinfeng , Huang Zhenglan , Gao Miao 
Published: June 2024

Abstract
Background
Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain.

Methods
The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining.

Results
We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice.

Conclusions
These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.
An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression
Authors: Zhang Junyou , Wang Qilin , Qi Sihan , Duan Yingying , Liu Zhaoshuo , Liu Jiaxin , Zhang Ziyi , Li Chunyan 
Published: June 2024

Abstract
Background
Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma.

Methods
Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3.

Results
An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4.

Conclusions
Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.
POEMS syndrome with undetectable M-protein: a case report and literature review
Authors: Xue Han-Yue , Zhou Lin , Yuan Qin-Zhao , Zhang Yang , Hao Yi-Qun , Chen Shao-Wei , Wang Hong-Kun , Wei Fang 
Published: June 2024

Abstract
Background
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria.

Case presentation
We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone.

Conclusions
Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.
Endovascular repair for thoracic aortic pseudoaneurysm induced by pedicle screw implantation: a case report with 8 years follow-up
Authors: Zhou Shufen , Han Hui , Zhang Yidan , Shu Chang , Luo Mingyao 
Published: June 2024

Abstract
Background
Pedicle screw instrument surgeries can result in the development of aortic pseudoaneurysm, which is a rare yet potentially severe complication; therefore, the purpose of this work is to describe the case of pseudoaneurysm of the thoracic aorta caused by the severe migration of a pedicle screw after surgery.

Case presentation
We herein report a patient who underwent endovascular repair for the pseudoaneurysm of the descending thoracic aorta following thoracic vertebral fixation surgery. A 28–80 mm covered stent was initially inserted through the right femoral artery, and intraoperative aortography revealed a minor extravasation of contrast material. Subsequently, an additional 28–140 mm covered stent was implanted. The patient recovered well during the 8-year follow-up period.

Conclusions
Vascular complications resulting from spinal surgery are severe and rare, necessitating early diagnosis and intervention.
Transcriptome analysis of Kunming mice responses to the bite of Xenopsylla cheopis
Authors: Lun Xinchang , Shi Yuan , Wang Yiguan , Zhao Ning , Liu Qiyong , Meng Fengxia , Song Xiuping , Wang Jun , Lu Liang 
Published: June 2024

Abstract
Background
Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites.

Methods
RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Results
A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable.

Conclusions
Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites.

Graphical Abstract
Keeping up with the pathogens: improved antimicrobial resistance detection and prediction from Pseudomonas aeruginosa genomes
Authors: Madden Danielle E. , Baird Timothy , Bell Scott C. , McCarthy Kate L. , Price Erin P. , Sarovich Derek S. 
Published: June 2024

Abstract
Background
Antimicrobial resistance (AMR) is an intensifying threat that requires urgent mitigation to avoid a post-antibiotic era. Pseudomonas aeruginosa represents one of the greatest AMR concerns due to increasing multi- and pan-drug resistance rates. Shotgun sequencing is gaining traction for in silico AMR profiling due to its unambiguity and transferability; however, accurate and comprehensive AMR prediction from P. aeruginosa genomes remains an unsolved problem.

Methods
We first curated the most comprehensive database yet of known P. aeruginosa AMR variants. Next, we performed comparative genomics and microbial genome-wide association study analysis across a Global isolate Dataset (n = 1877) with paired antimicrobial phenotype and genomic data to identify novel AMR variants. Finally, the performance of our P. aeruginosa AMR database, implemented in our AMR detection and prediction tool, ARDaP, was compared with three previously published in silico AMR gene detection or phenotype prediction tools—abritAMR, AMRFinderPlus, ResFinder—across both the Global Dataset and an analysis-naïve Validation Dataset (n = 102).

Results
Our AMR database comprises 3639 mobile AMR genes and 728 chromosomal variants, including 75 previously unreported chromosomal AMR variants, 10 variants associated with unusual antimicrobial susceptibility, and 281 chromosomal variants that we show are unlikely to confer AMR. Our pipeline achieved a genotype-phenotype balanced accuracy (bACC) of 85% and 81% across 10 clinically relevant antibiotics when tested against the Global and Validation Datasets, respectively, vs. just 56% and 54% with abritAMR, 58% and 54% with AMRFinderPlus, and 60% and 53% with ResFinder. ARDaP’s superior performance was predominantly due to the inclusion of chromosomal AMR variants, which are generally not identified with most AMR identification tools.

Conclusions
Our ARDaP software and associated AMR variant database provides an accurate tool for predicting AMR phenotypes in P. aeruginosa, far surpassing the performance of current tools. Implementation of ARDaP for routine AMR prediction from P. aeruginosa genomes and metagenomes will improve AMR identification, addressing a critical facet in combatting this treatment-refractory pathogen. However, knowledge gaps remain in our understanding of the P. aeruginosa resistome, particularly the basis of colistin AMR.
Acyclovir extravasation in a newborn: a case report
Authors: Shamel Shirin , Zarkesh Mohammad Reza 
Published: June 2024

Abstract
Objective
Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation.

Case report
A female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women’s Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase.

Conclusion
Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.
An end-to-end method for predicting compound-protein interactions based on simplified homogeneous graph convolutional network and pre-trained language model
Authors: Zhang Yufang , Li Jiayi , Lin Shenggeng , Zhao Jianwei , Xiong Yi , Wei Dong-Qing 
Published: June 2024

AbstractIdentification of interactions between chemical compounds and proteins is crucial for various applications, including drug discovery, target identification, network pharmacology, and elucidation of protein functions. Deep neural network-based approaches are becoming increasingly popular in efficiently identifying compound-protein interactions with high-throughput capabilities, narrowing down the scope of candidates for traditional labor-intensive, time-consuming and expensive experimental techniques. In this study, we proposed an end-to-end approach termed SPVec-SGCN-CPI, which utilized simplified graph convolutional network (SGCN) model with low-dimensional and continuous features generated from our previously developed model SPVec and graph topology information to predict compound-protein interactions. The SGCN technique, dividing the local neighborhood aggregation and nonlinearity layer-wise propagation steps, effectively aggregates K-order neighbor information while avoiding neighbor explosion and expediting training. The performance of the SPVec-SGCN-CPI method was assessed across three datasets and compared against four machine learning- and deep learning-based methods, as well as six state-of-the-art methods. Experimental results revealed that SPVec-SGCN-CPI outperformed all these competing methods, particularly excelling in unbalanced data scenarios. By propagating node features and topological information to the feature space, SPVec-SGCN-CPI effectively incorporates interactions between compounds and proteins, enabling the fusion of heterogeneity. Furthermore, our method scored all unlabeled data in ChEMBL, confirming the top five ranked compound-protein interactions through molecular docking and existing evidence. These findings suggest that our model can reliably uncover compound-protein interactions within unlabeled compound-protein pairs, carrying substantial implications for drug re-profiling and discovery. In summary, SPVec-SGCN demonstrates its efficacy in accurately predicting compound-protein interactions, showcasing potential to enhance target identification and streamline drug discovery processes.Scientific contributionsThe methodology presented in this work not only enables the comparatively accurate prediction of compound-protein interactions but also, for the first time, take sample imbalance which is very common in real world and computation efficiency into consideration simultaneously, accelerating the target identification and drug discovery process.
Role of NLRP3 inflammasome in central nervous system diseases
Authors: Zhang Lu , Tang Yufen , Huang Peng , Luo Senlin , She Zhou , Peng Hong , Chen Yuqiong , Luo Jinwen , Duan Wangxin , Xiong Jie , Liu Lingjuan , Liu Liqun 
Published: June 2024

AbstractThe central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.
An expanded analysis of local fractional integral inequalities via generalized $(s,P)$-convexity
Authors: Li Hong , Lakhdari Abdelghani , Jarad Fahd , Xu Hongyan , Meftah Badreddine 
Published: June 2024

AbstractThis research aims to scrutinize specific parametrized integral inequalities linked to 1, 2, 3, and 4-point Newton-Cotes rules applicable to local fractional differentiable generalized$(s,P)$(s,P)-convex functions. To accomplish this objective, we introduce a novel integral identity and deduce multiple integral inequalities tailored to mappings within the aforementioned function class. Furthermore, we present an illustrative example featuring graphical representations and potential practical applications.