bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics
Authors: Gordon Jackson M , Phizicky David V , Schärfen Leonard , Brown Courtney L , Arias Escayola Dahyana , Kanyo Jean , Lam TuKiet T , Simon Matthew D , Neugebauer Karla M 
Published: June 2024

Abstract
Polyadenylation controls mRNA biogenesis, nucleo-cytoplasmic export, translation and decay. These processes are interdependent and coordinately regulated by poly(A)-binding proteins (PABPs), yet how PABPs are themselves regulated is not fully understood. Here, we report the discovery that human nuclear PABPN1 is phosphorylated by mitotic kinases at four specific sites during mitosis, a time when nucleoplasm and cytoplasm mix. To understand the functional consequences of phosphorylation, we generated a panel of stable cell lines inducibly over-expressing PABPN1 with point mutations at these sites. Phospho-inhibitory mutations decreased cell proliferation, highlighting the importance of PABPN1 phosphorylation in cycling cells. Dynamic regulation of poly(A) tail length and RNA stability have emerged as important modes of gene regulation. We therefore employed long-read sequencing to determine how PABPN1 phospho-site mutants affected poly(A) tails lengths and TimeLapse-seq to monitor mRNA synthesis and decay. Widespread poly(A) tail lengthening was observed for phospho-inhibitory PABPN1 mutants. In contrast, expression of phospho-mimetic PABPN1 resulted in shorter poly(A) tails with increased non-A nucleotides, in addition to increased transcription and reduced stability of a distinct cohort of mRNAs. Taken together, PABPN1 phosphorylation remodels poly(A) tails and increases mRNA turnover, supporting the model that enhanced transcriptome dynamics reset gene expression programs across the cell cycle.
Alternative splicing of a potato disease resistance gene maintains homeostasis between growth and immunity
Authors: Sun Biying , Huang Jie , Kong Liang , Gao Chuyun , Zhao Fei , Shen Jiayong , Wang Tian , Li Kangping , Wang Luyao , Wang Yuanchao , Halterman Dennis A , Dong Suomeng 
Published: June 2024

Abstract
Plants possess a robust and sophisticated innate immune system against pathogens and must balance growth with rapid pathogen detection and defense. The intracellular receptors with nucleotide-binding leucine-rich repeat (NLR) motifs recognize pathogen-derived effector proteins and thereby trigger the immune response. The expression of genes encoding NLR receptors is precisely controlled in multifaceted ways. The alternative splicing (AS) of introns in response to infection is recurrently observed but poorly understood. Here we report that the potato (Solanum tuberosum) NLR gene RB undergoes AS of its intron, resulting in 2 transcriptional isoforms, which coordinately regulate plant immunity and growth homeostasis. During normal growth, RB predominantly exists as an intron-retained isoform RB_IR, encoding a truncated protein containing only the N-terminus of the NLR. Upon late blight infection, the pathogen induces intron splicing of RB, increasing the abundance of RB_CDS, which encodes a full-length and active R protein. By deploying the RB splicing isoforms fused with a luciferase reporter system, we identified IPI-O1 (also known as Avrblb1), the RB cognate effector, as a facilitator of RB AS. IPI-O1 directly interacts with potato splicing factor StCWC15, resulting in altered localization of StCWC15 from the nucleoplasm to the nucleolus and nuclear speckles. Mutations in IPI-O1 that eliminate StCWC15 binding also disrupt StCWC15 re-localization and RB intron splicing. Thus, our study reveals that StCWC15 serves as a surveillance facilitator that senses the pathogen-secreted effector and regulates the trade-off between RB-mediated plant immunity and growth, expanding our understanding of molecular plant–microbe interactions.
Is unilateral cerebellum sufficient? Insights from new cases of cerebellar agenesis and literature review
Authors: Deng Dingmei , Tao Bo , Yuan Yizhi , Ao Yongsheng , Qiu Lihua 
Published: June 2024

Abstract
The clinical manifestations of adult-acquired cerebellar diseases often surpass those of congenital cerebellar diseases, suggesting the significant role of the cerebellum in the developing brain. Moreover, emerging evidence from structural and functional magnetic resonance imaging indicates that the cerebellum is implicated not only in motor functions but also in non-motor domains such as cognition, emotion, and language. However, delineating the specific extent of cerebellar development required to prevent deficits in either motor or non-motor functions remains challenging. In this study, we present two new cases of unilateral cerebellar agenesis. One individual leads a nearly normal life, while the other exhibits mild cognitive impairment, mild depression, and severe autism, but maintains normal motor function. Van der Heijden et al. (2023) revealed that the brain can compensate for some, but not all, perturbations to the developing cerebellum, including motor deficits and impairments in social behaviors. Therefore, we hypothesize that comparing structural images from our patients and reviewing pertinent literature may elucidate the reasons for the varied clinical manifestations observed in patients with cerebellar agenesis.
Female education ban by the Taliban: A descriptive survey study on suicidal ideation, mental health, and health-related quality of life among girls in Afghanistan
Authors: Mohammadi Abdul Qadim , Neyazi Ahmad , Habibi Diva , Mehmood Qasim , Neyazi Mehrab , Griffiths Mark D 
Published: June 2024

Abstract

Background
Following the Taliban’s resurgence, Afghan girls were probited from attending school and university, likely causing adverse psychological effects. Therefore, the present study investigated depression, suicidal ideation, and quality of life (QoL) among Afghan girls banned from education by the Taliban.

Methods
A survey study assessed depression, suicidal ideation, and QoL among 426 females prohibited from attending secondary schools, high schools, and universities by the Taliban. The study used the CES-D 20 Scale to assess depression, and the WHOQOL-Bref Questionnaire to assess QoL. Associations between variables were tested with chi-square tests, and predictors of QoL were analyzed through multivariate regression analysis.

Results
Among the 426 participants, 87.6% exhibited depression symptoms and 49.8% reported suicidal thoughts. Significant predictors of overall QoL included monthly family income (B = 0.147, P = 0.001), recent others’ behavior toward participants (B = −0.247, P &lt; 0.001), physical illness (B = 0.110, P = 0.011), experiencing a recent traumatic event (B = 0.108, P = 0.015), depression (B = −0.159, P &lt; 0.001) and suicidal ideation (B = −0.187, P &lt; 0.001).

Conclusions
In Taliban-ruled Afghanistan, the results indicated that female students who have been prohibited from studying in classes have a high prevalence of depression and suicidal ideation. Having depression and suicidal ideation significantly predicted decreased quality of life among female students.
3D printing materials and 3D printed surgical devices in oral and maxillofacial surgery: design, workflow and effectiveness
Authors: Wang Xiaoxiao , Mu Min , Yan Jiazhen , Han Bo , Ye Rui , Guo Gang 
Published: June 2024

Abstract
Oral and maxillofacial surgery is a specialized surgical field devoted to diagnosing and managing conditions affecting the oral cavity, jaws, face and related structures. In recent years, the integration of 3D printing technology has revolutionized this field, offering a range of innovative surgical devices such as patient-specific implants, surgical guides, splints, bone models and regenerative scaffolds. In this comprehensive review, we primarily focus on examining the utility of 3D-printed surgical devices in the context of oral and maxillofacial surgery and evaluating their efficiency. Initially, we provide an insightful overview of commonly utilized 3D-printed surgical devices, discussing their innovations and clinical applications. Recognizing the pivotal role of materials, we give consideration to suitable biomaterials and printing technology of each device, while also introducing the emerging fields of regenerative scaffolds and bioprinting. Furthermore, we delve into the transformative impact of 3D-printed surgical devices within specific subdivisions of oral and maxillofacial surgery, placing particular emphasis on their rejuvenating effects in bone reconstruction, orthognathic surgery, temporomandibular joint treatment and other applications. Additionally, we elucidate how the integration of 3D printing technology has reshaped clinical workflows and influenced treatment outcomes in oral and maxillofacial surgery, providing updates on advancements in ensuring accuracy and cost-effectiveness in 3D printing-based procedures.
Do quality of life and work productivity change in early axial spondyloarthritis and non-axial spondyloarthritis patients after 2 years?
Authors: Bento da Silva Ana , Ramiro Sofia , Boel Anne , van Lunteren Miranda , Marques Mary Lucy , van de Sande Marleen , Fongen Camilla , Exarchou Sofia , Ramonda Roberta , van der Heijde Désirée , van Gaalen Floris 
Published: June 2024

Abstract

Objective
The objective of this study was to compare health-related quality of life (HRQoL) and work productivity in axial SpA (axSpA) and non-axSpA patients with chronic back pain of &lt;2 years.

Methods
Baseline and 2-year data for patients included in the SPondyloArthritis Caught Early cohort were analysed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey, and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire. Linear or zero-inflated negative binomial regression was conducted to compare 2-year outcomes between groups (axSpA and non-axSpA), adjusting for the baseline value, sex, age and use of NSAIDs.

Results
There were 265 axSpA and 108 non-axSpA patients: males 52% vs 26%, mean age 29 vs 31 years, respectively. At baseline, non-axSpA patients showed worse PCS (mean 28.6 axSpA vs 26.6 non-axSpA), presenteeism (31.1% vs 37.3%), absenteeism (8.2% vs 10.3%), WPL (34.7% vs 44.1%) and AI (39.6% vs 48.5%). MCS was not impaired in either group. After 2 years, PCS, presenteeism, WPL and AI significantly improved in both groups; absenteeism only improved in axSpA. In multivariable analysis, axSpA (vs non-axSpA) was associated with 22% less WPL [incidence rate ratio (95% CI): 0.78 (0.62; 0.98)] and 18% less AI [0.82 (0.69; 0.97)].

Conclusion
HRQoL and work productivity are more impaired in non-axSpA (vs axSpA) at baseline and also after 2 years. Although most outcomes improve in both groups, axSpA is associated with larger reductions in WPL and AI.
Linoleic acid‐derived diol 12,13‐DiHOME enhances NLRP3 inflammasome activation in macrophages
Authors: Valencia Robert , Kranrod Joshua W. , Fang Liye , Soliman Amro M. , Azer Brandon , Clemente‐Casares Xavier , Seubert John M. 
Published: June 2024

Abstract12,13‐dihydroxy‐9z‐octadecenoic acid (12,13‐DiHOME) is a linoleic acid diol derived from cytochrome P‐450 (CYP) epoxygenase and epoxide hydrolase (EH) metabolism. 12,13‐DiHOME is associated with inflammation and mitochondrial damage in the innate immune response, but how 12,13‐DiHOME contributes to these effects is unclear. We hypothesized that 12,13‐DiHOME enhances macrophage inflammation through effects on NOD‐like receptor protein 3 (NLRP3) inflammasome activation. To test this hypothesis, we utilized human monocytic THP1 cells differentiated into macrophage‐like cells with phorbol myristate acetate (PMA). 12,13‐DiHOME present during lipopolysaccharide (LPS)‐priming of THP1 macrophages exacerbated nigericin‐induced NLRP3 inflammasome activation. Using high‐resolution respirometry, we observed that priming with LPS+12,13‐DiHOME altered mitochondrial respiratory function. Mitophagy, measured using mito‐Keima, was also modulated by 12,13‐DiHOME present during priming. These mitochondrial effects were associated with increased sensitivity to nigericin‐induced mitochondrial depolarization and reactive oxygen species production in LPS+12,13‐DiHOME‐primed macrophages. Nigericin‐induced mitochondrial damage and NLRP3 inflammasome activation in LPS+12,13‐DiHOME‐primed macrophages were ablated by the mitochondrial calcium uniporter (MCU) inhibitor, Ru265. 12,13‐DiHOME present during LPS‐priming also enhanced nigericin‐induced NLRP3 inflammasome activation in primary murine bone marrow‐derived macrophages. In summary, these data demonstrate a pro‐inflammatory role for 12,13‐DiHOME by enhancing NLRP3 inflammasome activation in macrophages.
Comprehensive pan‐cancer analysis of the C2ORF40 expression: Infiltration associations and prognostic implications
Authors: Liu Yuxi , Hou Jiaxin , Zhao Yunrong , Zhou Jiangshan , Bai Shuhua , Ding Yi 
Published: June 2024

AbstractIn recent years, C2ORF40 has been identified as a tumor suppressor gene with multiple functions, including roles in cell proliferation, migration, and senescence. To explore the role of the C2ORF40 gene in different tumors, we used multiple databases for analysis. Compared to adjacent normal tissues, C2ORF40 is downregulated in a variety of malignant tumors, including tumors such as breast cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma and prostate cancer. Notably, low expression of the gene is significantly associated with poor overall survival and relapse‐free survival rates. In specific cancers including colon cancer and prostate cancer, the expression of C2ORF40 is correlated with the infiltration of CAFs. C2ORF40 is also involved in biological processes such as cell apoptosis and regulation of protein stability. In conclusion, C2ORF40 can hold promise as a prognostic marker for pan‐cancer analysis.
Disparities in Receipt of Adjuvant Immunotherapy among Stage III Melanoma Patients
Authors: Mulligan Kathleen M. , Kakish Hanna , Pawar Omkar , Ahmed Fasih Ali , Elshami Mohamedraed , Rothermel Luke D. , Bordeaux Jeremy S. , Sheng Iris Y. , Mangla Ankit , Hoehn Richard S. 
Published: June 2024

Objective:
Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment.

Methods:
We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume.

Results:
Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D.

Conclusions:
Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma.
Disparities in Survival Outcomes Among Patients With Metastatic Melanoma in Texas
Authors: Olateju Olajumoke A. , Mgbere Osaro , Thornton J. Douglas , Zeng Zhen , Essien Ekere J. 
Published: June 2024

Objectives:
Disparities exist in the length and quality of survival from melanoma. This study evaluated, in a Texas cohort, patient factors associated with melanoma survival and examined if newer immune-oncologic agents extend survival compared with conventional therapies.

Methods:
A retrospective analysis of patients diagnosed with metastatic melanoma from 2011 to 2018 in the Texas Cancer Registry database. Multivariable Cox proportional hazard regression was used to evaluate patient characteristics associated with cancer-specific survival (CSS) and overall survival (OS). The patient cohort was then grouped based on receipt of first-line immunotherapy or other therapies. The association between receipt of immunotherapy and survival was assessed with Kaplan-Meier analysis and inverse probability treatment weighted Cox regression.

Results:
There were 1372 patients with metastatic melanoma. Factors associated with increased melanoma mortality risk (CSS) included being male (HR: 1.13, 95% CI: 1.02-1.26), non-Hispanic black (HR: 1.28, 95% CI: 1.13-1.45), living in poorer counties (HR: 1.40, 95%CI: 1.20-1.64), and having multimorbidity (HR: 1.35, 95% CI: 1.05-1.74). All minority races and Hispanics had poorer OS compared with non-Hispanic Whites. Patients who received first-line immunotherapy had significantly longer median (interquartile range) survival (CSS: 27.00 [21.00 to 42.00] mo vs. 16.00 [14.00 to 19.00] mo; OS: 22.00 [17.00 to 27.00] mo vs. 12.00 [11.00 to 14.00] mo). They also had reduced mortality risk (HR for CSS: 0.80; 95% CI: 0.73-0.88; P<0.0001; HR for OS: 0.76; 95% CI: 0.69-0.83; P<0.0001) compared with the nonimmunotherapy cohort.

Conclusions:
This study showed differences in risks from melanoma survival based on patient demographic and clinical characteristics. Low socioeconomic status increased mortality risk, and first-line immunotherapy use favored survival. Health policies and tailored interventions that will promote equity in patient survival and survivorship are essential for managing metastatic melanoma.
FKBP3, a poor prognostic indicator, promotes the progression of LUAD via regulating ferroptosis and immune infiltration
Authors: Li Shengyi , Yang Lexin , Li Jing 
Published: June 2024

Background:
Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the molecular mechanism of FK506 binding protein 3 (FKBP3) in the progression of lung adenocarcinoma (LUAD).

Material and Method:
Cox regression was performed to obtain the prognosis related to differentially expressed genes (DEGs) in LUAD datasets from TCGA. We also downloaded the ferroptosis-related gene datasets from GeneCards. Venn diagram was performed to find the intersecting genes and FKBP3 was selected as the targeted gene by analyzing the diagnostic and prognostic values of Top10 intersecting genes. Moreover, univariate and multivariate analyses were performed to evaluate the association between clinicopathological factors and survival rates. GO/KEGG and GSEA analysis was performed to explore the function of FKBP3 in LUAD progression. Protein-protein interaction (PPI) network was performed via STRING database and the top10 hub genes were selected. Finally, the relationship between FKBP3 and immune infiltration was explored by ssGSEA analysis.

Results:
Firstly, 184 genes associated with the prognosis of LUAD and ferroptosis were obtained. FKBP3 was found to be significantly associated with a poor overall survival rate of LUAD patients. Immunohistochemical staining results showed that FKBP3 was highly located in cytoplasm and membrane of cells in LUAD tissues. PPI network analysis results showed that HDAC1, YY1, HDAC2, MTOR, PSMA3, PIN1, NCL, C14orf166, PIN4, and LARP6 were the top10 hub genes. Furthermore, spearman analysis results showed that the expression of FKBP3 was positively correlated with the abundance of Th2 cells and T helper cells.

Conclusion:
High level of FKBP3 was associated with poor prognostic outcomes of LUAD patients, which also inhibited immune infiltration in LUAD tissues. Additionally, FKBP3 was involved in regulating the ferroptosis process in LUAD patients. Thus, FKBP3 possessed the tumor promotion role might be involving in regulating ferroptosis and immune infiltration in LUAD progression.
Transplantation of acellular amniotic membrane seeded with adipose-derived mesenchymal stem cells in a rat model of intrauterine adhesion
Authors: Li Chunbo , Yao Liangfeng , He Fengquan , Hua Keqin 
Published: June 2024

Objective:
This study aimed to investigate the role of acellular amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) for the treatment of intrauterine adhesion.

Methods:
One hundred twenty female Spargue-Dawley rats were randomly divided into four groups: sham operation group (the uterus was picked out and incised without treatment), intrauterine adhesion group, the experimental group treated with AAM, and experimental group treated with AAM loaded with ADSCs. Histological and immunohistochemical analysis were performed on 3, 7, and 14 days after surgery to evaluate the degree of uterine fibrosis and regeneration of injured endometrium. RNA sequencing and real-time PCR were used to explore the potential mechanism by which ADSCs modulated immune response and promoted endometrial regeneration.

Results:
On 14 days after surgery, the endometrial thickness, number of glands, and degree of fibrosis reduction in the ADSCs/AAM group was higher than those in the AAM group, and similar to the sham operation group. RNA sequencing analysis showed that ADSCs can modulate local immune responses and promote the formation of functional endometrium. Meanwhile, we found that ADSCs significantly decreased the levels of pro-inflammatory cytokines (TNF-α and IL-1β) and increased the levels of anti-inflammatory cytokines (bFGF and IL-6).

Conclusion:
Our results demonstrated that AAM loaded with ADSCs can result in the regeneration of injured endometrium and fibrosis reduction. Meanwhile, ADSCs also regulated the immune microenvironment, which was beneficial to functional endometrial recovery.