bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of template denaturation prior to whole genome amplification on gene detection in high GC-content species, Burkholderia mallei and B. pseudomallei
Authors: Taitt Chris R. , Leski Tomasz A. , Compton Jaimee R. , Chen Amy , Berk Kimberly L. , Dorsey Robert W. , Sozhamannan Shanmuga , Dutt Dianne L. , Vora Gary J. 
Published: March 2024

Abstract
Objective
In this study, we sought to determine the types and prevalence of antimicrobial resistance determinants (ARDs) in Burkholderia spp. strains using the Antimicrobial Resistance Determinant Microarray (ARDM).

Results
Whole genome amplicons from 22 B. mallei (BM) and 37 B. pseudomallei (BP) isolates were tested for > 500 ARDs using ARDM v.3.1. ARDM detected the following Burkholderia spp.-derived genes, aac(6), blaBP/MBL-3, blaABPS, penA-BP, and qacE, in both BM and BP while blaBP/MBL-1, macB, blaOXA-42/43 and penA-BC were observed in BP only. The method of denaturing template for whole genome amplification greatly affected the numbers and types of genes detected by the ARDM. BlaTEM was detected in nearly a third of BM and BP amplicons derived from thermally, but not chemically denatured templates. BlaTEM results were confirmed by PCR, with 81% concordance between methods. Sequences from 414-nt PCR amplicons (13 preparations) were 100% identical to the Klebsiella pneumoniae reference gene. Although blaTEM sequences have been observed in B. glumae, B. cepacia, and other undefined Burkholderia strains, this is the first report of such sequences in BM/BP/B. thailandensis (BT) clade. These results highlight the importance of sample preparation in achieving adequate genome coverage in methods requiring untargeted amplification before analysis.
Identification of the prognostic value of LACTB2 and its correlation with immune infiltrates in ovarian cancer by integrated bioinformatics analyses
Authors: Cao Weiwei , Wang Chao , Zhang Yue , Yang Jiani , Luo Xiaomei , Zhao Yaqian , Wu Meixuan , Cheng Shanshan , Wang Yu 
Published: March 2024

AbstractOvarian cancer (OC) is one of the most common reproductive tumors in women, whereas current treatment options are limited. β-lactamase-like-protein 2 (LACTB2) has been observed to be associated with various cancers, but its function in OC is unknown. Therefore, we evaluate the prognostic value and the underlying function of LACTB2 in OC. In this study, high expression of LACTB2 was observed in OC compared with normal controls. Kaplan–Meier Plotter analysis revealed that overexpressed LACTB2 is strongly correlated with poor prognosis. We conducted GO/KEGG analysis to investigate the potential biological function of LACTB2 in OC. GESA analysis showed that LACTB2 was closely related to immune-related pathways. Subsequently, we explored the relationship between LACTB2 and 24 types of immune cells in OC. The results suggested that LACTB2 was positively associated with multiple tumor-infiltrating immune cells. Importantly, LACTB2 may modulate immune cell infiltration in OC to influence prognosis. In conclusion, LACTB2 can be used as a promising prognostic biomarker and immunotherapy target for OC.
In-depth proteome characterization of endometrium and extraembryonic membranes during implantation in pig
Authors: Gil Maria A. , Cambra Josep M. , Rodriguez-Martinez Heriberto , Cuello Cristina , Parrilla Inmaculada , Martinez Emilio A. 
Published: March 2024

Abstract
Background
Proteome characterization of the porcine endometrium and extraembryonic membranes is important to understand mother-embryo cross-communication. In this study, the proteome of the endometrium and chorioallantoic membrane was characterized in pregnant sows (PS) during early gestation (d 18 and 24 of gestation) and in the endometrium of non-pregnant sows (NPS) during the same days using LC-MS/MS analysis. The UniProtKB database and ClueGO were used to obtain functional Gene Ontology annotations and biological and functional networks, respectively.

Results
Our analysis yielded 3,254 and 3,457 proteins identified in the endometrium of PS and NPS, respectively; of these, 1,753 being common while 1,501 and 1,704 were exclusive to PS and NPS, respectively. In addition, we identified 3,968 proteins in the extraembryonic membranes of PS. Further analyses of function revealed some proteins had relevance for the immune system process and biological adhesion in endometrium while the embryonic chorion displayed abundance of proteins related to cell adhesion and cytoskeletal organization, suggesting they dominated the moment of endometrial remodeling, implantation and adhesion of the lining epithelia. Data are available via ProteomeXchange with identifier PXD042565.

Conclusion
This is the first in-depth proteomic characterization of the endometrium and extraembryonic membranes during weeks 3 to 4 of gestation; data that contribute to the molecular understanding of the dynamic environment during this critical period, associated with the majority of pregnancy losses.
Suppression of A-to-I RNA-editing enzyme ADAR1 sensitizes hepatocellular carcinoma cells to oxidative stress through regulating Keap1/Nrf2 pathway
Authors: Wang Houhong , Wei Xiaoyu , Liu Lu , Zhang Junfeng , Li Heng 
Published: March 2024

Abstract
Background
A-to-I RNA editing is an abundant post-transcriptional modification event in hepatocellular carcinoma (HCC). Evidence suggests that adenosine deaminases acting on RNA 1 (ADAR1) correlates to oxidative stress that is a crucial factor of HCC pathogenesis. The present study investigated the effect of ADAR1 on survival and oxidative stress of HCC, and underlying mechanisms.

Methods
ADAR1 expression was measured in fifty HCC and normal tissues via real-time quantitative PCR, and immunohistochemistry. For stable knockdown or overexpression of ADAR1, adeno-associated virus vectors carrying sh-ADAR1 or ADAR1 overexpression were transfected into HepG2 and SMMC-7721 cells. Transfected cells were exposed to oxidative stress agonist tBHP or sorafenib Bay 43-9006. Cell proliferation, apoptosis, and oxidative stress were measured, and tumor xenograft experiment was implemented.

Results
ADAR1 was up-regulated in HCC and correlated to unfavorable clinical outcomes. ADAR1 deficiency attenuated proliferation of HCC cells and tumor growth and enhanced apoptosis. Moreover, its loss facilitated intracellular ROS accumulation, and elevated Keap1 and lowered Nrf2 expression. Intracellular GSH content and SOD activity were decreased and MDA content was increased in the absence of ADAR1. The opposite results were observed when ADAR1 was overexpressed. The effects of tBHP and Bay 43–9006 on survival, apoptosis, intracellular ROS accumulation, and Keap1/Nrf2 pathway were further exacerbated by simultaneous inhibition of ADAR1.

Conclusions
The current study unveils that ADAR1 is required for survival and oxidative stress of HCC cells, and targeting ADAR1 may sensitize HCC cells to oxidative stress via modulating Keap1/Nrf2 pathway.
Cellular and clinical impact of protein phosphatase enzyme epigenetic silencing in multiple cancer tissues
Authors: Wiltshire Edward , de Moura Manuel Castro , Piñeyro David , Joshi Ricky S. 
Published: March 2024

Abstract
Background
Protein Phosphatase Enzymes (PPE) and protein kinases simultaneously control phosphorylation mechanisms that tightly regulate intracellular signalling pathways and stimulate cellular responses. In human malignancies, PPE and protein kinases are frequently mutated resulting in uncontrolled kinase activity and PPE suppression, leading to cell proliferation, migration and resistance to anti-cancer therapies. Cancer associated DNA hypermethylation at PPE promoters gives rise to transcriptional silencing (epimutations) and is a hallmark of cancer. Despite recent advances in sequencing technologies, data availability and computational capabilities, only a fraction of PPE have been reported as transcriptionally inactive as a consequence of epimutations.

Methods
In this study, we examined promoter-associated DNA methylation profiles in Protein Phosphatase Enzymes and their Interacting Proteins (PPEIP) in a cohort of 705 cancer patients in five tissues (Large intestine, Oesophagus, Lung, Pancreas and Stomach) in three cell models (primary tumours, cancer cell lines and 3D embedded cancer cell cultures). As a subset of PPEIP are known tumour suppressor genes, we analysed the impact of PPEIP promoter hypermethylation marks on gene expression, cellular networks and in a clinical setting.

Results
Here, we report epimutations in PPEIP are a frequent occurrence in the cancer genome and manifest independent of transcriptional activity. We observed that different tumours have varying susceptibility to epimutations and identify specific cellular signalling networks that are primarily affected by epimutations. Additionally, RNA-seq analysis showed the negative impact of epimutations on most (not all) Protein Tyrosine Phosphatase transcription. Finally, we detected novel clinical biomarkers that inform on patient mortality and anti-cancer treatment sensitivity.

Conclusions
We propose that DNA hypermethylation marks at PPEIP frequently contribute to the pathogenesis of malignancies and within the precision medicine space, hold promise as biomarkers to inform on clinical features such as patient survival and therapeutic response.
Suicidal ideation in Chinese patients with advanced breast cancer: a multi-center mediation model study
Authors: Zhang Yening , He Yi , Pang Ying , Su Zhongge , Wang Yu , Zhou Yuhe , Lu Yongkui , Jiang Yu , Han Xinkun , Song Lihua , Wang Liping , Li Zimeng , Lv Xiaojun , Wang Yan , Yao Juntao , Liu Xiaohong , Zhou Xiaoyi , He Shuangzhi , Song Lili , Li Jinjiang , Wang Bingmei , Tang Lili 
Published: March 2024

Abstract
Purpose
The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer.

Methods
Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI.

Results
SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p < 0.05). The ORs indicate that depression and distress have the strongest associations with SI. Health status has a significant indirect effect (OR=-0.044, p = 0.005) and a strong total effect (OR=-0.485, p < 0.001) on SI, mediated by insomnia severity and emotional distress.

Conclusions
There is a high SI prevalence among Chinese patients with advanced breast cancer. Our analysis revealed predictive pathways from poor health to heightened SI, mediated by emotional distress and insomnia. Regular management of distress and insomnia can decrease suicide risk in this vulnerable population.
Improving organic grape production: the effects of soil management and organic fertilizers on biogenic amine levels in Vitis vinifera cv., 'Royal' grapes
Authors: Kaya Ozkan , Yilmaz Turhan , Ates Fadime , Kustutan Fulya , Hatterman-Valenti Harlene , Hajizadeh Hanifeh Seyed , Turan Metin 
Published: March 2024

Abstract
Background
The integration of organic viticulture practices in grape cultivation represents a pivotal advancement towards sustainable agriculture, emphasizing the importance of environmentally friendly methods that enhance soil health, grape quality, and overall ecosystem biodiversity, thereby contributing significantly to the resilience and long-term sustainability of viticultural ecosystems. This study explored the effects of soil management practices, including chisel, disc harrow, and no tillage, as well as the impact of utilizing Antep radish, broccoli, and olive blackwater as fertilizer applications, on the biochemical composition, specifically biogenic amines (BAs), in the clusters of the 'Royal' grape cultivar within a vineyard setting.

Results
Throughout the three-year study, no tillage soil management consistently emerged as the most influential soil treatment for enhancing BAs in 'Royal' grape berries, especially in combination with Antep radish and olive blackwater fertilizer applications. Among fertilizer applications, the nontreated control vines consistently had the highest concentrations of critical BAs, such as putrescine, cadaverine, histamine, and dopamine, across different soil management practices. Among the soil management practices and fertilizer applications evaluated, the disc harrow soil management and olive blackwater fertilizer application generally yielded the lowest concentrations of BAs across several metrics.The PCA biplots indicated that experimental years have a similar effect on BA content in grape berries, with specific amines such as serotonin and dopamine being more affected in 2020, while cadaverine, histamine, spermidine, trimethylamine, and norepinephrine were more influenced in 2021, and putrescine, spermine, agmatine, and tryptamine in 2022.

Conclusion
These findings hold significant implications for organic agriculture, emphasizing the nuanced influence of soil management practices and organic fertilizers on the BA composition of grape berries. Our results indicate the potential of tailored agricultural strategies to enhance plant health and quality, aligning with the principles of sustainability and environmental stewardship inherent to organic farming.

Graphical Abstract
Glial-restricted progenitor cells: a cure for diseased brain?
Authors: Rogujski Piotr , Lukomska Barbara , Janowski Miroslaw , Stanaszek Luiza 
Published: March 2024

AbstractThe central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.
Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer
Authors: Thomas Georgia , Weiss Elisabeth , Del Buono Marco Giuseppe , Moroni Francesco , West Josh , Myers Rachel , Kontos Emily , Golino Michele , Abbate Antonio , Canada Justin M. 
Published: March 2024

Abstract
Background
Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy.

Methods
Ten patients (69 [61–76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured.

Results
The VO2peak was reduced at baseline (1.245 [0.882–1.605] L·min− 1; 70 [62–86] %-predicted) and significantly declined (1.095 [0.810–1.448] L·min− 1, P = 0.047; 62 [56–76] %-predicted, P = 0.005) at 6.0 [3.0–6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27–1.88] to 1.57 [1.12–1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56–65]% to 66 [57–68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7–41.6] vs. 12.8 [3.1–35.9]). The hsCRP increased significantly from 4.4 [1.4–5.8] to 6.1 [3.7–20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49–125] to 121 [88–191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8–25] to 15.5 [11.5–20]; P = 0.021) post-radiotherapy.

Conclusions
Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).
Irreversible methadone-induced GSTP1 downregulation in SH-SY5Y cells
Authors: Saify Khyber , Saadat Mostafa 
Published: March 2024

Abstract
Background
Methadone has been reported to downregulate the expression of glutathione S-transferase P1 (GSTP1) among nine antioxidant genes in SH-SY5Y cells after both short- and long-term treatment. GSTP1 plays a key role in the detoxification of many xenobiotics and is frequently associated with various diseases, especially tumors. The objective of this study is to determine whether this change is reversible.

Methods
Two different treatment protocols were used. The first protocol evaluated the reversibility of the GSTP1 mRNA change, while the second protocol evaluated the methylation status of the GSTP1 promoter site. To investigate the reversibility of the GSTP1 mRNA change, SH-SY5Y cells were treated with methadone. The drug was then removed from the medium and the cells were cultured in methadone-free medium for a period of time. GSTP1 mRNA levels were expressed as cycle threshold (Ct) values using TATA box-binding protein as a calibrator gene. Methylation at the promoter site was detected by bisulfite treatment.

Results
The analysis of variance revealed no significant change in GSTP1 mRNA levels in the cells after methadone was removed from the medium of methadone-treated cells. The study also examined the methylation status of a CpG island in the promoter of GSTP1 in the treated cells. The results demonstrate that although methadone downregulates the mRNA level of GSTP1 in treated cells, it does not induce methylation in the GSTP1 promoter region.

Conclusions
The expression of the GSTP1 remains downregulated even after methadone removal from SH-SY5Y cell culture medium; however, methylation of the GSTP1 promoter site does not play a role in this process.
Building typology of Albanian kulla stone houses in the Balkans
Authors: Jerliu Florina , Thaçi Kaltrina 
Published: March 2024

AbstractThis paper aims to establish a unified typology for the culturally significant kulla stone houses built in the cross-border region of Kosovo, Albania, and Montenegro during the 18th and 19th centuries. Despite some attempts at typological categorisation on the national level, a joint typology for this region currently needs to be improved. Based on existing literature and field research, the paper identifies the specificities of different geographical locations while validating the core attributes common to all typological variations. The findings suggest that the joint typological classification of kulla in the Balkans should primarily be based on architectural elements and, to some extent, setting, building materials and techniques, while functional composition is consistent across all types. The paper argues that defining a common typology for the Albanian kulla stone houses in the Balkans is crucial for evaluating, preserving, and developing kulla as serial properties and for their future regional development.
The language and landscape of the law in relation to consent in minors
Authors: Dosani Sabina 
Published: March 2024

SUMMARYThis commentary reflects on two articles on consent in those under 18 years of age, known in law as ‘minors’. I consider why the language and landscape of the law in relation to consent in this age group can be alienating to psychiatrists, interrogate the legal complexities regarding consent in children and adolescents, refer to key aspects of relevant case law and end with practical suggestions that might improve clinical practice with cases that have the potential for legal complexity.