bluuebunny/crossref_metadata_2025_split huggingface dataset:
SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency
Authors: Ruf Maximilian , Cunningham Sarah , Wandersee Alexandra , Brox Regine , Achenbach Susanne , Strobel Julian , Hackstein Holger , Schneider Sabine 
Published: February 2024

Abstract
Background
Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level.

Methods
Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot.

Results
The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells.

Conclusion
The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.
Role of ferroptosis in chronic kidney disease
Authors: Li Shiyang , Han Qiuxia , Liu Chang , Wang Yixue , Liu Fengxun , Pan Shaokang , Zuo Lihua , Gao Dan , Chen Kai , Feng Qi , Liu Zhangsuo , Liu Dongwei 
Published: February 2024

AbstractChronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment.
Connexin32 gap junction channels deliver miR155-3p to mediate pyroptosis in renal ischemia-reperfusion injury
Authors: Chen Liubing , Fang Hongyi , Li Xiaoyun , Yu Peiling , Guan Yu , Xiao Cuicui , Deng Zhizhao , Hei Ziqing , Chen Chaojin , Luo Chenfang 
Published: February 2024

Abstract
Objectives
To explore whether the gap junction (GJ) composed by connexin32(Cx32) mediated pyroptosis in renal ischemia-reperfusion(I/R) injury via transmitting miR155-3p, with aim to provide new strategies for the prevention and treatment of acute kidney injury (AKI) after renal I/R.

Methods
8–10 weeks of male C57BL/ 6 wild-type mice and Cx32 knockdown mice were divided into two groups respectively: control group and renal I/R group. MCC950 (50 mg/kg. ip.) was used to inhibit NLRP3 in vivo. Human kidney tubular epithelial cells (HK - 2) and rat kidney tubular epithelial cells (NRK-52E) were divided into high-density group and low-density group, and treated with hypoxia reoxygenation (H/R) to mimic I/R. The siRNA and plasmid of Cx32, mimic and inhibitor of miR155-3p were transfected into HK - 2 cells respectively. Kidney pathological and functional injuries were measured. Western Blot and immunofluorescent staining were used to observe the expression of NLRP3, GSDMD, GSDMD-N, IL - 18, and mature IL-18. The secretion of IL-18 and IL-1β in serum, kidney tissue and cells supernatant were detected by enzyme-linked immuno sorbent assay (ELISA) kit, and the expression of NLPR3 and miR155-3p were detected by RT-qPCR and fluorescence in situ hybridization (FISH).

Results
Tubular pyroptosis were found to promote AKI after I/R in vivo and Cx32-GJ regulated pyroptosis by affecting the expression of miR155-3p after renal I/R injury. In vitro, H/R could lead to pyroptosis in HK-2 and NRK-52E cells. When the GJ channels were not formed, and Cx32 was inhibited or knockdown, the expression of miR155-3p was significantly reduced and the pyroptosis was obviously inhibited, leading to the reduction of injury and the increase of survival rate. Moreover, regulating the level of miR155-3p could affect survival rate and pyroptosis in vitro after H/R.

Conclusions
The GJ channels composed of Cx32 regulated tubular pyroptosis in renal I/R injury by transmitting miR155-3p. Inhibition of Cx32 could reduce the level of miR155-3p further to inhibit pyroptosis, leading to alleviation of renal I/R injury which provided a new strategy for preventing the occurrence of AKI.
Revealing role of epigenetic modifiers and DNA oxidation in cell-autonomous regulation of Cancer stem cells
Authors: Ferrer-Diaz Alejandra I. , Sinha Garima , Petryna Andrew , Gonzalez-Bermejo Ruth , Kenfack Yannick , Adetayo Oluwadamilola , Patel Shyam A. , Hooda-Nehra Anupama , Rameshwar Pranela 
Published: February 2024

Abstract
Background
Breast cancer cells (BCCs) can remain undetected for decades in dormancy. These quiescent cells are similar to cancer stem cells (CSCs); hence their ability to initiate tertiary metastasis. Dormancy can be regulated by components of the tissue microenvironment such as bone marrow mesenchymal stem cells (MSCs) that release exosomes to dedifferentiate BCCs into CSCs. The exosomes cargo includes histone 3, lysine 4 (H3K4) methyltransferases - KMT2B and KMT2D. A less studied mechanism of CSC maintenance is the process of cell-autonomous regulation, leading us to examine the roles for KMT2B and KMT2D in sustaining CSCs, and their potential as drug targets.

Methods
Use of pharmacological inhibitor of H3K4 (WDR5–0103), knockdown (KD) of KMT2B or KMT2D in BCCs, real time PCR, western blot, response to chemotherapy, RNA-seq, and flow cytometry for circulating markers of CSCs and DNA hydroxylases in BC patients. In vivo studies using a dormancy model studied the effects of KMT2B/D to chemotherapy.

Results
H3K4 methyltransferases sustain cell autonomous regulation of CSCs, impart chemoresistance, maintain cycling quiescence, and reduce migration and proliferation of BCCs. In vivo studies validated KMT2’s role in dormancy and identified these genes as potential drug targets. DNA methylase (DNMT), predicted within a network with KMT2 to regulate CSCs, was determined to sustain circulating CSC-like in the blood of patients.

Conclusion
H3K4 methyltransferases and DNA methylation mediate cell autonomous regulation to sustain CSC. The findings provide crucial insights into epigenetic regulatory mechanisms underlying BC dormancy with KMT2B and KMT2D as potential therapeutic targets, along with standard care. Stem cell and epigenetic markers in circulating BCCs could monitor treatment response and this could be significant for long BC remission to partly address health disparity.
The clinical value of P-wave terminal force in lead V1 in evaluating pericardial thickness in tuberculous constrictive pericarditis
Authors: Ren Yanhong 
Published: February 2024

Abstract
Aim
To investigate the relationship between p wave terminal force (Ptfv1) and pericardial thickness in patients with tuberculous constrictive pericarditis.

Methods
From January 2018 to October 2022, 95 patients with tuberculous constrictive pericarditis who needed pericarditis dissection in a hospital were collected, and 3 patients who did not meet the criteria were excluded, a total of 92 cases. The absolute value of Ptfv1 in conventional electrocardiogram was tested before surgery, and pericardial thickness was measured by echocardiography and chest CT. Pericardial thickness was measured after pericardial dissection. Pearson correlation analysis was used, R software was used to make scatter plot, and non-parametric square test was used. The correlation of postoperative measurements with echocardiography, chest CT and absolute value of Ptfv1 was analyzed.

Results
Pearson correlation analysis was conducted with postoperative measurements and echocardiography measurements, postoperative measurements and chest CT measurements, and postoperative measurements and absolute value of Ptfv1. Pearson correlation analysis showed that the correlation coefficients between postoperative measurements and echocardiography, chest CT and Ptfv1 values were statistically significant. Scatter plot and nonparametric Chi-square test showed that postoperative measurements were consistent with absolute values of echocardiography, chest CT and Ptfv1 (p < 0.05). And this study found that the distribution of the value of Ptfv1 ≥ 5 was higher than the value of Ptfv1 < 5 after pericardiectomy (0.95:0.05) in the absolute value of Ptfv1 ≥ 0.04 which measured before pericardiectomy. The hypothesis was statistically significant (p < 0.05).

Conclusion
The absolute value of Ptfv1 in electrocardiogram can be used as an auxiliary diagnostic index to evaluate pericardial thickness in tuberculous constrictive pericarditis.
Knowledge graph construction based on granulosa cells transcriptome from polycystic ovary syndrome with normoandrogen and hyperandrogen
Authors: Liu Wensu , Tang Tianyu , Feng Jianwei , Wang Chunyu , Lin Lin , Wang Shengli , Zeng Kai , Zou Renlong , Yang Zeyu , Zhao Yue 
Published: February 2024

AbstractPCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.
Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses
Authors: Mi Jiarui , Jiang Qingwei , Qi Zhengwei , Liu Zhengye , Bai Xiaoyin , Zheng Xia , Wu Jiaguo , Fang Yanfei , Yang Aiming , Chen Haotian 
Published: February 2024

AbstractThe causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.
Oncogenic alterations in advanced NSCLC: a molecular super-highway
Authors: Friedlaender Alex , Perol Maurice , Banna Giuseppe Luigi , Parikh Kaushal , Addeo Alfredo 
Published: February 2024

AbstractLung cancer ranks among the most common cancers world-wide and is the first cancer-related cause of death. The classification of lung cancer has evolved tremendously over the past two decades. Today, non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, comprises a multitude of molecular oncogenic subsets that change both the prognosis and management of disease.Since the first targeted oncogenic alteration identified in 2004, with the epidermal growth factor receptor (EGFR), there has been unprecedented progress in identifying and targeting new molecular alterations. Almost two decades of experience have allowed scientists to elucidate the biological function of oncogenic drivers and understand and often overcome the molecular basis of acquired resistance mechanisms. Today, targetable molecular alterations are identified in approximately 60% of lung adenocarcinoma patients in Western populations and 80% among Asian populations. Oncogenic drivers are largely enriched among non-smokers, east Asians, and younger patients, though each alteration has its own patient phenotype.The current landscape of druggable molecular targets includes EGFR, anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B (BRAF), ROS proto-oncogene 1 (ROS1), Kirstin rat sarcoma virus (KRAS), human epidermal receptor 2 (HER2), c-MET proto-oncogene (MET), neurotrophic receptor tyrosine kinase (NTRK), rearranged during transfection (RET), neuregulin 1 (NRG1). In addition to these known targets, others including Phosphoinositide 3-kinases (PI3K) and fibroblast growth factor receptor (FGFR) have garnered significant attention and are the subject of numerous ongoing trials.In this era of personalized, precision medicine, it is of paramount importance to identify known or potential oncogenic drivers in each patient. The development of targeted therapy is mirrored by diagnostic progress. Next generation sequencing offers high-throughput, speed and breadth to identify molecular alterations in entire genomes or targeted regions of DNA or RNA. It is the basis for the identification of the majority of current druggable alterations and offers a unique window into novel alterations, and de novo and acquired resistance mechanisms.In this review, we discuss the diagnostic approach in advanced NSCLC, focusing on current oncogenic driver alterations, through their pathophysiology, management, and future perspectives. We also explore the shortcomings and hurdles encountered in this rapidly evolving field.
Plant-based diets and cardiovascular risk factors: a comparison of flexitarians, vegans and omnivores in a cross-sectional study
Authors: Bruns Anja , Greupner Theresa , Nebl Josefine , Hahn Andreas 
Published: February 2024

Abstract
Background
The growing trend towards conscious and sustainable dietary choices has led to increased adoption of flexitarian diets, characterised by plant-based eating habits with occasional consumption of meat and processed meat products. However, the cardiovascular disease (CVD) risk factors associated with flexitarian diets compared to both vegans and omnivores remain underexplored.

Methods
In this cross-sectional study, 94 healthy participants aged 25–45 years, categorized into long-term flexitarians (FXs ≤ 50 g/day of meat and meat products, n = 32), vegans (Vs, no animal products, n = 33), and omnivores (OMNs ≥ 170 g/day of meat and meat products, n = 29) were included. Various CVD risk factors were measured, including fasting blood samples for metabolic biomarkers, body composition analysis via bioimpedance, blood pressure measurements, arterial stiffness evaluated through pulse wave velocity (PWV) and metabolic syndrome (MetS) severity was determined using browser-based calculations (MetS-scores). Dietary intake was assessed using a Food Frequency Questionnaire (FFQ), diet quality was calculated with the Healthy Eating Index-flexible (HEI-Flex), while physical activity levels were recorded using the validated Freiburger questionnaire.

Results
The data showed that FXs and Vs had more beneficial levels of insulin, triglycerides, total cholesterol, and LDL cholesterol compared to OMNs. Notably, FXs revealed the most favorable MetS-score results based on both BMI and waistline, and better PWV values than Vs and OMNs. In addition, FXs and Vs reported higher intake rates of vegetables, fruit, nuts/seeds and plant-based milk alternatives.

Conclusion
The flexitarian diet appears to confer cardiovascular benefits. While Vs had the most favorable results overall, this study supports that reducing meat and processed meat products intake, as in flexitarianism, may contribute to CVD risk factor advantages.
What motivates public collaborators to become and stay involved in health research?
Authors: Røssvoll Toril Beate , Liabo Kristin , Hanssen Tove Aminda , Rosenvinge Jan H. , Sundkvist Elisabeth , Pettersen Gunn 
Published: February 2024

Abstract
Background
People with lived experience of health and illness are increasingly being involved in research. Knowing what creates interest in becoming involved in health research may help identify appropriate ways of facilitating meaningful involvement. The study aimed to investigate why people became public collaborators in health research and what helped sustain their commitment to staying involved.

Methods
Semistructured individual qualitative interviews were conducted with 11 Norwegian public collaborators recruited from patient organisations. To enhance the quality and relevance of this study, three public collaborators were involved in framing the study and in the data analysis. One of them is a coauthor of this paper. The interviews were analysed through reflexive thematic analysis, and two themes were generated.

Results
The first theme, ‘research as a vehicle to impact’ showed how interest in becoming involved in research was founded on the possibility of impacting healthcare through research. Other inspiring factors were how they appraised the relevance of the research, in addition to the public collaborators’ own sense of moral duty to advocate for research related to their own as well as others, illnesses or diseases. The second theme, ‘‘Acknowledgement and accessibility’, framed how the participants perceived appreciation of experiential knowledge as crucial for maintaining motivation in their role as public collaborators. Other promoters of sustained involvement presented were training for both public collaborators and researchers, adequate allowance as a means for visualising and valuing PPI, and accessible language.

Conclusions
This study contributes to the understanding of how to facilitate meaningful and sustainable PPI, which requires a safe space for collaboration and attention to accessibility. Facilitating meaningful involvement may, in turn, increase the potential impact and sustainability of PPI.
Emanuel syndrome due to unusual pattern
Authors: El-Bassyouni Hala T. , Ashaat Engy A. , Hamed Khaled , Rashed Maha , Abd-Elnaby Azza E. , Shehab Marwa 
Published: February 2024

Abstract
Background
The hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities.

Results
This study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome.

Conclusions
This case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.
The possible anti-inflammatory effect of extra virgin olive oil with colchicine in treatment of resistant cases of familial Mediterranean fever in a cohort of pediatric Egyptian patients
Authors: Osman Walla’a A. , Taher Heba , Darweesh Hanan , Abdel Samie Mai , Shaker Olfat G. , Labib Dina A. , Ateyya Hayam 
Published: February 2024

Abstract
Background
People of Mediterranean descent are primarily affected by the autoinflammatory genetic condition known as familial Mediterranean fever (FMF). The disease is resistant to colchicine therapy in 10–20% of patients. Numerous recent animal studies showed promising results of extra virgin olive oil (EVOO) to control inflammation. The objective of this study was to assess the effectiveness of combining EVOO with colchicine in the treatment of colchicine-resistant familial Mediterranean fever (CRFMF) patients.

Results
Both the frequency of episodes and inflammatory indicators significantly decreased after a three-month course of daily EVOO treatment with colchicine. The average erythrocyte sedimentation rate (ESR) of patients was 78.6 mm/h before the EVOO administration, and it dropped to 27.8 mm/h, after that. Additionally, after taking EVOO, the mean serum amyloid A (SAA) decreased from 123.82 mg/dl to 59.78 mg/L. Also, the average C-reactive protein (CRP) decreased from 34.22 to 7.84 mg/dl following its administration; the mean nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) level decreased from 134.92 to 64.23 pg/ml. The mean caspase-1 level decreased from 7.8 to 4.98 ng/ml; and the mean levels of cytokines, interleukin 6 (IL-6), interleukin 1 beta (IL-1 β), and tumor necrosis factor-alpha (TNF-α) decreased from 9.8, 18.14, and 52.7 pg/ml, respectively, to 5.95, 12.51, and 29.39 pg/ml. Finally following the administration of EVOO, there was a notable overall improvement in the quality of life of (CRFMF) patients.

Conclusion
EVOO demonstrated a significant positive impact when paired with the tolerated dosage of colchicine in the management of CRFMF. Improvements were observed in both clinical and laboratory settings, including a reduction in the attack frequency and serum levels of inflammatory markers, such as NLRP3, caspase-1, ESR, CRP, IL-1β, IL-6, and TNF-α without any negative side effects.