bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility
Authors: Chen Yu , Zhang Xiangzheng , Jiang Jiayin , Luo Mengjiao , Tu Haixia , Xu Chen , Tan Huanhuan , Zhou Xin , Chen Hong , Han Xudong , Yue Qiuling , Guo Yueshuai , Zheng Ke , Qi Yaling , Situ Chenghao , Cui Yiqiang , Guo Xuejiang 
Published: April 2023

Abstract
Background
Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized.

Results
Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa−/− mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs.

Conclusions
Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.
Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies
Authors: Fu Weili , Ge Minghao , Li Jian 
Published: April 2023

Abstract
Background
Acute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms.

Methods
10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot.

Results
Proteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis.

Conclusions
Comprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis.
Type 1 diabetes and diet-induced obesity predispose C57BL/6J mice to PM2.5-induced lung injury: a comparative study
Authors: Chen Shen , Li Miao , Zhang Rui , Ye Lizhu , Jiang Yue , Jiang Xinhang , Peng Hui , Wang Ziwei , Guo Zhanyu , Chen Liping , Zhang Rong , Niu Yujie , Aschner Michael , Li Daochuan , Chen Wen 
Published: April 2023

Abstract
Background
Pre-existing metabolic diseases may predispose individuals to particulate matter (PM)-induced adverse health effects. However, the differences in susceptibility of various metabolic diseases to PM-induced lung injury and their underlying mechanisms have yet to be fully elucidated.

Results
Type 1 diabetes (T1D) murine models were constructed by streptozotocin injection, while diet-induced obesity (DIO) models were generated by feeding 45% high-fat diet 6 weeks prior to and throughout the experiment. Mice were subjected to real-ambient PM exposure in Shijiazhuang City, China for 4 weeks at a mean PM2.5 concentration of 95.77 µg/m3. Lung and systemic injury were assessed, and the underlying mechanisms were explored through transcriptomics analysis. Compared with normal diet (ND)-fed mice, T1D mice exhibited severe hyperglycemia with a blood glucose of 350 mg/dL, while DIO mice displayed moderate obesity and marked dyslipidemia with a slightly elevated blood glucose of 180 mg/dL. T1D and DIO mice were susceptible to PM-induced lung injury, manifested by inflammatory changes such as interstitial neutrophil infiltration and alveolar septal thickening. Notably, the acute lung injury scores of T1D and DIO mice were higher by 79.57% and 48.47%, respectively, than that of ND-fed mice. Lung transcriptome analysis revealed that increased susceptibility to PM exposure was associated with perturbations in multiple pathways including glucose and lipid metabolism, inflammatory responses, oxidative stress, cellular senescence, and tissue remodeling. Functional experiments confirmed that changes in biomarkers of macrophage (F4/80), lipid peroxidation (4-HNE), cellular senescence (SA-β-gal), and airway repair (CCSP) were most pronounced in the lungs of PM-exposed T1D mice. Furthermore, pathways associated with xenobiotic metabolism showed metabolic state- and tissue-specific perturbation patterns. Upon PM exposure, activation of nuclear receptor (NR) pathways and inhibition of the glutathione (GSH)-mediated detoxification pathway were evident in the lungs of T1D mice, and a significant upregulation of NR pathways was present in the livers of T1D mice.

Conclusions
These differences might contribute to differential susceptibility to PM exposure between T1D and DIO mice. These findings provide new insights into the health risk assessment of PM exposure in populations with metabolic diseases.
Mitral valve repair with the use of the “Memo 3D ReChord” ring
Authors: Baikoussis Nikolaos G. , Koumallos Nikolaos , Aggeli Κonstantina 
Published: April 2023

Abstract
Background
From a variety of ring types, semirigid ring is more preferred for mitral annuloplasty during mitral valve repair particularly in patients whose native mitral saddle shape annulus is well maintained. During mitral annuloplasty artificial chord implantation with the appropriate neochord length is surgically challenging. We present our experience of using the Memo 3D ReChord, a semirigid ring with additional chordal guiding system for mitral valve repair.

Patients and methods
From September 2018 to February 2020, we successfully treated ten patients with severe (4+/4+) degenerative mitral valve regurgitation due to posterior leaflet prolapse with chordal rupture with the implantation Memo 3D ReChord and neo-chords.

Results
We implanted from one to three neo-chords and always a ring in our patients. None of the patients had any residual mitral valve regurgitation at the end of the repair and on their discharge evaluated through transesophageal and transthoracic echocardiography respectively. There was no mortality at 30-days or on midterm follow-up. During the 3-month follow-up no regurgitation was noticed either. We included in our study only the patients successfully treated. We also used it in two patients, who underwent valve replacement during the same operation due to mild to moderate mitral valve regurgitation.

Conclusions
This, in our knowledge, is the first Greek series of the implantation of the Memo 3D Rechord. The initial excellent results give us the enthusiasm to continue while long-term results and the durability of this technique are necessary to establish this semirigid annuloplastic ring in our every-day practice.
Acute Lung Injury in aortic dissection : new insights in anesthetic management strategies
Authors: Yang Ming 
Published: April 2023

AbstractAcute aortic dissection (AAD) is a severe cardiovascular disease characterized by rapid progress and a high mortality rate. The incidence of acute aortic dissection is approximately 5 to 30 per 1 million people worldwide. In clinical practice, about 35% of AAD patients are complicated with acute lung injury (ALI). AAD complicated with ALI can seriously affect patients’ prognosis and even increase mortality. However, the pathogenesis of AAD combined with ALI remains largely unknown. Given the public health burden of AAD combined with ALI, we reviewed the anesthetic management advances and highlighted potential areas for clinical practice.
TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC
Authors: Yang Si-bo , Zhou Zi-han , Lei Jin , Li Xiao-wen , Chen Qian , Li Bo , Zhang Ye-wei , Ge Yu-zhen , Zuo Shi 
Published: April 2023

AbstractTM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.
Green analytical chemistry and experimental design: a combined approach for the analysis of zonisamide
Authors: Elsheikh Soha G. , Hassan Abeer M. E. , Fayez Yasmin M. , El-Mosallamy Sally S. 
Published: April 2023

AbstractGreen analytical chemistry principles, as well as experimental design, are a combined approach adopted to develop sensitive reproducible stability indicating HPLC method for Zonisamide (ZNS) determination. The optimal conditions for three chromatographic parameters were determined using a central composite design of the response surface. Kromasil C18 column (150 mm × 4.6 mm, 5 µm) was utilized with ethanol, H2O (30:70 v/v) as a mobile phase at a flow rate of 1 mL/min at 35 °C. Good reproducibility and high sensitivity were achieved along (0.5–10 µg/mL) concentration range. In contrast, the TLC-densitometric method was performed on aluminum plates precoated with silica gel 60F254 as a stationary phase and chloroform: methanol: acetic acid (8:1.5:0.5 by volume) as a developing system. Reproducible results were obtained in the range of (2–10 μg/band). The chromatograms of HPLC and TLC were scanned at 280 nm and 240 nm, respectively. The suggested methods have been validated following ICH guidelines, and no statistically significant differences were detected between the results of the current study and the official USP method. It was also found that using experimental design implements the green concept by reducing the environmental impact. Finally, Eco-Scale, GAPI and AGREE were used to assess the environmental impacts of the suggested methods.
Can contrast-enhanced ultrasound differentiate the type of hepatic echinococcosis: cystic echinococcosis or alveolar echinococcosis?
Authors: Zhang Xuhui , Suolang Lamu , Ren Yelei , Wang Yifei , Jiang Yong , Zhong Xiaofei , Gou Zehui , Zhou Wu , Chen Juan , Li Yongzhong , Cai Diming 
Published: April 2023

Abstract
Background
Hepatic echinococcosis (HE) is a zoonotic disease caused by Echinococcus, and Echinococcus granulosus and E. multilocularis are the most common, causing cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Contrast-enhanced ultrasound (CEUS) is an imaging technique which has been recommended for identifying focal lesions in the liver. However, the effect of CEUS on the differentiation of hepatic echinococcosis type remains unclear.

Methods
Twenty-five patients with 46 HE lesions confirmed by histopathology in our hospital from December 2019 to May 2022 were reviewed by conventional ultrasound (US) and CEUS examinations, respectively. After US was completed, the CEUS study was performed. A bolus injection of 1.0–1.2 ml of a sulfur hexafluoride-filled microbubble contrast agent (SonoVue®) was administered. The images and clips of the lesions by US and CEUS were reviewed retrospectively. The lesions detected using US were evaluated including the location, size, morphology, margin, internal echogenicity and the internal Doppler signal. The lesions detected using CEUS were evaluated including the enhancement degree, enhancement pattern and enhancing boundary in different phases. The diagnoses of lesions by US or CEUS were respectively recorded. By taking the histopathology as the gold standard, the paired Chi-square test was performed with statistical software (IBM SPSS; IBM Corp., Armonk, NY, USA), and the results of differentiation of HE type by US and CEUS were statistically analyzed.

Results
A total of 46 lesions were involved in 25 patients, including 10 males (40.0%) and 15 females (60.0%) aged 15–55 (42.9 ± 10.3) years. By histopathology, 24 lesions of nine patients were diagnosed as CE and 22 lesions of 16 patients were diagnosed as AE. Among the 46 HE lesions, compared with histopathological examination, the accuracy rate was 65.2% and 91.3% in US and CEUS findings, respectively. Among the 24 CE lesions, 13 lesions were correctly differentiated by US, and 23 by CEUS. The difference between US and CEUS was statistically significant (Chi-square test, $${\chi }^{2}$$

χ

2

= 8.10, df = 23, P < 0.005). Among the total 46 HE lesions, 30 lesions were correctly differentiated by US, and 42 by CEUS. The difference between US and CEUS was statistically significant (Chi-square test, $${\chi }^{2}$$

χ

2

= 10.08, df = 45, P < 0.005).

Conclusions
CEUS is a more effective technique than US for differentiating the type of HE between CE and AE. It could be a reliable tool in the differentiation of HE.
Transforming growth factor beta 1 is associated with subclinical carotid atherosclerosis in patients with systemic lupus erythematosus
Authors: Gómez-Bernal Fuensanta , Quevedo-Abeledo Juan Carlos , García-González María , Fernández-Cladera Yolanda , González-Rivero Agustín F. , Martín-González Candelaria , González-Gay Miguel Á. , Ferraz-Amaro Iván 
Published: April 2023

Abstract
Background
Transforming growth factor beta (TGF-β1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-β1 has been linked to cardiovascular disease in the general population. The immunosuppressive effect of TGF-β1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-β1 with subclinical carotid atherosclerosis in patients with SLE.

Methods
The study included 284 patients with SLE. Serum levels of TGF-β1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-β1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance.

Results
Circulating TGF-β1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-β1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-β1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-β1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 [95% confidence interval 1.003–1.30], p = 0.045).

Conclusion
TGF-β1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.
Exploring QSAR models for activity-cliff prediction
Authors: Dablander Markus , Hanser Thierry , Lambiotte Renaud , Morris Garrett M. 
Published: April 2023

Abstract
Introduction and methodology
Pairs of similar compounds that only differ by a small structural modification but exhibit a large difference in their binding affinity for a given target are known as activity cliffs (ACs). It has been hypothesised that QSAR models struggle to predict ACs and that ACs thus form a major source of prediction error. However, the AC-prediction power of modern QSAR methods and its quantitative relationship to general QSAR-prediction performance is still underexplored. We systematically construct nine distinct QSAR models by combining three molecular representation methods (extended-connectivity fingerprints, physicochemical-descriptor vectors and graph isomorphism networks) with three regression techniques (random forests, k-nearest neighbours and multilayer perceptrons); we then use each resulting model to classify pairs of similar compounds as ACs or non-ACs and to predict the activities of individual molecules in three case studies: dopamine receptor D2, factor Xa, and SARS-CoV-2 main protease.

Results and conclusions
Our results provide strong support for the hypothesis that indeed QSAR models frequently fail to predict ACs. We observe low AC-sensitivity amongst the evaluated models when the activities of both compounds are unknown, but a substantial increase in AC-sensitivity when the actual activity of one of the compounds is given. Graph isomorphism features are found to be competitive with or superior to classical molecular representations for AC-classification and can thus be employed as baseline AC-prediction models or simple compound-optimisation tools. For general QSAR-prediction, however, extended-connectivity fingerprints still consistently deliver the best performance amongs the tested input representations. A potential future pathway to improve QSAR-modelling performance might be the development of techniques to increase AC-sensitivity.

Graphical Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of chronic kidney disease (CKD)
Authors: Roderburg Christoph , Krieg Sarah , Krieg Andreas , Demir Münevver , Luedde Tom , Kostev Karel , Loosen Sven H. 
Published: April 2023

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations.

Methods
Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models.

Results
A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p < 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73–1.86, p < 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91–2.37, p < 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76–1.95, p < 0.001).

Conclusions
The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.
Scalable and space-efficient Robust Matroid Center algorithms
Authors: Ceccarello Matteo , Pietracaprina Andrea , Pucci Geppino , Soldà Federico 
Published: April 2023

AbstractGiven a dataset V of points from some metric space, a popular robust formulation of the k-center clustering problem requires to select k points (centers) of V which minimize the maximum distance of any point of V from its closest center, excluding the z most distant points (outliers) from the computation of the maximum. In this paper, we focus on an important constrained variant of the robust k-center problem, namely, the Robust Matroid Center (RMC) problem, where the set of returned centers are constrained to be an independent set of a matroid of rank k built on V. Instantiating the problem with the partition matroid yields a formulation of the fair k-center problem, which has attracted the interest of the ML community in recent years. In this paper, we target accurate solutions of the RMC problem under general matroids, when confronted with large inputs. Specifically, we devise a coreset-based algorithm affording efficient sequential, distributed (MapReduce) and streaming implementations. For any fixed $$\varepsilon >0$$

ε
>
0

, the algorithm returns solutions featuring a $$(3+\varepsilon )$$

(
3
+
ε
)

-approximation ratio, which is a mere additive term $$\varepsilon$$
ε
away from the 3-approximations achievable by the best known polynomial-time sequential algorithms. Moreover, the algorithm obliviously adapts to the intrinsic complexity of the dataset, captured by its doubling dimension D. For wide ranges of $$k,z,\varepsilon , D$$

k
,
z
,
ε
,
D

, our MapReduce/streaming implementations require two rounds/one pass and substantially sublinear local/working memory. The theoretical results are complemented by an extensive set of experiments on real-world datasets, which provide clear evidence of the accuracy and efficiency of our algorithms and of their improved performance with respect to previous solutions.