bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LIM Protein AJUBA is a Potential Oncogenic Target and Prognostic Marker in Human Cancer via Pan-Cancer Analysis
Authors: Song Na , Liu Jia , Zhang Ke , Yang Jie , Cui Kai , Miao Zhuang , Zhao Feiyue , Meng Hongjing , Chen Lu , Chen Chong , Li Yushan , Shao Minglong , Su Wei , Wang Haijun 
Published: July 2022

Purpose: The LIM (Lin-11, Isl1, MEC-3) domain protein AJUBA is involved in multiple biological functions, and its aberrant expression is related to the occurrence and progression of various cancers. However, there are no analytical studies on AJUBA in pan-cancer.Methods: We performed a comprehensive pan-cancer analysis and explored the potential oncogenic roles of AJUBA, including gene expression, genetic mutation, protein phosphorylation, clinical diagnostic biomarker, prognosis, and AJUBA-related immune infiltration based on The Cancer Genome Atlas and Genotype-Tissue Expression databases.Results: The results revealed that the expression of AJUBA highly correlated with poor clinical outcomes in patients with different types of cancer. Meanwhile, AJUBA expression was positively correlated with cancer-associated fibroblasts in many human cancers, such as breast invasive carcinoma, colon adenocarcinoma, brain lower-grade glioma, lung adenocarcinoma (LUAD), and ovarian serous cystadenocarcinoma (OV). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that AJUBA is mainly involved in protein serine/threonine kinase activity, cell–cell junction, covalent chromatin modification, and Hippo signaling pathway.Conclusion: The pan-cancer study reveals the oncogenic roles of AJUBA and provides a comprehensive understanding of the molecular biological genetic information of AJUBA in various tumors.
The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers
Authors: Iborra-Egea Oriol , Aimo Alberto , Martini Nicola , Galvez-Monton Carolina , Burchielli Silvia , Panichella Giorgia , Passino Claudio , Emdin Michele , Bayes-Genis Antoni 
Published: July 2022

BackgroundLeft ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction ≤ 45%.MethodsWe compared the molecular effects of paroxetine and drugs for neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists), using a bioinformatic approach integrating transcriptomic data in a swine model of post-MI and available evidence from the literature and massive public databases.ResultsAmong standard therapies for MI, beta-blockers are the only ones acting directly upon GKR2, but the mechanism of action overlaps with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with respect to the AT2R-mediated anti-hypertensive response. Moreover, beta-blockers could have anti-fibrotic and anti-inflammatory effects through the regulation of myocyte-specific enhancer factors, endothelins and chemokines.ConclusionThe additive benefit of paroxetine on the background of the standard therapy for STEMI, which includes beta-blockers, is expected to be limited. Nonetheless, paroxetine becomes particularly interesting when a beta-blocker is contraindicated (for example, in hypotensive individuals) or poorly tolerated.
Tropical Cyclones Intensity Prediction in the Western North Pacific Using Gradient Boosted Regression Tree Model
Authors: Zhu Gangya , Li Qinglan , Zhao Wei , Lv Xinyan , Qian Chuanhai , Qian Qifeng 
Published: July 2022

As an artificial intelligence method, machine learning (ML) has been widely used in prediction models of high-dimensional datasets. This study proposes an ML method, the Gradient Boosted Regression Tree (GBRT), to predict the intensity changes of tropical cyclones (TCs) in the Western North Pacific at 12-, 24-, 36-, 48-, 60-, and 72-h (hr) forecasting lead time and the model is optimized by the Bayesian Optimization algorithm. The model predictands are the TCs intensity changes at different forecasting lead times, obtained from the best track data of the Shanghai Typhoon Institute (STI) and the Joint Typhoon Warning Center (JTWC) from 2000 to 2019. The model predictors are the synoptic variables, climatological and persistent variables derived from the reanalysis data obtained from the National Centers for Environmental Prediction (NCEP), and the sea surface temperature (SST) data obtained from the National Oceanic and Atmospheric Administration (NOAA). The results show that the GBRT model can capture the TCs intensity changes well for the succeeding 12-h, 24-h, 36-h, and 72-h. Compared with the traditional multiple linear regression (MLR) model, the GBRT model has better performance in predicting TCs intensity changes. Compared with the MLR model, R2 of the GBRT model for TCs intensity forecast increases by an average of 8.47% and 4.45% for STI data and JTWC data. MAE (RMSE) drops by 26.24% (25.14%) and 10.51% (4.68%) for the two datasets, respectively. The potential future intensity change (POT), the intensity changes during the previous 12 h (Dvmax), Initial storm maximum wind speed (Vmax), SST, and the Sea-Land ratio are the most significant predictors for the GBRT model in predicting TCs intensity change over the Western North Pacific.
OSL Dating of Paleo-Shorelines at Dagze Co, Central Tibetan Plateau
Authors: Wu Yang , Chen Yiwei , Huang Long , Ding Ping , Cui Hao , Wei Gangjian 
Published: July 2022

Well-preserved paleo-shoreline systems suggest lake shrinkage occurred in a vast region of the Tibetan Plateau, indicating dramatic paleo-environmental changes that linked closely to variations in Asian monsoon precipitation, glacial meltwater, and evaporation. The elevation and chronology of these shoreline features can be used to reconstruct lake level fluctuation history and regional paleo-climate. Here, we report optically stimulated luminescence (OSL) dating of 14 sediment samples from three of seven paleo-shorelines at south of Dagze Co, central Tibetan Plateau, using coarse-grained quartz and K-feldspar. Two fine grain silt samples were also measured. The results suggest the following: 1) The highest paleo-shoreline for Dagze Co has an elevation around 4,525 m (+55 m above modern lake). Its age is estimated to be 9.1 ± 0.5 to 9.6 ± 0.6 ka, suggesting a relative humid condition in the early Holocene. 2) After that, the lake level dropped ∼20 m and remained relatively stable (+35 m) from ∼8 to 5 ka, implying a dry condition with reduced runoff. Lake level further declined for ∼40 m since about 5 ka. 3) The general trend of shrinkage for Dagze Co broadly matches studies from adjacent lakes, suggesting a common pattern of lake’s evolution on the south/central plateau in the late Quaternary. The long-term decreasing trend of Asian monsoon precipitation should be the main reason.
Comparative Transcriptome Analyses of Geriatric Rats Associate Age-Related Erectile Dysfunction With a lncRNA-miRNA-mRNA Regulatory Network
Authors: Zhou Xuan , Cong Rong , Yao Liangyu , Zhou Xiang , Luan Jiaochen , Zhang Qijie , Zhang Xu , Ren Xiaohan , Zhang Tongtong , Meng Xianghu , Song Ninghong 
Published: July 2022

BackgroundThe key regulatory roles of long non-coding RNAs (lncRNAs) in age-related erectile dysfunction (A-ED) are unknown.AimThis study aimed to identify putative lncRNAs that regulate age-related erectile dysfunction via transcriptome analyses, and to predict their specific regulatory routes via bioinformatics methods.Methods22 geriatric male SD rats were divided into age-related erectile dysfunction (A-ED) and negative control (NC) groups after evaluations of intracavernous pressure (ICP). By comparative analysis of transcriptomes of cavernosal tissues from both groups, we identified differentially expressed lncRNAs, miRNAs, and mRNAs. Seven differentially expressed lncRNAs were selected and further verified by quantitative real-time polymerase chain reactions (RT-qPCR). The construction of the lncRNA-miRNA-mRNA network, the Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in Cytoscape.ResultsFrom comparative transcriptome analyses of A-ED and NC groups, 69, 29, and 364 differentially expressed lncRNAs, miRNAs, and mRNAs were identified respectively. Differentially expressed lncRNAs were culled to seven, which were all verified by qPCR. Three of these lncRNAs (ENSRNOT00000090050, ENSRNOT00000076482, and ENSRNOT00000029245) were used to build regulatory networks, of which only ENSRNOT00000029245 was successful. Moreover, GO and KEGG analyses demonstrated that these lncRNAs possibly regulated muscle myosin complex, muscle cell cellular homeostasis, and ultimately erectile function in rats through PI3K-Akt, fluid shear stress, and atherosclerosis pathways.ConclusionOur study identified differentially expressed lncRNAs, miRNAs, and mRNAs through comparisons of transcriptomes of geriatric rats. An identified lncRNA verified by qPCR, was used to construct a lncRNA-miRNA-mRNA regulatory network. LncRNA ENSRNOT00000029245 possibly regulated downstream mRNAs through this regulatory network, leading to apoptosis in the cavernous tissue, fibrosis, and endothelial dysfunction, which ultimately caused ED. These findings provide seminal insights into the molecular biology of aging-related ED, which could spur the development of effective therapeutics.
Sulfur-Oxidizing Bacteria From Coal Mine Enhance Sulfur Nutrition in Pigeonpea (Cajanus cajan L.)
Authors: Malviya Deepti , Varma Ajit , Singh Udai B. , Singh Shailendra , Singh Harsh V. , Saxena Anil K. 
Published: July 2022

The present investigation was carried out to isolate, identify, and characterize sulfur-oxidizing bacteria (SOB) from coal mines and to evaluate the efficient strains for their ability to influence plant growth and S uptake in pigeonpea. Thirteen bacterial isolates belonging toStenotrophomonas maltophilia(2),Stenotrophomonas pavanii(2),Rhizobium pusense(5),Bacillus velezensis(2), andPaenibacillus massiliensis(2) were obtained. Among these, seven strains that could reduce the pH of thiosulfate broth were further characterized for sulfur oxidation, plant growth-promoting (PGP) attributes, andin plantastudies. Among the seven strains characterized, maximum sulfate ion was recorded forS.maltophiliaDRC-18-7A (311.43 mg L−1) closely followed byS.pavaniiDRC-18-7B (273.44 mg L−1) andS.maltophiliaDRC-18-10 (265.75 mg L−1) after 21 days of inoculation. Among the PGP attributes quantified, maximum P solubilization was recorded in case ofS.maltophiliaDRC-18-7A (24.39 μg ml−1), while highest siderophore production and IAA production were recorded inS.maltophiliaDRC-18-10 (14.25%) andR.pusenseDRC-18-25 (15.21 μg ml−1), respectively.S.maltophiliaDRC-18-7A closely followed byS.pavaniiDRC-18-7B outperformed others in enhancing seed germination (%) and vigour indices. Results clearly indicated that microbial inoculants colonized the plant roots and developed biofilm on the root surface. It was further observed that plants treated with microbial inoculants induce an early formation of secondary and tertiary roots in the pigeonpea compared to the untreated control which was further confirmed by assessing the root architecture using the root scanner. Inoculation of these two strains to pigeonpea significantly enhanced plant growth parameters, the activity of reactive oxygen scavenging (ROS) enzymes, and accumulation of flavonoids, carotenoids, and proline both under sterilized and non-sterilized growth medium (sand and soil in 1:3 ratio). The application of microbial inoculants significantly increased the uptake of nitrogen, phosphorus, potassium, and sulfur in plant shoots. Further, transcript level of phosphate, potassium, and sulfur transporter genes significantly increases upon microbial inoculation leading to increased uptake and translocation of P, K, and S in the pigeonpea. The results indicate thatS.maltophiliaDRC-18-7A andS.pavaniiDRC-18-7B could be recommended as inoculants for pigeonpea to improve its growth and sulfur nutrition.
JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer
Authors: Liang Xisong , Zhang Hao , Wang Zeyu , Zhang Xun , Dai Ziyu , Zhang Jian , Luo Peng , Zhang Longbo , Hu Jason , Liu Zaoqu , Bi Changlong , Cheng Quan 
Published: July 2022

BackgroundJMJD8 has recently been identified as a cancer-related gene, but current studies provide limited information. We aimed to clarify its roles and the potential mechanisms in pan-cancer.MethodsPan-cancer bulk sequencing data and online web tools were applied to analyze JMJD8’s correlations with prognosis, genome instability, cancer stemness, DNA repair, and immune infiltration. Moreover, single-cell datasets, SpatialDB database, and multiple fluorescence staining were used to validate the association between JMJD8 expression and M2 macrophages. Further, we utilized ROCplotter and cMap web tool to analyze the therapeutic responses and screened JMJD8-targeted compounds, respectively, and we used AlphaFold2 and Discovery Studio to conduct JMJD8 homology modeling and molecular docking.ResultsWe first noticed that JMJD8 was an oncogene in many cancer types. High JMJD8 was associated with lower genome stability. We then found that high JMJD8 correlated with high expression of mismatch repair genes, stemness, homologous repair gene signature in more than 9 cancers. ESTIMATE and cytokine analyses results presented JMJD8’s association with immunosuppression. Also, immune checkpoint CD276 was positively relevant to JMJD8. Subsequently, we validated JMJD8 as the M2 macrophage marker and showed its connection with other immunosuppressive cells and CD8+ T-cell depression. Finally, potential JMJD8-targeted drugs were screened out and docked to JMJD8 protein.ConclusionWe found that JMJD8 was a novel oncogene, and it correlated with immunosuppression and DNA repair. JMJD8 was highly associated with immune checkpoint CD276 and was an M2 macrophage biomarker in many cancers. This study will reveal JMJD8’s roles in pan-cancer and its potential as a novel therapeutic target.
Adenosine Deaminase 2 Deficiency (DADA2): A Crosstalk Between Innate and Adaptive Immunity
Authors: Signa Sara , Bertoni Arinna , Penco Federica , Caorsi Roberta , Cafaro Alessia , Cangemi Giuliana , Volpi Stefano , Gattorno Marco , Schena Francesca 
Published: July 2022

Deficiency of Adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disorder presenting with a broad spectrum of clinical manifestations, including immunodeficiency, vasculopathy and hematologic disease. Biallelic mutations in ADA2 gene have been associated with a decreased ADA2 activity, leading to reduction in deamination of adenosine and deoxyadenosine into inosine and deoxyinosine and subsequent accumulation of extracellular adenosine. In the early reports, the pivotal role of innate immunity in DADA2 pathogenic mechanism has been underlined, showing a skewed polarization from the M2 macrophage subtype to the proinflammatory M1 subtype, with an increased production of inflammatory cytokines such as TNF-α. Subsequently, a dysregulation of NETosis, triggered by the excess of extracellular Adenosine, has been implicated in the pathogenesis of DADA2. In the last few years, evidence is piling up that adaptive immunity is profoundly altered in DADA2 patients, encompassing both T and B branches, with a disrupted homeostasis in T-cell subsets and a B-cell skewing defect. Type I/type II IFN pathway upregulation has been proposed as a possible core signature in DADA2 T cells and monocytes but also an increased IFN-β secretion directly from endothelial cells has been described. So far, a unifying clear pathophysiological explanation for the coexistence of systemic inflammation, immunedysregulation and hematological defects is lacking. In this review, we will explore thoroughly the latest understanding regarding DADA2 pathophysiological process, with a particular focus on dysregulation of both innate and adaptive immunity and their interacting role in the development of the disease.
Muscle Ultrasound as Imaging Domain of Frailty
Authors: Bencivenga Leonardo , Picaro Francesco , Ferrante Lorenzo , Komici Klara , Ruggiero Federico , Sepe Immacolata , Gambino Giuseppina , Femminella Grazia Daniela , Vitale Dino Franco , Ferrara Nicola , Rengo Carlo , Rengo Giuseppe 
Published: July 2022

IntroductionFrailty is a geriatric syndrome, a clinical state of vulnerability for developing dependency and/or death. Due to its multidimensional nature, Comprehensive Geriatric Assessment (CGA) constitutes the best strategy to evaluate frailty in older patients. Accumulation of deficits model synthesizes the global assessment of geriatric domains in the Frailty Index (FI) score. Muscle Ultrasound (MUS) has been employed to evaluate muscle mass wasting as tool to assess sarcopenia in late life. The present study aims to evaluate the association between CGA-based FI and MUS measures in a population of hospitalized older adults.MethodsPatients aged ≥65 years underwent CGA for the evaluation of the domains of health and functional status, psycho-cognition, nutritional status, socio-environmental condition. Following standard procedure, a CGA-based FI was elaborated, taking into account 38 multidimensional items. Muscle thicknesses (MT) of rectus femoris plus vastus intermedius were measured through MUS axial cross-section. Multivariable regression analysis was employed to determine factors associated with FI.ResultsThe study population consisted of 136 older patients, 87 men (63.9%), with median age of 74 (70–81) years, FI of 0.3 (0.21–0.46), and MT of rectus femoris plus vastus intermedius 29.27 (23.08–35.7) mm. At multivariable regression analysis, FI resulted significantly and independently associated with age and MT.ConclusionMuscle thicknesses of rectus femoris plus vastus intermedius, measured through MUS, resulted to be significantly related to FI in a population of hospitalized older patients. In the CGA-based assessment of frailty, MUS may constitute an additional imaging domain.
Unexpected Detection of Anti-SARS-CoV-2 Antibodies Before the Declaration of the COVID-19 Pandemic
Authors: Mahallawi Waleed , Ibrahim Nadir 
Published: July 2022

Background:Limited information is currently available regarding the global incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections prior to the declaration of the coronavirus disease 2019 (COVID-19) pandemic, which may result in improper conclusions regarding the timing of viral transmission.MethodsWe investigated the presence of specific antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in archived serum samples that were collected from 478 healthy blood donors and patients in Madinah, Saudi Arabia, between October 2019 and January 2020. Enzyme-linked immunosorbent assay (ELISA) was performed to measure SARS-CoV-2 IgM and IgG antibodies. In addition, rheumatoid factor (RF) and urea dissociation tests were performed in all samples, which showed seropositivity for the SARS-CoV-2 IgM antibody. Additionally, Chemiluminescence immunoassays (CLIA) targeting the RBD of the SARS-CoV-2 spike (S) protein were performed to confirm the seropositivity of the samples.ResultsOverall, 20 (4.18%) serum samples were detected by ELISA to have SARS-CoV-2 IgG or IgM antibodies. Of these, 12 (2.51%) samples were positive for IgM antibody, and 8 (1.67%) were positive for IgG antibody. The 12 samples positive for SARS-CoV-2 IgM antibody were subjected to RF and urea dissociation tests, and all samples were RF-negative. The ELISA results were negative for 7 (58.33%) samples when subjected to urea dissociation prior to ELISA, whereas the other 5 (41.67%) samples remained positive. These 5 samples remained positive for the anti-S RBD IgG antibody in the CLIA. In addition, 3 of the 8 samples with IgG positivity according to the ELISA remained positive in the CLIA. After reviewing their data, we discovered that the 8 CLIA-confirmed positive samples were obtained from returned travellers who had visited China during the 4-week period immediately preceding blood donation.ConclusionIn conclusion, we found evidence to support the early circulation of SARS-CoV-2 among persons who visited China a few months prior to the pandemic declaration. These results can be used to better define the spread of SARS-CoV-2 infections before the COVID-19 pandemic declaration. The detection of SARS-CoV-2 antibodies in individuals before the pandemic was declared in China could rewrite the pre-pandemic timeline.
Case Report: A 72-Year-Old Woman With Progressive Motor Weakness, Dry Eyes and High Levels of Serum Neurofilament Light Chain
Authors: Wendebourg Maria Janina , Kuhle Jens , Hardmeier Martin 
Published: July 2022

BackgroundDiagnosis of Amyotrophic Lateral Sclerosis (ALS) is challenging as initial presentations are various and diagnostic biomarkers are lacking. The diagnosis relies on the presence of both upper and lower motor neuron signs and thorough exclusion of differential diagnoses, particularly as receiving an ALS diagnosis has major implications for the patient. Sjögren's syndrome may mimic peripheral ALS phenotypes and should be considered in the work-up.CaseA 72-year-old female presented with a mono-neuropathy of the right leg and a complaint of dry eyes and mouth. Initial diagnostic work-up confirmed a regional sensorimotor neuropathy and a Sjögren's syndrome; a causal relationship was assumed. However, motor symptoms spread progressively despite immunosuppressive treatment, eventually including both legs, both arms and the diaphragm. Clinically, unequivocal central signs were lacking, but further along in the disease course, the atrophy pattern followed a split phenotype and deep tendon reflexes were preserved. Nerve biopsy did not show vasculitic infiltration; however, serum neurofilament light chain (sNfL) concentrations were and remained persistently highly elevated despite immunosuppressive treatment. Electrodiagnostic re-evaluation confirmed denervation in 3 regions. A diagnosis of familial ALS was finally confirmed by a C9orf 72 repeat expansion. Stationary sensory symptoms were best explained by a neuropathy associated with concomitant Sjögren's syndromeDiscussionOur instructive case shows the difficulties of diagnosing ALS in the setting of a peripheral symptom onset and a concurrent but unrelated condition also causing neuropathy. Such cases require high clinical vigilance and readiness to reappraise diagnostic findings if the disease course deviates from expectation. Recently proposed simplified diagnostic criteria, genetic testing and body fluid biomarkers such as sNfL may facilitate the diagnostic process and lead to an earlier diagnosis of ALS.