bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D in-vitro cultures of human bone marrow and Wharton’s jelly derived mesenchymal stromal cells show high chondrogenic potential
Authors: Lamparelli Erwin Pavel , Ciardulli Maria Camilla , Giudice Valentina , Scala Pasqualina , Vitolo Rosa , Dale Tina Patricia , Selleri Carmine , Forsyth Nicholas Robert , Maffulli Nicola , Della Porta Giovanna 
Published: September 2022

In this study, chondrogenic potentials of 3D high-density cultures of Bone Marrow (BM) and Wharton’s Jelly (WJ)-derived mesenchymal stromal cells (MSCs) was investigated by chondrogenesis- and cytokine-related gene expression over a 16-day culture period supplemented with human transforming growth factor (hTGF)-β1 at 10 ng/ml. In BM-MSC 3D models, a marked upregulation of chondrogenesis-related genes, such as SOX9, COL2A1, and ACAN (all p &lt; 0.05) and formation of spherical pellets with structured type II collagen fibers were observed. Similarly, WJ-based high-density culture appeared higher in size and more regular in shape, with a significant overexpression of COL2A1 and ACAN (all p &lt; 0.05) at day 16. Moreover, a similar upregulation trend was documented for IL-6 and IL-10 expression in both BM and WJ 3D systems. In conclusion, MSC-based high-density cultures can be considered a promising in vitro model of cartilage regeneration and tissue engineering. Moreover, our data support the use of WJ-MSCs as a valid alternative for chondrogenic commitment of stem cells in regenerative medicine.
Energetic electron irradiations of amorphous and crystalline sulphur-bearing astrochemical ices
Authors: Mifsud Duncan V. , Herczku Péter , Rácz Richárd , Rahul K. K. , Kovács Sándor T. S. , Juhász Zoltán , Sulik Béla , Biri Sándor , McCullough Robert W. , Kaňuchová Zuzana , Ioppolo Sergio , Hailey Perry A. , Mason Nigel J. 
Published: September 2022

Laboratory experiments have confirmed that the radiolytic decay rate of astrochemical ice analogues is dependent upon the solid phase of the target ice, with some crystalline molecular ices being more radio-resistant than their amorphous counterparts. The degree of radio-resistance exhibited by crystalline ice phases is dependent upon the nature, strength, and extent of the intermolecular interactions that characterise their solid structure. For example, it has been shown that crystalline CH3OH decays at a significantly slower rate when irradiated by 2 keV electrons at 20 K than does the amorphous phase due to the stabilising effect imparted by the presence of an extensive array of strong hydrogen bonds. These results have important consequences for the astrochemistry of interstellar ices and outer Solar System bodies, as they imply that the chemical products arising from the irradiation of amorphous ices (which may include prebiotic molecules relevant to biology) should be more abundant than those arising from similar irradiations of crystalline phases. In this present study, we have extended our work on this subject by performing comparative energetic electron irradiations of the amorphous and crystalline phases of the sulphur-bearing molecules H2S and SO2 at 20 K. We have found evidence for phase-dependent chemistry in both these species, with the radiation-induced exponential decay of amorphous H2S being more rapid than that of the crystalline phase, similar to the effect that has been previously observed for CH3OH. For SO2, two fluence regimes are apparent: a low-fluence regime in which the crystalline ice exhibits a rapid exponential decay while the amorphous ice possibly resists decay, and a high-fluence regime in which both phases undergo slow exponential-like decays. We have discussed our results in the contexts of interstellar and Solar System ice astrochemistry and the formation of sulphur allotropes and residues in these settings.
Recent developments in the design and synthesis of benzylpyridinium salts: Mimicking donepezil hydrochloride in the treatment of Alzheimer’s disease
Authors: Sepehri Saghi , Saeedi Mina , Larijani Bagher , Mahdavi Mohammad 
Published: September 2022

Background: Alzheimer’s disease (AD) is an advanced and irreversible degenerative disease of the brain, recognized as the key reason for dementia among elderly people. The disease is related to the reduced level of acetylcholine (ACh) in the brain that interferes with memory, learning, emotional, and behavior responses. Deficits in cholinergic neurotransmission are responsible for the creation and progression of numerous neurochemical and neurological illnesses such as AD.Aim: Herein, focusing on the fact that benzylpyridinium salts mimic the structure of donepezil hydrochlorideas a FDA-approved drug in the treatment of AD, their synthetic approaches and inhibitory activity against cholinesterases (ChEs) were discussed. Also, molecular docking results and structure–activity relationship (SAR) as the most significant concept in drug design and development were considered to introduce potential lead compounds. Key scientific concepts: AChE plays a chief role in the end of nerve impulse transmission at the cholinergic synapses. In this respect, the inhibition of AChE has been recognized as a key factor in the treatment of AD, Parkinson’s disease, senile dementia, myasthenia gravis, and ataxia. A few drugs such as donepezil hydrochloride are prescribed for the improvement of cognitive dysfunction and memory loss caused by AD. Donepezil hydrochloride is a piperidine-containing compound, identified as a well-known member of the second generation of AChE inhibitors. It was established to treat AD when it was assumed that the disease is associated with a central cholinergic loss in the early 1980s. In this review, synthesis and anti-ChE activity of a library of benzylpyridinium salts were reported and discussed based on SAR studies looking for the most potent substituents and moieties, which are responsible for inducing the desired activity even more potent than donepezil. It was found that linking heterocyclic moieties to the benzylpyridinium salts leads to the potent ChE inhibitors. In this respect, this review focused on the recent reports on benzylpyridinium salts and addressed the structural features and SARs to get an in-depth understanding of the potential of this biologically improved scaffold in the drug discovery of AD.
Facile synthesis, crystal structure, biological evaluation, and molecular modeling studies of N-((4-acetyl phenyl) carbamothioyl) pivalamide as the multitarget-directed ligand
Authors: Saeed Aamer , Ejaz Syeda Abida , Khalid Aqsa , Channar Pervaiz Ali , Aziz Mubashir , Wani Tanveer A. , Zargar Seema , Hassan Sidra , Ismail Hammad , Khalid Dania , Hashmi Muhammad Zaffar , Hökelek Tuncer , Aborode Abdullahi Tunde 
Published: September 2022

The crystal structure of N-((4-acetylphenyl)carbamothioyl)pivalamide (3) was synthesized by inert refluxing pivaloyl isothiocyanate (2) and 4-aminoacetophenone in dry acetone. The spectroscopic characterization (1H-NMR, 13CNMR, FT-IR) and single crystal assays determined the structure of synthesized compound (3). Systematic experimental and theoretical studies were conducted to determine the molecular characteristics of the synthesized crystal. The biological examination of (3) was conducted against a variety of enzymes i.e., acetyl cholinesterase (AChE), butyl cholinesterase (BChE), alpha amylase, and urease enzyme were evaluated. The crystal exhibited approximately 85% enzyme inhibition activity against BChE and AChE, but only 73.8 % and 57.9% inhibition activity against urease and alpha amylase was observed respectively. The theoretical calculations were conducted using density functional theory studies (DFTs) with the 6–31G (d, p) basis set and B3LYP functional correlation. The Frontier molecular orbital analysis revealed that the HOMO/LUMO energy gap was smaller, which corresponds to the molecule’s reactivity. In terms of reactivity, the chemical softness value was found to be in good agreement with experimental values. In Crystal structure analysis, the intramolecular N—H•••O hydrogen bond generates a S 6) ring motif and N—H•••O interactions exist in crystal structure between the centroids of neighboring parallel aromatic (C4-C9) rings with a centroid to centroid distance of 3.9766 (7)Å. These intermolecular interactions were useful in structural stabilization. The Hirshfeld surfaces and their related two-dimensional fingerprint plots were used for thorough investigation of intermolecular interactions. According to Hirshfeld surface analysis of the crystal structure the most substantial contributions to the crystal packing are from H ••• O and H ••• N/N ••• H interactions. Molecular docking studies were conducted to evaluate the binding orientation of synthesized crystal with multiple targets. The compound exhibited stronger interactions with AChE and BChE with binding energies of -7.5 and -7.6 kcal/mol, respectively. On the basis of in-vitro and in-silico findings, it is deduced that N-((4-acetylphenyl)carbamothioyl)pivalamide 3) possesses reactive and potent multiple target inhibitory properties.
Risk factors of in-hospital mortality in patients with pneumocystis pneumonia diagnosed by metagenomics next-generation sequencing
Authors: Hou Jun-Na , Liu Heng-Dao , Tan Qiu-Yue , Cao Feng-An , Wang Shi-Lei , Yao Meng-Ying , Zhao Yang-Chao 
Published: September 2022

ObjectivesThe metagenomic next-generation sequencing (mNGS) test is useful for rapid and accurate detection and identification of pathogenic microorganisms. The aim of the present study was to investigate the factors associated with in-hospital mortality in pneumocystis pneumonia (PCP) patients with mNGS-assisted diagnosis.MethodsOur study enrolled 154 patients with mNGS-positive PCP from August 2018 to February 2022 at the First Affiliated Hospital of Zhengzhou University respectively. Patients were divided into the survivor group (n=98) and the death group (n=56) according to whether in-hospital death occurred. Baseline characteristics, patients’ pre-hospital symptoms and patients’ CT imaging performance during hospitalization were carefully compared between the two groups. Risk factors for the occurrence of in-hospital death were sought by selecting indicators that were significantly different between the two groups for modelling and performing multiple logistic regression analysis.ResultsCompared with the in-hospital death patients, the survivors were younger and had higher levels of albumin (ALB) (age: 50.29 ± 14.63 years vs 59.39 ± 12.27 years, p&lt;0.001; ALB: 32.24 ± 5.62 g/L vs 29.34 ± 5.42g/L, p=0.002; respectively), while the levels of lactate dehydrogenase (LDH) and C-reactive protein CRP were lower (LDH: 574.67 ± 421.24 U/L vs 960.80 ± 714.94 U/L, p=0.001; CRP: 54.97 ± 55.92 mg/L vs80.45 ± 73.26 mg/L, p=0.018; respectively). Multiple logistic regression analysis revealed that age, the baseline LDH and CRP levels were all positively associated with high in-hospital mortality [age: OR(95%CI): 1.115 (1.062-1.172), p&lt;0.001; LDH: OR(95%CI): 1.002 (1.001-1.003), p&lt;0.001; CRP: OR(95%CI): 1.008 (1.000-1.017), p=0.045; respectively] while the platelet counts was negatively associated with it [OR(95%CI): 0.986 (0.979-0.992), p&lt;0.001].ConclusionsOld age, high baseline levels of LDH and CRP and low platelet counts were risk factors of the in-hospital mortality in mNGS positive PCP patients.
Platelet-derived TGF-β1 is related to portal vein thrombosis in cirrhosis by promoting hypercoagulability and endothelial dysfunction
Authors: Jiang Siyu , Ai Yingjie , Ni Liyuan , Wu Ling , Huang Xiaoquan , Chen Shiyao 
Published: September 2022

BackgroundPortal vein thrombosis (PVT) is a serious complication of cirrhosis accompanied by unclear pathogenesis. Transforming growth factor-beta (TGF-β) has been implicated in atherosclerosis and venous thrombosis whereas study regarding its part in PVT is lacking. The aim of this study was to explore the role of cytokine TGF-β1 in PVT and the potential mechanism.Materials and methodsWe included patients with cirrhotic gastroesophageal varices and divided them into two groups according to the presence of PVT. Serum levels of TGF-β1 were detected using Cytometric Bead Array kit and compared between two groups. Coagulation status was assessed using thromboelastography (TEG). Primary liver sinusoidal endothelial cells were treated with TGF-β1 and evaluated for endothelial dysfunction by RT-PCR.ResultsOur results uncovered that TGF-β1 (6,866.55 vs. 3,840.60 pg/ml, P = 0.015) significantly increased in the PVT group. Splenectomy might promote PVT by increasing platelet-derived TGF-β1 levels. Other cytokines showed no difference between PVT and non-PVT groups. Besides, TGF-β1 was correlated with platelet, fibrinogen, TEG-CI, TEG-MA, and TEG-α (coef = 0.733, 0.494, 0.604, 0.608, and 0.511; P &lt; 0.001, 0.027, 0.004, 0.004, and 0.021, respectively), which indicated a hypercoagulable state in PVT patients. RT-PCR of liver sinusoidal endothelial cells showed a markable increment of von Willebrand Factor (vWF), thrombomodulin(TM), intercellular adhesion moleclar-1(ICAM-1), and vascular endothelial growth factor(VEGF) after TGF-β1 treatment, suggesting the involvement of endothelial dysfunction.ConclusionElevated platelet-derived TGF-β1 exhibited association with hypercoagulability and promoting effect on endothelial dysfunction, closely related with PVT in cirrhotic patients.
The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials
Authors: Zhou Feifei , Du Nannan , Zhou Lulin , Wang Chenxi , Ren He , Sun Qiang 
Published: September 2022

BackgroundDiabetes mellitus (DM) is a global health problem, and it has become a shocking threat in the contemporary era. The objective of this study was to analyze the safety of sotagliflozin in patients with DM systematically and intuitively.MethodsOn November 15, 2021, literature retrieval was performed on PubMed, Web of Science, EBSCO, and Cochrane libraries. The meta-analysis results included genital mycotic infection, related-to-acidosis events, and other related adverse events, including diarrhea, severe nocturnal hypoglycemia event, and volume depletion. In addition, a subgroup analysis was also conducted based on different doses of sotagliflozin. Moreover, the patient-treated years analyzed in the study were 12 weeks, 24 weeks, and 52 weeks, respectively, for type 1 diabetes, and were 12 weeks, 22 weeks, and 52 weeks, respectively, for type 2 diabetes.ResultsThe results of this meta-analysis illustrated that sotagliflozin could increase the risk of genital mycotic infection for patients with T1D and T2D (RR: 3.49, 95% Cl: 2.54-4.79, p &lt; 0.001; RR: 2.83, 95% Cl: 2.04-3.93, p &lt; 0.001; respectively). In addition, the subgroup analysis showed that the drug doses that could increase the risk of genital mycotic infection were 400 mg and 200 mg (RR: 3.63, 95% Cl: 2.46-5.36, p &lt; 0.001; RR: 3.21, 95% Cl: 1.84-5.62, p &lt; 0.001; respectively) in T1D. Moreover, sotagliflozin could increase the risk of events related to acidosis in the patients of T1D, including acidosis-related adverse events, positively adjudicated diabetic ketoacidosis, acidosis-related event, and diabetic ketoacidosis (RR: 7.49, 95% Cl: 3.20-17.52, p &lt; 0.001; RR: 6.05, 95% Cl: 2.56-14.30, p &lt; 0.001; RR: 4.83, 95% Cl: 3.13-7.45, p &lt; 0.001; RR: 8.12, 95% Cl: 3.06-21.52, p &lt; 0.001; respectively). In the patients of T2D, sotagliflozin could not increase the risk of DKA (RR: 1.30, 95% Cl: 0.34-4.99, p = 0.70). About serious of acidosis-related adverse events, positively adjudicated diabetic ketoacidosis (DKA) and acidosis-related event, the included studies were not reported for T2D patients. As for the other related adverse events, sotagliflozin was found to be a risk factor for diarrhea and volume depletion in T1D patients (RR: 1.44, 95% Cl: 1.09-1.90, p = 0.01; RR: 2.50, 95% Cl: 1.33-4.69, p &lt; 0.01; respectively) and T2D patients (RR: 1.44, 95% Cl: 1.26-1.64, p &lt; 0.001; RR: 1.25, 95% Cl: 1.07-1.45, p &lt; 0.01; respectively).ConclusionsThis meta-analysis showed that the adverse events of sotagliflozin were tolerable to patients with DM, in terms of the incidence of genital mycotic infection, related-to-acidosis events, diarrhea, volume depletion, and severe nocturnal hypoglycemia events. In addition, the subgroup analysis of sotagliflozin dosage is considered to have great clinical significance for future guidance of sotagliflozin application in patients with DM.
Rio (1992) to Glasgow (2021): Three decades of inadequate mitigation of climate change and its slow onset effects
Authors: Stavi Ilan 
Published: September 2022

This study reviews the global increase in atmospheric greenhouse gas (GHG) concentrations, including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), alongside the accelerated climatic change and its slow onset effects (or events) between 1992 and 2021. The establishment of the United Nations Framework Convention on Climate Change (UNFCCC) in 1992, and the simultaneous UN Earth Summit in Rio de Janeiro, generated the international efforts to tackle climatic change. Over the years, the UNFCCC-Conference of the Parties (COP) has led the efforts in climate change mitigation and adaptation, with many sequential meetings across the world. Three decades later, at the COP26 meeting in Glasgow in 2021, it is evident that climate change impacts have substantially worsened. Despite some uncertainties, it seems that over the last three decades, the climate change slow onset events, including 1) increasing temperatures, 2) glacial retreat, 3) sea level rise, 4) ocean acidification, 5) soil salinization, 6) land and forest degradation, 7) loss of biodiversity, and 8) desertification, have substantially exacerbated. Simultaneously, other (non-GHGs related) anthropogenic impacts, including habitat fragmentation, land-use and sea-use change and misuse, species overexploitation, environmental pollution, infrastructure constructions, and urbanization, have considerably increased. With the aim of achieving the Shared Socio-Economic Pathways 1.9 (SSP1-1.9) or SSP1-2.6 ultimate goals—keeping global warming in 2,100 below 1.5°C or 2.0°C, respectively, compared to preindustrial levels—it may still be possible to avoid climate change’s irreversible tipping points. To reach this target, policymaking must become more decisive and proactive, with continuous risks assessment, frequent monitoring of outcomes and their compatibility to goals, implementing practical legislation tools, and assigning specific financial instruments, aimed at effectively tackling climate change slow onset events and related environmental issues. Substantial efforts should be invested in boosting climate change mitigation, while simultaneously targeting effective climatic change adaptation measures and promoting environmental conservation and restoration. Relying on tools such as the UN Sustainable Development Goals (SDGs) will sustain provisioning, supporting, regulating, and cultural ecosystem services, thus improving water-, food-, environmental-, energy-, economic-, health-, and governance-security, while lessening the risks of social unrest, violent conflicts, mass migration, and other humanitarian catastrophes.
Identification of m6A-related long non-coding RNAs for predicting prognosis and immune characterizations in gastric cancer
Authors: Zhang Xianhui , Wang Changjing , Liu Zhongxin , Si Yuan 
Published: September 2022

Background: N6-methyladenosine (m6A) mRNA modification triggers malignant behavior in tumor cells, which promotes malignant progression and migration of gastric cancer (GC). Nevertheless, studies on the prognostic value of m6A-related long non-coding RNA (MRlncRNA) in GC remain quite restricted. The study aimed to develop a reasonable predictive model to explore the prognostic potential of MRlncRNAs in predicting the prognosis of GC patients and monitoring the efficacy of immunotherapy.Methods: Transcriptomic and clinical data for GC were derived from TCGA. Next, univariate Cox, LASSO and multivariate Cox regression analyses were next used to identify prognostic MRlncRNAs, calculate risk scores and build risk assessment models. The predictive power of the risk models was then validated by Kaplan-Meier analysis, ROC curves, DCA, C-index, and nomogram. We attempted to effectively differentiate between groups in terms of immune cell infiltration status, ICI-related genes, immunotherapy responses, and common anti-tumor drug sensitivity.Results: A risk model based on 11 MRlncRNAs was developed with an AUC of 0.850, and the sensitivity and specificity of this model in predicting survival probability is satisfactory. The Kaplan-Meier analysis revealed that the low-risk group in the model had a significantly higher survival rate, and the model was highly associated with survival status, clinical features, and clinical stage. Furthermore, the model was verified to be an independent prognostic risk factor, and the low-risk group in the model had a remarkable positive correlation with a variety of immune cell infiltrates. The expression levels of ICI-related genes differed significantly between the different groups. Lastly, immunotherapy responses and common anti-tumor drug sensitivity also differed significantly between different groups.Conclusion: The risk model on the basis of 11-MRlncRNAs can serve as independent predictors of GC prognosis and may be useful in developing personalized treatment strategies for patients.
Prognostic N6-methyladenosine (m6A)-related lncRNA patterns to aid therapy in pancreatic ductal adenocarcinoma
Authors: Wang Yuxin , Ji Yutian , Xu Qianhui , Huang Wen 
Published: September 2022

Background: Mounting research studies have suggested the indispensable roles of N6-methyladenosine (m6A) RNA modification in carcinogenesis. Nevertheless, it was little known about the potential function of m6A-related lncRNAs in sample clustering, underlying mechanism, and anticancer immunity of pancreatic ductal adenocarcinoma (PDAC).Methods: PDAC sample data were obtained from TCGA-PAAD project, and a total of 23 m6A regulators were employed based on published articles. Pearson correlation and univariate Cox regression were analyzed to determine m6A-related lncRNAs with prognostic significance to identify distinct m6A-related lncRNA subtypes by consensus clustering. Next, the least absolute shrinkage and selection operator (LASSO) algorithm was applied for constructing an m6A-related lncRNA scoring system, further quantifying the m6A-related lncRNA patterns in individual samples. Gene set variation analysis (GSVA) was employed to assign pathway activity estimates to individual samples. To decode the comprehensive landscape of TME, the CIBERSORT method and ESTIMATE algorithm were analyzed. The half-maximal inhibitory concentration (IC50) of chemotherapeutic agents was predicted with the R package pRRophetic. Finally, a quantitative real-time polymerase chain reaction was used to determine TRPC7-AS1 mRNA expression in PDAC.Results: Two distinct m6A-related lncRNA patterns with different clinical outcomes, TEM features, and biological enrichment were identified based on 45 prognostic m6A-related lncRNAs. The identification of m6A-related lncRNA patterns within individual samples based on risk scores contributed to revealing biological signatures, clinical outcomes, TEM characterization, and chemotherapeutic effects. A prognostic risk-clinical nomogram was constructed and confirmed to estimate m6A-related lncRNA patterns in individual samples. Finally, the biological roles of TRPC7-AS1 were revealed in PDAC.Conclusion: This work comprehensively elucidated that m6A-related lncRNA patterns served as an indispensable player in prognostic prediction and TEM features. Quantitative identification of m6A-related lncRNA patterns in individual tumors will contribute to sample stratification for further optimizing therapeutic strategies.