bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of plasma cortisol in dementia, epilepsy, and multiple sclerosis: A Mendelian randomization study
Authors: Li Haiqi , Chen Kaili , Yang Le , Wang Qiaoli , Zhang Jiao , He Jinting 
Published: March 2023

BackgroundMany clinical studies have shown a correlation between plasma cortisol and neurological disorders. This study explored the causal relationship between plasma cortisol and dementia, epilepsy and multiple sclerosis based on Mendelian randomization (MR) method.MethodsData were taken from the summary statistics of a genome-wide association study, FinnGen consortium and United Kingdom Biobank. Dementia, epilepsy, and multiple sclerosis were used as outcomes, and genetic variants associated with plasma cortisol were used as instrumental variables. The main analysis was performed using the inverse variance weighted method, and the results were assessed according to the odds ratio (OR) and 95% confidence interval. Heterogeneity tests, pleiotropy tests, and leave-one-out method were conducted to evaluate the stability and accuracy of the results.ResultsIn two-sample MR analysis, the inverse variance weighted method showed that plasma cortisol was associated with Alzheimer’s disease (AD) [odds ratio (95% confidence interval) = 0.99 (0.98-1.00), P = 0.025], vascular dementia (VaD) [odds ratio (95% confidence interval) = 2.02 (1.00-4.05), P = 0.049)], Parkinson’s disease with dementia (PDD) [odds ratio (95% confidence interval) = 0.24 (0.07-0.82), P = 0.023] and epilepsy [odds ratio (95% confidence interval) = 2.00 (1.03-3.91), P = 0.042]. There were no statistically significant associations between plasma cortisol and dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and multiple sclerosis.ConclusionThis study demonstrates that plasma cortisol increase the incidence rates of epilepsy and VaD and decrease the incidence rates of AD and PDD. Monitoring plasma cortisol concentrations in clinical practice can help prevent diseases, such as AD, PDD, VaD and epilepsy.
Cytokine modulation in abdominal septic shock via the crucial role of IL-6 signaling in endothelial dysfunction
Authors: Ueno Takuya , Ikeda Toshiaki , Okihara Masaaki , Akashi Isao , Yokoyama Takayoshi , Kihara Yu , Konno Osamu , Nakamura Yuki , Iwamoto Hitoshi , Ueno Yu , Chandraker Anil 
Published: March 2023

BackgroundEarly recovery from shock improves prognosis in septic shock patients. We determined whether cytokine modulation by Continuous Renal Replacement Therapy (CRRT) following acute care surgery resulted in stable hemodynamics in them. To investigate our hypothesis, we measured proinflammatory cytokines IL-6, IL-1ra and the coagulation cascade activator plasminogen activator inhibitor-1 (PAI-1) following CRRT with polymyxin B immobilized fiber (PMX-DHP) which has been utilized as an adjuvant treatment option for patients with severe septic shock.Methods66 septic shock patients requiring 2 h direct hemoperfusion therapy PMX-DHP were included. 36 patients of them also received continuous hemodiafiltration (CHDF) after performing PMX-DHP. Circulatory dynamics and levels of inflammatory mediators, namely IL-6, IL-1ra, and PAI-1 were assessed before, immediately after, and 24 h initiation of PMX-DHP.ResultsMean Arterial Pressure (MAP) rose intentionally by PMX-DHP just after enforcement 24 h later (p &lt; 0.01). Levels of IL-6, IL-1ra, and PAI-1 significantly decreased after PMX-DHP (p &lt; 0.05) and this trend was observed up to 24 h post initiation of PMX-DHP (p &lt; 0.05). IL-6 modulation by PMX-DHP was enhanced with using CHDF and there was a significant correlation between IL-6 and MAP (p &lt; 0.0001). In addition, levels of Il-6 and PAI-1 showed a significant correlation.ConclusionOur data showed employing CRRT as cytokine modulators could be an additional therapeutic strategy to improve septic shock outcomes via the crucial role of IL-6 signaling in endothelial dysfunction.
Life stage-specific glycosylation of extracellular vesicles from Schistosoma mansoni schistosomula and adult worms drives differential interaction with C-type lectin receptors DC-SIGN and MGL
Authors: Kuipers Marije E. , Nguyen D. Linh , van Diepen Angela , Mes Lynn , Bos Erik , Koning Roman I. , Nolte-’t Hoen Esther N. M. , Smits Hermelijn H. , Hokke Cornelis H. 
Published: March 2023

Schistosomes can survive in mammalian hosts for many years, and this is facilitated by released parasite products that modulate the host’s immune system. Many of these products are glycosylated and interact with host cells via C-type lectin receptors (CLRs). We previously reported on specific fucose-containing glycans present on extracellular vesicles (EVs) released by schistosomula, the early juvenile life stage of the schistosome, and the interaction of these EVs with the C-type lectin receptor Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN or CD209). EVs are membrane vesicles with a size range between 30–1,000 nm that play a role in intercellular and interspecies communication. Here, we studied the glycosylation of EVs released by the adult schistosome worms. Mass spectrometric analysis showed that GalNAcβ1–4GlcNAc (LacDiNAc or LDN) containing N-glycans were the dominant glycan type present on adult worm EVs. Using glycan-specific antibodies, we confirmed that EVs from adult worms were predominantly associated with LDN, while schistosomula EVs displayed a highly fucosylated glycan profile. In contrast to schistosomula EV that bind to DC-SIGN, adult worm EVs are recognized by macrophage galactose-type lectin (MGL or CD301), and not by DC-SIGN, on CLR expressing cell lines. The different glycosylation profiles of adult worm- and schistosomula-derived EVs match with the characteristic glycan profiles of the corresponding life stages and support their distinct roles in schistosome life-stage specific interactions with the host.
Activation of the brain during motor imagination task with auditory stimulation
Authors: Li Long , Zhang Yanlong , Fan Liming , Zhao Jie , Guo Jing , Li Chenxi , Wang Jue , Liu Tian 
Published: March 2023

IntroductionAuditory stimulation is one of the most important influence factors in the cognitive process. It is an important guiding role in cognitive motor process. However, previous studies on auditory stimuli mainly focused on the cognitive effects of auditory stimuli on the cortex, while the role of auditory stimuli in motor imagery tasks is still unclear.MethodsIn order to explore the role of auditory stimuli in motor imagery tasks, we studied the EEG power spectrum distribution characteristics, frontal parietal mismatch negative (MMN) wave characteristics, and the Inter trial phase locking consistency (ITPC) characteristics of the prefrontal cognitive cortex and parietal motor cortex. In this study, 18 subjects were hired to complete the motor imagery tasks, induced by auditory stimuli of task related verbs and task independent nouns.ResultsEEG power spectrum analysis showed that the activity of the contralateral motor cortex was significantly increased under the stimulation of verbs, and the amplitude of mismatch negative wave was also significantly increased. ITPC is mainly concentrated in μ, α, and γ bands in the process of motor imagery task guided by the auditory stimulus of verbs, while it is mainly concentrated in the β band under the nouns stimulation. This difference may be due to the impact of auditory cognitive process on motor imagery.DiscussionWe speculate that there may be a more complex mechanism for the effect of auditory stimulation on the inter test phase lock consistency. When the stimulus sound has the corresponding meaning to the motor action, the parietal motor cortex may be more affected by the cognitive prefrontal cortex, thus changing its normal response mode. This mode change is due to the joint action of motor imagination, cognitive and auditory stimuli. This study provides new insight into the neural mechanism of motor imagery task guided by auditory stimuli, and provides more information on the activity characteristics of the brain network in motor imagery task by cognitive auditory stimulation.
Association of nonalcoholic fatty liver disease and liver fibrosis detected by transient elastography with serum retinol in American adults
Authors: Niu Xiaoxian , Liu Jian , Liu Kai 
Published: March 2023

Background and objectiveRetinol is a precursor of vitamin A, which is metabolized and maintained in the liver and is involved in the pathogenesis of the nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. The relationship between NAFLD and liver fibrosis with serum retinol levels remains insufficient and inconclusive. Our study aimed to investigate the correlation between NAFLD, fibrosis, and serum retinol levels in American adults.MethodsA cross-sectional analysis was conducted using information from the 2017–2018 cycle of the National Health and Nutrition Examination Survey (NHANES). The exposure factors were NAFLD and liver fibrosis status detected using transient elastography (TE), and the outcome was serum retinol levels. Weighted multivariate regressions were established to assess the correlation between NAFLD and liver fibrosis and serum retinol levels. Subgroup analyses were also performed.ResultsThis study included 3,537 participants. Compared to the group without NAFLD, NAFLD was positively correlated with serum retinol levels (β = 1.28, 95% CI: 0.19, 2.37). In the subgroup analysis, a positive correlation between NAFLD and serum retinol levels was found in people aged &lt; 60 years, Mexican Americans, and those with a body mass index (BMI) &lt; 25. On the contrary, compared to the group without liver fibrosis, there was a significant negative association between liver fibrosis and serum retinol (β = −3.46, 95% CI: −5.16, −1.75), especially in people aged &lt; 60 years, non-Hispanic white/black individuals, and people with a BMI ≥ 25.ConclusionOur study suggests that NAFLD status may be positively associated with serum retinol levels in adult patients, and liver fibrosis may be negatively associated with serum retinol levels. Further studies are required to examine the associations found in our study.
Use of the prognostic nutrition index as a predictive biomarker in small-cell lung cancer patients undergoing immune checkpoint inhibitor treatment in the Chinese alpine region
Authors: Wu Yunjiao , Yang Jing , Qiao Xinyi , Li Yingjie , Zhao Rui , Lin Tie , Li Xiaoli , Wang Meng 
Published: March 2023

BackgroundWhether the prognostic nutritional index (PNI), which is suggested to reflect systemic inflammation and nutritional status of patients, could be used as an effective prognostic factor for small-cell lung cancer (SCLC) has not yet been clarified. The purpose of this study was to verify the prognostic value of the PNI in SCLC patients treated with programmed cell death ligand-1/programmed cell death 1 (PD-L1/PD-1) inhibitors in the alpine region of China.MethodsSCLC patients treated with PD-L1/PD-1 inhibitors monotherapy or combined with chemotherapy between March 2017 and May 2020 were included. Based on the values of serum albumin and total lymphocyte count, the study population was divided into two groups: high and low PNI. The Kaplan-Meier method was used to compute the median survival time and the log-rank test was used to compare the two groups. To evaluate the prognostic value of the PNI, univariable and multivariable analyses of progression-free survival (PFS) and overall survival (OS) were performed. The correlations between PNI and DCR or ORR were calculated by Point biserial correlation analysis.ResultsOne hundred and forty patients were included in this study, of which, 60.0% were high PNI (PNI &gt; 49.43) and 40.0% were low PNI (PNI ≤ 49.43). Results indicated that the high PNI group had better PFS and OS than the low PNI group in the patients who received PD-L1/PD-1 inhibitors monotherapy (median PFS: 11.0 vs. 4.8 months, p &lt; 0.001 and median OS: 18.5 vs. 11.0 months, p = 0.004). Similarly, better PFS and OS were associated with an increase in PNI level in the patients who accepted PD-L1/PD-1 inhibitors combined with chemotherapy (median PFS: 11.0 vs. 5.3 months, p &lt; 0.001 and median OS: 17.9 vs. 12.6 months, p = 0.005). Multivariate Cox-regression model showed that high PNI was significantly related to better PFS and OS in patients who accepted PD-L1/PD-1 inhibitors monotherapy or combined with chemotherapy (PD-L1/PD-1 inhibitors monotherapy: PFS: HR = 0.23, 95% CI: 0.10–0.52, p &lt; 0.001 and OS: HR = 0.13, 95% CI: 0.03–0.55, p = 0.006; PD-L1/PD-1 inhibitors combined with chemotherapy: PFS: HR = 0.34, 95% CI: 0.19–0.61, p &lt; 0.001 and OS: HR = 0.53, 95% CI: 0.29–0.97, p = 0.040, respectively). Additionally, Point biserial correlation analysis between PNI and disease control rate (DCR) showed that PNI status was positively correlated with DCR in SCLC patients receiving PD-L1/PD-1 inhibitors or combined with chemotherapy (r = 0.351, p &lt; 0.001; r = 0.285, p &lt; 0.001, respectively).ConcussionsPNI may be a promising biomarker of treatment efficacy and prognosis in SCLC patients treated with PD-L1/PD-1 inhibitors in the alpine region of China.
Cuproptosis-related signature predicts prognosis, immunotherapy efficacy, and chemotherapy sensitivity in lung adenocarcinoma
Authors: Wu Gujie , Hu Qin , Chen Hongyu , He Min , Ma Huiyun , Zhou Lin , Xu Kun , Ren Hefei , Qi Juntao 
Published: March 2023

BackgroundCuproptosis is a novel form of programmed cell death that disrupts the tricarboxylic acid (TCA) cycle and mitochondrial function. The mechanism of cuproptosis is quite different from that of common forms of cell death such as apoptosis, pyroptosis, necroptosis, and ferroptosis. However, the potential connection between cuproptosis and tumor immunity, especially in lung adenocarcinoma (LUAD), is poorly understood.MethodsWe used machine learning algorithms to develop a cuproptosis-related scoring system. The immunological features of the scoring system were investigated by exploring its association with clinical outcomes, immune checkpoint expression, and prospective immunotherapy response in LUAD patients. The system predicted the sensitivity to chemotherapeutic agents. Unsupervised consensus clustering was performed to precisely identify the different cuproptosis-based molecular subtypes and to explore the underlying tumor immunity.ResultsWe determined the aberrant expression and prognostic relevance of cuproptosis-related genes (CRGs) in LUAD. There were significant differences in survival, biological function, and immune infiltration among the cuproptosis subtypes. In addition, the constructed cuproptosis scoring system could predict clinical outcomes, tumor microenvironment, and efficacy of targeted drugs and immunotherapy in patients with LUAD. After validating with large-scale data, we propose that combining the cuproptosis score and immune checkpoint blockade (ICB) therapy can significantly enhance the efficacy of immunotherapy and guide targeted drug application in patients with LUAD.ConclusionThe Cuproptosis score is a promising biomarker with high accuracy and specificity for determining LUAD prognosis, molecular subtypes, immune cell infiltration, and treatment options for immunotherapy and targeted therapies for patients with LUAD. It provides novel insights to guide personalized treatment strategies for patients with LUAD.
Determining the incidence of heart malformations in neonates: A novel and clinically approved solution
Authors: Bordbar Arash , Kashaki Mandana , Vafapour Maryam , Sepehri Amir A. 
Published: March 2023

BackgroundScreening for critical congenital heart defects should be performed as early as possible and is essential for saving the lives of children and reducing the incidence of undetected adult congenital heart diseases. Heart malformations remain unrecognized at birth in more than 50% of neonates at maternity hospitals. Accurate screening for congenital heart malformations is possible using a certified and internationally patented digital intelligent phonocardiography machine. This study aimed to assess the actual incidence of heart defects in neonates. A pre-evaluation of the incidence of unrecognized severe and critical congenital heart defects at birth in our well-baby nursery was also performed.MethodsWe conducted the Neonates Cardiac Monitoring Research Project (ethics approval number: IR-IUMS-FMD. REC.1398.098) at the Shahid Akbarabadi Maternity Hospital. This study was a retrospective analysis of congenital heart malformations observed after screening 840 neonates. Using a double-blind format, 840 neonates from the well-baby nursery were randomly chosen to undergo routine clinical examinations at birth and digital intelligent phonocardiogram examinations. A pediatric cardiologist performed echocardiography for each neonate classified as having abnormal heart sounds using an intelligent machine or during routine medical examinations. If the pediatric cardiologist requested a follow-up examination, then the neonate was considered to have a congenital heart malformation, and the cumulative incidence was calculated accordingly.ResultsThe incidence of heart malformations in our well-baby nursery was 5%. Furthermore, 45% of heart malformations were unrecognized in neonates at birth, including one critical congenital heart defect. The intelligent machine interpreted innocent murmurs as healthy heart sound.ConclusionWe accurately and cost-effectively screened for congenital heart malformations in all neonates in our hospital using a digital intelligent phonocardiogram. Using an intelligent machine, we successfully identified neonates with CCHD and congenital heart defects that could not be detected using standard medical examinations. The Pouya Heart machine can record and analyze sounds with a spectral power level lower than the minimum level of the human hearing threshold. Furthermore, by redesigning the study, the identification of previously unrecognized heart malformations could increase to 58%.
Evaluation of acute oral toxicity of Ipomoea turpethum extract loaded polymeric nanoparticles in Wistar rats
Authors: Swami Sanskriti , Mughees Mohd , Kauser Sana , Wajid Saima 
Published: March 2023

Introduction: The amalgamation of novel drug delivery techniques and potential drugs is considered the most promising tool for the treatment of diseases. In our study, we have employed N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid (NIPAAM-VP-AA) copolymeric nanoparticles for delivering Ipomoea turpethum root extract. I. turpethum is a perennial herb (Convolvulaceae family) and has been used as medicine for ages. The present study was conducted to evaluate the safety of I. turpethum root extract-loaded NIPAAM-VP-AA polymeric nanoparticles (NVA-IT) in Wistar rats.Methods: An acute oral toxicity study was conducted in accordance with OECD guidelines 423 for the testing of chemicals. Different doses of NVA-IT i.e., 5 mg/kg, 50 mg/kg, 300 mg/kg, and 2000 mg/kg were administered to female Wistar rats in a stepwise manner using oral gavage. The toxicity signs were thoroughly observed for the next 14 days. At the end of the study, the blood and vital organs were harvested for hematological, biochemical, and histopathological studies.Result: No mortality or pathological anomalies were observed even at the highest dose which exemplifies that the lethal dose would be more than 2000 mg/kg body weight (GSH category 5). Behavioral changes, biochemical parameters, and histopathology of vital organs were normal after NVA-IT administration.Conclusion: This study demonstrated that NVA-IT nanoparticles are non-toxic and can be considered for therapeutic use in different diseases, such as inflammation, CNS diseases, Cancer, etc.
Design, preparation, and in vitro evaluation of gastroretentive floating matrix tablet of mitiglinide
Authors: Patel Meenakshi , Shelke Santosh , Surti Naazneen , Panzade Prabhakar , Al-Keridis Lamya Ahmed , Upadhyay Tarun Kumar , Alshammari Nawaf , Saeed Mohd 
Published: March 2023

The present research is focused on developing floating matrix tablets of mitiglinide to prolong its gastric residence time for better absorption. Gastroretentive tablets were prepared using a direct compression technique with hydroxypropyl methylcellulose K15M (HPMC K15M) and sodium alginate as matrix-forming polymers and sodium bicarbonate as the gas-forming agent. A 32 full factorial design was adopted to optimize the flotation and release profile of the drug. The concentration of HPMC K15M and sodium alginate were taken as the independent variables, and the floating lag time, time required for 50% drug release, and time required for 90% drug release were taken as dependent variables. The compatibility between drug and excipients was assessed by Fourier transform infrared (FTIR) spectroscopy. The prepared tablets were evaluated for different parameters such as hardness, friability, drug content, floating time, in vitro dissolution, and stability. Dissolution data were analyzed using various kinetic models to ascertain the mechanism of drug release. Finally, a radiographic study was conducted to estimate the retention time of the optimized floating matrix tablets of mitiglinide inside the body. The results revealed that all the physical properties of the developed formulations were within standard limits. The formulation M3, with the maximum amount of both independent variables, was considered to be the optimized formulation based on the desirability value. In addition, the optimized M3 formulation showed stability for over 6 months, as evidenced by insignificant changes in lag time, drug release pattern, and other physical properties. Furthermore, radiographic examination indicated that the tablets remained afloat in gastric fluid for up to 12 h in the rabbit’s stomach. In conclusion, the developed floating matrix tablet of mitiglinide could be regarded as a promising formulation that could release the drug in the stomach at a controlled rate and, hence, offer better management of type II diabetes.
How do circadian rhythms and neural synchrony shape networked cooperation?
Authors: Vasiliauskaite Vaiva , Hausladen Carina I. 
Published: March 2023

This study investigates the effects of temporal changes at the individual and social levels and their impact on cooperation in social networks. A theoretical framework is proposed to explain the probability of cooperation as a function of endogenously driven periodic temporal variation and neural synchrony modeled as a diffusion process. Agents are simulated playing a prisoner’s dilemma game, with and without evolution, in a two-player setting and on networks. Most importantly, we find that temporal variation and synchrony influence cooperation patterns in a non-trivial way and can enhance or suppress cooperation, depending on exact parameter values. Furthermore, some of our results point to promising future research on human subjects. Specifically, we find that cooperators can dramatically increase their payoff—as opposed to defectors—if neural synchrony is present. Furthermore, the more heterogeneous the synchrony between two agents, the less they cooperate. In a network setting, neural synchrony inhibits cooperation, and variation in circadian patterns counteracts this effect.Call: Hidden Order Behind Cooperation in Social Systems.