bluuebunny/crossref_metadata_2025_split huggingface dataset:
No causal association between COVID-19 and sepsis: a bidirectional two-sample Mendelian randomization study
Authors: Lu Hao , Cao Yu , Zhong Ming 
Published: October 2023

BackgroundSepsis and COVID-19 have a well-established observable relationship. Whether COVID-19 increases the likelihood of developing sepsis and whether patients with sepsis are at increased risk for COVID-19 infection is unknown. Using a bidirectional 2-sample Mendelian randomization (TSMR) analysis techniques in sizable cohorts, we sought to answer this question.MethodsThe current study performed Mendelian randomization (MR) on publicly accessible genome-wide association study (GWAS) summary data in order to investigate the causal linkages between COVID-19 and sepsis. A Two-Sample MR(TSMR) analyses was performed. As instrumental variables, a COVID-19 dataset of single nucleotide polymorphisms (SNPs) with significance value smaller than 5*10-8 was employed and Sepsis dataset of SNPs with significance value smaller than 5*10-7was employed.ResultsThe results suggested that Very severe respiratory confirmed COVID-19(VSRC), hospitalized COVID-19(HC) and Infected COVID-19(IC) had no causal influence on sepsis risk using the inverse variance weighted (IVW) technique (VSRC OR = 1.000, 95% CI, 0.956-1.046, P = 0.996, HC OR = 0.976, 95% CI, 0.920-1.036, P = 0.430, IC OR = 0.923, 95% CI, 0.796-1.071, P = 0.291) and there was no causal effect of sepsis on the risk of VSRC, HC and IC (VSRC OR = 0.955, 95% CI, 0.844-1.173, P = 0.953, HC OR = 0.993, 95% CI, 0.859-1.147, P = 0.921, IC OR = 1.001, 95% CI, 0.959-1.045, P = 0.961).ConclusionsOur findings do not support a causal relationship between COVID-19 and sepsis risk, nor do they suggest a causal link between sepsis and COVID-19. The bidirectional relationship between COVID-19 and sepsis warrants further investigation in large cohorts.
Understanding the role of membrane cholesterol upon Epstein Barr virus infection in astroglial cells
Authors: Rani Annu , Tanwar Manushree , Verma Tarun Prakash , Patra Priyanka , Trivedi Pankaj , Kumar Rajesh , Jha Hem Chandra 
Published: October 2023

BackgroundEBV infection has long been postulated to trigger multiple sclerosis (MS) and anti-EBV antibodies showed a consistent presence in MS patients. Previous reports from our group have shown that the EBV infects different brain cells. Entry of the virus in neuronal cells is assisted by several host factors including membrane cholesterol. By using an inhibitor, methyl-β-cyclodextrin (MβCD), we evaluated the role of membrane cholesterol in EBV infection and pathogenesisMethodologyThe membrane cholesterol depleted cells were infected with EBV and its latent genes expression were assessed. Further, EBV-mediated downstream signalling molecules namely STAT3, RIP, NF-kB and TNF-α levels was checked at protein level along with spatial (periphery and nucleus) and temporal changes in biomolecular fingerprints with Raman microspectroscopy (RS).ResultsUpon treatment with MβCD, lmp1 and lmp2a suggested significant downregulation compared to EBV infection. Downstream molecules like STAT3 and RIP, exhibited a decrease in protein levels temporally upon exposure to MβCD while NF-kB levels were found to be increased. Further, the intensity of the Raman spectra exhibited an increase in triglycerides and fatty acids in the cytoplasm of EBV-infected LN-229 cells compared to MβCD+EBV. Likewise, the Raman peak width of cholesterol, lipid and fatty acids were found to be reduced in EBV-infected samples indicates elevation in the cholesterol specific moieties. In contrast, an opposite pattern was observed in the nucleus. Moreover, the ingenuity pathway analysis revealed protein molecules such as VLDLR, MBP and APP that are associated with altered profile of cholesterol, fatty acids and triglycerides with infection-related CNS disorders.ConclusionTaken together, our results underline the important role of membrane cholesterol over EBV entry/pathogenesis in astroglia cells which further trigger/exacerbate virus-associated neuropathologies. These results likely to aid into the prognosis of neurological disease like MS.
Identification of biomarkers related to immune and inflammation in membranous nephropathy: comprehensive bioinformatic analysis and validation
Authors: Zhang Pingna , Geng Yunling , Tang Jingyi , Cao Zijing , Xiang Xiaojun , Yang Kezhen , Chen Hongbo 
Published: October 2023

BackgroundMembranous nephropathy (MN) is an autoimmune glomerular disease that is predominantly mediated by immune complex deposition and complement activation. The aim of this study was to identify key biomarkers of MN and investigate their association with immune-related mechanisms, inflammatory cytokines, chemokines and chemokine receptors (CCRs).MethodsMN cohort microarray expression data were downloaded from the GEO database. Differentially expressed genes (DEGs) in MN were identified, and hub genes were determined using a protein-protein interaction (PPI) network. The relationships between immune-related hub genes, immune cells, CCRs, and inflammatory cytokines were examined using immune infiltration analysis, gene set enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA). Finally, the immune-related hub genes in MN were validated using ELISA.ResultsIn total, 501 DEGs were identified. Enrichment analysis revealed the involvement of immune- and cytokine-related pathways in MN progression. Using WGCNA and immune infiltration analysis, 2 immune-related hub genes (CYBB and CSF1R) were identified. These genes exhibited significant correlations with a wide range of immune cells and were found to participate in B cell/T cell receptor and chemokine signaling pathways. In addition, the expressions of 2 immune-related hub genes were positively correlated with the expression of CCR1, CX3CR1, IL1B, CCL4, TNF, and CCR2.ConclusionOur study identified CSF1 and CYBB as immune-related hub genes that potentially influence the expression of CCRs and pro-inflammatory cytokines (CCR1, CX3CR1, IL1B, CCL4, TNF, and CCR2). CSF1 and CYBB may be potential biomarkers for MN progression, providing a perspective for diagnostic and immunotherapeutic targets of MN.
Immune checkpoint inhibitor–associated myocarditis: a systematic analysis of case reports
Authors: Wang Caie , Zhao Guo , Zhang Zhen , Yang Lukui , Liu Shihao , Li Guifang , Wang Hongxia , Huang Jiaxin , Wang Shuhang , Li Ning 
Published: October 2023

BackgroundImmune checkpoint inhibitors (ICIs) therapy can be complicated by their potential cardiovascular toxicities, including myocarditis. Nowadays, no prospective trials have focused on ICI-associated myocarditis optimized management. Available evidence only come from case reports or series. A systematic case reports analysis was conducted to collect and evaluate emerging evidence of ICI-associated myocarditis to provide more information to clinicians.MethodsWe performed a literature search for eligible case reports or series published between January 2018 and May 2023 using the PubMed database. Then, we extracted interesting information via table form. Finally, this study included 113 publications on 106 patients with ICI-associated myocarditis.ResultsMyocarditis was found to be a highly life-threatening disease, with 53.8% of cases. Over half of cases were life-threatening (G4, 23.6%) or severe (G3, 35.8%) and required glucocorticoids. Higher rates of improvement were associated with the best response to ICI for complete response/partial response (72.7% vs. 53.9%), glucocorticoid administration (30% vs. 22%), and discontinuation of ICI (58.8% vs. 32.1%). Consequently, ICI-associated G3–G4 myocarditis should be treated with a combination of discontinuation of ICIs, high-dose glucocorticoids, other drugs, chemical drugs, plasma exchange, and life support. For moderate G1 or G2 cases, discontinuation of ICIs and regular-dose glucocorticoids should be considered.ConclusionOnce full recovery or improvement was achieved; glucocorticoids can be administered at low doses or stopped. Notably, re-challenge with ICIs appears feasible after resolution or meaningful improvement of myocarditis.
Comparison of RCI001 and corticosteroid on the effects on intraocular pressure in mice
Authors: Kim Soo Hyun , Ku Young-ah , Yoo Chungkwon , Kim Yong Ho , Kim Dong Hyun 
Published: October 2023

PurposeRCI001, a novel therapeutic candidate for the treatment of ocular inflammatory diseases, have demonstrated remarkable anti-inflammatory and antioxidant effects in various ocular experimental models. This study was to evaluate the effects of RCI001 on intraocular pressure (IOP) and compare them with those of corticosteroids in experimental mouse models.MethodsExperimental mice were randomly divided into naïve, phosphate-buffered saline (PBS), 0.1% dexamethasone (DEX-1), and 1% RCI001 (RCI) groups, and each reagent was pipetted into the right eye of the mouse at 10 μL thrice daily for 5 weeks. In addition, 20 μL of 0.1% dexamethasone was injected subconjunctivally into the right eye once weekly for 5 weeks in the DEX-2 group. The IOP was measured under anesthesia at baseline and twice weekly for 5 weeks. The △IOP (%) was defined as the change in IOP from baseline [△IOP (%) = (IOPweek5–IOPbaseline)/IOPbaseline × 100%]. The anterior segments were clinically and histologically examined.ResultsThere was no significant increase in IOP and △IOP (%) [values by week 3 (day 21) in any of the groups]. However, IOP and △IOP (%) in the DEX-2 group tended to increase slightly after day 10 compared with baseline. Compared with baseline IOP values, the DEX-1 group showed a statistically significant increase in IOP at weeks 4 and 5, and the DEX-2 group at week 5. The △IOP (%) of the DEX-1 and DEX-2 groups (%) at week 5 were 38.2% ± 5.8% and 38.4 ± 4.6%, respectively. However, the IOP in the RCI group did not increase significantly until week 5. The RCI group did not show notable corneal changes, such as epithelial defects or stromal opacities, at week 5. In addition, hematoxylin and eosin (H&amp;E) staining of corneas in the RCI group revealed healthy corneal epithelial, stromal, and endothelial integrity.ConclusionLong-term use of RCI001 did not induce significant IOP elevation or ocular surface changes, whereas topical corticosteroids significantly increased the IOP. Therefore, RCI001 may be an effective anti-inflammatory agent with a low risk of drug-induced IOP elevation.
Does muscle strength predict working memory? A cross-sectional fNIRS study in older adults
Authors: Cai Zhidong , Wang Xing , Wang Qiang 
Published: October 2023

ObjectivePrevious research has primarily focused on the association between muscle strength and global cognitive function in older adults, while the connection between muscle strength and advanced cognitive function such as inhibition and working memory (WM) remains unclear. This study aimed to investigate the relationship among muscle strength, WM, and task-related cortex hemodynamics.MethodsWe recruited eighty-one older adults. Muscle strength was measured using a grip and lower limb strength protocol. We measured the WM performance by using reaction time (RT) and accuracy (ACC) in the N-back task and the cortical hemodynamics of the prefrontal cortex (PFC) by functional near-infrared spectroscopy (fNIRS).ResultsWe found positive correlations between grip strength (p &lt; 0.05), 30-s sit-up (p &lt; 0.05) and ACC, negative correlation between grip strength (p &lt; 0.05) and RT. Furthermore, we observed positive correlations between grip strength and the level of oxygenated hemoglobin (HbO2) in dorsolateral prefrontal cortex, frontopolar area, ventrolateral prefrontal cortex (p &lt; 0.05), and negative correlations between grip strength and the level of deoxygenated hemoglobin (Hb) in left dorsolateral prefrontal cortex, frontopolar area, left ventrolateral prefrontal cortex (p &lt; 0.05). Additionally, we noticed positive correlations between RT and the level of Hb in left dorsolateral prefrontal cortex, right frontopolar area (p &lt; 0.05), and negative correlations between RT and the level of HbO2 in left dorsolateral prefrontal cortex, frontopolar area (p &lt; 0.05). However, the cortical hemodynamics did not mediate the relationship between muscle strength and WM performance (RT, ACC).ConclusionThe grip strength of older adults predicted WM in the cross-section study. The level of hemodynamics in PFC can serve as a predictor of WM.
Validating the early phototherapy prediction tool across cohorts
Authors: Daunhawer Imant , Schumacher Kai , Badura Anna , Vogt Julia E. , Michel Holger , Wellmann Sven 
Published: October 2023

BackgroundHyperbilirubinemia of the newborn infant is a common disease worldwide. However, recognized early and treated appropriately, it typically remains innocuous. We recently developed an early phototherapy prediction tool (EPPT) by means of machine learning (ML) utilizing just one bilirubin measurement and few clinical variables. The aim of this study is to test applicability and performance of the EPPT on a new patient cohort from a different population.Materials and methodsThis work is a retrospective study of prospectively recorded neonatal data from infants born in 2018 in an academic hospital, Regensburg, Germany, meeting the following inclusion criteria: born with 34 completed weeks of gestation or more, at least two total serum bilirubin (TSB) measurement prior to phototherapy. First, the original EPPT—an ensemble of a logistic regression and a random forest—was used in its freely accessible version and evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Second, a new version of the EPPT model was re-trained on the data from the new cohort. Third, the predictive performance, variable importance, sensitivity and specificity were analyzed and compared across the original and re-trained models.ResultsIn total, 1,109 neonates were included with a median (IQR) gestational age of 38.4 (36.6–39.9) and a total of 3,940 bilirubin measurements prior to any phototherapy treatment, which was required in 154 neonates (13.9%). For the phototherapy treatment prediction, the original EPPT achieved a predictive performance of 84.6% AUROC on the new cohort. After re-training the model on a subset of the new dataset, 88.8% AUROC was achieved as evaluated by cross validation. The same five variables as for the original model were found to be most important for the prediction on the new cohort, namely gestational age at birth, birth weight, bilirubin to weight ratio, hours since birth, bilirubin value.DiscussionThe individual risk for treatment requirement in neonatal hyperbilirubinemia is robustly predictable in different patient cohorts with a previously developed ML tool (EPPT) demanding just one TSB value and only four clinical parameters. Further prospective validation studies are needed to develop an effective and safe clinical decision support system.
Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study)
Authors: Alrashed Fatema , Abdullah Israa , Alfadhli Ahmad , Shehab Mohammad 
Published: October 2023

Background: About a third of patients with inflammatory bowel disease (IBD) do not respond to anti-tumor necrosis factor (anti-TNF) therapy. In our study, we evaluated the effectiveness of vedolizumab and ustekinumab in achieving clinical and endoscopic outcomes in anti-TNF-experienced patients with IBD.Methods: We conducted a retrospective cohort study. Electronic medical records of patients with moderate to severe IBD, who were previously received anti-TNF therapies, were reviewed and evaluated retrospectively in a gastroenterology center. Outcomes of patients treated with ustekinumab or vedolizumab after failing one anti-TNF agent were evaluated. The primary outcomes were the percentage of hospitalization, surgery, mucosal healing and steroid-free remission. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 in ulcerative colitis (UC) and an SES-CD score of less than 3 in Crohn’s disease (CD). Outcomes were quantified using descriptive analysis.Results: A total of 207 (130 CD: 77 UC) patients with IBD who had previously received one anti-TNF agent were included in the study. Of the total cohort, 62 (30.0%) patients were receiving vedolizumab, and 145 (70.0%) patients were on ustekinumab. 101 (77.6%) patients with CD who failed one anti-TNF therapy were on ustekinumab. Of these patients, 26 (19.7%) patients were hospitalized, and 12 (11.9%) patients had IBD-related surgery. 16 (16.1%) patients had at least one corticosteroid course. 60 (59.0%) patients with CD on ustekinumab achieved mucosal healing. 29 (22.3%) patients with CD who failed one anti-TNF therapy were receiving vedolizumab. Of those, 7 (25%) patients were hospitalized, and 11 (37.9%) patients had IBD-related surgery. 15 (51.0%) patients achieved mucosal healing. 44 (57.1%) patients with UC who failed one anti-TNF therapy were on ustekinumab. Of these 6 (14.1%) patients were hospitalized, 3 (7.0%) patients had IBD-related surgery and 13 (30%) patients had at least 1 corticosteroid course. 25 (57.0%) patients achieved mucosal healing. 33 (42.8%) patients with UC who failed one anti-TNF therapy were receiving vedolizumab. Of those, 6 (18.6%) patients were hospitalized, and 16 (49.6%) patients had at least 1 corticosteroid course. 17 (53.2%) patients achieved mucosal healing.Conclusion: Ustekinumab and vedolizumab were both effective in achieving clinical outcomes in patients with IBD after failing an anti-TNF agent. However, patients receiving ustekinumab had numerically higher percentages of reaching target outcomes than patients receiving vedolizumab. A prospective head-to-head trial is warranted to confirm these findings.
Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment
Authors: Zavaliangos-Petropulu Artemis , McClintock Shawn M. , Joshi Shantanu H. , Taraku Brandon , Al-Sharif Noor B. , Espinoza Randall T. , Narr Katherine L. 
Published: October 2023

IntroductionSubanesthetic ketamine is a rapidly acting antidepressant that has also been found to improve neurocognitive performance in adult patients with treatment resistant depression (TRD). Provisional evidence suggests that ketamine may induce change in hippocampal volume and that larger pre-treatment volumes might be related to positive clinical outcomes. Here, we examine the effects of serial ketamine treatment on hippocampal subfield volumes and relationships between pre-treatment subfield volumes and changes in depressive symptoms and neurocognitive performance.MethodsPatients with TRD (N = 66; 31M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg) over 2 weeks. Structural MRI scans, the National Institutes of Health Toolbox (NIHT) Cognition Battery, and Hamilton Depression Rating Scale (HDRS) were collected at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks post-treatment. The same data was collected for 32 age and sex matched healthy controls (HC; 17M/15F; age = 35.03 ± 12.2 years) at one timepoint. Subfield (CA1/CA3/CA4/subiculum/molecular layer/GC-ML-DG) volumes corrected for whole hippocampal volume were compared across time, between treatment remitters/non-remitters, and patients and HCs using linear regression models. Relationships between pre-treatment subfield volumes and clinical and cognitive outcomes were also tested. All analyses included Bonferroni correction.ResultsPatients had smaller pre-treatment left CA4 (p = 0.004) and GC.ML.DG (p = 0.004) volumes compared to HC, but subfield volumes remained stable following ketamine treatment (all p &gt; 0.05). Pre-treatment or change in hippocampal subfield volumes over time showed no variation by remission status nor correlated with depressive symptoms (p &gt; 0.05). Pre-treatment left CA4 was negatively correlated with improved processing speed after single (p = 0.0003) and serial ketamine infusion (p = 0.005). Left GC.ML.DG also negatively correlated with improved processing speed after single infusion (p = 0.001). Right pre-treatment CA3 positively correlated with changes in list sorting working memory at follow-up (p = 0.0007).DiscussionThese results provide new evidence to suggest that hippocampal subfield volumes at baseline may present a biomarker for neurocognitive improvement following ketamine treatment in TRD. In contrast, pre-treatment subfield volumes and changes in subfield volumes showed negligible relationships with ketamine-related improvements in depressive symptoms.
“If you weren't connected to the Internet, you were not alive”: experience of using social technology during COVID-19 in adults 50+
Authors: Ling Katrina , Langlois Danielle , Preusse Harrison , Rheman Jennifer M. , Parson Danya , Kuballa Sarah , Simecek Martin , Tsui Katherine M. , Fraune Marlena R. 
Published: October 2023

IntroductionLoneliness and social isolation reduce physical and mental wellbeing. Older adults are particularly prone to social isolation due to decreased connection with previous social networks such as at workplaces. Social technology can decrease loneliness and improve wellbeing. The COVID-19 pandemic prompted quarantine and social distancing for many people, creating a context of widespread social isolation.MethodIn the current study, we interviewed middle-aged and older adults' (n = 20) about their use of social technology when social isolation was common: during the early part of the pandemic while social isolation and masking were still required in the United States, between August 2020 and June 2021.We analyzed the data using three-phase coding. We compare our results against the model of the bidirectional and dynamic relationship between social internet use and loneliness.ResultsWe found that during the COVID-19 pandemic, our participants experienced decreased social interaction and moved toward online interaction. Participant use of social technology supported the stimulation hypothesis - that is, they used it to maintain existing relationships and social connection. The findings also add novel evidence that the stimulation hypothesis endures for older adults during enforced isolation (in this case due to the COVID- 19 pandemic).DiscussionBased on our data, we also propose adding the presence or realism of connection via social technology as a main factor to the model and engaging with construal level theory of social presence to fill in critical variables of this relationship. We further find that digital exclusion acts as a barrier to obtaining benefits from stimulation via social technology and recommend that further research examined digital exclusion in relation to the bidirectional and dynamic model. Finally, we discuss recommendations for improving social technology to benefit middle-aged and older adults.