bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate Drugs Screening for Behcet’s Disease Based on Bioinformatics Analysis and Mouse Experiments
Authors: Xia Qinyun , Lyu Chujun , Li Fang , Pang Binbin , Guo Xiaoyu , Ren He , Xing Yiqiao , Chen Zhen 
Published: June 2022

BackgroundBehcet’s disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models.MethodsBehcet’s disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation.ResultsA total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated “Cytokine- Cytokine receptor interaction”, “Inflammatory bowel disease (IBD)” and “IL-17 signaling Pathway”. In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice.ConclusionsThe functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD.
mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study
Authors: Pinchera Biagio , Spirito Lorenzo , Buonomo Antonio Riccardo , Foggia Maria , Carrano Rosa , Salemi Fabrizio , Schettino Elisa , Papa Fortuna , La Rocca Roberto , Crocetto Felice , Napolitano Luigi , Villari Riccardo , Gentile Ivan 
Published: June 2022

IntroductionIn solid organ transplant recipients, COVID-19 is associated with a poor prognosis because of immunosuppression. Some studies suggest a potential therapeutic role of mammalian Target of Rapamycin (mTOR) inhibitors in SARS-CoV-2 infection. This study aimed to assess the impact of mTOR employment on the evolution and outcome of SARS-CoV-2 infection in solid organ transplant recipients.MethodsWe enrolled kidney transplant patients attending the Azienda Ospedaliera Universitaria Federico II in Naples and followed up on these patients from March 2020 to June 2021. We evaluated the risk of acquiring the SARS-CoV-2 infection, the clinical presentation of the disease, and its outcome together with the type of immunosuppressive therapy. Finally, we assessed the impact of mTOR inhibitors on relevant clinical metrics of SARS-CoV-2 infection.ResultsWe enrolled 371 patients, of whom 56 (15.1%) contracted SARS-CoV-2 infection during the period of the study. There were no differences observed among the different immunosuppressive therapies concerning the risk of acquiring SARS-CoV-2 infection. In contrast, the type of immunosuppressive therapy had a significant impact on the outcome of the disease. In detail, patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease (OR = 0.8, 95, CI: (0.21–0.92), P = 0.041).ConclusionIn kidney transplant patients, the use of mTOR inhibitors as part of an immunosuppressive regimen is associated with a better prognosis in the case of COVID-19.
Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma
Authors: Zhou Bo , Li Manxiang , Chen Tianjun , She Jianqing 
Published: June 2022

BackgroundDurvalumab, as a PD-L1 inhibitor, is commonly used for the treatment of various cancers. Adverse events associated with the therapy include hepatitis, nephritis, dermatitis, and myocarditis. Especially, myocarditis as an adverse event after PD-L1 inhibitor therapy is characterized for its low incidence and high mortality.Case SummaryHere we present a rare case of a 67-year-old male with lung squamous cell carcinoma complicated with empyema who experienced myocarditis after only PD-L1 inhibitor durvalumab monotherapy. He presented with markedly decrease left ventricular ejection fraction, elevated Natriuretic peptide BNP, Troponin T, Troponin I, ESR, CRP and interleukin-6. The electrocardiogram showed sinus tachycardia, low voltage of limb leads, T wave inversion in anterior waves and V1-V3 QS type. Myocardial injury occurred in a short period and quickly returned to normal after glucocorticoids therapy.ConclusionThis case report is of clinical value for the treatment of PD-L1 related myocarditis.
Static Balance and Chair-Rise Performance in Neurogeriatric Patients: Promising Short Physical Performance Battery-Derived Predictors of Fear of Falling
Authors: Scholz Katharina , Geritz Johanna , Kudelka Jennifer , Rogalski Marten , Niemann Katharina , Maetzler Corina , Welzel Julius , Drey Michael , Prell Tino , Maetzler Walter 
Published: June 2022

Background:Fear of falling (FOF) negatively affects health-related quality of life and is common in neurogeriatric patients, however, related parameters are not well understood. This study investigated the relationship between FOF, physical performance (as assessed with the Short Physical Performance Battery and its subscores) and other aspects of sarcopenia in a sample of hospitalized neurogeriatric patients.MethodsIn 124 neurogeriatric patients, FOF was assessed with the Falls Efficacy Scale International (FES-I). Physical performance was measured using the Short Physical Performance Battery (SPPB) including walking duration, balance and five times sit-to-stand task (5xSST) subscores. Appendicular skeletal muscle mass (ASMM) was estimated with the cross-validated Sergi equation using Bioelectrical impedance analysis measures. The Depression im Alter-Skala (DIA-S) was used to assess depressive symptoms. Multiple regression models with FES-I score as outcome variable were computed using backward selection with AICc as selection criterion, including: (i) SPPB total score, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, use of a walking aid, DIA-S score and Montreal Cognitive Assessment (MoCA) score; and (ii) SPPB subscores, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, DIA-S score and MoCA score, once with and once without including use of a walking aid as independent variable.ResultsLower SPPB total score, as well as lower SPPB balance and 5xSST subscores were associated with higher FES-I scores, but SPPB walking duration subscore was not. Moreover, DIA-S, number of medications and use of a walking aid were significantly associated with FOF.ConclusionOur preliminary results suggest that -if confirmed by subsequent studies- it may be worthwhile to screen patients with low SPPB balance and 5xSST subscores for FOF, and to treat especially these mobility deficits in neurogeriatric patients with FOF. Moreover, training neurogeriatric patients to use their walking aids correctly, critical evaluation of medication and treating depressive symptoms may further help reduce FOF in this highly vulnerable cohort.
Extra-Cranial Carotid Artery Stenosis: An Objective Analysis of the Available Evidence
Authors: Abbott Anne L. 
Published: June 2022

Background and PurposeCarotid stenosis is arterial disease narrowing of the origin of the internal carotid artery (main brain artery). Knowing how to best manage this is imperative because it is common in older people and an important cause of stroke. Inappropriately high expectations have grown regarding the value of carotid artery procedures, such as surgery (endarterectomy) and stenting, for lowering the stroke risk associated with carotid stenosis. Meanwhile, the improving and predominant value of medical intervention (lifestyle coaching and medication) continues to be underappreciated.Methods and ResultsThis article aims to be an objective presentation and discussion of the scientific literature critical for decision making when the primary goal is to optimize patient outcome. This compilation follows from many years of author scrutiny to separate fact from fiction. Common sense conclusions are drawn from factual statements backed by original citations. Detailed research methodology is given in cited papers. This article has been written in plain language given the importance of the general public understanding this topic. Issues covered include key terminology and the economic impact of carotid stenosis. There is a summary of the evidence-base regarding the efficacy and safety of procedural and medical (non-invasive) interventions for both asymptomatic and symptomatic patients. Conclusions are drawn with respect to current best management and research priorities. Several “furphies” (misconceptions) are exposed that are commonly used to make carotid stenting and endarterectomy outcomes appear similar. Ongoing randomized trials are mentioned and why they are unlikely to identify a routine practice indication for carotid artery procedures. There is a discussion of relevant worldwide guidelines regarding carotid artery procedures, including how they should be improved. There is an outline of systematic changes that are resulting in better application of the evidence-base.ConclusionThe cornerstone of stroke prevention is medical intervention given it is non-invasive and protects against all arterial disease complications in all at risk. The “big” question is, does a carotid artery procedure add patient benefit in the modern era and, if so, for whom?
Inhibition of BET Protein Function Suppressed the Overactivation of the Canonical NF-κB Signaling Pathway in 6-OHDA-Lesioned Rat Model of Levodopa-Induced Dyskinesia
Authors: Wan Ying , Han Li , Rong Lu , Yang Shuyuan , Song Lu , Wu Na , Liu Zhenguo , Gan Jing 
Published: June 2022

BackgroundNeuroinflammation is involved in the mechanisms of levodopa-induced dyskinesia (LID). The canonical NF-κB activation signaling pathway plays a critical role in the neuroinflammation development and BET protein-induced NF-κB-mediated neuroinflammation. The inhibition of the BET protein function has been reported to alleviate LID; however, its association with the canonical NF-κB signaling pathway in the 6-OHDA-lesioned striatum of the LID rat model remains unknown. Accordingly, we identified the status of the canonical NF-κB signaling pathway in the 6-OHDA-lesioned striatum of the LID rat model and whether the anti-dyskinetic effect of the BET inhibitor JQ1 was associated with its suppression on NF-κB-mediated neuroinflammation.Methods6-OHDA PD rat models were treated with either L-dopa plus JQ1 or L-dopa alone. L-dopa treatment was given for 2 weeks, and the JQ1 treatment was given for 3 weeks and was initiated a week prior to L-dopa treatment. As a control, the sham rats were treated with JQ1 or Veh for 3 weeks. The ALO AIM assessment and cylinder test were performed during the treatment. Glial activation markers, pro-inflammatory substances, and critical proteins in the canonical NF-κB signaling pathway were tested in the lesioned striatum after the final treatment.ResultsJQ1 effectively alleviated LID without influencing motor improvement. In the lesioned striatum, L-dopa triggered an overactivation of the canonical NF-κB signaling pathway, with an increase in the phospho-IKKα/β, phospho-IκBα, and NF-κB nuclear translocation and its phosphorylation at Ser 536 and Ser 276 sites (p &lt; 0.01 vs. sham group). L-dopa induced an overexpression of the pro-inflammatory substances of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase (iNOS), and the glial activation markers CD68 and GFAP. All the molecular changes were greatly inhibited by JQ1.ConclusionL-dopa triggered an overactivation of the canonical NF-κB signaling pathway, leading to an enhanced neuroinflammation response in the 6-OHDA-lesioned striatum of LID rat models. The inhibition of the BET protein function significantly suppressed the activation of the canonical NF-κB signaling pathway in the striatum, alleviating the neuroinflammation response and the severity of LID.
Hyper-Immune Bovine Milk as an Immunological and Nutritional Supplement for COVID-19
Authors: Nili Hassan , Bouzari Majid , Attaran Hamid Reza , Ghalegolab Nader , Rabani Mohammad , Mahmoudian Ahmad 
Published: June 2022

Many different strategies have been used to fight against the Coronavirus disease (COVID-19) pandemic as a therapeutics or prophylaxis approaches. However, not enough attention has been paid to general and specific immune factors and nutritional components found in hyper-immunized dairy products. Hyper-immune bovine colostrum (HBC) has been used against many different respiratory and gastrointestinal tracts infections during past decades. An isolated dairy farm was established, and nine mixed Holstein X Simmental dairy cattle in their 6–7 months of gestation period were chosen for hyper-immunization with inactivated Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). For this, six cows were inoculated with 2 ml of 109.4/ml (TCID50) of the virus. As a control group, three cows were inoculated with the carrier without virus. Specific IgG level against the SARS-CoV-2 was measured before and after immunization in the sera, and in the colostrum and milk following parturition in hyper-immunized cows using indirect Enzyme-linked immunosorbent assay (ELISA). Neutralizing antibodies in the serum and colostrum was measured by a quantitative ELISA. The safety of the product was determined in40 healthy volunteers aged between 18–65 years old (13 females and 27 males) in the phase 1 clinical trial (https://www.irct.ir/trial/51259). No adverse effects were observed in the experimental cows. A very high level of IgG was observed in the first colostrum that sharply decreased in the following 7 days in the milk. The titer of specific neutralizing antibody in the colostrum samples was 69 times higher than the sera. No adverse effects and clinical complications were reported by the authorized ethics committee, and an official certificate on the safety of the product was issued. Beside other strategies, this approach could be used for large-scale and low-cost production of immune components to be used as a nutritional supplement to confront current SARS-CoV-2 and future pandemics.Clinical Trial Registration[https://www.irct.ir/trial/51259].
Nutrition Risk Screening and Related Factors Analysis of Non-hospitalized Cancer Survivors: A Nationwide Online Survey in China
Authors: Wang Fang , Dong Qi , Yu Kang , Li Rong-rong , Fu Ji , Guo Jia-yu , Li Chun-wei 
Published: June 2022

PurposesThis study investigated the nutritional problems and risks of Chinese non-hospitalized cancer survivors through an online survey.MethodsThe survey included nutritional and clinical questions distributed to non-hospitalized cancer survivors. All data were screened and analyzed with strict quality control. Nutrition Risk Screening-2002 (NRS-2002) was adopted and the related factors were analyzed.ResultsSix thousand six hundred eighty-five questionnaires were included. The prevalence of nutritional risk was 33.9%, which varied according to age, sex, cancer type, TNM staging, oncologic treatment, time interval since last treatment, etc. In the regression analysis, nutritional risk was associated with age, TNM staging, and nutrition support. Patients with leukemia and digestive cancer had the highest NRS-2002 score (3.33 ± 1.45 and 3.25 ± 1.61); the prevalence of nutritional risk (NRS-2002 ≥ 3) was 66.7 and 55.1%, respectively. Patients with a higher TNM stage had higher NRS-2002 scores in non-digestive cancer, which was not seen in digestive cancer. Among digestive, bone, nervous, and respiratory cancer patients, the NRS-2002 score mainly consisted of “impaired nutritional status,” which coincided with the “disease severity score” in leukemia patients. Nutrition intervention was achieved in 79.7 and 15.2% of patients with nutritional risk and no risk. Of the patients, 60.3% exhibited confusion about nutritional problems, but only 25.1% had professional counseling.ConclusionsRegular nutritional risk screening, assessment, and monitoring are needed to cover non-hospitalized cancer survivors to provide nutrition intervention for better clinical outcome and quality of life. By online survey, the nutritional risk of non-hospitalized cancer survivors was found high in China, but the nutrition support or professional consultation were not desirable. The composition of nutritional risk should also be aware of.
PRC2, Chromatin Regulation, and Human Disease: Insights From Molecular Structure and Function
Authors: Liu Xiuli , Liu Xin 
Published: June 2022

Polycomb repressive complex 2 (PRC2) is a multisubunit histone-modifying enzyme complex that mediates methylation of histone H3 lysine 27 (H3K27). Trimethylated H3K27 (H3K27me3) is an epigenetic hallmark of gene silencing. PRC2 plays a crucial role in a plethora of fundamental biological processes, and PRC2 dysregulation has been repeatedly implicated in cancers and developmental disorders. Here, we review the current knowledge on mechanisms of cellular regulation of PRC2 function, particularly regarding H3K27 methylation and chromatin targeting. PRC2-related disease mechanisms are also discussed. The mode of action of PRC2 in gene regulation is summarized, which includes competition between H3K27 methylation and acetylation, crosstalk with transcription machinery, and formation of high-order chromatin structure. Recent progress in the structural biology of PRC2 is highlighted from the aspects of complex assembly, enzyme catalysis, and chromatin recruitment, which together provide valuable insights into PRC2 function in close-to-atomic detail. Future studies on the molecular function and structure of PRC2 in the context of native chromatin and in the presence of other regulators like RNAs will continue to deepen our understanding of the stability and plasticity of developmental transcriptional programs broadly impacted by PRC2.
Transverse Sinus Stenting Reverses Medically Refractory Idiopathic Intracranial Hypertension
Authors: Reid Kate , Winters H. Stephen , Ang Timothy , Parker Geoffrey D. , Halmagyi G. Michael 
Published: June 2022

AimTo characterise the ophthalmic indications for, and ophthalmic efficacy of, transverse sinus stenting in adults with medically refractory idiopathic intracranial hypertension.MethodsA retrospective cohort study was undertaken on a single-author database of 226 successive patients with confirmed idiopathic intracranial hypertension (IIH). A total of 32 patients were identified who received a transverse sinus stent for medically refractory disease. This which was defined as visual threat and/or intolerance of maximal medical therapy. Patients with medically refractory disease proceeded to stenting, if found to have a significant transverse sinus stenosis gradient at catheter venography. Visual threat was quantified via the degree of papilledema on optical coherence tomography of the retinal nerve fibre layer, and via the visual field mean deviation. CSF opening pressure at lumbar puncture and cerebral venous sinus pressure measurements from catheter venography were correlated with the ophthalmic data, noting also intolerance of maximal medical therapy. Complications of stenting were fully assessed.ResultsMedically refractory IIH was found in 18% of the total cohort of IIH patients. 90% of those with medically refractory disease had a significant transverse sinus stenosis pressure gradient, and 80% proceeded to stenting. The intervention eliminated papilledema in 96% of stented patients, and allowed 81% to cease acetazolamide. The need for a further procedure was low at 6%, and the safety profile was favourable.ConclusionsMedically refractory disease in IIH is common (18%), and nearly always associated with a significant transverse sinus stenosis pressure gradient (90%). Endovascular stenting of the stenosis deserves wider uptake as a highly effective, safe, and usually definitive treatment. It safeguards vision by eliminating papilledema (96%), and allows most patients to cease acetazolamide (81%). By analogy with glaucoma, if acetazolamide is the prostaglandin of IIH and CSF diversion the emergency glaucoma filter, stenting is the minimally invasive glaucoma surgery.
Value of Literature Review to Inform Development and Use of Biologics in Juvenile Idiopathic Arthritis
Authors: Golhen Klervi , Winskill Carolyn , Yeh Cynthia , Zhang Nancy , Welzel Tatjana , Pfister Marc 
Published: June 2022

BackgroundJuvenile idiopathic arthritis (JIA) is one of the most common pediatric inflammatory rheumatic diseases (PiRDs). Uncontrolled disease activity is associated with decreased quality of life and chronic morbidity. Biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) have considerably improved clinical outcomes. For optimized patient care, understanding the efficacy-safety profile of biologics in subgroups of JIA is crucial. This systematic review based on published randomized controlled trials (RCTs) aims to assess efficacy and safety data for bDMARDs and JAKi with various JIA subgroups after 3 months of treatment.MethodsData for American College of Rheumatology (ACR) pediatric (Pedi) 30, 50, and/or 70 responses after 3 months of treatment were selected from RCTs investigating bDMARDs or JAKi in JIA according to predefined inclusion/exclusion criteria. Treatment and control arms were compared by calculating risk ratios (RRs) with 95% confidence intervals (CIs), and proportions of overall, serious adverse events (AEs) and infections were analyzed. Forest plots were generated to summarize efficacy and safety endpoints across studies, JIA subgroups, and type of biologics.ResultsTwenty-eight out of 41 PiRD RCTs investigated bDMARD or JAKi treatments in JIA. 9 parallel RCTs reported ACR Pedi 30, 50, and/or 70 responses 3 months after treatment initiation. All treatment arms showed improved ACR Pedi responses over controls. RRs ranged from 1.05 to 3.73 in ACR Pedi 30, from 1.20 to 7.90 in ACR Pedi 50, and from 1.19 to 8.73 in ACR Pedi 70. An enhanced effect for ACR Pedi 70 was observed with infliximab combined with methotrexate in PJIA vs. methotrexate monotherapy. A slightly higher risk of gastrointestinal AEs and infections was observed with treatment arms compared to placebo or methotrexate monotherapy.ConclusionInvestigated bDMARDs and JAKi showed superior treatment responses compared to controls after 3 months of treatment, which were more pronounced in ACR Pedi 50 and 70 than in ACR Pedi 30. Higher susceptibility to infections associated with bDMARDs or JAKi vs. control arms must be weighed against efficacious treatment of the underlying disease and prevention of disease-related damage. Additional RCTs are warranted to further inform development and utilization of biologics in JIA.