bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Ophthalmic Outcomes Following Venous Sinus Stenting in Idiopathic Intracranial Hypertension
Authors: Oyemade Kafayat A. , Xu Timothy T. , Brinjikji Waleed , Cutsforth-Gregory Jeremy K. , Lanzino Giuseppe , Kallmes David F. , Moss Heather E. , Dodd Robert , Bhatti M. Tariq , Chen John J. 
Published: June 2022

BackgroundOphthalmic outcomes following venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH) are not well characterized.Materials and MethodsA retrospective chart review was conducted on 86 consecutive patients with IIH who underwent venous sinus stenting at Mayo Clinic, Rochester, Minnesota and Stanford Medical Center, Palo Alto, California between May 2015 and October 2021. Patients with raised intracranial pressure from a non-IIH etiology were excluded. Clinical symptoms and neuro-ophthalmological data, including best corrected visual acuity (BCVA), visual field mean deviation, papilledema, and optical coherence tomography (OCT) peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GC-IPL), were analyzed. Baseline measurements before VSS and 3 months or more postoperatively were compared.ResultsEighty-six subjects (82 female) were included in this study, with a median age of 33 (16–68) years and a median body mass index of 36.69 (22.30–62.00) kg/m2. 85/86 (98.8%) had attempted prior management with medication, and 12/86 (14%) had prior surgical management with optic nerve sheath fenestration, ventriculoperitoneal shunt, or bariatric surgery. Prior to VSS, 67/86 (77.9%) had papilledema, 85/86 (98.8%) had headaches, and 68/86 (79.1%) had pulsatile tinnitus. For patients with both pre- and post-VSS data available, the average papilledema grade was 1.76 (0–5) (n = 74) and the average OCT pRNFL was 186.34 (52.00–588.00) µm (n = 70), prior to VSS. A median of 4.0 (interquartile range 3.3–5.4) months after VSS, the average papilledema grade improved to 0.39 (0–2), p &lt;0.001, and OCT pRNFL improved to 96.86 (47.00–168.00) µm, p &lt;0.001. 28/86 (32.6%) patients no longer required medication for high intracranial pressure. 14/85 (16.5%) patients reported complete resolution of their headache and 55/71 (77.5%) reported improvement in headache quality. 40/68 (66.7%) reported complete resolution of pulsatile tinnitus. OCT GC-IPL, BCVA, and visual field mean deviation did not significantly change pre- vs post-VSS.ConclusionsOur large consecutive case series corroborates smaller prior studies in demonstrating the overall efficacy of VSS for patients with IIH. We found both ophthalmic improvements, as demonstrated by the significantly reduced papilledema and pRNFL, and overall clinical symptom improvement.
Comparison of Respiratory Pathogens in Children With Lower Respiratory Tract Infections Before and During the COVID-19 Pandemic in Shanghai, China
Authors: Xu Menghua , Liu Pengcheng , Su Liyun , Cao Lingfeng , Zhong Huaqing , Lu Lijuan , Jia Ran , Xu Jin 
Published: June 2022

ObjectivesThis study aimed to assess the impact of COVID-19 on the prevalence of respiratory pathogens among hospitalized children with lower respiratory tract infections (LRTIs) in Shanghai.MethodsRespiratory specimens were collected from children with LRTIs in Children’s Hospital of Fudan University from February 2019 to January 2021 and common respiratory pathogens were detected using multiplex PCR. The data of 13 respiratory pathogens were analyzed and compared between the year of 2020 (from February 2020 to January 2021) and 2019 (from February 2019 to January 2020).ResultsA total of 1,049 patients were enrolled, including 417 patients in 2019 and 632 patients in 2020. In 2020, 27.53% of patients were tested positive for at least one pathogen, which was significantly lower than that in 2019 (78.66%). The top three pathogens were Mycoplasma pneumoniae (Mp), human adenovirus (ADV) and human rhinovirus (RV) in 2019, whereas RV, human respiratory syncytial virus (RSV) and human parainfluenza virus (PIV) were the predominant ones in 2020. The positive rates of Mp, ADV, RV, PIV, Influenza virus B (InfB), H3N2, and H1N1 were significantly decreased in 2020. RV was the most detectable respiratory pathogen in 2020, and become the most frequent pathogen in all five age groups. PIV had a high prevalence from October to December 2020 which was even higher than that in 2019. Influenza virus A (InfA) was not detected in 2020. Co-infection was significantly less frequent in 2020.ConclusionThe public health interventions aiming to eliminate COVID-19 have great impact on the prevalence of common respiratory pathogens. The prevalence of RV and PIV reminds us a possible resurgence of some pathogens.
Therapeutic Endoscopic Retrograde Cholangiopancreatography for Pediatric Hepato-Pancreato-Biliary Diseases: A Systematic Review and Meta-Analysis
Authors: Sun Rongjuan , Xu Xiaodan , Zheng Qipeng , Zhan Jianghua 
Published: June 2022

BackgroundHepato-pancreato-biliary (HPB) disease has different causes and types between children and adults, which has been increasingly diagnosed in the pediatric group. Endoscopic retrograde cholangiopancreatography (ERCP) has been gradually considered as a therapeutic method in adults, while in pediatric patients, there are not many reports of its usage. This systematic review and meta-analysis aims to assess the use condition of therapeutic ERCP in the management of pediatric HPB diseases.MethodsThis systematic literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane library databases to identify all relevant articles published from inception to February 2022 that evaluated therapeutic ERCP in pediatric patients with HPB diseases. The researchers included studies in which patients were less than 18 years old and underwent therapeutic ERCP procedures. A random-effects model was used to analyze the usage rate of therapeutic ERCP procedures, procedural success rates, adverse event rates, and the rate of different therapeutic procedures. Subgroup analysis, sensitivity analysis, and meta-regression were conducted to analyze the source of heterogeneity.ResultsA total of 33 articles were included. After homogenization, the overall use of therapeutic interventions accounts for 77% [95% confidence interval (CI) 74–81%] of all ERCP procedures. After excluding outlier studies, the estimation success rate of the therapeutic procedure is 74% (95% CI 69–79%), and adverse event rate is 8% (95% CI 6–10%). In our study, stent placement is the most common procedure, which makes up 75% (95% CI 65–86%) of all therapeutic procedures. In addition, the usage proportion of sphincterotomy (ST), stone extraction/removal, bougienage/balloon dilation is, respectively, 46% (95% CI 39–53%), 34% (95% CI 31–38%), and 26% (95% CI 22–29%).ConclusionThe ERCP procedure is gradually considered a therapeutic technique in pediatric patients, the proportion of therapeutic ERCP is 77% of total usage, which is increasing every year. Meanwhile, its success rate is relatively high. It reflects that this operation modality is promising in the treatment of HPB disorders and is gradually expanded as more branch technologies are being used. A variety of operations can be achieved through ERCP procedures, and more functions should be developed in the future.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022302911].
The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue
Authors: Konrat Robert , Papp Henrietta , Kimpel Janine , Rössler Annika , Szijártó Valéria , Nagy Gábor , Madai Mónika , Zeghbib Safia , Kuczmog Anett , Lanszki Zsófia , Gesell Tanja , Helyes Zsuzsanna , Kemenesi Gábor , Jakab Ferenc , Nagy Eszter 
Published: June 2022

Background and purpose: The COVID-19 pandemic continues to pose challenges, especially with the emergence of new SARS-CoV-2 variants that are associated with higher infectivity and/or compromised protection afforded by the current vaccines. There is a high demand for additional preventive and therapeutic strategies effective against this changing virus. Repurposing of approved or clinically tested drugs can provide an immediate solution.Experimental Approach: We applied a novel computational approach to search among approved and commercially available drugs. Antiviral activity of a predicted drug, azelastine, was tested in vitro in SARS-CoV-2 infection assays with Vero E6 cells, Vero cells stably overexpressing the human TMPRSS2 and ACE2 proteins as well as on reconstituted human nasal tissue using the predominant variant circulating in Europe in summer 2020, B.1.177 (D614G variant), and its emerging variants of concern; B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants. The effect of azelastine on viral replication was assessed by quantification of viral genomes by droplet digital PCR or qPCR.Key results: The computational approach identified major drug families, such as anti-infective, anti-inflammatory, anti-hypertensive, antihistamine, and neuroactive drugs. Based on its attractive safety profile and availability in nasal formulation, azelastine, a histamine 1 receptor-blocker was selected for experimental testing. Azelastine reduced the virus-induced cytopathic effect and SARS-CoV-2 copy numbers both in preventive and treatment settings upon infection of Vero cells with an EC50 of 2.2–6.5 µM. Comparable potency was observed with the alpha, beta and delta variants. Furthermore, five-fold dilution (containing 0.02% azelastine) of the commercially available nasal spray formulation was highly potent in inhibiting viral propagation in reconstituted human nasal tissue.Conclusion and Implications: Azelastine, an antihistamine available as nasal sprays developed against allergic rhinitis may be considered as a topical prevention or treatment of nasal colonization by SARS-CoV-2. A Phase 2 efficacy indicator study with azelastine-containing nasal spray that was designed based on the findings reported here has been concluded recently, confirming accelerated viral clearance in SARS-CoV-2 positive subjects.
Associations Between Asthma Diagnosis/Asthma Exacerbation and Previous Proton-Pump Inhibitor use: A Nested Case-Control Study Using a National Health Screening Cohort
Authors: Choi Hyo Geun , Min Chanyang , Yoo Dae Myoung , Tan Bruce K. , Kim Joo-Hee , Kim Hwan Il , Park Ji-Young , Park Sunghoon , Hwang Yong Il , Jang Seung Hun , Jung Ki-Suck 
Published: June 2022

Background: Proton-pump inhibitors (PPIs) block acid secretion from gastric parietal cells; however, recent studies have reported that PPIs have antioxidant and anti-inflammatory properties in various cells. Newer PPIs are stronger inhibitors of acid secretion; however, the anti-inflammatory effects of these drugs have not been assessed. We evaluated anti-inflammatory effect of PPIs on the development of asthma/asthma exacerbation (AE) in a national health screening cohort.Methods: This case-control study comprised 64,809 participants with asthma who were 1:1 matched with controls from the Korean National Health Insurance Service-Health Screening Cohort. Conditional logistic regression analysis was used to evaluate the effect of previous PPI use on an asthma diagnosis in all participants. Unconditional logistic regression was used to assess the effect of PPI use on AE in participants with asthma. These relationships were estimated in a subgroup analysis according to PPI generation.Results: Overall, PPI use increased the risk of asthma diagnosis [adjusted odds ratio (aOR) = 1.29, 95% confidence interval (CI) = 1.23–1.35, p &lt; 0.001]. Use of the first-generation PPIs was associated with asthma (aOR = 1.34, 95% CI = 1.18–1.52, p &lt; 0.001), while use of second-generation PPIs was not (aOR = 0.97, 95% CI = 0.82–1.15, p = 0.748). In contrast, overall PPI use decreased the risk of AE in participants with asthma (aOR = 0.79, 95% CI = 0.75–0.84, p &lt; 0.001), although this effect was observed only for second-generation PPIs (aOR = 0.76, 95% CI = 0.65–0.89, p = 0.001).Conclusion: PPI use increased the risk for subsequent asthma diagnosis. However, this effect was confined to first-generation PPIs. Second-generation PPIs decreased the risk of AE.
Evaluation of the Acute and Sub-Acute Oral Toxicity of Jaranol in Kunming Mice
Authors: Liu Tianlong , Zhang Yao , Liu Jing , Peng Junwen , Jia Xin , Xiao Yunfeng , Zheng Lanbing , Dong Yu 
Published: June 2022

Background: Jaranol has shown a wide range of pharmacological activities; however, no study has yet examined in vivo toxicity. The study aimed to investigate the oral acute and sub-acute toxicity of jaranol in mice.Methods: The acute toxicity was determined by a single oral dose of jaranol (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The jaranol (50, 100 and 200 mg/kg BW·d−1) was given by gavage for 28 days daily in the sub-acute study. The mouse body weight (BW), organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied in acute and sub-acute toxicity.Results: During the acute toxicity test, a single oral dose (2000 mg/kg) jaranol did not cause significant alteration in majority of the hematological indices. However, jaranol decreased the level of serum alanine aminotransferase and aspartate aminotransferase. Those results showed that the oral lethal dose 50 (LD50) of jaranol was higher than 2000 mg/kg BW, regardless of sex. In repeated daily oral doses (50, 100 and 200 mg/kg BW·d−1), no mortality was recorded in the various experimental groups. The jaranol reduced body weight gain (200 mg/kg BW·d−1), the relative spleen weight (all doses) and serum alanine aminotransferase activity (200 mg/kg BW·d−1). On the other hand, jaranol significantly elevated red blood cell count (100 and 200 mg/kg BW·d−1) and serum creatinine levels (200 mg/kg BW·d−1). Histological study revealed that spleen bleeding was identified in 200 mg/kg jaranol-treated mice.Conclusion: Jaranol was relatively safe in Kunming Mice when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on jaranol to ensure that its use is free of potential toxicity to humans.
Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate)
Authors: Ullah Farhad , Iqbal Zafar , Khan Amjad , Khan Saeed Ahmad , Ahmad Lateef , Alotaibi Amal , Ullah Riaz , Shafique Muhammad 
Published: June 2022

Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85–330.4 ± 4.19, PDI 0.119 ± 0.02–0.235 ± 0.008, zeta potential −0.163 ± 0.11–−5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs.
Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway
Authors: Gu Yang-Yang , Tan Xiao-Hui , Song Wen-Peng , Song Wei-Dong , Yuan Yi-Ming , Xin Zhong-Cheng , Wang Jia-Dong , Fang Dong , Guan Rui-Li 
Published: June 2022

Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction.Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay.Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway.Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway.
Prominent Effects of Berbamine Hydrochloride on Alzheimer’s Disease Model Mice
Authors: Chen Chang-lan , Wang Hai-li , Qian Feng , Liu Mei-hua , Guo Xiao-xuan , Lv Jing , Huang Jia-hui , Zhang Nai-zhi , Xiang Zheng 
Published: June 2022

Very few anti-Alzheimer’s disease (AD) drugs are clinically available at present due to the complex mechanism of Alzheimer’s disease. For the purpose of discovering potential anti-AD drugs in bisbenzylisoquinoline alkaloids, the anti-AD function and the mechanism of the function of berbamine hydrochloride (BBMH) were studied. Three kinds of AD model mice, double transgenic APP/PS1 AD mice, Gal-Alu AD mice induced by the intraperitoneal injection of d-galactose combined with the intragastric administration of aluminum trichloride, and Alu AD-like mice induced by stereotactic brain injection of aluminum trichloride, were administered with BBMH for 40 days at a dosage of 280 mg/kg/d. The effects of BBMH on the learning and memory behavior of the AD mice were studied through the Morris water maze experiment, and the influences of BBMH on the pathological features of AD, including the deposition of Aβ, the lesions of pyramidal cells (neurons), and the formation of neurofibrillary tangles, were studied by the immunohistochemical staining, hematoxylin-eosin staining, and silver staining of the brain tissues of the mice. The water maze experiment showed that BBMH could significantly improve the learning and memory abilities of three kinds of treated mice. Immunohistochemical staining showed that BBMH could significantly reduce the deposition of Aβ in the brain tissues of treated mice. Hematoxylin-eosin staining showed that BBMH could significantly alleviate the lesions of pyramidal cells in the hippocampal tissue of the mice. Silver staining showed that BBMH could significantly reduce the formation of neurofibrillary tangles in the hippocampal tissue of the mice. These results indicated that BBMH has significant anti-AD effects and the potential as an anti-AD drug. Western blot analysis of the brain tissue of the mice showed that the expression level of calpain, a Ca2+-dependent proteolytic enzyme, was significantly inhibited and the expression level of SelK, a selenoprotein mainly expressed in immune cells, was significantly increased. It is speculated that the anti-AD effect of BBMH is related to the improvement of the phagocytosis of microglial cells in brain tissues and macrophages migrated into the brain as well as the regulation of calcium homeostasis and calcium-dependent proteases in the brain tissues of the mice.
Effect of Prone Positioning With Individualized Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome Using Electrical Impedance Tomography
Authors: Mi Liangyu , Chi Yi , Yuan Siyi , He Huaiwu , Long Yun , Frerichs Inéz , Zhao Zhanqi 
Published: June 2022

Background: Positive end-expiratory pressure (PEEP) optimization during prone positioning remains under debate in acute respiratory distress syndrome (ARDS). This study aimed to investigate the effect of prone position on the optimal PEEP guided by electrical impedance tomography (EIT).Methods: We conducted a retrospective analysis on nineteen ARDS patients in a single intensive care unit. All patients underwent PEEP titration guided by EIT in both supine and prone positions. EIT-derived parameters, including center of ventilation (CoV), regional ventilation delay (RVD), percentage of overdistension (OD) and collapse (CL) were calculated. Optimal PEEP was defined as the PEEP level with minimal sum of OD and CL. Patients were divided into two groups: 1) Lower Optimal PEEPPP (LOP), where optimal PEEP was lower in the prone than in the supine position, and 2) Not-Lower Optimal PEEPPP (NLOP), where optimal PEEP was not lower in the prone compared with the supine position.Results: Eleven patients were classified as LOP (9 [8-9] vs. 12 [10-15] cmH2O; PEEP in prone vs. supine). In the NLOP group, optimal PEEP increased after prone positioning in four patients and remained unchanged in the other four patients. Patients in the LOP group had a significantly higher body mass index (26 [25-28] vs. 22 [17-25] kg/m2; p = 0.009) and lower ICU mortality (0/11 vs. 4/8; p = 0.018) compared with the NLOP group. Besides, PaO2/FiO2 increased significantly during prone positioning in the LOP group (238 [170-291] vs. 186 [141-195] mmHg; p = 0.042). CoV and RVD were also significantly improved during prone positioning in LOP group. No such effects were found in the NLOP group.Conclusion: Broad variability in optimal PEEP between supine and prone position was observed in the studied ARDS patients. Not all patients showed decreased optimal PEEP during prone positioning. Patients with higher body mass index exhibited lower optimal PEEP in prone position, better oxygenation and ventilation homogeneity.