bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Efficacy and Safety Between Standard, Accelerated Epithelium-Off and Transepithelial Corneal Collagen Crosslinking in Pediatric Keratoconus: A Meta-Analysis
Authors: Li Yuanjun , Lu Ying , Du Kaixuan , Yin Yewei , Hu Tu , Fu Yanyan , Xiang Aiqun , Fu Qiuman , Wu Xiaoying , Wen Dan 
Published: March 2022

PurposeThe purpose of the study is to compare the efficacy of standard epithelium-off CXL (SCXL), accelerated epithelium-off CXL (ACXL), and transepithelial crosslinking CXL (TECXL) for pediatric keratoconus.MethodsA literature search on the efficacy of SCXL, ACXL, and TECXL [including accelerated TECXL (A-TECXL)] for keratoconus patients younger than 18 years was conducted using PubMed, Cochrane Library, ClinicalTrials.gov, and EMBASE up to 2021. Primary outcomes were changes in uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) after CXL. Secondary outcomes were changes in best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), and central corneal thickness (CCT). Estimations were analyzed by weighted mean difference (WMD) and 95% confidence interval (CI).ResultsA number of eleven identified studies enrolled 888 eyes (SCXL: 407 eyes; ACXL: 297 eyes; TECXL: 28 eyes; A-TECXL: 156 eyes). For pediatric keratoconus, except for a significant greater improvement in BCVA at 24-month follow-up in SCXL (WMD = –0.08, 95%CI: –0.14 to –0.01, p = 0.03, I2 = 71%), no significant difference was observed in other outcomes between the SCXL and ACXL groups. SCXL seems to provide greater changes in UCVA (WMD = –0.24, 95% CI: –0.34 to –0.13, p &lt; 0.00001, I2 = 89%), BCVA (WMD = –0.09, 95% CI: –0.15 to –0.04, p = 0.0008, I2 = 94%), and Kmax (WMD = –1.93, 95% CI: –3.02 to –0.85, p = 0.0005, I2 = 0%) than A-TECXL, with higher incidence of adverse events.ConclusionFor pediatric keratoconus, both SCXL and ACXL appear to be comparable in the efficacy of visual effects and keratometric outcomes; SCXL seems to provide greater changes in visual and pachymetric outcomes than A-TECXL.
Cone Photoreceptors in Diabetic Patients
Authors: Elsner Ann E. , Walker Brittany R. , Gilbert Robert N. , Parimi Vamsi , Papay Joel A. , Gast Thomas J. , Burns Stephen A. 
Published: March 2022

PurposeCones in diabetic patients are at risk due to metabolic and vascular changes. By imaging retinal vessel modeling at high magnification, we reduced its impact on cone distribution measurements. The retinal vessel images and retinal thickness measurements provided information about cone microenvironment.MethodsWe compared cone data in 10 diabetic subjects (28–78 yr) to our published norms from 36 younger and 10 older controls. All subjects were consented and tested in a manner approved by the Indiana University Institutional Review Board, which adhered to the Declaration of Helsinki. Custom adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones and retinal microcirculation. We counted cones in a montage of foveal and temporal retina, using four non-contiguous samples within 0.9–7 deg that were selected for best visibility of cones and least pathology. The data were fit with a two parameter exponential model: ln(cone density) = a * microns eccentricity + b. These results were compared to retinal thickness measurements from SDOCT.ResultsDiabetic cone maps were more variable than in controls and included patches, or unusually bright and dark cones, centrally and more peripherally. Model parameters and total cones within the central 14 deg of the macula differed across diabetic patients. Total cones fell into two groups: similar to normal for 5 vs. less than normal for 2 of 2 younger diabetic subjects and 3 older subjects, low but not outside the confidence limits. Diabetic subjects had all retinal vascular remodeling to varying degrees: microaneurysms; capillary thickening, thinning, or bends; and vessel elongation including capillary loops, tangles, and collaterals. Yet SD-OCT showed that no diabetic subject had a Total Retinal Thickness in any quadrant that fell outside the confidence limits for controls.ConclusionsAOSLO images pinpointed widespread retinal vascular remodeling in all diabetic eyes, but the SDOCT showed no increased retinal thickness. Cone reflectivity changes were found in all diabetic patients, but significantly low cone density in only some. These results are consistent with early changes to neural, glial, or vascular components of the retinal without significant retinal thickening due to exudation.
Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials
Authors: Liu Jing , Jia WanYu , Yu Chen 
Published: March 2022

BackgroundPatients with end-stage renal disease (ESRD) are characterized with high risk of heart failure. Although mineralocorticoid receptor antagonists have beneficial effect on relieving cardiac fibrosis and, thus, reduce the incidence of cardiovascular disease and cardiac death, the therapeutic benefits and adverse effects are still controversial. We conducted a meta-analysis to measure the safety and efficacy of spironolactone in patients undergoing dialysis.MethodsA systematic search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Cochrane databases. Primary outcomes included changes in all-cause mortality (ACM), serum potassium concentration, incidence of hyperkalemia and gynecomastia (GYN). Secondary outcomes included changes in blood pressure (BP), left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Subgroup analysis and sensitivity analysis were further conducted. This research was registered with PROSPERO (International Prospective Register of Systematic Reviews; No. CRD42021287493).ResultsFifteen RCTs with 1,258 patients were enrolled in this pooled-analysis. Spironolactone treatment significantly decreased ACM (RR = 0.42, P &lt; 0.0001), CCV (RR = 0.54, P = 0.008) and LVMI (MD = −6.28, P = 0.002), also increased occurrence of GYN (RR = 4.36, P = 0.0005). However, LVEF (MD = 2.63, P = 0.05), systolic BP (MD = −4.61, P = 0.14) and diastolic BP (MD = −0.12, P = 0.94) did not change between two groups after treatment. Although serum potassium concentration was increased (MD = 0.22, P &lt; 0.0001) after spironolactone supplement, the risk of hyperkalemia remained unchanged (RR = 1.21, P = 0.31). Further subgroup analysis found more obvious advantageous as well as disadvantageous effects in Asian subjects than European or American ones. Also, with more than 9 months of treatment duration, patients achieved more favorable influence than shorter duration.ConclusionsThese results highlight the therapeutic effects of spironolactone on cardiovascular indexes, including ACM, CCV, and LVMI. However, the unignorable increase of GYN incidence and serum potassium level indicate that close monitor in dialysis-dependent patients, especially Asian patients, is essential.
Age-Associated Risk of Liver-Related Adverse Drug Reactions
Authors: Han Yan-zhong , Guo Yu-ming , Xiong Peng , Ge Fei-lin , Jing Jing , Niu Ming , Zhao Xu , Bai Zhao-fang , Song Hai-bo , Xiao Xiao-he , Wang Jia-bo 
Published: March 2022

ObjectiveAging population is generally considered more sensitive to adverse drug reactions (ADRs). Yet, big data-based quantitative evidence currently does not exist to support this concept. This study aims to investigate age-associated risks of liver-related ADR (L-ADR).MethodsSpontaneous reporting data from 2012 to 2016 were retrieved from the China National ADR Monitoring System. The risk ratio (RR) was used to quantify the relative risk of L-ADR of each age group. The reporting odds ratio (ROR) was used to quantify the correlation with the risk of L-ADR of each drug category or drug in older adults.ResultsTotally, 64,702 L-ADR reports were retrieved, covering ages from 1 to 116, with a median age of 49. The RR values increased exponentially with the increase of age, which indicates that the relative risk of L-ADR increased by 33% for every 10-year increase in age. The age cutoff point for relative high risk of L-ADR was estimated at 52.0 years old (RR = 1). In 17 categories composed of 270 drugs, the top 3 drug categories with a high correlation to the risk of L-ADR in older adults were antiarrhythmic (ROR, 5.75; 95% CI: 4.45–7.42), antilipemic (ROR, 4.77; 95% CI: 4.53–5.02), and antihypertensive (ROR, 2.97; 95% CI: 2.59–3.41).ConclusionsThis research illustrates quantitatively that aging is a potential risk factor for L-ADR, with a 33% increase in relative risk for every 10-year increase in age. Risk management should be addressed for older adults when those drugs with a high correlation to the risk of L-ADR are used.
A Structure-Related Fine-Grained Deep Learning System With Diversity Data for Universal Glaucoma Visual Field Grading
Authors: Huang Xiaoling , Jin Kai , Zhu Jiazhu , Xue Ying , Si Ke , Zhang Chun , Meng Sukun , Gong Wei , Ye Juan 
Published: March 2022

PurposeGlaucoma is the main cause of irreversible blindness worldwide. However, the diagnosis and treatment of glaucoma remain difficult because of the lack of an effective glaucoma grading measure. In this study, we aimed to propose an artificial intelligence system to provide adequate assessment of glaucoma patients.MethodsA total of 16,356 visual fields (VFs) measured by Octopus perimeters and Humphrey Field Analyzer (HFA) were collected, from three hospitals in China and the public Harvard database. We developed a fine-grained grading deep learning system, named FGGDL, to evaluate the VF loss, compared to ophthalmologists. Subsequently, we discuss the relationship between structural and functional damage for the comprehensive evaluation of glaucoma level. In addition, we developed an interactive interface and performed a cross-validation study to test its auxiliary ability. The performance was valued by F1 score, overall accuracy and area under the curve (AUC).ResultsThe FGGDL achieved a high accuracy of 85 and 90%, and AUC of 0.93 and 0.90 for HFA and Octopus data, respectively. It was significantly superior (p &lt; 0.01) to that of medical students and nearly equal (p = 0.614) to that of ophthalmic clinicians. For the cross-validation study, the diagnosis accuracy was almost improved (p &lt; 0.05).ConclusionWe proposed a deep learning system to grade VF of glaucoma with a high detection accuracy, for effective and adequate assessment for glaucoma patients. Besides, with the convenient and credible interface, this system can promote telemedicine and be used as a self-assessment tool for patients with long-duration diseases.
Relationship Between the Onset of Ménière's Disease and Sympathetic Hyperactivity
Authors: Ishii Masanori , Ishiyama Gail , Ishiyama Akira , Kato Yujin , Mochizuki Fumihiro , Ito Yusuke 
Published: March 2022

ObjectiveThe pathogenesis of Ménière's disease is still largely unknown; however, it is known to be strongly associated with stress. Excessive stress can cause hyperactivity of the sympathetic autonomic nervous system. With the aim of understanding changes in sympathetic hyperactivity before and after Ménière's disease, we compared autonomic nervous function in patients in a stable phase of Ménière's disease and that in healthy adults. We also gathered data over about 10 years on autonomic nervous function immediately before a Ménière's attack.Study DesignProspective study.PatientsAutonomic nervous function was analyzed in 129 patients in a stable phase of Ménière's disease 31 healthy adult volunteers. In nine patients, autonomic nervous function was also measured immediately before and after treatment of a vertigo attack.Main Outcome MeasurePower spectrum analysis of heart rate variability (HRV) of EEG/ECG and an infrared electronic pupillometer were used. Sympathetic and parasympathetic nervous function was measured.ResultsThere were no statistically significant differences in autonomic nervous function determined by HRV and electronic pupillometry between patients in a stable phase of Ménière's disease and healthy adults. Sympathetic function as measured by electronic pupillometry parameters VD and T5 showed no difference between the affected and unaffected sides in the baseline data measured in the stable phase (VD: affected side is 31.02 ± 6.16 mm/sec, unaffected side is 29.25 ± 5.73 mm/sec; T5: affected side is 3.37 ± 0.43 msec, unaffected side is 3.25 ± 0.39 msec). In contrast, all nine patients whose HRV data had been obtained just before an attack showed marked suppression of the parasympathetic nervous system and activation of the sympathetic nervous system. Electronic pupillometry also revealed an overactivation of the sympathetic nervous system on the affected side, just before the attacks. Analysis of sequential changes after the onset of an attack revealed that overactivation on the affected side was reduced after treatment, and no difference between affected and unaffected sides was observed 3 days after treatment.ConclusionDetailed analysis of autonomic nervous function showed that immediately before an attack of Ménière's disease, the sympathetic nervous system on the affected side was strongly overactivated.
Alterations of the White Matter in Patients With Knee Osteoarthritis: A Diffusion Tensor Imaging Study With Tract-Based Spatial Statistics
Authors: Cheng Shirui , Dong Xiaohui , Zhou Jun , Tang Chenjian , He Wenhua , Chen Yang , Zhang Xinyue , Ma Peihong , Yin Tao , Hu Yimei , Zeng Fang , Li Zhengjie , Liang Fanrong 
Published: March 2022

BackgroundFunctional and structural alterations in the gray matter have been observed in patients with knee osteoarthritis (KOA). However, little is known about white matter changes in KOA. Here, we evaluated fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) to investigate potential alterations in the white matter of patients with KOA.MethodsA total of 166 patients with KOA, along with 88 age- and sex-matched healthy controls were recruited and underwent brain magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were collected and analyzed using tract-based spatial statistics (TBSS). Statistical significances were determined at p &lt; 0.05 and were corrected by the threshold-free cluster enhancement (TFCE) method. Then, we evaluated potential correlations between FA, MD, AD, RD values and disease duration, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and visual analog scale (VAS) scores.ResultsFA values for the body of corpus callosum, splenium of corpus callosum, bilateral superior longitudinal fasciculus, cingulum, bilateral superior corona radiata, and right posterior corona radiata were significantly higher in patients with KOA than in healthy controls (p &lt; 0.05, TFCE corrected). Compared with healthy controls, patients with KOA also had significantly lower MD, AD, and RD values of the genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, corona radiata, right posterior thalamic radiation, superior longitudinal fasciculus, and middle cerebellar peduncle (p &lt; 0.05, TFCE corrected). Negative correlations were detected between WOMAC scores and AD values for the body of the corpus callosum and the splenium of the corpus callosum (p &lt; 0.05, FDR corrected).ConclusionPatients with KOA exhibited extensive white matter alterations in sensorimotor and pain-related regions. Longitudinal observation studies on the causation between abnormalities in the white matter tracts and KOA is needed in the future.
tDCS-Induced Memory Reconsolidation Effects: Analysis of Prominent Predicting Factors
Authors: Cotelli Maria , Ferrari Clarissa , Gobbi Elena , Binetti Giuliano , Manenti Rosa , Sandrini Marco 
Published: March 2022

BackgroundMemory impairment is among one of the greatest cognitive complaints in midlife and in old age. Considering the importance of good memory functioning in everyday life, it is crucial to study interventions that can reduce the natural decline in this cognitive function. Transcranial Magnetic Stimulation (TMS) studies have demonstrated that the lateral prefrontal cortex (PFC) plays a causal role in enhancing episodic memory recall through reconsolidation. Using a similar paradigm with transcranial direct current stimulation (tDCS) over the left lateral PFC, facilitation effects were observed in delayed memory retrieval in older adults with subjective memory complaints (SMCs) and amnestic Mild Cognitive Impairment (aMCI). However, it remains unclear which potential factors (i.e., tDCS group, cognitive reserve, education level, diagnosis and encoding performance) directly and/or indirectly modulate the tDCS-induced memory reconsolidation effects.MethodsWe reanalyzed data acquired in our previous tDCS studies with 22 SMC and 18 aMCI participants from the perspective of predicting delayed memory retrieval performance. These studies included a learning session on Day 1, a reactivation by a contextual reminder followed by 15 min of tDCS session on Day 2 (24 h after Day 1), and two retrieval sessions (free recall and recognition) tested on Days 3 and 30 (48 h and 30 Days after Day 1).ResultsUnivariate models showed that tDCS group (sham vs. active) significantly predicted memory recognition (but not free recall), evidenced by higher scores in the active tDCS group than in sham group, confirming our previous results. Encoding performance and diagnosis (SMC vs. aMCI) significantly predicted memory retrieval, suggesting higher performances in individuals with SMC than in those with aMCI. Regarding cognitive reserve, higher leisure time activity subscores significantly predicted better memory recognition. Finally, multiple models did not show any tDCS group × predictor interaction effects, indicating that the effects of the predictors on retrieval occurred irrespective of tDCS group.ConclusionOur results shed light on predicting factors of episodic memory retrieval in this reconsolidation paradigm in individuals with SMC and aMCI. The findings suggest that multifactorial interventions program may be most promising to slow cognitive decline and delay the onset of dementia.
Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus
Authors: Parker Dominic R. , Wiklendt Lukasz , Humenick Adam , Chen Bao Nan , Sia Tiong Cheng , Wattchow David A. , Dinning Phil G. , Brookes Simon J. H. 
Published: March 2022

BackgroundThe sympathetic nervous system inhibits human colonic motility largely by effects on enteric neurons. Noradrenergic axons, which branch extensively in the myenteric plexus, are integral to this modulatory role, but whether they contact specific types of enteric neurons is unknown. The purpose of this study was to determine the association of noradrenergic varicosities with types of enteric neurons.MethodsHuman colonic tissue from seven patients was fixed and dissected prior to multi-layer immunohistochemistry for human RNA binding proteins C and D (HuC/D) (pan-neuronal cell body labelling), tyrosine hydroxylase (TH, catecholaminergic labelling), Enkephalin (ENK), choline acetyltransferase (ChAT, cholinergic labelling) and/or nitric oxide synthase (NOS, nitrergic labelling) and imaged using confocal microscopy. TH-immunoreactive varicose nerve endings and myenteric cell bodies were reconstructed as three dimensional digital images. Data was exported to a purpose-built software package which quantified the density of varicosities close to the surface of each myenteric cell body.ResultsTH-immunoreactive varicosities had a greater mean density within 1 μm of the surface of ChAT +/NOS− nerve cell bodies compared with ChAT−/NOS + cell bodies. Similarly, ENK-immunoreactive varicosities also had a greater mean density close to ChAT +/NOS− cell bodies compared with ChAT−/NOS + cells.ConclusionA method for quantifying close associations between varicosities and nerve cell bodies was developed. Sympathetic axons in the myenteric plexus preferentially target cholinergic excitatory cells compared to nitrergic neurons (which are largely inhibitory). This connectivity is likely to be involved in inhibitory modulation of human colonic motility by the sympathetic nervous system.
Computational Identification of Guillain-Barré Syndrome-Related Genes by an mRNA Gene Expression Profile and a Protein–Protein Interaction Network
Authors: Wang Chunyang , Liao Shiwei , Wang Yiyi , Hu Xiaowei , Xu Jing 
Published: March 2022

BackgroundIn the present study, we used a computational method to identify Guillain–Barré syndrome (GBS) related genes based on (i) a gene expression profile, and (ii) the shortest path analysis in a protein–protein interaction (PPI) network.Materials and MethodsmRNA Microarray analyses were performed on the peripheral blood mononuclear cells (PBMCs) of four GBS patients and four age- and gender-matched healthy controls.ResultsTotally 30 GBS-related genes were screened out, in which 20 were retrieved from PPI analysis of upregulated expressed genes and 23 were from downregulated expressed genes (13 overlap genes). Gene ontology (GO) enrichment and KEGG enrichment analysis were performed, respectively. Results showed that there were some overlap GO terms and KEGG pathway terms in both upregulated and downregulated analysis, including positive regulation of macromolecule metabolic process, intracellular signaling cascade, cell surface receptor linked signal transduction, intracellular non-membrane-bounded organelle, non-membrane-bounded organelle, plasma membrane, ErbB signaling pathway, focal adhesion, neurotrophin signaling pathway and Wnt signaling pathway, which indicated these terms may play a critical role during GBS process.DiscussionThese results provided basic information about the genetic and molecular pathogenesis of GBS disease, which may improve the development of effective genetic strategies for GBS treatment in the future.
Association of Dietary Insulin Index and Dietary Insulin Load With Metabolic Health Status in Iranian Overweight and Obese Adolescents
Authors: Hajhashemy Zahra , Mirzaei Saeideh , Asadi Ali , Akhlaghi Masoumeh , Saneei Parvane 
Published: March 2022

BackgroundLimited data are available on the association of dietary insulin load (DIL) and dietary insulin index (DII) with health status in pediatrics. We aimed to investigate the relationship of DIL and DII with metabolic health status in Iranian overweight/obese adolescents.MethodsIn this cross-sectional study, using a multistage cluster random-sampling method, 203 overweight/obese adolescents (aged 12 to &lt;18 years) were included. A validated 147-item food frequency questionnaire (FFQ) was used for a dietary intake assessment. Glycemic and lipid profile, blood pressure (BP), and anthropometric indices were measured. Participants were categorized as metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) using the two methods of the International Diabetes Federation (IDF) and a combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR).ResultsAccording to IDF and IDF/HOMA-IR strategies, 38.9% (n = 79) and 33.0% (n = 67) of participants belonged to MUO category. After adjustments for potential confounders, subjects in the highest tertile of DIL in comparison with those in the lowest tertile had the odds ratio (OR) values of 8.44 (95% CI: 2.24–31.78) and 5.86 (95% CI: 1.39–24.58) for MUO based on IDF and IDF/HOMA-IR definitions, respectively. Moreover, after considering potential confounders, adolescents in the highest tertile of DII, compared to the lowest tertile, were, respectively, 6.93 (OR: 6.93; 95% CI: 2.59–18.57) and 5.26 (OR: 5.26; 95% CI: 1.85–14.97) times more likely to be MUO, based on IDF and IDF/HOMA-IR definitions. A significant decreasing trend was observed for OR of MUO in tertiles of DIL and DII. The stratified analysis revealed that these associations were stronger in obese participants; in overweight subjects, the association was not independent of confounders.ConclusionThis population-based study revealed that higher DIL and DII were strongly related to increased OR of MUO in Iranian adolescents, especially in obese participants. Further investigations, especially with a prospective design, are needed to affirm these findings.