bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study
Authors: Papadimitriou Dimitrios T. , Dermitzaki Eleni , Christopoulos Panagiotis , Livadas Sarantis , Grivea Ioanna N. , Mastorakos George 
Published: April 2024

BackgroundThe first phase of the GAIL study (“Girls treated with an Aromatase Inhibitor and Leuprorelin,” ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm).Objectives and hypothesesIn the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH.MethodsWe measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH.ResultsAH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH–PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1.ConclusionsIn early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.
Identification of diagnostic biomarkers and immune cell infiltration in coronary artery disease by machine learning, nomogram, and molecular docking
Authors: Jiang Xinyi , Luo Yuanxi , Li Zeshi , Zhang He , Xu Zhenjun , Wang Dongjin 
Published: April 2024

BackgroundCoronary artery disease (CAD) is still a lethal disease worldwide. This study aims to identify clinically relevant diagnostic biomarker in CAD and explore the potential medications on CAD.MethodsGSE42148, GSE180081, and GSE12288 were downloaded as the training and validation cohorts to identify the candidate genes by constructing the weighted gene co-expression network analysis. Functional enrichment analysis was utilized to determine the functional roles of these genes. Machine learning algorithms determined the candidate biomarkers. Hub genes were then selected and validated by nomogram and the receiver operating curve. Using CIBERSORTx, the hub genes were further discovered in relation to immune cell infiltrability, and molecules associated with immune active families were analyzed by correlation analysis. Drug screening and molecular docking were used to determine medications that target the four genes.ResultsThere were 191 and 230 key genes respectively identified by the weighted gene co-expression network analysis in two modules. A total of 421 key genes found enriched pathways by functional enrichment analysis. Candidate immune-related genes were then screened and identified by the random forest model and the eXtreme Gradient Boosting algorithm. Finally, four hub genes, namely, CSF3R, EED, HSPA1B, and IL17RA, were obtained and used to establish the nomogram model. The receiver operating curve, the area under curve, and the calibration curve were all used to validate the accuracy and usefulness of the diagnostic model. Immune cell infiltrating was examined, and CAD patients were then divided into high- and low-expression groups for further gene set enrichment analysis. Through targeting the hub genes, we also found potential drugs for anti-CAD treatment by using the molecular docking method.ConclusionsCSF3R, EED, HSPA1B, and IL17RA are potential diagnostic biomarkers for CAD. CAD pathogenesis is greatly influenced by patterns of immune cell infiltration. Promising drugs offers new prospects for the development of CAD therapy.
Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization
Authors: Chen Shixuan , Chen Zhenzhen , Xu Qingqing , Jiang Xia , Lin Chuyong , Ji Jing 
Published: April 2024

BackgroundTo investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways.MethodsWe used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways.ResultsGenetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04–1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01–1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72–0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23–1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively.ConclusionThis study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.
The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms
Authors: Chiu Shih-Chi , Fang Ting-Chun , Lei Hsin-Bei , Lin Yu-Hsuan , Chang Ming-Hong , Guo Yi-Jen 
Published: April 2024

BackgroundLimited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms.MethodsPD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson’s Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains.ResultsA total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p &lt; 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis.ConclusionOur results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.
Mechanoreceptor sensory feedback is impaired by pressure induced cutaneous ischemia on the human foot sole and can predict cutaneous microvascular reactivity
Authors: Howe Erika E. , Apollinaro Michael , Bent Leah R. 
Published: April 2024

IntroductionThe foot sole endures high magnitudes of pressure for sustained periods which results in transient but habitual cutaneous ischemia. Upon unloading, microvascular reactivity in cutaneous capillaries generates an influx of blood flow (PORH: post-occlusive reactive hyperemia). Whether pressure induced cutaneous ischemia from loading the foot sole impacts mechanoreceptor sensitivity remains unknown.MethodsPressure induced ischemia was attained using a custom-built-loading device that applied load to the whole right foot sole at 2 magnitudes (15 or 50% body weight), for 2 durations (2 or 10 minutes) in thirteen seated participants. Mechanoreceptor sensitivity was assessed using Semmes-Weinstein monofilaments over the third metatarsal (3MT), medial arch (MA), and heel. Perceptual thresholds (PT) were determined for each site prior to loading and then applied repeatedly to a metronome to establish the time course to return to PT upon unload, defined as PT recovery time. Microvascular flux was recorded from an in-line laser speckle contrast imager (FLPI-2, Moor Instruments Inc.) to establish PORH peak and recovery rates at each site.ResultsPT recovery and PORH recovery rate were most influenced at the heel and by load duration rather than load magnitude. PT recovery time at the heel was significantly longer with 10 minutes of loading, regardless of magnitude. Heel PORH recovery rate was significantly slower with 10minutes of loading. The 3MT PT recovery time was only longer after 10 minutes of loading at 50% body weight. Microvascular reactivity or sensitivity was not influenced with loading at the MA. A simple linear regression found that PORH recovery rate could predict PT recovery time at the heel (R2=0.184, p&lt;0.001).ConclusionIn populations with degraded sensory feedback, such as diabetic neuropathy, the risk for ulcer development is heightened. Our work demonstrated that prolonged loading in healthy individuals can impair skin sensitivity, which highlights the risks of prolonged loading and is likely exacerbated in diabetes. Understanding the direct association between sensory function and microvascular reactivity in age and diabetes related nerve damage, could help detect early progressions of neuropathy and mitigate ulcer development.
Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice
Authors: Hao Liyu , Yu Zeyue , Sun Jianhui , Li Zongyuan , Li Jianliang , Deng Yurong , Huang Hanhui , Huo Hairu , Li Hongmei , Huang Luqi 
Published: April 2024

IntroductionFunctional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder.MethodsIn this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora.ResultsThe results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces.DiscussionThe mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.
Adolescents’ use of online food delivery applications and perceptions of healthy food options and food safety: a cross-sectional study in the United Arab Emirates
Authors: Saleh Sheima T. , Osaili Tareq M. , Al-Jawaldeh Ayoub , Hasan Haydar A. , Hashim Mona , Mohamad Maysm N. , Qiyas Salma Abu , Al Sabbah Haleama , Al Daour Rameez , Al Rajaby Radhiya , Masuadi Emad , Stojanovska Lily , Papandreou Dimitrios , Zampelas Antonis , Al Dhaheri Ayesha S. , Kassem Hanin , Cheikh Ismail Leila 
Published: April 2024

IntroductionThis cross-sectional study aimed to assess Online food delivery applications (OFDA) usage trends among adolescent users in the United Arab Emirates (UAE), focusing on their perceptions of healthy food options and food safety (n = 532).MethodsSociodemographic information, frequency of OFDA use, factors affecting food choices, and perceptions of healthy food and food safety were investigated. A total perception score was calculated for each participant;ResultsMost participants used OFDAs weekly (65.4%), favoring fast food (85.7%). Factors like appearance and price drove food choices (65.0%), while taste and cost hindered healthy food orders (29.7 and 28.2%). Younger and frequent users had lower scores for perceiving healthy food, while seeking healthy options was associated with higher scores (p &lt; 0.05). Females and those seeking healthy food showed higher food safety scores (p &lt; 0.05).DiscussionThe study suggests tailored interventions to promote healthier choices and improve food safety perceptions among adolescents using OFDAs in the UAE.
Case Report: Novel compound heterozygous TPRKB variants cause Galloway-Mowat syndrome
Authors: Hiraide Takuya , Hayashi Taiju , Ito Yusuke , Urushibata Rei , Uchida Hiroshi , Kitagata Ryoichi , Ishigaki Hidetoshi , Ogata Tsutomu , Saitsu Hirotomo , Fukuda Tokiko 
Published: April 2024

BackgroundGalloway-Mowat syndrome (GAMOS) is a rare genetic disease characterized by early-onset nephrotic syndrome and microcephaly with central nervous system abnormalities. Pathogenic variants in genes encoding kinase, endopeptidase, and other proteins of small size (KEOPS) complex subunits cause GAMOS. The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants.Clinical reportHerein, we described a three-year-old male with GAMOS. He exhibited developmental delay, developmental regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. Brain magnetic resonance imaging revealed progressive brain atrophy, delayed myelination, T2-hypointense signals in the thalamus, and multiple intracranial abnormal signals on diffusion-weighted imaging. He presented with relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. Exome sequencing identified compound heterozygous missense and frameshift variants in TPRKB: c.224dup, p.(Ser76IlefsTer3) and c.247C&gt;T, p.(Leu83Phe).ConclusionsOur study supports that pathogenic TPRKB variants cause KEOPS complex-related GAMOS.
The construction of a nomogram to predict the prognosis and recurrence risks of UPJO
Authors: Ma Wenyue , Gao Hongjie , Chang Mengmeng , Lu Zhiyi , Li Ding , Ding Chen , Bi Dan , Sun Fengyin 
Published: April 2024

ObjectiveThis study was conducted to explore the risk factors for the prognosis and recurrence of ureteropelvic junction obstruction (UPJO).MethodsThe correlation of these variables with the prognosis and recurrence risks was analyzed by binary and multivariate logistic regression. Besides, a nomogram was constructed based on the multivariate logistic regression calculation. After the model was verified by the C-statistic, the ROC curve was plotted to evaluate the sensitivity of the model. Finally, the decision curve analysis (DCA) was conducted to estimate the clinical benefits and losses of intervention measures under a series of risk thresholds.ResultsPreoperative automated peritoneal dialysis (APD), preoperative urinary tract infection (UTI), preoperative renal parenchymal thickness (RPT), Mayo adhesive probability (MAP) score, and surgeon proficiency were the high-risk factors for the prognosis and recurrence of UPJO. In addition, a nomogram was constructed based on the above 5 variables. The area under the curve (AUC) was 0.8831 after self cross-validation, which validated that the specificity of the model was favorable.ConclusionThe column chart constructed by five factors has good predictive ability for the prognosis and recurrence of UPJO, which may provide more reasonable guidance for the clinical diagnosis and treatment of this disease.
Real-world evidence of the effects of sodium-glucose co-transporter 2 inhibitors on the dosing of diuretics in patients with heart failure: a retrospective cohort study
Authors: Alsalem Abdulaziz , Alsultan Mohammed M. , Alqarni Faisal , Almangour Abdullah , Alsharekh Lolwa , Alenazi Saleem , Alzahrani Saleh , Almanqour Raghad A. , Alazmi Abdullah , Alzahrani Abdullah 
Published: April 2024

Background: Heart failure (HF) was estimated to impact approximately 64 million individuals worldwide in 2017 and is predicted to rise in the coming years. Therefore, the aim of our study was to evaluate the effects of sodium-glucose transport protein 2 (SGLT2) inhibitors on the dosing of diuretics among individuals diagnosed with HF.Methods: A retrospective cohort study was conducted at Security Forces Hospital in Riyadh, Saudi Arabia, between January 2018 and August 2022. The study included adult patients who were diagnosed with heart failure and received dapagliflozin and/or diuretic. A descriptive analysis was conducted to identify significant differences between both groups by using the chi-square test for categorical variables and the Student’s t-test for continuous variables. A logistic regression model was also run to identify the odds of each event. Statistical significance was indicated by p values less than .05.Results: Overall reduction in diuretics was reported in 68 patients in the SGLT2 inhibitors plus diuretic therapy group, while in the diuretic therapy group 25 patients reported overall reduction in diuretics (OR = 4.81, 95% [2.74–8.45]). The reduction of the loop dose level was reported by 58 patients in the SGLT2 inhibitors plus diuretic group and by 25 patients in the diuretic group (OR = 3.48, 95% [1.98–6.11]). The discontinuation of thiazide was reported by 16 patients in the SGLT2 inhibitors plus diuretic therapy group, but by only two patients in the diuretic group (OR = 9.04, 95% [2.03–40.19]). After 6 months, ejection fraction was increased by 2.74 in the SGLT2 inhibitors plus diuretic group (p = .0019) and decreased by 2.56 in the diuretic group (p = .0485), both of which were statistically significant. The mean dose changes were decreased by 14.52 in the SGLT2 inhibitors plus diuretic group (p &lt; .0001), which was statistically significant.Conclusion: Treatment with SGLT2 inhibitors plus diuretic significantly reduced the patients’ diuretic requirements. Therefore, our finding supports the theoretical concept of minimizing the level of diuretic upon the initiation of SGLT2 inhibitors.
Construction of Yemilab
Authors: Park K. S. , Kim Y. D. , Bang K. M. , Park H. K. , Lee M. H. , So J. , Kim S. H. , Jang J. H. , Kim J. H. , Kim S. B. 
Published: April 2024

The Center for Underground Physics of the Institute for Basic Science (IBS) in Korea has been planning the construction of a deep underground laboratory since 2013 to search for extremely rare interactions such as dark matter and neutrinos. In September 2022, a new underground laboratory, Yemilab, was finally completed in Jeongseon, Gangwon Province, with a depth of 1,000 m and an exclusive experimental area spanning 3,000 m3. The tunnel is encased in limestone and accommodates 17 independent experimental spaces. Over 2 years, from 2023 to 2024, the Yangyang Underground Laboratory facilities will be relocated to Yemilab. Preparations are underway for the AMoRE-II, a neutrinoless double beta decay experiment, scheduled to begin in Q2 2024 at Yemilab. Additionally, Yemilab includes a cylindrical pit with a volume of approximately 6,300 m3, designed as a multipurpose laboratory for next-generation experiments involving neutrinos, dark matter, and related research. This article provides a focused overview of the construction and structure of Yemilab.