bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatic?—A Digital Diagnostic Decision Support Tool for Individuals Suspecting Rheumatic Diseases: A Multicenter Pilot Validation Study
Authors: Knevel Rachel , Knitza Johannes , Hensvold Aase , Circiumaru Alexandra , Bruce Tor , Evans Sebastian , Maarseveen Tjardo , Maurits Marc , Beaart-van de Voorde Liesbeth , Simon David , Kleyer Arnd , Johannesson Martina , Schett Georg , Huizinga Tom , Svanteson Sofia , Lindfors Alexandra , Klareskog Lars , Catrina Anca 
Published: April 2022

IntroductionDigital diagnostic decision support tools promise to accelerate diagnosis and increase health care efficiency in rheumatology. Rheumatic? is an online tool developed by specialists in rheumatology and general medicine together with patients and patient organizations. It calculates a risk score for several rheumatic diseases. We ran a pilot study retrospectively testing Rheumatic? for its ability to differentiate symptoms from existing or emerging immune-mediated rheumatic diseases from other rheumatic and musculoskeletal complaints and disorders in patients visiting rheumatology clinics.Materials and MethodsThe performance of Rheumatic? was tested using in three university rheumatology centers: (A) patients at Risk for RA (Karolinska Institutet, n = 50 individuals with musculoskeletal complaints and anti-citrullinated protein antibody positivity) (B) patients with early joint swelling [dataset B (Erlangen) n = 52]. (C) Patients with early arthritis where the clinician considered it likely to be of auto-immune origin [dataset C (Leiden) n = 73]. In dataset A we tested whether Rheumatic? could predict the development of arthritis. In dataset B and C we tested whether Rheumatic? could predict the development of an immune-mediated rheumatic diseases. We examined the discriminative power of the total score with the Wilcoxon rank test and the area-under-the-receiver-operating-characteristic curve (AUC-ROC). Next, we calculated the test characteristics for these patients passing the first or second expert-based Rheumatic? scoring threshold.ResultsThe total test scores differentiated between: (A) Individuals developing arthritis or not, median 245 vs. 163, P &lt; 0.0001, AUC-ROC = 75.3; (B) patients with an immune-mediated arthritic disease or not median 191 vs. 107, P &lt; 0.0001, AUC-ROC = 79.0; but less patients with an immune-mediated arthritic disease or not amongst those where the clinician already considered an immune mediated disease most likely (median 262 vs. 212, P &lt; 0.0001, AUC-ROC = 53.6). Threshold-1 (advising to visit primary care doctor) was highly specific in dataset A and B (0.72, 0.87, and 0.23, respectively) and sensitive (0.67, 0.61, and 0.67). Threshold-2 (advising to visit rheumatologic care) was very specific in all three centers but not very sensitive: specificity of 1.0, 0.96, and 0.91, sensitivity 0.05, 0.07, 0.14 in dataset A, B, and C, respectively.ConclusionRheumatic? is a web-based patient-centered multilingual diagnostic tool capable of differentiating immune-mediated rheumatic conditions from other musculoskeletal problems. The current scoring system needs to be further optimized.
Prevalence and Risk Factors of Gallbladder Stones and Polyps in Liaoning, China
Authors: Zhang Xinhe , Guan Lin , Tian Haoyu , Li Yiling 
Published: April 2022

ObjectiveTo investigate the incidence and risk factors of gallbladder stones and polyps in individuals undergoing physical examinations in Liaoning province, China.MethodsThis is a retrospective study of adults who underwent routine health examinations at Xikang Medical Center in Liaoning Province (Shenyang, Dandong, and Dalian) from 01/2016 to 12/2020. The routine health examination included anthropometry, blood tests, and liver ultrasound. Based on liver ultrasound results, patients were grouped into those with gallbladder stones, those with gallbladder polyps, those with both stones and polyps, and those with neither.ResultsOf the 284,129 included subjects, 6,537 (2.30%) were diagnosed with gallbladder stones, and 18,873 (6.64%) were diagnosed with gallbladder polyps. The overall prevalence in Liaoning province increased each year, peaking in 2020. The prevalence of gallbladder stones was higher among females than males (2.39% vs. 2.23%, respectively), while the prevalence of gallbladder polyps was higher among males. The gallbladder polyp group had higher BMI, FBG, SBP, DBP, TG, TC, LDL-C, HDL-C, AST, ALP, GGT, BUN, Scr, SUA. Except for HDL-C, all factors were also higher in the gallbladder stone group. Patients with fatty liver had a higher prevalence of gallbladder stones and polyps than participants without fatty liver.ConclusionThe prevalence of gallbladder stones and polyps in Liaoning varies by sex, economic status of the city of residence, BMI, and metabolic indicators.
Effectiveness of Endobronchial Ultrasound-Guided Transbronchial Biopsy Combined With Tissue Culture for the Diagnosis of Sputum Smear-Negative Pulmonary Tuberculosis
Authors: Lin Ching-Kai , Fan Hung-Jen , Yu Kai-Lun , Chang Lih-Yu , Wen Yueh-Feng , Keng Li-Ta , Ho Chao-Chi 
Published: April 2022

BackgroundMicroorganisms of tuberculosis (TB) are frequently difficult to identify from the airway specimen; therefore, lung biopsy for further histologic and microbiologic study is required. Endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) is used for the diagnosis of pulmonary malignancy, but is rarely in the TB population. The purpose of this study was to verify the effectiveness and safety of EBUS-TBB with histologic study and tissue culture in the diagnosis of sputum smear-negative pulmonary TB.MethodsPatients who underwent EBUS-TBB with histologic study and TB tissue culture for clinically suspected, but sputum smear-negative pulmonary TB from January 2016 to December 2018, were included. The accuracy of each diagnostic modality was calculated, respectively. Factors that might influence the positive rate of TB culture (washing fluid and tissue specimen) were also evaluated.ResultsOne hundred sixty-one patients who underwent EBUS-TBB for clinically suspected, but sputum smear-negative pulmonary TB, were enrolled, and 43 of them were finally diagnosed as having pulmonary TB. The sensitivity of washing fluid (a combination of smear, culture, and polymerase chain reaction for TB) and tissue specimen (a combination of pathology and tissue culture) via EBUS-TBB for TB diagnosis were 48.8 and 55.8%, respectively. The sensitivity for TB diagnosis would be elevated to 67.4% when both washing fluid and tissue specimens are used. The positive TB culture rate would not statistically increase with a combination of tissue specimens and washing fluid. Univariate analysis revealed that TB microorganisms would be more easily cultivated when lesions had an abscess or cavity on the computed tomography (CT) image (presence vs. absence; 62.5 vs. 26.3%, p = 0.022), heterogeneous echogenicity on the EBUS finding (heterogeneous vs. homogeneous; 93.3 vs. 21.4%, p = 0.001), or a necrotic pattern via histologic study (presence vs. absence; 70.6 vs. 30.8%, p = 0.013). Heterogeneous echogenicity in the EBUS finding was the independent predictor according to the results of multivariate analysis. None of our patients encountered major adverse events or received further intensive care after EBUS-TBB.ConclusionEndobronchial ultrasound-guided transbronchial biopsy is safe and effective for use in diagnosing sputum smear-negative pulmonary TB. EBUS echoic feature is also a predictor of the positive TB culture rate in pulmonary TB. However, tissue culture via EBUS-TBB has little effect in improving the positive TB culture rate.
The Effects of Helicobacter pylori Infection on Gastric Microbiota in Children With Duodenal Ulcer
Authors: Zheng Wei , Zhu Zhenya , Ying Jingjing , Long Gao , Chen Bo , Peng Kerong , Li Fubang , Zhao Hong , Jiang Mizu 
Published: April 2022

BackgroundHelicobacter pylori (H. pylori) infection is the main cause of chronic gastritis and duodenal ulcer in children. Little is known about the effect of H. pylori on gastric microbiota in children with duodenal ulcer. This study is aimed at the characteristics of gastric microbiota in children with duodenal ulcer on H. pylori infection.MethodsWe studied 23 children diagnosed with duodenal ulcer by gastric endoscopy because of the gastrointestinal symptoms, 15 children were diagnosed with H. pylori infection, while 8 children were without H. pylori infection. Endoscopic mucosal biopsy samples were obtained for DNA extraction. Microbiomes were analyzed by 16S rRNA profiling and microbial functions were predicted using the software Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).ResultsBacterial richness and diversity of gastric microbiota in duodenal ulcer with H. pylori-positive were lower than those negative. The gastric microbiota in H. pylori-positive group significantly reduced proportions of six phyla and fifteen genera; only Helicobacter taxa were more abundant in H. pylori-positive group. Co-expression network analysis showed a more complex network of interactions in the H. pylori-positive group than that in the H. pylori-negative group. For the predicted functions, lower abundance in the pathways of carbohydrate metabolism, signal transduction, amino acid metabolism, and lipid metabolism were found in H. pylori-positive group than the H. pylori-negative group. H. pylori colonization reduces a microbial community with genotoxic potential in the gastric mucosa of children with duodenal ulcer.ConclusionsThe presence of H. pylori significantly influences gastric microbiota and results in a lower abundance of multiple taxonomic levels in children with duodenal ulcer. Children with duodenal ulcer exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of children with H. pylori infection.Clinical Trial Registration[http://www.chictr.org.cn], identifier [ChiCTR1800015190].
Anxiety-Induced Sleep Disturbance and Associated Lifestyle Behaviors According to Sex in Argentine Adolescents
Authors: López-Gil José Francisco , Cavero-Redondo Iván , Tárraga López Pedro J. , Jiménez-López Estela , González Alberto Durán , Sequí-Domínguez Irene , Mesas Arthur Eumann 
Published: April 2022

PurposeThe aim of the current study was twofold: first, to determine the prevalence of anxiety-induced sleep disturbances among Argentine adolescents according to sex, and second, to identify the association between these sleep disturbances and lifestyle behaviors in this population.MethodsThis is a cross-sectional study with data from the Global School-based Student Health Survey (GSHS) in Argentina (2018). A total of 32,393 adolescents (aged 12–17 years; 53.4% girls) were included in the final analysis. Anxiety-induced sleep disturbances were assessed with the question “During the past 12 months, how often have you been so worried about something that you could not sleep at night?”ResultsThe prevalence of anxiety-induced sleep disturbances was higher in girls (17.4%) than in boys (7.9%) (p &lt; 0.001). In boys, results indicated that those who used marijuana (cannabis) (odds ratio [OR] = 1.46, 95% confidence interval [CI] 1.08–1.98), used amphetamine or methamphetamine (OR = 2.19, 95% CI 1.28–3.77), walked or biked to or from school (OR = 1.53, 95% CI 1.19–1.96), and spent 3 h or more in sedentary behaviors (OR = 1.35, 95% CI 1.05–1.74) were more likely to report anxiety-induced sleep disturbances. In girls, those who ate from a fast-food restaurant (OR = 1.24, 95% CI 1.05–1.47), consumed alcoholic beverages (OR = 1.45, 95% CI 1.19–1.75), smoked cigarettes (OR = 2.09, 95%CI 1.05–4.14), consumed any tobacco product (OR = 1.47, 95% CI 1.19–1.82), used amphetamine or methamphetamine (OR = 2.08, 95% CI 1.33–3.26), and those who spent 3 h or more in sedentary behaviors (OR = 1.32, 95% CI 1.11–1.57) were more likely to report frequent anxiety-induced sleep disturbances.ConclusionIn conclusion, considerable sex differences were observed with respect to the prevalence of anxiety-related sleep disturbances and associated lifestyle aspects.
Hyperdense Artery Sign and Clinical Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion
Authors: Hu Jinrong , He Wencheng , Zheng Bo , Huang Fang , Lv Kefeng , Liao Jiasheng , Chen Zhao , Jiang He , Wang Kuiyun , Wang Hongjun , Lei Yang , Liao Jiachuan , Sang Hongfei , Liu Shuai , Luo Weidong , Sun Ruidi , Yang Jie , Huang Jiacheng , Song Jiaxing , Li Fengli , Zi Wenjie , Long Chen , Yang Qingwu 
Published: April 2022

BackgroundThis study aimed to investigate the association between the hyperdense basilar artery sign (HBAS) on non-enhanced computed tomography (CT) and clinical outcomes in patients with acute basilar artery occlusion (BAO) who underwent endovascular treatment (EVT).MethodsEligible patients who underwent EVT due to acute BAO between January 2014 and May 2019 were divided into two groups based on HBAS. HBAS was assessed by two neuroradiologists using five grades on nonenhanced CT. The primary outcome was a favorable functional outcome (defined as a modified Rankin Scale [mRS] of 0–3) at 90 days. Secondary outcomes included successful recanalization and mortality within 90 days.ResultsAmong 829 patients with BAO as assessed with CT angiography, magnetic resonance angiography, or digital subtraction angiography, 643 patients were treated with EVT. Of these, 51.32% (330/643) had HBAS. Patients with HBAS were older and had more severe neurological deficits and a higher frequency of atrial fibrillation than those without HBAS. There was no significant difference in favorable outcome (adjusted odds ratio [aOR]: 1.354, 95% confidence interval [CI]: 0.906–2.024; p = 0.14), successful recanalization (aOR: 0.926, 95% CI: 0.616-−1.393; p = 0.71), and mortality (aOR: 1.193, 95% CI: 0.839–1.695; p = 0.33) between patients with or without HBAS. Subgroup analysis showed that the HBAS predicted a favorable outcome in patients aged &lt;60 years (aOR: 2.574, 95% CI: 1.234–5.368; p = 0.01) and patients with vertebral artery-V4 segment occlusion (aOR: 3.738, 95% CI: 1.212–11.530; p = 0.02). In patients with HBAS, the baseline National Institutes of Health Stroke Scale (NIHSS) score, posterior circulation–Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS), and stent retriever were associated with successful recanalization.ConclusionsOur study did not find a significant association between HBAS and favorable outcomes and successful recanalization in patients with BAO who underwent EVT. Moreover, large prospective studies are warranted to further investigate this relationship.
Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC–MSC–NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial
Authors: Yao Xiao-Ying , Xie Li , Cai Yu , Zhang Ying , Deng Ye , Gao Mei-Chun , Wang Yi-Shu , Xu Hui-Ming , Ding Jie , Wu Yi-Fan , Zhao Nan , Wang Ze , Song Ya-Ying , Wang Li-Ping , Xie Chong , Li Ze-Zhi , Wan Wen-Bin , Lin Yan , Jin Hai-Feng , Wang Kan , Qiu Hui-Ying , Zhuang Lei , Zhou Yan , Jin Yu-Yan , Ni Li-Ping , Yan Jia-Li , Guo Quan , Xue Jia-Hui , Qian Bi-Yun , Guan Yang-Tai 
Published: April 2022

BackgroundNeuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD.MethodsThe trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years.DiscussionAlthough hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients.Trial registrationThe study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.
Subclinical Atherosclerosis Could Increase the Risk of Hearing Impairment in Males: A Community-Based Cross-Sectional Survey of the Kailuan Study
Authors: Ruan Chunyu , Mao Xiang , Chen Shuohua , Wu Shouling , Wang Wei 
Published: April 2022

ObjectiveThe relationship between subclinical atherosclerosis and hearing impairment (HI) has not been widely considered. Brachial ankle pulse wave velocity (baPWV) is a good indicator of muscular artery elasticity and could be a feasible method to screen for subclinical atherosclerosis. Our study aimed to elucidate the relationship between baPWV and HI.MethodsThis cross-sectional study was based on the Kailuan cohort. All participants completed a standardized questionnaire and underwent physical examinations and laboratory assessments at recruitment. Since 2010, some participants received additional baPWV testing during follow-up visits, and some who were exposed to occupational hazards such as noise received a pure-tone average hearing threshold (PTA) test after 2014. Male subjects with a complete physical examination, baPWV, and PTA data were recruited for this study. HI was defined as PTA &gt; 25 dB. Multivariate linear and multivariate logistic regression analyses were used to evaluate the relationship between baPWV and PTA or HI.ResultsAmong 11,141 subjects, the age range was 18–65 years, with mean age of 43.3 ± 8.9 years, the average PTA was 20.54 ± 10.40 dB, and the detection rate of HI was 1,821/11,141 (16.3%). Subjects were divided into four subgroups according to baPWV quartile. As the baPWV quartile increased, age, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, high-density-lipoprotein cholesterol, fasting blood glucose, PTA, and proportions of subjects reporting smoking, alcohol consumption, hypertension, and diabetes increased significantly (p &lt; 0.05 for trend). The odds of HI were higher in the fourth quartile group [adjusted odds ratio (aOR): 1.33, 95% CI: 1.10–1.62] than in the first quartile group. For every 100 m/s increase in baPWV, the PTA increased by 13 dB (95% CI: 4–23). When we divided the subjects into young (5,478 subjects; age range 22–44 years; mean age 35.6 ± 5.5 years) or non-young subgroups (5,663 subjects; age range 45–65 years; mean age 50.7 ± 3.7 years) based on a cut-off age of 45 years, the aOR of the fourth quartile group increased to 2.65 (95% CI: 1.68–4.19), and the PTA increment increased to 18 dB (95% CI: 10–27) for every 100 m/s increase in baPWV in the young subgroup. However, this relationship became statistically insignificant in the non-young subgroup.ConclusionOur study revealed the quantitative relationship between baPWV and HI in the Kailuan cohort subjects, although the results are not universally consistent in different populations.
Activity of Estrogen Receptor β Agonists in Therapy-Resistant Estrogen Receptor-Positive Breast Cancer
Authors: Datta Jharna , Willingham Natalie , Manouchehri Jasmine M. , Schnell Patrick , Sheth Mirisha , David Joel J. , Kassem Mahmoud , Wilson Tyler A. , Radomska Hanna S. , Coss Christopher C. , Bennett Chad E. , Ganju Ramesh K. , Sardesai Sagar D. , Lustberg Maryam , Ramaswamy Bhuvaneswari , Stover Daniel G. , Cherian Mathew A. 
Published: April 2022

BackgroundAmong women, breast cancer is the leading cause of cancer-related death worldwide. Estrogen receptor α-positive (ERα+) breast cancer accounts for 70% of all breast cancer subtypes. Although ERα+ breast cancer initially responds to estrogen deprivation or blockade, the emergence of resistance compels the use of more aggressive therapies. While ERα is a driver in ERα+ breast cancer, ERβ plays an inhibitory role in several different cancer types. To date, the lack of highly selective ERβ agonists without ERα activity has limited the exploration of ERβ activation as a strategy for ERα+ breast cancer.MethodsWe measured the expression levels of ESR1 and ESR2 genes in immortalized mammary epithelial cells and different breast cancer cell lines. The viability of ERα+ breast cancer cell lines upon treatments with specific ERβ agonists, including OSU-ERb-12 and LY500307, was assessed. The specificity of the ERβ agonists, OSU-ERb-12 and LY500307, was confirmed by reporter assays. The effects of ERβ agonists on cell proliferation, cell cycle, apoptosis, colony formation, cell migration, and expression of tumor suppressor proteins were analyzed. The expression of ESR2 and genes containing ERE-AP1 composite response elements was examined in ERα+ human breast cancer samples to determine the correlation between ESR2 expression and overall survival and that of putative ESR2-regulated genes.ResultsIn this study, we demonstrate the efficacy of highly selective ERβ agonists in ERα+ breast cancer cell lines and drug-resistant derivatives. ERβ agonists blocked cell proliferation, migration, and colony formation and induced apoptosis and S and/or G2/M cell-cycle arrest of ERα+ breast cancer cell lines. Also, increases in the expression of the key tumor suppressors FOXO1 and FOXO3a were noted. Importantly, the strong synergy between ERβ agonists and ERα antagonists suggested that the efficacy of ERβ agonists is maximized by combination with ERα blockade. Lastly, ESR2 (ERβ gene) expression was negatively correlated with ESR1 (ERα gene) and CCND1 RNA expression in human metastatic ERα+/HER2- breast cancer samples.ConclusionOur results demonstrate that highly selective ERβ agonists attenuate the viability of ERα+ breast cancer cell lines in vitro and suggest that this therapeutic strategy merits further evaluation for ERα+ breast cancer.