bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures—A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography
Authors: Heilmeier Ursula , Joseph Gabby B. , Pasco Courtney , Dinh Nhan , Torabi Soheyla , Darakananda Karin , Youm Jiwon , Carballido-Gamio Julio , Burghardt Andrew J. , Link Thomas M. , Kazakia Galateia J. 
Published: March 2021

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p &lt; 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p &lt; 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p &lt; 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.
Complications and Comorbidities of Acromegaly—Retrospective Study in Polish Center
Authors: Rolla Małgorzata , Jawiarczyk-Przybyłowska Aleksandra , Halupczok-Żyła Jowita , Kałużny Marcin , Konopka Bogumil M. , Błoniecka Izabela , Zieliński Grzegorz , Bolanowski Marek 
Published: March 2021

IntroductionIn acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them.Materials and MethodsIt was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis.ResultsThe study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20–78) and 46 for men (range 24–76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent.ConclusionsIn our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.
Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies
Authors: Inoue Kosuke , Kitamoto Takumi , Tsurutani Yuya , Saito Jun , Omura Masao , Nishikawa Tetsuo 
Published: March 2021

The hypothalamus-pituitary-adrenal (HPA) axis plays an important role in primary aldosteronism. Aldosterone biosynthesis is regulated not only by angiotensin II in the renin-angiotensin-aldosterone system, but also by adrenocorticotropic hormone (ACTH), one of the key components of the HPA axis. Although previous studies have reported cortisol cosecretion in primary aldosteronism, particularly aldosterone-producing adenoma (APA), the clinical relevance of such aldosterone and cortisol cosecretion from APA and hypertension or other metabolic disorders has not been fully established. Several somatic mutations including KCNJ5 and CACNA1D are known to induce autonomous production of aldosterone in APA, and the aldosterone responsiveness to ACTH may vary according to each mutation. The ACTH stimulation test has been reported to be a useful tool to distinguish the subtypes of primary aldosteronism (e.g., unilateral vs bilateral) in some studies, but it has not been commonly applied in clinical practice due to limited evidence. Given the recent advancement of imaging, omics research, and computational approach, it is important to summarize the most updated evidence to disentangle the potential impact of cortisol excess in primary aldosteronism and whether the ACTH stimulation test needs to be considered during the diagnostic process of primary aldosteronism. In this article, we conducted a systematic review of epidemiological studies about (i) cortisol cosecretion in primary aldosteronism and (ii) the ACTH stimulation test for the diagnosis of primary aldosteronism (including subtype diagnosis). Then, we discussed potential biases (e.g., confounding bias, overadjustment, information bias, selection bias, and sampling bias) in the previous studies and introduced some advanced epidemiological/statistical methods to minimize these limitations. A better understanding of biases and epidemiological perspective on this topic would allow us to produce further robust evidence and balanced discussion about the causal mechanisms involving the HPA axis and clinical usefulness of the ACTH stimulation test among patients with primary aldosteronism.
Effects of Neutrophil-to-Lymphocyte Ratio Combined With Interleukin-6 in Predicting 28-Day Mortality in Patients With Sepsis
Authors: Liu Shuangqing , Wang Xinkun , She Fei , Zhang Wei , Liu Hongsheng , Zhao Xiaodong 
Published: March 2021

BackgroundThe current study aimed to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) combined with interleukin (IL)-6 on admission day and the 28-day mortality of septic patients.Material and MethodsWe conducted an observational retrospective study. Patients with presumed sepsis were included. We observed the correlation of studied biomarkers (NLR, IL-6, PCT, and CRP) and the severity scores (APACHE II and SOFA scores) by plotting scatter plots. The relationships of the studied biomarkers and 28-day mortality were evaluated by using Cox regression model, receiver-operating characteristic (ROC) curve, and reclassification analysis.ResultsA total of 264 patients diagnosed with sepsis were enrolled. It was revealed that IL-6 had the strongest correlation with both APACHE II and SOFA scores, followed by the NLR and PCT, and there was no obvious correlation between CRP and the illness severity. NLR and IL-6 were independent predictors of the 28-day mortality in septic patients in the Cox regression model [NLR, odds ratio 1.281 (95% CI 1.159–1.414), P &lt; 0.001; IL-6, odds ratio 1.017 (95% CI 1.005–1.028), P=0.004]. The area under the ROC curve (AUC) of NLR, IL-6 and NLR plus IL-6 (NLR_IL-6) was 0.776, 0.849, and 0.904, respectively.ConclusionOur study showed that the levels of NLR and IL-6 were significantly higher in the deceased patients with sepsis. NLR and IL-6 appeared to be independent predictors of 28-day mortality in septic patients. Moreover, NLR combined with IL-6 could dramatically enhance the prediction value of 28-day mortality.
Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review
Authors: Wang He-Xiao , Yang Yang , Hu Jing-Yuan , Zhang Li-Ming , Cai Yun-Fei , Guo Hao , Xiao Ting , Chen Hong-Duo , Gao Xing-Hua , Qiao Shuai 
Published: March 2021

BackgroundPemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases.PurposeTo investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients.MethodsAntibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies.Results98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (&lt; 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml.ConclusionPemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.
Fixel-Based Analysis of White Matter Degeneration in Patients With Progressive Supranuclear Palsy or Multiple System Atrophy, as Compared to Parkinson's Disease
Authors: Nguyen Thanh-Thao , Cheng Jur-Shan , Chen Yao-Liang , Lin Yu-Chun , Tsai Chih-Chien , Lu Chin-Song , Weng Yi-Hsin , Wu Yi-Ming , Hoang Ngoc-Thanh , Wang Jiun-Jie 
Published: March 2021

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism.Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination.Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD.Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.
Using Deep Neural Network to Diagnose Thyroid Nodules on Ultrasound in Patients With Hashimoto’s Thyroiditis
Authors: Hou Yiqing , Chen Chao , Zhang Lu , Zhou Wei , Lu Qinyang , Jia Xiaohong , Zhang Jingwen , Guo Cen , Qin Yuxiang , Zhu Lifeng , Zuo Ming , Xiao Jing , Huang Lingyun , Zhan Weiwei 
Published: March 2021

ObjectiveThe aim of this study is to develop a model using Deep Neural Network (DNN) to diagnose thyroid nodules in patients with Hashimoto’s Thyroiditis.MethodsIn this retrospective study, we included 2,932 patients with thyroid nodules who underwent thyroid ultrasonogram in our hospital from January 2017 to August 2019. 80% of them were included as training set and 20% as test set. Nodules suspected for malignancy underwent FNA or surgery for pathological results. Two DNN models were trained to diagnose thyroid nodules, and we chose the one with better performance. The features of nodules as well as parenchyma around nodules will be learned by the model to achieve better performance under diffused parenchyma. 10-fold cross-validation and an independent test set were used to evaluate the performance of the algorithm. The performance of the model was compared with that of the three groups of radiologists with clinical experience of &lt;5 years, 5–10 years, &gt;10 years respectively.ResultsIn total, 9,127 images were collected from 2,932 patients with 7,301 images for the training set and 1,806 for the test set. 56% of the patients enrolled had Hashimoto’s Thyroiditis. The model achieved an AUC of 0.924 for distinguishing malignant and benign nodules in the test set. It showed similar performance under diffused thyroid parenchyma and normal parenchyma with sensitivity of 0.881 versus 0.871 (p = 0.938) and specificity of 0.846 versus 0.822 (p = 0.178). In patients with HT, the model achieved an AUC of 0.924 to differentiate malignant and benign nodules which was significantly higher than that of the three groups of radiologists (AUC = 0.824, 0.857, 0.863 respectively, p &lt; 0.05).ConclusionThe model showed high performance in diagnosing thyroid nodules under both normal and diffused parenchyma. In patients with Hashimoto’s Thyroiditis, the model showed a better performance compared to radiologists with various years of experience.
High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations
Authors: Li Zhiheng , Chu Xinran , Gao Li , Ling Jing , Xiao Peifang , Lu Jun , Wang Yi , He Hailong , Li Jianqin , Hu Yixin , Li Jie , Pan Jian , Xiao Sheng , Hu Shaoyan 
Published: March 2021

BackgroundAberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients.MethodsA total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with &gt;50, 20–50, or &lt;20% of CD123 expressing blasts were grouped into CD123high, CD123low, and CD123neg, respectively. The correlation between CD123 expression and the patients’ clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically.ResultsOf 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123high. In the CCLG-ALL-2008 cohort, CD123high was significantly associated with chromosome hyperdiploidy (p &lt; 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123high displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123low and CD123neg. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts.ConclusionsA group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.
A Randomized Phase II Trial Comparing the Efficacy and Safety of Pioglitazone, Clarithromycin and Metronomic Low-Dose Chemotherapy with Single-Agent Nivolumab Therapy in Patients with Advanced Non-small Cell Lung Cancer Treated in Second or Further Line (ModuLung)
Authors: Heudobler Daniel , Schulz Christian , Fischer Jürgen R. , Staib Peter , Wehler Thomas , Südhoff Thomas , Schichtl Thomas , Wilke Jochen , Hahn Joachim , Lüke Florian , Vogelhuber Martin , Klobuch Sebastian , Pukrop Tobias , Herr Wolfgang , Held Swantje , Beckers Kristine , Bouche Gauthier , Reichle Albrecht 
Published: March 2021

Background: Most non-small cell lung cancers occur in elderly and frequently comorbid patients. Therefore, it is necessary to evaluate the efficacy of biomodulatory active therapy regimen, concertedly interfering with tumor-associated homeostatic pathways to achieve tumor control paralleled by modest toxicity profiles.Patients and Methods: The ModuLung trial is a national, multicentre, prospective, open-label, randomized phase II trial in patients with histologically confirmed stage IIIB/IV squamous (n = 11) and non-squamous non-small cell (n = 26) lung cancer who failed first-line platinum-based chemotherapy. Patients were randomly assigned on a 1:1 ratio to the biomodulatory or control group, treated with nivolumab. Patients randomized to the biomodulatory group received an all-oral therapy consisting of treosulfan 250 mg twice daily, pioglitazone 45 mg once daily, clarithromycin 250 mg twice daily, until disease progression or unacceptable toxicity.Results: The study had to be closed pre-maturely due to approval of immune checkpoint inhibitors (ICi) in first-line treatment. Thirty-seven patients, available for analysis, were treated in second to forth-line. Progression-free survival (PFS) was significantly inferior for biomodulation (N = 20) vs. nivolumab (N = 17) with a median PFS (95% confidence interval) of 1.4 (1.2–2.0) months vs. 1.6 (1.4–6.2), respectively; with a hazard ratio (95% confidence interval) of 1.908 [0.962; 3.788]; p = 0.0483. Objective response rate was 11.8% with nivolumab vs. 5% with biomodulation, median follow-up 8.25 months. The frequency of grade 3–5 treatment related adverse events was 29% with nivolumab and 10% with biomodulation. Overall survival (OS), the secondary endpoint, was comparable in both treatment arms; biomodulation with a median OS (95% confidence interval) of 9.4 (6.0–33.0) months vs. nivolumab 6.9 (4.6–24.0), respectively; hazard ratio (95% confidence interval) of 0.733 [0.334; 1.610]; p = 0.4368. Seventy-five percent of patients in the biomodulation arm received rescue therapy with checkpoint inhibitors.Conclusions: This trial shows that the biomodulatory therapy was inferior to nivolumab on PFS. However, the fact that OS was similar between groups gives rise to the hypothesis that the well-tolerable biomodulatory therapy may prime tumor tissues for efficacious checkpoint inhibitor therapy, even in very advanced treatment lines where poor response to ICi might be expected with increasing line of therapy.
Biochanin A Attenuates Ovariectomy-Induced Cognition Deficit via Antioxidant Effects in Female Rats
Authors: Zhou Yanmeng , Xu Bingbing , Yu Haiyang , Zhao Wei , Song Xinxin , Liu Yan , Wang Kainan , Peacher Nikoli , Zhao Xiaomin , Zhang Han-Ting 
Published: March 2021

Background: Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer’s disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated.Methods: All the rats except for the sham group underwent the resection of bilateral ovaries. Seven days after the OVX surgery, rats were randomly divided into six groups: sham, OVX, OVX + BCA (5 mg/kg), OVX + BCA (20 mg/kg), OVX + BCA (60 mg/kg), and OVX + estradiol (E2; 0.35 mg/kg), which were administrated daily by gavage for 12 weeks. Learning and memory were examined using the Morris water-maze test before the end of the experiment. Morphological changes of the rat hippocampus were observed by HE staining and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the hippocampus were measured. The effect of BCA on cell viability was measured in the presence of hydrogen peroxide (H2O2) using CCK8. Flow cytometry was used to measure neuronal apoptosis and reactive oxygen species (ROS) induced by H2O2. Expression of Bcl-2, Bax, and Caspase-3 was determined by Western blotting using hippocampal tissues and primary cultures of hippocampal neurons.Results: Chronic treatment with BCA mimicked the ability of E2 to reverse the deficit of learning and memory in the Morris water-maze test in OVX rats. BCA normalized OVX-induced morphological changes as revealed by HE staining and electron microscopy. In addition, BCA significantly decreased the levels of MDA, the biomarker of oxidative damage, and increased the activity of the intracellular antioxidant enzymes SOD and GSH-Px in OVX rats. Further, in primary cultures of hippocampal neurons, BCA reversed H2O2-induced decreases in cell viability and accumulation of ROS. Finally, BCA reversed OVX- or H2O2-induced increases in Bax and Caspase-3 and decreases in Bcl-2 in the hippocampus and primary cultures of hippocampal neurons.Conclusion: These results suggest that BCA improves memory through its neuroprotective properties in the brain under the circumstance of estrogen deficiency and can be used for treatment of memory loss in postmenopausal women.