bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and prognosis of Primary biliary cholangitis with esophagogastric varices.
Authors: Zhang Mingyue , Xie Huan , Gerussi Alessio , Han Lin , Chen Ying , Zhao Jun , Liang Qingsheng , Li Baosen , Invernizzi Pietro , Zou Zhengsheng , Gershwin ME , Sun Ying
Published: March 2022

Background and aims The development of esophagogastric varices (EGV) is one of the most common complications in patients with Primary biliary cholangitis (PBC); yet, factors associated with their development have been poorly characterized. In this cohort, we aimed to investigate the clinical factors associated with EGV in patients with PBC. Methods: The cohort study included patients with PBC who received esophagogastroduodenoscopy screening and ursodeoxycholic acid (UDCA) therapy at baseline. Liver-related death and liver transplantation were assessed as the endpoint, liver transplantation-free survival rates were estimated by using Kaplan–Meier methods, and Cox regression analysis was performed to identify the potential risk factors of endpoint events for PBC with EGV. Results The 690 patients included in this study had a mean age of 57 years old and 553 (80.1%) were females, 13 (7.9%) in the 165 PBC with no liver cirrhosis and 400 (76.2%) in the 525 PBC with liver cirrhosis had signs of EGV, and 215 (31.2%) patients of the cohort had bleeding esophagogastric varices as the first presentation at diagnosis. The median (Interquartile range) follow-up period was 4.0 (2.0, 6.0) years. During the follow-up duration, 99 patients progressed to liver-related deaths, and 23 patients underwent liver transplantation. The 5-year cumulative LT-free survival was 88.20% (95% CI 83.7-92.7) in PBC without EGV, and 80.90% (95% CI 80.0-89.9), 80.30% (95% CI 69.7-90.9), 75.70% (95% CI 68.3-83.1) among PBC with small, medium and large-sized esophageal varices at baseline, respectively (p =0.002). The 10-year cumulative LT-free survival was 68.8% (95% CI 53.9-82.8) in PBC without EGV, and 54.2% (95% CI 36.4-72.0), 51.6% (95% CI 29.9-73.3), 62.1% (95% CI 49.2-75.0) among PBC patients with small, medium and large-sized esophageal varices at baseline, respectively (p=0.001). History of endoscopic therapy and UDCA biochemical responder with Paris criteria for PBC with EGV were associated with a statistically significant reduced risk of LT or death (p =0.001 and p=0.007).Conclusions Endoscopic therapy and a favorable biochemical profile of UDCA can prolong the LT-free survival of PBC patients with EGV, despite the presence of large-sized esophageal varices.
Periodontal Disease Risk in Marfan Syndrome Patients Harboring a Possible Aortic Aneurysm or Dissection
Authors: Umezawa Kouta , Kajiwara Takako , Ishii Kyoko , Hasegawa Tatsuya , Suzuki Shigeto , Nakano Masato , Sawaguchi Mayu , Venkataiah Venkata Suresh , Yahata Yoshio , Ito Koki , Saiki Yoshikatsu , Saito Masahiro
Published: March 2022

BackgroundMarfan syndrome (MFS) is a systemic disorder of connective tissues caused by insufficient elastic fiber formation that leads to structural weakness and results in various tissue disorders, including cardiovascular and periodontal disease. Notably however, the risk of periodontal disease in MFS patients affected by an aortic aneurysm or dissection has not yet been clarified.MethodsWe investigated the periodontal condition in the following three groups: MFS patients diagnosed with an aortic aneurysm or dissection with a planned aortic surgery (MFS surgery), MFS patients who had already undergone aortic surgery (MFS post-surgery) and healthy control patients (Healthy). The periodontal condition of all of these patients was evaluated at their first visit, reassessed again at two-month after the first visit, and evaluated again at a six-month follow-up after the reassessment. ResultsA total of 14 participants, 3 MFS surgery patients, 4 MFS post-surgery patients and 7 healthy control volunteers were examined. Saliva examinations revealed no significant differences between any of the groups at the first visit, reassessment, or follow-up. Interestingly, the MFS surgery cases showed a higher BOP and PISA at the first visit and follow-up compared with the other groups. In contrast, the MFS surgery patients showed an improvement in their LVDd and EF values, both markers of cardiac function, at the reassessment and follow-up compared with the first visit. ConclusionsMFS associated with an aortic aneurysm or dissection leads to a higher risk of periodontal disease, indicating the need for more frequent oral hygiene maintenance in these patients. In addition, MFS patients who undergo frequent professional cleaning of their teeth show a lower onset of cardiovascular disease, suggesting that professional oral hygiene in these cases contributes to a healthier condition.
Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse skeletal muscle dysfunction in age-associated sarcopenia mice
Authors: Jia Yali , Wang Ailing , Wang Chao , Zhai Jinglei , Zhao Bichun , Liao Tuling , Cao Ning , Su Ruyu , He Lijuan , Li Yanhua , Yue Wen , Pei Xuetao
Published: March 2022

With the expansion of the ageing population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy ageing. However, there are no approved therapies for AAS. In this study, we first used clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to treat AAS in two classic mouse models (SAMP8 mice and D-galactose-induced ageing mice) and studied the effects at the behavioural, histological, cellular and molecular levels by means of behavioural tests, immunostaining, western blotting and others. Core data results showed that hUC-MSCs dramatically restored skeletal muscle strength and performance in two AAS mouse models via the mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding the cellular ageing. For the first time, we comprehensively evaluated and demonstrated the preclinical efficacy of clinical-grade hUC-MSCs in the treatment of AAS in two mouse models. Our study highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases.
Association between fetal-type posterior cerebral artery and intracranial anterior and posterior circulating atherosclerotic plaque on high-resolution MRI at 3.0T
Authors: Liu Dingqi , Xin Ruijing , Zhao Deng-Ling , Chen Xiao-Hui , Li Cheng
Published: March 2022

Objectives
Atherosclerotic high-risk plaque rupture is one of the important factors leading to ischemic stroke. The present study used HRMRI to quantitatively analyze the association between the fetal-type posterior artery and intracranial anterior and posterior circulating atherosclerotic plaques.
Materials and Methods
A total of 58 patients (25 patients with fetal-type posterior artery and 33 patients without fetal-type posterior artery) were included for 3.0T HRMRI scan analysis. The images of the MCA and VBA vessel wall on HRMRI were compared between the two groups based on the degree of stenosis, remodeling index, and eccentricity degree.
Results
Positive remodeling of MCA plaques was more frequently observed in the fetal-type posterior artery group than in the control group (P < 0.05). The remodeling Index (95% CI, 0.001–0.474; P = 0.015) was associated with fetal-type posterior artery following the adjustment for the confounding factors. No significant differences were found in the VBA plaque characteristics between the two groups (P > 0.05).
Conclusion
Fetal-type posterior artery promotes the development of atherosclerosis plaque and positive vessel remodeling in middle cerebral artery, whereas it exhibits no association with vertebrobasilar artery plaque formation.
Case Report of Angiocentric Glioma Lacking Epilepsy and Discuss Its Relationship With Epilepsy
Authors: Cheng HaiLun , Yin WeiHua , Xu QinQin , Shi XiaoXin
Published: March 2022

Background: Angiocentric glioma is a rare neuro tumor, the general public believes that the typical clinical feature of angiocentric glioma (AG) is a history of epilepsy. This case have unique research value because it is lack history of epilepsy, it is provide evidence to exploration of the causes of AG-related epilepsy symptoms.Case presentations: A 16-year-old boy came to the hospital because of dizziness and blurred vision. The patient's CT stan detected a solid mass in the right frontotemporal lobe. Histologic finding the tumor is predominantly composed of elongated tumor cells forming rings around the blood vessels, the immunohistochemical staining show GFAP、D2-40、S100、Vimentin have positive expression, and Ki-67 proliferation index is 1%~5%, FISH-tissue show MYB gene rearrangement detection. According these evidences, this case was diagnosed as angiocentric glioma. the patient's physical condition was stable and there was no recurrence after the operation.Conclusion: We believe that MYB gene break rearrangement is related to the cause of AG and MYB-QKI gene rearrangement may be one of the important causes of AG, but it is not directly related to AG-related epilepsy.
MDP regulates BMSC differentiation and bone formation through miR-384-5p/Lepr
Authors: Feng Yun-Zhi , Zhang Shao-Hui , Guo Yue , Chen Yun , Liu Qiong , Tan Li , Gao Zheng-Rong , Zhao Jie , Zhao Ya-Qiong , Feng Yao , Hu Jing , Ye Qing , Ou-Yang Zhe-Yue , Zhou Ying-Hui
Published: March 2022

The main components of bacterial flora are closely related to bone metabolism. Peptidoglycan-based muramyl dipeptide (MDP) is present in bacterial cell walls. We found an association of energy metabolism with MDP in mice fed different diets. Leptin receptor (Lepr) expression in alveolar bone and the femur was increased drastically in the high-fat-diet group with MDP (H-MDP) compared with that in the high-fat-diet control (H-NaCl) group and low-fat-diet (LFD) group. The bone mass of mice was decreased after MDP intervention in the LFD group whereas, in the high-fat-diet (HFD) group, it was increased upon MDP intervention. Micro-RNA (miR)-384-5p targeted and inhibited Lepr expression in vitro . We extracted the supernatants of osteocytes cultured under different conditions with MDP intervention to act on bone marrow stromal cells (BMSCs) and found that miR-384-5p could regulate epr expression and osteogenic differentiation in BMSCs. Our findings indicate a possible mechanism of periodontitis-associated alveolar bone changes caused by the main components of microflora.
PRMT5 regulates the NAD-SIRT1-p53 signal axis by affecting the methylation of CD38 at R58 to promote malignant tumor cell proliferation
Authors: Zhou Yanhong , Liang Lin , Yue Chunxue , Li Wentao , Gao Mengxiang , Zeng Feng , He Junyu , He Zhengxi , Jin Xi , Liao Qianjin , Luo Gengqiu , Li Xin
Published: March 2022

The cell surface receptor CD38 has NADase enzyme and cyclase activity and is necessary for immune cell activation and proliferation. CD38 is a molecular marker for hematological tumor prognosis and diagnosis; however, its role in solid tumors is unclear. This study aimed to explore the role and mechanism of CD38 in the proliferation of solid tumor cells. We found that protein arginine methyltransferase 5 (PRMT5) interacts with CD38 in solid tumor cell lines, resulting in increased levels of CD38. In addition, PRMT5 can methylate CD38 at arginine 58 (R58). Moreover, PRMT5-induced methylation of CD38 affected its enzymatic activity and the NAD level. Finally, in vitro experiments showed that PRMT5-induced methylation of regulates the activity of the CD38-NAD-SIRT1-p53-p21 signal axis to promote the proliferation of solid tumor cells. In summary, PRMT5 promotes malignant tumor cell proliferation by regulating the methylation status of CD38 in solid tumors such as cervical cancer, nasopharyngeal carcinoma, and lung cancer. CD38 R58 could be applied in the early diagnosis and clinical treatment of solid tumors.
Predictive Value of 68Ga-FAPI-04 PET/MR for Left Ventricular Remodeling in Patients with Acute Myocardial Infarction
Authors: Zhang Min , Quan Weiwei , Zhu Tianqi , Feng Shuo , Huang Xinyun , Meng Hongping , Du Run , Zhu Zhengbin , Qu Xuezheng , Li Ping , Yan Xiaoxiang , Zhang Ruiyan , Li Biao
Published: March 2022

Purpose
To observe longitudinal changes of myocardial fibroblasts activation by 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/MR in patients with ST-segment elevated myocardial infarction (STEMI), and assess its predictive value for late left ventricular remodeling (LVR).
Methods
Forty-two patients with STEMI were included in the study. 68Ga-FAPI-04 PET/MR was performed at baseline (5.1 ± 3.0 days) and at 12 months (12.0 ± 1.1 months) after STEMI. The extent of activated myocardial fibroblasts were quantified using 68Ga-FAPI-04 uptake volume (UV). Infarct size was expressed as late gadolinium enhancement (LGE) volume. LVR was defined as > 10% increase in left ventricular end-systolic volume (LVESV) from baseline to 12 months measured by echocardiography.
Results
Baseline 68Ga-FAPI-04 uptake volume (UV) was a significant predictor of the change in LVESV (B = 0.083, p = 0.023) from baseline to 12 months after AMI. The LVR group demonstrated higher 68Ga-FAPI-04 UV at baseline than the non-LVR group (p = 0.013). The area under the curve (AUC) of 68Ga-FAPI-04 UV at baseline for predicting the LVR reached 0.833 (p = 0.019), with sensitivity of 100.0% and specificity of 60.0%.
Conclusion
68Ga-FAPI-04 PET/MR is a useful tool to non-invasively quantify myocardial fibroblasts activation, and baseline 68Ga-FAPI-04 UV in the early stage of STEMI may have predictive value for the late LVR.
Solvent Dependency of Adsorption of Mercaptopurine on CC, AlN and BN Nanotubes and the Evaluation of Noncovalent Interactions
Authors: Al-Otaibi Jamelah S , Mary Y. Sheena , Mary Y. Shyma , Thomas Renjith
Published: March 2022

The performance of nanotubes (NT) of carbon (CC), aluminium-nitrogen (AlN) and boron-nitrogen (BN) as a sensor and nanocarrier for mercaptopurine (MCP) was investigated by means of theoretical approach. The calculated negative values of adsorption energy showed the interaction and adsorption of the drug. HOMO and LUMO distributions were only found on the NT counter portion of drug-nanotube not on MCP for AlN-NT and BN-NT while HOMO is over MCP and LUMO is over NT for CC-NT. The polarizability of MCP-NTs is greater than that of MCP. Raman wavenumbers of MCP are enhanced in NTs and hence NTs can act as a sensor for detection of MCP. Solvent dependency on adsorption behavior is also presented in the manuscript, where we found that AlN nanotube showed exceptionally high free energy of adsorption over other nanotubes in all solvent medium. Solvation free energies were also reported. Non covalent interaction scattered plot also showed significant inter molecular interaction between AlN nanotubes and the mercaptopurine when compared to other nanotubes under study.
Association Between Early Ondansetron Administration and In-Hospital Mortality in Critically Ill Patients: Analysis of the MIMIC-IV Database
Authors: Fang Yingying , Wang Xinghe , Xiong Chao
Published: March 2022

BackgroundWhile ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. MethodsThe MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings.ResultsIn total, 51342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63-0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34-0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42-0.76; P < 0.001) and 0.79 (95% CI 0.62-0.91; P < 0.001), respectively. A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62-0.90; P < 0.001) and 0.63 (95% CI 0.43-0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36-0.73; P < 0.001), and 0.26(95% CI 0.11-0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort.ConclusionsEarly OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group.
Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism
Authors: Liu Li , Peng Min-Zhi , Shao Yong-Xian , Li Xiu-Zhen , Zhang Kang-Di , Cai Yan-Na , Lin Yun-Ting , Jiang Min-Yan , Liu Zong-Cai , Su Xue-Ying , Zhang Wen , Jiang Xiao-Ling
Published: March 2022

The SLC25A32 dysfunction is associated with neural tube defects (NTDs) and exercise intolerance, but very little is known about disease specific mechanisms due to a paucity of animal models. Here, we generated homozygous (Slc25a32Y174C/Y174C and Slc25a32K235R/K235R) and compound heterozygous (Slc25a32Y174C/K235R) knock-in mice by mimicking the missense mutations identified from our patient. A homozygous knock-out (Slc25a32-/-) mouse was also generated. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice presented with mild motor impairment and recapitulated the biochemical disturbances of the patient. While Slc25a32-/- mice die in utero with NTDs. All Slc25a32 mutations did not hinder the mitochondrial uptake of folates but specifically blocked the uptake of flavin adenine dinucleotide (FAD). A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency was observed. Besides the flavoenzymes involved in fatty acid β-oxidation and amino acid metabolism impaired, Slc25a32-/- embryos still had a subunit of glycine cleavage system–dihydrolipoamide dehydrogenase damaged, resulting in glycine accumulation and glycine derived-formate reduction, which further disturbed folate-mediated one-carbon metabolism, leading to 5-methyltetrahydrofolate shortage and other folate intermediates accumulated. Maternal formate supplementation increased the 5-methyltetrahydrofolate levels and ameliorated the NTDs in Slc25a32-/- embryos. The Slc25a32K235R/K235R mice had no glycine oxidation defect but had another formate donor-choline metabolism interrupted and mitochondrial folates deficient. Formate supplementation increased mitochondrial folates amounts of mice, but this effect was not restricted to the Slc25a32 mutant mice. In summary, we established novel animal models, which enabled us to better understand the function of SLC25A32 and to elucidate the role of SLC25A32 dysfunction in human disease development and progression.
IL-7R and CCR7 Regulate Distinct Metabolic Pathways in Naïve T Cells to Promote T Cell Motility
Authors: Byrum Janie R , Gridley Rebekah , Torres David J , Mrass Paulus , Oruganti Sreenivasa Rao , Cannon Judy L
Published: March 2022

Naïve T cells movement through tissues, including through lymph nodes, requires ongoing energy supply for rapid motility promoting T cell scanning of dendritic cells and T cell activation. Rapid movement is facilitated by signaling through chemokine receptor CCR7, but how signaling to motility relates to T cell metabolism is not well understood. Conversely, whether signals including IL-7R which are known to regulate naïve T cell metabolism might impact motility is not known. We analyze how CCR7 and IL-7R regulate T cell motility and metabolism. Using Seahorse analysis, we find that CCL21 signaling to CCR7 decreases oxidative phosphorylation, but has no effect on glycolysis. In contrast, IL-7 promotes glycolysis but shows no effect on respiration. We demonstrate a previously unidentified role for IL-7/IL-7R in promotion of T cell motility in lymph nodes by imaging T cell movement in lymph nodes after inhibition of IL-7R and IL-7. Downstream of IL-7R, JAK3 and STAT5, but not mTOR, mediates rapid motility. Our results shed new light on how metabolism intersects with motility to promote more efficient T cell movement within lymph nodes to promote potential for DC scanning and interaction, potentially through differential means of ATP production.
High friction mechanism of ZDDP tribofilm based on in-situ AFM observation of nano-friction and adhesion properties
Authors: Sato Kaisei , Watanabe Seiya , Sasaki Shinya
Published: March 2022

Zinc dialkyl dithiophosphate (ZDDP) is a typical anti-wear additive that forms tribofilm on sliding surfaces and prevents adhesion wear but increases the friction force. In this study, the nano-friction and adhesion properties of ZDDP tribofilms were investigated by performing in-situ observations by atomic force microscopy to explore the relationship between the formation process and physical properties of ZDDP tribofilm. The results showed that the nano-friction force increased with the formation of the ZDDP tribofilm. In addition, the adhesion force on the ZDDP tribofilm increased with the friction force. It was confirmed that the Young's modulus and nanoindentation hardness of the ZDDP tribofilms were lower than those of steel. However, the contact areas calculated using the Hertz contact theory were similar. In addition, the shear strengths, calculated with the contact areas of the Hertz model, of the ZDDP tribofilm were substantially higher than those of steel. From the above, it was hypothesized that the high friction force of the ZDDP tribofilm was derived from the high adhesion layer at the surface.
Dating App Usage and Motivations for Dating App Usage are Associated with Increased Disordered Eating
Authors: Blake K. , Portingale J. , Giles S. , Griffiths S. , Krug Isabel
Published: March 2022

Purpose
The centrality of physical appearance in dating app environments may constitute an appearance related pressure that increases the likelihood of body dissatisfaction (BD) and disordered eating (DE). Although dating app use has been linked to BD and DE, prior research has neglected the role of individuals’ dating app use motivations and relevant traits in eating pathology. To address these gaps, the current study investigated whether dating app usage moderated the effects of appearance-based rejection sensitivity (appearance-RS), fear of negative evaluation (FNE), emotion dysregulation, and perceived social rank on DE, and the unique association between individuals’ dating app use motivations and DE.
Methods
Participants (N = 690) completed baseline measures of demographic and trait variables including dating app usage.
Results
DE was positively associated with female gender, higher body mass index, a history of eating disorder (ED) diagnosis, appearance-RS, and emotion dysregulation. Dating app users were more likely to report DE symptoms, appearance-RS, and emotion dysregulation. No investigated predictor was moderated by dating app usage, but four of the six measured motivations for using dating apps were associated with DE among the dating app user sample.
Conclusion
Given that DE behaviors can lead to EDs, the present findings suggest that lifetime dating app usage may constitute a socio-cultural appearance pressure which confers DE risk.
Level of evidence
: Level V; descriptive study
Pattern dynamics of a vegetation model with nonlocal interactions
Authors: Liang Juan , LI LI , JIN ZHEN , Wu Yong Ping , Feng Guo Lin , Li Bai-Lian , Sun Gui-Quan
Published: March 2022

In order to understand the mechanism of water uptake by vegetation, we propose a vegetation-water model which represents nonlocal effect via nonlocal delay in this paper. By mathematical analysis, the condition of producing steady pattern is obtained. Furthermore, the amplitude equation which determines the type of Turing pattern is obtained by nonlinear analysis method. The corresponding vegetation pattern and evolution process under different intensity of nonlocal effect in roots of vegetation are given by numerical simulations. There is a positive correlation between the intensity of nonlocal effect and vegetation density, that is, the vegetation density increases with the increase of the intensity of nonlocal effect. Numerical simulation shows that as intensity of nonlocal effect increased, the isolation degree of vegetation pattern increases which indicates that the robustness of the ecosystem decreases. Besides, the results reveal that with the water diffusion coeffificient increase, the vegetation pattern transitions: stripe pattern→mix pattern→spot pattern emerge which predicts transitions from stripe vegetation to bare soil. Our results show the effects of intensity of nonlocal effect and diffusion coeffificient on vegetation distribution, which provides theoretical basis for the study of vegetation.
Improving the Accuracy of Estimates of the Pulse Sequence Period Using the Methodology of Complete Sufficient Statistics
Authors: Жучков Константин , Vasilchenko Mikhail , Zagrebneva Anna , Zavyalov Alexey
Published: March 2022

ࣧ Using a model of a sequence of quasi-rectangular pulses as an example, an approach was illustrated to assess their period, taking into account the off-duty factor and the squareness coefficient of the pulses. Complete sufficient statistics (CSS) methodology was used. An analytical expression for the pulse repetition was presented. It was shown that for the value of the sample size (n > 8) the relative root-mean square error of the repetition period estimation by CSS is shown as a significantly smaller error than that of the traditional estimate, which is only asymptotically effective. In addition to theoretical calculations, simulation results confirming the achieved effect are presented. The results obtained are applicable for the design of the control and measuring equipment of the oil and gas industry.
The Role of Ki-67 in HR+/HER2- Breast Cancer: a Real-world Study of 956 Patients
Authors: Ma Qin , Liu Xin-Lan
Published: March 2022

Purpose: This retrospective study aimed to determine the most suitable cut-off value of Ki-67 expression and further explore the prognostic effect of Ki-67 in hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry, The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer; compared with the commonly used threshold value of Ki-67(14%) in clinic at present, the consistency of the two value is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the increase of grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P<0.001). During the follow-up that 61 patients developed recurrence or metastasis which Ki-67 low expression was found in 21 cases and high expression in 40 cases, the patients with Ki-67 ≥ 22.5% had a 2.937 higher risk of early recurrence and metastasis than the patients with Ki-67< 22.5%, the DFS in patients with high Ki-67 expression was lower than the patients with low Ki-67 expression (96% VS 89%, P<0.05). The common position of distant metastasis were bone, liver and lung, and rare metastases were adrenal gland, bone marrow and pericardium. Recurrence and metastasis mostly occurred in the second and third year after operation, and multi-site metastasis was more common.Conclusions: The cut-off value of Ki-67 expression in HR+/HER2- breast cancer is 22.5%; The patients with Ki-67 ≥ 22.5% had a 2.937 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%.
Surgical Outcomes of Congenital Heart Disease in Down Syndrome: Tertiary Centre Experience – Focus on the Electrical Conduction System
Authors: Ebrahim Mohammad , Balool Joud Al , Saegh Asia Al , Menshawi Hesham , Almeeri Nasreldeen , Elsayed Moustafa , Al-Saiedi Faisal , Lyubomudrov Vadim
Published: March 2022

Purpose: To document outcomes of cardiac surgical repair in Down syndrome (DS) patients with specific focus on the associated electrical conduction morbidities, ultimately leading to a higher incidence of pacemaker implantation (PMI). Methods: A retrospective study conducted between 2011 to 2020. Results: A total of 167 DS patients undergoing 204 surgeries were included. The mean gestational age (GA) and mean weight were 37.3 weeks and 5.5 kg respectively. Complete atrioventricular septal defect (AVSD) was the most common diagnosis. Pre-operative ECG revealed superior axis deviation (SAD) in 92% and 32% of patients with AVSD and isolated perimembranous ventricular septal defect (VSD), respectively (p < 0.01). Postoperative right bundle branch block (RBBB) was observed in 83% of patients post AVSD repair, and in 55% of patients following perimembranous VSD repair (p = 0.04). Ten patients underwent post-operative pacemaker implantation (PMI). Reintervention rate was around 8.9%. Three mortalities were encountered throughout the study period, 2 of which were in-hospital deaths. Conclusion: Low mortality was observed, however, a higher rate of PMI requirements noted with risk factors including lower age and weight.
An integrated Framework for Breast Mass Classification and Diagnosis using Stacked Ensemble of Residual Neural Networks
Authors: Baccouche Asma , Garcia-Zapirain Begonya , Elmaghraby Adel
Published: March 2022

A computer-aided diagnosis (CAD) system requires automated stages of tumor detection, segmentation, and classification that are integrated sequentially in one framework to assist the radiologists with a final diagnosis decision. In this paper, we introduce the final step of breast mass classification and diagnosis using a stacked ensemble of residual neural network (ResNet) models (i.e. ResNet50V2, ResNet101V2, and ResNet152V2). The work presents the task of classifying the detected and segmented breast masses into malignant or benign, and diagnosing the Breast Imaging Reporting and Data System (BI-RADS) assessment category with a score from 2 to 6 and the shape as oval, round, lobulated, or irregular. The proposed methodology was evaluated on two publicly available datasets, the Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM) and INbreast, and additionally on a private dataset. Comparative experiments were conducted on the individual models and an average ensemble of models with an XGBoost classifier. Qualitative and quantitative results show that the proposed model achieved better performance for 1) Pathology classification with an accuracy of 95.13%, 99.20%, and 95.88%; 2) BI-RADS category classification with an accuracy of 85.38%, 99%, and 96.08% respectively on CBIS-DDSM, INbreast, and the private dataset; and 3) shape classification with 90.02% on the CBIS-DDSM dataset. Our results demonstrate that our proposed integrated framework could benefit from all automated stages to outperform the latest deep learning methodologies.
The Development and Verification for Reliability and Validity of a Japanese Version of Greene et al.'s Moral Dilemma Questionnaire
Authors: TAKIMOTO YOSHIYUKI , Yasumura Akira
Published: March 2022

Background: A difference exists in people's judgements between the switch case and pedestrian bridge case of the trolley problem, which is explained by the concept of personalness or directness. The moral dilemma task questionnaire developed by Greene, which comprises personal and impersonal moral dilemmas, is useful for clarifying people's moral judgements. However, the validity of Green’s questionnaire was not validated. We developed and validated a Japanese version of this questionnaire. Methods and Results: Ten new questions were added to the Japanese version using double translation and its internal validity was tested. A second survey was conducted on the same participants one month after the first survey (n=231). The intraclass correlation coefficient by retest was found to be 0.781. Conclusion: Reproducibility, internal consistency, and criterion-related validity were confirmed by retesting the Japanese version of the moral dilemma task by Greene et al. The current study proved the reliability of the original version.
Birth and Regulation of head Extension to Guide Manual perineal Assistance (BREGMA) study
Authors: Abouelhassan Abdelrahman , Kalis Vladimir , Schüssler Marc , Awwad Hassan , Hassan Rania , Ismail Khaled M
Published: March 2022

Introduction and Hypothesis: The exact positioning of the dominant hand at the time of manual perineal protection is not clearly specified. The overarching aim of this work was to collect data on the bregma to posterior fourchette distance (BFD), as a surrogate measure for the degree of fetal head extension, and maternal perineal body length (PBL) at the time of manual perineal protection (MPP). Methods: This was a two-center study. Term cephalic singleton nulliparous women having spontaneous vaginal delivery were considered eligible for recruitment into the study. Once crowning was diagnosed and just prior the initiation of manual perineal protection (MPP) or cutting an episiotomy, the BFD and PBL were measured using a standardized measurement protocol.Results: A total of 100 women (50 women in each center) were recruited into the study. The overall mean BFD was 2.8 ± 0.5 cm. The overall mean PBL was 4.4 ± 0.8 cm. There were no statistically significant differences between the measurements taken in both units regarding BFD or PBL (p = 0.81 and 0.10 respectively). There was a weak correlation between both measurements.Conclusion: This is the first study to generate data on the bregma to fourchette distance and the perineal body length just prior to fetal head expulsion. This information will probably be useful to inform future biomechanical computational modeling studies to optimize hands and fingers placement during manual perineal protection.
Prognosis by novel staging systems incorporating tumor biology in estrogen receptor positive and human epidermal growth factor receptor negative breast tumors
Authors: Vane Marissa , Traa Fenna , Roozendaal Lori van , Kuijk Sander van , Engelen Sanne , Maaren Marissa van , Siesling Sabine , de Wilt Johannes , Smidt Marjolein
Published: March 2022

Purpose The prognostic stage group and Bioscore are novel staging systems for breast cancer patients. They provide a better view on five-year disease-specific survival (DSS) compared to the traditional staging system. Five-year follow-up might not be sufficient for ER+HER2- tumors. This study determines five- and 10-year recurrence-free survival (RFS) for the anatomic and prognostic stage group of the 8 th AJCC TNM and Bioscore staging system, and compares these systems for ER+HER2- breast cancer patients. Methods All newly diagnosed ER+HER2- breast cancer patients treated with primary surgery in 2005 were included from the Netherlands Cancer Registry with a ten-year follow-up. All patients were staged according to 8 th AJCC TNM (both anatomic and prognostic stage group) and the Bioscore staging system. Five- and 10-year RFS was compared using Kaplan-Meier analysis. The ability to discriminate groups was quantified by the concordance statistic (c-statistic). Results Five-year RFS ranged from 65.0-91.1% (anatomic) and from 40.9-91.8% (prognostic stage group). The Bioscore staging system ranged from 54.9-92.1%. Ten-year RFS rates were 52.9-84.9% (anatomic stage), 31.8-84.6% (prognostic stage) and 47.1-85.1% (Bioscore). All systems similarly discriminated groups with comparable c-statistic score (five- and 10-year 0.58-0.60). The prognostic stage group identified a group (IIIC) with very poor prognosis (31.8%) which could not be identified using the other staging systems (10-year RFS for 52.8% for anatomic IIIC and 47.1% for Bioscore 6). Conclusion All three staging systems similarly discriminated groups for ER+HER2- breast cancer patients with a five- and 10-year follow-up. However, the prognostic stage group showed a wider distribution of the 10-year RFS compared to anatomic stage group and Bioscore staging system.
Gender Stereotypes when Applying Bloom’s Taxonomy by Preservice Teacher's
Authors: Karama Muneer Jebreel
Published: March 2022

The aim of this research was to examine the gender stereotypes between preservice teachers (33 preservice teachers;4 male, 29 female) by applying Bloom’s Taxonomy in their educational course, “ Measurement & Evaluation.” Each student was assigned to formulate behavioral goals, according to Blooms six classification levels, and by the end of the course. The research questions for the study were: Do the verbs (actions) and nouns of Bloom’s Taxonomy which were written by preservice teachers connotative any gender stereotypes? Were there differences between females and males in their use of gender stereotypes? Were there differences between preservice teachers according to their academic field (13 applied biology, 13 applied mathematics, 6 applied physics, and 1applied chemistry) toward gender stereotypes? The analysis of the data showed that preservice teachers had gender stereotypes (more than 70% of them are masculine verbs and nouns) in writing verbs (actions), and nouns, during they are designing Bloom’s Taxonomy. Moreover, there are no are significant differences between females and males in their tendency toward apply gender stereotypes due to males, and their academic field. In light of these findings and results, the scholar powerfully endorses that the course needs to be used to develop a gender balance, and eliminate gender stereotypes.
Novel Method to Systematically Resolve Global Warming by Removing CO2 from the Air and Turning it Into Formic Acid
Authors: Köntös Zoltán
Published: March 2022

The CO2 concentration in the atmosphere is a major problem with global warming being one of the main effects of the increased CO2 concentration. The recapture of CO2 from the atmosphere represents one of the most revolutionary ways of dealing with the problem. This study proposes the removal of high CO2 concentration in the Earth’s atmosphere relying on a photocatalytic conversion of CO2 into formic acid. The use of readily available materials such as water and light makes the process easily adaptable. The study conducts an experiment on the photocatalytic conversion of CO2 into formic acid using a RK-X reactor. Experiments conducted by the study returned 2.6g/L of formic acid achieved through the photocatalytic CO2 conversion which can be easily restarted and adopted on a large scale basis with the right investment. The study proves that the conversion of CO2 into formic acid is very much possible and highlights the practical applications of the process through the benefits associated with formic acid. The formic acid produced could act as a hydrogen carrier due to the formic acid’s properties that make it one of the best hydrogen energy carriers hence allowing for energy from the sun to be converted and stored in chemical bonds.
Z-RNA and the flipside of the SARS Nsp13 helicase
Authors: Herbert Alan , Shein Alex , Poptsova Maria
Published: March 2022

We present evidence that the severe acute respiratory syndrome coronavirus (SARS) non-structural protein 13 (Nsp13) modulates the Z-RNA dependent regulated cell death pathway of necroptosis (1). We show that Z-prone sequences (called flipons (2)) exist in coronavirus and provide a signature that enables identification of the animal viruses which have become human pathogens. We also identify a potential RHIM in Nsp13. These two observations allow us to suggest a model in which Nsp13 may regulate Z-RNA-initiated RHIM-dependent cell death outcomes at two steps. The first step involves possible new ATP-independent Z-flipon helicase activity in Nsp13, which is distinct from the activity of the canonical A-RNA helicase. This activity unwinds/quenches nascent Z-RNAs, preventing their sensing by ZBP1. The second step involves RHIM-dependent inhibition of ZBP1, RIPK3 and/or RIPK1, preventing cell death downstream of Z-RNA sensing. Together the RHIM and Z-flipon helicase have the potential to alter the host response to the virus and the effectiveness of drugs targeting the NSP13 helicase.
Morphological characteristics of the infrapatellar fat pad
Authors: Edama Mutsuaki , Otsuki Tomofumi , Yokota Hirotake , Hirabayashi Ryo , Sekine Chie , Maruyama Sae , kageyama Ikuo
Published: March 2022

The purpose of this study was to clarify the morphological characteristics of the infrapatellar fat pad (IFP) in Japanese cadavers and to elucidate the relationship between morphological characteristics of the IFP and degeneration of the patellofemoral joint. This investigation examined 41 legs from 25 Japanese cadavers. Morphological measurement was performed by one examiner, and the proximal IFP, IFP body length, width, and IFP volume were measured. The morphological characteristics of IFP proximal were used to categorize three types of IFP: Type I, IFP proximal located on medial and lateral sides of the patella; Type II, IFP proximal only located medially; and Type III, absence of IFP proximal medially and laterally. Articular surfaces were graded as macroscopically intact or mildly altered (Grade I), moderately altered (if fissuring or fibrillation was observed; Grade II), or severely altered (if eburnation was present; Grade III). Type I was identified in 36.6%, Type II in 48.8%, and Type III in 14.6%. IFP medial proximal was seen in 85%, IFP lateral proximal in 36.6%, and loop type was 2.4%. Grade II was significantly more frequent than Grades I or III in Type II, and Grade III was significantly more frequent than Grades I or II in Type III. In addition, IFP volume was significantly larger in Type I than in Types II or III. Causal relationships remain unclear, but the deformation of patellofemoral joint may be related to decreased IFP volume (atrophy).
Investigation of optical properties of Er3+-doped Ga1As39S60 glasses quenched in salt batch media
Authors: rezvani mohammad , Dizaj Amin Yousefi , Ahmadi Pouya
Published: March 2022

Er3+ - doped (0.5-2%wt) Ga1As39S60 glasses were synthesized by melting appropriate amounts of Ga, As, S as starting materials in rotating furnace and consequently quenching in salt batch media (NaNO3 + KNO3) with the temperature of 130\(℃\). X-ray diffraction spectra and FESEM micrograph showed the amorphous nature and homogeneous structure of the prepared samples with no clusters. The glass transition temperature of samples was increased from 183\(℃\) to 206\(℃\) by increasing Er3+ amount from 0.5 to 2%wt. The effects of Er3+ on absorption coefficient\(\left(\alpha \right)\), Fermi energy level(EF), direct and indirect forbidden bands, and Urbach energy were investigated and later ones were increased from 1.75 to 1.77ev, from 1.80 to 1.84 ev, from 2.05 to 2.08 ev and from 0.10 to 0.11 ev, respectively with increasing Er3+ ions (0.5-2%wt) which confirmed the modifying role of Er3+ ions in Ga-As-S system.
Evaluating a ten years training course in child psychiatry in Jimma, South-West Ethiopia
Authors: Abera Mubarek , Hailu Yohannes , Kerebih Habtamu , Gruber-Frank Christine , Frank Reiner
Published: March 2022

Background: In Ethiopia, as many other low-and middle income-countries, health professionals, particularly of mental health workers are scarce. The purpose of this paper is therefore to describe the process of developing, establishing and evaluating a training course for child psychiatry within this program.Method: Cooperation between local and foreign institutions and instructors used to offer the course in child psychiatry between 2010 and 2019. The core elements of the course were to train mental state description from locally produced video examples, make decisions on possible disorders, do occupational activities and design psychosocial interventions. Patient-oriented method of teaching was implemented. The basic structures of course development were a phase of preparation, a focus on case presentations during the course, mutual feedback and evaluation, and a workup after the course. The concept in the method of teaching was adapted in an iterative process according to the needs of patients and evaluations of participants and teachers overtime. Results: From 2010 to 2019 eight courses were organized. A total of 71 trainees took part in the courses successfully. The initial step was to establish collaboration with guest lecturers and implementation of the teaching program. Each course contributed to expand the course materials subsequently. Main modifications were to elaborate on the mental state description successively to get a feeling for children's’ problems by age and severity. The second period was a phase of transition from guest lecturers to local trainers. At the request of graduates, a refresher course was held in 2017. Relying on an OSCE format, clinical abilities could be updated within one weekend. Capacity building was a major aim of the program. Three graduates developed to be trainers in child mental health and they subsequently continued the course on their own. Alongside the teaching program, an outpatient clinical service for children established by the lead author is now running at Jimma University.Conclusion: The establishment of the training program was time consuming. The long-term commitment of local and guest teachers enabled them to develop culturally appropriate solutions for the local context. A similar approach could be applied to other settings.