bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding gene Gpr151
Authors: Lee Bohm , Lee Jinyoung , Jeon Yewon , Kim Hyemin , Kwon Minjae , Shin Jung Eun , Cho Yongcheol
Published: March 2021

Gene expression profiling in response to nerve injury has been mainly focused on protein functions of coding genes to understand mechanisms of axon regeneration and to identify targets of potential therapeutics for nerve repair. However, the protein functions of several highly injury-induced genes including Gpr151 for regulating the regenerative ability remain unclear. Here we present an alternative approach focused on non-coding functions of the coding genes, which led to the identification of the Gpr151 RNA function as a molecular sponge via its interaction with RNA-binding proteins such as CSDE1. Gpr151 promotes axon regeneration by the function of its 5’- untranslated region (5’UTR) and expression of an engineered form of the 5’UTR improves regenerative capacity in vitro and in vivo in both sciatic nerve and optic nerve injury models. Our data suggest that searching injury-induced coding genes potentially functioning by their non-coding regions is required for the RNA-based gene therapy for improving axon regeneration.
Sevoflurane Post-Conditioning Alleviated Hypoxic-Ischemic Brain Injury in Neonatal Rats by Inhibiting Endoplasmic Reticulum Stress-Mediated Autophagy via IRE1 Signalings
Authors: Niu Jiayuan , Wu Ziyi , Xue Hang , Zhang Yahan , Gao Qiushi , Li Chang , Zhao Ping
Published: March 2021

Post-conditioning with sevoflurane, a volatile anesthetic, has been proved to be neuroprotective against hypoxic-ischemic brain injury (HIBI). Our previous research showed that autophagy is over-activated in a rat model of neonatal HIBI, and inhibition of autophagy confers neuroprotection. There is increasing recognition that autophagy can be triggered by activating endoplasmic reticulum (ER) stress. This study aimed to explore: i) the relationship between ER stress and autophagy in the setting of neonatal HIBI; and ii) the possible roles of ER stress-mediated autophagy and IRE1 signalings in the neuroprotection of sevoflurane post-conditioning against neonatal HIBI. Seven-day-old rats underwent left common artery ligation followed by 2 h hypoxia (8% O2 / 92% N2). The relationship between ER stress and autophagy was examined by ER stress inducer (tunicamycin), ER stress inhibitor (4-PBA), or autophagy inhibitor (3-MA). Rats in the sevoflurane post-conditioning groups were treated with 2.4% sevoflurane for 30 min after HIBI induction. The roles of ER stress-mediated autophagy and the IRE1/JNK/beclin1 signaling pathway in the neuroprotection afforded by sevoflurane were examined by ER stress inducer (tunicamycin) and the IRE1 inhibitor (STF-083010). HIBI over‑activated ER stress and autophagy in neonatal rats. HIBI-induced autophagy was significantly aggravated by tunicamycin but blocked by 4-PBA; however, HIBI-induced ER stress was not affected by 3-MA. Sevoflurane post-conditioning significantly alleviated ER stress, autophagy, cell apoptosis, and cognitive impairments, which were remarkably abolished by tunicamycin. Also, tunicamycin blocked sevoflurane-induced downregulation of IRE1/JNK/beclin1 signaling pathway. Whereas, IRE1 inhibitor could reverse the effects of tunicamycin. ER stress contributes to autophagy induced by HIBI. Furthermore, sevoflurane post-conditioning significantly protects against HIBI in neonatal rats by inhibiting ER stress-mediated autophagy via IRE1/JNK/beclin1 signaling pathway.
Scalable High-Speed Hybrid Complementary Integrated Circuits based on Solution-Processed Organic and Inorganic Transistors
Authors: Wei Xiaozhu , Kumagai Shohei , Makita Tatsuyuki , Tsuzuku Kotaro , Yamamura Akifumi , Sasaki Mari , Watanabe Shun , Takeya Jun
Published: March 2021

Printed electronics offer a cost-efficient way to realise flexible electronic devices. The combined use of p-type and n-type semiconductors would yield silicon-like integrated circuits with low power consumption and stability. However, printing complementary circuits is challenging due to a lack of suitable material systems. To counter this, we employed a hybrid system to integrate p-type organic semiconductors (OSCs) and n-type amorphous metal oxide semiconductors (MOSs). These damage-free patterned OSC- and MOS-based thin-film transistors with improved process durability allowed the fabrication of hybrid complementary circuits on flexible substrates. These inverters functioned well even after exposure to air for 5 months. A large noise margin and power gain of 38 were realised with a supply voltage as low as 7 V. Furthermore, a five-stage ring oscillator with a stage propagation delay of 1.3 µs was achieved, which is the fastest operation ever reported for printed, flexible complementary inverters.
Machine learning model to predict mental health crisis from electronic health records
Authors: Garriga Roger , Matić Aleksandar , Mas Javier , Abraha Semhar , Nolan Jon , Harrison Oliver , Tadros George
Published: March 2021

Timely identification of patients who are at risk of mental health crises opens the door for improving the outcomes and for mitigating the burden and costs to the healthcare systems. Due to high prevalence of mental health problems, a manual review of complex patient records to make proactive care decisions is an unsustainable endeavour. We developed a machine learning model that uses Electronic Health Records to continuously identify patients at risk to experience a mental health crisis within the next 28 days. The model achieves an area under the receiver operating characteristic curve of 0.797 and an area under the precision-recall curve of 0.159, predicting crises with a sensitivity of 58% at a specificity of 85%. The usefulness of our model was tested in clinical practice in a 6-month prospective study, where the predictions were considered clinically useful in 64% of cases. This study is the first one to continuously predict the risk of a wide range of mental health crises and to evaluate the usefulness of such predictions in clinical settings.
FastGLLVM: Big Data Ordination Towards Intensive Care Event Count Cases
Authors: Caraka Rezzy Eko , Chen Rung Ching , Lee Youngjo , HUANG SU-WEN , CHIOU SHYUE-YOW , Pardamean Bens
Published: March 2021

Background: In the heart data mining and machine learning, dimension reduction is needed to remove the multicollinearity. Meanwhile, it has been proven to improves the interpretation of the parameter model. In addition, dimension reduction is also can increase the time of computing in high dimensional data. Methods: In this paper, we perform high dimensional ordination towards event counts in intensive care hospital , following emergency department (ED 1), First Intensive Care Unit (ICU1), Second Intensive Care Unit (ICU2), Respiratory Care Intensive Care Unit (RICU), Surgical Intensive Care Unit (SICU), Subacute Respiratory Care Unit (RCC), Trauma and Neurosurgery Intensive Care Unit (TNCU), Neonatal Intensive Care Unit (NICU) which use the Generalized Linear Latent Variable Models (GLLVM’s). Results: During the analysis, we measure the performance and calculate the time computing of GLLVM with employing variational approximation and Laplace approximation, and compare the different distributions including Negative Binomial, Poisson, Gaussian, ZIP, and Tweedi, respectively. Conclusions: In a nutshell, GLLVM’s leads as best performance reaching the accuracy 98% comparing other methods. In line with this, we get the best model negative binomial and Variational approximation which provides the best accuracy by accruacy value of AIC, AICc, and BIC. In a nutshell, our best model is GLLVM-VA Negative Binomial with AIC 7144.07 and GLLVM-LA Negative Binomial with AIC 6955.922.
Improving Antibacterial and Anti-biofilmic properties of urological catheters with Eucalyptus, Rosemary, Green tea and Ziziphora extracts by impregnation method
Authors: Akhlaghi-Ardekani Najme , Mohebbi-Kalhori Davod , samimi Abdolreza , Karazhyan Reza
Published: March 2021

The main complications of urinary catheters are the bacteria's biofilm formation and the urinary tract infection caused by gram-positive and gram-negative bacteria. In the recent years, the attention has changed its direction toward the antimicrobial, anti-biofilmic, and hydrophobicity effects of herbal extracts. Some of these extracts can inhibit the colonization of the two bacteria Staphylococcus aureus and Escherichia coli which are resistant to antibiotics. These bacteria can stick to the surface of polymer materials due to their hydrophobicity. Thus, antibacterial hydrophilic herbal extracts are supposed to help reduce the risk of the surficial infection if they are used to impregnate the urinary catheters. In this research, the extracts of these four plants eucalyptus, rosemary, green tea and ziziphora were used as the antibacterial agents. After the impregnation and modification of the sample catheters, they were tested by AFM, FE-SEM, ATR-FTIR methods to measure their mechanical, chemical, and hydrophilic properties, during the 21-day experiment period, compared to non-impregnated ones. The tests showed the silicone catheters impregnated by the herbal extracts have some significant anti-biofilmic and antibacterial properties (P˂0.0001) due to the increase in their hydrophilic property. The impregnated catheters could be release the extracts and killed bacteria in 21 days Therefore; some herbal extracts can be good alternatives to chemical drugs.
Elevated Serum Levels of Herpes Virus Entry Mediator and IL-5 in Cough Variant Asthma Versus Classic Asthma Patients
Authors: Yao Can , Yang Zhong , Chen Dandan , Fang Wei , Zhang Yu , Li Binbin , Li Sinian , Chen Rongchang , Shi Fei
Published: March 2021

BackgroundCough variant asthma (CVA) is a special phenotype of asthma. The precise inflammatory features of patients with CVA, however, is still unclear. We aimed to elucidate the differential inflammatory features in patients with CVA in contrast to patients with classic asthma (CA). MethodsA total of 68 patients with persistent uncontrolled asthma (34 with CVA, 34 with CA) in Shenzhen People’s Hospital between August 2018 and May 2019 were enrolled. We collected the demographic data, pulmonary function test (PFT) parameters, hematological variables, and several serum biomarkers. Receiver operating characteristic (ROC) curves were generated to evaluate the values of biomarkers for distinguishing between CVA and CA. ResultsCompared with CA group, CVA group had a higher percentage of females (73.5 vs. 50%, P = 0.046), lower proportion of asthma family history (5.9 vs. 29.4%, P = 0.011), shorter disease course [12.0 (4.8, 39) vs. 96.0 (48.0, 240.0) months, P < 0.001], and better pulmonary function (P all < 0.05). Increased levels of blood eosinophil count [0.35 (0.13, 0.94) vs. 0.34 (0.01, 0.53) X109/L, P = 0.045], eosinophil percentage [6.3 (3.0, 9.8) vs. 4.4 (0.2, 8.4) %, P = 0.046], serum IL-5 [104.19 (89.03, 199.66) vs. 84.57 (26.87, 103.58) ng/L, P = 0.011], and serum herpesvirus entry mediator (HVEM) [128.53 (100.89, 204.83) vs. 90.71 (37.05, 108.08) pg/mL, P = 0.002] were also found in CVA patients compared to those in CA patients. The logistic analysis revealed that serum HVEM had a strong predictive power for CVA group (OR = 1.105, P = 0.015). The sensitivities and specificity of serum HVEM and IL-5 to distinguish between CVA and CA at optimal cut-offs were 85.0% and 61.1%; 85.0% and 61.1%, respectively. AUCs of serum HVEM and IL-5 were 0.789 and 0.739, respectively. Furthermore, serum HVEM and IL-5 had no correlation with PFT parameters in CVA group (P all > 0.05).ConclusionsElevated serum levels of HVEM and IL-5 are exhibited in CVA patients, which may indicate their important roles in the pathogenesis and progression of CVA.
MiR-1-3p Downregulation Delays Endochondral Ossification of the Acetabular Roof in DDH
Authors: Ding Rui , liu xijuan , zhang jian , yuan jinghong , zheng sikuan , cheng xigao , Jia Jingyu
Published: March 2021

Background: Developmental dysplasia of the hip (DDH) is a highly prevalent hip disease among children. However, its pathogenesis remains unclear. MiRNAs are important regulators in cartilage development. In previous study, miRNA high-throughput sequencing on an animal model of DDH showed a low level of miR-1-3p in the cartilage of acetabular roof (ARC), but its role in DDH pathogenesis was not addressed. Therefore, our aim was to investigate the effects of miR-1-3p in the ARC.Methods: The X-ray examination was performed to confirm acetabular dysplasia, MRI imaging and HE staining was conducted to further evaluate the ARC thickness in each animal model. The FISH was used to confirm the expression of miR-1-3p in the ARC and chondrocytes. The target gene of miR-1-3p was predicted by bioinformatics database. The dual-luciferase reporter gene assay was used to confirm the targeting relationship between miR-1-3p and SOX9. The gene expression of miR-1-3p, SOX9, RUNX2 and collagen type X by QPCR analysis. The relative proteins level was detected by western blot analysis. The level of SOX9, RUNX2 and collagen type X in the ARC through immunohistochemistry analysis. Alizarin Red S staining was used to observe the mineralized nodules produced by chondrocytes.Results: The low expression of miR-1-3p in the ARC of DDH. SOX9 is miR-1-3p target gene. Downregulation the expression of miR-1-3p in vitro and demonstrated significantly reduced chondrocytes generated mineralized nodules, as opposed to the control. We also confirmed that, with miR-1-3p silencing, SOX9 expression was upregulated, whereas expression of genes associated with endochondral osteogenesis RUNX2 and collagen type X were downregulated. To confirm the involvement of miR-1-3p silencing in abnormal ossification through SOX9, we also performed a rescue experiment where SOX9 silencing restored the low expression of RUNX2 and collagen type X, produced by miR-1-3p downregulation. Lastly, the elevated SOX9 levels and reduced RUNX2 and collagen type X levels in the ARC of DDH rabbits were also verified, using immunohistochemistry, RT-PCR, and western blot. Conclusion: The low expression of mir-1-3p in the ARC of DDH, which may be the cause of the acetabular roof abnormal endochondral ossification in DDH.
An Evaluation of Thrombotic Tendency by Whole-Body Enhanced CT Scan for Critical COVID-19 Pneumonia: A Case Series Study
Authors: Ogawa Fumihiro , Oi Yasufumi , Nakajima Kento , Matsumura Reo , Nakagawa Tomoki , Miyagawa Takao , Abe Takeru , Takeuchi Ichiro
Published: March 2021

Background: Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified.Case presentation: We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19.Discussion: Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed. Conclusions: Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary.
Histological Analysis of Induced Membranes in Patients Whose Bone Defects Were Treated With the Masquelet Technique to Identify Factors Affecting the Vascularity of Induced Membranes
Authors: Niikura Takahiro , Jimbo Naoe , Komatsu Masato , Oe Keisuke , Fukui Tomoaki , Matsumoto Tomoyuki , Hayashi Shinya , Matsushita Takehiko , Sakai Yoshitada , Itoh Tomoo , Kuroda Ryosuke
Published: March 2021

BackgroundRich vascularity of the induced membrane (IM) is important for Masquelet reconstruction surgery. The factors affecting IM vascularity are not completely understood. This study aimed to investigate these factors using histological samples of human IMs.MethodsWe retrospectively evaluated 36 patients whose bone defects were treated using the Masquelet technique. Two clinical pathologists analyzed histological sections of IM pieces (1-cm2). The number of blood vessels per 1 mm2 was counted and compared among men and women, femur or tibia, with and without free flap surgery, antibiotic impregnation to the cement, osteogenesis inside the membrane, smoking, and diabetes mellitus. The number of blood vessels within the same patient was compared among different time points. Correlation analysis was performed among blood vessel numbers and patient age, duration of cement spacer placement, and histological grading scales (inflammation, foreign body reaction, and fibrosis).ResultsIM formation with rich vascularity and some inflammation, foreign body reaction, and fibrosis was histologically confirmed in all patients. We found 37.4 ± 19.1 blood vessels per 1 mm2. Blood vessel numbers were significantly lower in patients with than in those without free flap surgery. Blood vessel numbers were higher in patients with osteogenesis inside the IM. No significant correlations were found in any of the analyses.ConclusionSex, patient age, smoking, diabetes mellitus, femur or tibia, duration of cement spacer placement, and antibiotic impregnation to the cement did not affect IM vascularization. IM vascularization was reduced in patients with than in those without free flap surgery.
Association of Accelerated Long-term Forgetting and Senescence-related Blood-borne Factors in Asymptomatic Individuals From Families With Autosomal Dominant Alzheimer’s Disease
Authors: Yang Jianwei , Kong Chaojun , Jia Longfei , Li Tingting , Quan Meina , Li Yan , Lyu Diyang , Li Fangyu , Jin Hongmei , Li Ying , Wang Qigeng , Jia Jianping
Published: March 2021

Background: Accelerated long-term forgetting has been identified in preclinical Alzheimer’s disease (AD), and is attributed to a selective impairment of memory consolidation in which hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD). Methods: We analyzed data of 39 asymptomatic participants (n=18 ADAD mutation carriers, n=21 non-carriers) from the Chinese Familial Alzheimer’s Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min and 7 days. Peripheral blood concentrations of candidate pro-aging factors (C-C motif ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants. Results: Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall (β= -0.46, p=0.002), figure recall (β= -0.44, p=0.004) and list recognition (β= -0.37, p=0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: β=0.39, p=0.007; CCL11 versus list recognition: β=0.44, p=0.002).Conclusions: Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting.
Applications of Various Range Shifters for Proton Pencil Beam Scanning Radiotherapy
Authors: Lin Haibo , Shi Chengyu , Huang Sheng , Shen Jiajian , Kang Minglei , Chen Qing , Zhai Huifang , McDonough James , Tochner Zelig , Deville Curtiland , II Charles B. Simone , Both Stefan
Published: March 2021

Background: A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. Methods: three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB) and couch top bolus (CTB). HN patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at snout positions: 15 cm, 25 cm, and 35 cm. A solid water phantom with the ALB placed at 0, 10 and 20 cm air gaps to the phantom surface was also measured using a single-field optimized pencil beam scanning field. The two dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at iso-center and compared with the treatment planning system. Results: A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for a head-and-neck target and an MRS as complimentary for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. Conclusion: We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of URPS and MRS. We recommend the removable UB to be employed for the brain and HN treatments only while an automated MRS is used for all proton beams that require RS but not convenient or feasible to UB.
Primary Hepatic Choriocarcinoma in a Male Patient: A Case Report and Literature Review
Authors: Zhao Ke , Rao Ke , Chen Xin , Chen Si , Xu Haifeng
Published: March 2021

BackgroundChoriocarcinoma is a rare malignant tumor and rarely occurs outside the gonads. Primary hepatic choriocarcinoma is more infrequent, with hidden clinical manifestations, rapid progress, and extremely poor prognosis. Only more than 10 cases were publicly reported in the world. Therefore, there is still a lack of deep understanding of the diagnosis and treatment of the disease.Case presentationWe report a case of primary hepatic choriocarcinoma in a man diagnosed by pathology. A 65-year-old male patient presented with fever and anorexia, nothing but mild jaundice of the skin and sclera was found on physical examination. Abdominal enhanced magnetic resonance imaging (MRI) showed a huge mass in the right hepatic lobe. Fludeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) scan showed increased uptake in the liver and sigmoid colon and no uptake in the testes. The patient underwent the right hepatectomy, and postoperative pathology showed that the tumor was primary hepatic choriocarcinoma. Then he received one course of adjuvant chemotherapy. Then he developed severe myelosuppression and was transferred to the intensive care unit for further treatment. He eventually died of severe liver failure about 100 days after surgery. Primary hepatic choriocarcinoma is extremely rare, and its diagnosis is challenging.ConclusionsPrimary hepatic choriocarcinoma is a rare and highly malignant tumor with a poor prognosis. We believe that this differential diagnosis should be considered in liver tumor patients. The effective treatment for this disease is still to be explored.
Terrestrial stilling will continue during the 21st century
Authors: Chen Deliang , Deng Kaiqiang , Azorin-Molina Cesar , Yang Song , Zhang Gangfeng , Minola Lorenzo
Published: March 2021

The near-surface wind speed over land has declined in recent decades, a trend known as terrestrial stilling (TS)1-2. However, recent studies have indicated a reversal of the TS in the Northern Hemisphere (NH) during the last decade3-6, triggering renovated interest in the wind speed changes. Here we show that the TS in the NH mid-latitudes will continue in all seasons throughout the 21st century, especially in summer. The recent reversal of TS is most likely a multi-decadal fluctuation related to the Pacific and Atlantic climate variations, rather than a secular trend. A new paradigm of the future TS is further proposed, which is related to an intensified subsidence inversion over the mid-latitudes, caused by enhanced tropical and subtropical convections. This study reveals the important role of global warming in reducing the near-surface wind speed on long time scales. The continuing TS means a long-term strategy for wind energy production needs to be developed, particularly for the NH mid-latitude countries.
Costs of inpatient hospitalisations in the last year of life in older New Zealanders: a cohort study
Authors: Scott Oliver , Gott Merryn , Edlin Richard , Moyes Simon , Muru-Lanning Marama , Kerse Ngaire
Published: March 2021

BackgroundRapidly ageing populations means that many people now die in advanced age. This paper investigated public hospital and long-term care home costs in the 12 months before death in Māori and non-Māori of advanced age in New Zealand.MethodsData from an existing longitudinal study (LiLACS NZ) was used, in which 937 older New Zealanders were enrolled in 2010. At the time of this study, 213 Māori and 241 non-Māori in the cohort had died. National Health Index numbers were linked to the hospitalisation National Minimum Dataset to ascertain public hospitalisation and care home costs in the last year of life. ResultsThe average total publicly funded hospital and long-term care home costs in the 12 months prior to death were $16,211 and $17,351 for Māori and non-Māori respectively. Non-Māori tended to have long lengths of stay in their last year of life, and non-Māori men had the highest proportion with high costs and long lengths of stay in care homes. Costs in the last year of life were 8.1 times higher in comparison to costs for individuals who did not die in the same time period. ConclusionDespite New Zealand’s commitment to providing an equitable level of healthcare, this study illustrated that ethnic and gender disparities are still apparent at the end of life. This raises questions as to whether money at the end of life is being spent appropriately, and how it could potentially be more equitably targeted to meet the diverse needs of older people and their families.
One-Year Outcomes of Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients Regarding Preoperative BMI, Gender, and Age
Authors: Tabasi Mohsen , Farsimadan Marziye , Iranpour Hamidreza , Elyasinia Fezzeh , Yazdannasab Mohammad Reza , Siadat Seyed Davar , Soroush Ahmadreza
Published: March 2021

The outcome of laparoscopic sleeve gastrectomy (LSG), one of the most common bariatric surgery (BS) procedure, may differ depending on the patient’s age, gender, preoperative BMI. In this study, we aimed to evaluate the efficacy of LSG technique on weight loss, obesity-associated co-morbidities and complications in patients undergoing LSG over three months and one year, regarding their age, gender, and BMI. The LSG associated complications in participants regarding their preoperative BMI (<39.9 and >39.9), age (30-40 and 40-50), and gender were assessed after 2 3 and 12 months. Besides, the remission and improvement rates of comorbid conditions in patients were examined after 12 months of LSG. Our results showed that LSG led to a significant weight loss in the resolution of obesity-associated co-morbidities and different complications after one year. No significant difference was found in the improvement and the resolution of obesity-associated co-morbidities according to gender. Also, the class 3 patients had significantly higher rates of hearing loss after 12 months and had higher levels of depression and brittle nails three months after the surgery. The younger patients also showed a significantly higher percentage of dry skin, intolerance to bread, and menstrual disorder compared to the older group.
M2 macrophage-secreted Slit3 intensifies sympathetic nerve function in adipose tissue and enhances thermogenesis: A long-term cold adaption way
Authors: Wang Yina , Tang Yan , He Zhihui , Ma Hong , Li Jiashen , Liu Yang , Yang Qiqi , Pan Dongning , Qian Shu-Wen , Tang Qi-Qun
Published: March 2021

Beiging of white adipose tissue (WAT) is capable of adaptive thermogenesis and dissipating energy. The beiging processes have been associated with the increase of anti-inflammatory M2 macrophages, however the function of M2 macrophage on beiging and the underlying mechanism are not fully understood. Here we identified a macrophage cytokine Slit3 by analyzing the transcriptome of M2 macrophages collected with FACS in inguinal WAT (iWAT) of mice after cold exposure. Once released from macrophages, Slit3 bound to the ROBO1 receptor on sympathetic neuron and activated tyrosine hydrolase (TH) through PKA and CaMKⅡ signaling, and thus stimulated norepinephrine (NE) synthesis and release. NE acts on adipocytes and stimulate thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT depot acquired local adipocytes with beiging phenotype and enhanced thermogenesis. In addition, mice bearing the myeloid inactivation of Slit3 were cold intolerant and gained more weight due to the lowered metabolic rate. Collectively, we demonstrate Slit3 is a macrophage cytokine and promotes beiging and thermogenesis through intensifying the sympathetic nerve function. As the expanded M2 macrophages are integral cell population in adipose tissue, the macrophage-Slit3-sympathetic neuron-adipocyte axis assures the long-term cold adaption.
Direct Evidence of Cobalt Oxyhydroxide Formation on a La0.2Sr0.8CoO3 Perovskite Water Splitting Catalyst
Authors: Boucly Anthony , Artiglia Luca , Fabbri Emiliana , Palagin Dennis , Aergerter Dino , Pergolesi Daniele , Novotny Zbynek , Comini Nicolo , Diulus J. Trey , Huthwelker Thomas , Ammann Markus , Schmidt Thomas
Published: March 2021

Understanding the mechanism of oxygen evolution reaction (OER) on perovskite materials is of great interest to tailor the synthesis of better catalyst materials. Despite the huge amount of literature reports, the complexity of catalytic systems and scarce in situ and operando surface sensitive spectroscopic tools render the detection of active sites and the understanding of the reaction mechanisms challenging. Here, we carried out and compared in situ and ex situ ambient pressure X-ray photoelectron spectroscopy experimental procedures on a La0.2Sr0.8CoO3 perovskite OER catalyst. Experimental results show that segregated surface strontium, which is present in the as prepared sample, is leached into the electrolyte after immersion, leading to surface cobalt active sites enrichment. Such cobalt-enriched oxide surface evolves into a new phase, whose spectral feature is detected in situ, during/after OER. With the help of theoretical simulations, such species is assigned to cobalt oxyhydroxide, providing a direct evidence of its crucial role in the reaction.
‘Relearning How to Think’: A Brief Online Intervention to Modify Biased Interpretations in Emotional Disorders. Study Protocol for a Randomised Controlled Trial
Authors: Nieto Inés , Vazquez Carmelo
Published: March 2021

Background: Cognitive biases seem to play an important role in the development and maintenance of emotional disorders such as depression and anxiety. Novel procedures, known as Cognitive Bias Modification (CBM), aim to reduce these dysfunctional information processing modes. This study develops a brief online intervention program to modify biased interpretations in depression and anxiety, overcoming some methodological issues that have been addressed in previous literature. Methods: Volunteer participants will be recruited via social media, posters and universities. They will be randomly assigned to an experimental group or a waiting list control group. Both groups will attend two assessment sessions at the lab. The assessments will consist of questionnaires measuring cognitive and emotional variables as well as three experimental tasks to measure cognitive biases (i.e., attention, memory and interpretation). After the first assessment session, only participants in the experimental group will receive a link to follow the four-sessions program at home. All participants will receive, via email, follow-up questionnaires two weeks and three months after the second assessment session.Discussion: This study will test an online program potentially beneficial to modify cognitive variables in disorders such as depression and anxiety. Several limitations of previous CBM procedures are addressed and the impact of the program both on cognitive performance and clinical symptoms will be explored.Trial registration: This trial was prospectively registered on June 17, 2019 with the ClinicalTrials.gov NCT03987477
Spindle cell variant of medullary thyroid carcinoma: a clinicopathologic study of four cases
Authors: Wang Yan Xia , Yang Shoujing
Published: March 2021

BackgroundMedullary thyroid carcinoma (MTC) is a malignant tumor derived from C cells. It accounts for about 10% of all thyroid malignancies. More than 14 histological variants have been described. Among them, spindle cell variant is extremely rare.Case presentationHere we describe 4 cases of spindle cell variant of MTC collected from 2012 to 2019. Ultrasound showed solid and hypoechoic nodules. Three patients underwent total thyroidectomy and regional lymph node dissection, and 1 patient underwent thyroid mass resection. Histologically, the tumors showed spindle shaped cells in bundles or interlaced arrangement, separated by hyalinised fibrous stroma that contained amyloid deposits. Immunohistochemistry showed that the tumor cells were positive for calcitonin, chromogranin A, synaptophysin, CD56, and TTF-1, but negative for other lineage-specific markers.ConclusionsWe report 4 rare cases of spindle cell variant of MTC. Due to its rarity and special morphology, the diagnosis of spindle cell variant MTC relies on its morphology and immunohistochemical markers to avoid misdiagnosis.
Current issues facing disaster nursing education in Saudi Arabia
Authors: Brinjee Duaa , Thobaity Abdulellah Al , Ahmari Waleed Al , Almalki Mohammed
Published: March 2021

Background: : An important aspect of disaster preparedness for nurses is that they be ready to respond with a high level of competence. This scoping review aimed to identify current issues related to the education and training of disaster nurses in Saudi Arabia.Methods: This scoping review was conducted using the Joanna Briggs Institute (JBI) methodology. The search involved several different databases in the Saudi Digital Library (SDL), including CINAHL, Science Direct, Scopus, Wiley, and the Education Resources Information Center (ERIC). The search keywords were “disaster,” “nursing,” “education,” “training,” “knowledge,” and “preparedness.” In addition, specific inclusion and exclusion criteria were applied to narrow down the search to only relevant articles. Results: Several gaps in the education of disaster nurses were found in the review, which can be summarized in five different domains: insufficient simulations and drills, inadequate education programs, a lack of formal education, difficulty following guidelines, and difficulty accessing up-to-date educational resources.Conclusion: It is imperative that the highlighted issues related to disaster nursing education in Saudi Arabia be addressed to further develop the educational system in this regard. Future research should aim to determine how to address these issues to enhance the performance of nurses during disaster situations.
Apatinib Enhances Chemosensitivity of FLT3-ITD Mutations acute Myeloid Leukemia Cells to Homoharringtonine Via VEGFR2 Pathway
Authors: Shi Yuanfei , Zhang Yan , Shen Huafei , Ye Xiujin , Jin Jie , xie wanzhuo
Published: March 2021

Purpose: The significance of vascular endothelial growth factor receptor (VEGFR)-3 in numerous solid tumors and acute myeloid leukemia (AML) has been demonstrated, but Apatinib remains largely unexplored. In this study, we explored whether Apatinib combined with HHT could kill AML cell lines and its possible mechanisms. Methods: All cell lines were treated with Apatinib and HHT in different concentrations with control, Apatinib alone, HHT alone, and Apatinib combined with HHT. The changes of IC50 were measured by CCK8 assay, apoptosis rate, cell cycle, and mitochondrial membrane potential in each group were measured by flow cytometry. Finally, the possible cytotoxicity mechanism was analyzed by Western blotting. Results: Our results noted that Apatinib combined with HHT remarkably inhibited cell proliferation, reduced the capacity of colony-forming, and induced apoptosis and cell cycle arrest in AML cells. Mechanistically, Apatinib and HHT play a role as a suppressor in the expression of VEGFR2 and the downstream signaling cascades, such as the PI3K, MAPK, and Stat3 pathways. Conclusion: Our preclinical data demonstrate that Apatinib combined with HHT exerts a better anti-leukemia effect than Apatinib alone by inhibiting the VEGFR2 signaling pathway, suggesting the potential role for Apatinib and HHT in the treatment of AML.
Prognostic Factors and Epidemiology of Open Globe Injuries from Western Sydney: A Twelve-Year Review
Authors: Ho Haochi , Foo Jane , Li Yi-Chiao , Bobba Samantha , Go Christopher , Chandra Jaya , Fung Adrian
Published: March 2021

BackgroundTo identify prognostic factors determining final visual outcome following open globe injuries.MethodsRetrospective case series of patients presenting to Westmead Hospital, Sydney, Australia with open globe injuries from 1st January 2005 to 31st December 2017. Data collected included demographic information, ocular injury details, management and initial and final visual acuities.ResultsA total of 104 cases were identified. Predictors of poor final visual outcomes included poor presenting visual acuity (p < 0.001), globe rupture (p < 0.001), retinal detachment (p < 0.001), Zone III wounds (p < 0.001), hyphema (p=0.003), lens expulsion (p = 0.003) and vitreous hemorrhage (p < 0.001). Multivariate analysis demonstrated presenting visual acuity (p < 0.001), globe rupture (p = 0.013) and retinal detachment (p = 0.011) as being statistically significant for predicting poor visual outcomes. The presence of lid laceration (p = 0.197) and uveal prolapse (p = 0.667) were not significantly associated with the final visual acuity. ConclusionsPoor presenting visual acuity, globe rupture and retinal detachment are the most important prognostic factors determining final visual acuity following open globe injury.
Investigation of Transient Eye Closure associated with Bright light in the Patients with Intermittent Exotropia
Authors: Choi Won Jong , Jang Yeonji , Kim Seung-Joon , Jung Jae Ho
Published: March 2021

Background: To present a simple method to evaluate transient eye closure (TEC) under bright light using binocular pupillometry in children with intermittent exotropia (IXT). Methods: Sixty-one children with IXT were studied using binocular pupillometry. Each patient was exposed to each phase as follows: scotopic phase (darkness) for 3,300 ms, mesopic phase for 200 ms, scotopic phase for 3,300 ms, low-intensity white light phase (10 cd/m2) for 200 ms, scotopic phase for 3,300 ms, and high-intensity white light phase (100 cd/m2) for 200 ms. TEC was present if the subject closed eyes immediately more than half in response to light, compared with the one in the scotopic phase. We assessed the agreement between TEC and self-reporting photosensitivity, and also evaluated the associated factors for the presence of TEC in IXT patients.Results: With the new method to evaluate TEC under different light intensities, 27 (44.3%) of the 61 IXT patients showed TEC, and 34 (55.7%) did not demonstrate TEC. TEC under high-intensity white light had a strong correlation with photosensitivity (r = 0.77). The smaller angle of deviation at near was associated with the presence of TEC, with statistical significance (p = 0.04). Normal sensory status at distance was significantly associated with TEC (p < 0.01). Multivariate analysis using multiple logistic regression analysis showed that normal sensory status was significantly associated with TEC (p = 0.02).Conclusions: The test using binocular pupillometry is useful in identifying TEC related to bright light, and the presence of TEC was strongly correlated with photosensitivity in patients with IXT.
Reaction products of Sm2Zr2O7 with calcium-magnesium- aluminum-silicate (CMAS) and their evolution
Authors: Wang Yinghua , Ma Zhuang , Liu Ling , Liu Yanbo
Published: March 2021

During flight, many silicates (sand, dust, debris, fly ash, etc.) are ingested by an engine. They melt at high operating temperatures on the surface of Thermal barrier coatings (TBCs) to form calcium-magnesium-aluminum-silicate (CMAS) amorphous settling. CMAS erodes TBCs and causes many problems, such as composition segregation, degradation, cracking, and disbanding. As a new generation of TBC candidate materials, rare-earth zirconates (Sm2Zr2O7) have good CMAS resistance properties. The reaction products of Sm2Zr2O7 and CMAS and their subsequent changes were studied by the reaction of Sm2Zr2O7 and excess CMAS at 1350°C. After 1 h of reaction, Sm2Zr2O7 powders were not completely eroded. The reaction products were Sm-apatite and c-ZrO2 solutions. After 4 h of reaction, all Sm2Zr2O7 powders were completely eroded. After 24 h of reaction, Sm-apatite disappeared, and the c-ZrO2 solution remained.
Brain region-specific spread of Lewy body pathology in synucleinopathies is governed by α-synuclein conformations.
Authors: Bartels Tim , de Boni Laura , Watson Aurelia Hays , Zaccagnini Ludovica , Kim Nora , Sanderson John , Jiang Haiyang , Martin Elodie , Cantlon Adam , Rovere Matteo , Liu Lei , Sylvester Marc , Lashley Tammaryn , Dettmer Ulf , Jaunmuktane Zane
Published: March 2021

The α-synuclein protein (αS) is the major constituent of pathological neuronal inclusions both in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) with differential brain region-specific pathology patterns and clinical presentations. Two hypotheses that were recently put forward were either that of brain-region specific vulnerability or that of different αS aggregates, “strains”, that would affect different brain regions via “prion-like” spread. What governs these patterns, their hypothesized “prion-like” progression and region-specific vulnerability to αS aggregation in different synucleinopathies is still largely unknown. Data collected in the last decade suggests that αS can exhibit in different conformations under physiological and/or pathological conditions, which in turn help govern aggregation propensity. The cytosolic unfolded, monomeric form of αS (αSCU) is aggregation-prone and can misfold into soluble, toxic oligomers, protofilaments, and amyloid fibrils with self-templating properties, while the cytosolic helically folded, multimeric form (αSCH) resists disease-associated changes.
Impact of BRCA Mutation on the Survival and Risk of Contralateral Breast Cancer in Asian Breast Cancer Patients
Authors: Lin Po-Han , Chen Shin-Cheh , Tseng Ling-Ming , Chang King-Jen , Huang Ai-Chu , Cheng Kuo-Chih , Yang Karen , Wu Hui-Chen , Chao Tsu-Yi , Chang Yuan-Ching , Lin Peng-Chan , Kuo Wen-Hung , Kuo Wen-Lin , Lin Ching-Hung , Chen Huo-Mu , Yeh Dah-Cherng , Liu Liang-Chih , Liu Chun-Yu , Wang Ming-Yang , Lo Chiao , Lu Yen-Shen , Huang Chiun-Sheng
Published: March 2021

Purpose Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. MethodsA total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical pathologic characteristics, survival and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. Results The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years-old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, p<0.001). The risk of CBC was significantly higher in BRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. ConclusionOur study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.
Pyridoxine Stimulates Filaggrin Production in Human Epidermal Keratinocytes
Authors: Fujishiro Miyuki , Yahagi Shoichi , Takemi Shota , Sakai Takafumi , sakata ichiro
Published: March 2021

Pyridoxine (PN), one of the vitamers of vitamin B6, plays an important role in the maintenance of epidermal function and is used to treat acne and rough skin. Clinical studies have revealed that PN deficiency causes skin problems such as seborrheic dermatitis and stomatitis. However, the detailed effects of PN and its mechanism of action in epidermal function are poorly understood. In this study, we examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN specifically causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation. In addition, PN treatment caused an increase in the production of filaggrin protein in a concentration-dependent manner. Treatment with P2x purinoceptor antagonists, namely, pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate and TNP-ATP hydrate, induced an increase in the filaggrin protein levels. Moreover, we showed that elevated filaggrin production induced upon PN treatment was suppressed by ATP (known as P2x purinoceptor agonist). This study is the first to report that PN causes an increase in filaggrin transcription and production, and these results suggest that PN-induced filaggrin production may be a useful target as a daily care component in atopic dermatitis, wherein filaggrin levels are specifically reduced.