bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Small-Molecule Inhibitor Displays Its Therapeutic Potency Through Mitochondria-Mediated Apoptosis And Autophagy In Melanoma
Authors: Bai Jun , Wang Hailan , Sun Changzhen , Wang Jianv , Liu Li , Zhang Qingbi
Published: December 2021

Melanoma is the most aggressive skin cancer with high mortality. It is vital to develop novel low toxicity drugs with anti-proliferation activity and metastasis suppressive activity in melanoma. Here, we reported a novel anti-tumor drug SCZ0148, and then investigated its inhibition effect on melanoma. The anticancer efficacy of SCZ0148 was confirmed by using cytotoxicity test, colony formation assay, wound-healing assay, cell apoptosis detection, mitochondrial potential assay, reactive oxygen species (ROS) production and western-blot analysis. The cytotoxicity test showed that SCZ0148 inhibited melanoma cell lines proliferation in a dose- and time-dependent manner without obvious toxicity and side effects on normal cells. The results of the colony formation assay were in agreement with the cytotoxicity test. In addition, SCZ0148 induced melanoma cell apoptosis and promoted cell destructive autophagy through the ROS-mediated mitochondrial apoptosis pathway. Notably, SCZ0148 significantly inhibited the migration of melanoma cells through the matrix metalloprotein 9 (MMP-9) mediated pathway. In conclusion, these findings suggest that SCZ0148 may be a potential therapeutic drug to inhibit the proliferation and metastasis of melanoma.
A 10-year Retrospective Study of Lung Cancer in Uganda
Authors: Bogere Naghib , Bongomin Felix , Katende Andrew , Omaido Blair Andrew , Namukwaya Elizabeth , Mayanja-Kizza Harriet , Walusansa Victoria
Published: December 2021

Background: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at Uganda Cancer Institute (UCI). Methodology: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. Results: Of the 207 patients enrolled, 56.5% (n=117) were female, median age was 60 years (range: 20-94), 78.7% (n=163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n=48). Majority had non-small cell lung cancer (96.6%, n=200) with 74.5% (n=149) adenocarcinoma and 19% (n=38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n=199) in stage IV. Chemotherapy (44.9%, n=93) and biological therapy (34.8%, n=72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7%, 29.7%, 11.8% and 1.7% respectively. The median survival time was 4.4 months and was not different between NSCLC and SCLC (4.5 vs. 3.9 months respectively, p=.335). Conclusion: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer predominantly occurring in females and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early screening and improve outcomes.
Aircraft Detection in Remote Sensing Image based on Multi-scale Convolution Neural Network with Attention Mechanism
Authors: Wang Xianfeng , Yu Changqing , Huang Lei , Zhang Shanwen
Published: December 2021

Detecting aircraft from remote sensing image (RSI) is an important but challenging task due to the variations of aircraft type, size, pose, angle, complex background and small size of aircraft in RSIs. An aircraft detection method is proposed based on multi-scale convolution neural network with attention (MSCNNA), consisting of encoder, decoder, attention and classification. In MSCNNA, the multiple convolutional and pooling kernels with different sizes are utilized to learn the multi-scale discriminant features, and the global attention mechanism (GAM) is employed to capture the spatial and channel dependencies and adaptively preserve the relationships of the entire image. Compared with the standard deep CNN, multi-scale convolution neural networks (CNN) and GAM are integrated to learn the multi-scale features for aircraft detection, especially small aircrafts. Experiment results on the aircraft image dataset of the public EORSSD dataset show that the proposed method outperforms the state-of-the-art method on the same dataset and the obtained multi-size aircraft edge is clearer.
An Extended Kalman Filtering Technique for Geodetic First Order Data Assimilation
Authors: Kalu Ikechukwu , Ndehedehe Christopher E. , Okwuashi Onuwa , Eyoh Aniekan E.
Published: December 2021

Data assimilation allows merging of different sources of data to estimate possible states of a system as it evolves in time. This therefore supports the idea of combining classical observations with Global Positioning System (GPS) observations to improve the integrity of first order geodetic controls in Nigeria. Given that these geodetic controls, which were established using traditional techniques and whose algorithms are still in use, the task of optimizing the coordinate values of these monuments to improve efficiency and accuracy in conventional geodetic operations around Nigeria is still a challenge. This study introduces the Extended Kalman Filter (EKF) technique for the modeling of these observations and their uncertainties in addition to exogenous noise, which is handled by an approximate set-valued state estimator. The proposed EKF provides a feasible linearization process in merging classical and GPS data collection modes as shown in our study. For each discrete time in the analysis step, it employs the Kalman gain computation, which attempts to weigh and balance uncertainties between the estimate and observation before proceeding to the analysis step. In this setup, the EKF constrains the system state in order to balance and strengthen the integrity of these first order monuments. The relationship of the derived system state with GPS coordinates (R2 = 0.85) and classical observations (R2 = 0.92) over Nigeria using a multi linear regression analysis is considerably strong. This outcome provides insight to the performance of the test algorithm and builds on the usefulness of data assimilation techniques in geodetic operations.
The Objective Conditions Study and Optimization of Digital Imaging System on Color Measurement：Case with Jadeite
Authors: Liu Ziyuan , Guo Ying , Shang Yanran , Yuan Bin
Published: December 2021

The application of digital imaging to color measurement is more and more extensive, which also provides new ideas for gemology. In this paper, the single-factor experiment method and orthogonal experiment design are used to study the influence parameters of the digital imaging system (DIS) on gem color measurement. Among them, the illuminance has the most significant impact on the measurement results, followed by the exposure time, and the change of the measurement distance has an insignificant impact on the results; through range analysis and analysis of variance, the most suitable measurement parameters for red jadeite are 1600lx, 12500ms, 25cm.
Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma
Authors: Zhao Ju , Yang Hanshan , Hu Hui , Liu Chao , Wei Min , Zhao Yumei , Chen Yudan , Cui Yongxia , Chen Ping , Xiong Kang , Lu Yun , Yang Linglin , Yang Hongru
Published: December 2021

Purpose: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). We aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in NPC patients.Patients and methods: We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescent staining in 182 NPC tissue samples.Results: A significant correlation was identified between the PD-L1 and Siglec-15 expression (P=0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression were associated with improved overall survival (P=0.025) and Siglec-15 expression were associated with improved distant failure-free survival (P=0.048). Meanwhile, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of overall survival (P=0.020) and distant failure-free survival (P=0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression were found to have significant advantages with regard to overall survival, compared to other groups (P=0.037).Conclusion: PD-L1 and Siglec-15 may represent novel biomarkers for predicting NPC patient prognosis. Siglec-15 could be considered as a potential target for the development of therapeutics for NPC treatment in the future.
A Decade of Molecular Preimplantation Genetic Diagnosis of 350 Blastomeres for Beta-Thalassemia Combined with HLA Typing, Aneuploidy Screening and Sex Selection in Iran
Authors: Keshvar Yeganeh , Sabeghi Solmaz , Sharifi Zohreh , Fatemi Kiyana Sadat , Fouladi Panti , Khah Shahrzad Younesi , Rahiminejad Faezeh , Joudaki Atefeh , Amini Masoume , Bagherian Hamideh , Novin MarefatGhaffari , Movahedin Mansoureh , Mojbafan Marzieh , Zeinali Sirous
Published: December 2021

Background: Preimplantation genetic diagnosis (PGD) has been developed to detect genetic disorders before pregnancy which is usually done on blastomeres biopsied from 8-cell stage embryos obtained from in vitro fertilization method (IVF).Here we report molecular PGD results for diagnosing of beta thalassemia (beta-thal) which are usually accompanied with evaluating chromosomal aneuploidies, HLA typing and sex selection.Methods: In this study, haplotype analysis was performed using short tandem repeats (STRs) in a multiplex nested PCR and the causative mutation was detected by Sanger sequencing.Results: We have performed PGDs on 350 blastomeres from 55 carrier couples; 142 blastomeres for beta-thal only, 75 for beta-thal and HLA typing, 76 for beta-thal in combination with sex selection, and 57 for beta-thal and aneuploidy screening. 150 blastomeres were transferable, 15 pregnancies were happened, and 11 babies born.We used 6 markers for beta-thal, 36 for aneuploidy screening, 32 for sex selection, and 35 for HLA typing. To our knowledge combining all these markers together and the number of STR markers are much more than any other studies which have ever done.Conclusions: PGD is a powerful diagnostic tool for carrier couples who desire to have a healthy child and wish to avoid medical abortion.
Evaluation of Postsurgical Stability And Condylar Morphology In Skeletal Class II Patients With Condylar Resorption Following Orthognathic Surgery
Authors: Wang Minjiao , Zhao Hanjiang , Wang Xiangyu , Qian Yifeng , Yu Hongbo , Shen Steve GF
Published: December 2021

Background: To retrospectively evaluate postsurgical stability and condylar morphology for skeletal class II malocclusion patients with condylar resorption (CR) treated with orthognathic surgery.Methods: Thirty-five patients treated with combined orthodontic and orthognathic surgery between 2014 and 2018 were enrolled in this retrospective study. CT scans were acquired preoperatively (T0), 2–7 days after surgery (T1), and 1 year postoperatively (T2). The amount of mandibular advancement, postsurgical relapse, condylar morphology and joint spaces were analysed respectively. Statistical analysis was performed using R, version 3.4.3 (R Development Core Team 2010).Results: The average mandibular advancement and counter-clockwise rotation were 5.51 mm and -2.82 degrees respectively. The average relapse was 1.08 mm (19.6% of the advancement) and 1.13 degrees. The condylar volume showed a postoperative reduction of 161.86 mm3(13.7% of initial condylar volume). AJS increased after surgery and gradually returned to its original state, while SJS and PJS decreased and remained stable. Surgical advancement of B point was significantly correlated with skeletal relapse. The optimal cut-off values were as follows: MP-FH (40.75°); ramus height (51.125 mm); SJS (1.63 mm); surgical displacement (4.72 mm); CCR (-4.3°); AJSC (1.07 mm).Conclusions: Skeletal class II patients with CR have a high risk of postsurgical condylar resorption, which was most related to nonsurgical risk factors such as gender(female) and condylar angle. Condylar had moved posteriorly to the concentric position after surgery and remained quite stable through the 1-year follow-up. Preoperative skeletal patterns such as lower ramus height and surgical procedures such as larger advancement of the mandible were closely associated with sagittal relapse of the mandible.
Design and Transition of an Emergency E-Learning Pathology Course for Medical Students Evaluation of a Novel Course Concept
Authors: Holzmann-Littig Christopher , Jedlicska Nana , Wijnen-Meijer Marjo , Liesche-Starnecker Friederike , Schmidt-Bäse Karen , Weimann Katja , Konukiewitz Björn , Schlegel Jürgen
Published: December 2021

Background
Around the world, medical schools emergency-created countless e-learning offerings during the COVID-19 pandemic to provide instruction despite the pandemic. The question now is how to capitalize on this momentum of digitization and how to harness the medical e-learning content created for the future. We have analyzed the transition of a pathology course to show what needs to be considered during such a transition.
Methods
In the summer semester of 2020, the pathology course at the Technical University of Munich was completely converted to an asynchronous online course. This content was adapted in winter 2021 and incorporated into a flipped classroom concept in which research skills were trained at the same time.
Results
Screencasts and lecture recordings were the most popular asynchronous teaching formats. Students reported developing a higher interest in pathology and research through group work. The amount of content was very challenging for some students.
Conclusion
Flipped classroom formats are a viable option when using the pre-existing contents. We recommend checking the contents for technical and didactic quality and optimizing them if necessary. Content on research skills can be combined very well with clinical teaching content.
Evaluation of The 10 Warning Signs In Immunodeficient Patients: Additional Suggestions
Authors: Eldeniz Fadime Ceyda , Gül Yahya , Yorulmaz Alaattin , Güner Şükrü Nail , Keles Sevgi , Reisli İsmail
Published: December 2021

Objective: Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID are sufficient for the diagnosis of SID, and explored the possibility of additional signs.Methods: This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each “Yes” answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. Results: The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. Conclusions: The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.
Cholesterol Sensor SCAP Contributes to Sorafenib Resistance by Regulating Autophagy in Hepatocellular Carcinoma
Authors: Li Danyang , Yao Yingcheng , Rao Yuhan , Huang Xinyu , Wei Li , You Zhimei , Zheng Guo , Hou Xiaoli , Su Yu , Varghese Zac , Moorhead John F , Chen Yaxi , Ruan Xiong Z
Published: December 2021

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the fourth leading cause of cancer-related death worldwide. Sorafenib is currently acknowledged as a standard therapy for advanced HCC. However, acquired resistance substantially limits the clinical efficacy of sorafenib. Therefore, further investigations of the associated risk factors are highly warranted.Methods: We analysed a group of 78 HCC patients who received sorafenib treatment after liver resection surgery. The expression of SCAP and its correlation with sorafenib resistance in HCC clinical samples were determined by immunohistochemical analyses. Overexpression and knockdown approaches in vitro were used to characterize the functional roles of SCAP in regulating sorafenib resistance. The effects of SCAP inhibition in HCC cell lines were analysed in proliferation, apoptosis, and colony formation assays. Autophagic regulation by SCAP was assessed by immunoblotting, immunofluorescence and immunoprecipitation assays. The combinatorial effect of a SCAP inhibitor and sorafenib was tested using nude mice.Results: Hypercholesterolemia was associated with sorafenib resistance in HCC treatment. The degree of sorafenib resistance was correlated with the expression of the cholesterol sensor SCAP and consequent deposition of cholesterol. SCAP is overexpressed in HCC tissues and hepatocellular carcinoma cell lines with sorafenib resistance, while SCAP inhibition could improve sorafenib sensitivity in sorafenib-resistant HCC cells. Furthermore, we found that SCAP-mediated sorafenib resistance was related to decreased autophagy, which was connected to decreased AMPK activity. A clinically significant finding was that lycorine, a specific SCAP inhibitor, could reverse acquired resistance to sorafenib in vitro and in vivo.Conclusions: SCAP contributes to sorafenib resistance through AMPK-mediated autophagic regulation. The combination of sorafenib and SCAP targeted therapy provides a novel personalized treatment to enhance sensitivity in sorafenib-resistant HCC.
Novel Biomarker NEDD1 and Its Analysis in Hepatocellular Carcinoma
Authors: Ding Xiaopeng , Yu Jiahao , Shi Xin , Li Kangwei , Ma Shuoyi , Ren Pengwei , Xuan Guoyun , Han Ying , Zhou Xinmin
Published: December 2021

Background: NEDD1 (NEDD1 Gamma-Tubulin Ring Complex Targeting Factor) plays a crucial impact in regulating cell cycle and the development of scirrhous gastric cancer. However, the role of NEDD1 hasn’t been reported in hepatocellular carcinoma (HCC) so far. The aim of this research is to explore the role of NEDD1 on the development and prognosis of HCC. Methods: HCC-related data were download from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA) were conducted by the LinkedOmics database. Results: The expression of NEDD1 has significant difference between tumor and adjacent normal tissues in HCC (P＜0.01). We also found that NEDD1 was an independent risk factor in HCC patients (HR 1.643, 95%CI 1.125–2.398; P = 0.01). The study also demonstrated that NEDD1 expression was significantly relevant to the expression of several immune checkpoint genes, including CTLA-4, PD-L1 and PD-1. GSEA revealed that Cell cycle, MicroRNAs in cancer and Ribosome pathways were significantly enriched in NEDD1 overexpression phenotype. By integrating NEDD1 with other relevant factors, we constructed the prognostic nomogram to help the improvement of the prognosis for patients with HCC. The data from the International Cancer Genome Consortium (ICGC) database were used as an independent external validation of our prognostic model. Conclusion: The expression level of NEDD1 was negatively correlated to the prognosis of HCC patients and it may be a promising therapeutic target of HCC, which probably be able to predict the efficacy of immunotherapy for HCC patients.
Nicotinamide Riboside Promotes Mfn2-mediated Mitochondrial Fusion in Diabetic Hearts through the SIRT1-PGC1α-PPARα Pathway
Authors: Hu Lang , Guo Yanjie , Song Liqiang , Wen He , Sun Nan , Wang Ying , Qi Bingchao , Liang Qi , Geng Jing , Liu Xuteng , Fu Feng , Li Yan
Published: December 2021

Background: Myocardial dysfunction is associated with an imbalance in mitochondrial fusion/fission dynamics in patients with diabetes. However, effective strategies to regulate mitochondrial dynamics in the diabetic heart are still lacking. This study investigated whether Nicotinamide riboside (NR) supplementation protects against diabetes-induced cardiac dysfunction by regulating mitochondrial fusion/fission and further explored the underlying mechanisms.Methods: Obese diabetic (db/db) and lean control (db/+) mice were each given NR oral supplementation in this study. NAD+ Content was determined in mice hearts and primary neonatal cardiomyocytes. Cardiac function was detected by echocardiography. Mitochondrial dynamics were analyzed by transmission electron microscopy in vivo and by confocal microscopy in vitro. Results: Here, we show an evident decrease in NAD+ level and mitochondrial fragmentation in the hearts of leptin receptor-deficient diabetic (db/db) mouse model. NR supplementation significantly increased NAD+ content in the diabetic heart tissues. Furthermore, NR treatment increased Mfn2 expression, promoted mitochondrial fusion, suppressed oxidative stress, reduced cardiomyocyte apoptosis and consequently improved cardiac function in db/db mice. In neonatal primary cardiomyocytes cultured in a high-glucose/high-fat medium, NR treatment also promoted mitochondrial fusion, suppressed mitochondria-derived ROS production and reduced cardiomyocyte apoptosis, which were all reversed when Mfn2 was knocked down. Mechanistically, chromatin immunoprecipitation (ChIP) and luciferase report assay analysis revealed that PGC1α and PPARα interdependently regulated Mfn2 transcription by binding to its promoter region. NR treatment elevated NAD+ levels and activated SIRT1, resulting in the deacetylation of PGC1α and promoting the transcription of Mfn2. Furthermore, the inhibition of SIRT1, PGC1α or PPARα blunted the positive effects of NR supplementation on Mfn2 expression and mitochondrial fusion. Conclusion: NR attenuates the development of diabetes-induced cardiac dysfunction by promoting mitochondrial fusion through the SIRT1-PGC1α-PPARα pathway, with PGC1α and PPARα being the interdependent co-regulatory factors for Mfn2. The promotion of mitochondrial fusion via oral supplementation of NR may be a potential strategy for delaying cardiac complications in patients with diabetes.
Gravida Serum POSTN and PAPPA as the Potential Biomarkers for Fetal Congenital Heart Disease Based on Quantitative and Qualitative Proteomics
Authors: Xia Yi , Cheng Lin , Duan Jie , Ma Jianhong , Liu Juan , Lu Dan , Zhang Yuanzhen
Published: December 2021

Background: Fetal congenital heart disease is the most common congenital defect worldwide. It has some missed diagnoses and a lack of disease biomarkers. We aim to seek objective biomarkers for noninvasive prenatal diagnosis of fetal congenital heart disease to reduce the missed diagnosis and explore its mechanism,Methods: This study used data-independent acquisition and parallel reaction monitoring to explore potential protein biomarkers that co-exist in gravida serum and fetal amniotic fluid. Moreover, logistic regression and ROC curve to establish the diagnostic model of fetal congenital heart disease potential biomarkers and molecular biology experiments were performed to validate proteomics results and explore the mechanism. Results: Proteomics and bioinformatics results show that 12 proteins co-exist in gravida serum and amniotic fluid. We identified POSTN and PAPPA in GS as candidate biomarkers and established the diagnostic model with a sensitivity of 100%, a specificity of 95% and the AUC value of 0.968 to diagnose congenital heart disease. In addition, the results of ELISA, IHC, and RT-PCR were consistent with those of proteomics. Moreover, POSTN may involve in fetal congenital heart disease through the TGF-beta signaling pathway. Conclusion: It is the first time to find that POSTN and PAPPA in GS are related to fetal congenital heart disease, contributing to developing a novel noninvasive prenatal method to diagnose fetal congenital heart disease and reduce congenital disabilities.
Cyclic Experiments and Global Buckling Design of Steel-Angles-Assembled Buckling-Restrained Braces
Authors: Tong Jing-Zhong , Zhang En-Yuan , Guo Yan-Lin , Yu Chao-Qun
Published: December 2021

Compared with traditional BRB, the steel-angles-assembled buckling-restrained brace (SAA-BRB) is an innovative BRB with light-weight, accurate control of the geometrical dimensions, easy installation and convenient disassembly. The SAA-BRB is composed of an external restraining system and a cruciform-sectional inner core. The external restraining system is assembled by four steel angles with the connection of high-strength bolts, and the spacers are installed between the inner core and the restraining system. In this study, the hysteretic behavior of SAA-BRB was investigated by experiments and finite element (FE) simulations. Firstly, three SAA-BRB specimens with different restraining ratios were tested under cyclic loads to investigate the hysteretic performance. It was found that all specimens exhibited stable responses and satisfactory energy-dissipating capabilities during the whole loading process. Then, a refined FE model was established, and its validity in predicting the hysteretic responses of SAA-BRB was verified by the experiments. Moreover, based on the yielding criteria of the outmost fiber for the restraining member section, a design formula for the restraining ratio requirements to avoid global buckling of the SAA-BRB was deduced. Finally, extensive parametric analysis was conducted to verify the accuracy of the design formula by changing the geometric dimensions (the restraining ratio) of models. It was found that the proposed formula for the restraining ratio requirement could lead to a conservative prediction with reasonable accuracy, thus providing valuable references for global buckling design of SAA-BRBs in engineering practice.
Performance of the BinaxNOW COVID-19 Antigen Rapid Diagnostic Test for the Detection of SARS-CoV-2
Authors: Gonzalez Fernando A Ocampo , Moore Nicholas M
Published: December 2021

Background: Diagnosis of COVID-19 disease primarily relies on nucleic acid amplification tests (NAAT) that amplify and detect viral RNA in specimens. These methods are expensive and time consuming. Antigen-based rapid diagnostic tests can substantially decrease turnaround time.Methods: We analyzed paired anterior nares swabs collected from symptomatic patients and asymptomatic healthcare workers being tested COVID-19. One swab was used for a direct RDT and the results were compared to NAAT.Results: 89 paired specimens were evaluated. The positive percent agreement (PPA) for the antigen RDT was 68.2%, and the negative percent agreement (NPA) was 98.5%. Despite a low PPA, the Κ statistic was 0.733 indicating substantial agreement with the NAAT result. The median cycle number in paired specimens with concordant results was significantly lower than in discordant specimens (21.3 versus 32.3; P=0.003).Conclusions: The RDT showed modest PPA and high NPA when compared to NAAT. The quick TAT and use of an inexpensive test more frequently could be useful in settings in which results from NAAT testing is delayed.
Statin Therapy May Be Associated with Reduced Mortality Risk of Sepsis Patients: A Retrospective Study from the MIMIC-IV Database
Authors: Shi Jian , Zhou Shiyu , Chen Kerong , Dai Xingui , Li Lulan , Chen Zhongqing , Wu Feng , An Shengli , Zeng Zhenhua
Published: December 2021

BackgroundIt is controversial whether statin therapy is beneficial for sepsis patients. A large retrospective cohort study was conducted to evaluate the association between statin therapy and mortality in sepsis patients.MethodsAdult (≥18 years) sepsis patients were enrolled and divided into two groups: the statin group and the no-statin group. Data including demographic features, vital signs, laboratory tests, and comorbidities from MIMIC-IV v1.0 were extracted. Delirium was assessed via the Confusion Assessment Method for the ICU (CAM-ICU). Ninety-day mortality, 28-day mortality and the incidence of delirium after statin therapy were evaluated using multivariable logistic analysis, the PSM model and subgroup analysis based on univariate analysis. ResultsIn univariate analysis and multivariable logistic analysis, statin therapy showed a significant association with both reduced 28-day and 90-day mortality (90-day mortality: OR 0.58, 95% CI: 0.46-0.72, p<0.001; 28-day mortality: OR 0.47, 95% CI: 0.37-0.60, p<0.001), while no relationship was found between statin therapy and delirium (OR 0.92, 95% CI: 0.49-1.72, p=0.787). In further PSM model and subgroup analyses or sensitivity analysis, consistent results were shown. ConclusionStatin therapy is significantly associated with 28-day and 90-day mortality without decrease in the incidence of delirium.
The Correlation Between Novel Survival-related Alternative Splicing Signature and Prognostic Prediction and Immune Microenvironment in Clear Cell Renal Cell Carcinoma
Authors: Jian Wengang , Wang Gang , Yu Yipeng , Cai Licheng , Yu Yongchun , Xue Wei , Wang Tengda , Meng Yuyang , Xia Zhinan , Yao Wenhao , Zhang Cheng
Published: December 2021

BackgroundAlthough extensive researches related alternative splicing (AS) as the prognostic markers of patients in cancers, which remains unknown in clear cell renal cell carcinoma (ccRCC), especially in immunotherapy. Therefore, a novel survival-associated AS signature was established to predict prognosis of patients and explored its correlation with immune cell infiltration or immune checkpoint expression to explain the phenomenon of resistance to immunotherapy in ccRCC.Methodsccording to AS data, clinical information and gene expression data in ccRCC, overall survival-related AS events was identified and further the AS-related prognostic risk model established by LASSO regression and multi-Cox regression analysis was evaluated by Kaplan-Meier survival analysis, the ROC curves and a nomogram model. Then we clarified the biological processes and pathways by GSEA, and further measured the immune cell infiltration by ESTIMATE, CIBERSORT and ssGSEA. Finally we analysed the clinical features and immune features of different parental genes, and quested the splicing factors regulating riskScore-related AS events by Spearman correlation analysis.ResultsWe obtained the most significant 5 AS events, including C4orf19|69001|AT, UACA|31438|AP, FAM120C|89237|AT, TRIM16L|39629|AP and SEC31A|100881|ES, to establish the prognostic risk model, and further illustrated the stability and importance of the riskScore prognostic signatures. Then we found that in high risk group, most of the top 10 GO enrichments and the KEGG pathway were closely related to the immunity, and the higher immune cell infiltration, and higher expression of classic immune checkpoints such as PD1 and CTLA4. In addition, 6 different parental genes were obtained, including C4orf19, ARHGAP24 DNASE1L3, P4HA1, SLC39A14 and TAF1D. These 6 genes could not be the independent prognostic signatures, but the expression of these genes was closely related to immune cells infiltration and the expression of immune checkpoints. Finally, we got aberrant 52 splicing factors regulating riskScore-related AS events.ConclusionOur study discovered that overall survival-related AS events mediated by aberrant splicing factors can be constructed a prognostic risk model to predict prognosis of patiens and utilized to index the situation of immune cell infiltration and immune checkpoint expression that impact tumor immune microenvironment in ccRCC.
Cognitive performance and specific aspects of language processing are associated with Oldowan-like chert flaking and retouch
Authors: Gabrić Petar , Banda Marko , Karavanić Ivor
Published: December 2021

Experimental data suggesting a co-evolutionary relationship between Palaeolithic stone toolmaking, and cognition and language remain limited to indirect findings of neurophysiological studies. Furthermore, retouch and quartz flaking remain uninvestigated. We recruited thirteen subjects and taught them to produce quartz choppers and chert sidescrapers in either a verbal or gestural condition. Two raters rated on a 5-point scale the subjects’ performances on specific steps of the two stone toolmaking tasks. Subjects also performed on a neuropsychological battery encompassing visuospatial, executive functioning, and linguistic tasks. Given the small sample size, the results should be regarded as exploratory and preliminary. There was only limited evidence that verbal compared to gestural teaching facilitated acquisition. Quartz chopper manufacture was not associated with cognitive performance. Conversely, chert flaking and retouch were moderately and strongly associated with visuospatial working memory and executive functioning. Specific aspects of chert flaking were also associated with verbal fluency performance, showing, among others, moderate and strong positive associations with the productivity and rate of production of syntactically transitive verbs on action fluency. Controversially assuming similar results would have been obtained by testing extinct hominins, our results possibly suggest Oldowan hominins relied on modern-like visuospatial working memory and executive functioning during chert knapping. Furthermore, some prerequisites for aspects of action language and syntactic transitivity in modern humans might have been to some degree present in Oldowan hominin populations. We conclude by proposing that the quality of performance on Oldowan knapping may not reflect the full level of cognitive capacities of Oldowan populations.
Estimating the economic burden of typhoid in children and adults in Blantyre, Malawi: a costing cohort study
Authors: Limani Fumbani , Smith Christopher , Wachepa Richard , Chafuwa Hlulose , Meiring James , Noah Patrick , Patel Pratiksha , Patel Priyanka , Debellut Frédéric , Pecenka Clint , Gordon Melita A. , Bar-Zeev Naor
Published: December 2021

BackgroundTyphoid causes preventable death and disease. The World Health Organizationrecommends Typhoid Conjugate Vaccine for endemic countries, but introductiondecisions depend on cost-effectiveness. We estimated household and healthcareeconomic burdens of typhoid in Blantyre, Malawi.MethodsIn a prospective cohort of culture-confirmed typhoid cases at two primary- and areferral-level health facility, we collected direct medical, non-medical costs (2020 U.S. dollars) to healthcare provider, plus indirect costs to households.ResultsFrom July 2019-March 2020, of 109 cases, 63 (58%) were <15 years old, 44 (40%)were inpatients. Mean hospitalization length was 7.7 days (SD 4.1). For inpatients,mean total household and provider costs were $93.85 (95%CI: 68.87-118.84) and$296.52 (95%CI: 225.79-367.25), respectively. For outpatients, these costs were$19.05 (95%CI: 4.38-33.71) and $39.65 (95%CI: 33.93-45.39), respectively.Household costs were due mainly to direct non-medical and indirect costs, medicalcare was free. Catastrophic illness cost, defined as cost >40% of non-food monthlyhousehold expenditure, occurred in 48 (44%) households.ConclusionsTyphoid can be economically catastrophic for families, despite accessible free medicalcare. Typhoid is costly for government healthcare provision. These data make aneconomic case for TCV introduction in Malawi and the region and will be used to derivevaccine cost-effectiveness.
Genomic analyses identify biological processes of miR-125 mediated breast cancer cells
Authors: Guo Hongmei , Zhang Wei , Liu Guangqi , Chang Tingxiang , Gu Hanming
Published: December 2021

miRNAs contain suppressive and oncogenic properties to regulate the progression of cancers. The expression of miR-125b expression is reported to be consistently low in breast cancers. However, the function and mechanism of miR-125b are not fully understood in breast cancers. In our study, our objective is to identify the DEGs and biological processes in the miR-125b mediated breast cancer cells by analyzing the RNA-seq data. The GSE123358 dataset was produced by the Illumina HiSeq 2000 (Homo sapiens). The KEGG and GO analyses showed the mitochondria and endoplasmic reticulum oxidative phosphorylation pathways are the main processes in miR-125b mediated breast cancer. Moreover, we identified ten interactive molecules including UQCRQ, CALR, HNRNPU, ATP5G1, NDUFB11, UQCRH, HSP90B1, TGOLN2, SAP18, and XPOT. Thus, our study may benefit the treatment of breast cancer by using miR-125b.
Clinical characteristics and disease patterns of patients with relapsing polychondritis: a retrospective cohort
Authors: Wang Dong , Guan Lujia , Dong xin , Zhu Xiaofan , Tong Zhaohui
Published: December 2021

Background Relapsing polychondritis (RP) is a rare autoimmune disease affected various cartilage, Patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to allocated RP patients into two subgroups by chest computed tomography (CT) and compare the clinical features and disease patterns of each group.Methods A retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Patients were divided into two groups: respiratory involvement group and non-respiratory involvement group according to chest CT.Results In our study, respiratory involvement found in 59.7% (n=43) patients, which had higher rate of costochondritis, fewer rate of Inflammatory eye disease and auricular chondritis than those in non-respiratory involvement. Compared with non-respiratory involvement subgroup, The incidence of pulmonary infection marginally increased and those inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, further subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Finally, 5 patients died during the follow-up in this cohort with a median follow-up time of 6 years (range 3-8 years).Conclusion 59.7% of patients had respiratory involvement according to chest CT findings in our cohort, which had a strong inverse relationship between respiratory and auricular, ocular involvement. Increase inflammatory indexes were not correlated with pulmonary infection, suggesting that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not found significant in two subgroups.
Newborn skin maturity models for gestational age prediction
Authors: Reis Zilma Silveira Nogueira , Guimarães Rodney Nascimento , Romanelli Roberta Maia de Castro , Gaspar Juliano de Souza , Neves Gabriela Silveira , Vale Marynea Silva do , Nader Paulo de Jesus H , de Moura Martha David Rocha , Vitral Gabriela Luíza Nogueira , Reis Marconi Augusto Aguiar dos , Pereira Marcia Margarida Mendonça , Marques Patrícia Franco , Nader Silvana Salgado , Harff Augusta Luize , Beleza Ludmylla de Oliveira , de Castro Maria Eduarda Canellas , Souza Rayner Guilherme , Pappa Gisele Lobo , de Aguiar Regina Amélia Pessoa Lopes
Published: December 2021

A multicenter clinical trial evaluated the accuracy of a novel device to detect preterm newborns. A portable multiband reflectance photometric device assessed 781 newborns’ skin maturity and used machine learning models to predict reference gestational age, adjusting it to birth weight and antenatal corticosteroid therapy exposition. The day difference between the reference and the test had a median of -1.4 (IQR: -2.1). Using established methods such as comparator ultrasound and last menstrual period (LMP), the medians were 0 (IQR: 4) and 0.01 (IQR: 4), respectively. For prematurity discrimination, the area under the receiver operating characteristic curve (AUROC) was 0.986 (95% CI: 0.977 to 0.994). In newborns with absent or unreliable LMP, the intent-to-discriminate analysis showed that the test generated correct classifications 95.8% of the time. The assessment of the newborn's skin maturity adjusted by learning models promises accurate pregnancy dating at birth without the use of antenatal ultrasound reference.
Perceptions of Nursing Students Regarding Clinical Teaching and Learning During COVID-19 at Selected Higher Education Institutions in Lesotho
Authors: Nyangu Isabel , Rathobei Libuseng
Published: December 2021

Nursing students and their clinical instructors in higher education institutions are faced with challenges regarding their clinical teaching and learning strategies during the COVID-19 pandemic. This study aimed to determine the perceptions of nursing students regarding clinical teaching and learning during the COVID-19 pandemic. A non-experimental descriptive quantitative research design was used to collect data from 300 nursing students who were enrolled at selected higher education institutions in the 2021/22 academic year in Lesotho. Convenience sampling was used to recruit the respondents who completed a structured self-report questionnaire. Permission to conduct the study was granted by relevant authorities (ID147-2021). Data were analysed using the Statistical Package of Social Sciences (SPSS vs 23) and presented using tables and graphs and described analytically. The findings of the current study show that the minimum age of participants was 19 years and the maximum age was 39 years. The majority of respondents were female (69%: n=207) and studying for a BSc degree in Nursing and Midwifery (49%: n=146). Most nursing students had adequate knowledge, skills, and attitudes to prevent Covid-19 in the clinical area and simulation laboratories. They felt that clinical instructors and preceptors were available and competent to assist them in completing their clinical competencies and procedure file logbooks. Nursing students gained expertise in performing clinical procedures as they were able to perform return demonstrations in the simulation laboratory and clinical areas. Whilst clinical facilities and simulation laboratories had adequate Covid-19 prevention protocols and tools, there was inadequate personal protective equipment available. Conclusively, the perceptions of nursing students regarding clinical teaching and learning during Covid-19 were positive. More support for adequate personal protective equipment for nursing students remains crucial.
Prime n solutions of the Brocard’s Problem
Authors: Singh Devansh
Published: December 2021

In this paper on the [1]“Brocard’s Problem” , I have worked on case when n is prime and n divides m-1. Necessary conditions on m are given in Theorem and Corollaries.I used necessary and sufficient condition of primes. Assuming that n is prime and divides m-1, I applied Inverse Laplace Transform on the obtained equation and got a polynomial function which is easier to deal with. I worked with zero of the polynomial function and got lower bound of p which was not useful as p tends to infinity, but solving quartic equation which I have given at the end could give significant upper, lower bounds of p.What would happen to those upper, lower bounds if p tends to infinity?
A macroscopic link between interhemispheric tract myelination and cortico-cortical interactions during action reprogramming
Authors: Lazari Alberto , Salvan Piergiorgio , Verhagen Lennart , Cottaar Michiel , Papp Daniel , Werf Olof van der , Gavine Bronwyn , Kolasinski James , Webster Matthew , Stagg Charlotte , Rushworth Matthew , Johansen-Berg Heidi
Published: December 2021

Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.
Estimation of Genetic Parameters of Biomass Production and Composition Traits in Miscanthus Sinensis Using a Staggered-start Design
Authors: Raverdy Raphael , Mignot Emilie , Arnoult Stéphanie , Fingar Laura , Bodineau Guillaume , Griveau Yves , Volant Solenne , Brancourt-Hulmel Maryse
Published: December 2021

Traits for biomass production and composition make Miscanthus a promising bioenergy crop for different bioconversion routes. They need to be considered in miscanthus breeding programs as they are subjected to genetic and genetic x environment factors. The objective was to estimate the genetic parameters of an M. sinensis population grown during four years in two French locations. In each location, the experiment was established according to a staggered-start design in order to decompose the year effect into age and climate effects. Linear Mixed Models were used to estimate genetic variance, genotype x age, genotype x climate interaction variances and residual variances. Individual plant broad-sense heritability means ranged from 0.42 to 0.62 for biomass production traits, and were more heritable than biomass composition traits with means ranging from 0.26 to 0.47. Heritability increased through time for most of the biomass production and composition traits. Low genetic variance along with large genotype x age and genotype x climate interaction variances tended to decrease the heritability of biomass production traits for young plant ages. Most of the production traits showed large interaction variances for age and climate in both locations, while biomass composition traits highlighted large interaction variances due to climate in Orléans. The genetic and phenotypic correlations between biomass production and composition traits were moderate and positive, while hemicelluloses were negatively correlated with all traits. Efficient genetic progress is achievable for miscanthus breeding when plants get older. The joint improvement of biomass production and composition traits would help provide a better response of miscanthus to selection.