bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural insights on RNA bridging HIV-1 Vif and antiviral factor APOBEC3G
Authors: Kouno Takahide , Shibata Satoshi , Shigematsu Megumi , Hyun Jaekyung , Kim Tae Gyun , Matsuo Hiroshi , Wolf Matthias
Published: January 2023

HIV-1 hijacks a host ubiquitin ligase complex using a viral infectivity factor, Vif, to degrade the antiviral factor, APOBEC3G (A3G) [1-5]. Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of the viral counteraction mechanism. Amino acid determinants of A3G and Vif have been identified, and molecular structures of all components have been determined individually [6-8]; however, no evidence-based atomic configuration of their interface has been published, and the molecular mechanism of A3G recognition by Vif remains unknown. Here, we report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present a conclusive atomic model of the A3G-Vif interface, which assembles in 1:2 stoichiometry via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitroubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand, i.e., Vif preferentially recognizes RNA-bound A3G. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.
Physical Performance Determinants in Competitive Youth Swimmers: A Systematic Review
Authors: Price Todd Vincent Christopher , Legg Hayley , Cimadoro Giuseppe
Published: January 2023

Background Youth swimming performance is determined by several physiological, biomechanical and anthropometric characteristics. This review aimed to identify physical performance determinants of youth swimming performance, assessing strength, power, anaerobic, aerobic and body composition measures. Methods Searches were conducted in electronic databases (PubMed and Web of Science) using keywords relating to swimming and physiological measures, supplemented by citation searching of similar reviews. A total of 795 studies were identified in the initial search. The following inclusion criteria were used: participants were competitive/trained swimmers; swimming time-trial or event was conducted; data was provided on one or more physiological parameters; study was published in English and peer-reviewed. A total of 43 studies met the inclusion criteria. Risk of bias was assessed using Joanna Briggs Institute (JBI) checklist. Results Cross-sectional studies scored between 4–8 and randomised-controlled trials scored 8–9 on their respective JBI checklists. Youth swimming performance was determined by muscle strength, muscle power, lean body mass, anaerobic and aerobic metabolism measures in most studies, where improved performance values of these variables were conducive to swimming performance. Bodyfat % did not have a clear relationship with SP in youth performers. Conclusions Findings of this review suggest that greater levels of muscle strength, muscle power and lean body mass are favourable in swimming performance, with muscle strength and muscle power particularly beneficial for start and turn performance. Anaerobic and aerobic metabolism measures were good determinants of swimming performance, with middle- and long-distance events more influenced by the latter. Bodyfat % has a nuanced relationship with swimming performance, where further investigation is required. Findings were inconsistent across studies, potentially due to unidentified confounding factors. The evidence suggests enhanced physiological factors of strength, power and lean body mass in youth swimmers improves overall swim performance.
Dolutegravir based therapy showed CD4+ T cell count recovery and viral load suppression among ART naïve HIV positive individuals: A longitudinal evaluation
Authors: Gebremedhin Teshager , Ayenalem Melak , Adem Mohammed , Geremew Demeke , Aleka Yetemwork , Kiflie Amare
Published: January 2023

Background: Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization (WHO) for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4+ T-cells count recovery and viral load suppression has not been studied yet in Ethiopia, where HIV is endemic. Therefore, we aimed to assess the effect of DTG-based therapy on CD4+ T-cell count and viral load count among HIV-positive patients in Ethiopia.
Methods: A longitudinal prospective cohort study was conducted from July 2020–February 2021. 109 HIV-positive individuals who are ART naive but plan to initiate DTG-based therapy were recruited. HIV viral ribonucleic acid (RNA) copies were determined using a CD4+ T-cell count and quantitative polymerase chain reaction (PCR). To compute the difference in viral load and CD4+ T-cell counts between the baseline, 3rd, and 6th months, a Friedman test was used.
Results: The study included 109 HIV-positive people who had never received antiretroviral medication. Participants taking DTG-based treatment showed significantly decreasing median (IQR) values of viral load count (copies/mL) from 446,812 (237,649.5–732,994.5) at baseline to 34 (23.5–46) at 3 months and 0.0 (0–19) at 6 months of treatment follow-up. Although the treatment increases the proportion of participants with HIV-1 RNA 50 copies/mL from 0 (0% at baseline) to 87 (79.8%) and 100 (91.7%) at the 3rd and 6th months of treatment, respectively, On the other hand, the CD4+ T-cell count increased significantly during treatment: median (IQR): 209 (81.5–417.5) versus 291 (132–522) versus 378 (181.–632.5) cells/L at baseline, the 3rd and 6th months of the treatment follow-up period, respectively.
Conclusion: We found dolutegravir-based therapy was a promising option with high virological suppression rates and CD4+ T-cell count recovery demonstrating a restoration of cellular immunity. More over Viral load suppression rates were high after the initiation of the treatment.
Irisin attenuates ethanol-induced behavioral deficits in mice through activation of Nrf2 and inhibition of NF-κB pathways
Authors: Jiang Xi , Lao Wendie , Lin Qian , Cao Haoran , Chen Lei , Chen Jin , Yu Xuefeng
Published: January 2023

This study aims to investigate the effect of irisin on ethanol-induced behavioral deficits and explore the underlying mechanisms. A mouse model of ethanol addiction/withdrawal was constructed through chronic ethanol administration. Depressive-like behaviors were evaluated by the tail suspension test and forced swimming test, and anxiety-like behaviors were evaluated by the marble-burying test and elevated plus maze test. The expression of Nrf2 was measured by western blotting. Levels of inflammatory mediators (NF-κB, TNF-α, IL-1β and IL-6) and oxidative stress factors (ROS, MDA, GSH and SOD) were detected by ELISA. The ethanol-induced PC12/BV2 cell injury model was used to elucidate whether the effect of irisin on ethanol-induced neurological injury was related to anti-inflammatory and antioxidant mechanisms. Ethanol-induced ethanol preference and emotional deficits were improved by chronic irisin treatment; however, these improvements were partly reversed by cotreatment with the Nrf2 inhibitor ML385. Further results implied that the improvement effect of irisin on behavioral abnormalities may be related to its anti-inflammatory and antioxidant effects. In detail, irisin inhibited ethanol-induced abnormal expression of ROS and MDA and upregulated the expression of GSH and SOD. Meanwhile, irisin treatment inhibited ethanol-induced overexpression of NF-κB, TNF-α, IL-1β and IL-6 in the hippocampus and cerebral cortex. The regulation of oxidative stress factors by irisin was reversed after ML385 treatment. In the in vitro study, overexpression of oxidative stress factors in ethanol-treated PC12 cells was inhibited by irisin treatment; however, the prevention was reversed after the knockdown of Nrf2 siRNA. Moreover, ethanol-induced overexpression of inflammatory mediators in BV2 cells was also inhibited by irisin treatment. Irisin improved depressive and anxiety-like behaviors induced by ethanol addiction/withdrawal in mice, and this protection was greatly associated with the NF-κB-mediated anti-inflammatory signaling pathway and Nrf2-mediated antioxidative stress signaling pathway.
Development of Revised ResNet-50 for Diabetic Retinopathy Detection
Authors: Lin Chun-Ling , Wu Kun-Chi
Published: January 2023

Diabetic retinopathy (DR) produces bleeding, exudation, and new blood vessel formation conditions. DR can damage the retinal blood vessels and cause vision loss or even blindness. If DR is detected early, ophthalmologists can use lasers to create tiny burns around the retinal tears to inhibit bleeding and prevent the formation of new blood vessels, in order to prevent deterioration of the disease. Imaging examination is a valuable technique for doctors in the prediction and treatment of diseases. The rapid improvement of deep learning has made image recognition an effective technology; it can avoid misjudgments caused by different doctors’ evaluations and help doctors to predict the condition quickly. Therefore, this paper adopts visualization and preprocessing in the ResNet-50 model to improve module calibration, to enable the model to predict DR accurately.
Polygenic Contributions to Performance on the Balloon Analogue Risk Task
Authors: Nurmi Erika , Laughlin Christopher , de Wit Harriet , Palmer Abraham , MacKillop James , Cannon Tyrone , Bilder Robert , Poldrack Russell , Congdon Eliza , Sabb Fred , Seaman Lauren , McElroy Jude , Libowitz Mark , Weafer Jennifer , Gray Joshua , Dean Andy , Hellemann Gerhard , London Edythe
Published: January 2023

Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n=1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n=911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r=0.13, p=0.000012, pFDR=0.000052), as did the reciprocal analysis (r=0.09, p=0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p=3.24 x 10-8) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p=0.00047, pFDR=0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use.
A Novel Honey Badger Algorithm with Golden Sinusoidal Survival Rate Selection
Authors: Wang Fengxian , Bi Senlin , Feng Shaozhi , Zhang HuanLong
Published: January 2023

The original Honey Badger Algorithm as one of the newest meta¬heuristic techniques has a better convergence speed. However, HBA has the potential disadvantages of poor convergence accuracy, insufficient balancing among exploration and exploitation, and the propensity to slip into local optimization. In this paper, a novel golden sinusoidal survival honey badger algorithm is proposed. Firstly, an opposing learning and chaos mechanism are applied to the initial individual generation so that they can be distributed throughout the entire search area, which improves the precision of initial populations. Secondly, in the position update phase, we use a nonlinear convergence strategy to balance the weight of prey in the next walk and to increase the global search ability. After that, evaluating the quality of honey badger by golden sinusoidal survival rate and updating precocious individuals by Lévy flight, through which the premature convergence of the algorithm can be avoided. Finally, 23 benchmark function, CEC2019 tests are employed to assess the effectivity of improved algorithm. Test results indicate that the algorithm's capabilities to evolve, to extricate the local optimal and to detect the global optimal placements are enhanced.
The Mediating Role of Perceived Behavioral Control on the Relationship between Entrepreneurship Education and Entrepreneurial Intentions of University Students in Ethiopia
Authors: Aga Messele Kumilachew
Published: January 2023

Unemployment of graduates from higher education institutions become a common phenomenon in Ethiopia. To minimize this problem entrepreneurship development and promoting an entrepreneurial ecosystem have been considered as a remedy. Among others, this could be achieved through fostering entrepreneurship education. Hence, the purpose of this paper is to investigate the mediating role of perceived behavioral control in the relationship between entrepreneurship education and entrepreneurial intentions in Ethiopian Universities. Explanatory research design was used and data were collected by a self-administered questionnaire from a sample of 335 undergraduate students who took the course entrepreneurship in four Ethiopian universities. Structural Equation Modeling (SEM) approach using AMOS software was employed and confirmed both measurement and structural model fit before analysis. Then, the findings revealed that entrepreneurship education has a positive and significant effect on entrepreneurial intentions and perceived behavioral control. Moreover, perceived behavioral control positively predicts entrepreneurial intentions. The findings further explained that perceived behavioral control has a partial mediating effect on the relationship between entrepreneurship education and entrepreneurial intentions. Therefore, universities in Ethiopia should work on different initiatives that enhance knowledge, attitude, and skills of students on entrepreneurship that could help them to develop perceived behavioral control so as to enhance their intentions to become nascent entrepreneur after their graduation.
Pericarotid fat stranding at CT angiography:a marker of the short-term prognosis of acute ischemic stroke
Authors: Liu Ying , Zhao Yinan , Guo Zhongping , Li Mengshuang , Shan Hangsheng , Zhang Yonggang , Miao Chongchang , Gu Yan
Published: January 2023

Purpose
Perivascular epicardial fat stranding detected in the coronary CT angiography was associated with culprit lesion and provided helpful information of risk for ACS. This study aimed to evaluate the potential clinical significance of pericarotid fat stranding (PCFS) and investigate the association between PCFS and short-term prognosis of acute stroke with head and neck CT angiography (CTA).
Methods
This study included 80 patients (mean age 69.69士11.03; 58 men) who underwent both head and neck CTA and magnetic resonance imaging (MRI) within 2 weeks. Baseline characteristics, PCAT attenuation, plaque characteristics, ischemic penumbra, infarct core volume, infarct core growth rate (CGR) and grade of collateral status between PCFS group and non-PCFS group were recorded, these data were compared by using two-sample t,Mann-Whitney U,Fisher tests and Spearman’s correlation test.
Results
We found that patients with PCFS had a significantly higher PCAT density than non-PCFS patients (-55.75 ± 5.53 vs -65.82 ± 9.65;P༜0.001 ). Those with PCFS showed a larger infarct core volume (166.43 ± 73.07 vs 91.43 ± 55.03;P = 0.001 ) and faster CGR (39.57 ± 12.01 vs 19.83 ± 32.77;P༜0.001), and that the frequency of adverse prognosis was more significant than in control subjects (83.33% vs 19.11%). The difference was statistically significant.
Conclusions
We discovered that individuals with PCFS had greater CGR, which was substantially related with a worse outcome in acute stroke patients with ipsilateral carotid atherosclerosis. Recognition of PCFS may help to predict stroke prognosis and allow doctors to take early action to improve patient prognosis.
Novel approach to extract candidate outcomes from literature for a standard outcome set: A case- and simulation study
Authors: Veen Kevin , Joseph A , Sossi F , Jaber P Blancarte , Lansac E , Das-Gupta Z , Aktaa S , Takkenberg JJM
Published: January 2023

Aims
Standard outcome sets enable the value-based evaluation of health care delivery. Whereas the attainment of expert opinion has been structured using methods such as the modified-Delphi process, standardized guidelines for extraction of candidate outcome measures from literature are lacking. As such, we aimed to describe a novel methodology to obtain a comprehensive list of candidate outcome measures for potential inclusion in standard outcome datasets.
Methods
We designed a three-key steps to develop a list of candidate outcome measures to evaluate healthcare and applied these steps for the development of the international consortium of health outcome measures Heart valve disease dataset to illustrate the method. Our methodological approach involves: 1) Benchmark review of relevant registries and Clinical Practice Guidelines; 2) Applying machine learning to screen (using frequent words in abstracts) the studies that have been extracted from a systematic search of the literature using only the disease term; and 3) Extracting the candidate outcome measures from randomly selected batches of the retrieved studies iteratively until saturation is reached. Batch cutoff choices were investigated using data of 1000 simulated cases.
Results
Simulation showed that on average 98% (range 92% to 100%) saturation is reached using a 100-article batch initially, with 25 articles in the subsequent batches. On average 1.7 repeating rounds (range 1-5) of 25 new articles were necessary to achieve saturation.
Conclusion
In this paper a standardized three-pillar approach is proposed to identify relevant outcome measures for a standard dataset. This approach creates a balance between comprehensiveness and feasibility in conducting literature reviews for the identification of candidate outcome measures.
Mutual regulation mechanism of the O-GlcNAcylation enzyme pair revealed by Cryo-EM structure of human OGT–OGA complex
Authors: Gao Haishan , Lu Ping , Liu Yusong , He Maozhou , Cao Ting , Yang Mengquan , Qi Shutao , Yu Hongtao
Published: January 2023

O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins1–4. In response to nutritional and hormonal signals, O-GlcNAcylation regulates diverse cellular processes by modulating the stability, structure, and function of target proteins. Misregulation of O-GlcNAcylation is implicated in cancer, diabetes, and neurodegeneration5–7. A single pair of enzymes, the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), catalyzes the addition and removal of O-GlcNAc on over 3,000 proteins in the human proteome8,9. How OGT selects its native substrate(s) and maintains the homeostatic control of O-GlcNAcylation of so many substrates against OGA are not understood. Here we show that chemically induced degradation of OGT co-depletes OGA in human cells, suggesting the existence of a stable OGT–OGA complex in vivo. The cryo-electron microscopy (cryo-EM) structures of human OGT and the OGT–OGA complex reveal that OGT forms a functionally important scissor-shaped dimer. A long flexible OGA segment occupies the extended substrate-binding groove of OGT and positions a serine for O-GlcNAcylation, thus preventing OGT from modifying other substrates. Conversely, OGT disrupts the functional dimerization of OGA and occludes its active site, resulting in the blocking of access by other substrates. This unexpected but direct mutual inhibition between OGT and OGA limits futile O-GlcNAcylation cycles and maintains O-GlcNAc homeostasis.
Bibliometric analysis of global research trends in post-stroke depression: hotspots and frontiers
Authors: Ma Wei , Li Xiangling , Yang Yi-Bao , Zhai Yang , Xie Ting-Ting , Gong Zhi-Ying , Lan Baixin , Liu Jiao , Mo Xue-Ni
Published: January 2023

Background
Post-stroke depression(PSD) is one of the most common complications of stroke which affects recovery and quality of patients’ life adversely. PSD also is a significant source of burden for caregivers. Recently, the number of publications on PSD has been an increasing worldwide that means PSD has attracted more and more attention. Therefore, a more comprehensive understanding of the publications on PSD is now required. The purpose of this paper is to analyze the research status, discover the hotspots and frontiers about PSD.
Methods
The publications’ raw data was retrieved from the Web of Science Core Collection on September 19, 2022. Impact Factor (IF) and Journal Citation Reports (JCR) segments of the publications were obtained from the Web of Science website. Visualization analysis was performed on CiteSpace and VOSviewer.
Results
From 2012 to 2022, the number of citations and publications about PSD increased exponentially year by year. Finally, a total of 3268 publications related to PSD were identified. China (867) and the US (738) had the most publications; Capital Med Univ and Univ Melbourne were the most prolific institutions. Ungvari GS and Hackett ML were the most active authors and the most prolific and co-cited, respectively. Journal of stroke cerebrovascular diseases (131 articles) was the highest output. Among the 3268 publications, International journal of stroke had the most citations (43.9 times), Stroke has the most citations (2,990) and the highest H-index value. The citation burst for 8 co-cited references lasts until 2022. Finally, this paper divided the hot spots into four categories: cluster 1 (study on risk factors of PSD), cluster 2 (clinically relevant research on PSD), cluster 3 (mechanisms of PSD), and cluster 4 (the Treatment Study for PSD).
Conclusion
PSD research is one research main area worldwide. This work demonstrated the knowledge structure and the evolution of the PSD research field and predictdresearches trends through visual analysis. The study of clinical treatment and prevention of PSD will instead of the study of the mechanism in the future. This study provides reference for future research of PSD.
3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress
Authors: Wu Song-Tao , Han Shan-Shan , Xu Xi-Ming , Sun Hai-Jun , Zhou Hua , Shang Kun , Liu Zi-Hao , Liang Shu-Juan
Published: January 2023

Background: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following exploratory abdominal laparotomy.
Methods: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30 and 150 mg/kg) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) were measured at 24 h after surgery.
Results: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions.
Conclusions: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.
Labor markets for health supply chain management in Rwanda: a qualitative study of stakeholder perspectives
Authors: Meier Erin , Brown Andrew N. , McHenry Bridget , Buki Ines K. Gege , Egharevba Michael , Kabatende Joseph
Published: January 2023

Background. Effective supply chains for health products require an adequate, skilled workforce for supply chain management (SCM). Rwanda faces challenges in human resources for SCM, including limited capacity for SCM at different levels. Understanding of the factors influencing the supply of and demand for SCM professionals in Rwanda is necessary to ensure the labor market contains an adequate workforce. This study identifies the perspectives of key stakeholders in the supply chain management sector about the factors influencing the supply of and demand for SCM professionals.
Methods. Data were collected in semi-structured, group and one-on-one interviews with 35 key stakeholders involved in the supply chain management labor market from March and April 2019. Interviewees were categorized according to their role in the labor market as system actors, functional actors involved in the supply of SCM workers, and functional actors involved in the demand for SCM workers. Interviewees were asked open-ended questions about factors influencing the demand for and the supply of SCM workers, and recommendations for improvement. Interviews were analyzed thematically. A final validation workshop was held, and the results were also reviewed by the Ministry of Health.
Results. Stakeholders agreed that skills mismatch between SCM workers’ skills and the competencies jobs require impacts the supply of workers. Lack of career structure for SCM, lack of professional definitions for health supply chain management, and SCM curricula that do not match the needs of the workplace contribute to this gap. The demand for SCM professionals is poorly defined in terms of the numbers of professionals needed and skills workers require. Financial limitations hinder demand for health SCM professionals.
Conclusions. This study adds to the understanding of factors influencing the SCM labor market in Rwanda by documenting perspectives from government ministries, professional organizations, universities, and employers from SCM organizations. Improving the SCM labor market in Rwanda and the availability of the skilled cadres required for the effective management of health supply chains in Rwanda requires a coordinated effort by the Ministry of Health, private SCM companies, professional associations, education sector, and policy makers.
Nonunion surgery of trochanteric fractures (AO 31-A2) with a sliding hip screw.
Authors: Röell Boudewijn , Leijnen Michiel , Ritchie Ewan , Timmermans Marieke
Published: January 2023

Introduction
Sliding hip screws (SHS) or cephallomedullary nails (CMN) are the fixation methods for proximal femur fractures (AO 31-A2). There is no consensus on the preferred treatment. 2-4% of these proximal femur fractures treated with a CMN develop a nonunion. Our objective was to review our results when replacing the CMN with a SHS in treating nonunion of trochanteric fractures.
Method
From 2013 until 2020, information was collected regarding all patients with a nonunion of a proximal femur fracture (AO 31-A2) that were initially treated with a CMN in a non-academic teaching hospital with a high volume of proximal femur fractures. All patients with a nonunion of the proximal femur fracture underwent an operation where the CMN was replaced with a SHS. Baseline characteristics were recorded, as well as union rate and complications regarding the secondary surgery.
Results
In total 15 patients were treated with removal of the CMN and placement of the SHS in the study period. 80% were female, average age was 72.3 years when primary surgery was performed. Most patients complained of pain during weight bearing due to the nonunion (N = 13). Mean time until revision surgery was 9.6 months. Consolidation of the nonunion was achieved in 93.3% of the cases. Pain relief was accomplished within 2 months. Complications were registered in 5 patients.
Conclusion
A SHS is an easy and effective secondary intervention when dealing with a nonunion of a trochanteric fracture (AO 31-A2) with high union rates without the necessity for bone grafting. Due to the higher complication rate in revision surgery, the patient should be well informed prior to surgery.
Synergistic, long-term effects of glutamate dehydrogenase 1 deficiency and mild stress on cognitive function and mPFC gene and miRNA expression
Authors: Gaisler-Salomon Inna , Asraf Kfir , Zaidan Hiba , Natoor Baylasan
Published: January 2023

Glutamate abnormalities in the medial prefrontal cortex (mPFC) are associated with cognitive deficits. We previously showed that homozygous deletion of glutamate dehydrogenase 1 (Glud1), a metabolic enzyme critical for glutamate metabolism, in CNS leads to schizophrenia-like behavioral abnormalities and increased mPFC glutamate; mice heterozygous for CNSGlud1deletion (C-Glud1+/−mice) showed no cognitive or molecular abnormalities. Here, we examined the protracted behavioral and molecular effects of mild injection stress on C-Glud1+/−mice. We found spatial and reversal learning deficits, as well as large-scale mPFC transcriptional changes in pathways associated with glutamate and GABA signaling, in stress-exposed C-Glud1+/−mice, but not in their stress-naïve or WT littermates. Interestingly, these effects were observed several weeks following stress exposure, and the expression levels of specific glutamatergic and GABAergic genes differentiated between high and low reversal learning performance. An increase in MiR203-5p expression immediately following stress may provide a translational regulatory mechanism to account for the delayed effect of stress exposure on cognitive function. Our findings show that chronic glutamate abnormalities interact with acute stress to induce cognitive deficits, and resonate with gene x environment theories of schizophrenia. Stress-exposed C-Glud1+/- mice may model a schizophrenia high risk population, which is uniquely sensitive to stress-related ‘trigger’ events.
Plant Leaf Species Identification Using LBHPG Feature Extraction and Machine Learning Classifier Technique
Authors: Jadhav Sachin B.
Published: January 2023

The paper presents the identification and classification of Indian agricultural crop species using a novel combined Local Binary Histogram Pattern of Gradient (LBHPG) image feature extraction technique. Initially, a partition of the leaf image background is done through the newly developed Fast Adaptive Fuzzy C-mean Clustering (FAFCM) technique. After that, leaf objects within the image are identified using the LBHPG method. For the classification, KNN, PNN, and SVM shallow machine learning classifiers are used for crop species identification. The performance evaluation is done by using LBP and HOG individually along with the new proposed LBHPG technique for classification using KNN, PNN, and SVM Classifiers. The performance evaluation is based on six metrics parameters of the confusion matrix, viz., accuracy, sensitivity, specificity, precision, recall, and F-measure. The experimental results show that the proposed novel LBHP feature extraction technique with PNN Classifier gives the highest accuracy of 94.58%.
The Establishment of a Recombinant Polymerase Amplification Technique for the Detection of Mouse Poxvirus
Authors: Lian Yuexiao , Zhang Mengdi , Zhu Yujun , Wu Miaoli , Huang Bihong , Xiao Li , Shi Kehang , Li Peide , Cong Feng , Wang Huanan
Published: January 2023

Background: Ectromelia virus (ECTV) is the pathogen of mousepox, which has a limited host range and a high mortality rate. In the past century, ECTV has affected laboratory mouse colonies worldwide. Recombinant polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method.
Results: In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed.The sensitivity of the RPA assay is 100 copies of the genome per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 52 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement.
Conclusions: In conclusion, this RPA assay, especially in low-resource settings, provides a novel alternative for sensitive, simple, and specific identification of ECTV.
Relationship between different levels of ROX index and the prognosis of patients receiving high-flow nasal oxygen therapy in ICU
Authors: Chong Meng , Ma Li
Published: January 2023

Objective: This study aimed investigate the relationship between different levels of ROX index and the prognosis of patients with nasal high-flow oxygen therapy in intensive care unit (ICU).
Methods: In this retrospective study, we collected patients receiving high-flow nasal oxygen therapy enrolled in the intensive care unit of our hospital between 2017 and 2022 . The ROX index was calculated according to the physiological indicators of the patients on the first day of admission to the ICU, and they were divided into three subgroups: Q1 (ROX index<3.85), Q2 (ROX index 3.85-4.88) and Q3 (ROX index>4.88). Baseline clinical characteristics and clinical outcomes were compared among the three groups. The Kaplan Meier curves were drawn to compare the 28-day and 60-day survival rates of patients in the three groups, and the prognosis of patients receiving nasal high-flow oxygen therapy in the intensive care unit was further explored by subgroup analysis. COX regression analysis was used to verify the association between the three groups and these indicators.
Results: A total of 517 patients with HFNC were enrolled, including 231 patients in Q1 group, 137 patients in Q2 group and 149 patients in Q3 group. Compared with the other two groups, the Q3 group had lower body temperature, heart rate, APACHE II score,serum anion gap, procalcitonin and neutrophil ratio at the beginning of admission. The number of patients with acute respiratory failure and MODS was less than the other two groups. The number of patients using noninvasive mechanical ventilation was also less than that in the other two groups. In addition, patients in Q3 group had a lower rate of death at both 28 and 60 days than those in the Q1 and Q2 groups, and survivors used noninvasive mechanical ventilation less frequently. Subgroup analysis also showed that the lower the ROX index, the higher the mortality of HFNC patients at the subgroup level.
Conclusion: The ROX index at the beginning of intensive care unit admission can predict the prognosis of patients with high-flow nasal cannulas. The higher the ROX index level, the better the prognosis of patients.
Genomics prominent role of the PAX family in Tumorigenesis
Authors: Choudhury Shouhartha
Published: January 2023

The tumour in the brain is a glial cell origin. Tumour factors govern cell fate during development. The murine PAX family control the transcription of embryonic cell lineages and contribute an immense role during development. PAX1-PAX9 genes assist in the origination of neural crest in the NS (nervous system). Also, paired-box-associated genes emerged with numerous derivatives during neurogenesis. So, the tumorigenesis in CNS suggested a novel molecular signature found among factors in neurogenesis. An early study demonstrated the paired-box domain involved genes degraded by molecular and immunogenic mechanisms in tumours such as Wilms tumour, Rhabdomyosarcoma, Brain tumour, and Lymphoma. The paired-box domain-mediated genes in tumour development are the subject of rigorous investigation of proliferation and prevention of apoptotic strategy. Therefore, I performed a genome-wide analysis to prevail enlightenment on PAX domains in the mammalian genome. In this study, I observed paired-box domains containing genes in two organisms (i.e. Homo sapiens and Mus musculus). In this document, my analysis data provided that the PAX domain-containing genes promote a unique group of proto-oncogenes. Also, the analysis data suggested PAX3 (target gene) and the number of PAX domain-initiated genes in the PAX family. My observation concluded the PAX domain-containing genes control the equilibrium between growth and polarity in multi-functional cells. The normal functions of the PAX3 gene might be a feature of tumour biology. In contrast, the fusion genes (PAX3 and FOXO1) potentially target for cancer-immunotherapy.
Design of a potential Sema4A based multiepitope vaccine to combat triple-negative breast cancer: An immunoinformatic approach
Authors: Paranthaman Priyanga , Veerappapillai Shanthi
Published: January 2023

Immunotherapy is revamping the therapeutic strategies for TNBC owing to its higher mutational burden and tumour-associated antigens. One of the most intriguing developments in cancer immunotherapy is the focus on peptide-based cancer vaccines. Thus, the current work aims to develop an efficient peptide-based vaccine against TNBC that targets Sema4A, which has recently been identified as a major regulator of TNBC progression. Initially, the antigenic peptides derived from Sema4A were determined and evaluated based on their capability to provoke immunological responses. The assessed epitopes were then linked with a suitable adjuvant (RpfB and RpfE) and appropriate linkers (AAY, GPGPG, KK, and EAAAK) to preclude junctional immunogenicity. Eventually, docking and dynamics simulations are performed against TLR-2, TLR-4, TLR-7 and TLR-9 to assess the interaction between the vaccine construct and TLR receptors, as the TLR signalling pathway is critical in the host immune response. The developed vaccine was then exposed to in silico cloning and immune simulation analysis. The findings suggest that the designed vaccine could potentially evoke significant humoral and cellular immune responses in the intended organism. Considering these outcomes, the final multi-epitope vaccine could be employed to serve as an effective choice for TNBC management and may open new avenues for further studies.
Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-causing mutations
Authors: Stern Shani , Hussein Yara , Tripathi Utkarsh , Choudhary Ashwani , Nayak Ritu , Peles David , Rosh Idan , Djamus Jose , Spiegel Ronen , Garin-Shkolnik Tali
Published: January 2023

Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over 1000 genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from a first degree relative without the mutation. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by increased sodium currents, increased amplitude and rate of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3–5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.
Cellulosic surfaces endowed with chemical reactivity by physical adsorption of functionalized polysaccharides
Authors: Bouchut Arthur , Cathala Bernard , Moreau Céline , Lecourt Michael , Petit-Conil Michel , Pettignano Asja , Bernard Julien , Charlot Aurélia , Fleury Etienne
Published: January 2023

A strategy to functionalize cellulosic surfaces through physical adsorption of xyloglucan (XG) and carboxymethyl cellulose (CMC) derivatives bearing allyl or alkyne groups is reported. A set of functional polymer derivatives with degrees of substitution -DS- ranging from 0.4 to 0.44 are first prepared through epoxide ring opening of allyl glycidyl ether (AGE) or propargyl glycidyl ether (PGE) under mild basic aqueous medium. Contrary to alkyne-based materials, radical copolymerization allyl-XG or -CMC derivatives with acrylamide/acrylic acid leads to the formation of hydrogels confirming thereby their reactivity. Investigations into the deposition of these derivatized polysaccharides on Whatman paper and wood pine fibers further (spraying aqueous solutions, drying and desorption step in water) show that physisorption of the chains is not altered by the DS or by the nature of the anchored groups. QCM-D measurements highlight a high affinity of Allyl-XG for cellulose surface. Confocal Raman mapping of cellulosic substrates modified with alkyne derivatives indicate that the surface covering is quantitative and that the diffusion of the chains within the substrate can reach 40 µm. This aqueous functionalization/spraying procedure is a promising method to confer new ajustable properties to a range of cellulosic substrates in an eco-sustainable manner.
Laminin fragments conjugated with perlecan’s growth factor–binding domain differentiate human induced pluripotent stem cells into skin dermal stem cells
Authors: Sugiyama-Nakagiri Yoriko , Yamashita Shiho , Taniguchi Yukimasa , Shimono Chisei , Sekiguchi Kiyotoshi
Published: January 2023

Deriving stem cells to regenerate full-thickness human skin is important for treating skin disorders without invasive surgical procedures. Our previous protocol to differentiate human induced pluripotent stem cells (iPSCs) into skin-derived precursor cells (SKPs) as a source of dermal stem cells employs mouse fibroblasts as feeder cells and is therefore unsuitable for clinical use. Herein, we report a feeder-free method for differentiating iPSCs into SKPs by customizing culture substrates. We immunohistochemically screened for laminins expressed in dermal papillae (DP) and explored the conditions for inducing the differentiation of iPSCs into SKPs on recombinant laminin E8 (LM-E8) fragments with or without conjugation to domain I of perlecan (PDI), which binds growth factors through heparan sulphate chains. Several LM-E8 fragments, including those of LM-111, 121, 332, 421, 511, and 521, supported iPSC differentiation into SKPs without PDI conjugation. However, the SKP yield was significantly enhanced on PDI-conjugated LM-E8 fragments. SKPs induced on PDI-conjugated LM-E8 fragments retained the gene expression patterns characteristic of SKPs, as well as the ability to differentiate into adipocytes, osteocytes, and Schwann cells, as was the case with SKPs induced on feeder cells. Thus, PDI-conjugated LM-E8 fragments are promising agents for inducing iPSC differentiation into SKPs in clinical settings.
Comprehensive proteomic analysis of cerebrospinal fluid exosomes derived from non-small cell lung cancer related leptomeningeal carcinomatosis
Authors: Hou Lan , Chen Xin , Qi Xuejiao , Zou Yueli , He Junying , Bu Hui
Published: January 2023

Background
Leptomeningeal carcinomatosis might happen in late non-small cell lung cancer patients and causes a poor median survival period. CSF of leptomeningeal carcinomatosis patients is a special kind of tumor microenvironment. Exosomes are key components of tumor microenvironment and participate in a variety of physiological and pathological processes. There is a great need of comprehensive proteomic analysis of exosomes in these patients.
Methods
In this study, exosomes in CSF derived from different groups (leptomeningeal carcinomatosis group, non-small cell lung cancer group without leptomeningeal carcinomatosis and normal group) were isolated by ultracentrifugation and proteomics analysis was performed by label-free method.
Results
A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. 20 proteins were differentially expressed between groups. In protein-protein interaction network analysis, ACTB, ENO1, TIMP1 and RTN4R had higher betweenness than others.
Conclusions
This study is the first comprehensively CSF exosomes proteomic profile of leptomeningeal carcinomatosis patients. Further research is needed to clarify the importance of ACTB, ENO1, TIMP1 and RTN4R in leptomeningeal carcinomatosis patients.
Moleculer cloning, prokaryotic expression and its application potential evaluation of interferon (IFN)-ω of forest musk deer
Authors: WU Xi , YANG Wei , LUO Yan , CHENG Jian-guo , FU Wen-long , ZHOU Lei , WU Jie , WANG Yin , ZHONG Zhi-jun , YANG Ze-xiao , YAO Xue-ping , REN Mei-shen , LI Yi-meng , LIU Jie , DING Hui , CHEN Jia-nan
Published: January 2023

Forest musk deer (Moschus berezovskii) are currently a threatened species under conservation, and the development of captive populations is restricted by health problems. To evaluate the application potential of interferon (IFN)-ω in the prevention and control of forest musk deer disease, 5 forest musk deer IFN-ω (fmdIFNω) gene sequences were successfully obtained by homologous cloning method for the first time. FmdIFNω5 was selected and recombinant fmdIFNω protein (rIFNω) was successfully expressed by pGEX-6P-1 plasmid and E. coli expression system. The obtained protein was used to stimulate forest musk deer lung fibroblasts cells FMD-C1 to determine its regulatory effect on interferon-stimulated genes (ISGs). In addition, an indirect ELISA method based on anti-rIFNω serum was established to detect endogenous IFN-ω levels in 8 forest musk deer. The results showed that there were 18 amino acid differences among the 5 fmdIFNω subtypes, all of which had the basic structure to exert the activity of type Ⅰ IFN and were close to Cervus elaphus IFN-ω in the phylogenetic tree. The protein expressed was 48 kDa, and the transcription levels of all ISGs were increased in FMD-C1 cells stimulated by rIFNω, and the amount of transcription accumulation was time-dependent. Meanwhile, Anti-rIFNω serum of mice could react with both rIFNω and forest musk deer serum, and the OD450nm value of forest musk deer serum with the most obvious symptoms was the highest. These results indicate that IFN-ω has great potential as an antiviral drug and an early indication of innate immunity, which is of great significance for the prevention and control of forest musk deer diseases.