bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in small cell lung cancer: Epidemiology and genetics
Authors: Hou Jia , Li Wenyuan , Zhang Shirong , Tan Deli , Zhu Yue , Lv Kejia , Guo Hui
Published: May 2022

The incidence of small cell lung cancer (SCLC) in females has markedly increased over the last decades. However, sex differences in SCLC lack large database-based studies. The present study was aimed at exploring sex differences in SCLC. We used 18234 cases from the SEER database (1973-2015) to describe the epidemiologic feature of SCLC, and 120 cases from TCGA and two datasets from GEO databases to analyze genetic patterns of sex differences in SCLC. Survival analyses were conducted with log-rank tests and Cox proportional hazard models. Our results showed that female SCLC patients had smaller size of tumor, fewer metastasis, and lower stages in comparison to male patients, and females had significantly better OS and CSS than males with SCLC. Moreover, elder age, white race, large tumor size, advanced stage and distant metastasis were risk factors for mortality in both female and male SCLC patients. In SCLC, the expression levels of AMPH, GRIN2C and WNT4 were higher in males, and HOXA5 was more expressed in females. Notably, RB1 was more frequently mutated in female patients. We confirmed that female sex was associated with more favorable clinicopathological factors and better outcome of SCLC; Females and males also differed in gene expression levels, gene mutation frequency and types. This study highlights the need to consider sex as an important variable for improving SCLC diagnosis and treatment.
Brain Tumor Segmentation Using Modified U-Net
Authors: sami eman , ebied hala , Amin Safaa , Hassaan Mosab
Published: May 2022

Purpose: Planning and evaluating the extent of the spread of brain tumors for the treatment is the main challenge. Magnetic resonance imaging (MRI) has been shown as a great diagnostic tool for brain tumors without harmful radiation. We have found in using the traditional U-net, that there are some errors in identifying the tumor, so we wanted to develop this method so that it overcomes some errors in determining the tumor in the traditional method. Methods: We demonstrate a way to segment the brain tumor using modify U-net networks. Then compared with traditional U-net, modified U-net, k-means, and thresholding segmentation. The experiments were carried out using three multimodal brain tumor image segmentation datasets (FIGSHARE database), which contain 3929 abnormal (with a tumor) and normal brain MRI images, 100 images obtained from “The Cancer Imaging Archive (TCIA)” and BraTS 2019 challenge which include 4600 cases (normal and abnormal) of HGG (high-grade glioma) and LGG(low-grade glioma).Results: Through this study, the modified U-net achieved higher accuracy than other methods.Conclusion: Determining the tumor inside the human brain is an important matter to preserve human life. We used old and modern techniques and modified the basic form of the traditional U-net. The above-mentioned techniques were compared and the experiment was done on many data from different sources. It was found that the modified U-net is the best accurate..
Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer
Authors: Wu Xiang , Zhou Shuping , Zhou Xinhua , Xu Xiao , Wang Luoluo , Ruan Yi , Lu Jun , Li Haili , Xu Hongfeng , Ma Xinyi , Li Hong
Published: May 2022

Background: The common sites of colorectal cancer metastasis are the surrounding lymph nodes, liver, and lung, while ectopic metastases of the lung and pancreas are extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer.Case presentation: A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. Enhanced computed tomography revealed pancreatic metastasis. A laparoscopic distal pancreatectomy (combined with splenectomy) was performed. Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported.Discussion: For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. Computed tomography and pathological histology have an excellent diagnostic value for pancreatic metastasis. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.
Functional Exploration of SNP Mutations in HIF2αb Gene Correlated with Hypoxia Tolerance in Blunt Snout Bream (Megalobrama amblycephala)
Authors: Zhao Shan-Shan , Su Xiao-Lei , Yang Hui-Qi , Zheng Guo-Dong , Zou Shu-Ming
Published: May 2022

Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia environment. Hypoxia-inducible factor (HIF) is the most critical factor in HIF pathway, which strictly regulates the hypoxia stress process of fish. In this study, we found six hifα genes in blunt snout bream that demonstrated different expression under hypoxia conditions. In HEK293T cells, all six hifαs were detected to activate HRE region by luciferase reporter assay. More importantly, we identified two linkage-disequilibrium SNP sites at exon 203 and 752 of hif2αb gene in blunt snout bream. Haplotype II (A203A752) and its homozygous diplotype II (A203A203A752A752) appeared frequently in a selected strain of blunt snout bream with hypoxia-tolerance. Diplotype II has a lower oxygen tension threshold for loss of equilibrium (LOEcrit) over a similar range of temperatures. Moreover, its erythrocyte number increased significantly (p < 0.05) than those in diplotype I and diplotype III strains at 48 h of hypoxia. The enzymes related with hypoxia tolerant traits, i.e. reduced glutathione, superoxide dismutase and catalase, were also significantly (p < 0.05) induced in diplotype II than those in diplotype I or III. In addition, the expression of epo in the liver of diplotype II was significantly (p < 0.01) higher than those in the diplotype I or III strains at 48 h of hypoxia. Taken together, our results found that the hypoxia-tolerant related diplotype II of hif2αb has the potential used as a molecular marker in future genetic breeding of hypoxia-tolerant strain.
The multifunctionality of green corridors during pandemic lockdowns: a case study of Riobamba city, Ecuador
Authors: Morales Janeth , Yang QingJuan , Poyan Sayed Mustafa
Published: May 2022

Context:
The pandemic has demonstrated several weaknesses and inequalities in the way society live and develops within cities, the economic losses, the massive contagions, and above all the lack of control and people's lack of awareness of the situation.
Objectives:
This study tries to attempt, city lacking in green spaces, towards a city with green and sustainable planning, and the association between urban greenery and physical activity during the Covid-19, as well as proposing urban green corridors as a planning tool for urban green areas.
Methods:
The research method was applied Bibliographic analysis which focuses on the importance of green areas, health, wellbeing, and multifunctional, and City analysis based on surveys to understand the residents' behavior during the pandemic.
Results:
Green and recreational spaces in Riobamba was exposed by all those who could not cope with the lockdown, since only 8% of those surveyed stayed at home, while 70% left their homes for green or recreational spaces within the urban area and 23% left the city in search of parks or nature reserves. This shows, how the quality of green areas can positively affect people’s behaviors during the Covid-19. The diagnosis, highlighted the preservation of natural areas, urban reforestation, re-naturalization of spaces or urban voids.
Conclusions:
The urban green corridor is conceived as a system where several spaces are connected, creating two interactions: the first is how the city can provide the necessary infrastructure during a crisis, and the second is how it energizes and prioritizes the health and supply systems for urban residents, creating safe spaces for each of the city's sectors.
Survival Status and its predictors among Patients Admitted to Pediatric Intensive Care Unit at Selected Tertiary Care Hospitals in Ethiopia: A Prospective Observational Study
Authors: Bacha Amente Jorise , Gadisa Diriba Alemayehu , Negera Getandale Zeleke
Published: May 2022

Background: Advances in pediatric intensive care have radically improved the prognosis for critically sick patients. Despite high burden of critically ill patients in low-income countries, there is scarce evidence on the incidence of mortality and its predictors among patients admitted to Intensive care unit (ICU) in Ethiopia. Therefore, we designed this study to determine the survival status and predictors of mortality among patients admitted to pediatric ICU at selected tertiary care hospitals in Ethiopia.Methods: A prospective observational study involving 206 admitted patients from October 2020 to May 30, 2021 was conducted in selected tertiary care hospital in Ethiopia. Data were collected on socio-demographic, clinical characteristics, treatment-related variables and entered into Epi-data version 4.6, and then exported to SPSS version 23.0 for analysis. Kaplan-Meier was used to compare the survival experience of the patients and Cox regression was used to identify independent predictors of in-ICU mortality. The hazard ratio was used as a measure of the strength of association and a p-value of < 0.05 was considered to declare statistical significance. Results: Fifty-nine (28.6%) patients were died during follow-up time, and the incidence of mortality was 3.6 deaths per 100 person-day observation. The mean ± SD survival times among patients with infectious and non-infectious related illnesses were 19.96 ± 1.84 and 27.24 ± 2.52 days respectively (log rank p = 0.08). Respiratory failure 19 (32.2%) was the commonest cause of death. In-ICU complications (AHR: 2.13; 95%CI: [1.02, 4.42]; p = 0.04), sepsis diagnosis (AHR: 2.43; 95%CI: [1.24, 4.78]; p = 0.01), GCS<8 (AHR: 1.96; 95%CI: [1.12, 3.43]; p = 0.02), use of sedative drugs (AHR: 2.40; 95%CI: [1.16, 4.95]; p = 0.02) were linked with increased risk of in-ICU mortality. In contrast, the use of mechanical ventilation was associated with decreased mortality (AHR: 0.45; 95%CI: [0.21, 0.92]; p = 0.03).Conclusion: The study found high incidence of in-ICU mortality among admitted pediatrics patients in selected Ethiopian tertiary care hospitals. In-ICU complications, sepsis diagnosis, GCS<8, and patient use of sedative drugs were independent predictors of in-ICU mortality. Prudent follow up is warranted for those patients with aforementioned risk factors.
Expanding the CRISPR/Cas genome-editing scope in Xenopus tropicalis
Authors: Shi Zhaoying , Jiang Hao , Liu Guanghui , Shi Songyuan , Zhang Xuan , Chen Yonglong
Published: May 2022

Background: The true diploid frog, Xenopus tropicalis (X. tropicalis) is an excellent genetic model organism. To date, the CRISPR/Cas-mediated genome editing methods established in this species are mostly based on SpCas9 that requires the stringent NGG protospacer-adjacent motif (PAM) for target recognition, which limits its genome editing scope. Thus, it is highly desirable to circumvent this limitation.Results: Through one-cell stage injection of Cas/gRNAs into X. tropicalis embryos, we evaluated the mutagenic efficiency of 8 different Cas variants using T7EI assay, Sanger DNA sequencing, or deep sequencing. Our data indicate that SaCas9 and KKH SaCas9 are highly effective in frogs, which could be used for direct phenotyping in G0 embryos. In contrast, VQR Cas9, xCas9 3.7, SpG Cas9, and SpRY Cas9 were ineffective in X. tropicalis embryos and no activity was detected for iSpyMac Cas9. We also found that LbCas12a/crRNA RNP complexes with paired crRNAs efficiently induced small fragment deletions in X. tropicalis embryos. Conclusion: SaCas9 and KKH SaCas9 are robust gene targeting tools in X. tropicalis embryos. LbCas12a/crRNA RNP complexes are useful for inducing DNA fragment deletions in frog embryos. These tools expand the CRISPR/Cas genome editing scope in X. tropicalis and increase the flexibility for various genome editing applications in frogs.
Computer-aided Diagnosis through Medical Image Retrieval in Radiology
Authors: Silva Wilson , Gonçalves Tiago , Härmä Kirsi , Schröder Erich , Obmann Verena Carola , Barroso María Cecilia , Poellinger Alexander , Reyes Mauricio , Cardoso Jaime S.
Published: May 2022

Currently, radiologists face an excessive workload, which leads to high levels of fatigue, and consequently, to undesired diagnosis mistakes. Decision support systems can be used to prioritize and help radiologists making quicker decisions. In this sense, medical content-based image retrieval systems can be of extreme utility by providing well-curated similar examples. Nonetheless, most medical content-based image retrieval systems work by finding the most similar image, which is not equivalent to finding the most similar image in terms of disease and its severity. Here, we propose an interpretability-driven and an attention-driven medical image retrieval system. We conducted experiments in a large and publicly available dataset of chest radiographs with structured labels derived from free-text radiology reports (MIMIC-CXR-JPG). We evaluated the methods on two common conditions: pleural effusion and (potential) pneumonia. As ground-truth to perform the evaluation, query/test and catalogue images were classified and ordered by an experienced board-certified radiologist. For a profound and complete evaluation, additional radiologists also provided their rankings, which allowed us to infer inter-rater variability, and yield qualitative performance levels. Based on our ground-truth ranking, we also quantitatively evaluated the proposed approaches by computing the normalized Discounted Cumulative Gain (nDCG). We found that the Interpretability-guided approach outperforms the other state-of-the-art approaches and shows the best agreement with the most experienced radiologist. Furthermore, its performance lies within the observed inter-rater variability.
Incidence and Risk factors of Venous Thromboembolism in the Perioperative Period of Spine Surgery at a Tertiary Care Hospital
Authors: Konbaz Faisal , Bourghli Anouar , Eissa Sami Al , Helal Fahad Al , Abalkhail Majed , Tahan Husam Al , Farraj Abdulrahman Al , Jafari Salman Al , Dusari Rakan Al
Published: May 2022

Introduction:Spine Surgery is considered a moderate risk for developing Venous Thromboembolism (VTE). To our knowledge, no study has been done to determine the incidence of VTE in our local population. We aim to study this and determine the factors associated with developing VTE post spine surgery. Material and Methods:A retrospective chart review was conducted to analyze 892 adult patients who underwent either an elective or emergency spine surgery. Demographics, length of surgery and hospital stay, diagnosis, and location of surgery in addition to the type of trauma, if applicable, were collected. Furthermore, spiral computed tomography was used to diagnose pulmonary embolism (PE), and duplex ultrasound was used to diagnose deep vein thrombosis (DVT) pre- and post-operatively. Results:800 patients were included. The overall incidence of VTE was 4.1%. In addition, Lumbar spine was the most common location operated on. Increasing age and length of hospital stay were both significantly associated with development of VTE. Furthermore, cervical spine surgery had a lower incidence of VTE compared to other locations which was statistically significant. Lastly, non-ambulatory patients had a higher risk of having VTE compared to patient who were able to ambulate post-operatively. Conclusion:The incidence of VTE after spine surgery is considered low but carries high rates of morbidity and mortality. Increased age and prolonged hospital stay increases its risk while early ambulation lowers it. Larger prospective study is needed to identify the best prophylactic anticoagulation regimen. Prophylactic measures against VTE are highly recommended, especially amongst high-risk patients. IRB approval:This study has been submitted and approved by the Institutional Review Board (IRB).
Research on the distribution ratio of variants and the proportion of variant types in different conditions of SCN1A Seizure Disorders using ClinVar
Authors: Tian Yuan , Cui Shihong , Ren Chenchen , Li Ying , Zhang Hua , Yang Bo , Peng Jia , Yuan Erfeng , Guo Yaqing , Yuan Enwu , Liu Ling
Published: May 2022

The aim of this study was to clarify the distribution of SCN1A variants in each condition of SCN1A seizure disorders and the proportion of the SCN1A variant types in different conditions of SCN1A seizure disorders.This study consisted of querying SCN1A variants in ClinVar, reclassificating ClinVar P/LP SCN1A missense variants provided by a singgle submitter, validating conditions of SCN1A Seisure Disorders by reclassification of P/LP variants and screening variant types of conditions of SCN1A Seisure Disorders by validation.The result showed that most of the P/LP SCN1A missense variants provided by a single submitter in ClinVar remained at the P/LP level (247/383), and a few variants were converted from P/LP to VUS (136/383). The condition "Early infantile epileptic encephalopathy with suppression bursts" shown in ClinVar was actually all other conditons, such as Dravet syndrome/Severe myoclonic epilepsy of infancy(DS/SMEI)(69/89) and Generalized epilepsy with febrile seizures plus/Borderline severe myoclonic epilepsy of infancy(GEFS+/SMEB) (3/89). Both in missense and trunction, DS/SMEI-related SCN1A variants had the highest proportion (291/371, 78.4%),and there were still quite a few some SCN1A variants are associated with other conditions such as GEFS+, FMH, DEE, Lennox-Gastaut Syndrome and Intractable childhood epilepsy with generlaized tonic-clonic seizures (80/371, 21.6%).This provided data support for clinicians to grasp the severity of epilepsy caused by these SCN1A variants.
Identification and validation of WsMYB34 transcription factor for salt tolerance and induced secondary metabolism in Withania somnifera
Authors: Sharma Lakee , Maurya Bipin , Pandey Saurabh , Rai Krishna Kumar , Pandey-Rai Shashi Pandey
Published: May 2022

In the present study, we have identified a R2R3 type MYB protein from Withania somnifera, i.e., MYB34 (WsMYB34), known for plant development and stress tolerance. MYB transcription factors (MYB TF) have been widely implicated in conferring biotic and abiotic stress tolerance in medicinal plants. To validate this notion, we have analyzed the impact of different concentrations of NaCl on Withania somnifera and the potential of MYB protein in affecting the growth and development by acting as TFs in regulating the expression of defence-related genes and secondary metabolites. Since structural and functional characteristics of MYB TF in W. somnifera remains largely unknown, in-silico analysis was exploited to understand conserved binding motifs, phylogeny, 3-D structure, and role in regulating stress-responsive genes. Based on the domain analysis and phylogenetic assessment, WsMYB34 was found to be a R2R3 type MYB protein, which is phylogenetically closer to Solanum pennellii. In addition, interaction analysis depicted the binding capacity of WsMYB34 protein on the promoter region of a triterpenoid synthesising gene viz; CYP85A69 (having CAACTG cis-regulatory sequence). The comparative microarray analysis also offered the role of WsMYB34 in abiotic stress tolerance. Exposure to NaCl imposed increased withanolide and flavonoid contents and significantly up-regulated the expression of key genes for withanolide and WsMYB34 gene by 0.93–3.68 fold 2.61–3.47 fold respectively. The CYP85A9 gene was also induced by 3.47 fold at 150mM NaCl. In addition, NaCl also affected growth and biochemical behaviour of W. somnifera. Thus, these findings depicted the role of WsMYB34 protein in plant salt tolerance.
Effect of Diffusion Kinetics on the Ice Nucleation Temperature Distribution
Authors: Stratta Lorenzo , Arsiccio Andrea , Pisano Roberto
Published: May 2022

The nucleation behavior of water is crucial in many fields, spanning meteorology, glaciology, biology, and astrophysics. We here report observations suggesting an effect of diffusion kinetics in water on the nucleation temperature distribution of ice. We performed differential scanning calorimetry analyses of repeated freeze/thaw cycles and investigated the effect of several variables on the regularity of the distributions obtained. We intriguingly observed that the thawing temperature and residence time above 0°C affect the width of the measured distributions. Specifically, conditions of enhanced diffusion translated into broader, more scattered distributions, while conditions of limited diffusion translated into narrower, more regular distributions. We propose a theoretical explanation centered on the temperature dependence of diffusion kinetics in water based on our experimental findings.
Identification and Validation of HEPACAM family member 2 is Correlated with Immune Infiltration as a Prognostic Biomarker in colon adenocarcinoma
Authors: Wang Shuai , Ruan Guo-Tian , Xu Sheng , Zhu Zhou , Qing Yan , He Chun-Gang , Kong Fan-Biao , Dong Chen-Cheng , Lin Jia-Wei , Zhang Xiang-Cheng , Zhou Bing-Chuan , Gong Yi-Zhen , Liao Cun , Zhang Lei , Pang Li-Ming
Published: May 2022

Background: Several studies give a superficial description that HEPACAM family member 2 (HEPACAM2) seems to be a prognostic biomarker in colon adenocarcinoma (COAD). While, systematic and in-depth research about diagnostic and prognostic value of HEPACAM2 in COAD patients is lacked. Besides, relationship between HEPACAM2 gene expression levels and immune cell infiltration is unclear. Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value from different databases. Secondly, a cohort of Guangxi COAD patients was established to verify HEPACAM2 expression pattern and diagnostic value. Thirdly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. We also utilized joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes. Finally, we explored the relationship between HEPACAM2 gene expression levels and immune cell infiltration.Results: In several biological databases, HEPACAM2 mRNA expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a high diagnostic value in COAD. The qPCR verification results in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues (P<0.001), and the diagnostic value was high in COAD (AUC=0.892). The prognostic value analysis showed that low expression of HEPACAM2 gene had a poorer overall survival (OS) in COAD patients when compared with those with high expression ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better overall survival of COAD.Conclusion: This study suggested that the HEPACAM2 may be a diagnostic and prognostic biomarker for COAD. Besides, HEPACAM2 was involved with immune response progress, Chemokine signaling pathway, Ras signaling pathway and Hematopoietic cell lineage.
Oversharing by honey bees and the spread of viruses
Authors: Lamas Zachary , Ryabov Eugene , Hawthorne David , Evans Jay
Published: May 2022

Deformed wing virus (DWV) is an emerging insect pathogen efficiently transmitted through communicable and vector-borne routes with Apis mellifera. Continual transmission of DWV between hosts and vectors is required for maintenance of the pathogen within the population, and this vector-host-pathogen system offers unique disease transmission dynamics for pathogen maintenance between vector and a social host. In a series of experiments, we study how vector-vector, host-host and host-vector transmission routes maintain DWV in a honey bee population. We found co-infestations on shared hosts allowed for movement of DWV from mite to mite. Additionally, two social behaviors of the honeybee, trophallaxis and cannibalization of pupae, provide routes for communicable transmission from bee to bee. Communicable circulation of the virus solely amongst hosts was then shown to act as a reservoir of DWV for naïve Varroa to acquire and subsequently vector the pathogen. Our findings illustrate communicable transmission between hosts can maintain and influence the future acquisition and vectoring of a pathogen by a vector. There are a handful of other infectious diseases, both zoonotic and which impact human health, that have potentially similar transmission dynamics.
Oxidative metabolic pathway of diquat mediated by aldehyde oxidase and its detoxification effect in vitro
Authors: Mao Zhengsheng , Yu Youjia , Wu Yuxuan , Huang Shuainan , Chu Chunyan , Jiang Qiaoyan , Cao Yue , Xie Weiran , Zhang Jinsong , Sun Hao , Chen Feng
Published: May 2022

Diquat (DQ) is a fast-acting herbicide that kills both weeds and grasses and is widely used in the agricultural industry. The reported DQ poisoning cases have significantly increased in recent years. However, there is no effective antidote for the treatment of DQ poisoning. In this study, aldehyde oxidase (AOX) has been validated as the vital enzyme involved in the DQ oxidative metabolism. The metabolism of DQ to diquat monopyridone (DQ M) was significantly inhibited by AOX inhibiters including raloxifene and hydralazine. The source of oxygen atom incorporated into DQ M was proved to be from water with H218O incubation experiment which further corroborated DQ M formation via AOX metabolism. The tissue distribution of DQ M in vivo and generation of DQ M in vitro by tissue co-incubation were consistent with AOX mRNA expression in tissues. The molecular docking analysis results also showed that DQ could bind to AOX. These results collectively demonstrated that AOX played a crucial in the metabolism of DQ to DQ M. Furthermore, the cytotoxicity of DQ was higher than DQ M at the same concentrations in HCCLM3, Huh7, A549, 16HBE, HEK293T and GMC cells. This study is the first to reveal the oxidative metabolic enzyme of DQ and the toxicity of DQ and its metabolite providing an important reference for clinical management of DQ poisoning.
Simulating groundstate and dynamical quantum phase transitions on a superconducting quantum computer
Authors: Dborin James , Wimalaweera Vinul , Barratt Fergus , Ostby Eric , O'Brien Thomas , Green Andrew
Published: May 2022

We optimise a translationally invariant, sequential quantum circuit on a superconducting quantum
device to simulate the groundstate of the quantum Ising model through its quantum critical point.
We further demonstrate how the dynamical quantum critical point found in quenches of this model
across its quantum critical point can be simulated. Our approach avoids finite-size scaling effects by
using sequential quantum circuits inspired by infinite matrix product states. We provide efficient
circuits and a variety of error mitigation strategies to implement, optimise and time-evolve these
states.
Left ventricular myocardial mass index associated with cardiovascular and renal prognosis in IgA nephropathy
Authors: Sági Balázs , Késői István , Vas Tibor , Csiky Botond , Nagy Judit , Kovács Tibor József
Published: May 2022

Introduction.
In chronic kidney disease (CKD), like in IgA nephropathy (IgAN), cardiovascular (CV) mortality and morbidity are many times higher than in the general population, and left ventricular hypertrophy (LVH) is an independent risk factor for CV disease. This follow-up study investigated the association between left ventricular mass index (LVMI) and renal or cardiovascular outcomes.
Methods.
We examined 118 IgAN patients. LVMI and LV geometry were investigated using echocardiography. The primary combined endpoints were total mortality, major CV events, and end-stage renal disease. Secondary endpoints, i.e. - cardiovascular or renal endpoints, - were also examined separately.
Results.
67% were males, mean age 53.5 ± 13.5. Mean follow-up time: 184 months. LVMI inversely correlated with eGFR (corr. coefficient: -0.365; p < 0.01). We divided the patients into two groups based on the LVMI cut-off suggested by the literature. The presence of LVH caused a worse prognosis in primary (p < 0.001), renal endpoints (p = 0.01), and also in CV endpoints (p = 0.001). The higher LVMI in men significantly worsened the prognosis in all endpoints. Concentric hypertrophy meant a worse prognosis. Independent predictors of LVMI were gender and eGFR in uni- and multivariate regression and hemoglobin levels only in logistic regression. Independent predictors of the primary endpoint were LVMI, eGFR, gender, obesity, HT, DM, and metabolic syndrome in Cox regression analysis.
Conclusion.
Increased LVMI may predict the progression to end-stage renal disease and CV events in IgAN. Determining LVMI may be a useful parameter not only in CV risk but also in the stratification of renal risk in CKD.
In vitro structural maturation of the primordial pre-40S coupled with U3 snoRNA release and central pseudoknot formation
Authors: Hurt Ed , Beckmann Roland , Cheng Jingdong , Berninghausen Otto , Venuta Giuseppe La , Lau Benjamin
Published: May 2022

The 90S>pre-40S transition is a decisive step in eukaryotic small subunit biogenesis leading to a primordial pre-40S (state Dis-C), where the U3 snoRNA keeps the nascent 18S rRNA locally immature. We in vitro reconstitute the ATP-dependent U3 release from this particle, catalyzed by the helicase Dhr1, and follow this process by cryo-EM revealing two successive pre-40S intermediates, Dis-D and Dis-E. The latter has lost not only U3 but all residual 90S factors including the GTPase Bms1. In vitro remodeling likewise induced the formation of the central pseudoknot, a universally conserved tertiary RNA structure that comprises the core of the small subunit decoding center. Thus, we could structurally reveal a key tertiary RNA folding step that is essential to form the active 40S subunit.
Histopathological and Immunohistochemical Features of Small to Big Satellite Nevus Uncover the Nevogenesis of Large/Giant Congenital Melanocytic Nevus
Authors: Gu Jieyu , Wei Boxuan , Gao Bowen , Duan Ran , Sheng Lingling , Zheng Danning , Bao Yongyang , Xie Feng
Published: May 2022

The nevogenesis of large/giant congenital melanocytic nevus (lgCMN) is a complex biological process involving several integral prenatal stages. Limited by ethical concerns, the understanding of whether lgCMN develops from the epidermis to the dermis or in the opposite direction remains controversial. With the present study of the accompanying satellite nevi, we hypothesized that lgCMN developed from epidermis to dermis. The satellite nevi were subdivided into 3 groups: big (diameter > 10 mm), medium (> 5 mm but ≤ 10 mm), and small (≤ 5 mm). Haematoxylin and eosin and immunohistochemical staining (SOX10, Ki67, p16) were performed to compare the nevocyte infiltration depth as well as the positive-stained cell proportions among these satellite nevi. In small satellite nevi, less deeply the nevocytes infiltrated the dermis, as well as more cells in the epidermis expressed SOX10 and Ki67 and fewer cells in the dermis expressed p16 than in big satellite nevi. Additionally, two specimens were obtained from each of 4 patients who underwent serial resections of lgCMN at an average interval of 1.75 years to examine the histopathological changes between them. In the present study, satellite nevi of different sizes represent different stages of lgCMN from early to late, deepening our comprehension of the sequential stages of lgCMN nevogenesis. Initially, abnormal nevocytes seeded, proliferated and spread along the epidermis. At specific locations, some nevocytes formed nests and gradually penetrated into the dermis. Eventually, the nevocytes infiltrated the dermis and entered a homeostatic state. This study provides new evidence supporting the theory of epidermal-to-dermal nevogenesis in lgCMN.
Development of a new 17-item Asthenopia Survey Questionnaire(ASQ-17) using Rasch Analysis
Authors: Lin Na , Li Xiaoman , Tian Li , Li Zhihua , Mao Jieli , Zhang Jiafang , Chen Jie , Lu Fan , Deng Ruzhi
Published: May 2022

Purpose
To develop a new 17-item Asthenopia Survey Questionnaire(ASQ-17) by Rasch analysis, and to evaluate a score to predict for its clinical application.
Methods
This cross-sectional study was conducted in the Eye Hospital of Wenzhou Medical University from January 2018 to January 2021. A total of 739 participants were recruited and 680 were involved in the result analysis. Three rounds of Rasch analysis was used to analyze the psychometric characteristics of items and options, and the receiver operating characteristic curve was used to obtain the cut-off value.
Results
Four phases were involved in the analyses. Phase 1 assessed the original ASQ-19, which has nineteen items and seven options. Phase 1 adjusted the item scoring mode to a four-point Likert response rating scale and combined the 18th and 19th items into a single one item, then ASQ-18 was obtained. Phase 2 analysis resulted in deleting the 11th item, and the ASQ-17 was obtained. Phase 3 and 4 assessed the new ASQ-17. All the evaluation indexes of ASQ-17 were acceptable. Infit and Outfit MnSq values of all items were 0.67 ~ 1.48, the variance explained by the principal component and the unexplained variance explained by the first contrast were 53.90%~59.40% and 1.50 ~ 1.80 in three dimensions. The curve peak of 0,1,2,3 scores in each dimension were separated from each other and in the same order. PSR and PSI values were 2.80 and 0.89, respectively. The functional differences of each item by gender were − 0.23 ~ 0.51logit, by age were − 0.36 ~ 0.62 logit. The mean person location was − 0.80logit. The mean score of dimension A (9.5 ± 4.1 vs 3.5 ± 3.2), B(7.3 ± 3.3 vs 2.5 ± 2.7), C(4.3 ± 2.2 vs 1.4 ± 2.0) and total (21.1 ± 8.1 vs 7.4 ± 7.0) in asthenopia participants were significantly higher than that of non-asthenopia (p values < 0.001). The area under curve(AUC) in two groups was 0.899 (p value < 0.001). Youden’s index was up to the maximum value 0.784 when the cut-off value was 12.5, and the sensitivity and specificity index were 100% and 78.4%, respectively.
Conclusion
The new ASQ-17 is an effective assessment tool for asthenopia with an optimal cut-off threshold value 12.5, which is suitable for diagnosis and curative effect evaluation.
Green synthesis of bioactive hydroxyapatite/cellulose composites from food industrial wastes
Authors: Abdelraof Mohamed , Farag Mohammad M. , Al-Rashidy Zainab Mohammed , Ahmed Hanaa Y. A. , El-Saied Houssni , Hasanin Mohamed S.
Published: May 2022

This work aimed at the preparation of cost-effective bioactive composites based on bacterial cellulose (BC) and eggshell or hydroxyapatite (HAp) by a green method using bacteria. HAp was prepared from eggshell wastes, and another one was synthesized from chemical precursors for comparison. The BC productivity was evaluated, and the resultant composites were characterized by XRD, FTIR, and SEM/EDX. Furthermore, the biodegradation and bioactivity were assessed in SBF, and the cell viability was studied against oral normal cells. The results showed that the productivity of BC was not affected by HAp at lower concentrations; however, the yield was decreased at higher concentrations. Moreover, the eggshell was converted to Ca3(PO4)2 in BC/eggshell composite, while HAp in the composites contained either eggshell-derived HAp or chemically-derived HAp was a combination of Ca3(PO4)2 and HAp phases. The in vitro bioactivity test in SBF showed that all composites were induced the formation of a bone-like apatite layer on their surface. Finally, the in vitro cell viability test was confirmed good biocompatibility against the composites which expectedly are as pure as to be used safely in different biomedical applications.
Extensive multiregional urea elevations in vascular dementia point towards a novel shared mechanism of disease amongst the age-related dementias
Authors: Philbert Sasha , Xu Jingshu , Scholefield Melissa , Patassini Stefano , Church Stephanie J. , Unwin Richard D. , Roncaroli Federico , Cooper Garth J.S.
Published: May 2022

Vascular dementia (VaD) is one of the most common causes of dementia amongst the elderly. Despite this, the molecular basis of VaD remains poorly characterised when compared to other age-related dementias. Probably as a result, therapeutic options are largely restricted to repurposing medication currently used in Alzheimer’s disease (AD) which, however, offer limited therapeutic benefit. Pervasive cerebral elevations of urea have recently been reported in AD, Huntington’s disease (HD), and Parkinson’s disease dementia (PDD); however, a similar analysis was not yet available for VaD. Here we utilised ultra-high-performance liquid chromatography tandem-mass spectrometry (UHPLC-MS/MS) to measure urea levels from seven cerebral regions in post-mortem tissue from cases of VaD (n = 10) and matched controls (n = 8/9). Brain-urea measurements from our previous investigations of AD, HD, and PDD, quantified using corresponding mass-spectrometry techniques, were also used to generate comparisons with VaD. Elevated urea levels ranging from 2.2- to 2.4-fold-change in VaD cases were identified in six out of the seven regions analysed. These elevations are similar in magnitude to those observed in uraemic encephalopathy, a CNS disorder characterised by accumulation of urea in the cerebral tissues. Fold-elevation of urea was highest in the basal ganglia and hippocampus (2.4-fold-change), consistent with the observation that these regions are severely affected in VaD. When compared with other age-related dementias, VaD displayed the lowest overall fold-increase, followed by HD (3.4-fold), PDD (4.3-fold), and AD (5.3-fold). Taken together, these data not only describe, for the first time, a multiregional elevation of brain-urea levels in VaD, but also imply the existence of a common urea-mediated disease mechanism that is now known to be present in at least four of the main age-related dementias. If the precise origin of this urea phenotype can be identified, brain-urea metabolism may be a viable target for the experimental treatment of multiple age-related dementias.
R- and S-ketamine abrogate lipopolysaccharide-induced depressive-like behavior through microglial modulation: a differential anti-inflammatory and neurotrophic effect of the enantiomers
Authors: Filho Adriano Chaves , Los Deniele , Soares Michele , Juca Paloma , de Queiroz Tatiana , Silva Francisco Eliclecio Rodrigues da , Saraiva Karina , Silva Amanda , Azul Francisco Vinicius Serra , Leal Luzia Kalyne , Peixoto Christina , Macedo Danielle S
Published: May 2022

Depression is a disabling mental disorder associated with increased proinflammatory cytokines and glial activation. Ketamine (KET), a racemic mixture of the R- and S-KET enantiomers, emerged as a rapid antidepressant drug. This study investigates the microglial modulatory and synaptogenic effects of R- and S-KET in a lipopolysaccharide (LPS)-induced depression model. Male rats were challenged with LPS and, 24h later, received R-KET or S-KET (10 mg/kg, IP). Two h later, these animals were evaluated for depression-like behaviors and adverse psychomimetic effects. Also, BV2 microglial cultures were challenged with LPS and exposed to R- or S-KET. Both enantiomers reversed LPS-induced depression-like behaviors and increased plasma corticosterone. LPS caused intense hippocampal glial activation, demonstrated by microglial (Iba1) and astrocytic (GFAP) markers, accompanied by increased nitrite, pro-inflammatory cytokines TNFα and IL-6, and M1 microglial phenotype markers (iNOS and CD86 mRNA). Both enantiomers attenuated Iba1 and GFAP hippocampal increase, but only S-KET induced an M2 phenotype, indicated by the higher arginase activity, IL-4, IL-10, and expression of M2a response genes (LGLAS3 and IGF-1). In the BV2 cells, S-KET increased arginase activity, IL-4, and IL-10 levels. Both enantiomers reversed the LPS-induced changes in synaptic ultrastructure and synaptosome viability. Only S-KET increased the density and the presence of mature spines in the dentate gyrus. Also, S-KET increased hippocampal BDNF maturation and boosted its secretion by BV2 microglia. Therefore, the present study demonstrated, for the first time, the unique immunomodulatory profile of S-KET, promoting a reparative M2 phenotype and protecting synaptic structures from the LPS-associated damage.
Identification and analysis of B cell epitopes of hemagglutinin of H1N1 influenza virus
Authors: Feng Qing , Huang Xiao-Yan , Feng Yang-Meng , Sun Li-jun , Sun Jing-Ying , Li Yan , Xie Xin , Hu Jun , Guo Chun-Yan
Published: May 2022

The frequent variation of influenza virus hemagglutinin (HA) antigen is the main cause of influenza pandemic. Therefore, the study of B cell epitopes of HA is of great significance in the prevention and control of influenza virus. In this study, the cleavage vaccine of 2009 H1N1 influenza virus was used as immunogen, and the monoclonal antibodies (mAbs) were prepared by conventional hybridoma fusion and screening techniques. The characteristics of mAbs were identified by ELISA method, Western-blot test and hemagglutination inhibition test (HI). Using the obtained mAbs as a tool, the B cell epitopes of HA were predicted by ELISA blocking test, sandwich ELISA method and computer simulation method. Finally, four mAbs against HA antigen of H1N1 influenza virus were obtained. The results of ELISA and computer prediction showed that there were at least two types of epitopes on HA of influenza virus. This study provides experimental data for improving the prediction of HA epitopes of influenza viruses and developing potential influenza vaccines, and also provides a new method for the prediction of other pathogenic microorganisms.
N-acetylcysteine Regulates Dental Follicle Stem Cell Osteogenesis and Oral Bone Repair via ROS scavenging
Authors: Meng Zhaosong , Liu Jiacheng , Feng Zhipeng , Guo Shuling , Wang Mingzhe , Wang Zheng , Sui Lei , Li Hongjie
Published: May 2022

Background
Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for oral bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based oral bone regeneration.
Methods
DFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro. Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate oral bone regeneration in tooth extraction sockets after local transplantation of NAC, DFSCs or NAC-treated DFSCs.
Results
5 mM NAC-treated DFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; 10 mM NAC was not beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between DFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, DFSCs or NAC-treated DFSCs were safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated DFSCs possessing the best effect.
Conclusions
The proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based oral bone regeneration.
A retrospective clinical comparative study of intramedullary nailing and minimally invasive plate osteosynthesis for extra-articular distal tibia fractures
Authors: Wang Chaofeng , Huang Qiang , Lu Dongsheng , Duan Ning , Zhang Conming , Wang Qian , Ma Teng , Zhang Kun , Li Zhong
Published: May 2022

The treatment of extra-articular distal tibia fractures is a difficult challenge. Minimally invasive plating osteosynthesis (MIPO) and intramedullary nailing (IMN) are satisfactory extra-articular distal tibia fractures. The optimal surgical treatment for extra-articular distal tibia fractures remains controversial. The purpose of this retrospective study was to compare the clinical and functional outcomes of patients with extra-articular distal tibia fractures treated with MIPO or IMN. For this retrospective study, a total of 266 patients with closed extra-articular distal metaphysis (OA type 43-A) or closed distal tibial fracture (AO type 42) were enrolled and included; 110 patients were treated with MIPO, and 156 patients underwent IMN. There was no significant difference in the primary operation union rate, AOFAS score, deep surgical site infection or malalignment between the MIPO and IMN groups. However, there was a longer operation time, more prospective times, more intraoperative blood loss and more frequent anterior knee pain in the IMN groups than in the MIPO group. There was a significantly shorter time to union in the IMN group than in the MIPO group (138.8 ± 11.0 vs. 153.5 ± 17.1 days, p < 0.05) and a lower superficial surgical site infection in the IMN group than in the MIPO group (1.9% vs. 8.2%, p < 0.05). We found that extra-articular distal tibia fractures can be treated satisfactorily with IMN or MIPO. Pollor blocking screws have a main role in improving the efficacy of IMN. Regardless of the operation time, intraoperative blood loss and occurrence of anterior knee pain, IMN was recommended as the choice to treat extra-articular distal tibia fractures.