bluuebunny/crossref_metadata_2025 huggingface dataset:
PPARγ expression in chorionic villus tissue in relation to unexplained recurrent miscarriage
Authors: Li Dan , Wang Fen , Li Xue , Jiao Yong-Hui
Published: July 2022

Objective To study the differential expression of PPARγ in the villus tissue of patients with unexplained recurrent miscarriage and to explore the role of PPARγ in the development of unexplained recurrent miscarriage. Methods Pregnant women attending the obstetrics and gynecology outpatient clinic and wards of the People's Hospital of Xinjiang Autonomous Region from January 2019 to June 2021 were collected. 20 patients with unexplained recurrent miscarriage (in early pregnancy) and 20 patients with normal pregnancy who voluntarily terminated their pregnancy were each selected, and the chorionic villus tissues were collected from both groups. The differential expression of PPARγ mRNA in the chorionic villus tissues of the two groups was detected by real-time fluorescence quantitative PCR , and the differential expression of PPARγ protein in the chorionic villus tissues of the two groups was detected by Western blot and immunohistochemistry. The results showed that PPARγ in the chorionic villus tissues of URSA patients was higher than that in the chorionic villus tissues of normal pregnancy patients (P<0.001)，the expression of PPARγ protein in the chorionic villus tissues of URSA patients was found to be significantly higher than that in the normal pregnancy group using Western blot and immunohistochemistry(P<0.001).Conclusion PPARγ was highly expressed in the chorionic villus tissues of unexplained miscarriage, suggesting that PPARγ may be involved in the development of unexplained recurrent miscarriage.
Genetic characterization of Dengue virus serotype 1 circulating in Reunion Island, 2019- 2021, and the Seychelles, 2015-2016
Authors: Hafsia Sarah , Barbar Tatiana , Wilkinson David A , Atyame Célestine , Biscornet Leon , Bibi Jastin , Louange Meggy , Gedeon Jude , De Santis Olga , Flahault Antoine , Cabie André , Bertolotti Antoine , Mavingui Patrick
Published: July 2022

Background An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion.Methods: Nucleic acids were extracted from blood samples collected from dengue positive patients, DENV-1 was identified by RT-PCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies.Results: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5). Conclusions: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated.
MicroRNA-650 regulates the pathogenesis of Alzheimer’s Disease through targeting Cyclin-Dependent Kinase 5
Authors: Lin Li , Liu Xiaodong , Cheng Xuejun , Li Yuijing , Gearing Marla , Levey Allan , Huang Xiaoli , Li Ying , Jin Peng , Li Xuekun
Published: July 2022

Alzheimer’s disease (AD) pathogenesis features progressive neurodegeneration, amyloid-β plaque formation and neurofibrillary tangles. Ample evidence has indicated the involvement of epigenetic pathways in AD pathogenesis. Here, we show that expression of microRNA 650 (miR-650) is altered in brains from AD patients. Furthermore, we found that the processing of primary miR-650 to mature miR-650 is misregulated. Bioinformatic analysis predicted that miR-650 targets the expression of three AD-associated components: Apolipoprotein E (APOE), Presenilin 1 (PSEN1), and Cyclin-Dependent Kinase 5 (CDK5), and we have experimentally confirmed that miR-650 is able to significantly decrease the expression of APOE, PSEN1, and CDK5 in vitro. Importantly, the overexpression of miR-650 was further shown to significantly reduce the CDK5 level and ameliorate AD pathologies in APP-PSEN1 transgenic mice. Overall, our results indicate that miR-650 influences AD pathogenesis through regulation of CDK5.
EDA-E7 activated DCs induces specific cytotoxic T lymphocyte immune responses against HPV expressing cervical cancer in human setting
Authors: Feng Juan , Liu Yongliang , Zhuang Na , Chai Zixuan , Liu Limei , Qian Cheng , Li Jiatao , Shan Juanjuan
Published: July 2022

Background
Cervical cancer is a major cause of cancer death in women worldwide. Human papillomavirus (HPV) infection especially genotypes 16 and 18 is the main factor induces cervical lesions. Targeting HPV viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment.
Methods
Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8 + T cells response in mouse. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as specific antitumor T cell response.
Results
We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect can work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848 and CpG2216. EDA-E7 matured DCs could activate T cells and trigger anti-tumor response in vitro. Single RNA sequencing and T cell target killing assay confirmed the activation of T cells by EDA-E7 matured DCs.
Conclusions
Therapeutic vaccination with EDA-E7 fusion protein is effective for human cervical carcinoma treatment.
Ultra-thin double barrier AlGaN/GaN high threshold voltage HEMT with graded AlGaN/Si3N4 gate and p-type buffer layer
Authors: dong kexiu , Zhang Yangyi , Wang Bingting
Published: July 2022

An ultra-thin double barrier enhancement mode (E-mode) AlGaN/GaN high electron mobility transistor (HEMT) with p-type buffer layer and Si 3 N 4 /graded p-AlGaN gate is proposed and investigated by Silvaco TCAD. The simulation results show that the designed HEMT can obtain a high threshold voltage over 5.0 V and large gate swing. The maximum gate leakage current is 3.11×10 -4 A/mm at 30 V gate voltage, which decreases four orders of magnitude compared to the conventional double barrier HEMTs. Due to the p-type buffer layer, the cut-off frequency for the proposed HEMT is raised over three-times compared to the conventional double barrier structure HEMT with n-type buffer layer. Meanwhile the designed HEMT exhibits high breakdown voltage and large current-gain. Moreover, the impacts of Si 3 N 4 layer thickness under gate and GaN channel layer thickness are analyzed. Both layers play significantly roles in obtaining high threshold voltage for the device by adjusting the conduction band energy of AlGaN/GaN interface quantum well.
Prediction of amyloid PET positivity via machine learning algorithms trained with EDTA-based blood amyloid-β oligomerization data
Authors: Youn Young Chul , Kim Hye Ryoun , Shin Hae-Won , Jeong Hae-Bong , Han Sang-Won , Pyun Jung-Min , Ryoo Nayoung , Park Young Ho , Kim SangYun
Published: July 2022

Background: The tendency of amyloid-β oligomer (AβO) formation in the blood, measured with Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ), is a valuable biomarker for Alzheimer’s disease (AD), which has been verified using heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAβ and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. Methods: The performance of EDTA-based MDS-OAβ in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAβ level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset.Results: The Random Forest showed best performance in MDS-OAβ predicting amyloid PET positivity with other features showed an accuracy of 77.14±4.21% and a F1-value of 85.44±3.10 %. The order of significance in contributing features was MDS-OAβ, MMSE, Age and APOE. The Support Vector Machine using the MDS-OAβ value only showed an accuracy of 71.09±3.27% and F-1 value of 80.18±2.70%. Conclusions: The Random Forest model using EDTA-based MDS-OAβ combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.
Planning Lane Changes using Advance Visual and Haptic Information
Authors: Frissen Ilja , Mars Franck
Published: July 2022

Taking a motor planning perspective, this study investigates whether haptic force cues displayed on the steering wheel are more effective than visual cues in signaling the direction of an upcoming lane change. Licensed drivers drove in a fixed-base driving simulator equipped with an active steering system for realistic force-feedback. They were instructed to make lane changes upon registering a directional cue. Cues were delivered according to the movement precuing technique employing a pair of precues and imperative cues which could be either visual, haptic, or crossmodal (a visual precue with a haptic imperative cue, and vice versa). The main dependent variable was response times. Additional analyses were conducted on steering wheel angle profiles and error rates. Conditions with a haptic imperative cue produced considerably faster responses than conditions with a visual imperative cue, irrespective of the precue modality. Valid and invalid precues produced the typical gains and costs, with one exception. There appeared to be little cost in response time or steering errors associated with invalid cueing when both cues were haptic. The results are consistent with the hypothesis that imperative haptic cues facilitate action selection while visual stimuli require additional time-consuming cognitive processing.
Beauty and the Sharp Fangs of the Beast: Degree of Angularity Predicts Perceived Preference and Threat
Authors: Friedenberg Jay , Lauria Gina , Hennig Kaitlyn , Gardner Isabel
Published: July 2022

Preference for angular vs. curved forms has a long history in psychology but few of the many studies conducted have examined actual degree of angularity. In two experiments we present observers with randomly positioned and randomly oriented texture displays of angles viewed within a circular frame. The angle conditions varied from 0°-180° in 20° increments, covering the entire spectrum of possibilities including acute, obtuse, right, and straight line angles. In Experiment 1, 25 undergraduates rated the perceived beauty of these displays. In Experiment 2, the same stimulus set and procedure were used with 27 participants instead judging perceived threat. Based on the findings in the literature, we predicted that sharper angles would be judged less beautiful and more threatening. The results were mostly confirmed. Acute angles are preferred less but there are also distinct preferences for right angles and straight lines, perhaps due to their greater familiarity in constructed environments. There was a consistent and anticipated finding for threat in the second study: the sharper an angle the greater its perceived threat. Fear of sharp objects as assessed in a personality questionnaire was found to positively correlate with threat judgements. Future work should look more closely at degree of angularity in embedded object contours and at individual response differences.
Needle-based gastrocnemius lengthening: A novel ultrasound-guided non- invasive technique
Authors: Marcos Álvaro Iborra , Martínez Manuel Villanueva , Díaz Homid Fahandezh-Saddi
Published: July 2022

Background: Gastrocnemius tendon lengthening is performed to treat numerous conditions of the foot and ankle. Gastrocnemius shortening has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flat foot deformity, and metatarsalgia. Ultrasound-guided ultraminimally invasive lengthening of the gastrocnemius is a step forward in this type of surgery. It can be performed in both legs simultaneously without ischemia using only local anesthesia plus sedation and without the need for a cast or immobilization. The truly novel advantage of the procedure is that it can be performed in the office, without specific surgical instruments. The aim of our research was to prove the effectiveness and safety of a new closed needle-based ultrasound-guided surgical procedure for lengthening the gastrocnemius tendon.Methods and ResultsWe performed ultrasound-guided gastrocnemius tendon lengthening using a needle in 8 fresh frozen specimens (3 left and 5 right). None of the specimens had been affected by disease or undergone previous surgery that could have affected the surgical technique.We used a linear transducer with an 8- to 17-Mhz linear transducer and the beveled tip of an Abbocath as a surgical blade to perform the lengthening procedure. The gastrocnemius Achilles tendon recession was entirely transected in all 8 specimens, with no damage to the sural nerve or vessels. The improvement in dorsal flexion was 15°. Conclusion: Needle-based ultrasound-guided gastrocnemius tendon lengthening is safe, since the surgeon can see all structures clearly, thus minimizing the risk of damage. The absence of a wound obviates the need for stitches, and recovery seems to be faster. The procedure can be performed in a specialist's office, as no specific surgical instruments are required. This technique could be a valid option for gastrocnemius lengthening and may even be less traumatic than using a hook-knife, as in our previous description.
In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner
Authors: Manzoni Olivier , Iezzi Daniela , Caceres-Rodriguez Alba
Published: July 2022

Cannabidiol (CBD), one of the main components of cannabis, is generally considered safe, despite the lack of studies on the possible consequences of its consumption during critical periods of neurodevelopment, including prenatal life. Although CBD crosses the placenta and its use during pregnancy is steadily increasing, the impact of gestational CBD exposure on early life is unknown. Here, we combined behavioral exploration and deep learning to assess how in utero exposure to low doses of CBD alters pre-weaning behaviors in mouse pups of both sexes. The data reveal that pups from CBD-treated dams exhibit sex-specific alterations in weight growth, homing behavior, and the syllabic repertoire of ultrasonic vocalizations. Thus, prenatal CBD is associated with alterations in innate behavioral responses and communication skills.
Molecular Characterization of Coxsackievirus B5 from the Sputum of Pneumonia Children Patients of Kunming, Southwest China
Authors: Tan Miao , Suo Jiale , Zhang Zhilei , He Wenji , Tan Li , Jiang Haiyan , Li Ming , He Juan , Pan Yue , Xu Bin , Yan Lingmei , Bin Songtao , Gan Zhengyan , Sun Yuxing , Jiang Hongchao , Sun Qiangming , Zhang Zhen
Published: July 2022

Background
Coxsackievirus B5 (CVB5) can cause respiratory infections. However, the molecular epidemiological information about CVB5 in respiratory tract samples is still limited. Here, we report five cases in which CVB5 was detected in sputum sample of pneumonia children patients from Kunming, southwest China.
Methods
CVB5 isolates were isolated in H1-HeLa cells. Whole-genome sequencing of CVB5 isolates from sputum was performed using segmented PCR, and phylogenetic, mutation and recombination analysis, followed by prediction of the tertiary protein structure.
Results
A total of five CVB5 complete genome sequences were obtained. No obvious homologous recombination signals comparing with other CVBs were observed in the five isolates. Phylogenetic analysis showed that the five CVB5 sputum isolates were from a independent branch in genogroup E.
Conclusions
We unexpectedly found five cases of CVB5 infection instead of rhinoviruses infection during our routine surveillance of rhinoviruses in respiratory tract samples. All five patients were hospitalized with pneumonia symptoms and were not tested for enterovirus during their hospitalization. This report suggests that enterovirus surveillance in patients with respiratory symptoms should be strengthened.
Transmission Dynamics of Human Herpesvirus 6 and 7 from Whole Genome Sequences of Families
Authors: Chrisman Brianna , He Chloe , Jung Jae-Yoon , Stockham Nate , Paskov Kelley , Wall Dennis
Published: July 2022

While hundreds of thousands of human whole genome sequences (WGS) have been collected in the effort to better understand genetic determinants of disease, these whole genome sequences have less frequently been used to study another major determinant of human health: the human virome. Using the unmapped reads from WGS of over 1,000 families, we present insights into the human blood DNA virome, focusing particularly on human herpesvirus (HHV) 6A, 6B, and 7. In addition to extensively cataloguing the viruses detected in WGS of human whole blood and lymphoblastoid cell lines, we use the family structure of our dataset to show that household drives transmission of several viruses, and identify the Mendelian inheritance patterns characteristic of inherited chromsomally integrated human herpesvirus 6 (iciHHV-6A). Consistent with prior studies, we find that 0.6\% of our dataset's population has iciHHV, and we locate candidate integration sequences for these cases. We document genetic diversity within exogenous and integrated HHV species and within integration sites of HHV-6. Finally, in the first observation of its kind, we present evidence that suggests widespread de novo HHV-6B integration and HHV-7 integration and reactivation in lymphoblastoid cell lines. These findings show that the unmapped read space of WGS is a promising source of data for virology research.
Novel Compound Heterozygous Mutations of MTHFR Gene in a Chinese family with homocystinuria due to MTHFR deficiency
Authors: Lu Yitong , Zhao Shaozhi , Yang Hua , Wang Xiaolei , Miao Chen , Liu Hongwei , Zhang Xinwen , He Xiaohui
Published: July 2022

Background Homocystinuria due to methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. The purpose of this study is to expand the mutation site of MTHFR gene and provide genetic counseling for this family.Methods A couple came to our hospital for pre-pregnancy genetic counseling. We collected the family history and detailed clinical information, then performed whole-exome sequencing, and analyzed the pathogenicity of the candidate mutations.Results We found that the father of the proband had homocystinuria, the proband and his brother had low blood methionine levels at birth, and the brain MRI showed brain dysplasia. The third fetus was found to have a broadened triangle of the bilateral ventricle at 19 weeks of pregnancy. The compound heterozygous mutations of c. 602A>C (p.His201Pro) and c.1316T>C (p.Leu439Pro) of MTHFR gene in the first three fetuses were found by whole-exome sequencing. The heterozygous c.602A>C mutation of MTHFR gene is a novel missense mutation that has been submitted to the ClinVar with Variation ID 992662.Conclusions In consideration of the clinical phenotype, family history, and result of genetic testing, we speculated that both patients may have homocystinuria due to MTHFR deficiency. Homocystinuria due to MTHFR deficiency caused by compound heterozygous mutations composed of the MTHFR gene in this family may be associated with cerebral atrophy and cerebral dysplasia. The novel compound heterozygous mutations broaden the mutation spectrum of the MTHFR gene and enhance the application of genetic counseling and carrier screening in rare diseases.
Animal Species Identification Utilising DNAs Extracted from Traditionally Manufactured Gelatin
Authors: Kuramata Haruki , Hashiba Miho , Kai Yuriko , Nishizawa Kazuhisa , Inoue Tsuyoshi , Kikuchi-Ueda Takane , Uetsuki Manabu , Yamauchi Kazuya , Fujisawa Akira , Oshikane Hiroyuki
Published: July 2022

Gelatin, sourced from collagen, is an acid-, alkali- or enzymatically hydrolysed product obtained from animal skins and bones, having been widely used for manufacture of various cultural properties, e.g. as a water-soluble binder for dissolving pigments, and as a glue for musical instruments and traditional crafts along with human history. The identification of animal species in gelatin, hence, possibly provide one of critical clues for understanding the lifestyles, the cultural backgrounds and the technologies which might have been already extinct or being threatened with extinction. However, there has been no valid method established to date for identifying the animal species from the traditional gelatins. We herein report that the nucleic acids contents (dsDNA, ssDNA and miRNA) from commercially-available gelatins manufactured according to the classical procedures (wanikawa) exhibited much higher (about 10 times) than those from the modern gelatins through industrialised process (yonikawa), suggesting that DNA analysis using the gelatins from cultural assets could be substantially feasible. Moreover, we here illustrate partial successes in the animal species identification coupled with DNA barcoding technique, hopefully paving the way for scientifically more reliable animal species identifications of archaeological specimens.
Rutin attenuates oxidative stress via PHB2-mediated mitophagy in MPP + - induced SH-SY5Y cells
Authors: Lai Xiaoyi , Zhang Yongjiang , Wu Jiannan , Shen Mengmeng , Yin Shiyi , Yan Junqiang
Published: July 2022

Background and Purpose
Oxidative stress plays a crucial role in the occurrence and development of Parkinson's disease (PD). Rutin, a natural botanical ingredient, has been shown to have antioxidant properties. This study aimed to investigate the neuroprotective effect and mechanism of rutin in PD.
Methods
MPP+(1-methyl-4-phenylpyridinium)-treated SH-SY5Y cells were used as a PD model. SH-SY5Y cells were transfected with human PHB2-shRNA lentiviral particles to interfere with the expression of PHB2(Prohibitin2). Intracellular oxidative damage was analyzed by detecting ROS(Reactive oxygen species), MDA(Malondialdehyde) and MMP(Mitochondrial membrane potential). The protein expression of Nrf2(Nuclear factor E2-related factor 2), HO-1(Heme oxygenase-1), NQO1(NADPH quinone oxidoreductase-1) and PHB2, TOM20(Translocase of outer mitochondrial membrane 20), LC3II/LC3I(Microtubule-associated protein II light chain 3 (LC3II) to microtubule-associated protein I light chain 3 (LC3I)) were detected with western blotting. In addition, we observed the expression of PHB2 and LC3II/LC3I by immunofluorescence staining.
Results
MPP+ treatment significantly increased the ROS, MDA generation and the level of MMP depolarization, decreased the protein expression of Nrf2, HO-1, NQO1 and TOM20, PHB2, LC3II/LC3I. However, rutin treatment significantly decreased the ROS, MDA generation and the level of MMP depolarization, increased the protein expression of Nrf2, HO-1, NQO-1 and TOM20, PHB2, LC3II/LC3I. Silencing of PHB2 followed by treatment with MPP+ and rutin obviously increased the ROS, MDA generation and the level of MMP depolarization. At the same time, the protein expression of Nrf2, HO-1, NQO-1 and TOM20, LC3II/LC3I were obviously decreased.
Conclusions
Rutin inhibits MPP+-induced oxidative damage in SH-SY5Y cells through PHB2-mediated mitophagy. Rutin can be used as a potential drug for the prevention and treatment of PD.
The Framing of time-dependent machine learning risk prediction models among young individuals with acute coronary syndromes
Authors: Carvalho Luiz Sergio , Alexim Gustavo , Nogueira Ana Claudia , Fernandez Marta , Rezende Tito , Avila Sandra , Reis Ricardo , Soares Alexandre Anderson , Sposito Andrei
Published: July 2022

Acute coronary syndrome (ACS) is a common cause of death in individuals older than 55 years. Although younger individuals are less frequently seen with ACS, this clinical event has increasing incidence trends and triggers considerable economic burden. Young individuals with ACS (yACS) are usually underrepresented and show idiosyncratic epidemiologic features compared to older subjects. These differences may justify why available risk prediction models usually penalize yACS with higher false positive rates compared to older subjects. We hypothesized that exploring temporal framing structures such as prediction time, observation windows and window shifts, coupled with subgroup-specific prediction, could improve time-dependent prediction metrics. In a large cohort of ACS individuals (nglobal_cohort=6341 and nyACS=2242), the predictive accuracy for adverse clinical events in ACS was optimized by using specific rules for yACS and splitting short-term and long-term prediction windows, leading to the detection of 80% of events, compared to 68% by using a rule designed for the global cohort.
Modulation of vascular reactivity by reductive stress associated with excessive consumption of Hibiscus Sabdariffa Linnaeus
Authors: Manzano-Pech Linaloe , Guarner-Lans Verónica , Díaz-Díaz Eulises , Soto María Elena , Pérez-Torres Israel
Published: July 2022

Reductive stress (RS) increases the reducing equivalents and components of the antioxidant system that can disturb redox homeostasis. Hibiscus Sabdariffa Linnaeus (HSL) has antioxidant properties and provides compounds that favor the functioning of the antioxidant systems, and excess in its consumption could lead to RS. The goal was to evaluate the vascular reactivity modulation by RS associated to the HSL infusions consumption of different percentages. 40 male Wistar rats were divided into 4 groups. Group 1; Control, Groups 2, 3 and 4; were supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. Vascular reactivity, morphological changes, and different components of antioxidant systems were evaluated in the thoracic aorta including glucose-6-phosphate dehydrogenase, glutathione-S-transferase, thioredoxin-reductase, glutathione, selenium, thiols, lipoperoxidation, and 3-nitrityrosine. Vasoconstriction was increased and vasorelaxation decreased. These alterations were reversed by O2− and H2O2. The wall thickness and elastic fibers (p = 0.004 and p = 0.02, respectively), the glucose-6-phosphate dehydrogenase (p = 0.02), thioredoxin-reductase, lipoperoxidation, glutathione (p = 0.01), and selenium (p = 0.04) were increased but decreased thiols (p < 0.001), 3-nitrityrosine (p = 0.04) and glutathione-S-transferase (p = 0.0005) in groups 3 and 4. The excess antioxidants provided by the HSL infusions at 3% and 6% modify vascular reactivity, increasing the enzymatic antioxidant system, and depleting ROS, thus leading to RS.
A novel nomogram for adult primary perihilar cholangiocarcinoma and considerations concerning lymph node dissection
Authors: Liu Zehan , Liu Shuangqing , Wang Ming , Li Xinye , Wang Xiangyu , Yang Qin , Wang Ximo , Zhang Qi
Published: July 2022

Objective To construct a nomogram that can predict the survival rate of patients with perihilar cholangiocarcinoma.Methods Data from 1808 patients diagnosed with perihilar cholangiocarcinoma between 2004 and 2015 were extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into training and validation sets. The nomogram was established by machine learning and Cox model. The discriminant ability and prediction accuracy of the nomogram were evaluated by concordance index (C-index), receiver operator characteristic (ROC) curve and calibration curve. Kaplan-Meier curves show the prognostic value of the associated risk factors and classification system. Results Machine learning and multivariate Cox risk regression model showed that sex, age, tumor differentiation, primary tumor stage(T), lymph node metastasis(N), TNM stage, surgery, radiation, chemotherapy, lymph node dissection were associated with the prognosis of perihilar cholangiocarcinoma patients relevant factors (P < 0.05). A novel nomogram was established. In the training set, the area under the ROC curve for 3-year and 5-year survival was 0.745 and 0.749, respectively. The validation set AUC for 3-year and 5-year survival was 0.754 and 0.745, respectively. In patients with stage T1 and N0 perihilar cholangiocarcinoma, the prognosis of ≥ 4 lymph nodes dissected was better than that of 1- 3 lymph nodes dissected (P<0.01). Conclusion The nomogram prognostic prediction model can provide a reference for evaluating the prognosis and survival rate of patients with perihilar cholangiocarcinoma. Patients with stage T1 and N0 perihilar cholangiocarcinoma have more benefits by increasing the number of lymph node dissection.
Semantic Cut Elimination for the Logic of Bunched Implications and Structural Extensions, Formalized in Coq
Authors: Frumin Dan
Published: July 2022

The logic of bunched implications (BI) is a substructural logic that forms the backbone of separation logic, the much studied logic for reasoning about heap-manipulating programs.Although the proof theory and metatheory of BI are mathematically involved, the formalization of important metatheoretical results is still incipient.In this paper we present a self-contained formalized, in the Coq proof assistant, proof of a central metatheoretical property of BI: cut elimination for its sequent calculus, as well the extension of cut elimination to sequent calculus with arbitrary structural rules. The presented proof is semantic, in the sense that is obtained by interpreting sequents in a particular ``universal'' model.This results in a more modular and elegant proof than a standard Gentzen-style cut elimination argument, which can be subtle and error-prone in manual proofs for BI.In particular, our semantic approach avoids unnecessary inversions on proof derivations, or the uses of cut reductions and the multi-cut rule. Our prof is modular and also robust. We demonstrate how our method scales to (i) all extensions of BI with arbitrary structural rules, and (ii) an extension with an S4-like ▯ modality.
Dietary supplementation with full-fat Hermetia illucens larvae and multi-probiotics as a substitute for antibiotics improves the growth performance, gut health, and antioxidative capacity of weaned pigs
Authors: Phaengphairee Pheeraphong , Boontiam Waewaree , Wealleans Alexandra , Hong Jinsu , Kim YooYong
Published: July 2022

Background: The widespread use of antibiotics (such as amoxicillin) in the food animal production industry has led to the proliferation of multi-antibiotic resistant pathogens. In this study, we examined whether dietary supplementation with full-fat black soldier fly larvae (BSFL; alone or in combination with multi-probiotics) is an effective alternative to dietary antibiotics in weaning piglets. We also tested the effects of these diets on growth performance, nutrient digestion, intestinal morphology, and oxidative stress in weaned pigs. A total of 80 crossbred piglets [(Landrace × Large White) × Duroc] were randomly allotted to four diet groups: positive control (PC) diet supplemented with 0.02% amoxicillin; negative control (NC) diet without addition; BSFL12 diet (NC + 12% full-fat BSFL); and BSFL + Pro diet (BSFL + 0.1% multi-probiotics, including Bacillus subtilis, B. licheniformis, and Saccharomyces cerevisiae). All groups had five replicates, with four piglets per replicate. Results: Dietary BSFL + Pro improved the final body weight, overall average daily gain, gain-to-feed ratio, and decreased the diarrhoea rate of piglets. Compared to the NC diet, the BSFL12 and BSFL + Pro diets improved nutrient digestibility (dry matter, crude protein, and ether extract) and increased the serum levels of immunoglobulin A and glutathione peroxidase, while reducing the levels of proinflammatory cytokines (interleukin-1β and tumour necrosis factor alpha) and serum malondialdehyde. The relative weight of the spleen was significantly higher and cecum pH was significantly lower in pigs fed the BSFL + Pro diet than in those fed the NC diet. Pigs fed the BSFL12 and BSFL + Pro diets had longer duodenal villi, a higher ratio of villus height to crypt depth, and shorter crypt depth. The BSFL + Pro diet also increased faecal Lactobacillus spp. counts and reduced Escherichia coli counts compared with PC and NC, respectively. Conclusions: Dietary supplementation with BSFL or BSFL + multi-probiotics can improve the growth performance and intestinal health of pigs, and may be an effective strategy to replace antibiotic supplementation in weaned pigs.
Honesty Factor (HF) based Security Breach Management Technique in Cognitive Radio Network
Authors: Varatharajan Brinda , Bhuvaneshwari M.
Published: July 2022

The authors have requested that this preprint be removed from Research Square.
Sensitization of resistant cells with a BET bromodomain inhibitor in a cell culture model of deep intrinsic resistance in breast cancer
Authors: Singh Balraj , Sarli Vanessa N. , Milligan Ryan D. , Kinne Hannah E. , Shamsnia Anna , Washburn Laura J. , Lucci Anthony
Published: July 2022

Background: Cell culture models of cancer typically favor proliferative but therapy-sensitive cells because body-like selection pressures are absent. To address this limitation of cell culture, we previously described a function-based selection strategy to model deep intrinsic resistance in cultures of triple-negative breast cancer cells. To determine the validity of this approach in identifying noncytotoxic drugs that could inhibit the relapse of poor-prognosis minimal residual disease in breast cancer, we used our novel cell culture model to evaluate a well-known BET bromodomain inhibitor, JQ1, which modulates cancer epigenome. Methods: We treated highly metabolically adaptable (SUM149-MA) cells and their control parental SUM149-Luc cell line with JQ1 for long periods to determine its efficacy at inhibiting resistant cells. To measure JQ1-mediated sensitization of resistant cancer cells, we first eradicated approximately 99% of relatively chemotherapy-sensitive cancer cells in culture dishes by long treatments with doxorubicin or paclitaxel, and then analyzed the remaining resistant cells for survival and growth into colonies. Our methods were designed to reveal resistant cancer cells while minimizing the contribution of the vast majority of nonresistant cells that simply proliferate in cell culture. We also performed Western blotting to determine whether JQ1 treatment affected PD-L1 protein levels in cancer cells. Results: After 20 days of treatment with 1-2 µM JQ1, which killed a majority of cells in the parental cell line, a large number of SUM149-MA cells survived, consistent with their pan-resistant nature. Interestingly, though, the JQ1 treatment sensitized resistant cancer cells in both the SUM149-MA and SUM149-Luc cell lines to subsequent treatment with doxorubicin and paclitaxel. In addition, combination, rather than sequential, treatment with JQ1 and doxorubicin was also effective in overcoming resistance. Notably, JQ1-treated cancer cells also had significantly lower levels of PD-L1 protein than did untreated cells. Conclusions: Our results suggest that the noncytotoxic drug JQ1 could inhibit the growth of resistant breast cancer cells at the minimal residual disease stage, prior to relapse. Because it can also reduce PD-L1 protein levels, JQ1 may reduce tumor-mediated immune suppression and improve response to immune therapy targeting PD-L1. In all, our results support the validity of a cell culture-based approach for modeling a cancer adaptability phenotype, namely the opportunistic switching of cancer cells between quiescence and proliferation.
Theil-Sen Regressive Miyaguchi–Preneel based Cryptographic Hash Blockchain for Secure Data Transmission using Remote Sensing Data in IoT
Authors: B Sharmila , T Kalavathi Devi
Published: July 2022

IoT is the maximum current Internet that integrates various intelligent devices used by management or individuals to maintain a variety of applications, including smart health and environmental monitoring, remote sensing data analysis. IoT, devices interfere and interact with each other, and this poses a number of security threats. But, because of this freedom, there is a strong need for consistent security to exchange data between IoT devices. For solving this issue, in this manuscript Theil-Sen Regressive Miyaguchi–Preneel Cryptographic Hash Blockchain is proposed for secure data transmission using remote sensing data (TSR-MPCHB-SDT-RSD). To improve the security of data transfer, Theil-Sen Regression and Miyaguchi-Preneel Cryptographic based Blockchain technology is introduced. IoT devices are used to collect remote sensing data. At first, Theil-Sen Regression is used to analyze the data collected on the basis of geometric neutrality. This process reduces the processing time of secure data transfer. MPCHB is then used for secure data transfer. The Miyaguchi-Preneel cryptographic function is used to generate a confusing value of each data. The hash data then generated is transferred to an authorized hub, which avoids unauthorized additions. This helps to improve the data confidentiality and integrity ratio. Finally the proposed method is simulated using the java language. Evaluation metrics such as data confidentiality ratio, data reliability ratio, process time average delay, average power consumption and blockchain data transfer efficiency are measured. Then the simulation performance of the proposed TSR-MPCHB-SDT-RSD method provides 91.03%, 92.11%, 85.33% and 93.78% higher data confidentiality rate, 96.12%, 97.66%, 88.26% and 93.11% higher data integrity rate and 65.12%, 44.33%, 71.59% and 69.36% minimum processing rate which are compared with existing method like Blockchain-Envisioned Secure Data Delivery and Collection Scheme for IoT-Enabled Internet of Drones for Secure Data Transmission using Remote Sensing Data (BESDDC-IOD-RSD), blockchain-assisted health record management using IoT for Secure Data Transmission using Remote Sensing Data (BIoTHR-SDT-RSD), Lamport Merkle Digital Signature Generation blockchain for Secure Data Transmission using Remote Sensing Data (LMDSG-SDT-RSD) and Ant Colony optimization with Multi Kernel Support Vector Machine based blockchain for Secure Data Transmission using Remote Sensing Data (ACOMKSVM-SDT-RSD).
Modified Case-Based Reasoning Model Helps Fertility Subspecialist Doctor Handle the Revision Stage and Answer Accurately In-Vitro Fertilization Program Patient’s Questions
Authors: Sembiring Irwan , Christianto Paminto Agung , Sediyono Eko
Published: July 2022

Eighty two percent of in-vitro fertilization (IVF) program patients immediately ask fertility subspecialist doctors via SMS/Whatsapp messenger app when they feel different symptoms than what they usually feel. However, the high workload has been fertility subspecialist doctors’ obstacle to immediately reply these IVF program patients’ anxious questions. On the other hand, the long time it takes to receive a reply increases IVF program patients’ anxiety and, in turn, the high anxiety affects the success rate of IVF program, making it all the more important to help fertility subspecialist doctors deal with their obstacles. The weakness of Case-Based Reasoning (CBR) model is that the recommendation accuracy score is lower than that of modified CBR model and it makes the workload of fertility subspecialist doctors greater who have been busy dealing with the revision stage. To overcome this weakness, the Chris Case-Based Reasoning (CCBR) similarity formula is applied to CBR model and it combines with the Rule-Based Reasoning (RBR) model. The measurement of Confusion Matrix in the performance of CBR model combination which uses the CCBR similarity formula with RBR model suggests that the accuracy score increases to 47% and the precision score remains 100%, hence this model is declared capable of helping fertility subspecialist doctors handle the revision stage and accurately answer IVF program patients’ anxious questions.The limited scope of research makes it impossible for this research finding to be used as a standard model just yet for it needs to be tested for a wider scope.
High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis
Authors: Lei Pu , Wang Ziming
Published: July 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune infiltration and biological function in ccRCC are still poorly understood.Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed by multiple databases, including TCGA, GEO, TIMER, and ﻿UALCAN. Kaplan–Meier survival analysis; ﻿Gene set enrichment analysis (GSEA); ﻿Gene ontology enrichment (GO);Kyoto Encyclopedia of Genes and Genomes (KEGG); Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using ﻿TCGA ccRCC ﻿profiles. Protein-Protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by ﻿immunohistochemistry assay using the ccRCC tissue chip. Finally, MTT assay, colony formation assay, ﻿cell flow cytometry analysis, EdU staining assay, wound healing assay, transwell migration, and invasion assay were conducted to assess the biological function of GTSE1 in vitro. ﻿Results: GTSE1was overexpressed in ccRCC tissues and cells, and the overexpression of GTSE1 was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its co-expressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction such as T cell activation and innate immune response through multiple signaling pathways including the P53 signaling pathway and T cell receptor signaling pathway. Furthermore, we observed a significant relationship between the GTSE1 expression and immune infiltrating levels of different immune cells in ccRCC. Biological functional studies also demonstrated that GTSE1 could promote malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, invasion capacity, and decreasing the sensitivity of ccRCC cells to cisplatin. Conclusion: Our results indicate that GTSE1 serving as a potential oncogene that can promote the malignant progression and cisplatin resistance in ccRCC. Additionally, High GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.
Gelatinous zooplankton versus Algerian environmental factors
Authors: KHAMES Ghollame Ellah Yacine , ALIOUA Zakia , KHERCHOUCHE Aldjia , HAFFERSSAS Aziz
Published: July 2022

Factors governing gelatinous zooplankton distributions and dispersal have long interested pelagic ecologists. The objective of the present study was to investigate the distribution of gelatinous zooplankton in relation to environmental parameters of coastal Algeria (Southwestern Mediterranean Sea). The zooplankton samples were collected on nine stations located in the central (Sidi Fredj) and western (Habibas Islands) sectors of the Algerian coast during 2012 and 2013. A total of 48 species belonging to 4 groups: Cnidaria, Tunicata, Chaetognathae and Mollusca have been recorded. Their composition showed a variable distribution in both investigated zones according to ANOSIM (p < 0.05) whatever the sampling period and between May and July for Habibas Islands and confirmed by NMDS, but no differences were detected between the sampling periods for Sidi Fredj. The redundancy analysis was used to identify different sample assemblages. It showed relationships between temperature, salinity and chlorophyll a with zooplankton abundances. Temperature was found to be the strongest explanatory variable for some Cnidaria (e.g. Aglaura hemistoma, Rhopalonema velatum, Liriope tetraphylla and Pelagia noctiluca) and Appendicularia (e.g. Oikopleura longicauda, Oikopleura fusiformis and Fritillaria pellucida) while, the development of Doliolum nationalis and Creseis virgula were related to salinity variations.
Neutrophil-lymphocyte Ratio is a Negative Prognostic Biomarker for Luminal A Breast Cancer
Authors: Xiang Yimei , Zhang Ningning , Lei Haike , Wu Jing , Wang Wenting , Zhang Huan , Zeng Xiaohua
Published: July 2022

Background
Inflammation plays an important role in the occurrence, development and metastasis of tumors. The neutrophil-lymphocyte ratio (NLR) is widely used to evaluate global inflammation in various tumor types. However, the prognostic role of NLR in patients with Luminal A breast cancer is rarely reported. The purpose of this study was to investigate the relationship between preoperative NLR and the survival rate of patients with Luminal type A.
Methods
This study collected the data of 226 Luminal A breast cancer patients who were eligible in the Chongqing University Cancer Hospital from January 2011 to December 2016, and analyzed the relationship between preoperative NLR and survival time. The cutoff value of NLR was defined by ROC curve, and the overall survival (OS) time was estimated by Kaplan-Meier method. Cox analysis was performed to determine the correlation between clinicopathological parameters and prognosis.
Results
The OS of patients with NLR lower than 2.0 was significantly longer than that of patients with higher NLR (P < 0.0001). In the univariable cox regression analysis, the NLR, T stage (T3-T4 vs. T1-T2) and histology grade (II-III vs. I) were all significantly associated with OS. In the multivariable cox regression analysis, the NLR and the histology grade (II-III vs. I) were independent factors, the hazard ratio was 36.003 (95% CI: 4.912–263.92, P < 0.0001) and 1.924 (95% CI: 1.14–3.25, p = 0.014) respectively.
Conclusions
The results suggest that higher preoperative NLR related to worse prognosis in Luminal A breast cancer, NLR has a high prognostic value for patients with Luminal A breast cancer and preoperative NLR can be used as a reference index to evaluate the prognosis of Luminal A breast cancer.