bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
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

Abstract
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

Abstract
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

Abstract
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.