bluuebunny/crossref_metadata_2025 huggingface dataset:
Relevance of Pharmacogenetic Polymorphisms With Response to Docetaxel, Cisplatin, and 5-Fluorouracil Chemotherapy in Esophageal Cancer.
Authors: Nomura Hisanaga , Tsuji Daiki , Ueno Shohei , Kojima Takashi , Fujii Satoshi , Yano Tomonori , Daiko Hiroyuki , Demachi Ken , Itoh Kunihiko , Kawasaki Toshikatsu
Published: October 2021

Purpose: Docetaxel, cisplatin, and 5-fluorouracil (DCF) have high response rates, but severe neutropenia is frequently observed. The occurrence of neutropenia is associated with high histological response in solid tumors, and it might be associated with tumor shrinkage after DCF therapy. This study aimed to determine the genetic polymorphisms involved in the clinical response to preoperative DCF therapy in esophageal cancer patients.Methods: We included 56 patients with measurable lesions who received preoperative DCF therapy for esophageal cancer. Twenty-one genetic polymorphisms were analyzed, and univariate logistic regression analysis was used to evaluate the association between genetic polymorphisms and tumor shrinkage. A multivariate logistic regression analysis adjusted for T category and tumor location and a univariate analysis for potential genetic factors with P values < 0.05 were performed to explore the predictive factors and to estimate odds ratios and their 95% confidence intervals.Results: No patient achieved a complete response, whereas 20 patients achieved a partial response, 31 patients had stable disease, and 5 patients had progressive disease. Although no association was found between pharmacokinetic-related gene polymorphisms, XRCC3 rs17997944 was extracted as the only genetic factor that affected tumor shrinkage (P = 0.033) by univariate analysis. The multivariate analysis adjusted for T category and tumor site also showed that XRCC3 rs1799794: AA was a predictive factor that affected tumor shrinkage (odds ratio, 0.243; 95% confidence interval, 0.065–0.914; P = 0.036).Conclusion: XRCC3 rs1799794, which is involved in homologous recombination, is a genetic factor that affects clinical responses to DCF therapy.
Synthesis and Evaluation of Novel, Selective, Functionalized γ-butyrolactones as Sigma-2 Ligands
Authors: Blass Benjamin E , Gao Rong , Blattner Kevin M. , Gordon John C. , Pippin Douglas A. , Canney Daniel J.
Published: October 2021

The sigma-2 (σ2) receptor was discovered nearly 40 years ago and was recently identified as the Transmembrane Protein 97 (TMEM97, also known as MAC30 (Meningioma-associated protein). Aberrant σ2 activity has been linked to disease and conditions such as schizophrenia, Alzheimer’s disease, neuropathic pain, traumatic brain injury, and cancer. The utility of σ2 as a therapeutic target is currently under investigation in numerous laboratories. Herein, we report on the synthesis and evaluation of a series of novel, functionalized γ-butyrolactones that are potent σ2 receptor ligands.
Neoadjuvant Therapy of Metformin is Associated with Good Tumor Response After Preoperative Concurrent Chemoradiotherapy for Rectal Cancer
Authors: Han Jeonghee , kim Jong Ho , Lee Jin-Won , Han Sang Hyup , kim Hae-sung
Published: October 2021

Metformin is associated with good tumor response in preoperative concurrent chemoradiotherapy (CCRT) for rectal cancer. This study aims to demonstrate that the timing of metformin is related to the tumor response on preoperative CCRT for rectal cancer. From January 2010 to December 2017, 232 patients who underwent curative resection after preoperative CCRT were reviewed. Patients were divided into groups with or without diabetes or metformin. The timing of metformin administration was divided based on before and after initiation of chemoradiotherapy. Multivariate logistic regression analysis was used to identify predictors for tumor response. Tumor downstaging (p = 0.02) and good response rates of tumor regression grade (TRG) (p = 0.008) were significantly higher in the group administered metformin before CCRT than other groups. In the multivariate analysis, metformin administration before CCRT was a significant factor in predicting tumor downstaging (odds ratio [OR] 10.31, 95% confidence interval [CI]: 1.76 - 102.08, p = 0.02) and good TRG (OR 12.55, 95% CI: 2.38 - 80.24, p = 0.004). In patients with rectal cancer who underwent preoperative CCRT, neoadjuvant therapy of metformin before CCRT was significantly associated with good tumor response and tumor downstaging.
Comparison of clinical characteristics between mild chronic bronchitis and severe chronic bronchitis in patients with chronic obstructive pulmonary disease
Authors: Choi Joon Young , Yoon Hyoung Kyu , Lee Sang Yeub , Kim Jin Woo , Choi Hye Sook , Kim Yu-Il , Jung Ki-Suck , Yoo Kwang Ha , Kim Woo Jin , Rhee Chin Kook
Published: October 2021

Background

Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB vs. severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores.
Methods

This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥3; severe CB was defined as CAT1 and CAT2 scores ≥4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB vs. CB patients and in patients with mild CB vs. severe CB.
Results

Among the 2,162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB.
Conclusions

CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.
Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents
Authors: Lumpuy-Castillo J. , Vales-Villamarín C. , Mahíllo-Fernández I. , Pérez-Nadador I. , Soriano-Guillén L. , Lorenzo Oscar , Garcés C.
Published: October 2021

Background: In the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. Methodology: Five ACE2-single nucleotide polymorphisms (SNP); rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related with CV risk factors, were analyzed in a general population of adolescents and tested for potential associations with anthropometric and plasma parameters.Results: Girls (n=461) exhibited lower rates of overweight and obesity, blood pressure, and glycemia than boys (n=412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, their highest levels of TG were linked to rs879922, rs233575, and rs2158083, and the highest TG/HDL-C ratio was assocated with rs879922 and rs233575. The upper levels of TC and LDL-C was associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dl was related with rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00 -2.61)]. The cut-off level for TC ≥ 170 mg/dl was associated with rs2074192 [OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. In addition, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related with higher prevalence of overweight/obesity and TG elevation. Conclusion: The expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.
In Vitro and in Vivo Anti-Inflammatory and Anticoagulant Activities of Myrciaria Plinioides D. Legrand Ethanol Leaf Extract
Authors: Marmitt Diorge Jônatas , Bitencourt Shanna , Coura Chistiane Oliveira , Berger Markus , Faleiro Dalana , Kich Débora Mara , Caye Bruna , Immich Sheila Mariele , Frota Annyta Fernandes , Beys-da-Silva Walter O. , Guimarães Jorge Almeida , Benevides Norma Maria Barros , Laufer Stefan , Goettert Márcia Inês
Published: October 2021

Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides. In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.
Design, Synthesis, And Evaluation of Functionalized Diamino-butylbenzamides As Selective Dopamine D3 Receptor Ligands
Authors: Blass Benjamin E , Chen Peng-Jen , Taylor Michelle , Griffin Suzy A , Gordon John C , Luedtke Robert R
Published: October 2021

Substance use disorder remains a major, unmet medical need. Cocaine is one of the most commonly abused recreational drugs and in 2018, there were over 5.5 million current cocaine users. There are no approved therapies for the treatment of cocaine use disorder, but the D3 dopamine receptor has been identified as a potential therapeutic target. We have identified a series of functionalized diamino-butylbenzamides that are potent D3 binders with moderate to high selectivity for D3 over D2.
Elevating Photooxidation of Methane to Formaldehyde via TiO2 Crystal Phase Engineering
Authors: Jiang Yuheng , Zhao Wenshi , Li Siyang , Wang Shikun , Fan Yingying , Wang Fei , Qiu Xueying , Zhu Yanfei , Zhang Yin , Long Chang , Tang Zhiyong
Published: October 2021

Photocatalytic conversion of methane to value-added products under mild conditions, which represents a long-sought-after goal for industrial sustainable production, remains extremely challenging to afford high production and selectivity using cheap catalysts. Herein, we present the crystal phase engineering of commercially available anatase TiO2 via simple thermal annealing to optimize the structure-property correlation. Biphase catalyst of anatase (90%) and rutile (10%) TiO2 exhibits the exceptional performance in the oxidation of methane to formaldehyde under the reaction condition of water solvent, oxygen atmosphere and full-spectrum light irradiation. An unprecedented production of 24.27 mmol gcat-1 with an excellent selectivity of 97.4% towards formaldehyde is acquired at room temperature after a 3 h reaction. Both experimental results and theoretical calculation disclose that the crystal phase engineering of TiO2 lengthens the lifetime of photogenerated carriers and favors the formation of intermediate methanol species, thus maximizing the efficiency and selectivity in aerobic oxidation of methane to formaldehyde. More importantly, the feasibility of scale-up production of formaldehyde is demonstrated by inventing the "pause-flowing" reactor. This work opens the avenue towards industrial methane transformation in a sustainable and economical way.
In Vtro Maturation Outcomes of hCG-primed Unstimulated Cycles in Patients with Polycystic Ovarian Syndrome: a Single-center Experience
Authors: Kim Myung Joo , Choe Seung-Ah , Park Eun A , Kim Ran , Kim You Shin
Published: October 2021

Backgound: IVM has emerged as a safe and promising alternative procedure to conventional in vitro fertilization (IVF) for minimizing the risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS. Despite the comparable obstetric and perinatal outcomes, there are no definite factors known to affect the outcomes of IVM.Methods: Retrospective analysis of a total of 313 women with PCOS undergoing 427 hCG-primed IVM cycles between January 2010 and February 2016 at the Fertility Center of CHA Gangnam Medical Center, Seoul, Korea. The number of retrieved oocytes and maturation, fertilization, and implantation rates were analyzed. Results: After transferring a mean of 2.4 ± 0.5 fresh embryos, the clinical pregnancy rate was 39.1% (n = 167), and the live birth rate was 30.7% (n = 131) with the implantation rate of 20.9%. The numbers of retrieved (18.1 ± 9.7 vs. 15.6 ± 8.7, p = 0.014), fertilized (8.6 ± 5.2 vs. 6.6 ± 3.8, p < 0.001) oocytes; good-quality embryos (1.3 ± 0.9 vs. 1.0 ± 0.9, p = 0.001); and blastocyst transfer cycles (22 vs. 15, p < 0.001) were significantly higher in the live birth group than in the no live birth group. Among the factors associated with live births, retrieved oocytes had a slightly positive effect on live birth (RR = 1.03; 95% CI, 1.00, 1.06; p = 0.021).Conclusions: It seems that the number of retrieved oocytes has a favorable effect in increasing the clinical pregnancy rate and live birth rate during hCG-primed IVM procedure in women with PCOS. Physicians’ skills and cautious efforts may be required to retrieve a higher number of oocytes in IVM procedures.
Prognostic Value and Computer Image Analysis of p53 in Mantle Cell Lymphoma
Authors: Zhang Yue-Hua , Xiang Xiao-Yu , Gao Li-Min , Liu Wei-Ping
Published: October 2021

Background: P53 has different prognostic cut-off values in different mantle cell lymphoma (MCL) studies, and p53 immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation，which might be inaccurate. This study aimed to investigate the optimal cut-off value of p53 for predicting prognosis and the possibility of computer image analysis identifying the positive rate of p53 in patients with mantle cell lymphoma (MCL). Methods: We used QuPath software to determining the p53 positive rate and compared it to the data obtained by manual counting and semiquantitative estimation. Using Youden index and Kaplan-Meier survival curve analysis, we generated survival curves. Chi-squared (χ2) test was used to compared MCL cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compared manual counting, computer image analysis and semiquantitative estimation.Results: The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) compared to p53 < 20% (P < 0.0001). MCL patients with blastoid/pleomorphic variant cell morphology had more p53 ≥ 20% than classical type (P < 0.0001). And a strong correlation between computer image analysis and manual counting p53 in the same areas in MCL patients (spearman's rho = 0.966, P < 0.0001). Conclusions: MCL patients with p53 ≥ 20% have a shorter OS, and a blastoid/pleomorphic variant tendency. Computer image analysis could reflect the actual positive rate of p53 and is a more attractive alternative than semiquantitative estimation in MCL.
Differences in ICSI Utilization Rates Among States With Insurance Mandates for ART Coverage
Authors: Zagadailov Pavel , CHO Kyung S , SEIFER David B
Published: October 2021

Background
Assisted reproductive technology (ART) insurance mandates promote more selective utilization of ART clinic resources including intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ICSI utilization differs by state insurance mandates for ART coverage and assess if such a difference is associated with male factor, preimplantation genetic testing (PGT), and/or live birth rates.
Methods
In this retrospective analysis of the Centers for Disease Control (CDC) data from 2018, ART clinics in ART-mandated states (n=8, AR, CT, HI, IL, MD, MA, NJ, RI) were compared individually to one another and with non-mandated states in aggregate (n=42) for use of ICSI, male factor, PGT, and live birth rates. ANOVA was used to evaluate differences between ART-mandated states and non-mandated states. Individual ART-mandated states were compared using Welch t-tests. Statistical significance was determined by Bonferroni Correction.
Results
There were significant differences in ICSI rates (%, mean ± SD) between MA (53.3 ± 21.3) and HI (90.7 ± 19.6), p = 0.028; IL (86.5 ± 18.7) and MA, p = 0.002; IL and MD (57.2 ± 30.8), p = 0.039; IL and NJ (62.0 ± 26.8), p = 0.007; between non-mandated states in aggregate (79.9 ± 19.9) and MA, p = 0.006, and NJ (62.0 ± 26.8), p = 0.02. Male factor rates of HI (65.8 ± 16.0) were significantly greater compared to CT (18.8 ± 8.7), IL (26.0 ± 11.9), MA (26.9 ± 6.6), MD (29.3 ± 9.9), NJ (30.6 ± 17.9), and non-mandated states in aggregate (29.7 ± 13.7), all p < 0.0001. No significant differences were reported for use of PGT and/or live birth rates across all age groups regardless of mandate status.
Conclusions
ICSI use varied significantly among ART-mandated states while demonstrating no differences in live birth rates. These data suggest that the prevalence of male factor and the presence of a state insurance mandate are not the only factors influencing ICSI use. It is suggested that other non-clinical factors may impact the rate of ICSI utilization in a given state.
Dual Regulation of Lipid Droplet-triacylglycerol Metabolism and ERG9 Expression for Improved β-carotene Production in Saccharomyces Cerevisiae
Authors: Bu Xiao , Lin Jing‑Yuan , Duan Chang‑Qing , Koffas Mattheos , Yan guoliang
Published: October 2021

BackgroundThe limitation of storage space, product cytotoxicity and the competition for precursor is the major challenges for efficiently overproducing carotenoid in engineered non-carotenogenic microorganisms. In this work, to improve β-carotene accumulation in Saccharomyces cerevisiae, a strategy that simultaneous increases cell storage capability and strengthens metabolic flux to carotenoid pathway was developed using exogenous oleic acid (OA) combined with metabolic engineering approaches.ResultsThe direct separation of lipid droplets (LDs), quantitative analysis and genes disruption trial indicated that LDs are major storage locations of β-carotene in S. cerevisiae. However, due to the competition for precursor between β-carotene and LDs-triacylglycerol biosynthesis, enlarging storage space by engineering LDs related genes has minor promotion on β-carotene accumulation. Adding 2 mM OA significantly improved LDs-triacylglycerol metabolism and resulted in 36.4% increase in β-carotene content. The transcriptome analysis was adopted to mine OA-repressible promoters and IZH1 promoter was used to replace native ERG9 promoter to dynamically down-regulate ERG9 expression, which diverted the metabolic flux to β-carotene pathway and achieved additional 31.7% increase in β-carotene content without adversely affecting cell growth. By inducing an extra constitutive β-carotene synthesis pathway for further conversion precursor farnesol to β-carotene, the final strain produced 11.4 mg/DCW and 142 mg/L of β-carotene, which is 107.3% and 49.5% increase respectively over the parent strain. Conclusions﻿This strategy can be applied in the overproduction of other heterogeneous FPP-derived hydrophobic compounds with similar synthesis and storage mechanisms in S. cerevisiae.
Synergistic Cytotoxic Effect of Honey bee venom and Cisplatin on Tongue Squamous Cell Carcinoma
Authors: Khalil Sabreen Gamal , El-Bolok Amr Helmy Mustafa , El-Gayar Sherif Farouk , Sholkamy Maii Ibrahim
Published: October 2021

Background: Cancer is a serious issue that has a significant effect on the health of all human communities. Tongue cancer is one of the most common head and neck cancers in the world. In the medical world, cancer therapy is a major challenge. Nowadays, natural compounds are important resources of many anti-cancer medications. Venom from honey bees possesses potent anti-cancer effects. Cisplatin is a chemotherapeutic drug that has been used for decades to treat cancer cells. Recently, Combination therapy has been a popular treatment choice for cancer patients.This study aimed to investigate the synergistic cytotoxic effect of honey bee venom (BV) and cisplatin on tongue squamous cell carcinoma cell line (SCC-25).Methods: The cytotoxic effect was determined using Methyl Thiazol Tetrazolium (MTT) assay, microscopic examination, P53 and caspase-3 were quantified by Real-Time Polymerase chain reaction (RT-PCR) and statistical analysis.Results: The findings revealed that the tested drugs' cytotoxic potential against SCC-25 cells is dose dependent. The half-maximal inhibitory concentration (IC50) value of MTT assay of BV/cisplatin mix decreased significantly compared to IC50 values of BV and cisplatin in sole formulation. Microscopic examination showed that BV and cisplatin alone and in combination mainly produced apoptotic cell death. Regarding RT-PCR results, P53 and caspase-3 expression were significantly increased in SCC-25-treated cells (P= 0.0001).Conclusions: The combined use of BV and cisplatin induced marked synergistic cytotoxic effect on SCC-25 cell line.
The Prediction of Chronicity in Patients with Acute and Sub-Acute Non-Specific Low Back Pain and Associated Risk Factors: A Case-Control Study
Authors: Sadeghi-Yarandi Mohsen , Ghasemi Mohammad , Ghanjal Ali , Sepandi Mojtaba , Soltanzadeh Ahmad
Published: October 2021

Background: Chronic low back pain is one of the most common musculoskeletal disorders in different countries that people of any age can experience many times. This study aimed to predict the chronicity of non-specific acute and sub-acute LBP and related risk factors among cases referred to physiotherapy clinics.Methods: This case-control study was performed among 420 patients suffered from acute, sub-acute and chronic LBP referred to two physiotherapy centers in Tehran-Iran in 2020. Data were obtained using the Fear-Avoidance Beliefs Questionnaire (FABQ), Patient Health Questionnaire (PHQ-9), Pain Catastrophic Scale (PCS-13), Tampa Scale for Kinesiophobia (TSK-11), Pittsburgh Sleep Quality Index (PSQI), Walker's Health-Promoting Lifestyle Questionnaire, Roland Morris Disability Questionnaire (RMDQ) and Numerical Pain Rating Scale (NPRS). Data analysis was performed by applying independent sample t-test, chi-square, and multiple logistic regression in SPSS software version 25. IBM Amos version 22 was employed for path analysis.Results: The mean age and body mass index in all patients were 43.94 ± 6.72 years and 25.69 ± 3.54 kg.m-2, respectively. It was found that some demographic parameters (i.e. weight, BMI, job, type of occupational task performance, history of low back pain, work shift, underlying diseases and income), some cognitive parameters ( i.e. fear-avoidance beliefs, kinesiophobia, catastrophic pain, and depression), some lifestyle parameters (i.e. health responsibility, physical activity and interpersonal relationships), sleep quality and pain related disability were among the most critical risk factors in the chronicity of acute and sub-acute LBP (P < 0.05).Conclusion: Personal, psychological, and psychosocial parameters can be among the most critical predictors in the chronicity of acute and sub-acute non-specific LBP. Hence, paying attention to all the mentioned factors at the beginning of patients' treatment to create a targeted treatment algorithm and prevent the conversion of acute and sub-acute into chronic LBP has particular importance.
A Combination of Blood Lymphocytes and AST Levels Distinguish Patients with Small Hepatocellular Carcinomas from Non Cancer Patients.
Authors: Carr Brian I. , Bag Harika Gozukara , Ince Volkan , Akbulut Sami , Ersan Veysel , Usta Sertac , Isik Burak , Ogut Zeki , Tuner Adem , Yilmaz Sezai
Published: October 2021

PurposeHCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically-available and cheap potential blood tests as biomarkers for screening patients at risk for HCC.MethodsA comparison was made of commonly used blood count and liver function parameters in a group of patients (n=101) with small HCCs (<3cm) or without HCC (n=275), who presented for liver transplantation in our institute. ResultsSignificant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein amongst the tumor characteristics, were found to be significantly different amongst the 2 HCC groups, as well as levels of blood total bilirubin, ALKP and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients.ConclusionThe combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.
The Dark Triad Moderates the Association Between Orthorexia Nervosa and Relationship (Dis)Satisfaction
Authors: Brunett Kaitlin , Oberle Crystal
Published: October 2021

PurposePast research has revealed a link between orthorexia nervosa (ON) and relationship dissatisfaction, which has in turn been found to be correlated with the Dark Triad traits. The current study investigated the association ON has with seeking out relationships and with relationship satisfaction, while also assessing a potential moderating effect of the Dark Triad.MethodRecruited from Reddit forums, 788 adults completed an online survey with scales assessing ON symptomology, relationship satisfaction, relationship seeking, and the Dark Triad. ResultsGreater ON symptomatology was associated with greater levels of all aspects of the Dark Triad (Machiavellianism, narcissism, and psychopathy), as well as with lower levels of relationship satisfaction (among those in committed romantic relationships) and a lower likelihood of seeking new romantic relationships (among single participants). A regression analysis revealed that the Dark Triad moderated the association between ON and relationship satisfaction, whereby this association was not significant at high levels of the Dark Triad. ConclusionThe current research highlights that at low and medium levels of the Dark Triad, greater ON symptomology is associated with lower levels of satisfaction in romantic relationships. Level of evidenceLevel V, descriptive cross-sectional study
Paper-based genetic assays with bioconjugated gold nanorods and an automated readout pipeline
Authors: Borri Claudia , Centi Sonia , Chioccioli Sofia , Bogani Patrizia , Micheletti Filippo , Gai Marco , Grandi Paolo , Laschi Serena , Tona Francesco , Barucci Andrea , Zoppetti Nicola , Pini Roberto , Ratto Fulvio
Published: October 2021

BackgroundPaper-based biosensors featuring immunoconjugated gold nanoparticles have gained extraordinary momentum in recent times as the platform of choice in key cases of field applications, including the so-called rapid antigen tests for SARS-CoV-2. Here, we propose a revision of this format, one that may leverage on the most recent advances in materials science and data processing. In particular, we focus on an amplifiable DNA rather than a protein target, and we assess the replacement of gold nanospheres with anisotropic nanorods, which are about 10-fold brighter and multiplexable. ResultsBy comparison with a gold-standard method for dot-blot readout with digoxigenin, we show that gold nanorods entail much faster and easier processing, at the cost of a higher detection limit (from below 1 to 10 ppm in the case of plasmid DNA containing a target transgene). In addition, we test a complete workflow for systematic acquisition and machine-learning regression of photographs of dotblot membranes as a tool to gain more analytical sensitivity and potential for quantification. A leaveone-out strategy for training and validation with as few as 36 sample instances already improves the detection limit reached by the naked eye by a factor around 2. ConclusionsTaken together, we conjecture that the synergistic combination of new materials and innovative tools for data processing may bring the analytical sensitivity of paper-based biosensors to approach the level of lab-grade molecular tests.
On Different Aspects of The Optical Rogue Waves Nature
Authors: Belic Milivoj R. , Nikolic Stanko N , Ashour Omar A. , Aleksic Najdan B.
Published: October 2021

Rogue waves are giant nonlinear waves that suddenly appear and disappear in oceans and optics. We discuss the facts and fictions related to their strange nature, dynamic generation, ingrained instability, and potential applications. We present rogue wave solutions to the standard nonlinear Schrödinger equation that models many propagation phenomena in nonlinear optics. We propose the method of mode pruning for suppressing the modulation instability of rogue waves. We demonstrate how to produce stable Talbot carpets –-- recurrent images of light and plasma waves –-- by rogue waves, for possible use in nanolithography. We point to instances when rogue waves appear as numerical artefacts, due to an inadequate numerical treatment of modulation instability and homoclinic chaos of rogue waves. Finally, we display how statistical analysis based on different numerical procedures can lead to misleading conclusions on the nature of rogue waves.
Orthopaedic Surgical Intervention and Type I Osteoporosis Are Risk Factors For Acute Febrile Reaction After Zoledronic Acid Treatment For Osteoporosis: A Case-Control Study
Authors: Wu Hongliang , Zheng Sihang , Tian Ye , Zhang Enchong , Xing Ruida , Hossain Mohammad Showkat , Jing Shengjie , Gong Helong , Li Yan
Published: October 2021

BackgroundAcute febrile reaction often occurs though zoledronic acid is a widely used first-line drug for osteoporosis. This study aimed to investigate the characteristics and risk factors of acute febrile reaction after zoledronic acid in the orthopaedic field, including surgical intervention.Methodsa total of 517 patients diagnosed with primary osteoporosis and treated with zoledronic acid from January 2012 to December 2020 were collected, including 40 males and 477 females, 262 patients with type I, 255 patients with type II, 230 patients with fresh fracture, and 209 patients with the operation. Summarize the characteristics of overall fever rate, fever degree, occurrence time, and duration of the acute febrile reaction. The effects of gender, white blood cell, neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), type of osteoporosis, degree of osteoporosis, fresh fracture, operation, and zoledronic acid medication history on acute febrile reaction were analyzed by univariate, logistic regression, ROC curve analysis. The differences in fever rate in different fracture operation sites were further compared.ResultsIn 517 patients, 175 cases (33.85%) developed acute febrile reaction within 36h after medication with less than 60h duration. Univariate analysis showed significant differences in NLR, type and degree of osteoporosis, fresh fracture, operation, and zoledronic acid history between the fever and non-fever groups (P<0.05). Logistic regression and ROC curve analysis further showed that the fever rate of patients with the operation was higher (OR = 1.975, P < 0.01, area under ROC curve was 0.654). The fever rate of patients with type I osteoporosis was higher ((OR = 2.137, P < 0.01, area under ROC curve was 0.437), and the fever rate of patients with zoledronic acid history was lower ((OR = 0.124, P < 0.01, area under ROC curve was 0.340). The fever rate of joint fracture patients (56.60%) was significantly higher than that of spine fracture patients (38.54%) (P < 0.05).ConclusionWhen zoledronic acid was used to treat primary osteoporosis in orthopaedic patients, the rate of acute febrile reaction was 33.85%, orthopaedic surgical intervention, type I osteoporosis, and the first zoledronic acid treatment might be independent risk factors.
EmPHasis-10 Health-Related Quality of Life and Exercise Capacity in Chronic Thromboembolic Pulmonary Hypertension After Balloon Angioplasty: A Cross-Sectional Study
Authors: Sakamoto Hayato , Goda Ayumi , Tobita Kazuki , Takeuchi Kaori , Kikuchi Hanako , Inami Takumi , Tamura Yuichi , Kohno Takashi , Yamada Shin , Soejima Kyoko , Satoh Toru
Published: October 2021

Background
Whether pulmonary haemodynamic parameters and functional capacity are associated with quality of life (QoL) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. This study aimed to evaluate disease-specific QoL with the emPHasis-10 questionnaire and assess its determinants in CTEPH patients with normalised pulmonary haemodynamics.
Methods
This cross-sectional study included 143 patients with CTEPH (median age, 68 [58–75] years; men/women, 51/136; use of home oxygen therapy [HOT], 51 patients [27%]) after balloon pulmonary angioplasty (BPA) with normalised mean pulmonary artery pressure (PAP) <25 mmHg at rest. Right heart catheterisation was performed, followed by the 6-minute walk test (6MWD) and the emPHasis-10 questionnaire.
Results
The median PAP and pulmonary vascular resistance were 18 (15–21) mmHg and 2.2 (1.7–2.9) Wood units, respectively. The median emPHasis-10 score was 14 (range, 8–24), whereas the median 6MWD was 447 (385–517) m. Univariate linear regression analysis showed that the emPHasis-10 score was associated with 6MWD (β = -0.476 [95% CI -0.604, -0.348], p < 0.001) and HOT (β = 0.214 [95% CI 0.072, 0.356], p = 0.003), but not with haemodynamic parameters. Multiple regression analysis revealed that a higher emPHasis-10 score was associated with lower 6MWD (β = -0.475 [95% CI -0.631, -0.319], p < 0.001).
Conclusion
Health-related QoL was associated with exercise capacity and the use of HOT, but not haemodynamic parameters, in patients with CTEPH after BPA with normalised haemodynamics. Improvements in exercise capacity may lead to further improvements in QoL.
Discussion on the damping factor and improvement of the Levenberg-Marquardt method
Authors: Zhu Wenwu
Published: October 2021

The ill-posed problem is the key obstacle to obtain the accurate inversion results in the geophysical inversion field, and the Levenberg-Marquardt1, 2(hereinafter referred to as the L-M method) method has been widely used as it can effectively improve the ill-posed problems. However, the inversion results obtained by the L-M method are usually stable but incorrect, the reason is that the damping factor in the L-M method is difficult to solve, and it is usually approximated with a positive constant by experience or through some fitting methods. This paper uses the binary gravity model to demonstrate that the damping factor in the L-M method cannot be regarded as a positive constant only, it should have the following characteristics: (i) the damping factor is a vector, not just a constant; (ii) the values of the vector are composed of both positive and negative constants, not just positive constants; (iii) the corresponding value in the vector is close or equal to ∞ when the corresponding density block’s value is close or equal to zero. Even if the above characteristics have been found in the L-M method, it is difficult to reasonably estimate the damping factor as the damping factor oscillate severely due to the third characteristic, and the improved L-M method is proposed which effectively avoids the damping factor’s severe oscillation problem. The strategy of obtaining the reasonable damping factor is given finally.
Upregulation of TGF-b-induced HSP27 by HSP90 inhibitors in osteoblasts
Authors: Kuroyanagi Gen , Tokuda Haruhiko , Fujita Kazuhiko , Kawabata Tetsu , Sakai Go , Kim Woo , Hioki Tomoyuki , Tachi Junko , Matsushima-Nishiwaki Rie , Otsuka Takanobu , Iida Hiroki , Kozawa Osamu
Published: October 2021

Background: Heat shock protein (HSP) 90 functions as a molecular chaperone and is constitutively expressed and induced in response to stress in many cell types. We have previously demonstrated that transforming growth factor-b (TGF-b), the most abundant cytokine in bone cells, induces the expression of HSP27 through Smad2, p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in mouse osteoblastic MC3T3-E1 cells. This study investigated the effects of HSP90 on the TGF-b-induced HSP27 expression and the underlying mechanism in mouse osteoblastic MC3T3-E1 cells. Methods: Clonal osteoblastic MC3T3-E1 cells were treated with the HSP90 inhibitors and then stimulated with TGF-b. HSP27 expression and the phosphorylation of Smad2, p44/p42 MAPK, p38 MAPK, and SAPK/JNK were evaluated by western blot analysis. Result: HSP90 inhibitors 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib significantly enhanced the TGF-b-induced HSP27 expression. HSP90 inhibitors, geldanamycin, onalespib, and 17-DMAG did not affect the TGF-b-stimulated phosphorylation of Smad2. Geldanamycin did not affect the TGF-b-stimulated phosphorylation of p44/p42 MAPK or p38 MAPK but significantly enhanced the TGF-b-stimulated phosphorylation of SAPK/JNK. Onalespib also increased the TGF-b-stimulated phosphorylation of SAPK/JNK. Furthermore, SP600125, a specific inhibitor for SAPK/JNK, significantly suppressed onalespib or geldanamycin’s enhancing effect of the TGF-b-induced HSP27 expression levels. As for the canonical BMP signaling pathway, BMP-4 failed to induce the expression of HSP27 in osteoblastic MC3T3-E1 cells. Conclusion: Our results strongly suggest that HSP90 inhibitors upregulated the TGF-b-induced HSP27 expression and that these effects of HSP90 inhibitors were mediated through SAPK/JNK pathway in osteoblasts.
A Multivariate Multi-Step LSTM Forecasting Model for Tuberculosis Incidence With Model Explanation in Liaoning Province, China
Authors: Yang Enbin , Zhang Hao , Guo Xinsheng , Liu Zhen , Liu Yuanning
Published: October 2021

Purpose: In addition to COVID-19, tuberculosis (TB) is the respiratory infectious disease with the highest incidence in China. We aim to design a series of forecasting models and find the factors that affect the incidence of TB, thereby improving the accuracy of the incidence prediction. Results: In this paper, we developed a new interpretable prediction system based on the multivariate multi-step Long Short-Term Memory (LSTM) model and SHapley Additive exPlanation (SHAP) method. Moreover, four accuracy measures are introduced into the system: Root Mean Square Error, Mean Absolute Error, Mean Absolute Percentage Error, and symmetric Mean Absolute Percentage Error. Meanwhile, the Autoregressive Integrated Moving Average (ARIMA) model and seasonal ARIMA model are established. The multi-step ARIMA-LSTM model is proposed for the first time to examine the performance of each model in the short, medium, and long term, respectively. Compared with the ARIMA model, each error of the multivariate 2-step LSTM model is reduced by 12.92%, 15.94%, 15.97%, and 14.81% in the short term. The 3-step ARIMA-LSTM model achieved excellent performance, with each error decreased to 15.19%, 33.14%, 36.79%, and 29.76% in the medium and long term. We provide the local and global explanation of the multivariate single-step LSTM model in the field of incidence prediction, pioneering. Conclusion: The multivariate 2-step LSTM model is suitable for short-term forecasts, and the 3-step ARIMA-LSTM model is appropriate for medium- and long-term forecasts. In addition, the prediction effect was better than similar TB incidence forecasting models. The SHAP results indicate that the five most crucial features are maximum temperature, average relative humidity, local financial budget, monthly sunshine percentage, and sunshine hours.
Cytotoxic and Radiosensitising Effects of a Novel Thioredoxin Reductase Inhibitor in Brain Cancers
Authors: Yao Anqi , Storr Sarah J. , Inman Martyn , Barwell Lucy , Moody Christopher J. , Martin Stewart G.
Published: October 2021

The thioredoxin (Trx) system, a key antioxidant pathway, represents an attractive target for cancer therapy. This study investigated the chemotherapeutic and radiosensitising effects of a novel Trx reductase (TrxR) inhibitor, IQ10, on brain cancer cells and the underlying mechanisms. Five brain cancer cell lines and a normal cell type were used. TrxR activity and expression were assessed by insulin reduction assay and Western blotting respectively. IQ10 cytotoxicity was evaluated using growth curve, resazurin reduction and clonogenic assays. Radiosensitivity was examined using clonogenic assay. Reactive oxygen species levels were examined by flow cytometry and DNA damage assessed by immunofluorescence. Epithelial-mesenchymal transition (EMT) related genes expression was examined by RT-PCR array. IQ10 significantly inhibited TrxR activity but did not affect the Trx system protein expression in brain cancer cells. The drug exhibited potent anti-proliferative and cytotoxic effects against brain cancer cells under both normoxic and hypoxic conditions in both 2D and 3D systems, with IC50s in the low micromolar range. It was up to ~1000 fold more potent than temozolomide. IQ10 substantially sensitised various brain cancer cells to radiation, with such effect being due, in part, to functional inhibition of TrxR, making cells less able to deal with oxidative stress, and leading to increased oxidative DNA damage. IQ10 significantly downregulated EMT associated gene expression suggesting potential antiinvasive and antimetastatic properties. This study suggests that IQ10 is a potent anticancer agent, and could be used as either a single agent or combined with radiation, to treat brain cancers.
Sequencing Analysis and Enzyme Activity Assay of SrUGT76G1 Revealed the Mechanism Toward on/off Production of Rebaudioside-A in Stevia Plants
Authors: Lucho Simone Ribeiro , Amaral Marcelo do , Bianchi Valmor , Almagro Lorena , Ferrer Maria , Calderon Antonio , Braga Eugenia jacira
Published: October 2021

Stevia plants is known for its ability to synthesize steviol glycosides (SGs), a natural sweetener blend. Stevioside (STEV) and Rebaudioside-A (Reb-A) are the main SGs. However, Reb-A is more palatable than STEV and shows reduced bitter aftertaste. SrUGT76G1 catalyzes the conversion of STEV to Reb-A, improving their organoleptic properties. The better understanding of the structure/activity of SrUGT76G1 would allow shedding light up on on/off production of Reb-A in stevia plants. Thus, we analyzed the STEV and Reb-A content in stevia leaves of plants from Brazil and Spain and did not find detectable levels of Reb-A in Brazilian samples (off production). For this reason, we used a sequencing tool to study at the genetic and structural level the SrUGT76G1 gene. Changes in key amino acid residues in Brazilian samples were found, such as Leu204Phe, Thr284Leu and Leu126Ile. Leu204Phe mutants can narrow substrate-binding pocket to favor flavonoids recognition and decrease SGs synthesis, while Thr284 is considered key for 1,3-glucosylation of SGs, including Reb-A. These punctual mutations may partly explain the lack of functionality of UGT76G1 enzyme and off production of Reb-A in stevia plants from Brazil. Following this trend, Brazilian samples exhibited a T-to-A substitution, resulting in premature stop codon. As expected, the relative expression of SrUGT76G1 gene showed a higher level in Spanish samples than in Brazilian ones. Collectively, the results presented here show the structure-activity interplay of SrUGT76G1 enzyme and provide new insights on structural features and its role toward Reb-A synthesis.
Viral Etiology of Acute Gastroenteritis In Mozambique, 2014 – 2019
Authors: Bero Diocreciano Matias , Chilaúle Jorfélia José , Langa Jerónimo , de Deus Nilsa
Published: October 2021

Stool samples collected from National Surveillance of Diarrheal in five sentinel sites in three regions of Mozambique, between May 2014 and December 2019 from 2126 children under 15 years of age with acute gastroenteritis were tested for five different etiological viral. Rotavirus, norovirus, astroviruses and adenovirus was screened by Enzyme immunoassay and reverse transcription-PCR for enteroviruses. Rotavirus was detected in 23.4%, enteroviruses in 14.1%, adenoviruses in 6.3%, astroviruses in 3.3% and norovirus in 2.7%. Rotavirus infection remains the main cause of diarrhea in Mozambique, despite the reduction in cases after the introduction of the rotavirus vaccine.
Fuzzy covering-based rough set on two different universes and its application
Authors: Yang Bin
Published: October 2021

In this paper, we propose a new type of fuzzy covering-based rough set model over two different universes by using Zadeh’s extension principle. We mainly address the following issues in this paper. First, we present the definition of fuzzy β-neighborhood, which can be seen as a fuzzy mapping from a universe to the set of fuzzy sets on another universe and study its properties. Then we define a new type of fuzzy covering-based rough set model on two different universes and investigate the properties of this model. Meanwhile, we give a necessary and sufficient condition under which two fuzzy β-coverings to generate the same fuzzy covering lower approximation or the same fuzzy covering upper approximation. Moreover, matrix representations of thefuzzy covering lower and fuzzy covering upper approximation operators are investigated. Finally, we propose a new approach to a kind of multiple criteria decision making problem based on fuzzy covering-based rough set model over two universes. The proposed models not onlyenrich the theory of fuzzy covering-based rough set but also provide a new perspective for multiple criteria decision making with uncertainty.