bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-based deep learning nomogram for prediction of early metachronous liver metastases in rectal cancer
Authors: Zhao Rui , Wan Lijuan , Chen Shuang , Peng Wenjing , Zhao Qing , Ye Feng , Zhao Xinming , Zhang Hongmei
Published: August 2022

Background
To investigate the potential of deep learning nomogram based on MRI for predicting early metachronous liver metastases (EMLM) in patients with rectal cancer.
Methods
A total of 170 patients with rectal cancer were enrolled and divided into training (2,080 images and later augmented to 12,480 images, 130 patients) and test (640 images, 40 patients) sets. A deep learning model was developed based on T2WI images using a 3D residual network (3D-ResNet). A clinical model based on independent predictors was then constructed via multivariate logistic regression. The nomogram was constructed by integrating the deep learning model with clinical model.
Results
The deep learning model exhibited good performance with AUCs of 0.856 and 0.812 in the training and test sets, respectively. Multivariate logistic regression revealed that mr-N stage (OR, 2.260; 95% CI: 1.322–3.865; p = 0.003) and mr-EMVI (OR, 2.682; 95% CI: 1.204–5.976; p = 0.016) were independent predictors of EMLM. The clinical model based on mr-N stage and mr-EMVI was developed with AUCs of 0.738 and 0.754 in the training and test sets, respectively. A nomogram was constructed based on three variables: deep learning signature, mr-N stage, and mr-EMVI. The AUCs of the nomogram were 0.906 and 0.895 in the training and test sets, respectively. The predictive performance of the nomogram was significantly superior to that of the clinical model and the deep learning model in both the training and test sets (p < 0.05).
Conclusions
The nomogram combining deep learning signature, mr-N stage and mr-EMVI may aid in the clinical prediction of EMLM in patients with rectal cancer.
Heparin-perfusion therapy for thrombosis of the intra- and extrahepatic portal and mesenteric vein.
Authors: Misbahuddin-Leis Mohammed , Ademi Burhan , Ankolvi Muzaffer , Dubasz Krisztina , Mishra Manisha , Riechmann Maren , Graeb Christian , Radeleff Boris
Published: August 2022

Background:Although as stated many times in the literature, the initial treatment of acute and subacute portal vein thrombosis (PVT) consists of intravenous anticoagulation with heparin, but there is still a huge uncertainty among physicians regarding whether the patient should be better taken to more invasive therapies. Case Presentation:We henceforth report on a 61-year-old patient, who presented in our emergency room with a subacute thrombosis of the intra- and extrahepatic portal and superior mesenteric vein (SMV) and venous congestion of 20-30 cm of the small intestine with a quick and complete remission of the PVT under sole i.v. Heparin-perfusor therapy with repetitive CT-follow-ups without any complications. Molecular genetic analysis found combined genetic mutations of the gene factor 2 (c.20210G>A, heterozygotic), SERPINE1 (-675 5G>4G, heterozygotic), and the MTHFR gene.Conclusion:Early diagnosis and immediate initiation of heparinization in patients with PVT and SMVT, could not only reverse the initial intestinal ischemia but also suffice as the sole mode of treatment, preventing the subsequent need for radiological and surgical interventions. Furthermore, molecular genetic counseling should be always taken under consideration when the cause of PVT remains unknown
RRSC-128AEAD: An Efficient Randomized Lightweight Stream Cipher Supports Authenticated Encryption with Associated Data
Authors: Chatterjee Runa , Chakraborty Rajdeep , Elngar Ahmed A.
Published: August 2022

A proposed stream cipher, RRSC-128AEAD, supports authenticated encryption with associated data (AEAD) for checking both the authenticity and integrity of the message. This cipher includes a key and a nonce of size 128-bit each as input. It produces two different pseudo-random bit streams in parallel. One is used for encryption and another one is used for authentication purposes. It generates 64-bit MAC, based on the National Institute of Standards and Technology standardized (NIST) value, for lightweight security. The cipher efficiency in terms of randomness is analyzed by an online NIST statistical test suite. The design is compared with NIST standardized stream cipher GRAIN-128AEAD. The proposed cipher proves its efficiency in key reintroduction and probability of avoiding key leakage compared to GRAIN-128AEAD. Although both cipher initialization times are the same, some features like two independent bit streams, large internal states, and variable-length associated data and masking technique together made this proposed cipher stronger and more efficient against various types of attacks.
Novel function of a putative TaCOBL ortholog associated with cold response
Authors: Liu Fangfang , Wan Ying-Xiu , Cao Wen-Xin , Zhang Qi-Qi , Li Yao , Li Yan , Zhang Ping-Zhi , Si Hong-Qi
Published: August 2022

Background The cell wall plays crucial roles in establishing the morphology of plant cells and defense response to biotic and abiotic stresses. The plant COBRA protein family plays an important role in secondary cell wall biosynthesis and the orientation of cell expansion, which have been extensively studied in Arabidopsis thaliana, maize, rice, etc., but no systematic studies were conducted in wheat. Methods and Results In this study, the full-length sequence of TaCOBLs was obtained by homology cloning from wheat, and a conserved motif analysis confirmed that TaCOBLs belonged to the COBRA protein family. qRT-PCR results showed that the TaCOBL transcripts were induced by abiotic stresses, including cold, drought, salinity, and abscisic acid (ABA). Two haplotypes of TaCOBL-5B (Hap5B-a and Hap5B-b), harboring one indel (----/TATA) in the 5’ flanking region (-550 bp), were found on chromosome 5BS. A co-dominant marker, Ta5BF/Ta5BR, was developed based on the polymorphism of the two TaCOBL-5B haplotypes. Significant correlations between the two TaCOBL-5B haplotypes and cold resistance were observed under four environmental conditions. Conclusion Hap5B-a, a favored haplotype acquired during wheat polyploidization, may positively contribute to enhanced cold resistance in wheat. Based on the promoter activity analysis, the Hap5B-a promoter containing a TATA-box was more active than that of Hap5B-b without the TATA-box under low temperature. Our study provides valuable information indicating that the TaCOBL genes are associated with cold response in wheat.
A unified earthquake catalog for Northern Algeria based on an advanced moment magnitude scale using a robust regression method
Authors: Boudebouda Afaf , Athmani Allaeddine , Das Ranjit
Published: August 2022

The establishment of a homogenous earthquake catalog is a basic requirement for attaining a detailed seismological analysis and an improved seismic hazard assessment. Accordingly, the current research paper aims to present a reliable instrumental homogeneous earthquake catalog for the northern part of Algeria. This unified catalog is compiled using regional empirical relationships derived from converting different magnitude scales to an advanced physical-based moment magnitude scale suggested in the recent literature and denoted by Mwg. The regression methodology used in this study is called the New General Orthogonal Regression approach (N.GOR), which was selected since it is the most trustworthy procedure for scaling the magnitudes to Mwg. To highlight the significance of using the N.GOR, the obtained outcomes of the scaling relations were compared with those issued from the conventional general orthogonal regression (GOR) method, which is deemed to be the most dependable methodology used worldwide for magnitude conversion problems. The unified earthquake catalog was assembled from 1954 to 2022. Reliably converting the original magnitudes into homogenized moment magnitude leads to a complete and consistent unified earthquake catalog. Indeed, the homogenized moment magnitude catalog presented in this paper could provide reliable data for studying earthquakes distribution and the assessment of seismic hazards in the north of Algeria.
Assessment of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with High Myopia
Authors: Wang Xin , He Qing , Zhao Xiaoyu , Li Haoru , Liu Lin , Wu Di , Wei Ruihua
Published: August 2022

BackgroundPrevious reports have suggested that inflammation levels play a crucial role in the pathogenesis of high myopia (HM). The aim of this study was to investigate the relationship between HM and systemic inflammation using the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).MethodsOverall, 100 age- and sex-matched participants were recruited for the study, including 50 eyes in the non-HM (NHM) group and 50 eyes in the HM group. Ocular examinations and blood tests were performed. The NLR and PLR values were calculated from complete blood counts. Receiver operating characteristic (ROC) curves and optimal cut-off values were used to determine the optimal values of the NLR and PLR to distinguish between the HM and NHM groups.ResultsThe values of NLR and PLR were significantly elevated in the HM group compared with those in the NHM group (P < 0.001 and P = 0.010, respectively). Axial length (AL) was significantly correlated with the NLR (r = 0.367, P < 0.001) and PLR (r = 0.262, P = 0.009). In the ROC analysis, the NLR value to distinguish between the HM and NHM groups was 0.728; the best cut-off value was 2.68, with 76% sensitivity and 62% specificity. The PLR value to distinguish between the HM and NHM groups was 0.650; the best cut-off value was 139.69, with 52% sensitivity and 76% specificity.ConclusionThe findings of this study indicate that the development of HM may be associated with systemic inflammation measured using the NLR and PLR.Trial Registration: The study was registered on December 28, 2021 (http://www.chictr.org.cn; ChiCTR2100054834).
A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer
Authors: Li Jia-Ke , Liu Hai , Zhang Hui-Wen , Li Jun , Liang Zhuo-Tao
Published: August 2022

Purpose
Colorectal cancer (CRC) is the 3rd most prevalent malignant tumour globally. Although significant strides have been made in diagnosis and treatment, its prognosis at the moment remains unpromising. Therefore, there is an urgent and desperate need to identify novel biomarkers of CRC and evaluate its mechanism of tumourigenesis and development.
Methods
JASPAR and RNAinter databases are used to analyze target genes associated with colorectal cancer. Western blotting, q-PCR and immunohistochemistry et, al. were used to detect the level of MNX1 in patients with colorectal cancer, and Chip-PCR was used to detect the targeted binding ability of E2F4 and MNX1. The cells and animal models overexpressed MNX1 and E2F4 were constructed by siRNA transfection.
Results
Herein, MNX1 was highly expressed and linked to favourable overall survival curves in colorectal cancer. The functional assay revealed that MNX1 overexpression could promote proliferation, migration, and invasion of CRC cells. Based on the prediction of the JASPAR and RNAinter databases, the transcription factor, E2F4, was bound to the MNX1 promoter region. The Chromatin Immunoprecipitation (ChIP) assay verified the interactions between MNX1 and E2F4 in CRC. Additionally, we found that sh-E2F4 markedly downregulated the MNX1 levels and reduced CRC progression in vivo and in vitro, which reversed MNX1 overexpression.
Conclusion
Therefore, our research discovered that E2F4-mediated abnormal MNX1 expression promotes CRC progression and could become a novel diagnostic or therapeutic target of CRC.
An Inventive Method for Graphene-Based Optofluidic Tweezer to Actively Detection, Sorting, and Manipulation of Nano-bioparticles below 2.5 nm
Authors: Gholizadeh Elnaz , Jafari Behnam , Golmohammadi Saeed
Published: August 2022

This work proposes a novel design composed of graphene nanoribbons-based optofluidic tweezers to manipulate and sort bio-particles with radii below 2.5 nm. The suggested structure has been numerically investigated by the finite difference time domain (FDTD) method employing Maxwell's stress tensor analysis (MST). The finite element method (FEM) has been used to obtain the electrostatic response of the proposed structure. The tweezer main path is a primary channel in the center of the structure, where the microfluidic flow translates the nanoparticle toward this channel. Concerning the microfluid's drag force, the nanoparticles tend to move along the length of the main channel. The graphene nanoribbons are fixed near the main channel at different distances to exert optical forces on the moving nanoparticles in the perpendicular direction. In this regard, sub-channels embedding in the hBN layer on the Si substrate deviate bio-particles from the main path for particular nanoparticle sizes and indices. Intense hotspots with electric field enhancements up to 900 times larger than the incident light are realized inside and around the graphene ribbons. Adjusting the gap distance between graphene nanoribbon and the main channel allows us to separate the individual particle with a specific size from others, thus guiding that in the desired sub-channel. Furthermore, we demonstrated that in a structure with a large gap between channels, particles experience weak field intensity, leading to a low optical force that is insufficient to detect, trap, and manipulate nanoparticles. By varying the chemical potential of graphene associated with the electric field intensity variations in the graphene ribbons, we realized tunability in sorting nanoparticles while structural parameters remained constant. In fact, by adjusting the graphene Fermi level via the applied gate voltage, nanoparticles with any desired radius will be quickly sorted. Moreover, we exhibited that the proposed structure could sort nanoparticles based on their refractive indices. Therefore, the given optofluidic tweezer can detect bio-particles with immense accuracies, such as cancer cells and viruses of tiny size.
WITHDRAWN: Causal Strength Account for Violations of the Screening-off Rule in Causal Reasoning
Authors: Liang Yuan , Duan Xu , Wu Guoqiang , Cao Chenqian , Yan Hao
Published: August 2022

As a core of Causal Bayes networks, Screening-off rule is usually violated by people. Two experiments were conducted to investigate causal strength’s role in the violations of screening-off rule. Experiment 1 tested whether participants would follow the screening-off rule by examining the probability judgment of target nodes which would be influenced by the state of non-target nodes in common cause and chain models. Experiment 2 examined whether the probability judgment of target nodes would be influenced by causal strength judgment of their common cause in the common cause model (or of the middle node in the chain model). Both experiments used binary variables. Results showed that participants’ causal inferences increased with their perceived causal strength which grew with the presence proportion of other causal-related variables. Findings suggested that the causal strength explanation could offer the best prediction for people’s causal inferences, indicating people were sensitive to explicit causal strength of events and made causal inferences according to the strength. Thus, people’s causal inferences may not violate the screening-off rule.
Mendelian Randomization Identified CHRNE as a Potential Drug Target for Alzheimer’s disease
Authors: Li Ming-Li , Yang Yang , Song Bo , Yang Jing , Fan Li-Yuan , Xu Yuming
Published: August 2022

Since clinical trials of novel therapeutics for Alzheimer’s disease (AD) have been largely disappointing, drug repurposing may provide an effective approach to identifying therapeutics to treat AD. In this study, two-sample Mendelian randomization analysis was employed to evaluate brain and blood transcriptomic data for 1263 actionable proteins targeted by approved drugs or in the clinical phase of drug development. The genome-wide association studies included 17008 patients with AD and 37154 controls to predict the potential target gene for AD. CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit) mRNA expression increased the risk for AD in both the brain and the blood. Bayesian colocalization analysis confirmed that this was not coincidentally due to linkage disequilibrium. Furthermore, the proteins encoded by CHRNE were mainly expressed on the surface of microglia. The trials of drugs targeting CHRNE should be prioritized to design future functional studies and therapy for AD.
Predator-induced phenotypic plasticity during early biological evolution and ROS suppression in the brain of Xenopus tropicalis
Authors: Mori Tsukasa , Machida Kazumasa , Kudou Yuki , Kimishima Masaya , Sassa Kaito , Goto-Inoue Naoko , Minei Ryuhei , Ogura Atsushi , Kobayashi Yui , Kamiya Kentaro , Nakaya Daiki , Yamamoto Naoyuki , Kashiwagi Akihiko , Kashiwagi Keiko
Published: August 2022

Predator-induced adaptive phenotypic plasticity is essential for evolution. However, Xenopus tropicalis tadpoles do not exhibit distinct phenotypes when exposed to new predation threats. Here, we investigated adaptions within their brain. Principal component analysis using morphological parameters indicated that short-term predation threats (24 hr) altered tadpole morphology unlike the control or 5 day-out treatment (exposure to predation for 5 days and then no exposure for 5 days). Whole-brain ingenuity pathway and metabolome analyses revealed that free radicals, superoxide dismutase, glycogenesis, and pyruvate were elevated after 6 hr of predation pressure. Hemoglobin was also synthesized in the brain, forming oxyhemoglobin in the midbrain and hindbrain to reduce radical production. Furthermore, ATP production through glycolysis was promoted, while β-oxidation and the tricarboxylic acid cycle were downregulated. We also predicted increases in microtubule dynamics, neuronal branching, and neuritogenesis. Therefore, X. tropicalis tadpoles can adapt to predation stress through changes within their central nervous system.
Influence of alkyl chain length on the tribological performance of choline ionic liquids as water-based lubricating additives under electric field conditions
Authors: Wang Ruozheng , Yan Xiaoyan , Zhao Shuping , Sun Chufeng , Yang Zhaozhao , Xiang Wenjun , Wang Xingwei , Zhou Chunyu , Yu Qiangliang , Yu Bo , Cai Meirong , Zhou Feng
Published: August 2022

To develop green lubricants and improve the lubricating properties of water, three choline-type ionic liquids with different alkyl chain lengths were designed and synthesised as water-based additives. The tribological behaviour of these ionic liquids as a water-based lubricating additives in an ethylene glycol system was systematically studied under an external electric field. The results show that under current-carrying lubrication, the [Ch][SA] ionic liquid exhibits excellent anti-friction and anti-wear properties with increasing alkyl chain length. Mechanistic analysis showed that the [Ch][SA] ionic liquid could strongly adsorb on the metal surface to form a physical adsorption film. At the same time, during the friction process, the [Ch][SA] ionic liquid forms a dense tribochemical reaction film with the metal substrate, which effectively blocks direct contact between the friction pairs. The excellent anti-friction and anti-wear properties are the result of the synergistic effect of the physical adsorption film and the chemical reaction film.
The relationship between serum C-reactive protein and senile hypertension
Authors: He Le , Fan Chenyang , Li Gang
Published: August 2022

Background: Hypertension has become an important health risk factor in the 21st century, especially for the elderly. Studies have confirmed that inflammation is involved in the development of hypertension and that the inflammatory marker C-reactive protein(CRP) is significantly associated with hypertension. Therefore, in this study, we aimed to explore the CRP correlation with hypertension in the elderly. Methods: Serum CRP levels were measured in 196 hospitalized patients, and the CRP level was used as a criterion to divide them into the group with elevated CRP (>10 mmol/L, n=120) and the group with normal CRP (0 < CRP ≤ 10 mmol/L, n=76). and the patient's baseline characteristics were collected and compared between the groups, and the correlation between CRP and other factors and hypertension in the elderly was analyzed by multi-factor logistic regression. Results: The prevalence of hypertension, coronary artery disease and joint reactive inflammation was significantly higher in the group with elevated CRP. There was also a significant association between the use of alcohol, low density lipoprotein cholesterol (LDL-C) and steroids and elevated CRP; logistic regression showed that elevated CRP (OR=2.13, 95% CI: 1.14-3.99, p=0.019), body mass index (BMI) (OR= 1.10, 95% CI:1.01-1.90, p=0.030), diabetes (OR=2.68, 95% CI:1.24-5.79, p=0.012) were positively associated with hypertension, while statins use was negatively associated with hypertension (OR=0.49, 95% CI: 0.25-0.94, p=0.013).Conclusions: Elevated CRP, BMI, and diabetes are positively associated with hypertension in the elderly, and early screening for CRP and initiation of treatment may help prevent further inflammatory responses in hypertension.
Effect of Tri-n-butyl phosphate (TnBP) on neurobehavior of Caenorhabditis elegans
Authors: Tang Jielin , Qin Jinyan , Kuerban Guzailinuer , Li Jiayi , Zhou Qinyu , Zhang Hongdan , Sun Rongli , Yin Lihong , Pu Yuepu , Zhang Juan
Published: August 2022

As an emerging flame retardant, organic phosphate flame retardants have been extensively used worldwide. The aim of this study is to determine the effects of TnBP on neurobehavior of Caenorhabditis elegans (C. elegans) and its mechanisms. L1 larvae of wild-type C. elegans N2 and transgenic nematodes (BZ555, DA1240 and EG1285) were exposed to TnBP of 0, 0.1, 1, 10 and 20 mg/L for 72 hours, respectively. Then, we observed that TnBP inhibited the body length and body width, increased the head swings and body bends, reduced the pump contraction times and chemical trend index, and increased the production of reactive oxygen species (ROS), altered the expression of genes (mev-1 and gas-1) related to mitochondrial oxidative stress, increased the expression of genes (pmk-1, sek-1 and nsy-1) related to p38 MAPK signal pathway, increased the production of dopamine, glutamate and Gamma-Amino Butyric Acid (GABA). When changes of motor behaviors were taken as the endpoint of toxicity evaluation, we found that the pmk-1 mutants led to the sensitivity of nematodes to TnBP. Therefore, the results showed that TnBP had harmful effects on the neurobehavior of nematodes, oxidative stress might be one of the mechanisms of neurotoxicity, and the activation of p38 MAPK signal pathway might play a protective role for nematodes against the harmful effects induced by TnBP. The research results revealed the potential effects of TnBP on the neurobehavior of C. elegans, put forward new expectations for the study of environmental hygiene and human survival risks of organic phosphate flame retardants.
Crust Macrofracturing as the Evidence of the Last Deglaciation
Authors: Aleshin Igor , Kholodkov Kirill , Kozlovskaya Elena , Malygin Ivan
Published: August 2022

Machine learning methods were applied to reconsider the results of several passive seismic experiments in Finland. We created datasets from different stages of the receiver function technique and processed them with one of basic machine learning algorithms. All the results were obtained uniformly with the k-nearest neighbors algorithm. The first result is the Moho depth map of the region. Another result is the delineation of the near-surface low S-wave velocity layer. There are three such areas in the Northern, Southern, and central parts of the region. The low S-wave velocity in the Northern and Southern areas can be linked to the geological structure. However, we attribute the central low S-wave velocity area to a large number of water-saturated cracks in the upper 1-5 km. Analysis of the structure of this area leads us to the conclusion that macrofracturing was caused by the last deglaciation.
Leukocyte CH25H is a potential diagnostic and prognostic marker for lung adenocarcinoma
Authors: Zhang Jun , Xu Lidong , Gao Jun , Li Jieyi , Zhao Xiaokai , Yang Pengmin , Ge Yujun , Guo Dawei , Liu Zhonghua , Wang Xiyong , Gu Wenchao , Wang Pengli , Hu Xun , Gong Ziying , Zhang Daoyun
Published: August 2022

ObjectivesMetastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Materials/methodsOnline public databases were used to analyze the differential expression, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. ResultsThe expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan–Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). ConclusionOur study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.
FTD-tau S320F mutation stabilizes local structure and allosterically promotes amyloid motif-dependent aggregation
Authors: Chen Dailu , Wosztyl Aleksandra , Mullapudi Vishruth , Bali Sofia , Vacquer-Alicea Jaime , Melhem Shamiram , Seelaar Harro , Swieten John van , Diamond Marc , Joachimiak Lukasz
Published: August 2022

Amyloid deposition of the microtubule-associated protein tau is a unifying theme in a multitude of neurodegenerative diseases. Disease-associated missense mutations in tau are associated with frontotemporal dementia (FTD) and enhance tau aggregation propensity. However, the molecular mechanism of how mutations in tau promote tau assembly into amyloids remains obscure. There is a need to understand how tau folds into pathogenic conformations to cause disease. Here we describe the structural mechanism for how an FTD-tau S320F mutation drives spontaneous aggregation. We use recombinant protein and synthetic peptide systems, computational modeling, cross-linking mass spectrometry, and cell models to investigate the mechanism of spontaneous aggregation of the S320F FTD-tau mutant. We discover that the S320F mutation drives the stabilization of a local hydrophobic cluster which allosterically exposes the 306VQIVYK311 amyloid motif. We identify a suppressor mutation that reverses the S320F aggregation phenotype through the reduction of S320F-based hydrophobic clustering in vitro and in cells. Finally, we use structure-based computational design to engineer rapidly aggregating tau sequences by optimizing nonpolar clusters in proximity to the S320 site revealing a new principle that governs the regulation of tau aggregation. We uncover a mechanism for regulating aggregation that balances transient nonpolar contacts within local protective structures or in longer-range interactions that sequester amyloid motifs. The introduction of a pathogenic mutation redistributes these transient interactions to drive spontaneous aggregation. We anticipate deeper knowledge of this process will permit control of tau aggregation into discrete structural polymorphs to aid design of reagents that can detect disease-specific tau conformations.
Impact of preoperative white blood cell count on long-term outcome in patients undergoing surgery for colorectal cancer: a retrospective observational study
Authors: Wang Bei , Li Lihong , Wang Shilai , Zhou Changming , Sun Zhirong , Weng Meilin
Published: August 2022

Purpose: This study aimed to explore the correlation between preoperative white blood cell (WBC) count and the outcome in patients who underwent surgery for colorectal cancer (CRC) and the potential marker to predict the outcome.Patients and methods: A total of 8121 Chinese patients at Fudan University Shanghai Cancer Center (FUSCC) undergoing colectomy, Dixon’s or Mile’s, for CRC from January 2008 to December 2014 were enrolled in present study. Based on that the WBC optimal cut-off value was ﻿7*109, the patients were divided into two groups, the moderate leukocytosis group (the leukocytosis group) and non-leukocytosis group. The impact of preoperative WBC count on disease-free survival (DFS) and overall survival (OS) was investigated using the Kaplan-Meier method and Cox proportional hazard models.Results: Moderate leukocytosis (≥﻿7*109) was recognized as a prognostic factor for survival independently. Moderate leukocytosis was significantly associated with male sex (P﻿＜0.001), advanced T stage (P﻿＜0.001), TNM stage (P﻿＜0.001), and no preoperative chemotherapy (P﻿＜0.001). Moderate leukocytosis group was corelated with poorer overall survival (OS) (P﻿＜0.001) and disease-free survival (DFS) (P=0.024) than non-leukocytosis group. In the multivariate analysis, the moderate leukocytosis group had a 19.6% higher risk in OS (HR=1.196, 95CI%:1.088-1.314, P<0.001) and had a 13.1% higher risk in DFS (HR=1.131, 95CI%:1.016-1.259, P=0.024) than the non-leukocytosis group. We found that the association with preoperative moderate leukocytosis and poorer OS (P﻿＜0.001) or DFS (P﻿=0.001) in patients with no preoperative chemotherapy in subgroup analysis.Conclusions: Preoperative moderate leukocytosis is associated with shorter OS, DFS indicating poor outcome in CRC patients after surgery.
Combined treatment with ruxolitinib and MK-2206 inhibits the JAK2/STAT5 and PI3K/AKT pathways via apoptosis in MDA-MB-231 cells
Authors: Celik Esin Guvenir , EROGLU Onur
Published: August 2022

Background: Due to deficiencies in the expression of hormone receptors, such as PR, ER and HER2, it is challenging to treat triple-negative breast cancer (TNBC), which does not respond to single targeted therapy. Ruxolitinib is a Janus kinase (JAK)1/JAK2 inhibitor. MK-2206 is an allosteric AKT inhibitor. Due to the limited activities of ruxolitinib and MK-2206 for monotherapy, the need for cotreatment with other drugs has emerged. This study is the first to examine the effects of ruxolitinib and MK-2206 cotreatment on apoptosis and JAK2/STAT5 and PI3K/AKT signaling in MDA-MB-231 breast cancer cells. Additionally, this work aimed to decrease the side effects of ruxolitinib and increase its anticancer effects with MK-2206 cotreatment.Methods and Results: Cell viability was reduced in a dose- and time-dependent manner after exposure to ruxolitinib, MK-2206 or both for 48 h, as shown by MTT assay. Ruxolitinib had a synergistic antiproliferative effect, as demonstrated by colony formation and wound healing assays. The effects of ruxolitinib, MK-2206 and their combination on apoptosis, as well as PI3K/AKT and JAK/STAT signaling, were examined by western blot analyses. Cotreatment with ruxolitinib and MK-2206 reduced proliferation with the dual inhibition of JAK2/STAT5 and PI3K/AKT signaling by decreasing PI3K, AKT, JAK2, STAT5, Caspase-9, Caspase-7, PARP, c-Myc, and Bcl-2 and increasing P53 and PTEN protein expression.Conclusions: Our results revealed the roles of P53 and PTEN in the regulation of apoptosis and the PI3K/AKT and JAK2/STAT5 signaling pathways. The dual inhibition of JAK2/STAT5 and PI3K/AKT may reduce metastasis by decreasing tumor cell survival.
Impacts of Lysinibacillus sphaericus on mosquito larval community composition and larval competition between Culex pipiens and Aedes albopictus
Authors: McMillan Joseph R. , Olson Michael , Petruff Tanya , Shepard John J. , Armstrong Philip
Published: August 2022

Effectiveness of mosquito larvicide active ingredients (AI), such as Lysinibacillus sphaericus, varies between species. To examine how differential effectiveness of L. sphaericus influences larval community dynamics, we performed two experiments. We performed a field experiment in which containers were seeded with a standardized nutrient treatment, mosquitoes colonized the containers, and then containers received one of three L. sphaericus applications. We then performed competition assays between Culex pipiens and Aedes albopictus in low nutrient environments using multiple interspecific ratios and the presence/absence of a low dose of L. sphaericus. Field results demonstrated elimination of Culex spp. from the treated containers while container breeding Aedes spp. proliferated across all treatments. Lysinibacillus sphaericus did not influence competition between Cx. pipiens and Ae. albopictus, and the L. sphaericus application eliminated Cx. pipiens in all treatment replicates while survival of Ae. albopictus was similar between treated and untreated containers across interspecific ratios. Lysinibacillus sphaericus is an effective AI for control of Culex spp. However, different AIs should be utilized in habitats containing non-Culex genera while a mix of AIs should be utilized where coexistence of multiple genera is expected or confirmed.
The Effect of Educational Intervention Based on the Trans Theoretical Model on the Physical Activity Level of Diabetic Patients in Iran: A Educational Trial Study
Authors: Bahrami Mahdie , Mousavi Saghi , Ghoozlu Khadije Jahangasht
Published: August 2022

Introduction: Regular physical activity can reduce mortality in patients with diabetes and prevent its complications. Planning to change behavior in these people in order to improve self-care is very crucial. The present study aimed to investigate the effect of an educational intervention based on the Trans Theoretical Model (TTM) on the physical activity level of diabetic patients. Methods: In this educational trial study, 120 patients with type 2 diabetes were included in the study in Rasht city. So that they were divided into two groups of intervention (60 people) and control (60 people) using 2 random block methods, and they completed the questionnaires of physical activity and the constructs of the change stages model. Then the educational intervention, including lectures, pamphlets, and educational CDs, was provided to the intervention group, while the control group did not receive any education. After one month of follow-up, the patients completed the questionnaire again. Data were analyzed using SPSS.v20. Results: The results showed that there was no significant difference between the intervention and control groups regarding regular physical activity before the educational intervention. However, after the intervention, the mean score of physical activity in the intervention group was higher than that of the control group, and this difference was statistically significant (P = 0.004). In relation to the distribution of physical activities change stages, a statistically significant difference was observed in the intervention group after the educational intervention (p<0.001). Conclusion: The results showed that educating diabetic patients regarding physical activity based on the TTM was effective in progressing the behavior change stages and increasing the regular physical activity score of the patients. Therefore, it is recommended to design and implement educational programs to promote physical activity level based on behavior change theories in order to improve the control and management of type 2 diabetes.
A selective laser-based sensor for fugitive methane emissions
Authors: Mhanna Mhanna , Sy Mohamed , Farooq Aamir
Published: August 2022

A mid-infrared laser-based sensor is reported for the quantification of fugitive methane emissions. The sensor is based on a distributed feedback inter-band cascade laser (DFB – ICL) operating near 3.3 µm. Wavelength tuning with cepstral analysis is employed to isolate methane absorbance from (1) fluctuations in the baseline laser intensity, and (2) interfering species. Cepstral analysis creates a modified form of the time-domain molecular free-induction-decay (m-FID) signal to temporally separate optical and molecular responses. The developed sensor is insensitive to baseline laser intensity imperfections and spectral interference from other species. Accurate measurements of methane in the presence of a representative interfering species, benzene, are performed by careful selection of the scan index (ratio of laser tuning range to spectral linewidth) and initial and final time of m-FID signal fitting. The minimum detection limit of the sensor is ~ 50 ppm which can be enhanced with an optical cavity. The proposed sensing strategy can be utilized to measure methane leaks in harsh environments and in the presence of interfering species.
N6-methyladenosine writer KIAA1429 modulates the proliferation/migration of endothelial cells for atherosclerosis
Authors: Rong Jian , Jie Yingxin , Zhao Hui
Published: August 2022

Increasing evidence illustrates the important roles of N6-methyladenosine (m6A) in progression of atherosclerosis (AS). However, the connections between m6A modification and AS pathophysiological process are unknown. Here, this work investigated the expression profile of m6A methyltransferase KIAA1429 in AS pathology and explored its undergoing m6A-dependent molecular mechanism. Results indicated that KIAA1429 was remarkedly up-regulated in oxidative low-density lipoprotein (ox-LDL) treated human umbilical vein endothelial cells (HUVECs). KIAA1429 overexpression inhibited proliferation/migration in ox-LDL-administrated HUVECs, while, KIAA1429 knockdown repressed the proliferation and migration. Mechanistically, ROCK2 mRNA was post-transcriptionally upregulated by KIAA1429 in response to Actinomycin D administration through m6A modified site binding on ROCK2 mRNA. Collectively, our study demonstrates the functional regulation of KIAA1429 on ox-LDL-induced HUVECs via m6A/ROCK2 axis. These findings provide new insights for m6A-mediated epigenetics in AS.
A green spectrofluorimetric approach for the versatile determination of Bilastine in real human plasma and pharmaceutical preparations with content uniformity testing
Authors: Derayea Sayed M. , El-Din Khalid M. Badr , Ahmed Ahmed S. , Khorshed Ahmed , Oraby Mohamed
Published: August 2022

A green spectrofluorimetric method for determining Bilastine (BIL) was described. The method is very sensitive, simple, and quick. The suggested method was depend on the measurement of the original fluorescence of BIL in 1.0 M sulfuric acid at an emission wavelength of 385 nm after an excitation at 272 nm. The method was evaluated by ICH requirements. The relationship between BIL concentrations and the fluorescence intensities was linear in a range of 10.0–500.0 ng mL− 1, and the correlation coefficient was 0.9999. The detection limit was 2.9 ng mL− 1 and quantitation limit was 8.8 ng mL− 1. The suitable sensitivity and selectivity of the suggested method enabled its application successfully in analyzing BIL in real human plasma with appropriate recoveries from 95.72% to 97.2 %, as well as in pharmaceutical preparations without any interfering effect from plasma components or pharmaceutical excipients. Additionally, the suggested method was utilized efficiently for content uniformity test.
Blemish identification in Co-variance of Disease using Data Mining Techniques
Authors: Aneeshkumar A. S.
Published: August 2022

Data mining is an established domain used to identify influenced or associated aspects and its occurrence for the forecasting and future predictions in several fields. These information are statistically consistent, substantial facts and formerly unknown. Health care is one of the major data mining application area. In health related organizations, the techniques of data mining are used to observe characteristics of a disease or a particular medical condition and formation of its treatment. Liver enzymes are useful for accountable physical and chemical activities in the body and its variations will affects other relevant functionalities of our body. Diabetes Mellitus is a state, where the body does not produce enough insulin to convert blood sugar to energy. The influence of diabetes in liver disordered patients are the base of this study. Chi-squared automatic interaction detector is applied in this paper to determine the contribution of Liver disease to diabetes mellitus and vice-versa.
Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia progression and clinical responses in head and neck cancer patients
Authors: Suzuki Yusuke , Naito Takafumi , Shibata Kaito , Hosokawa Seiji , Kawakami Junichi
Published: August 2022

Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia progression and clinical responses in head and neck cancer patients. Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Serum albumin level was negatively correlated with the plasma concentrations of aprepitant at 24 hours after a 3-day aprepitant treatment. The patients with Glasgow Prognostic Score (GPS) 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. In conclusion, cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.
Quantitative Assessments of Finger Individuation with an Instrumented Glove
Authors: Conway Brian J , Taquet Léon , Boerger Timothy F , Cornell Sarah , Krucoff Kate B , Schmit Brian D , Krucoff Max O
Published: August 2022

Background:In clinical and research settings, hand dexterity is often assessed as finger individuation, or the ability to move one finger at a time. Despite its clinical importance, there is currently no standardized, sufficiently sensitive, or fully objective platform for these evaluations.Methods:Here we developed two novel individuation scores and tested them against a previously developed score (1) using a commercially available instrumented glove and data collected from 20 healthy adults. Participants performed individuation for each finger of each hand as well as whole hand open-close at two study visits separated by several weeks. Using the three individuation scores, intra-class correlation coefficients (ICC’s) and minimal detectable changes (MDC) were calculated. Individuation scores were further correlated with subjective assessments to assess validity.Results:We found that each score emphasizes different aspects of individuation performance while generating scores on the same scale (0 [poor] to 1 [ideal]). These scores are repeatable, but the quality of these metrics vary by both equation and finger of interest. For example, index finger intra-class correlation coefficients (ICC’s) were 0.90 (< 0.0001), 0.77 ([< 0.001), and 0.83 (p < 0.0001), while pinky finger ICC’s were 0.96 (p < 0.0001), 0.88 (p < 0.0001), and 0.81 (p < 0.001) for each score. Similarly, MDCs also vary by both finger and equation. In particular, thumb MDCs were 0.068, 0.14, and 0.045, while index MDCs were 0.041, 0.066, and 0.078. Furthermore, objective measurements correlated with subjective assessments of finger individuation quality for all three equations (ρ=-0.45, p < 0.0001; ρ=-0.53, p < 0.0001; ρ=-0.40, p < 0.0001).Conclusions:Here we evaluate the nuances of each objective scoring system and discuss ideal translational applications into motor physiology and rehabilitations labs, orthopedic hand and neurosurgery clinics, and even operating rooms for real-time objective scoring during peripheral nerve and awake brain operations for each equation. This work represents the first healthy participant data set for this translatable and objective measurement and scoring platform.
Afforestation strengthens aggregational differentiation of soil nutrients and microbiomes in erosive degraded ecosystem
Authors: Chen Peng , Wang Li , Li Jun-Ya , Wan Wenjie , Zhang Run-Qin , Liu Yi , Li Zhi-Guo
Published: August 2022

Aims
Afforestation has been viewed as the most effective natural method to restore the erosive degraded ecosystem. However, the effect of soil inherent heterogeneity on soil quality, microbial community dynamics and assembly after afforestation in rocky desertification area remains indistinct.
Methods
In the present study, we set up 3 standard quadrats for each soil type, i.e., bareland, farmland and woodland, in the study area and separated the soils into four aggregate size fractions. Soil nutrition status, enzymatic activities, bacterial and fungal community composition in different aggregate fractions were determined.
Results
Generally, afforestation promoted soil nutrients and enzyme activities, and strengthened their aggregational differentiation. Interestingly, the aggregational differentiation of bacterial alpha-diversity was more sensitive to afforestation than fungal alpha-diversity. Conversely, afforestation caused that more fungal taxa were susceptible to soil aggregates than bacterial taxa. In the bareland, deterministic process was the decisive factor for the bacterial community, while fungal community was determined by both stochastic and deterministic processes. Afforestation regulated the balance between stochastic and deterministic processes Dispersal limitation, belonging to stochastic process, determined bacterial community assembly; whereas, fungal community assembly was governed by variable selection belonging to deterministic process.
Conclusions
Afforestation on the bareland promoted the aggregation differentiation of soil nutrients, microbial community composition and diversity, and changed the mechanism of microbial community assembly in the rocky desertification area of Danjiangkou Reservoir. This study provides critical insights into the responses of soil nutrition and microbial community to vegetation restoration at the soil aggregate level.