bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-task Learning and Ensemble Approach to Predict Cognitive Scores for Patients with Alzheimer's Disease
Authors: Ma Daren , Pabalan Christabelle , Rajagopal Abhejit , Akanksha Akanksha , Interian Yannet , Raj Ashish 
Published: June 2022

Abstract
During its chronic degenerative course, Alzheimer's Disease takes a huge toll on the cognitive abilities of patients. Assessment of current and future cognition is an integral component of a diagnosis of dementia, and therefore an important clinical and scientific goal. Unfortunately, subjective, time-consuming and operator-sensitive clinical surveys or neuropyschiatric batteries remain the only viable method of assessing cognition. Given that MRI is the most prevalent, cost-effective, and clinically important imaging modality, it may be considered a suitable predictor of cognition. Yet, it has hitherto proved very challenging to predict one from the other. Here we propose that an image-based Deep Learning model can be custom-built to achieve this goal. We designed a novel multi-task UNet model to predict the subjects’ current and future cognition (via ADAS-Cog scores), taking as input baseline T1-weighted MRI and demographic risk factors. The key innovation in the model is that it seeks to solve two adjacent but relevant tasks: image segmentation into tissue types; and prediction of cognition. The first task gives a high-accuracy segmentation of the brain, comparable to other cutting edge segmentation methods. The features trained from the segmentation task are used in the cognition task. This combination is shown to be far superior to stand-alone single-shot models of cognition. We achieved excellent accuracy in both baseline and time-series forecast of ADAS-Cog scores. Through further feature map analysis made on the receptive fields, we were able to impart much-needed interpretability to the model, critical for real-world clinical practice. This study constitutes the best-reported performance of any comparable approach, and opens the door towards machine-based tracking of AD progression.
Effects of high pressure treatments (ultra-high hydrostatic pressure and high pressure homogenization) on bighead carp (Aristichthys nobilis) myofibrillar protein native state and its hydrolysate
Authors: Chen Mengting , Wang Lan , Wu Wenjin 
Published: June 2022

Abstract
The impacts of four treatments ultra-high hydrostatic pressure (UHP), high pressure homogenization (HPH), combined UHP + HPH (U-H), and HPH +UHP (H-U) on bighead carp (Aristichthys nobilis) myofibrillar protein (BMP) structure, functional hydrolysis property to pepsin, and antioxidant activity of hydrolysates were investigated. All treatments led to increase in low-molecular-weight BMP, the BMP stability, and hydrophobic group exposure, but decrease in total sulfhydryl content and BMP particle size, thus resulting in increased hydrolysis and antioxidant capacity of enzymatic hydrolysates. U-H treated BMP exhibited the highest surface hydrophobicity (924.5±1.0), zeta potential absolute value (18.88±0.11 mV), hydrolysis degree (54.5±1.6%), and antioxidant activity, but the lowest α-helix (21.84±2.61%), intrinsic fluorescence spectrum intensity, total sulfhydryl (7.24±0.07 μmol/g), and mean particle size (182.57±2.23 nm). Therefore, U-H might be a promising pretreatment to prepare bioactive peptide.
Differences in gene mutation profiles of colon cancer patients with or without a KRAS mutation
Authors: Chang Shujian , Zhou Yudan , Wu Ruirong , Ge Xiaosong , Pu Yong 
Published: June 2022

Abstract
RAS plays an important role in the carcinogenesis of colorectal epithelial cells, but RAS mutations are only present, at most, in approximately 50% of patients. In order to compare the gene mutation profiles of patients with or without a KRAS mutation, the clinicopathological data of 858 patients and NGS test results of 1697 patients with colorectal cancer were used in this analysis. In 858 patients, the mutation rate of KRAS was 50.8% (i.e., 436/858). Only 2 out of 349 (0.5%) KRAS mutant patients had a BRAF mutation, while 25 out of 422 (5.9%) KRAS wild-type patients had a BRAF mutation (p < 0.0001). The median OS of patients with a mutant or wild-type KRAS were 83.47 months and not reached, respectively (HR: 0.8147; 95% CI: 0.6271–1.051; p = 0.1153). The NGS results showed that in RAS mutant patients, genes with a high mutation rate mainly included APC, TP53, PIK3CA, Smad4, and Fbxw7, and in RAS wild-type patients, genes with a high mutation rate mainly included TP53, APC, LRP1B, MYC, and BRAF. The mutation rates of BRAF and EGFR in the RAS wild-type group were 15% and 9%, respectively, while they were only 3% in the RAS mutant group. The mutation rate of PIK3CA in the RAS mutant group was 31%, while that in the RAS wild-type group was 14%. The mutation rate of APC was 72.2% (i.e., 687/952). The mutation rate of the gene, RNF43, in the APC wild-type group was 5.23 times higher than that in the APC mutant group, and the gene, NSD1, in the APC wild-type group was 0.07 times higher than that in the APC mutant group. The mutation rate of TP53 was 78.2% (i.e., 744/952). The mutation rate of MLH1 in the TP53 wild-type group was 8.42 times higher than that in the TP53 mutant group, which was significantly higher than that in the TP53 mutant group. Generally, the gene mutation profiles were significantly different between KRAS mutation and wild-type colorectal cancer patients. A single gene mutation may be sufficient to cause the dysfunction of a signal transduction pathway, and APC, TP53, or RAS are not necessary for the carcinogenesis of sporadic colorectal cancer.
Tim-3/Galectin-9 pathway and expression of CD8 + Treg cells and related factors in patients with alveolar echinococcosis
Authors: Zhao Hui , Ma Yuyu , Tian Fengming , Li Bin , Xiao Ning , Mo Xiaojin , Min Hongyue , Cai Xuanlin , Zhang Ting , Ma Xiumin , aibibula madinaimu 
Published: June 2022

Abstract
Objective: Host immune status plays a crucial role in the parasitism, lesion activity and disease progression of Echinococcus multilocularis (EM). Therefore, by demonstrating that the Tim-3/galactose lectin-9 signaling pathway has an immunosuppressive function and the expression of CD8 + Treg cells and related factors in patients with alveolar encephalopathy (AE), this study can determine the relationship and function of the Tim-3/galactose lectin-9 understanding signaling pathway with CD8 + Treg cells in AE. Methods: The proportions of CD8 + Treg cells, CD8 + CD28 + IL-10 + T cells, CD8 + CD28 + TGF-β + T cells and Tim-3 + CD8 + Treg cells in peripheral blood were first determined in control subjects (n=30), and AE patients (n=33) were examined by flow cytometry. Foxp3 and Tim-3 / Galectin-9 mRNA levels in peripheral blood PBMC from control and AE patients were then measured by QRT-PCR. Finally, the expression of IL-10, TGF-β and Tim-3 / Galectin-9 in the infected livers of AE patients was verified by immunohistochemistry.Results: 1. The proportions of peripheral blood CD8 + Treg cells (P<0.001), CD8 + CD28 + IL-10 + T cells (P<0.001) and CD8 + CD28 + TGF-β + T cells (P<0.001) were significantly higher in AE patients than in controls. 2. The expression of Tim-3 was significantly upregulated in peripheral blood CD8 + Treg cells in AE patients (P <0.001). 3. Foxp3 (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001)) mRNA levels were significantly elevated in peripheral blood PBMC from AE patients, and Foxp3 and Tim-3 (r 2 =0.489, P<0.001) with galactose lectin-9 (r 2 =0.366, P=0.047) mRNA levels were positively correlated. 4. Infected individuals showed higher expression of IL-10 (P<0.001), TGF-β (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001) in the livers of AE patients than in the distal part of the infection, with IL-10 expression (r 2 =0.852, P<0.001; r2=0.803 P<0.001) 、TGF-β (r 2 =0.770 P<0.001 ;r 2 =0.806, P<0.001) was positively correlated with Tim-3/galactose lectin-9. Conclusion: This study hypothesized that high expression of Tim-3 on the surface of CD8 + Treg cells in AE patients increases the number and function of CD8 + Treg cells and that expression of the Tim-3/galactose lectin-9 pathway promotes the expression of the transcription factor Foxp3 and the inhibitory cytokines IL-10 and TGF-β. This phenomenon is not conducive to the elimination of multifocal echinococcosis in patients, which ultimately leads to persistent exacerbation of the infection.
Adolescent Triple-negative Breast Cancer with Germline Mutation of both BRCA1 and TP53: A Case Report
Authors: Chen Dongmei , Yuan Mengqi , Zhang Ying , Zhang Chenyang , Wan Donggui 
Published: June 2022

Abstract
Almost 5–10% of breast cancer cases have inherited mutations. TP53 tumor suppressor gene is frequently mutated in human malignancies, including breast cancer. In addition, BRCA1 and BRCA 2 are the most frequently mutated genes in breast cancer. Nearly 80% of BRCA1 mutation carriers are diagnosed with breast cancer at a young age before menopause. There are currently no report of early onset breast cancer with both BRCA1 and TP53 germline mutations. Here, we report the case of a 14-years-old female diagnosed with triple-negative breast cancer (TNBC) with a family history of malignant tumors. The cancer metastasized to multiple lymph nodes 1 year and 4 months after surgery, and the progression-free survival (PFS) after subsequent chemotherapy and surgery has been over 2 years and 9 months. The patient’s white blood cells were screened against a panel of 11 cancer-related genes, and both germline mutations of BRCA1 and TP53 were identified. Genetic tests on the patient’s family members revealed the same BRCA1 mutation in her father and brother but no mutation was detected in other members. The case indicates that a multiple gene panel screening should be performed for the family members of breast cancer patients with an early age of onset and a family history of cancer.
Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography
Authors: Lichtenegger Antonia , Tamaoki Junya , Licandro Roxane , Mori Tomoko , Mukherjee Pradipta , Bian Lixuan , Makita Shuichi , Matsusaka Satoshi , Kobayashi Makoto , Baumann Bernhard , Yasuno Yoshiaki 
Published: June 2022

Abstract
Breast cancer is a leading cause of death in female patients worldwide. Further research is needed to get a deeper insight into the mechanisms involved in the development of this devastating disease and to find new therapy strategies. The zebrafish is an established animal model, especially in the field of oncology, which has shown to be a promising candidate for pre-clinical research and precision-based medicine. To investigate cancer growth in vivo in zebrafish, one approach is to explore xenograft tumor models. In this article, we present the investigation of a juvenile xenograft zebrafish model using a Jones matrix optical coherence tomography (JM-OCT) prototype. Immunosuppressed wild-type fish at one-month post-fertilization were injected with human breast cancer cells and control animals with phosphate buffered saline in the tail musculature. In a longitudinal study, the scatter, polarization, and vasculature changes over time were investigated and quantified in control versus tumor injected animals. A significant decrease in birefringence and an increase in scattering signal was detected in tumor injected zebrafish in comparison to the control once. This work shows the potential of JM-OCT as a non-invasive, label-free, three-dimensional, high-resolution, and tissue-specific imaging tool in pre-clinical cancer research based on juvenile zebrafish models.
Neural activation during semantic processing in older adults
Authors: Garcia Amanda , Cohen Ronald , Porges Eric , Williamson John , Woods Adam 
Published: June 2022

Abstract
Neural activation on fMRI during semantic processing was examined in 38 older adults, 55–85 years of age, experiencing successfully cognitive aging, without mild cognitive impairment (MCI) or evidence of neurodegenerative disease. A mixed event-related block paradigm on which judgements were made as to whether semantic (abstract and concrete) and phonemic (rhyme) word-pairs were associated or unassociated during task-dependent fMRI. As hypothesized, greater activation intensity occurred during the processing of associated vs. unassociated, and to semantic vs. phonemic word-pairs in putative semantic hubs-control areas (angular gyrus, anterior middle temporal gyrus, and inferior frontal gyrus), and in secondary association areas. Several areas activated more to unassociated word-pairs, notably the hippocampus and thalamus. Cortical area exhibited similar activation intensity between semantic conditions, though several areas activated more during either abstract or concrete processing. Activation intensity of the left inferior frontal gyrus was greater during abstract processing, but not in the left angular or anterior temporal gyri. Greater age was associated with relatively few differences in cortical activation, though greater right homologous activation occurred in the angular gyrus, supramarginal gyrus, and the precuneus during the processing of strongly vs. weakly associated concrete word-pairs. Activation intensity did not differ across semantic conditions with greater age otherwise, suggesting that neural response of the semantic hubs, control and secondary cortical association areas is relatively preserved in older adults without MCI or neurodegenerative disease. Age-associated differences in neural activation are likely task-dependent, evident when there is greater demand for semantic control and generation among older adults.
Precise Identification of Cancer Recurrent Driven Targets for Sequential Treatment in Metastatic Gastric Cancer and Melanoma
Authors: Shu Chuanjun , Cui Jiahua , Chen Junjie , Zhang Yi , Ren Yanlin , Li Jin , Chen Dongyin , Ding Kun , Li Aiping , Zhang Ruiwen , He Jingdong , Shu Yongqian , Zhou Jianwei 
Published: June 2022

Abstract
Background: Because of intratumor heterogeneity, most patients with solid tumor received limit benefits from the first line regimen. The intratumor heterogeneous molecules are known to drive tumor progression, therapeutic resistance, and disease relapse at late stage across many cancers. The strategy of precise identify the cancer recurrent drive-related heterogeneous molecules from residual tumor tissues is the urgent and unmet clinical need, and it will help clinicians to optimal match the approved cancer-cross-drugs.Methods: The potential cancer recurrent driven targets recognition algorithm was constructed based on proteomics data followed by signal network analysis of tumor tissues before and after treatment. The weight and ranking of the candidate targets were further determined according to advanced research progress and related network databases. Sequential therapies were conducted to confirm the role of cancer recurrent driven molecules in mice with lung metastasis of either BGC823 or B16F10 cells.Results: The algorithm system was established successfully for precise identifying the cancer driven targets from the metastatic lung tumor foci. Thirty-eight candidate targets were identified from residual metastatic foci of GC (gastric cancer) in mice model; and 5 of 38 targets including JWA, MDM2, FASN, USP9X, and PFN1 were sequentially treated with target-specific peptide or inhibitors in BALB/c nude mice; similarly, 5 of 54 candidate targets including JWA, MDM2, SMAD3, IDH1/2, and mTOR were identified from the metastatic lung foci of melanoma and treated sequentially in C57BL/6 mice. Data showed that each additional sequential therapy of new target significantly reduced GC lung metastasis and prolonged the survival in melanoma lung metastasis mice. Meanwhile, both JWA and MDM2 were identified as re-cyclable targets for treatment in both GC and melanoma models. Together, our results may make possible for real individual therapeutic regimens on metastatic GC and melanoma.Conclusions: The highlight of our study should be the tumor recurrent driven targets recognition approach which may pave the way for the rational design of improved therapies against resistant malignancies. More importantly, the recognition algorithm may get into translational significance, and make possible for real precise individual therapeutic regimen of every cancer cases.
Exploring the nano-polishing mechanisms of Invar
Authors: Wang Wan , Hua Dongpeng , Luo Dawei , Zhou Qing , Eder Stefan J. , Li Shuo , Wang Zhijun , Wang Haifeng 
Published: June 2022

Abstract
With the rapid development of nano-polishing technology, ultra-precise micro-nano components require tighter tolerances for the surface engineering of the Invar alloy. Due to its low hardness and high chemical activity, it is a challenge to reveal the nano-polishing mechanism experimentally. In this work, we studied the effect of polishing parameters on the nano-polishing properties of Invar by molecular dynamics simulation, and experiments were conducted to verify the simulation results. Our findings indicate that higher polishing speed and shallower polishing depth with optimized rolling torque can lead to a reduction of the subsurface damage layer thickness as well as an improvement in polishing efficiency and surface quality. The nano-polishing mechanism is revealed, showing that effective removal occurs only in the plowing regime and the cutting regime, which require sufficient rolling and sliding depths, respectively. Furthermore, an analytic removal theory was developed that excellently describes and predicts the polishing behavior of Invar. This work provides a guideline for improving the polishing precision, surface quality, and material removal efficiency for Invar work pieces.
Optimization of ultrasound-assisted production of ergosterol from Penicillium brevicompactum by Taguchi statistical method
Authors: Alinaghi Masoumeh , Vali Nasim , Fatemi Seyed-Safa-Ali 
Published: June 2022

Abstract
Ergosterol as a primary metabolite and precursor of vitamin D2, is the most plentiful mycosterols in the fungal cell membrane. Process optimization to increase the yield and productivity of biological products is a topic of interest. Ultrasonic waves have many applications in biotechnology, like cell disruption, and production enhancement of primary and secondary metabolites. This study disclosed an optimal condition for ultrasound-assisted production (UAP) of ergosterol from Penicillium brevicompactum MUCL 19011 using L9 Taguchi statistical method. The intensity (IS), time of sonication (TS), treatment frequency (TF), and number of days of treatment (DT) were allocated to study the effects of ultrasound on ergosterol production. The results were analyzed using Minitab version 19. The maximum ergosterol, 11 mg/g cell dry weight (CDW), was produced on the tenth day while all factors were at a low level. The days of treatment with a contribution of 45.48% was the most significant factor for ergosterol production. For the first time, this study revealed the positive effect of ultrasound on the production of ergosterol. Ergosterol production increased 73 % (4.63 mg/g CDW) after process optimization. Finally, a mathematical model of ultrasound factors with a regression coefficient of R2 = 0.978 was obtained in the ergosterol production.
Viral Metagenomics Identifies a Novel Recombinant Murine Astrovirus from Rattus norvegicus in Jiangsu, China
Authors: Li Wang , Li Xin , Hu Haitao , Xu Juan , Qian Jin , Ni Pin , Zhou Xiaobin , Han Junling , Zhao Yan , Gong Qin , Dong Surong , Peng Hailin , Zhou Chenglin 
Published: June 2022

Abstract
Murine astrovirus (MuAstV) is widespread infection among wild and laboratory rats (Rattus norvegicus) and mice (Mus musculus). In this study, using viral metagenomics method, a near-complete genome of astrovirus isolate, named TZ-AST, was identified from Rattus norvegicus in mainland of China for the first time. Phylogenetic analysis showed that isolate TZ-AST and representative Murine astrovirus isolates cluster into one group and the isolate shares 90.2% nucleotide sequence of ORF1a similarity with a USA isolate SJ001 (Genbank Accession No.: MK395165), while sharing 94.9% nucleotide sequence of ORF2 similarity with another USA isolate MAV1 (Genbank Accession No. MF175075). This indicated that TZ-AST might be a recombinant. Complete genome sequences of MuAstV, together with that of TZ-AST were peformed recombination analysis using RDP 5.0. Results showed that TZ-AST with higher sequence similarity to the major parent MuAstV (MK395165), in the region of 494–2028 nt, while in the region of 5010–6259 nt, TZ-AST displayed higher sequence similarity to minor parent MuAstV (MF175075). Phylogenetic trees based on the genome region of 494–2028 nt and 5010–6259 nt were constructed respectively and comfirmed that TZ-AST is a novel Recombinant. Epidemiologic study showed that the prevalence rate of astrovirus was 17.4% in Rattus norvegicus in Taizhou, China.
A Structural Equation Model-Based Study on The Status and Influencing Factors of Acute Exacerbation Readmission in Elderly Patients with Chronic Obstructive Pulmonary Disease within 30 Days
Authors: Lu Hong-Yan , Zhang Rui , Chang Yan , Zhang Xiao-Na , Zhao Jie , Li Xin-Dan , Feng Xiang-Kai 
Published: June 2022

Abstract
Objective To investigate the situation of acute exacerbation readmission in elderly patients with Chronic Obstructive Pulmonary Disease (COPD) within 30 days, and to explore the influencing factors of readmission by structural equation model, so as to provide evidence for medical staff to take effective intervention measures. Methods Convenience sampling method was used to select 1120 elderly COPD patients from respiratory department of 13 general hospitals in Ningxia region from April 2019 to August 2020 for questionnaire survey. The participants completed the questionnaire containing general data questionnaire, Modified Medical Research Council (mMRC), Activities of Daily Living (ADL), the Geriatric Depression Scale (GDS), and COPD Assessment Test (CAT) scale. Results The readmission rate of acute exacerbation within 30 days in elderly COPD patients was 21.52%; The modified model fits well. Fitting results showed that seasonal factors, family rehabilitation, age factors and overall status were the direct influencing factors of acute exacerbation readmission in elderly COPD patients within 30 days. Smoking status is not only a direct factor for acute exacerbation of readmission within 30 days, but also an indirect effect through disease status; Disease status and chronic disease are not only direct factors for acute exacerbation of readmission within 30 days, but also indirectly through overall status. Conclusions The rate of acute exacerbation readmission within 30 days in elderly patients with COPD is high, While taking measures to prevent readmission based on direct influencing factors, attention should be paid to the interaction between factors.