bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cetuximab as first-line treatment for metastatic colorectal cancer (mCRC): A model-based economic evaluation
Authors: Putri Septiara , Saldi Siti Rizny F. , Khoe Levina Chandra , Setiawan Ery , Megraini Amila , Santatiwongchai Benjarin , Nugraha Ryan R. , Permanasari Vetty Y. , Nadjib Mardiati , Sastroasmoro Sudigdo , Armansyah Armansyah 
Published: August 2022

Abstract
Objectives
To assess the cost-effectiveness of cetuximab in combination with chemotherapy fluorouracil, oxaliplatin, and leucovorin (FOLFOX) or fluorouracil, irinotecan and leucovorin (FOLFIRI) compared to standard chemotherapy alone as a first-line treatment for metastatic colorectal cancer (mCRC) with positive KRAS wild type patients in Indonesia.
Methods
A cost-utility analysis applying Markov model was constructed, with a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital billings. Meanwhile, direct non-medical costs, indirect costs, and utility data were collected by directly interviewing patients. We applied 3% discount rate for both costs and outcomes. Probabilistic sensitivity analysis was performed to explore the model's uncertainty. Additionally, using payer perspective, budget impact analysis was estimated to project the financial impact of treatment coverage.
Results
There was no significant difference in life years gained (LYG) between cetuximab plus FOLFOX/FOLFIRI and chemotherapy alone. The incremental QALY was only one month, and the incremental cost-effectiveness ratio (ICER) was almost approximately IDR 3 billion/QALY for cetuximab plus chemotherapy. Using 1–3 GDP per capita (IDR 140 million) as the current threshold, the cetuximab plus chemotherapy was not cost-effective. The budget impact analysis resulted that if cetuximab plus chemotherapy remain included in the benefits package under the Indonesian national health insurance (NHI) system, the payer would need more than IDR 1 trillion for five years.
Conclusions
The combination of cetuximab and chemotherapy for mCRC is unlikely cost-effective and has a substantial financial impact on the system.
Health-related quality of life and associations on socio-demographic and clinical factors in schizophrenia based on the QLICD-SC scale: A cross-sectional study
Authors: Rao Shuying , Liu Yuxi , Xian Junding , Lin Zhixiong , Wang Dandan , Xue Benli , Wan Chonghua 
Published: August 2022

Abstract
Background: Schizophrenia is a long course mental disease which poses heavy burdens to patients and quality of life can reflect treatment effect. But a small number of specificity scales have been developed. By using the scale Quality of Life Instruments for Chronic Diseases-Schizophrenia (V2.0)(QLICD-SC))(V2.0) which is modular and sensitivity integrating Chinese culture, this paper aims at providing evidence for developing countermeasures to improve patients’ quality of life. Methods: 163 people who met the diagnostic criteria for schizophrenia of the International Classification of Diseases(10th Revision)(ICD-10) and were hospitalized at the Affiliated Hospital of Guangdong Medical University from May 2014 to December, 2015 were selected. Paper-based questionnaires were administered to the patients to collect their basic information. Patients' clinical objective indexes, including blood routine, urine routine, blood biochemical examination, blood gas analysis etc. were collected by reviewing the medical records. Statistical description was applied to analyse the distribution of basic characteristics of depressed patients. Simple correlation analysis was used to explore the correlations between domains scores of the QLICD-SC(V2.0) and clinical objective indexes and multiple linear regression was used to further screen for correlates.Results: There were 163 participants, ranging in age from 16 to 69, with a 30.67±11.44 average age. The majority of them were men(57.1%), had a high school diploma(77.9%), and were married (65.6%). Physical function, psychological function, social function, specific module and total scale each had QOL ratings of 61.09, 48.02, 63.21, 33.01 and 49.09, respectively. According to multiple linear regression, the variables included in the model are education, sex, eosinophilic granulocyte, hematocrit, percentage of monocytes, phosphorus (R2=0.065~0.222, P<0.05).Conclusion: Some clinical indicators such as hematocrit and socio-demographic factors may reflect alterations in the quality of life of individuals with schizophrenia.
Manufacturing Wood-Plastic Composites and their Thermal Performance in Building Envelope
Authors: Sarheed Majed Al , Sedaghat Ahmad , Malayer Mahdi Ashtian , Salem Hayder , Oloomi Seyed Amir Abbas , Hussam Wisam K. , Anazi Abeer Abdullah Al , Sharifpur Mohsen 
Published: August 2022

Abstract
Wood-plastic composites (WPCs) are becoming one of the most attractive materials in building envelopes. In addition to WPCs' architectural and design attraction, they can enhance the thermal performance of buildings by acting as insulation materials. The thermal performance of building materials requires new experimental methods that can simulate true indoor/outdoor temperatures. In this study, a simple quasi-steady heating film (QSHF) method is devised to measure the thermal conductivity of WPC samples utilizing blocks of standard materials with known thermal conductivity. QSHF device uses a 10cm×10cm×0.5mm silicon heating film controlled by a temperature regulator and several transparent acrylic square blocks of the same size with 10mm thickness as the standard materials along with various specially designed WPC samples for Kuwait. The WPC samples' top surface is considered the cold side of the system, which is open to indoor temperatures of 22 to 23 oC. The bottom layer is maintained at fixed temperatures ranging from 25 to 55 oC to simulate the outdoor temperatures of a hot subtropical desert environment like Kuwait. The thermal conductivity of several WPCs type namely FB16, FB18W, CD, and TD were obtained as 0.0912, 0.1174, 0.3453, and 0.3078 W/m.K, respectively. Experimental results for DP45-1 were not consistent at different temperatures. hence Multiphysics CFD simulation was conducted for DP45 which shows strong 2D effects. A typical building sample was also modelled in TRNSYS to compare cooling loads with and without WPC. Also, the limitations and advantages of using QSHF method are discussed.
Designing of Nonlinear component of Block Cipher by a Moufang Loop and its Application in Image Encryption
Authors: Hussain Tasawwar , Shah Tariq , Ali Asif , Gul Rizwan , Hussain Muhammad 
Published: August 2022

Abstract
In this paper, we propose an algorithm for constructing a nonlinear component of block cipher by using the non-associative class of Moufang Loops (ML) and with the help of this nonlinear component design a cryptosystem for image encryption. The ML includes excellent features such as the inverse of zero elements, weak associativity, and fewer constraints in comparison with cyclic groups and Galois fields. The construction of a nonlinear component (substitution box, briefly, S-box) consists of bijective loop operations and permutations. There are two permutations, first by using a bijective map and second by using ML. This proposed S-box is used in an image encryption scheme. The encryption scheme consists of five steps. Firstly, the plain image is converted into the matrix and multiplies this matrix with an upper triangular matrix of ones. Then, substitute this output matrix with the values of the S-box and shuffle the pixels by using a logistic map. After this, multiply this output matrix with a self-invertible matrix. The evaluation of the proposed S-box with different algebraic and statistical analyses like nonlinearity test, strict avalanche criterion, bit independence criterion, linear approximation probability, and differential approximation probability indicates the strength of the proposed S-box. The presented procedure of image encryption also delivers excellent security in response to known cryptographic assaults as founded by the many statistical analysis and security assessments.
Automating Rey Complex Figure Test scoring using a deep learning-based approach: A potential large-scale screening tool for congnitive decline
Authors: Park Jun Young , Seo Eun Hyun , Yoon Hyung-Jun , Won Sungho , Lee Kun Ho 
Published: August 2022

Abstract
Background: The Rey Complex Figure Test (RCFT) has been widely used to evaluate neurocognitive functions in various clinical groups with a broad range of ages. However, despite its usefulness, the scoring method is as complex as the figure. Such a complicated scoring system can lead to the risk of reducing the extent of agreement among raters. Although several attempts have been made to use RCFT in clinical settings in a digitalized format, little attention has been given to develop direct automatic scoring that is comparable to experienced psychologists. Therefore, we aimed to develop an artificial intelligence (AI) scoring system for RCFT using a deep learning (DL) algorithm and confirmed its validity.Methods:A total of 6,680 subjects were enrolled in the Gwangju Alzheimer’s and Related Dementia cohort registry, Korea from January 2015 to June 2021. We obtained 20,040 scanned images using three images per subject (copy, immediate recall, and delayed recall) and scores rated by 32 experienced psychologists. We trained the automated scoring system using the DenseNet architecture. To increase the model performance, we improved the quality of training data by re-examining some images with poor results (mean absolute error (MAE) 5 [points]) and re-trained our model. Finally, we conducted an external validation with 150 images scored by five experienced psychologists.Results: For five-fold cross-validation, our first model obtained MAE = 1.24 [points] and R-squared ( ) = 0.977. However, after evaluating and updating the model, the performance of the final model was improved (MAE = 0.95 [points], = 0.986). Predicted scores among cognitively normal, mild cognitive impairment, and dementia were significantly differed. For the 150 independent test sets, the MAE and between AI and average scores by five human experts was 0.64 [points] and 0.994, respectively.Conclusion: We concluded that there was no fundamental difference between the rating scores of experienced psychologists and those of our AI scoring system. We expect that our AI psychologist will be able to contribute to screen the early stages of Alzheimer’s disease pathology in medical checkup centers or large-scale community-based research institutes in a faster and cost-effective way.
Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
Authors: Jo Yong Suk , Rhee Chin Kook , Yoon Hyoung Kyu , Park Chan Kwon , Lim Jeong Uk , An Tai Joon , Hur Jung 
Published: August 2022

Abstract
Background
Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO.
Methods
We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system.
Results
Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model.
Conclusion
We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.
Effectiveness of anti-VEGF treatment in wet Age-related Macular Degeneration; an evaluation of silent reading performance with eye movement analysis
Authors: Ktistakis Emmanouil , Simos Panagiotis , Tsilimbaris Militiadis K , Plainis Sotiris 
Published: August 2022

Abstract
Purpose: To evaluate silent reading performance by means of eye fixation analysis before and after anti-VEGF treatment in wet AMD (wAMD) patients.Methods: Twenty wAMD patients who underwent anti-VEGF treatment, in one eye, served as the AMD group. Twenty adults without ocular pathology, served as the control group. Central Retinal Thickness (CRT) and near visual acuity (VA) were assessed at baseline and after 3-4 months following their first visit. Reading performance was evaluated using short passages of 0.4 logMAR print size at 40 cm distance. Eye movements were recorded using a video eyetracker. Data analysis included computation of reading speed, fixation duration, number of fixations, and percentage of regressions.Results: In the AMD group, silent reading speed in the treated eye correlated well with CRT reduction and improved significantly by an average of 15.9±28.5 wpm (p=0.041). This improvement was accompanied by an average reduction of 0.24±0.38 in fixations per word (p=0.023). The corresponding improvement in monocular VA was not statistically significant, as was the case with other eye fixation parameters. Conclusion: VA tests may underestimate the potential therapeutic effects following anti-VEGF treatment. Evaluating silent reading performance and eye fixation parameters may better characterize the effectiveness of therapeutic approaches in wAMD patients.
Dilatation of the Bridging Cerebral Veins in Multiple Sclerosis Correlates with Fatigue and Suggests an Increase in Pressure
Authors: Bateman Grant Alexander , Bateman Alexander Robert , Lechner-Scott Jeannette 
Published: August 2022

Abstract
There is a physiological similarity between the hydrodynamics of hydrocephalus and multiple sclerosis (MS). Children with hydrocephalus have been found to have a significant enlargement of the cortical veins within the subarachnoid space, suggesting an increase in venous pressure. The purpose of this study is to discover if there is dilatation of the veins within the subarachnoid space in multiple sclerosis and to estimate the pressures required to maintain any enlargement found. 103 patients with MS were compared with a control group of 50 patients. Post contrast 3DT1 images were used. The cross-sectional area of the bridging cortical veins and the vein of Galen were measured. In MS, the superficial territory cortical veins were 29% larger and the veins of Galen were 25% larger than the controls. There is evidence of a significant increase in the bridging vein transmural pressure in MS, estimated to be approximately 6.5 mmHg in the superficial cortical veins. MS patients with significant fatigue have larger cortical veins than those who are not significantly fatigued.
Non-Hermitian chiral degeneracy of gated graphene metasurfaces
Authors: Kim Teun-Teun , Baek Soojeong , Park Sang-Hyun , Oh Donghak , Lee Kanghee , Lee Sang-Ha , Lim Hosub , Ha Taewoo , Park Hyun Sung , Zhang Shuang , Yang Lan , Min Bumki 
Published: August 2022

Abstract
Non-Hermitian degeneracies, also known as exceptional points (EPs), have been the focus of much attention due to their singular eigenvalue surface structure. Nevertheless, as pertaining to a non-Hermitian metasurface platform, the reduction of an eigenspace dimensionality at the EP has been investigated mostly in a passive repetitive manner. Here, we propose an electrical and spectral way of resolving chiral EPs and clarifying the consequences of chiral mode collapsing of a non-Hermitian gated graphene metasurface. More specifically, the measured non-Hermitian Jones matrix in parameter space enables the quantification of nonorthogonality of polarisation eigenstates and half-integer topological charges associated with a chiral EP. Interestingly, the output polarisation state can be made orthogonal to the coalesced polarisation eigenstate of the metasurface, revealing the missing dimension at the chiral EP. In addition, the maximal nonorthogonality at the chiral EP leads to a blocking of one of the cross-polarised transmission pathways and, consequently, the observation of enhanced asymmetric polarisation conversion. We anticipate that electrically controllable non-Hermitian metasurface platforms can serve as an interesting framework for the investigation of rich non-Hermitian polarisation dynamics around chiral EPs.
Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington’s disease transgenic mouse
Authors: Niu Li , Yang Shiming , Wang Weixi , Ye Cui-fang , Li He 
Published: August 2022

Abstract
Background: Huntington’s disease (HD) is a neurodegenerative disease that involves a complex combination of psychiatric, cognitive and motor impairments. Synaptic dysfunction has been implicated in HD pathogenesis. However, the mechanisms have not been clearly delineated. Synaptic vesicular zinc is closely linked to modulating synaptic transmission and maintaining cognitive ability. It is signifcant to assess zinc homeostasis for further revealing the pathogenesis of synaptic dysfunction and cognitive impairment in HD. Results: Histochemical staining by autometallography indicated that synaptic vesicular zinc was decreased in the hippocampus, cortex and striatum of N171-82Q HD transgenic mice. Analyses by immunohistochemistry, Western blot and RT-PCR found that the expression of zinc transporter 3 (ZnT3) required for transport of zinc into synaptic vesicles was obviously reduced in these three brain regions of the HD mice aged from 14 to 20 weeks and BHK cells expressing mutant huntingtin. Signifcantly, dual-luciferase reporter gene and chromatin immunoprecipitation assays demonstrated that transcription factor Sp1 could activate ZnT3 transcription via its binding to the GC boxes in ZnT3 promoter. Moreover, mutant huntingtin was found to inhibit the binding of Sp1 to the promoter of ZnT3 and down-regulate ZnT3 expression, and the decline in ZnT3 expression could be ameliorated through overexpression of Sp1. Conclusions: This is frst study to reveal a signifcant loss of synaptic vesicular zinc and a decline in ZnT3 transcriptional activity in the HD transgenic mice. Our work sheds a novel mechanistic insight into pathogenesis of HD that mutant huntingtin down-regulates expression of ZnT3 through inhibiting binding of Sp1 to the promoter of ZnT3 gene, causing disruption of synaptic vesicular zinc homeostasis. Disrupted vesicular zinc ultimately leads to early synaptic dysfunction and cognitive defcits in HD. It is also suggested that maintaining normal synaptic vesicular zinc concentration is a potential therapeutic strategy for HD.
Grain-size model for hydraulic conductivity estimation of porous media
Authors: Chandel Abhishish , Shankar Vijay 
Published: August 2022

AbstractHydraulic conductivity (k) is an important hydraulic parameter of porous media, and its accurate prediction plays a vital role in sub-surface flow investigations. The study uses the borehole soil samples to develop a k model using parameters, effective grain-size (d10), and standard deviation (σ). The influence of d10 and σ on the k and evaluation of k values via four empirical models is also assessed in this study. For soil samples, the k increases with the increase in the d10 grain-size and decreases with the increase in the σ value. The evaluation of k via empirical models infers that the Hazen model performs well in the estimation of k values. The evaluation of k using various statistical indicators points towards low error statistics (MAE, RMSE, and BIAS) and high determination coefficient (R2) between the measured and developed model-based k values, which substantiate the efficacy of the developed model as compared to the existing empirical models for estimating the k. To establish the versatility of the developed grain-size model, its validation was done using independent soil samples for estimating k values.
Entering the Sugar Rush Era: Revisiting the Antihyperglycemic
Activities of Biguanides after a Century of Metformin Discovery
Authors: de Oliveira Neto Xisto Antonio , Barssotti Leticia , Fiori-Duarte Ana Thereza , de Lima Barbosa Helena Cristina , Kawano Daniel Fábio 
Published: August 2022

Abstract:
The development of clinically viable metformin analogs is a challenge largely to be overcome. Despite being an extremely efficient drug for the treatment of type 2 diabetes mellitus, multiple studies were conducted seeking to improve its hypoglycemic activity or to ameliorate aspects such as the low oral absorption and the incidence of gastrointestinal side effects. Furthermore, efforts have been made to attribute new activities, or even to expand the pre-existing ones, that could enhance its effects in the diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this manuscript, we describe the analogs of metformin developed in the last three decades, highlighting the lack of computationally based rational approaches to guide their development. We also discuss this is probably a consequence of how unclear the mechanism of action of the parent drug is and highlight the recent advances towards establishment of the main molecular target(s) for metformin. We also explored the binding of metformin, buformin and phenformin to the mitochondrial respiratory chain complex I through molecular docking analyses and reviewed the prospects of applying computational tools to improve the success in the development of such analogs. Therefore, it becomes evident the wide range of molecular targets, as well as the multiple activities displayed by metformin, make this drug a promising prototype for the development of novel entities, particularly for the treatment of type 2 diabetes mellitus.
The Structure–property Relationships of Clinically Approved Protein
Kinase Inhibitors
Authors: Choi Kihang 
Published: August 2022

Background:
Protein kinase inhibitors have become one of the most successful classes of small-molecule drugs during the last decades. In modern drug discovery, considering ‘drug-like’ physicochemical and pharmacokinetic properties as early as possible in drug design is widely acknowledged as an important strategy to reduce drug attrition rates.

Methods:
In this review, clinically approved 25 protein kinase inhibitors and their key analogues reported in medicinal chemistry literature were compared for their biological, physicochemical, and pharmacokinetic properties. Although there is no common trajectory to follow through complex drug discovery campaigns, knowledge of the structure–activity relationship obtained from the successful lead optimization studies might be extended to other drug design efforts.

Results:
Among more than 70 protein kinase inhibitors clinically approved around the world, the structure–activity relationships of 25 inhibitors and their key analogues are compiled from medicinal chemistry literature, in which detailed results from the ‘lead-to-candidate’ stage are available with associated property data. For the other inhibitors, such information has not been disclosed in the literature, or the available data is limited and not sufficient to provide clear structural analysis.

Conclusion:
The structure–property relationships summarized for 25 inhibitors and their analogues illustrate general guidelines for lead optimization and candidate selection, and this information could be extended for better property-based drug design in the future.