bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Changes in Land Use and Coverage on the Ibicuí River Basin
Authors: Leal Desirreé Cristine Pena Vieira , Adam Katiúcia do Nascimento , Hüffner Anelise Nardi , Fernandes Lindemberg Lima , Sena Manoel José dos Santos
Published: October 2022

The need to manage water resources and the way they behave in the face of changes in land use are essential for managing a watershed. In this context, a large basin modeling tool was applied to simulate the flow regime of the Ibicuí River basin considering two land use scenarios. The results were used to analyze the changes in the maximum and minimum annual and monthly average flows. The greatest change in land use was the forest coverage reduction associated to agriculture land use. As a result, an increase in the average monthly flows and in the reference flow Q90 was verified. In some sub-basins, a significant modification in the reference Q90 flow and maximum flow was verified. The Mann Whitney test showed that the results were accurate. The results indicated that changes in forest coverage and land use have an impact in the flow regime in the Ibicuí Watershed. The procedure used in this research can be applied to simulate future scenarios of land use and its impacts in the sub-basin´s flow rates.
Superpixel Driven Unsupervised Deep Image Super-resolution
Authors: Yang Jun , Zhang Chao , Xu Li , Luo Bing
Published: October 2022

Most of the existing deep learning-based image super-resolution methods require a large number of datasets or ground truth. However, these methods are not suitable for the restoration of real image with different domains. Recently, Deep Image Prior (DIP) based on single-image explores image prior and uses network structure as implicit image prior to recover images, but it ignores the explicit prior information of the actual image itself. The addition of image prior can effectively alleviate the ill-posed problem in the image restoration model. Therefore, in this paper, we propose an unsupervised deep image super-resolution (SR) method that based on segmentation driven. Intuitively, clear image has a clearer segmentation boundary. It will drive deep neural networks (DNN) to obtain higher performance SR image when forcing the restored image to have clear boundary. In order to make energy flow into DIP better, we use the fully convolutional networks-based (FCN-based) superpixel method, and we use back propagation to inject the gradient generated by segmentation entropy energy into DIP to obtain lower energy optimization parameters. Experiments show that the image generated by our method has clearer boundary and better performance than that generated by DIP on Set5, Set14 and BSD100.
Channel Splitting-and-Merging Connection in Neural Networks
Authors: Zhu Meng , Min Weidong , Han Qing , Zhan Guowei , Fu Qiyan , Li Jiahao
Published: October 2022

Neural networks have achieved success in both computer vision and natural language processing. The existing state-of-the-art neural networks dedicate to increase model complexity for improving performance. However, this causes two problems. One is that these neural networks cannot be deployed in computationally limited platforms. The other is that these neural networks cannot meet real-time requirements for large resolution input. To alleviate the two problems, we propose a novel skip connection method called channel splitting-and-merging (CSM) connection, which is aimed to directly replace the residual connection method in neural networks while reducing parameters and running latency. By dissecting the channel shuffle connection method, it is found that channel splitting and channel merging operations efficiently reduce model complexity. Therefore, we introduce these two operations into the residual mapping for reducing model complexity. A range of tasks show that replacing the residual connection method with our CSM connection method effectively reduces parameters and FLOPs at a little cost of losing performance. The experimental results show that our CSM connection outperforms the channel shuffle connection method while utilizing less inferring time and equal number of parameters.
The relationship between headache- attributed disability and lost productivity. 3. Attack frequency is the dominating variable
Authors: Husøy Andreas , Katsarava Zaza , Steiner Timothy J
Published: October 2022

Background
In an earlier paper, we examined the relationship between headache-attributed disability, measured as proportion of time in ictal state (pTIS), and lost productivity. In a linear model, we found positive and significant associations with lost paid worktime, lost household worktime and total lost productivity (paid + household), but with high variance, which was increased when headache intensity was introduced as a factor. We speculated that analyses based on headache frequency alone as the independent variable, eliminating both the subjectivity of intensity estimates and the uncertainties of duration, might show stronger associations.
Methods
Focusing on migraine, we used individual participant data (IPD) from 16 countries surveyed either in population-based studies or in the Eurolight project. These data included frequency (headache days/month), usual attack duration (hours), usual headache intensity (“not bad”, “quite bad”, “very bad”) and lost productivity from paid and household work according to enquiries using the Headache-Attributed Lost Time (HALT) questionnaire. We used multiple linear regressions, calculating regression equations along with unstandardized and standardized regression coefficients. We made line and bar charts to visualize relationships.
Results
There was no collinearity between the independent variables. Both frequency and intensity were highly significant predictors of lost productivity in all multiple linear regressions, with linear relationships in both genders between frequency and lost productivity from both paid and household work. Visualizations showed that relationships between intensity and lost productivity were more or less linear in both genders, while the impact of duration varied little across the range of 2–24 hours. The standardized regression coefficients demonstrated that frequency was a much better predictor of lost productivity from paid work than intensity or duration.
Conclusion
In the relationship between migraine-attributed impairment (symptom burden) and lost productivity, frequency (migraine days/month) is the dominating variable – more important than headache intensity and far more important than episode duration. This has major implications for current practice in headache care and for health policy and health-resource investment. Preventative drugs, grossly underutilized in current practice, offer a high prospect of economic benefit (cost-saving), but new preventative drugs are needed with better efficacy and/or tolerability.
The Effect of Cybercrime on Financial Institutions: A Case Study of Mumuadu Rural Bank, Osino in the Fanteakwa District - Eastern Region, Ghana
Authors: Ghann Patricia , Owiredu Joseph , laryea Samuel Afotey
Published: October 2022

Crimes committed via the internet and other electronic media are a growing threat and an important subject to most organizations. This is because most organizations rely on the internet to provide services to customers. Thus, the use of the inter-networked system of communication in organizations such as the banks poses challenges to both customers and organizations on daily basis. This study analyses cybercrime activities and their effects on Financial Institutions; a case study of Mumuadu Rural Bank Limited, Osino in the Fanteakwa District - Eastern Region. The study was guided by three objectives and used a mixed-method (both qualitative and quantitative) approach in data collection. The total estimated sample size was 30 staff out of a population of thirty – two (32). A questionnaire was used to obtain information from 29 respondents who were randomly selected from the population while an interview was used to solicit further details from the bank’s General Manager who was purposively selected. The findings revealed that cybercrime and information security breaches have reached an alarming proportion with negative consequences on financial Industries. As a result, the bank has different insurance accounts set aside to protect customers against losses that may arise from cybercrime attacks or other related losses that may affect customers. It also emerged that young people in the district mostly indulge in cybercrime activities with the motive of living a luxurious life due to economic hardship attributed to unemployment, and lack of strong policies or legislation. Furthermore, the study also recorded a high rate of respondents who cited a loss of customer confidence due to cybercrime which has led to the loss of lives of customers and a reduction of revenue target of the bank as part of the effects of cybercrime on the bank. Additionally, the research identified some knowledge gaps and consequently recommended that cyber insurance policies be available and also be strengthened to help financial institutions compensate those who may be victims of a cybercrime attack. Furthermore, the paper suggests that organizations be constantly updated by the Security Agencies on the emerging techniques that are deployed by cybercriminals.
Effect of Nano Urea on Growth and Yield of Potato in Lower Gangetic Planes of West Bengal
Authors: Dutta Debashis
Published: October 2022

In today’s world it is the need of the hour to adopt new technology to sustain the production of future. Nano technology is gaining popularity for its efficiency over various applied field of science. In agriculture the nano materials have a huge impact on efficiency of fertilizer pesticides etc. As it requires in very less quantity and has a negligible residual effect the environment is safe with the innovation of Nano fertilizer. Keeping this view into account an experimental Trial at farmer’s field was carried out at Berui village in Hooghly District of West Bengal during the winter (rabi) season of 2019 – 20 under the supervision of Berui Cooperative, KVK-Hooghly, BCKV and IFFCO with nano-Urea, nano-Zn and nano-Cu using RBD design with 10 treatments and 3 replications. Experimental results revealed that highest tuber yield was obtained in T-7 (50% N+100% P & K+ 2 spray of nano-Urea), and that was followed by T-10 (50% N + 100% P & K + 50% Zn + 1 spray each of Nano-Urea, Zn and Cu) and T-8 (100% N-P-K + 50% Zn + 2 spray of Nano-Zn). The performance of nano fertilizers, Nano- Urea, was quite promising and economically viable as compared to 100% recommended dose with commercial fertilizers (RDF).
Deep Residual Learning with Attention Mechanism for Breast Cancer Classification
Authors: Toa Chean Khim , Elsayed Mahmoud , Sim Kok Swee
Published: October 2022

Invasive Ductal Carcinoma (IDC) is a common form of breast cancer that can be found in women. In traditional medical practice, physicians have to manually test and classify the areas which they suspect to be cancerous. However, the literature strongly shows that that the process manual segmentation done by the medical practitioners, is neither time-efficient nor accurate as it depends on their subjective judgment. The model called Residual Attention Neural Network Breast Cancer Classification (RANNBCC) is introduced in this paper to help medical practitioners in the cancer diagnostic process. RANNBCC utilizes Residual Neural Network (ResNet) as an expert-supportive method to help medical practitioners in cancer diagnosis. The implementation of RANN-BCC can support the classification of Whole Slide Imaging (WSI) into non-IDC and IDC without prior information about the presence of a cancerous lesion. The result of classification shows that the RANN-BCC model achieved 92.45% accuracy, 0.98 recall, 0.91 precision, and 0.94 F-score which outperform other models such as CNN, AlexNet, Residual Neural Network 34 (ResNet34), and Feed Forward Neural Network. The developed RANN-BCC model aims to help medical experts classify IDC and non-IDC of breast cancer by learning the feature content of medical images.
Bioaccumulation of trace elements in vegetables grown in various anthropogenic conditions
Authors: Kaledin Anatoly , Stepanova Marina
Published: October 2022

Hazardous compounds accumulate in plants and animals as a result of anthropogenic impact. Trace elements, such as heavy metals, move up in the system of snow – soil – water – plant – animal. When contaminants accumulate in plants that serve as animal feed, they eventually accumulate in the animals that consume the feed because heavy metals usually enter living organisms via digestive tract, i.e., with food.

In 2003–2021, we studied fodder plants grown and harvested by urban zoological organizations, e.g., zoos, nature corners, etc. This research covered the Central Federal District represented by the cities of Moscow, Ivanovo, Yaroslavl, and Uglich. The empirical part of the study relied on a combination of modern ecological, biochemical, and statistical methods. A KVANT-2AT atomic absorption spectrometer was used to define the trace elements and their quantities.

Broccoli proved to be the most resistant feed vegetable to all the toxic elements in this study. Kohlrabi, sweet potato, and dill had low content of lead and cadmium, while garlic was highly resistant to cadmium and arsenic. Spinach, fennel, potatoes, beets, and bell peppers, which were used as fodder in metropolis conditions, exceeded the maximal permissible concentration of heavy metals. The samples obtained from the Moscow Zoo contained by 1.98 times more zinc, by 1.06 times more copper, and by 89.47 times more lead than average. The samples from Ivanovo accumulated the greatest extent of iron, which exceeded the average level by 3.26 times. The vegetables from Uglich and Ivanovo had the lowest concentration of zinc, which was by 67.86 and 62.70% below the average, respectively. The samples from Yaroslavl contained by 33.08% less copper. In 2003–2021, feed vegetables grown in the Central Federal District had an average increase in zinc, copper, and lead by 1.13, 1.45, and 2.80 times, respectively. The level of iron stayed almost the same throughout 2018–2021, while that of arsenic gradually decreased in concentration. The accumulation level of zinc, copper, iron, and arsenic in feed vegetables appeared to depend on the concentration of their water-soluble metal forms in the soil.

Therefore, forage agriculture in urban areas requires constant chemical and toxicological tests to prevent contaminated feed from entering animal diet.
Heart rate variability in female Wistar rats under conditions of different physical activity
Authors: Korobova Viktoria N. , Vorvul Anton O. , Bobyntsev Igor I. , Khabibulin Ramis R. , Kostiunin Ilia N.
Published: October 2022

Objective: to study the characteristics of heart rate variability in female Wistar rats under conditions of normal wakefulness, moderate physical activity and during recovery. Materials and methods. The study was carried out on 48 female Wistar rats aged 5-6 months. Heart rate variability (HRV) was recorded using Physiobelt 2.5.1 (Neurobotics, Russia). HRV analysis was performed using statistical, geometric, and spectral indicators. Physical activity was created using a two-minute treadmill run at a speed of 15 m/min at an angle of 15°. During the experiment we made 3 records of cardiosignal in each anumal: 1 - before the load, 2 - immediately after the load, 3 - after 15-minute rest. Results. Physical activity led to significant changes in a number of statistical and geometric indexes, but no differences in the spectral indexes of all the records were not found. In this regard, we performed cluster analysis on TP, HF, LF indexes of the record 1 that allowed us to form 2 groups: with low and high spectrum values (LSV and HSV). In each group, we observed significant changes in the values of HRV indexes between the records: in the group with LSV, physical activity led to a change in HR, RRNN, Mo, HF (ms2), LF (ms2, %), VLF (ms2, %), LF/HF, IC, in the group with HSV - HR, RRNN, Mo, Amo, IVR, PAPR, VLF (ms2), LF (%), IC. 15-minute recovery contributed to a further change in the value of HRV parameters. Conclusion. The results of the current study demonstrated that physical activity led to activation of the sympathetic nervous system, mobilization of neurohumoral regulation, as well as a change in the level of regulation of the cardiorhythm from peripheral to the central one. The analysis of HRV parameters in females with LSV and HSV allowed us to establish the features of neurohumoral regulation of the functional state of the organism in groups of animals initially different in spectral characteristics.
Raw Materials. Half Creatures and Complete Nature in Shelley’s Frankenstein and Homunculus in Goethe’s Faust II
Authors:   Associate professor, Ph.D., National Library of Norway., Berg Siv Frøydis
Published: October 2022

Why did Mary Shelley’s famous Creature meet its ends in the eternal ice of the Arctic Sea? What made it possible for Goethe’s Homunculus to finally break free in the Classic Walpurgis Night? Both remote places fulfill the destinies of two of the most famous laboratory-made artificial human beings in Western literature, the Creature of Frankenstein, and the “little man”, Homunculus. They are born as half-creatures: Shelley’s Monster as pure body, Homunculus as pure spirit, locked up in a phial. Their lives on earth circle around one purpose: to create themselves as complete human beings, by achieving what they miss: a soul for Shelley’s Creature, a body for Goethe’s Homunculus. This article aims to present a systematic purification and comparison of the creations, lives, and ends of the Monster and Homunculus. My thesis is that each of them literally embodies two opposite and contemporary views of nature, identified in their own time as respectively materialistic and vitalistic positions. By comparing these life spans it is possible to shed light on Shelley’s and Goethe’s literary investment in the debate.
A Model Text Recommendation System for Engaging English Language Learners: Facilitating Selections on CEFR
Authors:   Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias de la Computación, México., Escobar-Acevedo Adelina , Guerrero-García Josefina ,   Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias de la Computación, México., Guzmán-Cabrera Rafael
Published: October 2022

A pedagogically informed multimodal education system is defined by how well reading tasks are assigned to students in a contemporary classroom. A source that becomes a provider of readings is the web, where it is possible to find information on practically all areas of knowledge and in a wide variety of languages. However, selecting the appropriate material for the level and theme becomes a tedious job to which language teachers must devote a significant amount of their time. Selecting suitable readings to accompany the teaching-learning process is thus not a ‘trivial’ task. Basic-level texts for language competence are easy to recognize and obtain but as is seen in the case of the Common European Framework of Reference for Languages recommendations (CEFR), selection of appropriate texts that impart language competencies, especially of vocabulary and grammar at higher levels of communicativeness, selection becomes increasingly complex for teachers. Furthermore, the suggested readings should be raked by complexity in accordance with student capabilities. We suggest, that automatic classifiers based on CEFR levels may help in this process of selections from the already available corpora of authentic texts on the web. The existing facility of access of readers to such material on the web may come to the aid of automated classifiers. Teachers use interest to motivate reading in classrooms, but automatic recommendation systems will allow specific or even individualized recommendations. The authors explore the impact of such multimodal methods on the acquisition of better linguistic and communicative skills.
Imagining India / Hinduism from Chile
Authors:   Professor, Pontificia Universidad Católica de Chile. Chile., Correa Felipe Luarte
Published: October 2022

Indian culture expresses itself in Chile’s daily life that, until recently, would have been unthinkable both for its real and mental remoteness. Undoubtedly, this is a consequence of globalization and the rapid flow of ideas and practices of the last decades, but it is also due to the sustained increase in the presence of the Indian community in Chile from the mid-’80s onwards, with the economic opening during that time creating favorable conditions for the increased number of Indian immigration in Chilean society. India’s cultural identity is marked by its religious way of life and in general, Hindu immigrants – as a result of the characteristics of Hinduism – have tended to reproduce their culture and religion while having to adjust to local circumstances. Consequently, both are renegotiated. This process implies an enormous effort of adaptability, which is necessary to be able to develop themselves in the new country without having to abandon the cultural baggage they bring with them, creating new strategies of action that at the same time imply and generate new ways of relating and redefining their identity referents.
Language Contestation on The Virtual Linguistic Landscape of The Government Website of Bali, Indonesia
Authors:   Universitas Pendidikan Ganesha, Bali, Indonesia., Paramarta I Made Suta , Artawa Ketut , Satyawati Made Sri , Purnawati Ketut Widya , Suputra Putu Eka Dambayana , Sudana Putu Ayu Prabawati
Published: October 2022

National, local, and international language contestation in Bali has been the government’s concern. The national language policy places Indonesian in the most prominent position, and the local regulation allegedly focuses on the Balinese salience. While most linguistic landscape (LL) research in Bali is conducted on physical LL, few have been conducted on the virtual linguistic landscape (VLL) setting. This study shows the language contestation of Indonesian, Balinese, and foreign languages on the official website of the government of Bali province. Furthermore, the analysis was based on the language contestation point of view and Bakhtinian’s centripetal and centrifugal forces. The results showed that the Indonesian language is the most dominant. Additionally, the Balinese language functions to convey Bali’s identity, and foreign languages play an important role in informational functions for viewers. The Indonesian language represents the centripetal force of centralization, and the existence of Balinese and foreign languages shows the centrifugal force indexes the decentralization efforts.
Book Review: Beyond the Metros: Anglo-Indians in India’s Smaller Towns and Cities
Authors:   Centre for the study of Social Systems, School of Social Sciences, Jawaharlal Nehru University, New Delhi, Biswas Kanchan
Published: October 2022

This edited book with a foreword by Sekhar Bandyopadhyay is the outcome of New Zealand India Research Institute project funding to focus on the Anglo-Indian community’s life experiences beyond metropolitans. It aimed to de-stereotype the image of the ethnic religio-cultural minority, who are prominently seen as standing testimony to exotic speech, dress, food and lifestyle. A further attempt has been made to question the constitutional ‘homogenized’ definition of the community. This book deployed ‘pluralism’ (foreword p. ix) to theoretically study the minority group. As Sekhar Bandyopadhyay wrote about the central argument, “…there is no single authentic version of an Anglo-Indian, despite a single constitutional definition” (p.viii).
Survival between Being and Doing: An Existential Reading of Doris Lessing’s The Fifth Child
Authors:   College of Arts and Science, Prince Sattam Bin Abdulaziz University., Sharene Anney Alice
Published: October 2022

The study aims at exploring the existential approach that Doris Lessing has adopted in portraying the character of Harriet Lovat in The Fifth Child. The work presents a conflict between society and the individual that the protagonist, Harriet Lovatt has to undergo and overcome in the process of personal choice. She is given the freedom to choose between what she wants and what society wants her to do. In doing so, she demonstrates full responsibility for such choices. In this novel, the choices and the decisions that the protagonist makes follow from an existential way of thinking. Thus, the approach of the author in portraying the character of the protagonist is examined from an existential standpoint. Lessing skillfully weaved the prevailing cultural and social circumstances of Harriet’s community with the question of being and survival in her quest for a meaningful existence. She refuses to be controlled by the traditional codes of sexual liberation before marriage and to have a traditional family after it. Having become a mother of an abnormal child, Harriet also goes on to make decisions that reinforce her existential status. This study presents Harriet as capable of revealing personal awareness and choice by rejecting the prevailing norms in her community as a young woman before marriage and as a wife and a mother afterward.
Novel construction of the catalyst from red mud by the pyrolysis reduction of glucose for the peroxymonosulfate-induced degradation of m-cresol
Authors: Chen Hongliang , Li Longjiang , Zhang Yutao
Published: October 2022

Red mud of low cost is regarded as a promising alternative to heterogeneous catalysts for activating peroxymonosulfate (PMS) to degrade m-cresol. Improper valence states of metal oxides and coated active substances in red mud greatly hampered its wide application. To solve this problem, the modified red mud (WRMG/700) was prepared by the pyrolysis reduction of glucose in N2 atmosphere. X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectrum (XPS) analysis confirmed the production of Fe3O4, MnO and NiO in red mud and their gathering on the surface of particles. WRMG/700 exhibited the excellent performance toward PMS activation for the m-cresol degradation with 99.02% degradation efficiency and a pH-independent catalytic activity between initial pH 3–8. The removal efficiency of COD increased with the reaction time under the optimized degradation conditions. The free radical scavenging experiments and electron paramagnetic resonance (EPR) test confirmed 1O2 played a dominant role during m-cresol degradation in the WRMG/700/PMS system, implying m-cresol degradation was a non-radical oxidation process. Accordingly, the possible reaction mechanism was proposed. WRMG/700 retained its activation performance even after five recycles. This study showed a low cost and simple operation process for m-cresol elimination.
Optimization of constructed wetlands on purifying black-odorous water and their potential purification mechanism
Authors: Chen Chun-xing , Yang Feng-juan , Deng Yang-yang , A Dan
Published: October 2022

Black-odorous water has become a common and widespread problem in recent decades. In this study, nine constructed wetlands (CWs) with different flow types, filters, plants, and hydraulic loadings were designed according to an orthogonal array (L9 (34), and were used for the purification of black-odorous water in summer and winter. The results showed that CWs are regarded as effective to purify black-odorous water in both seasons. Microbial degradation is the major removal pathway of pollutants in CWs during summer, while the joint effect of biodegradation and adsorption is the main treatment route during winter. Flow type and hydraulic loading appear to be the most important factors impacting the purification performance of CWs, by changing the redox condition of systems and retention time of contaminants, respectively. ‘Vertical flow-zeolite filter-high loading’ is proposed as the best parameter selection for CWs on the purification of black-odorous water: among them, CWs with vertical flow have better oxygen transport capacity that is conductive to aerobic processes of pollutants, zeolite substrates may adsorb more nitrogen via ion exchange, higher hydraulic loadings can extend the contact time between contaminants and filters, and regulate the water temperature for microbial activity.
Long Non-coding RNA LINC00473 Promotes Breast Cancer Progression
via miR-424-5p/CCNE1 Pathway
Authors: Zhang Chao , Yang Ting
Published: October 2022

Background:

There has been a large increase in the incidence of breast cancer (BC) among
women. LINC00473 is a cancer-related lncRNA, participating in the progression of many cancers, but
its role in the progression of BC awaits more elaboration.

Methods:

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify
LINC00473, miR-424-5p, and cyclin E1 (CCNE1) mRNA expression levels in BC tissues and cells.
Cell counting kit-8 (CCK-8) assay was employed to detect the cell viability; the cell migration and
invasion abilities were evaluated by the Transwell assay. Western blot and immunohistochemistry
(IHC) were adopted to study CCNE1 protein expression; dual-luciferase reporter assay was performed
to clarify the targeting relationships among LINC00473, miR-424-5p, and CCNE1.

Results:

LINC00473 expression was elevated in BC tissues and cell lines, which was associated with
lymph node metastasis and higher clinical stage of the patients with BC. LINC00473 proved to be a
molecular sponge for miR-424-5p; LINC00473 knockdown impeded the growth, migration, invasion,
and epithelial-mesenchymal transition of BC cells, while these effects were abolished by miR-424-5p
inhibitors; miR-424-5p targeted CCNE1 to restrain its expression. LINC00473 positively regulated
CCNE1 expression, and CCNE1 restoration counteracted the effects induced by LINC00473
knockdown in BC cells.

Conclusion:

LINC00473 facilitates the progression of BC through miR-424-5p/CCNE1 axis.
Toxicological Advancements in Cocaine Detection: A Review
Authors: Patanè Federico Giuseppe , Maria Maglitto Andreana Nicoletta , Esposito Massimiliano , Cocimano Giuseppe , Di Nunno Nunzio , Salerno Monica , Sessa Francesco
Published: October 2022

Cocaine, also known as methyl benzoylecgonine, is one of the most used
drugs of abuse and one of the oldest; however, there has been a recent increase in the consumption
of this substance. This trend has once again caught the attention of the scientific
community. We discuss the current knowledge about this drug, focusing our attention
on the forensic approach. Despite the fact that the cut-off of positivity to cocaine in drug
tests is quite high, most current tests are able to detect much lower concentrations and
could improve forensic sciences in both post-mortem investigations and in people screening.
Immunological assays possessing substantial cross-reactivity to cocaine are particularly
useful for screening oral fluid, hair, and post-mortem blood, where significant concentrations
of the drug can be found. Liquid chromatography has now supplanted the previous
techniques because it is very sensitive and specific and allows samples to be analyzed
in a shorter time with only minimal sample preparation. Recent studies have focused
on increased sensitivity, reduced processing times, and cheaper analysis.
A Deep Dive in the Involvement of the Cerebellum in Epilepsy: A Neuroanatomical and Cellular Approach
Authors: Rubio Carmen , Moreno Wilhelm , Ochoa Ernesto , Uribe Eric
Published: October 2022

Objective:

The purpose of this article is to describe the state-of-art of neuroanatomical and cellular aspects of the cerebellum in epilepsy.

Background:

Over the years, cerebellum epileptogenesis has been widely studied. There is growing evidence linking the cerebellum with this pathology by several other structures involved: mainly the limbic system, thalamus, cerebral cortex, red nucleus, and reticular formation. As a result, these anatomical and cellular changes in the cerebellum might trigger the genesis and propagation of seizures.

Discussion:

We herewith outline the cerebellum's deep nuclei physiological pathways, responsible for seizure spread via ion channels and neurotransmitter dysfunction. Additionally, we describe the shifts in seizures produced after cell death, gene expression, and protein interaction with their respective molecular and anatomical pathways.

Conclusion:

Finally, we highlight the role played by the cerebellum in seizure propagation to the brain and how it can be counteracted in some subtypes of drug-resistant epilepsy.
Mast Cell's Role in Cytokine Release Syndrome and Related Manifestations of
COVID-19 Disease
Authors: Özdemir Öner , Göksu Erol Azize Yasemin , Dikici Ümmügülsüm
Published: October 2022

Background-aim:

In this narrative review, firstly we describe the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of its infection in humans. Later, the importance of mast cells in SARS-CoV-2 infection and their role in Coronavirus Disease 2019 (COVID-19) will be discussed. SARS-CoV-2 is a transmissible agent frequently detected in some mammalian species and nowadays also in humans.

Methods:

Literature data published in PubMed that covered mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease was reviewed by the authors independently and collectively. Recommendations for the management of cytokine release syndrome and related manifestations were made by the authors.

Results:

Mast cells are concentrated in environments where they encounter viruses, bacteria, and toxins, especially in the skin, nasal mucosa, lungs, airways, gastrointestinal tract, and meninges, to prevent their entry into the human body. Once SARS-CoV-2 enters the host, it stimulates one of them, mast cells, together with pre-existing innate immune cells that form a defensive barrier in the submucosa of the respiratory tract and nasal cavities against pathogenic microorganisms. The roles of mast cells in SARS-CoV-2 -induced hyper inflammation and cytokine storms have recently been one of the hot topics mostly discussed in the literature.

Conclusion:

Physicians should keep in mind the mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease. Mast cell-targeting therapies (eg, H1 and H2 receptor antagonists) can reduce the severity and course of the disease when used after complications associated with COVID-19 are suspected or seen.
Residual Right-to-Left-Shunt Following Transcatheter Patent Foramen Ovale
Closure: The Role of Antithrombotic Treatment
Authors: Katsianos Efstratios , Oikonomou Evangelos , Kalogeras Konstantinos , Manousaki Alexandra , Kalantzis Charalambos , Pantelidis Panteleimon , Vavuranakis Michael-Andrew , Aggeli Konstantina , Siasos Gerasimos , Tsioufis Costas , Vavuranakis Manolis
Published: October 2022

Background:

Transcatheter closure of patent foramen ovale (PFO) is a highly effective therapy for
patients with left circulation thromboembolism, not attributable to other conditions.

Objectives:

This retrospective cohort study investigates the impact of baseline foramen ovale anatomy on the
severity of the postclosure shunt.

Methods:

Patients with PFO, who underwent percutaneous closure, were followed up for at least 5 years postimplantation.
Patients were classified into two groups based on the presence of high-risk features of the baseline
PFO anatomy. At the follow-up follow-up, residual right-to-left shunt was assessed for the high and non-highrisk
anatomy groups, via transcranial Doppler at rest and after performing the Valsalva maneuver, with the injection
of agitated saline.

Results:

38 patients were examined after a mean follow-up period of 9 ± 3 years after implantation. After retrospective
evaluation of the baseline transthoracic and transesophageal echo studies, 14 patients with high-risk
PFO anatomy were identified. The degree of the residual right-to-left shunt, as assessed by the number of microbubbles
was higher in the high-risk PFO anatomy group compared to the non-high-risk group, both at rest
[1.50 (IQR: 0.00-3.25) vs. 0.00 (IQR: 0.00-0.00), p < 0.001] and post-Valsalva maneuver [7.50 (IQR: 1.50-
10.25) vs. 0.00 (IQR: 0.00-3.75), p = 0.003]. Furthermore, in the high-risk group, more microbubbles were detected
at rest (p = 0.008) and post-Valsalva (p = 0.002) in subjects without antiplatelet treatment compared to
subjects on prolonged antiplatelet therapy.

Conclusions:

Baseline PFO anatomy affects the severity of the residual right-to-left shunt. Prolonged antiplatelet
therapy may benefit patients with high-risk anatomical features.
Cabozantinib Carries the Risk of Drug-Drug Interactions via Inhibition of UDPglucuronosyltransferase
(UGT) 1A9
Authors: Wang Zhe , Jiang Lili , Wang Xiaoyu , Yin Hang , Wang Zhen , Lv Xin , Liu Yong
Published: October 2022

Background:

Cabozantinib is a multiple receptor tyrosine kinases inhibitor (TKI) approved to treat progressive,
metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. Drugdrug
interactions (DDIs) for cabozantinib have been identified involving the role of cytochromes P450. Although the
previous study reported that cabozantinib showed a slight inhibition of UDP-glucuronosyltransferase (UGT) 1A1 at
the highest concentration tested, there are no reports on the potential for UGTs-mediated-DDIs. Hence, the current
study aims to address this knowledge gap.

Objective:

This study aimed to investigate the inhibitory effect of cabozantinib on human UGTs and to quantitatively
evaluate the DDI potential via UGT inhibition.

Methods:

The inhibitory effects of cabozantinib on UGTs were determined by measuring the formation rates for 4-
methylumbelliferone (4-MU) glucuronide and trifluoperazine N-glucuronide using recombinant human UGT
isoforms in the absence or presence of cabozantinib. Inhibition kinetic studies were conducted to determine the type
of inhibition of cabozantinib on UGTs and the corresponding inhibition constant (Ki) value. In vitro-in vivo extrapolation
(IVIVE) was further employed to predict the potential risk of DDI in vivo.

Results:

Cabozantinib displayed potent inhibition of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and
2B15. Cabozantinib exhibited noncompetitive inhibition towards UGT1A1 and 1A3 and inhibition towards UGT1A7
and 1A9. The Ki,u values (mean ± standard deviation) were calculated to be 2.15±0.11 μM, 0.83±0.05 μM, 0.75±0.04
μM and 0.18 ± 0.10 μM for UGT1A1, 1A3, 1A7 and 1A9, respectively. Co-administration of cabozantinib at the
clinically approved dose of 60 mg/day or 140 mg/day may result in approximately a 26% to 60% increase in the
systemic exposure of drugs predominantly cleared by UGT1A9, implying a high risk of DDIs.

Conclusion:

Cabozantinib has the potential to cause DDIs via the inhibition of UGT1A9; therefore, additional attention
should be paid to the safety of the combined use of cabozantinib and drugs metabolized by UGT1A9.
Inverted U-shaped Relationship Between Mean Platelet Volume/Platelet
Count Ratio and Post-thrombolytic Early Neurological Deterioration in
Patients with Mild and Moderate Stroke
Authors: Wang Zhen , Liu Xinfeng , Xu Wei , Guo Hongquan , Li Huiping , Song Kangping , Li Fangyi
Published: October 2022

Objective:

The objective of this study is to investigate the relationship between mean
platelet volume (MPV)/platelet count (PC) ratio and post-thrombolytic early neurological deterioration
(END) in patients with mild and moderate stroke.

Methods:

Mild and moderate stroke patients treated with intravenous thrombolysis (IVT) at the
Affiliated Changsha Central Hospital of the University of South China between January 2016 and
March 2022 were prospectively and consecutively enrolled. END was defined as an increase in the
total National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or an increase in the
motor items of ≥1 point within 24 hours after IVT treatment. Logistic regression and restricted cubic
spline models were used to estimate the relationship between the MPV/PC ratio and postthrombolytic
END.

Results:

Among the 406 patients recruited, 64 (15.8%) patients developed END. Patients in the first
quintile of MPV/PC ratio (adjusted OR = 0.27, 95% CI = 0.11-0.66, p = 0.004) and the fifth quintile
(adjusted OR = 0.26, 95% CI = 0.10-0.69, p = 0.007) had a significantly lower risk of END compared
with those in the third quintile. Restricted cubic spline analysis revealed an inverted U-shaped
relationship between the MPV/PC ratio and END (p for nonlinearity = 0.016). MPV/PC ratio cut-off
value associated with the highest END risk was 51.0. An MPV/PC ratio ≤ 51.0 was shown to be
positively associated with END (adjusted OR = 1.07, 95% CI = 1.02-1.14, p = 0.012), while an
MPV/PC ratio >51.0 was negatively associated with END (adjusted OR = 0.94, 95% CI = 0.88-1.00,
p = 0.040). A significant interaction existed between the MPV/PC ratio and age in the low MPV/PC
ratio group (p = 0.012). MPV/PC ratio was positively associated with END only in patients ≥ 60
years, whereas this association was insignificant in patients < 60 years.

Conclusion:

An inverted U-shaped relationship between the MPV/PC ratio on admission and postthrombolytic
END was identified in patients with mild and moderate stroke, with a threshold
MPV/PC ratio of 51.0. The MPV/PC ratio closer to the threshold was associated with a higher risk
of post-thrombolytic END.
Screening for Genetic Mutations Associated with Early-Onset Alzheimer’s
Disease in Han Chinese
Authors: Liu Cuicui , Cong Lin , Zhu Min , Wang Yongxiang , Tang Shi , Han Xiaojuan , Zhang Qinghua , Tian Na , Liu Keke , Liang Xiaoyan , Fa Wenxin , Wang Nan , Hou Tingting , Du Yifeng
Published: October 2022

Background:

Early-onset Alzheimer’s disease (EOAD) is highly influenced by genetic factors.
Numerous mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1 and
PSEN2) have been identified for EOAD, but they can only account for a small proportion of EOAD
cases.

Objective:

This study aimed to screen genetic mutations and variants associated with EOAD among
Han Chinese adults.

Methods:

This study included 34 patients with EOAD and 26 controls from a population-based study
and neurological ward. We first sequenced mutations in APP/PSENs and then performed whole-exome
sequencing in the remaining patients with negative mutations in APP/PSENs to screen for additional
potential genetic variants. Among patients who were negative in genetic screening tests, we further
evaluated the risk burden of genes related to the Aβ metabolism-centered network to search for other
probable causes of EOAD.

Results:

We identified 7 functional variants in APP/PSENs in 8 patients, including 1 APP mutation (p.
Val715Met), 3 PSEN1 mutations (p. Phe177Ser; p. Arg377Met; p. Ile416Thr), and 3 PSEN2 mutations
(p. Glu24Lys; p. Gly34Ser; p. Met239Thr). Of the remaining 26 EOAD cases without mutations in
APP/PSENs, the proportion of carrying rare variants of genes involved in Aβ and APP metabolism was
significantly higher than that of controls (84.6% vs. 73.1%, P=0.042). Thirty-one risk genes with 47
variants were identified in 22 patients. However, in 26 normal subjects, only 20 risk genes with 29
variants were identified in 19 subjects.

Conclusions:

Our findings demonstrate the role of APP/PSENs mutations in EOAD, identifying a new
PSEN2 missense mutation, and further offer valuable insights into the potential genetic mechanisms of
EOAD without APP/PSENs mutations among Han Chinese.
Impact of GSTT1 and GSTM1 Polymorphisms in the Susceptibility to
Philadelphia Negative Chronic Myeloid Leukaemia
Authors: Elderdery Abozer Y. , Idris Hadeil M.E. , Tebien Entesar M. , Diab Nada Abdalfatah , Hamza Siddiqa M.A. , Suliman Bandar A. , Alhamidi Abdulaziz H. , Omer Nawal Eltayeb , Mills Jeremy
Published: October 2022

Materials and Methods:

We report on a case-control study with 126 participants, divided into 26 patients
with Ph-ve CML (57.7% male, 42.3% female) and 100 healthy volunteers (51% male, 49% female)
with no medical history of cancer as a control population. All Ph-ve CML patients were diagnosed
according to standard hematologic and cytogenetic criteria based on CBC, confirmed by Reverse
Transcriptase Polymerase Chain Reaction (RT-PCR) to determine the presence or absence of the BCRABL
gene, followed by bone marrow (BM) examination.

Background:

Our research aimed to clarify the role of genetic polymorphisms in GST (T1
and M1) in the development of Ph-ve CML.

Results:

Of the 26 studied cases, 50% had the GSTT1 null genotype against 21% of the control group,
a statistically significant difference (CI= 1.519 - 9.317; p-value= 0.004). The GSTM1 null genotype
was detected in 23.1% of cases and 35% of controls, a difference not statistically significant (OR=
0.557; CI= 0.205-1.515; p-value= 0.252). The distribution of GSTT1 and GSTM1 polymorphisms was
also examined according to gender, age and ethnic grouping; these findings revealed no statistically
significant differences.

Conclusion:

Our study reveals a strong correlation between GSTT1 polymorphism and Ph-ve CML,
whereas the data for GSTM1 polymorphisms indicates no role in the initial development of the disease.
More studies are required to further clarify these and other genes' roles in disease development.
Recent Developments in Microfluidic Paper-based Analytical Devices for
Pharmaceutical Analysis
Authors: Khamcharoen Wisarut , Kaewjua Kantima , Yomthiangthae Phanumas , Anekrattanasap Ananyaporn , Chailapakul Orawon , Siangproh Weena
Published: October 2022

In the last decade, due to the global increase in diseases, drugs for biomedical applications have increased dramatically. Therefore, there is an urgent need for analytical tools to monitor, treat, investigate, and control drug compounds in diverse matrices. The new and challenging task has been looking for simple, low-cost, rapid, and portable analytical platforms. The development of microfluidic paper-based analytical devices (µPADs) has garnered immense attention in many analytical applications due to the benefit of cellulose structure. It can be functionalized and serves as an ideal channel and scaffold for the transportation and immobilization of various substances. Microfluidic technology has been considered an effective tool in pharmaceutical analysis that facilitates the quantitative measurement of several parameters on cells or other biological systems. The µPADs represent unique advantages over conventional microfluidics, such as the self-pumping capability. They have low material costs, are easy to fabricate, and do not require external power sources. This review gives an overview of the current designs in this decade for µPADs and their respective application in pharmaceutical analysis. These include device designs, choice of paper material, and fabrication techniques with their advantages and drawbacks. In addition, the strategies for improving analytical performance in terms of simplicity, high sensitivity, and selectivity are highlighted, followed by the application of µPADs design for the detection of drug compounds for various purposes. Moreover, we present recent advances involving µPAD technologies in the field of pharmaceutical applications. Finally, we discussed the challenges and potential of µPADs for the transition from laboratory to commercialization.