bluuebunny/crossref_metadata_2025 huggingface dataset:
C-Reactive Protein-To-Lymphocyte Ratio Is a Novel Biomarker for Predicting the Long-Term Efficacy of Ustekinumab Treatment in Ulcerative Colitis
Authors: Koshiba Ryoji , Kakimoto Kazuki , Mizuta Noboru , Numa Keijiro , Kinoshita Naohiko , Nakazawa Kei , Hirata Yuki , Miyazaki Takako , Nakamura Shiro , Nishikawa Hiroki
Published: September 2023

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.
Na+/H+ Exchangers (NHEs) in Mammalian Sperm: Essential Contributors to Male Fertility
Authors: Gardner Cameron , James Paul
Published: September 2023

Na+/H+ exchangers (NHEs) are known to be important regulators of pH in multiple intracellular compartments of eukaryotic cells. Sperm function is especially dependent on changes in pH and thus it has been postulated that NHEs play important roles in regulating the intracellular pH of these cells. For example, in order to achieve fertilization, mature sperm must maintain a basal pH in the male reproductive tract and then alkalize in response to specific signals in the female reproductive tract during the capacitation process. Eight NHE isoforms are expressed in mammalian testis/sperm: NHE1, NHE3, NHE5, NHE8, NHA1, NHA2, NHE10, and NHE11. These NHE isoforms are expressed at varying times during spermatogenesis and localize to different subcellular structures in developing and mature sperm where they contribute to multiple aspects of sperm physiology and male fertility including proper sperm development/morphogenesis, motility, capacitation, and the acrosome reaction. Previous work has provided evidence for NHE3, NHE8, NHA1, NHA2, and NHE10 being critical for male fertility in mice and NHE10 has recently been shown to be essential for male fertility in humans. In this article we review what is known about each NHE isoform expressed in mammalian sperm and discuss the physiological significance of each NHE isoform with respect to male fertility.
Alternative Splicing Variation: Accessing and Exploiting in Crop Improvement Programs
Authors: Dwivedi Sangam L. , Quiroz Luis , Reddy Anireddy S.N. , Spillane Charles , Ortiz Rodomiro
Published: September 2023

Alternative splicing (AS) is a gene regulatory mechanism modulating gene expression in multiple ways. AS is prevalent in all eukaryotes including plants. AS generates two or more mRNAs from the precursor mRNA (pre-mRNA) to regulate transcriptome complexity and proteome diversity. Advances in next-generation sequencing, omics technology and bioinformatics tools, and computational methods provide new opportunities to quantify and visualize AS-based quantitative trait variation associated with plant growth, development, reproduction, and stress tolerance. Domestication, polyploidization and environmental perturbation may evolve novel splicing variants associated with agronomically beneficial traits. To date, pre-mRNAs from many genes are spliced into multiple transcripts that cause phenotypic variation for complex traits, both in model plant Arabidopsis and field crops. Cataloguing and exploiting such variation may provide new paths to enhance climate resilience, resource-use efficiency, productivity, and nutritional quality of staple food crops. This review provides insights into AS variation alongside gene expression analysis to select for novel phenotypic diversity for use in breeding programs. AS contributes to heterosis, enhances plant symbiosis (mycorrhiza and rhizobium), and provides a mechanistic link between the core clock genes and diverse environmental clues.
Re-Emerging Parasitic Infections of the Central Nervous System (CNS) in Europe
Authors: TUNALI Varol , KORKMAZ Metin
Published: September 2023

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for the introduction and establishment of these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed by these emergent infections.
Expression, Function and Trafficking of the Human ABCG2 Multidrug Transporter Containing Mutations in an Unstructured Cytoplasmic Loop
Authors: Mózner Orsolya , Zámbó Boglarka , Bartos Zsuzsanna , Gergely Anna , Szabó Kata Sára , Jezsó Bálint , Telbisz Ágnes , Várady György , Homolya László , Hegedűs Tamás , Sarkadi Balázs
Published: September 2023

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2, on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation incompetent T362A, or the phosphorylation mimicking T362E variants in this loop, had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.
Abrus Precatorius Leaf Bioactives: In Vivo Anti-Diabetes Mellitus Type-1 Activity, PPARA and SCD as Novel Targets
Authors: TAOFEEK OLUWASEUN , OYEWOLE OLAWALE , SULAIMON LATEEF , AKINUOYE PRECIOUS , DOGARA\ DENNIS , AJALA FARUQ , JODA ENIOLA , AFOLABI SAMUEL , ADAMU JUMAI , AMINU BIDEMI , OLORUNDARE FLORENCE
Published: September 2023

ObjectivesAbrus precatorius (AP) is a medicinal plant seldomly studied for its beneficial effects and as such significant gap exists in understanding the basis by which AP leaf bioactives (APLBs) elicit beneficial effects against diabetes mellitus (DM) type-1. MethodsWe estimated DM type-1 related parameters - total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days followed by histopathological analysis of kidney and liver sections. APLBs were collected from GCMS fractions, database and literature searches and common targets were cross-intersected with annotated DM type-1 genes from experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, their protein-protein interaction network was constructed and analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, Cytoscape, PyRx, and Discovery Studio to provide insight into the potential molecular basis of APLBs in DM-type-1.Results 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p <0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea & creatinine while hepatorenal photomicrographs indicated moderate safety of use. Erucic acid, oleic acid, phytol and stigmasterol interact with 25 type-1 DM biomarkers revealed to be enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction and van der Waals forces from docking study. ConclusionThis study demonstrated the potency of APLBs in vivo against type-1 DM. The potential basis of action has been studied from computational perspective. Future interests may provide additional experimental data into mechanisms by which APLBs elicit this remarkable ability.
Differential Responders of a Mixed Meal Tolerance Test Associated with Type 2 Diabetes Risk Factors and Gut Microbiota- Data from the MEDGI-Carb Randomized Controlled Trial
Authors: Skantze Viktor , Hjorth Therese , Wallman Mikael , Brunius Carl , Dicksved Johan , Pelve Erik , Esberg Anders , Vitale Marilena , Giacco Rosalba , Costabile Giuseppina , Bergia Robert E. , Jirstrand Mats , Campbell Wayne W , Riccardi Gabriele , Landberg Rikard
Published: September 2023

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades and the identification of differential glycemic responders can aid tailored treatment for prevention of pre-diabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among partic-ipants with elevated T2DM risk, to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary inter-vention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females, 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distin-guish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.
Mapping Geodesic Orbits around Cosmic Strings using Iterated Maps and Correlation with Disclination Intensity
Authors: Lobo Matheus , Carneiro Fernando
Published: September 2023

Cosmic strings can arise from spontaneous phase transitions during the inflationary period and are describable as disclination topological defects in spacetime. Analytical integration of the geodesic equations for a particle around a cosmic string reveals distinct orbit patterns dependent on the disclination intensity $\beta_{0}$. After its interaction with the cosmic string, the particle's behavior becomes random. To categorize these patterns, we describe the geodesic motion as iterated maps of a discrete parameter. Through the stabilization values of these functions, we correlate the scattering angle and the number of loops for the particle with $\beta_{0}$. Therefore, we interpret the gravitational field mathematically as an instructor of a particle's next position, given its previous one. We find that the radial function in the small displacement limit is similar to the logistic map. This leads us to conjecture the potential of the discrete parameter being a multiple of Planck's time, suggesting a method for the geometric discretization of spacetime around a cosmic string.
Tumor-Infiltrating iNKT Cells Activated through C-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing murine Melanoma Cells
Authors: Correa-Lara Maximiliano V.M , Lara-Vega Israel , Nájera-Martínez Minerva , Domínguez-López María Lilia , Reyes-Maldonado Elba , Vega-López Armando
Published: September 2023

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.
Imaging-Based Biomarkers in Neurological Diseases-A Critical Review
Authors: Kale Mayur B. , Wankhede Nitu L. , Taksande Brijesh G. , Upaganlawar Aman B. , Umekar Milind J. , Koppula Sushruta , Kopalli Spandana Rajendra
Published: September 2023

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.
Patient-Specific 3D Virtual Surgical Planning using Simulated Fluoroscopic Images to Improve Sacroiliac Joint Fusion
Authors: Kampkuiper Nick , Nellensteijn Jorm , Hekman Edsko , Tuijthof Gabriëlle , Lankheet Steven , Koenrades Maaike , Schröder Femke
Published: September 2023

Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve perioperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Routinely collected survey data on the added value of VSP were also evaluated. Ten interventions were performed on 10 patients by the same surgeon, comprising 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. The VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The average Likert scale score of the survey was 4.7, suggesting a positive role of VSP for SIJF. Planned positions of the implants could be reproduced in surgery with clinically acceptable accuracy and VSP was a valuable asset for the surgeon.
Effects of forest therapies on stress, depression, and anxiety levels: A systematic review
Authors: Paredes-Céspedes Diana Marcela , Vélez Norida , Parada-López Alejandra , Toloza Yesith , Téllez Eliana M. , Portilla Claudia , Gonzalez Carolina , Blandón Leany , Santacruz Juan Carlos
Published: September 2023

Background: The mental state is important in the health/illness process. Including stress, depression and anxiety. Nature immersion therapies have been implemented as a valid method for reducing these disorders. The aim will evaluate the effect of forest intervention therapies on levels of stress, depression, and anxiety. Methods: We searched for randomized clinical trials related to stress, anxiety and depression levels. Risk of bias was assessed according to the guidelines of the Cochrane Handbook for International Systematic Reviews. Results: We identified and synthesized eight publications. Two studies for cortisol showed significant differences between the pre-test and post-test levels in the intervention groups. One study including Natural killer cells, that reported a significant decrease in the intervention group compared to the control group. Two studies used the Stress Response Inventory, indicated a significant reduction in stress levels in the intervention group compared to the control group. Regarding Restorative Out-come Scale, no significant differences were found. Three studies were selected for the evaluation of anxiety and depression levels according to the Positive and Negative Affect Schedule. Four studies used The Profile of Mood States scale; no significant difference was observed. Conclusions: There is limited evidence to recommend forest bathing for reducing these disorders.
Edible Coatings as Alternative to Traditional Food Packaging: Enhancing Fruits and Vegetables Shelf-Life
Authors: Perez-Vazquez A. , Barciela P. , Carpena M. , Prieto And M.A.
Published: September 2023

In the past years, consumers have increased their interest to buy healthier food products, rejecting those products with more additives and giving preference to the fresh ones. Moreover, the current environmental situation has made society more aware of the importance of reducing the production of plastic and food waste. In this way and considering the Food Industry need of reducing the food spoilage along the food chain, edible coating has been considered as an eco-friendly food packaging that can replace traditional plastic packaging providing an improvement in the product’s shelf-life. Edible coating are thin layers applied straightaway on the food materials’ surface, that are made of biopolymers that usually incorporate other elements, such as nanoparticles or essential oils, to improve their physicochemical properties. These materials must provide a barrier that can prevent the pass of water vapor and other gasses, the microbial growth, the moisture loss, and the oxidation, so the shelf-life could be extended. The aim of this review was to compile the current data available to give a global vision of the formulation process and the different ways to improve the characteristics of the coats applied in both fruits and vegetables. In this way, the suitability of compounds in by-products produced during the Food Industry chain were also considered for the edible coating production.
Распространение вариантов вируса SARS-COV-2, вызывающих интерес (VOI) и субвариантов Omicron, находящихся под наблюдением (VUM), на основе количества их геномов, депонированных в базу данных GISAID за неделю со 2 по 8 сентября 2023 г.
Authors: Дмитриева Людмила , Краснов Ярослав , Чумачкова Елена , Осина Наталья , Зимирова Анастасия , Иванова Александра , Карнаухов Игорь , Караваева Татьяна , Щербакова Светлана , Кутырев Владимир
Published: September 2023

В обзоре представлена информация по циркулирующим в настоящее время вариантам вируса SARS-COV-2 вызывающих интерес (VOI) и субвариантов Omicron, находящихся под наблюдением (VUM), геномные последовательности которых размещены в международной базе данных GISAID за неделю со 2 по 8 сентября 2023 г.
Анализ динамики эпидемического процесса COVID-19 в мире за неделю с 02.09.2023 г. по 08.09.2023 г.
Authors: Зимирова Анастасия , Поспелов Михаил , Иванова Александра , Дмитриева Людмила , Чумачкова Елена , Карнаухов Игорь , Щербакова Светлана , Кутырев Владимир
Published: September 2023

В обзоре представлен анализ эпидемиологической ситуации в странах мира по COVID-19 за неделю с 02.09.2023 г. по 08.09.2023 г.
The effect of dialogic-practical work on secondary school students mechanics achievement
Authors: Belay Ewonetu Bantie , Alemu Mekbib , Tadesse Mesfin
Published: September 2023

This study aimed to examine the effects of dialogic-practical work on secondary school students‘ mechanics' achievement. It also examined whether the students‘ mechanics achievement would vary with achievement levels. A quasi-experimental pre- and post-test research design was used. The study participants were 91 students from two secondary schools in Bahir Dar town, Ethiopia. The treatment group conducted dialogic-practical work and the comparison group carried out recipe-based practical work. A 25-item Mechanics Achievement Test was used for data collection. A paired- and independent sample t-tests were performed to analyze the data. It was found that there was a statisitcally significant difference in mechanics achievement between the dialogic-and recipe-based practical work groups, t (76) = 7.80, p < .001, d= 1.76. It also indicated that the dialogic-practical work resulted more improvements in mechanics achievement of the different achievement levels as compared to the recipe-based practical work. This suggests that students who engaged in dialogic practical work enhanced their mechanics achievement more than students who simply follow prescribed recipes. It is important to raise physics teachers’ awareness about the benefits of dialogic-practical work to enhance students’ mechanics' achievement.
Canva-assisted Learning of Inquiry Sequences (LOIS)-based e-worksheet effectiveness
Authors: Herlina Kartini , Ertikanto Chandra , Nyeneng I Dewa Putu , Suane Wayan , Wicaksono B Anggit , Divia Bizry Cahya
Published: September 2023

Education in Indonesia has undergone a transformation that was initially conventional but now necessitates the integration of technology. Materials for teaching that can aid students in learning are required. The purpose of this study is to explain how well the e-worksheet for learning dynamic fluid physics works. This research uses a modified ADDIE model for research and development. The viability of the e-worksheet is estimated using a learning accomplishment test. The subjects of this review were thirty understudies in class XI at SMA Negeri 5 Bandar Lampung. The side effect of the test shows that the feasibility of e-worksheets in the control class is low given the low rules of learning based on revelation learning. The effectiveness of e-worksheets in the experimental class is very high.
Students’ problem solving skill in nuclear physics course through NPIRL
Authors: Hartini Sri , Liliasari Liliasari , Sinaga Parlindungan
Published: September 2023

This study aimed to describe students’ problem solving skill in nuclear physics course through the implementation of the Nuclear Physics Inquiry Remote Laboratory (NPIRL). This study employed a pre-experimental quantitative method. The research design was one group pretest-posttest design. The subject of the study was 14 physics students at a university in Banjarmasin, South Kalimantan. In selecting the research subjects, the researchers used purposive sampling technique. The instrument used was a problem-solving skills test in the form of an essay consisting of five questions, and each question consisted of six indicators in problem solving skill according to the Osborn-Parnes Creative Problem Solving (CPS). This research found that the N-gain of students' problem solving skill was 0.32 in the medium category. There are four indicators of problem-solving skills that are categorized as medium: objective finding, fact finding, problem finding and idea finding.  Two other low-category indicators are solution finding and acceptance finding. Based on these findings, it is concluded that students’ problem solving skill in nuclear physics course through NPIRL have increased.
PILOT PROJECT OF AN ETHICAL CODE OF SUBJECTS IMPLEMENTING ACTIVITY OF CREATING, APPLYING AND UTILIZING MEDICAL PRODUCTS BASED ON BIOPRINTING TECHNOLOGIES, INTERACTING WITH PATIENTS AND CELL DONORS, TURNOVER OF DONOR CELLS, BIOINK AND BIOPRINT TISSUE (ORGAN) CONSTRUCTS
Authors:   Kazan Innovative University named after V.G.Timiryasov (KIU), Shutova Albina A. , Begishev Ildar R. ,   Kazan Innovative University named after V.G.Timiryasov (KIU)
Published: September 2023

The pilot project of an ethical code of subjects implementing activity of creating, applying and utilizing medical products based on bioprinting technologies, interacting with patients and cell donors, turnover of donor cells, bioink and bioprint tissue (organ) constructs is a corpus of general principles of professional ethics and main rules of official conduct to be followed by the subjects implementing activities of creating, applying and utilizing medical products based on bioprinting technologies, interacting with patients and cell donors, turnover of donor cells, bioink and bioprint tissue (organ) constructs, aimed at strengthening the authority of medical staff, enhancing patients’ trust towards bioprinting technologies and preventing potential negative effects as a result of their application. The code is intended for legal scientists and practical lawyers, medical staff, members of human ethics committees, experts in medical ethics, representatives of law-making authorities, government agencies, business community and non-governmental organizations, patients, and a broad circle of readers interested in the issues of digital transformation of the healthcare system.
High Throughput Assessment of Gut Bacterial Tyrosine Decarboxylase Activity for Predicting Peripheral Levodopa Loss in Parkinson's Disease
Authors: Sieders Mink , Esteban Carmen Aranzamendi , Stratidakis Panagiotis kelefiotis , Aidy Sahar El
Published: September 2023

Parkinson's disease (PD), a prevalent neurodegenerative disorder, is commonly managed through oral levodopa administration. However, the enzymatic activity of specific gut bacteria, particularly tyrosine decarboxylase (TDC), can metabolize levodopa, potentially leading to diminishing treatment effectiveness over time. Current methods for assessing TDC activity in PD patients focus mainly on genetic markers, lacking a robust and precise assay to measure gut bacterial TDC activity. Building upon prior research demonstrating levodopa conversion to dopamine using bacterial cultures and rat jejunum samples, we present an enhanced protocol to accurately quantify TDC activity in human fecal samples. This high-throughput approach employs fermentation reactions with fecal-derived bacteria, measuring TDC activity by converting supplemented levodopa to dopamine through Ultra-Performance Liquid Chromatography coupled with Electrochemical Detection (UPLC-ED). Serving as a predictive biomarker for levodopa loss, this method allows preparation of 96 fecal sample fermentation cultures within ~7 h. A single individual can conduct the protocol, with completion time varying based on factors such as sample size and time points collected.
Microorganisms and Heavy Metal Contamination in Complementary and Herbal Medicine Creams in Saudi Arabia: a prospective experimental study
Authors: Alharbi Sarah F. , Althbah Ameerah I. , Mohammed Amal H. , Alrasheed Mishaal A. , Ismail Mukhtar , Allemailem Khaled S. , Alnuqaydan Abdullah M , Baabdullah Ahmed Mohammed , Alkhalifah Azzam
Published: September 2023

Introduction: Herbal medicine is a medical system based on the utilization of plants or plant extracts for therapy. The continual increase in global consumption and the trade of herbal medicine has raised safety concerns in many regions. These concerns are mainly linked to microbial and heavy metal contamination.
Methods: This study was performed using an experimental design. A total of 47 samples were used in the experiments, which were tested for bacterial contamination, alongside 32 samples for heavy metal analysis. Bacterial contamination was determined by the streak plate method and further processed to determine their antimicrobial susceptibility patterns using MicroScan WalkAway96 pulse; heavy metals were determined using a spectrometer instrument.
Results: A total of 58 microorganisms were isolated. All samples were found to be contaminated with at least one organism except one sample. The majority of the isolated bacterial species were gram negative bacteria, such as Klebsiella spp., Pseudomonas spp. and E. coli. Furthermore, most of the gram-positive bacteria were found to be multi-drug resistant. Moreover, for heavy metals, all samples had levels exceeding the regulatory limits.
Conclusion: This study demonstrated the presence of bacteria and heavy metals in samples of herbal medicines. These findings suggest the potential risks for those patients who use herbal medicine.
Longitudinal Dissociation of the conduction system during His/LBBP Bundle Pacing: A Case Report
Authors: Li Licheng , Jiang Fei , Xu Ning , Jiang Longfu
Published: September 2023

Background
Evidence of the conduction system longitudinal dissociation was rare.
Case presentation
We report a case of a third-degree atrioventricular block. During HB pacing (HBP) lead deployment, widening and splitting of HB potential and intrahisian Wenckebach phenomenon were recorded in intracardiac electrogram. Then, we began unipolar HBP at 2 V/0.5 ms.The paced QRS exhibited morphology identical to that during intrinsic rhythm, indicating selective capture of the HB. After stopping screw; three different QRS patterns were recorded at unipolar 1.3mv/0.5ms pacing. During His injury repairment, the H1-H2 interval was gradually shortened, the H1 potential was seems invisible and integrated into H potential. When LBB electrode was screwed in at 2V/0.5ms continuous pacing condition, the His lead showed obvious double potential reverse transmission (H2-H1) at the presence of S-LBBP.
Conclusion
The interesting finding in this case provided further electrophysiological evidences for longitudinal dissociation of the conduction system.
Mechanisms of Tibetan Medicine Sophora Moorcroftiana Alkaloids for Treatment of Lung Cancer based on the Network Pharmacology, Molecular Docking and cell Experimental Verification
Authors: ji peng , zhao nianshou , wu fanlin , wei yanming , laba cidan , wujin cuomu , hua yongli , yuan ziwen , yao wanling
Published: September 2023

Background
Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance.
Methods
The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets – LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding.
Results
We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc, Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells.
Conclusions
results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.
Damage and weakening effects of blasting on anchored rock mass
Authors: Xu Xingliang , Lei Yongchao , Tian Suchuan , Hu Weichao , Shi Hao
Published: September 2023

During blasting excavation of roadways, dynamic load is an important cause of damage to anchored rock mass and threatens the reliability of anchoring structures. Through theoretical analysis and numerical simulation, we studied the propagation of blasting stress waves based on anchor strengthening and damage and weakening of anchored rock mass and obtained damage characteristics of anchored rock mass under blast loading. The research results demonstrate that anchorage can reduce parameters, such as Poisson’s ratio, initial damage to the rock mass, and the attenuation coefficient of blasting load therein. The main causes of damage are high blasting load and stress wave reflection on structural planes of fractures. Moreover, the damage coefficient decreases then stabilises before increasing as the rock mass changes from being anchored to being blasted. Damage under blasting load shows zonal characteristics: a severely damaged zone, a damage transition zone, and damage vanishing zone can be seen along the axis of a roadway. The worst damage in shallow parts influences the reliability of anchoring structures, while the damage transition zone shields the anchored rock mass from deeper damage. The research results have important theoretical and guiding significance for design of bolt anchorage systems under blast load.
Robust Regression for interval valued data
Authors: Palanisamy T. , Rajesh Adithya Narayan , Giri greeshma
Published: September 2023

This paper presents robust regression technique of a multiple linear regression model for interval valued data that contains outliers. The proposed technique construct two models separately for mid values and spread values of the intervals. The parameters of the model involving mid values are estimated by iterative reweighted least squares technique. The estimation of the parameters of the model involving spread is accomplished by iterative reweighted quadratic programming. The quadratic programming ensures the constraints on the parameters that they are positive. Also, the proposed work detects the outliers. We have evaluated the proposed robust regression estimation technique using a Monte Carlo simulation study and a real time data. The results show the proposed estimation technique outperforms similar existing estimation.
Mathematics Subject Classification: 62F35 . 62J05
Prediction of Resilience based on Parenting Styles and Coping Strategies in Patients with Psychosomatic Disorders
Authors: Sobhani Sogand , Jamilian Hamidreza , Paknejad Iman
Published: September 2023

The present research was conducted aiming at predicting the resilience based on parenting styles and coping strategies in patients with psychosomatic disorders. The statistical population of the present research consisted of all patients suffering from psychosomatic disorders who had visited medical clinics related to Medical Sciences (University) of Arak County in 2019-20. The statistical sample includes 347 women, aged 18 to 55 years-old, who were selected by available sampling. Data collection tool included Young parenting styles, Moss and Billings coping strategies questionnaire and Connor and Davidson resilience questionnaire. Pearson's correlation coefficient and multiple regression analysis were used to analyze the data. The findings showed that parenting styles (dependency, preoccupied/untransformed self) have a negative and significant relationship with resilience. Coping strategies focused on emotion, coping focused on physical restraint or physicalization of problems have a negative and significant relationship with resilience and have a positive and significant relationship with coping strategies focused on problem-solving and coping focused on cognitive evaluation. According to the findings, it can be concluded that it is possible to pave the way for increasing resilience and preventing the development of psychosomatic disorders by creating suitable conditions during the childhood, improving parent-child relationships, and by strengthening coping strategies focused on problem-solving and coping focused on cognitive evaluation.
Three Gorges Dam: Influence of water quality on the density of schistosome-transmitting Oncomelania hupensis in the Dongting Lake Area, China
Authors: Wang Jiamin , Gong Yanfeng , Tong Yixin , Jiang Honglin , Xu Ning , Yin Jiangfan , Huang Junhui , Chen Yue , Jiang Qingwu , Zhou Yibiao
Published: September 2023

Schistosomiasis is a severe infectious disease and snails contribute to its transmission. Many factors, including water quality, affect the distribution of snails. This study collected the data on snails and indicators related to water quality in the Dongting Lake area from the period of 1998–2014. Water quality indexes such as permanganate index (CODMn), five-day biochemical oxygen demand (BOD5), total nitrogen (TN) and total phosphorus (TP) in correction with snail density were first examined using the Mann-Kendall (M-K) test. And then a Bayesian spatial-temporal model was constructed to evaluate the effect of water quality on snail density adjusting for meteorological factors and spatial-temporal variations. The results showed that the density of snails in the Dongting Lake area was influenced by water quality. The growth and reproduction of snails were promoted at a low pollution concentration, while inhibited at a high pollution concentration. These findings might provide valuable insights for relevant authorities to monitor the quality of water environment through investigating snail density.
Using a large language model (ChatGPT) to assess risk of bias in randomized controlled trials of medical interventions: protocol for a pilot study of interrater agreement with human reviewers
Authors: Rose Christopher James , Ringsten Martin , Bidonde Julia , Glanville Julie , Berg Rigmor C , Cooper Chris , Muller Ashley Elizabeth , Bergsund Hans Bugge , Meneses-Echavez Jose F , Potrebny Thomas
Published: September 2023

Background
Risk of bias (RoB) assessment is an essential part of systematic reviews of treatment effect. RoB assessment requires reviewers to read and understand each eligible trial and depends on a sound understanding of trial methods and RoB tools. RoB assessment is a highly skilled task, subject to human error, and can be time-consuming and expensive. Machine learning-based tools have been developed to streamline the RoB process using relatively simple models trained on limited corpuses. ChatGPT is a conversational agent based on a large language model (LLM) that was trained on an internet-scale corpus and demonstrates human-like abilities in many areas, including healthcare. LLMs might be able to perform or support systematic reviewing tasks such as assessing RoB, which may reduce review costs, time to completion, and error.
Objectives
To assess interrater agreement in overall (cf. domain-level) RoB assessment between human reviewers and ChatGPT, in randomized controlled trials of interventions within medicine.
Methods
We will randomly select 100 individually- or cluster-randomized, parallel, two-arm trials of medical interventions from recent Cochrane systematic reviews that have been assessed using the RoB1 or RoB2 family of tools. We will exclude reviews and trials that were performed under emergency conditions (e.g., COVID-19) that may not exhibit typical RoB, as well as public health and welfare interventions. We will use 25 of the trials and human RoB assessments to engineer a ChatGPT prompt for assessing overall RoB, based on trial methods text. We will obtain ChatGPT assessments of RoB for the remaining 75 trials and human assessments. We will then estimate interrater agreement.
Results
The primary outcome for this study is overall human-ChatGPT interrater agreement. We will report observed agreement with an exact 95% confidence interval, expected agreement under random assessment, Cochrane’s 𝜅, and a p-value testing the null hypothesis of no difference in agreement. Several other analyses are also planned.
Conclusions
This study is likely to provide the first evidence on interrater agreement between human RoB assessments and those provided by LLMs and will inform subsequent research in this area.
Do we need immunobiological drugs for treating anterior autoimmune uveitis in a tertiary referral center?
Authors: Araujo Leticia Cezar , Macagnani Fernanda Lourenço , Cabianca Camila Ávila Megda , Alves Daniela Pereira Castro , Costa Lívia Laila Soares , Caldeira Maria Thereza Gomes , Vieira Amanda Alexia Rodrigues , Furtado João Marcello Fortes , Oliveira Rodrigo , Luppino-Assad Rodrigo
Published: September 2023

Purpose
To evaluate the use of immunobiological drugs in anterior autoimmune uveitis in patients referred by rheumatologists and ophthalmologists to an autoimmune ocular diseases clinic.
Methods
Retrospective chart analysis of anterior autoimmune uveitis cases referred to a Rheumatology-Ophthalmology collaborative unit between January 2010 and January 2021. This unit receives cases almost exclusively referred by other ophthalmologists, mainly from a Uveitis Unit, or other rheumatologists.
Results
40 patients were identified and studied. The majority were women (24, 60.0%), with a mean age of 44,8 years old (SD = 16). Many patients had no identifiable underlying systemic disease (21, 52.5%). Ten (25.0%) were associated with either ankylosing spondylitis or undifferentiated spondyloarthropathy. Other associated conditions were rheumatoid arthritis (2, 5.0%), juvenile idiopathic arthritis (5, 12.5%), reactive arthritis (1, 2.5%) and psoriatic arthritis (1, 2.5%). Twenty-seven (67.5%) of the patients presented no sign of disease activity at the time of the latest evaluation (median remission period in months 14.5, IQR 0–27.5). Of these, 19 patients (70.3%) had received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), for the most part methotrexate (15, 78.9%) and sulfasalazine (n = 6, 31.6%). Fourteen (73.7%) used csDMARD only. Only 7 (25.9%) individuals in the remission group used immunobiological drugs (bDMARD), 3 (42.8%) of which had strictly articular disease activity as drug indication. Thus, only 14.8% of patients needed bDMARD to achieve remission. The most commonly used bDMARD were TNF-alpha antagonists, mainly adalimumab (5, 71.4%).
Conclusion
Although prospective, group-controlled studies are necessary to establish the best treatment for anterior autoimmune uveitis, this study suggests that only a small group of individuals would need an immunobiological agent to achieve, even in a population of primarily challenging cases.