bluuebunny/crossref_metadata_2025 huggingface dataset:
A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation
Authors: Fang Yu-Ming , Chen Wei-Can , Zheng Wan-Jing , Yang Yu-Shen , Zhang Yan , Chen Xin-Li , Pei Meng-Qin , Lin Shu , He He-Fan
Published: August 2023

Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord’s poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair in vitro and in vivo, effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.
Identifying major predictors for parenting stress in a caregiver of autism spectrum disorder using machine learning models
Authors: Choi Hangnyoung , Kim Jae Han , Kim Hwiyoung , Cheon Keun-Ah
Published: August 2023

Introduction

Previous studies have investigated predictive factors for parenting stress in caregivers of autism spectrum disorder (ASD) patients using traditional statistical approaches, but their study settings and results were inconsistent. Herein, this study aimed to identify major predictors for parenting stress in this population by developing explainable machine learning models.

Methods

Study participants were collected from the Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, the Republic of Korea between March 2016 and October 2020. A total of 36 model features were used, which include subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) for caregivers’ psychopathology, Social Responsiveness Scale-2 for core symptoms, and Child Behavior Checklist (CBCL) for behavioral problems. Machine learning classifiers [eXtreme Gradient Boosting (XGBoost), random forest (RF), logistic regression, and support vector machine (SVM) classifier] were generated to predict severe total parenting stress and its subscales (parental distress, parent-child dysfunctional interaction, and difficult child). Model performance was assessed by area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. We utilized the SHapley Additive exPlanations tree explainer to investigate major predictors.

Results

A total of 496 participants were included [mean age of ASD patients 6.39 (SD 2.24); 413 men (83.3%)]. The best-performing models achieved an AUC of 0.831 (RF model; 95% CI 0.740–0.910) for parental distress, 0.814 (SVM model; 95% CI 0.720–0.896) for parent-child dysfunctional interaction, 0.813 (RF model; 95% CI 0.724–0.891) for difficult child, and 0.862 (RF model; 95% CI 0.783–0.930) for total parenting stress on the test set. For the total parenting stress, ASD patients’ aggressive behavior and anxious/depressed, and caregivers’ depression, social introversion, and psychasthenia were the top 5 leading predictors.

Conclusion

By using explainable machine learning models (XGBoost and RF), we investigated major predictors for each subscale of the parenting stress index in caregivers of ASD patients. Identified predictors for parenting stress in this population might help alert clinicians whether a caregiver is at a high risk of experiencing severe parenting stress and if so, providing timely interventions, which could eventually improve the treatment outcome for ASD patients.
Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction
Authors: Yue Suru , Wang Jia , Zhao Yumei , Ye Enlin , Niu Dongdong , Huang Jiasheng , Li Xiaolin , Hu Yiling , Hou Xuefei , Wu Jiayuan
Published: August 2023

Background

Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients.

Methods

The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan–Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out.

Results

This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397–0.921, p = 0.019], 0.618 (95% CI: 0.398–0.960, p = 0.032), and 0.626 (95% CI: 0.411–0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results.

Conclusion

Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.
Small-molecule inhibitors of kinases in breast cancer therapy: recent advances, opportunities, and challenges
Authors: Bansal Isha , Pandey Amit Kumar , Ruwali Munindra
Published: August 2023

Breast cancer is the most common malignancy in women worldwide and despite significant advancements in detection, treatment, and management of cancer, it is still the leading cause of malignancy related deaths in women. Understanding the fundamental biology of breast cancer and creating fresh diagnostic and therapeutic strategies have gained renewed focus in recent studies. In the onset and spread of breast cancer, a group of enzymes known as kinases are extremely important. Small-molecule kinase inhibitors have become a promising class of medications for the treatment of breast cancer owing to their capacity to specifically target kinases involved in the growth and progression of cancer. The creation of targeted treatments that block these kinases and the signalling pathways that they activate has completely changed how breast cancer is treated. Many of these targeted treatments have been approved for the treatment of breast cancer as clinical trials have demonstrated their great efficacy. CDK4/6 inhibitors, like palbociclib, abemaciclib, and ribociclib, EGFR inhibitors such as gefitinib and erlotinib and HER2-targeting small-molecule kinases like neratinib and tucatinib are some examples that have shown potential in treating breast cancer. Yet, there are still difficulties in the development of targeted medicines for breast cancer, such as figuring out which patient subgroups may benefit from these therapies and dealing with drug resistance problems. Notwithstanding these difficulties, kinase-targeted treatments for breast cancer still have a lot of potential. The development of tailored medicines will continue to be fuelled by the identification of novel targets and biomarkers for breast cancer as a result of advancements in genomic and proteomic technology.
Promoting anti-racism in the legal system: an application of the STYLE framework
Authors: Fix Rebecca L. , Thurston Idia B. , Johnson Renee M. , Andrisse Stanley
Published: August 2023

Racism is a critical social problem, and we present a framework to guide professionals in engaging in anti-racist practices. Professionals on the frontlines in psychology and related fields such as social work and public health have a responsibility to engage in anti-racist practices. Part of the professional role must be to advocate for justice through increased proximity to the issues and engagement in anti-oppressive practices. The current discourse introduces a framework through which people working in psychology and other related professions can promote anti-racism work, highlighting the legal system for illustrative purposes. While some professionals in psychology may not have direct experience with the legal system, many of the individuals served by psychologists do (e.g., clients/patients, students, community members). Our framework is represented by the acronym STYLE (Self-examination, Talk about racism, Yield time to anti-racism work, Learn about structural racism, Evaluate policies and practices). The goal of STYLE is to expand anti-racism science and practice within psychology and related fields. We describe new roles for professionals in dismantling health inequities and offer specific pathways to develop critical partnerships toward this aim. STYLE explicitly encourages active, intentional involvement of affected community members in the development and evaluation of approaches to health services. To achieve equity and to promote individual and organizational growth in anti-racism and ultimately anti-oppression work, professionals must focus on changing their STYLE.
Evaluation and management of symptomatic duodenal diverticula: a single-center retrospective analysis of 647 patients
Authors: Ren Jiaqiang , Ding Jiachun , Su Tong , Wu Shuai , Chen Fan , Li Jie , Wang Zheng , Han Liang , Wu Zheng
Published: August 2023

Aims

To explore the clinical characteristics of patients with symptomatic duodenal diverticula and to generalize how to make appropriate treatment choices for this group of patients.

Materials and methods

From January 2010 to September 2020, a total of 647 patients with duodenal diverticula (DD) were included in this study. 345 of them with relevant symptoms were divided into the symptomatic group and the other 302 patients were in the asymptomatic group.

Results

Among all patients, most DD were located in the periampullary area, <1 cm in size, and single in number. The distribution of DD localized in the 2nd portion/periampullary (P = 0.002/P < 0.001) and with a 1 cm size cut-off value (P = 0.003) was significantly different between the symptomatic and asymptomatic groups. Multivariate Logistics analysis further suggests that diverticular size (<1 cm, 1–3 cm) and combined biliary comorbidities (bile duct stones and gallstones, primary bile duct stones, cholangitis without bile duct stones) may be factors influencing the choice of treatment modality. Of all patients undergoing surgical treatment, a total of 7 cases developed various postoperative complications, and no one died.

Conclusions

Patients with DD ≥1 cm or located in the periampullary were more likely to be symptomatic. The specific size of the DD and the combination of specific biliary comorbidities may have an impact on the choice of treatment modality.
An analysis of substantiated complaints made about incidents of poor livestock welfare, in Victoria, Australia.
Authors: Williams Natarsha , Chaplin Sarah , Hemsworth Lauren , Shephard Richard , Fisher Andrew
Published: August 2023

Incidents of poor welfare on farm in Victoria, Australia, are generally identified during an investigation that follows receipt of a complaint. Using deidentified records of complaints received by the Victoria State Government between 2011 and 2020, this study aimed to describe the source, number and the relationship between rainfall/stock prices and substantiated welfare complaints (SWC). Only incidents involving non-dairy cattle, sheep and goats in extensive farming systems will be considered. The main source of complaints received by the Victorian Government is the general public. Almost half of all complaints were made for cattle (48%), 39% for sheep, 11% for mixed species, and 2% for goats. The number of SWC varied between months, each year and across the different regions of Victoria. The ratio of the actual mean rainfall of the last three seasons to the long-term mean of the last three seasons of rainfall (RL3SR) and livestock prices together were the best predictors of the total number of SWC (adjusted R square value for heavy lamb-RL3SR was highest (0.590), followed by merino lamb-RL3SR (0.588), goat-RL3SR (0.545) and steer-RL3SR (0.478) all were significant (p ≤ 0.05)). The rainfall by region and town were not good predictors of the number of SWC. There was a correlation between rainfall and the number of SWC, possibly due to changes in pasture availability. Favorable seasonal conditions however, were not protective of livestock welfare and it is likely a number of factors may be implicated.
Characteristics and Driving Factors of Precipitation-Use Efficiency across Diverse Grasslands in Chinese Loess Plateau
Authors: Ren Zongping , Qiao Hailiang , Xiong Ping , Peng Jianbo , Wang Bo , Wang Kaibo
Published: August 2023

Understanding the characteristics of the precipitation-use efficiency (PUE) of grassland ecosystems and its drivers is critical for predicting how ecosystem functions will respond to future climate change. In this study, we investigated several covarying biotic and abiotic factors (e.g., biomass, coverage, diversity, precipitation, temperature, and humid index (HI)) of 81 sites across a broad natural grassland gradient in the Loess Plateau of China to determine how PUE changes along a precipitation gradient and to assess the effects of biotic and abiotic factors on PUE. Our results showed that HI, below-ground biomass (BGB), vegetation coverage, and species diversity were the most important biotic factors in controlling PUE. HI had a higher positive indirect effect on PUE mainly through its influence on community characteristics. Our results suggest that precipitation and community characteristics are both important for the precipitation-use efficiency of natural grasslands across the arid and semiarid areas of the Loess Plateau. Additionally, improving the vegetation structure and increasing species diversity can help enhance the adaptability of grassland ecosystems to climate change.
Taxonomic Notes and Nomenclatural Corrections on Four Sphaeromatid Isopod Generic Names (Crustacea: Isopoda: Sphaeromatidae)
Authors: Boyko Christopher B.
Published: August 2023

Details regarding the synonymy of Nesaea Leach, 1814 and Dynamene Leach, 1814 are given and a type species is selected for Dynamene. The genus Heteruropus Verhoeff, 1942 is shown to be the senior objective synonym of Harrieta Kensley, 1987 and an expanded synonymy list for the type species, Heteruropus faxoni (Richardson, 1905) is provided.
Derivative Formulas and Gradient of Functions with Non-Independent Variables
Authors: Lamboni Matieyendou
Published: August 2023

Stochastic characterizations of functions subject to constraints result in treating them as functions with non-independent variables. By using the distribution function or copula of the input variables that comply with such constraints, we derive two types of partial derivatives of functions with non-independent variables (i.e., actual and dependent derivatives) and argue in favor of the latter. Dependent partial derivatives of functions with non-independent variables rely on the dependent Jacobian matrix of non-independent variables, which is also used to define a tensor metric. The differential geometric framework allows us to derive the gradient, Hessian, and Taylor-type expansions of functions with non-independent variables.
Combined Therapies with Taxane-Based Chemotherapeutic Drugs in Prostate Cancer: Novel Insights and Future Directions
Authors: Coelho Rafaella S. , Rocha Sandra M. , Maia Cláudio J.
Published: August 2023

Oncologic disease is a significant global health issue that causes thousands of deaths annually, and it has a significant impact on the quality of life of patients. Prostate cancer (PCa) is the second most diagnosed cancer and the fourth leading cause of cancer-related death in men in the Western world. Delineation of pathogenetic pathways and key driver molecular alterations involved in PCa development has provided a roadmap for the evaluation of biomarkers in predicting disease outcome and to identify potential therapeutic targets. Chemotherapeutic agents introduced from the 1990s include the taxanes (paclitaxel, docetaxel, and cabazitaxel), which are the anticancer drugs used most frequently for PCa treatment. This review presents the current knowledge about the onset and development of PCa, the state of the art of the use of taxane-based therapy, and their combination with targeting different transmembrane oncoproteins in PCa. The silencing of some transmembrane proteins can improve taxane sensitivity, and therefore may be a mechanism to improve the effectiveness of these drugs in PCa treatment. This combined therapy needs to be explored as a potential therapeutic agent for reducing cell proliferation, migration, and invasiveness in PCa.
Predicting Soil Carbon Sequestration and Harvestable C-Biomass of Rice and Wheat by DNDC Model
Authors: Shaukat Muhammad , Hoshide Aaron Kinyu , Muhammad Sher , Arshad Irshad Ahmad , Mushtaq Muhammad , de Abreu Daniel Carneiro
Published: August 2023

Several biogeochemical models have been applied to understand the potential effects of management practices on soil organic carbon (SOC) sequestration, crop growth, and yield. In this study, the denitrification and decomposition (DNDC) model was used to simulate soil SOC dynamics and harvested C-biomass in rice–wheat rotation under organic/inorganic fertilization with conventional tillage (CT) and reduced tillage (RT). Before calibration, DNDC underpredicted harvestable grain C-biomass of rice where percent difference (PD) varied from 29.22% to 42.14%, and over-simulated grain C-biomass of wheat where PD was −55.01% with 50% nitrogen–phosphorus–potassium (NPK) and 50% animal manure applied under the CT treatment. However, after calibration by adjusting default values of soil and crop parameters, DNDC simulated harvestable grain C-biomass of both crops very close to observed values (e.g., average PD ranged from −2.81% to −6.17%). DNDC also predicted the effects of nutrient management practices on grain C-biomass of rice/wheat under CT/RT using d-index (0.76 to 0.96) and the calculated root mean squared error (RMSE of 165.36 to 494.18 kg C ha−1). DNDC simulated SOC trends for rice–wheat using measured values of several statistical indices. Regression analysis between modeled and observed SOC dynamics was significant with R2 ranging from 0.35 to 0.46 (p < 0.01), and intercept ranging from 0.30 to 1.34 (p < 0.65). DNDC demonstrated that combined inorganic and organic fertilization may result in higher C-biomass and more SOC sequestration in rice–wheat systems.
Research Progress of Organic Corrosion Inhibitors in Metal Corrosion Protection
Authors: Zhao Wenwen , Li Feixiang , Lv Xianghong , Chang Jianxiu , Shen Sicong , Dai Pan , Xia Yuan , Cao Zhongyue
Published: August 2023

Metal materials are vulnerable to corrosion in the process of production and service, which often leads to serious disasters, including the decline of the performance of metal components and the shortened service life, and even causes catastrophic accidents and ecological damage. Adding a certain amount of corrosion inhibitors (CIs) to the corrosive medium is a simple, efficient, and economical anti-corrosion method to slow down and restrain the corrosion of metal materials. Organic corrosion inhibitors (OCIs) are considered to have good application prospects and are widely used for surface anti-corrosion of metal materials, as they generally have advantages such as good metal adsorption, low oxidation resistance, good thermal and chemical stability, and green environmental protection. This paper systematically summarized some major OCIs, including alkyl chains, imidazoles, and pyridines, and their structural characteristics, as well as the action mechanism of OCIs. Moreover, this paper discusses some natural compounds used as environmentally friendly CIs and provides a prospect for the development trend of OCIs.
Mental Gravity: Depression as Spacetime Curvature of the Self, Mind, and Brain
Authors: Kent Lachlan
Published: August 2023

The principle of mental gravity contends that the mind uses physical gravity as a mental model or simulacrum to express the relation between the inner self and the outer world in terms of “UP”-ness and “DOWN”-ness. The simulation of increased gravity characterises a continuum of mental gravity which states includes depression as the paradigmatic example of being down, low, heavy, and slow. The physics of gravity can also be used to model spacetime curvature in depression, particularly gravitational time dilation as a property of MG analogous to subjective time dilation (i.e., the slowing of temporal flow in conscious experience). The principle has profound implications for the Temporo-spatial Theory of Consciousness (TTC) with regard to temporo-spatial alignment that establishes a “world-brain relation” that is centred on embodiment and the socialisation of conscious states. The principle of mental gravity provides the TTC with a way to incorporate the structure of the world into the structure of the brain, conscious experience, and thought. In concert with other theories of cognitive and neurobiological spacetime, the TTC can also work towards the “common currency” approach that also potentially connects the TTC to predictive processing frameworks such as free energy, neuronal gauge theories, and active inference accounts of depression. It gives the up/down dimension of space, as defined by the gravitational field, a unique status that is connected to both our embodied interaction with the physical world, and also the inverse, reflective, emotional but still embodied experience of ourselves.
Generalized Bell Scenarios: Disturbing Consequences on Local-Hidden-Variable Models
Authors: Mazzari André , Ruffolo Gabriel , Vieira Carlos , Temistocles Tassius , Rabelo Rafael , Terra Cunha Marcelo
Published: August 2023

Bell nonlocality and Kochen–Specker contextuality are among the main topics in the foundations of quantum theory. Both of them are related to stronger-than-classical correlations, with the former usually referring to spatially separated systems, while the latter considers a single system. In recent works, a unified framework for these phenomena was presented. This article reviews, expands, and obtains new results regarding this framework. Contextual and disturbing features inside the local models are explored, which allows for the definition of different local sets with a non-trivial relation among them. The relations between the set of quantum correlations and these local sets are also considered, and post-quantum local behaviours are found. Moreover, examples of correlations that are both local and non-contextual but such that these two classical features cannot be expressed by the same hidden variable model are shown. Extensions of the Fine–Abramsky–Brandenburger theorem are also discussed.
Study on the Influence of Coal Structure and Oxidation Performance by Endogenous Bacterium
Authors: Dong Xuanmeng , Wang Fusheng , Guo Liwen , Han Tiesheng
Published: August 2023

In order to solve the defects of traditional coal spontaneous combustion prevention technology in a closed goaf, a strain of aerobic endogenous bacteria was isolated from coal and used as a blocking raw material. Based on the metabolic and reproductive characteristics of microorganisms, the experimental study on the inhibition of coal spontaneous combustion by microorganisms was carried out. The colonies were isolated and purified by the dilution concentration plate method and the scribing plate method. The growth morphology of microorganisms was analyzed, and the growth curve was determined. The strains were identified by seamless cloning technology for high-throughput sequencing. The surface morphology of coal was analyzed by SEM, the differences of oxidation characteristic temperature points were analyzed by TG–DTG–DSC images, a programmed heating experiment was used to analyze the concentration of the indicator gas CO, and the changes in microscopic groups before and after microbial action were analyzed by FTIR and XPS spectra. Therefore, the inhibition of coal oxidation by endogenous bacteria was verified from macroscopic and microscopic perspectives. The results show that the coal bacteria isolated from the coal is Lysinibacilus sp. After the culture of Lysinibacilus sp., the surface of the coal demonstrated less detritus, and was relatively smooth. In the early stage of low temperature oxidation of coal spontaneous combustion, the characteristic temperature point of coal oxidation and the reaction between coal and O2 could be delayed by Lysinibacilus sp., and the total heat release was reduced in the combustion process. Not only that, Lysinibacilus sp. could also reduce the CO concentration during coal heating. After the coal was decomposed by Lysinibacilus sp., the C=C thick ring skeleton structure had little effect; however, the aromatic substitution pattern changed. This bacterium had an effect on the C-O bond, reducing the percentage of -CH2- and increasing the percentage of -CH3. It might also use the crystalline water in coal for life activities. The carboxyl carbon in coal changed the most, with a decrease of 12.03%, so it might become the carbon source required for microbial growth. The reproductive metabolism of microorganisms also affected the form of nitrogen, and the percentage of pyridine nitrogen in coal was reduced. The ratio of single-bond carbon to double-bond carbon in raw coal was about 3:2, but after this bacterial action, the ratio of the two was about 1:1. The analytical conclusions of XPS and FTIR spectra were consistent, and the results supported each other.
Engineering Attributes of Ternary Geopolymer Mortars Containing High Volumes of Palm Oil Fuel Ash: Impact of Elevated Temperature Exposure
Authors: Huseien Ghasan Fahim , Kubba Ziyad , Ghoshal Sib Krishna
Published: August 2023

Geopolymer mortars made from various waste products can appreciably reduce carbon dioxide emissions and landfill-related issues, making them viable substitutes for ordinary Portland cement, a workhorse in the concrete industry. Thus, a series of ternary geopolymer mortars were made and characterized to determine the effects of exposure to elevated temperatures (from room temperature up to 900 °C) on their engineered (residual compressive strength, weight loss, and slant shear bond strength) and microstructural properties. These mortars, which contain fly ash, ground blast furnace slag, and a high volume of palm oil fuel ash, were designed to activate via the incorporation of an alkali activator solution at a low concentration (molarity of 4). The elevated temperature-mediated deterioration of the ternary geopolymer mortar was quantified using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The results revealed an improvement in the ternary geopolymer mortars’ resistance against elevated temperatures when the palm oil fuel ash level in the mortar matrix was raised from 50 to 70% and when slag was replaced by fly ash. It was asserted that the proposed ternary geopolymer mortars may contribute to the advancement of green concretes demanded by the construction sectors.
An Explicit–Implicit Spectral Element Scheme for the Nonlinear Space Fractional Schrödinger Equation
Authors: Liu Zeting , Yin Baoli , Liu Yang
Published: August 2023

In this paper, we solve the space fractional nonlinear Schrödinger equation (SFNSE) by developing an explicit–implicit spectral element scheme, which is formulated based on the Legendre spectral element approximation in space and the Crank–Nicolson leap frog (CNLF) difference discretization in time. Both mass and energy conservative properties are discussed for the spectral element scheme. Numerical stability and convergence of the scheme are proved. Numerical experiments are performed to confirm the high accuracy and efficiency of the proposed numerical scheme.
Medical Nature-Based Rehabilitation Program for Individuals with Exhaustion Syndrome: Changes in Quality of Life, Exhaustion Symptoms and Overall Health
Authors: Petitt Eleanor , Rolander Bo , Johnsson Per
Published: August 2023

Stress-related health problems have increased sharply over the last two decades and have become a serious issue at all levels of society. In the Jönköping Region in southern Sweden, a nature-based rehabilitation (NBR) program for adults with Exhaustion Syndrome has been developed and then implemented into the Swedish National Healthcare System. The main aim of this study was to investigate the effectiveness of this NBR-program. This was achieved by examining patients’ quality of life, exhaustion symptoms and overall health using self-assessment instruments, comparing the results before participation to immediately after, three months after and six months after. With a sample size of 67 participants, the results show a statistically significant improvement for all points. From a public health perspective, and with background knowledge of the nature of the patient group under treatment, the studied program would appear to be effective and economic, having a satisfied patient group as well as a favourable comparison with the outcomes of other research programs. Although the results are promising, as this is a naturalistic field study, there is no control group, and further research is encouraged. We suggest randomised controlled studies, longitudinal studies and investigation of mediators.
Closed-Loop Medication Management with an Electronic Health Record System in U.S. and Finnish Hospitals
Authors: Shermock Susan B. , Shermock Kenneth M. , Schepel Lotta L.
Published: August 2023

Many medication errors in the hospital setting are due to manual, error-prone processes in the medication management system. Closed-loop Electronic Medication Management Systems (EMMSs) use technology to prevent medication errors by replacing manual steps with automated, electronic ones. As Finnish Helsinki University Hospital (HUS) establishes its first closed-loop EMMS with the new Epic-based Electronic Health Record system (APOTTI), it is helpful to consider the history of a more mature system: that of the United States. The U.S. approach evolved over time under unique policy, economic, and legal circumstances. Closed-loop EMMSs have arrived in many U.S. hospital locations, with myriad market-by-market manifestations typical of the U.S. healthcare system. This review describes and compares U.S. and Finnish hospitals’ EMMS approaches and their impact on medication workflows and safety. Specifically, commonalities and nuanced differences in closed-loop EMMSs are explored from the perspectives of the care/nursing unit and hospital pharmacy operations perspectives. As the technologies are now fully implemented and destined for evolution in both countries, perhaps closed-loop EMMSs can be a topic of continued collaboration between the two countries. This review can also be used for benchmarking in other countries developing closed-loop EMMSs.
A Microfluidic Experimental Method for Studying Cell-to-Cell Exosome Delivery–Taking Stem Cell–Tumor Cell Interaction as a Case
Authors: Peng Xing Yue (Larry) , Su Pengxiang , Guo Yaxin , Zhang Jing , Peng Linghan , Zhang Rongrong
Published: August 2023

Cell-to-cell communication must occur through molecular transport in the intercellular fluid space. Nanoparticles, such as exosomes, diffuse or move more slowly in fluids than small molecules. To find a microfluidic technology for real-time exosome experiments on intercellular communication between living cells, we use the microfluidic culture dish’s quaternary ultra-slow microcirculation flow field to accumulate nanoparticles in a specific area. Taking stem cell–tumor cell interaction as an example, the ultra-slow microcirculatory flow field controls stem cell exosomes to interfere with tumor cells remotely. Under static coculture conditions (without microfluidics), the tumor cells near stem cells (<200 µm) show quick breaking through from its Matrigel drop to meet stem cells, but this ‘breaking through’ quickly disappears with increasing distance. In programmed ultra-slow microcirculation, stem cells induce tumor cells 5000 μm far at the site of exosome deposition (according to nanoparticle simulations). After 14 days of programmed coculture, the glomeration and migration of tumor cells were observed in the exosome deposition area. This example shows that the ultra-slow microcirculation of the microfluidic culture dish has good prospects in quantitative experiments to study exosome communication between living cells and drug development of cancer metastasis.
Extract of Artemisia dracunculus L. Modulates Osteoblast Proliferation and Mineralization
Authors: Scott Matthew C. , Bourgeois Aleah , Yu Yongmei , Burk David H. , Smith Brenda J. , Floyd Z. Elizabeth
Published: August 2023

Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2′,4′-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity.
Isolation, Identification and Antimicrobial Resistance Analysis of Canine Oral and Intestinal Escherichia coli Resistant to Colistin
Authors: Zheng Hui-Hua , Yu Chao , Tang Xin-Yue , Du Chong-Tao , Xie Guang-Hong
Published: August 2023

In recent years, the antimicrobial resistance in Escherichia coli has gradually developed into a global problem. These resistant bacteria could be transmitted to humans through animal feces in the environment or direct contact with pets, leading to a problem in bacterial treatment for humans and animals. Now, the antibiotic resistance of oral and intestinal microbiota from dog origins remains unclear in China. Therefore, this study first analyzed the current colistin resistance of oral and intestinal microbiota from dog origins in mainland China. A total of 536 samples were collected from dogs in mainland China and, respectively, cultured on the SS and MacConkey agar plate containing colistin (4 μg/mL) to obtain bacteria, and the antibiotic-resistance phenotype of Escherichia coli was investigated for nine antibiotics. Results showed that a total of 2259 colistin-resistant bacteria were isolated from samples and identified, and among them, the isolated rate of Escherichia coli (34.01%, 769/2259) was relatively higher than that of other bacteria. Subsequently, it was found that the resistance of these Escherichia coli was very severe by exploring its resistance to different antibiotics, particularly to three common antibiotics in a clinic which were ceftriaxone, ampicillin and trimethoprim/sulfamethoxazole, with the resistance rates of 60.60% (466/769), 57.22% (440/769), and 53.06% (408/769), respectively. Moreover, the simultaneous resistance of Escherichia coli to one or more antibiotics was determined, and 69.96% (538/769) strains have defined the resistance to both two or more antibiotics, and even 13 of Escherichia coli strains that were resistant to all nine antibiotics, indicating that the Escherichia coli from dog origins has severe antibiotic resistance in the clinic. In conclusion, this study guided the use of antibiotics and could draw attention to antibiotic resistance in veterinary clinical treatment for animals in the future.
Tear Biomarkers and Alzheimer’s Disease
Authors: Kaštelan Snježana , Braš Marijana , Pjevač Neda , Bakija Ivana , Tomić Zora , Pjevač Keleminić Nada , Gverović Antunica Antonela
Published: August 2023

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative brain disorder that represents the most common type of dementia. It poses a significant diagnostic challenge that requires timely recognition and treatment. Currently, there is no effective therapy for AD; however, certain medications may slow down its progression. The discovery of AD biomarkers, namely, magnetic resonance imaging, positron emission tomography and cerebrospinal fluid molecules (amyloid-β and tau) has advanced our understanding of this disease and has been crucial for identifying early neuropathologic changes prior to clinical changes and cognitive decline. The close interrelationship between the eye and the brain suggests that tears could be an interesting source of biomarkers for AD; however, studies in this area are limited. The identification of biomarkers in tears will enable the development of cost-effective, non-invasive methods of screening, diagnosis and disease monitoring. In order to use tears as a standard method for early and non-invasive diagnosis of AD, future studies need to be conducted on a larger scale.
Dynamics of the Apo µ-Opioid Receptor in Complex with Gi Protein
Authors: Lima Mira Raya Paula de , Bezerra Rubem Francisco Silva , Serafim David Denis Bento , Sena Junior Diniz Maciel
Published: August 2023

Opioid receptors, particularly the µ-opioid receptor (μOR), play a pivotal role in mediating the analgesic and addictive effects of opioid drugs. G protein signaling is an important pathway of μOR function, usually associated with painkilling effects. However, the molecular mechanisms underlying the interaction between the μOR and G protein remain poorly understood. In this study, we employed classical all-atom molecular dynamics simulations to investigate the structural changes occurring with the μOR-G protein complex under two different conditions: with the G protein in the apo form (open) and with the GDP bound G protein (closed, holo form). The receptor was in the apo form and active conformation in both cases, and the simulation time comprised 1µs for each system. In order to assess the effect of the G protein coupling on the receptor activation state, three parameters were monitored: the correlation of the distance between TM3 and TM6 and the RMSD of the NPxxYA motif; the universal activation index (A100); and the χ2 dihedral distribution of residue W2936.48. When complexed with the open G protein, receptor conformations with intermediate activation state prevailed throughout the molecular dynamics, whereas in the condition with the closed G protein, mostly inactive conformations of the receptor were observed. The major effect of the G protein in the receptor conformation comes from a steric hindrance involving an intracellular loop of the receptor and a β-sheet region of the G protein. This suggests that G-protein precoupling is essential for receptor activation, but this fact is not sufficient for complete receptor activation.
Studies on the Role of Compartmentalized Profiles of Cytokines in the Risk of Hepatocellular Carcinoma
Authors: Fasolato Silvano , Del Bianco Paola , Malacrida Sandro , Mattiolo Adriana , Gringeri Enrico , Angeli Paolo , Pontisso Patrizia , Calabrò Maria Luisa
Published: August 2023

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is frequently diagnosed late due to the absence of symptoms during early disease, thus heavily affecting the overall survival of these patients. Soluble immunological factors persistently produced during cirrhosis have been recognized as promoters of chronic inflammation and neoplastic transformation. The aim of this pilot study was to evaluate the predictive value of the cytokine profiles for HCC development. A Luminex xMAP approach was used for the quantification of 45 proteins in plasma and ascitic fluids of 44 cirrhotic patients without or with HCC of different etiologies. The association with patient survival was also evaluated. Univariate analyses revealed that very low levels of interleukin 5 (IL-5) (<15.86 pg/mL) in ascites and IL-15 (<12.40 pg/mL) in plasma were able to predict HCC onset with an accuracy of 81.8% and a sensitivity of 95.2%. Univariate analyses also showed that HCC, hepatitis B virus/hepatitis C virus infections, low levels of IL-5 and granulocyte-macrophage colony-stimulating factor in ascitic fluids, and high levels of eotaxin-1, hepatocyte growth factor and stromal-cell-derived factor 1α in plasma samples were factors potentially associated with a poor prognosis and decreased survival. Our results suggest a potential protective role of some immune modulators that may act in the peritoneal cavity to counteract disease progression leading to HCC development.
Changes in α-Synuclein Posttranslational Modifications in an AAV-Based Mouse Model of Parkinson’s Disease
Authors: Brembati Viviana , Faustini Gaia , Longhena Francesca , Outeiro Tiago Fleming , Bellucci Arianna
Published: August 2023

Parkinson’s disease (PD) pathology is characterized by the loss of dopaminergic neurons of the nigrostriatal system and accumulation of Lewy bodies (LB) and Lewy neurites (LN), inclusions mainly composed of alpha-synuclein (α-Syn) fibrils. Studies linking the occurrence of mutations and multiplications of the α-Syn gene (SNCA) to the onset of PD support that α-Syn deposition may play a causal role in the disease, in line with the hypothesis that disease progression may correlate with the spreading of LB pathology in the brain. Interestingly, LB accumulate posttranslationally modified forms of α-Syn, suggesting that α-Syn posttranslational modifications impinge on α-Syn aggregation and/or toxicity. Here, we aimed at investigating changes in α-Syn phosphorylation, nitration and acetylation in mice subjected to nigral stereotaxic injections of adeno-associated viral vectors inducing overexpression of human α-Syn (AAV-hα-Syn), that model genetic PD with SNCA multiplications. We detected a mild increase of serine (Ser) 129 phosphorylated α-Syn in the substantia nigra (SN) of AAV-hα-Syn-injected mice in spite of the previously described marked accumulation of this PTM in the striatum. Following AAV-hα-Syn injection, tyrosine (Tyr) 125/136 nitrated α-Syn accumulation in the absence of general 3-nitrotirosine (3NT) or nitrated-Tyr39 α-Syn changes and augmented protein acetylation abundantly overlapping with α-Syn immunopositivity were also detected.
Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study
Authors: Syed Zeba A. , Milman Tatyana , Fertala Jolanta , Steplewski Andrzej , Fertala Andrzej
Published: August 2023

Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA’s positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly.
The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids
Authors: Chuang Tsai-Der , Ton Nhu , Rysling Shawn , Quintanilla Derek , Boos Drake , Gao Jianjun , McSwiggin Hayden , Yan Wei , Khorram Omid
Published: August 2023

The objective of this study was to determine if the aberrant expression of select genes could form the basis for the racial disparity in fibroid characteristics. The next-generation RNA sequencing results were analyzed as fold change [leiomyomas/paired myometrium, also known as differential expression (DF)], comparing specimens from White (n = 7) and Black (n = 12) patients. The analysis indicated that 95 genes were minimally changed in tumors from White (DF ≈ 1) but were significantly altered by more than 1.5-fold (up or down) in Black patients. Twenty-one novel genes were selected for confirmation in 69 paired fibroids by qRT-PCR. Among these 21, coding of transcripts for the differential expression of FRAT2, SOX4, TNFRSF19, ACP7, GRIP1, IRS4, PLEKHG4B, PGR, COL24A1, KRT17, MMP17, SLN, CCDC177, FUT2, MYO5B, MYOG, ZNF703, CDC25A, and CDCA7 was significantly higher, while the expression of DAB2 and CAV2 was significantly lower in tumors from Black or Hispanic patients compared with tumors from White patients. Western blot analysis revealed a greater differential expression of PGR-A and total progesterone (PGR-A and PGR-B) in tumors from Black compared with tumors from White patients. Collectively, we identified a set of genes uniquely expressed in a race/ethnicity-dependent manner, which could form the underlying mechanisms for the racial disparity in fibroids and their associated symptoms.