bluuebunny/crossref_metadata_2025 huggingface dataset:
The Management of Hepatic Encephalopathy from Ward to Domiciliary Care: Current Evidence and Grey Areas
Authors: Bellafante Daniele , Gioia Stefania , Faccioli Jessica , Riggio Oliviero , Ridola Lorenzo , Nardelli Silvia
Published: December 2023

Hepatic Encephalopaty (HE) is a common complications of advanced liver disease and acute liver failure. It is a condition that features both neurological and psychiatric symptoms, that affects mortality, morbidity and quality of patients and caregivers’ life. HE diagnosis is generally an exclusion diagnosis. Once the patient is admitted to hospital, clinical examination, blood tests and eventually neuroimaging should be performed in order to rule out other causes of acute brain dysfunction. Moreover, HE recognizes various precipitants that can potentially promote its onset, alone or in combination, that must be identified. Once the diagnostic process is complete, a correct treatment should be started. The anti-HE treatment is based on a combination of correction of precipitants and non-absorbable disaccharides and non-absorbable antibiotic, such as rifaximin. Once the patient is discharged from the hospital, specific anti-HE therapy should be maintained in order to prevent other HE episodes.
Harmonizing the Development of Local Socioeconomic Scenarios: A Participatory Downscaling Approach Applied in Five European Case Studies
Authors: Vafeidis Athanasios Thomas , Reimann Lena , Ellen Gerald Jan , Goransson Gunnel , Koers Gerben , Van Well Lisa , Vollstedt Bente , Tsakiris Maureen , Oen Amy
Published: December 2023

Scenario analysis is a widely employed method for addressing uncertainties when assessing the physical and socio-economic impacts if climate change. Global scenarios have been extensively used in this context. However, these scenarios are in most cases not suitable for supporting local analyses. On the other hand, locally developed scenarios may lack the global context, thus having limited comparability with or transferability to other locations. The Shared Socioeconomic Pathways, which have been primarily developed for climate impact research, provide the possibility to extend the existing global narratives and adapt them to local characteristics in order to develop locally relevant scenarios. Here, we propose a methodological framework for producing harmonized scenarios across different case studies. This framework was developed in the EVOKED project and combines elements of top-down and bottom-up approaches to develop local scenarios for five regions in northern Europe. We employ the SSP as boundary conditions and, in cooperation with stakeholders from these five regions, develop local scenarios for a range of SSP. The developed sets of scenarios are consistently informed by global developments and are therefore comparable with other downscaled scenarios developed in different regions. At the same time, they have been based on local participatory processes, thus being locally credible and relevant to the needs of stakeholders. The local scenarios constitute a climate service per se as they can raise stakeholder awareness of the processes that will drive risk, exposure, and adaptive capacity in the future and inform discussions on mitigation strategies and adaptation pathways.
Practical Recommendation of Mapping a Model for Collaboration of Health Care Facilities, Diagnostic Laboratories, and Research Institutions: Management of Drug Resistant Tuberculosis in Rural Eastern Cape
Authors: Faye Lindiwe Modest , Bokop Carine , Sineka Ncomeka , Gumede Thulani , Vasaikar Sandeep , Apalata Teke , Dlatu Ntandazo
Published: December 2023

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various drugs in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model information is based on three published manuscripts; therefore, this is a follow-up study. The model will also serve as a practical guide to monitor and evaluate epidemiological TB management plans.
Spontaneous Coronary Artery Dissection as a Cause of Acute Myocardial Infarction in COVID-19 Patients: A Case Report and Review of the Literature
Authors: Papageorgiou Angeliki , Moulias Athanasios , Papageorgiou Athanasios , Karampitsakos Theodoros , Apostolos Anastasios , Tsigkas Grigorios , Davlouros Periklis
Published: December 2023

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines’ storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, rather than thrombolysis performed, to avoid potential adverse events of the latter in the setting of SCAD.
Charting the Knowledge and Patterns of Non-steroidal Anti-inflammatory Drugs Usage in Hail Population, Saudi Arabia: Insights into the Adverse Effect Profile
Authors: Altahini Abdullah T , Aburas Waled S , Aljarwan Saud F. , Alsuwayagh Suliman A. , Alqahtani Naif F. , Alquwaiay Saleh , Anwar Sirajudheen
Published: December 2023

(1) Background: It is crucial to provide safe and knowledgeable healthcare practices because no research has been done on the knowledge and usage patterns of NSAIDs among the Hail population. (2) Method: Structured questionnaires were utilized to gather data from 399 individuals in Hail, Saudi Arabia for the cross-sectional analysis. The study assessed participants' knowledge regarding NSAIDs, patterns of use, reasons for use, and awareness of potential side effects. (3) Results: In the study, the gender distribution indicated that 170 participants (42.61%) were male, while 229 (57.39%) were female. Gender, occupation, and marital status showed non-significant associations (p>0.01), except for menstrual cycle and joint pain, where marital status displayed significant associations. Age had significant associations with muscle pain, menstrual cycle, and joint pain (p<0.01). Education and monthly income exhibited non-significant associations for all the reasons. The regression analysis demonstrated that gender played a significant role, with females having higher odds of knowledge (AOR = 1.75, 95% CI 1.10-2.88) than males. Age also had a notable impact, with individuals aged 50-59 (AOR = 0.21, 95% CI 0.07-0.66) exhibiting lower odds of knowledge. Education holding a Ph.D (AOR = 3.50, 95% CI 0.54-22.51) and business as an occupation (AOR = 6.12, 95% CI 1.10-35.10) had significantly higher odds of knowledge while housewives (AOR = 0.76, 95% CI 0.25-2.27) had lower odds. Meanwhile, >50% of the participants had knowledge of adverse events related to the use of NSAIDs while 25% had no knowledge. Moreover, 59 (25.766%) participants reported discomfort with the use of NSAIDs. In addition, 50% and >75% of participants’ considered NSAIDs can cause peptic ulcers and damage kidneys, respectively (4) Conclusions: This study shed light on the knowledge and patterns of NSAIDs use in the population of Hail, Saudi Arabia. While NSAIDs are commonly utilized for pain management, there exists a need for improved public awareness regarding potential risks and safe usage practices. Healthcare providers and policymakers should consider these insights to develop targeted educational initiatives and healthcare interventions to promote safe and informed NSAID utilization in the region.
Design Characterization and Incorporation of the Alkaline Alumino-Silicate Binder in Temperature Insulating Composites
Authors: Kryvenko Pavlo , Rudenko Igor , Konstantynovskyi Oleksandr , Gelevera Oleksandr
Published: December 2023

The paper covers the development of formulations and technology for low energy building materials based on the alkaline alumino-silicate binder and appropriate for special purposes. The microstructure of the binder was investigated using scanning electron microscopy and atomic force microscopy. The identification of the phase compositions was done by means of X-ray diffraction. By leach rate measurement and chemical analysis of pore liquid, the linkage of the alkali metal ions in water-insoluble composites was researched. The dependence of structure formation on mix design and curing conditions was investigated. Specific examples of manufacture and application of binder-based glues and adhesives have been considered, incl. ones for low-temperature insulating composite materials, heat insulation perlite-based materials, heat insulation of industrial boilers, and the fire resistant heat insulating system. The advantages of the binder-based temperature insulating composites compared to traditionally used ones are shown.
Global and Local Enhancement of Low-light Endoscopic Images
Authors: Mou En , Wang Huiqian , Yang Meifang , Cao Enling , Chen Yuanyuan , Ran Chunlan , Pang Yu
Published: December 2023

Endoscopic medical images can suffer from uneven illumination, low contrast, and lack of texture information due to the use of point directional light sources and the presence of narrow tissue structures, posing diagnostic difficulties for physicians. In this paper, a deep learning-based supervised illumination enhancement network is designed for low-light endoscopic images, aiming to improve both global illumination and local details. Initially, a global illumination enhancement module is formulated utilizing a higher-order curve function to improve global illumination. Secondly, a local feature extraction module incorporating dual attention is designed to capture local detailed features. Considering the significance of color fidelity in biomedical scenarios, the designed loss function prioritizes introducing color loss to alleviate image color distortion. Compared with seven state-of-the-art enhancement algorithms on Endo4IE endoscopic datasets, experimental results show that the proposed method can better enhance low-light endoscopic images and avoid image color distortion. It provides an efficient method to enhance images captured by endoscopes which can effectively assist clinical diagnosis and treatment.
A 3D Point Cloud Classification Method based on Adaptive Graph Convolution and Attention
Authors: Yue YaoWei , Li XiaoNan , Peng Yun
Published: December 2023

In recent years, there has been significant growth in the ubiquity and popularity of three dimensional(3D) point clouds, with an increasing focus on the classification of 3D point clouds. To extract richer features from point clouds, many researchers have turned their attention to various point set regions and channels within irregular point clouds. However, this approach has limited capability in attending to crucial regions of interest in 3D point clouds and may overlook valuable information from neighboring features during feature aggregation. Therefore, this paper proposes a novel 3D point cloud classification method based on global attention and adaptive graph convolution. The method consists of two main branches: the first branch com-putes attention masks for each point, while the second branch employs adaptive graph convolu-tion to extract global features from the point set. It dynamically learns features based on point interactions, generating adaptive kernels to effectively and precisely capture diverse relationships among points from different semantic parts. Experimental results demonstrate that the proposed model achieves 93.8% in overall accuracy and 90.8% in average accuracy on the ModeNet40 dataset.
Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11
Authors: Mathew Marilyn , Sivaprakasam Sathish , Dharmalingam-Nandagopal Gunadharini , Sennoune Souad R. , Nguyen Nhi T. , Jaramillo-Martinez Valeria , Bhutia Yangzom D. , Ganapathy Vadivel
Published: December 2023

The amino acid transporters SLC38A5 and SLC7A11 are upregulated in triple-negative breast cancer (TNBC). SLC38A5 transports glutamine, methionine, glycine and serine, and therefore activates mTOR signaling and induces epigenetic modifications. SLC7A11 transports cystine and increases cellular levels of glutathione, which protects against oxidative stress and lipid peroxidation via glutathione peroxidase, a seleno (Se)-enzyme. The primary source of Se is dietary Se-methionine (Se-Met). Since SLC38A5 transports methionine, we examined its role in Se-Met uptake in TNBC cells. We found that SLC38A5 interacts with methionine and Se-Met with comparable affinity. We also examined the influence of Se-Met on Nrf2 in TNBC cells. Se-Met activated Nrf2 and induced expression of Nrf2-target genes, including SLC7A11. Our previous work discovered niclosamide, an antiparasitic drug, as a potent inhibitor of SLC38A5. Here we found SLC7A11 to be inhibited by niclosamide with an IC50 value in the range of 0.1-0.2 M. In addition to the direct inhibition of SLC38A5 and SLC7A11, pretreatment of TNBC cells with niclosamide reduced the expression of both transporters. Niclosamide decreased glutathione levels, inhibited proliferation, suppressed GPX4 expression, increased lipid peroxidation, and induced ferroptosis in TNBC cells. It also significantly reduced the growth of the TNBC cell line MB231 in mouse xenografts.
Comparison of the Links between Tobacco Smoking, Use of Smokeless Tobacco and Periodontal Health: A Scoping Review
Authors: Olagunju Mobolaji Timothy , Abodunrin Olunike Rebecca , Alade Omolola Titilayo , Folayan Morenike Oluwatoyin
Published: December 2023

The aim of the scoping review was to map out studies that compared the effect of smoking tobacco and smokeless tobacco on periodontal health. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework. The search for articles was conducted in five electronic databases namely: Scopus, CINAHL, Web of Science, Medline, and PubMed. The search yielded two eligible articles for full-text screening. The two studies were cross-sectional in design, conducted in India and they both used bivariate analysis for comparison of the effects of tobacco smoking and the use of smokeless tobacco on the health of the periodontium without adjusting for confounders. The two studies used 10 measures to assess the health of the periodontium namely: Periodontal probing depth, clinical attachment level, gingival index, and periodontal index, plaque index score, debris index score, calculus index score, gingival inflammation, bleeding on probing and pocket depth. Periodontal probing depth, periodontal index, calculus index score and pocket depth worse for tobacco smoking when compared with smokeless tobacco users. Both studies seem to concur on worse pocket depths for tobacco smokers than for users of smokeless tobacco.
Development of a Novel Lightweight Utility Pole Using a New Hybrid Reinforced Composite—Part 2: Numerical Simulation and Design Procedure
Authors: Wu Qianjiang , Taheri Farid
Published: December 2023

The first paper of this two-part series paper discussed the development of a novel lightweight 3D wood dowel-reinforced glass epoxy hybrid composite material (3DdrFRP) and its manufacturing procedures. It also experimentally compared the performance of scaled utility poles made from conventional 2D E-glass epoxy and 3DdrFRP materials. In the second part, we developed robust finite element (FE) models in LS-DYNA, calibrated them based on experimental results, and used them to simulate the performance of equivalent 2D and 3D poles, proving the integrity of the numerical model. Additionally, we developed a simplified analytical calculation method for engi-neers to determine the stiffness of 3D-DrFRP poles accurately and quickly.
Effects of Model Specific Parameters on the Development of Custom Module in PX4 Autopilot Software-In-The-Loop
Authors: Tullu Abera , Jung Sunghun , Lee Sangchul , Ko Sangho
Published: December 2023

Software-In-The-Loop (SITL) simulation tools have been extensively used in development of safety-critical software. Utilizing these tools substantially accelerates software development eliminating potential risks and resource costs of physical experiments. This paper investigates the effects of model specific parameters on the development and testing of custom module in PX4 SITL environment. Models of a fixed-wing unmanned aerial vehicle with vertical takeoff and landing capabilities and steerable sensor platform/gimbal are used as case study for this investigation. The effects of parameters of these aerial vehicle and sensor platform models are taken into consideration in the development of custom module that controls the dynamics of steerable sensor platform mounted on the vehicle model. The work also presents steps necessary to customize PX4 SITL and Gazebo simulation environment to incorporate parameters of the vehicle and sensor platform models in the development and testing process of custom module. Based on these instances, simulation results are obtained and discussed. The results show that reliability of PX4 SITL simulation framework is justified by proper customization and integration of PX4 SITL and Gazebo simulator.
Autoimmune Hepatitis: From Evolution to Current Status: A Pathologist’s Perspective
Authors: Sakhuja Puja , Goyal Surbhi
Published: December 2023

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune mediated liver disease which progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance for young women but may be seen in children and elderly. Diagnosis requires integration of clinical, biochemical and serologic parameters along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a pre-requisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the Original Scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH.

This review article will describe the evolving diagnostic criteria for AIH with their limitations and utility, with an emphasis on the role of liver histology in diagnosis and management of AIH.
Generating Patient-Derived HCC Cell Lines Suitable for Predictive In-Vitro and In-Vivo Drug Screening by Orthotopic Transplantation
Authors: Staffeldt Lisa , Mattert Gregor , Riecken Kristoffer , Rövenstrunk Götz , Volkmar Anika , Moustafa Mohamed , Heumann Asmus , Jücker Manfred , Fehse Boris , Schumacher Udo , Lüth Stefan , Kah Janine
Published: December 2023

Hepatocellular carcinoma (HCC) results in high mortality due to ineffective systemic therapy. Human immortalized cell lines are commonly used to study anti-tumour effects in the context of new anti-tumour therapies and tumour biology. As immortalized cell lines have limited biological relevance and heterogeneity compared to primary cells, patient-derived tumour tissues and corresponding immune cells are the gold standards for studying the complexity of individual tumour entities. However, culturing primary HCC cells has a low success rate. Here, we aimed to establish a reproducible approach to preserve the patient-derived liver cancer cells for in vitro and in vivo studies. The underlying study aimed to establish an in vitro pre-screening platform to test treatment options' effectivity and dosage, e.g., for new substances, autologous modified immune cells, or combined therapies in HCC. We initially employed 15 surgical resection specimens from patients with different HCC entities for isolation and preservation. The isolated liver cancer cells from four HCC-diagnosed patients were used for orthotopic transplantation into the healthy liver of immunodeficient mice, allowing them to grow for six months before human liver cancer cells were isolated and cultured. As a result, we generated and characterized four new primary-like liver cancer cell lines. Compared to immortalized HCC cell lines, freshly generated liver cancer cells displayed individual morphologies and heterogenous protein-level characteristics. We assessed their ability to proliferate, migrate, form spheroids, and react to common medications compared to immortalized HCC cell lines. All four liver cancer cell lines exhibit strong migration and colony-forming characteristics in vitro, comparable to extensively investigated immortalized HCC cell lines. Moreover, the four etiological different liver cancer cell lines displayed differences in the response to 5-FU, Sorafenib, Axitinib and Interferon-alpha treatment, ranking from non-responders to responders depending on the applicated medication. In sum, we generated individual patient-derived liver cancer cell lines suitable for predictive in vitro drug screenings and moreover for xenograft transplantations to realize the in vivo investigation of drug candidates. We overcame the low cultivation success rate of liver cancer cells derived from patients and analyzed their potential to serve a pre-clinical model.
SARS‐COV‐2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms
Authors: Móvio Marilia Inês , Carneiro Giovana , Lopes Martines Isabella , Barros de Lima Gilmara , Sasaki Sergio Daishi , KIhara Alexandre Hiroaki , Poole Emma , Nevels Michael , Carlan da Silva Maria Cristina
Published: December 2023

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in damage to the lungs and other organs. This remarkable increase in cytokines and other inflammatory molecules is primary caused by viral proteins, in particular ORF8, a unique accessory protein specific to SARS-CoV-2. In addition to its role in cytokine induction, ORF8 is attributed with various other functions, including its ability to evade type I interferon responses. Despite the evidence, the mechanisms through which ORF8 exerts these functions remains a subject of controversy. In this mini review, we discuss the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6. We also discuss data from our studies indicating that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs).
Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia
Authors: Jang Yunseon , Koh Jeong Suk , Park Jung-Hyun , Choi Suyoung , Duong Pham Thi Thuy , Heo Bu Yeon , Lee Sang Woo , Kim Jung Yeon , Lee Myung-Won , Kim Seok-Hwan , Song Ik-Chan
Published: December 2023

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.
VRAM flap for pelvic floor reconstruction after pelvic exenteration and abdominoperineal excision
Authors: Faur Ionut Flaviu , Clim Adelina , Dobrescu Amadeus , Prodan Catalin , Hajjar Rami , Pasca Paul , Capitanio Marco , Nati Ionel , Tarta Cristi , Isaic Alexandru , Noditi George , Totolici Bogdan , Duta Ciprian , Lazar Gabriel
Published: December 2023

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.
Toxoplasma gondii Infection in Patients Submitted to Liver Transplantation
Authors: Pintos Gabriela Beltrame , Pires Francielly Camilla Bazílio Laurindo , Silva Rita Cássia Martins Alves , Silva Junior Francisco Inaldo Mendes , Zini Nathália , Da Silva Renato F , De Mattos Luiz Carlos , Brandão Cinara Cássia
Published: December 2023

Background: The liver has emerged as a frequent transplanted organ which can transmit T. gondii between seropositive donors and seronegative recipients. Associated with the immunosuppressive therapy of recipients, the presence of cysts in donor livers elevate the risk of severe toxoplasmosis in recipients. Objectives: The objective of the study was to verify the frequencies of positive serology in liver graft donors and their respective recipients, as well as to verify whether their clinical signs presented post-transplant are associated with the serological status of recipients. Patients and methods: All data on liver transplant recipients from 2008 to 2018 were obtained from the MVPeP electronic medical records of the Liver Transplant Service of FUNFARME/FAMERP. IgM and IgG anti-T. gondii antibody serology was investigated by chemiluminescence. According to the serological profile, four groups of recipients were assessed (G1: IgG-/IgM-; G2: IgG+/IgM-; G3: IgG+/IgM+, G4: IgG-/IgM+). Results: The numbers of recipients according to the serological profile groups were: G1: 20 (41.7%), G2: 26 (54.1%; G3: 2 (4.2%). No cases were found for G4. Post-transplant clinical manifestations such as fever without defined cause, lung nodules, headache, hepatosplenomegaly, encephalopathy and hepatitis (A, B and C) were reported in all groups. Conclusions: This study demonstrates that there is a high prevalence of T. gondii infection in liver recipients and, therefore, screening should be intensified. Furthermore, a high incidence of co-infection with hepatitis A was identified especially in patients who died in the post-transplant period.
Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?
Authors: Lonez Caroline , Breman Eytan
Published: December 2023

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this therapy to other malignancies and broader patient populations. However, several limitations remain, including those associated with the time-consuming and highly personalized manufacturing of autologous CAR-Ts. Technologies to establish “off-the-shelf” allogeneic CAR-Ts with low alloreactivity are currently being developed, with a strong focus on gene editing technologies. Although these technologies have many advantages, they have also strong limitations including double-strand breaks in the DNA with associated multiple safety risks as well as the lack of modulation. As an alternative, non-gene editing technologies provide an interesting approach to support the development of allogeneic CAR-Ts in the future, with possibilities of fine-tuning gene expression and easy development. Here we will review the different ways allogeneic CAR-Ts can be manufactured and discuss which technologies are currently used. The biggest hurdles for successful therapy of allogeneic CAR-Ts will be summarized and finally an overview of the current clinical evidence for allogeneic CAR-Ts in comparison to its autologous counterpart will be given.
Transcriptomic Analysis of CRISPR/Cas9-Mediated TDP1-Knockout HEK293A Cells
Authors: Dyrkheeva Nadezhda S. , Zakharenko Alexandra L. , Malakhova Anastasia A. , Okorokova Larisa S. , Shtokalo Dmitry N. , Medvedev Sergey P. , Tupikin Alexey A. , Kabilov Marsel R. , Lavrik Olga I.
Published: December 2023

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.
The Comminution of Chert Gravel by Microwave Irradiation for Reuse Optimization of Quarry Areas
Authors: Tzibulsky Mark , Frid Vladimir
Published: December 2023

Chert rock is a by-product of sand quarrying (about 40% in the geological section). All attempts to use ordinary technologies for aggregate production from chert have been economically unsuccessful, resulting in significant chert "waste" accumulation covering vast quarry areas. This paper presents the study results of the effect of microwave irradiation on the mechanical properties of chert gravel, which is mineralogically relatively homogenous and consists of fine quartz grains. The results show that an increase in irradiation time decreases the strength of chert gravel (by a factor of 4-6 for the 2.5 min of irradiation), while the quenching changes the fractional content of the samples after the crushing test, decreasing the Gravel-to-Sand ratio.
Structured Program for Developing Psychomotor Skills of Institutionalized Children with SEN
Authors: Daniel Rosu , Florin Cojanu , Paul Visan Florinel , Nicoleta Samarescu , Augustina Ene Mariana , Ioan Muntean Raul , Vasile Ursu Emil
Published: December 2023

Adapted and personalized motor activities prove to be effective for meeting the specific needs of children with SEN, tailoring to their unique limitations and abilities. Our focus was to craft and apply a structured program for psychomotor abilities development, targeting balance and motor-cognitive skills. The study aims to enhance the behavior and psychomotor manifestations of 28 students with SEN (aged 12-14) from two institutional centers in Romania. The "Sfântul Ștelian" Inclusive Education School Center of Costesti, Arges (CC-12 subjects), and the "Sfânta Filofteia" Inclusive Education School Center of Ștefănești (CS-16 subjects). Across a 36-week training regimen, participants engaged in sessions lasting 30 minutes, twice weekly. Evaluation of their psychomotor skills involved a battery of tests: assessing balance, both with eyes open and closed, brain processing speed, upper limb motor laterality. Initial and final data were gathered to assess their motor development and physical state. Instruments utilized included the Optojump Next optical system for movement analysis, Witty SEM intelligent semaphore, Sensamove balance miniboard. Statistical analysis compared the initial and final assessments using the Kolmogorov-Smirnov test and Wilcoxon Z test. Out of the total comparisons made between the initial and final assessments for the evaluation of the psychomotor component, statistically significant differences were found in only 37.5% of these comparisons.
Life History Traits of Aedes aegypti across Different Climatic Zones of Burkina Faso
Authors: Sanon Aboubakar , Wang Lanjiao , Moungou Abakoudjiga Arsene , Delang Leen , Badolo Athanase
Published: December 2023

Aedes aegypti is the main vector of various arboviruses including dengue, yellow fever, Zika and chikungunya virus. This mosquito species originated in Africa but has a wide range of distribution, colonising various ecological zones. The transmission dynamics of arboviruses depends on environmental factors, but also on mosquito life history traits including development time, fecundity, and longevity. The objective of the current study was to assess the Aedes aegypti immature development time, adult longevity, fecundity and body variation from different sampling localities. Aedes aegypti mosquitoes were collected as eggs from different geographical zones and cohorts of mosquitoes were reared in standardized laboratory conditions to assess the life history traits parameters. Emerged adults were discriminated into morphotypes according to the density of white scales on the first abdominal tergite. The means of fecundity, longevity, development time and body size were assessed, and linear models were fitted to the traits parameters to assess the effects of other covariables. Average Aedes aegypti development time was estimated to 7.35 days; 7.40 days; 6.98 days and 7.40 days respectively for Dori, 1200 logements, Bobo-Dioulasso and Toudweogo. The fecundity did not vary across study sites and was not associated with the body size. The longevity varied according to the study sites with the mosquitoes from Bobo-Dioulasso having the longest longevity while the shortest longevity was found at Dori. Fed mosquitoes had longer longevity compared to unfed ones. Morphological identification showed that Aedes aegypti aegypti-like mosquitoes were more predominant than Aedes aegypti formosus-like mosquitoes in all the study sites, suggesting the predominance of Aedes aegypti in the urban environment. Our data suggest that the geographical origin of Aedes aegypti mosquitoes in Burkina Faso has a little effect on its life history traits.
A Data-Driven Approach to Team Formation in Software Engineering Based on Personality Traits
Authors: Vasiljević Jan , Lavbič Dejan
Published: December 2023

Collaboration among individuals with diverse skills and personalities is crucial in producing high-quality software. The success of any software project depends on the team’s cohesive functionality and mutual complementation. This study introduces a data-centric methodology for forming Software Engineering (SE) teams centred around personality traits. Our study analyzed data from an SE course where 157 students in 31 teams worked through four project phases and were evaluated based on deliverables and instructor feedback. Using the Five Factor Model (FFM) and a variety of statistical tests, we determined that teams with higher levels of extraversion and conscientiousness and lower neuroticism consistently performed better. We examined team member interactions and developed a predictive model using extreme gradient boosting. The model achieved a 74% accuracy rate in predicting inter-member satisfaction rankings. Through graphical explainability, it underscored incompatibilities among members, notably those with differing levels of extraversion. Based on our findings, we introduce a team formation algorithm using Simulated Annealing (SA), built upon the insights from our predictive model and additional heuristics.
Stress Resilience (Proprioceptive and Verbal Individual Differences) in Onco-Patients, Sportsmen and Controls
Authors: Liutsko Liudmila , Malova Yulia V. , Vinokurova Ekaterina , Polikanova Irina , Poddubnij Sergey E. , Muinos Ruben , Leonov Sergey , Gutierrez-Maldonado José
Published: December 2023

The characteristics of response to stressful situations depend on a complex of factors such as personality traits, emotional regulation, health state, features of the nervous system, motor functions and proprioception. In cases of disruption of the brain's dopamine system due to disease or chemotherapy, hormone discharge due to stress, changes in emotions and proprioception may occur. The aim of our study was to find the relationship of stress resilence in verbal test and individual differences performed in proprioceptive test in onco-patients, sportsmen and group of control; as well as to observe the differences between these groups in the verbal stress resistance and individual differences proprioceptive tests. The results showed that onco-patients were less resistant as per verbal stress resistance outcomes for a major part of variables compared to other groups. The sportsmen were superior in verbal Risk and Control dimensions compared to other groups; but less in Positive Affectiveness. The proprioceptive test perfomance revealed the only statistically significant difference in performance in the dimension related to Mood, showing more Pessimism in the sportsmen group, but more Optimism in the oncopatients at temperamental (or intrisinc) level. The obtained results can be used by psychologists, therapists, coach and healthcare when needed to attend the specific needs of public, being pateints or sportsmen, etc.
Steroid Metabolome Analysis in Dichorionic Diamniotic Twin Pregnancy
Authors: Černý Andrej , Hill Martin , Vosatkova Michala , Laštůvka Zdeněk , Pařízek Antonín
Published: December 2023

Steroid hormones have diverse roles in pregnancy; some, such as progesterone and its metabolites, help stabilise pregnancy and can very likely influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies, such as premature delivery, preeclampsia, and intrahepatic cholestasis. To date, only a few studies have performed steroid analysis in multiple pregnancies. However, these studies offered a limited analysis of the steroidome in children and mothers with multiple pregnancies. Our team and a team from the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group and singleton pregnancies as the control group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35+3 to 39+3 weeks, while it was 38+1 to 41+1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies.
Harnessing Nanotechnology for Improved Treatment for Inflammatory Cardiovascular Disorders
Authors: Fareed Muhammad , Förster Carola Yvette , Shityakov Sergey
Published: December 2023

Cardiovascular disease (CVD) accounts for nearly one-third of all global fatalities, establishing itself as a leading cause of death. To address this pressing issue, there is a growing demand for improved diagnostic methods and secure, non-invasive imaging techniques that can deliver precise insights into the progression of CVD. The success of personalized therapy for CVD depends on a couple of critical factors: accurate diagnosis and early detection. Therapeutic options for conditions like CVD, which develop over several decades, are highly specific to the individual's condition and the stage of the disease. In the field of biomedicine, nanotechnology has become increasingly prominent as a tool with diverse applications, including diagnostics, biosensing, and drug delivery. This review article offers an in-depth look at the most recent developments in the utilization of nanotechnology for detecting and managing prevalent cardiovascular diseases, providing valuable insights into this crucial area of healthcare research.
Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism
Authors: Nasheuer Heinz P. , Meaney Anna Marie , Hulshoff Timothy , Thiele Ines , Onwubiko Nichodemus O.
Published: December 2023

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.
Oscillation Resynchronization in a Photosensitive Reaction-Diffusion System
Authors: Shi Da , Tan YuJin , Zhang Qian , Ren Lin
Published: December 2023

: Oscillation synchronization through diffusion-based communication of active materials can lead to emergence of diverse patterns and collective behaviors. A detailed general description of the formation process of synchronization or resynchronization dynamics is a challenging task. We employ a photosensitive Belousov-Zhabotinsky reaction-diffusion model (within a gel media) to investigate the recovery process of oscillation synchronization between a pair of gel patches. The recovery time for oscillation resynchronization can be modulated by patch-distance, species of signaling molecules, intensity and duration of illumination. Analysis reveals that the “switch effect” of the gel-distance and the “promotion effect” from illumination on the oscillation resynchronization originate from the competition between processes of photo-promotion of oscillation, diffusion of signaling molecules (HBrO2 and Br-) and disproportionation of HBrO2. These results will benefit studies on bio-inspired active materials and soft motors.
Endometrial CAFs Resist Effect of Antitumor Drugs In A Patient-Derived 2-Cell Hybrid Co-Culture Model
Authors: Sulaiman Raed , Aske Jennifer C , Lin Xiaoqian , Dale Adam , Gaster Kris , Espaillat Luis Rojas , Starks David , De Pradip , Dey Nandini
Published: December 2023

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.