Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Spectrum of VEGF Inhibitors’ Toxicities from Systemic to Intra-Vitreal Usage in Medical Practice

Simple Summary Vascular Endothelial Growth Factor inhibitors (VEGFi), commonly employed for diverse medical conditions such as advanced neoplasms and ocular diseases, pose potential adverse effects. This review delineates the principal VEGFi utilized in clinical practice and investigates the causes, recognition, management, and prevention of VEGFi toxicities. Its aim is to assist oncologists in both clinical practice and the design of clinical trials. Abstract The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field of medicine, given the high incidence of various pathological conditions necessitating VEGF inhibition within the general population. These conditions encompass a range of advanced neoplasms, such as colorectal cancer, non-small cell lung cancer, renal cancer, ovarian cancer, and others, along with ocular diseases. The utilization of VEGFi is not without potential risks and adverse effects, requiring healthcare providers to be well-prepared for identification and management. VEGFi can be broadly categorized into two groups: antibodies or chimeric proteins that specifically target VEGF (bevacizumab, ramucirumab, aflibercept, ranibizumab, and brolucizumab) and non-selective and selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed to impede intracellular signaling of the VEGF receptor (RTKi, receptor tyrosine kinase inhibitors). The presentation and mechanisms of adverse effects resulting from VEGFi depend primarily on this distinction and the route of drug administration (systemic or intra-vitreal). This review provides a thorough examination of the causes, recognition, management, and preventive strategies for VEGFi toxicities with the goal of offering support to oncologists in both clinical practice and the design of clinical trials.
Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

Alzheimer’s disease and Parkinson’s disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central nervous system responsible for severe disability. An aberrant immune response is the cause of myelin destruction that covers axons in the brain, spinal cord, and optic nerves. Systemic lupus erythematosus is an autoimmune disease characterized by alteration of B cell activation, while Sjögren’s syndrome is a heterogeneous autoimmune disease characterized by altered immune responses. The etiology of all these diseases is very complex, including an interrelationship between genetic factors, principally immune associated genes, and environmental factors such as infectious agents. However, neurodegenerative and autoimmune diseases share proinflammatory signatures and a perturbation of adaptive immunity that might be influenced by herpesviruses. Therefore, they might play a critical role in the disease pathogenesis. The aim of this review was to summarize the principal findings that link herpesviruses to both neurodegenerative and autoimmune diseases; moreover, briefly underlining the potential therapeutic approach of virus vaccination and antivirals.
Overcoming Chemotherapy Resistance in Metastatic Cancer: A Comprehensive Review

The management of metastatic cancer is complicated by chemotherapy resistance. This manuscript provides a comprehensive academic review of strategies to overcome chemotherapy resistance in metastatic cancer. The manuscript presents background information on chemotherapy resistance in metastatic cancer cells, highlighting its clinical significance and the current challenges associated with using chemotherapy to treat metastatic cancer. The manuscript delves into the molecular mechanisms underlying chemotherapy resistance in subsequent sections. It discusses the genetic alterations, mutations, and epigenetic modifications that contribute to the development of resistance. Additionally, the role of altered drug metabolism and efflux mechanisms, as well as the activation of survival pathways and evasion of cell death, are explored in detail. The strategies to overcome chemotherapy resistance are thoroughly examined, covering various approaches that have shown promise. These include combination therapy approaches, targeted therapies, immunotherapeutic strategies, and the repurposing of existing drugs. Each strategy is discussed in terms of its rationale and potential effectiveness. Strategies for early detection and monitoring of chemotherapy drug resistance, rational drug design vis-a-vis personalized medicine approaches, the role of predictive biomarkers in guiding treatment decisions, and the importance of lifestyle modifications and supportive therapies in improving treatment outcomes are discussed. Lastly, the manuscript outlines the clinical implications of the discussed strategies. It provides insights into ongoing clinical trials and emerging therapies that address chemotherapy resistance in metastatic cancer cells. The manuscript also explores the challenges and opportunities in translating laboratory findings into clinical practice and identifies potential future directions and novel therapeutic avenues. This comprehensive review provides a detailed analysis of strategies to overcome chemotherapy resistance in metastatic cancer. It emphasizes the importance of understanding the molecular mechanisms underlying resistance and presents a range of approaches for addressing this critical issue in treating metastatic cancer.
Collagen Matrix to Restore the Tympanic Membrane: Developing a Novel Platform to Treat Perforations

Modern otology faces challenges in treating tympanic membrane (TM) perforations. Instead of surgical intervention, alternative treatments using biomaterials are emerging. Recently, we developed a robust collagen membrane using semipermeable barrier-assisted electrophoretic deposition (SBA-EPD). In this study, a collagen graft shaped like a sponge through SBA-EPD was used to treat acute and chronic TM perforations in a chinchilla model. A total of 24 ears from 12 adult male chinchillas were used in the study. They were organized into four groups. The first two groups had acute TM perforations and the last two had chronic TM perforations. We used the first and third groups as controls, meaning they did not receive the implant treatment. The second and fourth groups, however, were treated with the collagen graft implant. Otoscopic assessments were conducted on days 14 and 35, with histological evaluations and TM vibrational studies performed on day 35. The groups treated with the collagen graft showed fewer inflammatory changes, improved structural recovery, and nearly normal TM vibrational properties compared to the controls. The porous collagen scaffold successfully enhanced TM regeneration, showing high biocompatibility and biodegradation potential. These findings could pave the way for clinical trials and present a new approach for treating TM perforations.
Implantation and Decidualization in PCOS: Unraveling the Complexities of Pregnancy

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, affecting 5–15% globally with a large proportion undiagnosed. This review explores the multifaceted nature of PCOS and its impact on pregnancy, including challenges in fertility due to hormonal imbalances and insulin resistance. Despite restoring ovulation pharmacologically, women with PCOS face lower pregnancy rates and higher risks of implantation failure and miscarriage. Our review focuses on the complexities of hormonal and metabolic imbalances that impair endometrial receptivity and decidualization in PCOS. Disrupted estrogen signaling, reduced integrity of endometrial epithelial tight junctions, and insulin resistance impair the window of endometrial receptivity. Furthermore, progesterone resistance adversely affects decidualization. Our review also examines the roles of various immune cells and inflammatory processes in the endometrium, contributing to the condition’s reproductive challenges. Lastly, we discuss the use of rodent models in understanding PCOS, particularly those induced by hormonal interventions, offering insights into the syndrome’s impact on pregnancy and potential treatments. This comprehensive review underscores the need for advanced understanding and treatment strategies to address the reproductive complications associated with PCOS, emphasizing its intricate interplay of hormonal, metabolic, and immune factors.
Dynamics of land acquisition, challenges and opportunities by the Ganga expressway project in North India: A case study

The ongoing developmental projects in India require land in terms of both quantity and quality. An acquisition of land causes large scale displacement of people, most of which are farmers who lose their land and thus their livelihood, as three-fourth of the country’s population lives in countryside and agriculture is the only livelihood option. The Ganga Expressway Project launched by the government of Uttar Pradesh to construct eight lane expressway connecting 20 districts and 36 sub-districts along the banks of the river Ganga with other parts of the state. This expressway project will be the longest (1047Km in length) and costliest one in the country that will cover about 15,000 hectares of rural land. The present study was under taken in a sampled village of Aligarh district to find out the problems and future prospects for the people directly influenced by the project. The study envisages the impact of the project on land market of the catchments’. The study results out that how much of the project is welcomed by the farmers of the village who not only lose the land but also their livelihood.
Prevalence of Toxoplasma gondii IgG Antibodies and Associated Risk Factors in Psychiatric Patients from Western Romania: A Cross-Sectional Study

Infection with the coccidian parasite Toxoplasma gondii was associated with an increased risk of several mental disorders. We conducted a case–control study of 464 consecutive psychiatric patients and assessed the prevalence of IgG antibodies against T. gondii and the potential risk factors associated with infection. T. gondii-specific antibodies were determined using a chemiluminescence assay. A questionnaire was utilized to assess the potential correlation between risk factors and Toxoplasma gondii seropositivity. IgG antibodies were found in 325 (70.04%) of the patients. We observed a higher likelihood of positive IgG antibodies against Toxoplasma gondii in older individuals, patients residing in rural areas, and females. We also noted associations between Toxoplasma gondii infection and certain risk factors, like activities that involve contact with soil, low-income levels, and limited educational attainment. Our findings indicate a high prevalence of T. gondii infection among psychiatric patients from Western Romania and provide new information regarding the potential risk factors associated with T. gondii in this population group. This study may serve as a foundation for future research and the development of preventive strategies.
Methodological Challenges and Confounders in Research on the Effects of Ketogenic Diets: A Literature Review of Meta-Analyses

Several meta-analyses have found a positive association between a popular type of “fad diet”, ketogenic diets, and their effect on anthropometric and blood parameters. However, the non-specific inclusion criteria for meta-analyses may lead to incorrect conclusions. The aim of this literature review is to highlight the main confounders and methodological pitfalls of meta-analyses on ketogenic diets by inspecting the presence of key inclusion criteria. The PubMed, Embase, and Web of Science databases and the Cochrane Database of Systematic Reviews were searched for meta-analyses. Most meta-analyses did not define the essential parameters of a ketogenic diet (i.e., calories, macronutrient ratio, types of fatty acids, ketone bodies, etc.) as inclusion criteria. Of the 28 included meta-analyses, few addressed collecting real, re-measured nutritional data from the ketogenic diet and control groups in parallel with the pre-designed nutritional data. Most meta-analyses reported positive results in favor of ketogenic diets, which can result in erroneous conclusions considering the numerous methodological pitfalls and confounders. Well-designed clinical trials with comparable results and their meta-analyses are needed. Until then, medical professionals should not recommend ketogenic diets as a form of weight loss when other well-known dietary options have been shown to be healthy and effective.
Diversity of Culturable Bacteria from the Coral Reef Areas in the South China Sea and Their Agar-Degrading Abilities

The South China Sea (SCS) is abundant in marine microbial resources with high primary productivity, which is crucial for sustaining the coral reef ecosystem and the carbon cycle. Currently, research on the diversity of culturable bacteria in the SCS is relatively extensive, yet the culturable bacteria in coral reefs has been poorly understood. In this study, we analyzed the bacterial community structure of seawater samples among Daya Bay (Fujian Province), Qionghai (Hainan Province), Xisha Islands, and the southern South China Sea based on culturable methods and detected their abilities for agar degradation. There were 441 bacterial strains, belonging to three phyla, five classes, 43 genera, and 101 species, which were isolated by marine agar 2216E (MA; Becton Dickinson). Strains within Gammaproteobacteria were the dominant group, accounting for 89.6% of the total bacterial isolates. To investigate vibrios, which usually correlated with coral health, 348 isolates were obtained from TCBS agar, and all isolates were identified into three phylum, three classes, 14 orders, 25 families, and 48 genera. Strains belonging to the genus Vibrio had the greatest number (294 strains), indicating the high selectivity of TCBS agar for vibrios. Furthermore, nineteen strains were identified as potentially novel species according to the low 16S rRNA gene similarity (<98.65%), and 28 strains (15 species) had agar-degrading ability. These results indicate a high diversity of culturable bacteria in the SCS and a huge possibility to find novel and agar-degrading species. Our study provides valuable microbial resources to maintain the stability of coral ecosystems and investigate their roles in the marine carbon cycle.
Maternal Visceral Fat in Prediction of Gestational Diabetes Mellitus

Objective: To determine the diagnostic performance of maternal abdominal visceral adipose tissue thickness, measured by ultrasound, in predicting gestational diabetes mellitus (GDM). Patients and methods: A prospective diagnostic study was conducted on low-risk pregnant women attending our antenatal care clinic. All underwent abdominal visceral adipose tissue (VAT) measurement by two-dimension transabdominal ultrasound twice, at late first trimester (gestational age: GA 11–14 weeks) and second trimester (GA 18–22 weeks). All patients underwent a two-step approach for screening and diagnosis of GDM between GA 24 and 28 weeks. Results: A total of 141 women were recruited into the study; including 32 (22.7%) women with GDM, and 109 (77.3%) women of non-GDM, between GA 24 and 28 weeks. The means VAT at the 1st, 2nd trimester and the difference of VAT of GDM group were 4.0 ± 0.27 cm, 5.7 ± 1.12 cm, and 1.6 ± 0.91 cm respectively. The means VAT at 1st, 2nd trimester and the difference of VAT of non-GDM group were 3.8 ± 1.01 cm, 5.4 ± 1.07 cm, and 1.6 ± 1.12 cm respectively. There were no significant differences of VAT measurements (1st, 2nd and the difference) between both groups. The VAT thickness was slightly greater in the GDM group but the mean differences between 1st and 2nd trimester were comparable between the two groups. The diagnostic performance of VAT, maternal age and body mass index (BMI) in predicting GDM was comparable. Conclusion: Measurement of maternal visceral adipose thickness in early pregnancy is not effective in predicting GDM among Thai women, which is different from most studies conducted on western women. However, a trend of higher VAT in the GDM group was noted.
Predicting Braess's paradox of power grids using graph neural networks.

As an increasing number of renewable energy generators are integrated into the electrical grid, the necessity to add new transmission lines to facilitate power transfer and ensure grid stability becomes paramount. However, the addition of new transmission lines to the existing grid topology can lead to the emergence of Braess's paradox or even trigger grid failures. Hence, predicting where to add transmission lines to guarantee stable grid operation is of utmost importance. In this context, we employ deep learning to address this challenge and propose a graph neural network-based method for predicting Braess's paradox in electrical grids, framing the problem of adding new transmission lines causing Braess's paradox as a graph classification task. Taking into consideration the topological and electrical attributes of the grid, we select node features such as degree, closeness centrality, and power values. This approach assists the model in better understanding the relationships between nodes, enhancing the model's representational capabilities. Furthermore, we apply layered adaptive weighting to the output of the graph isomorphism network to emphasize the significance of hierarchical information that has a greater impact on the output, thus improving the model's generalization across electrical grids of varying scales. Experimental results on the IEEE 39, IEEE 57, and IEEE 118 standard test systems demonstrate the efficiency of the proposed method, achieving prediction accuracies of 93.8%, 88.8%, and 88.1%, respectively. Model visualization and ablation studies further validate the effectiveness of this approach.
Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient

Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1-mutated AML patient with an initial low ratio of FLT3-ITD (low-risk ELN-2017), treated with midostaurin combined with standard chemotherapy as front-line treatment, and with salvage therapy plus gilteritinib following allogenic stem cell transplantation after relapse. Simultaneous single-cell DNA sequencing and cell-surface immunophenotyping was used in diagnostic and relapse samples to understand the clinical scenario of this patient and to reconstruct the clonal composition of both tumors. Four independent clones were present before treatment: DNMT3A/DNMT3A/NPM1 (63.9%), DNMT3A/DNMT3A (13.9%), DNMT3A/DNMT3A/NPM1/FLT3 (13.8%), as well as a wild-type clone (8.3%), but only the minor clone with FLT3-ITD survived and expanded after therapy, being the most represented one (58.6%) at relapse. FLT3-ITD was subclonal and was found only in the myeloid blast population (CD38/CD117/CD123). Our study shows the usefulness of this approach to reveal the clonal architecture of the leukemia and the identification of small subclones at diagnosis and relapse that may explain how the neoplastic cells can escape from the activity of different treatments in a stepwise process that impedes the disease cure despite different stages of complete remission.
Finnish Centre of Excellence in Physics, Chemistry, Biology and Meteorology of Atmospheric Composition and Climate Change

markku Kulmala1)*, hanna K. lappalainen1)2), Jaana Back1)3), ari laaksonen2)4), eero nikinmaa3), marja-liisa riekkola5), timo vesala1), Yrjo viisanen2), tuula aalto2), michael Boy1), miikka Dal maso6), mikael ehn1), hannele hakola2), Pertti hari3), Kari hartonen5), Kaarle hameri1), teemu holtta1)3), heikki Junninen1), leena Jarvi1), theo Kurten1)5), antti lauri1), tuomas laurila2), Katrianne lehtipalo1)7), heikki lihavainen2), anna lintunen3), ivan mammarella1), hanna e. manninen1), tuukka Petaja1), mari Pihlatie1), Jukka Pumpanen3), Janne rinne1), sami romakkaniemi4), taina ruuskanen1), mikko sipila1), sanna sorvari1)2), hanna vehkamaki1), annele virtanen4), Douglas r. Worsnop1)2)4)8) and veli-matti Kerminen1)
Analysis of the exposure of Polish lakes to flood risk

Abstract Flooding constitutes one of the main natural hazards in Poland, which causes enormous social, economic and environmental losses. The main causes of the occurrence of floods include intensive rainfall, rapid melting of snow and ice cover, as well as strong gusts of wind from the sea. Based on the resilience theory (resistance, elasticity), which constitutes an efficient tool for the description of the social-ecological system capability or components thereof to mitigate the effects of dangerous events, as well as the capability of reconstructing and adapting the system to new conditions, the authors have analysed the exposure of Polish lakes to flood risks with a probability of occurrence Q0.2%, Q1% and Q10%. In order to determine the level of exposure of lakes to the risk of flooding by flood waters, studies were conducted using the flood hazard and flood risk maps which were developed under the Project entitled “IT System of the Country’s Protection against Extreme Hazards”. The result of the efforts of the group of authors is the determination of the number of lakes, which are located in the flood risk area Q0.2%, Q1% and Q10%, including division into risk level groups (low, moderate and high). The results presented in the paper may constitute a contribution to further, more detailed studies concerning assessment of the vulnerability of Polish lakes located in the flood prone area.
Optimizing Optical Dielectrophoretic (ODEP) Performance: Position- and Size-Dependent Droplet Manipulation in an Open-Chamber Oil Medium

An optimization study is presented to enhance optical dielectrophoretic (ODEP) performance for effective manipulation of an oil-immersed droplet in the floating electrode optoelectronic tweezers (FEOET) device. This study focuses on understanding how the droplet’s position and size, relative to light illumination, affect the maximum ODEP force. Numerical simulations identified the characteristic length (Lc) of the electric field as a pivotal factor, representing the location of peak field strength. Utilizing 3D finite element simulations, the ODEP force is calculated through the Maxwell stress tensor by integrating the electric field strength over the droplet’s surface and then analyzed as a function of the droplet’s position and size normalized to Lc. Our findings reveal that the optimal position is xopt = Lc + r, (with r being the droplet radius), while the optimal droplet size is ropt = 5Lc, maximizing light-induced field perturbation around the droplet. Experimental validations involving the tracking of droplet dynamics corroborated these findings. Especially, a droplet sized at r = 5Lc demonstrated the greatest optical actuation by performing the longest travel distance of 13.5 mm with its highest moving speed of 6.15 mm/s, when it was initially positioned at x0 = Lc + r = 6Lc from the light’s center. These results align well with our simulations, confirming the criticality of both the position (xopt) and size (ropt) for maximizing ODEP force. This study not only provides a deeper understanding of the position- and size-dependent parameters for effective droplet manipulation in FEOET systems, but also advances the development of low-cost, disposable, lab-on-a-chip (LOC) devices for multiplexed biological and biochemical analyses.