bluuebunny/crossref_metadata_2025 huggingface dataset:
N-methyladenosine-modified PIAS1 promotes microglia polarization to M1 by regulating PPARγ SUMOylation in Inflammatory Bowel Disease-associated hyperalgesia
Authors: Huang Yulin , Xu Rui , Hou Bailing , Sun Yu’e , Mao Yanting , Yang Yan , Gu Xiaoping , Zhang Wei , Ma Zhengliang
Published: September 2023

Background and Aims: Large number of nociceptive signals produced by intestinal inflammation are transmitted to the spinal dorsal horn, leading to microglia polarization, which is of great significance in mediating central sensitization. Emerging evidence indicate that m6A modification regulates a dynamic macrophage polarization. However, it remains unsolved to link polarization of microglia regulated by m6a modification to inflammatory bowel disease (IBD) associated hyperalgesia. Methods IBD-induced hyperalgesia was assessed by paw withdrawal mechanical threshold in a murine colitis model induced by dextran sulphate sodium (DSS). MeRIP sequence was performed on the LPS-treated primary microglia. The biological role and mechanism of m6A modified PIAS1 in microglia polarization and central sensitization were determinedin vitroandin vivo. Results The level of m6A RNA was significantly increased in the spinal dorsal cord of colitis mice, accompanied by microglia polarization to M1-proinflammatory phenotype, and METTL3 was the main regulator involved in the abundant m6A RNA modification. Moreover, MeRIP sequence identified PIAS1 acts anti-inflammatory function though promoting PPARγ SUMOylation in regulating microglia polarization. Mechanistically, the m6A reader YTHDF2 directly recognized and bound to the m6A site on PIAS1 mRNA and reduced PIAS1 mRNA stability. Overexpression YTHDF2 decreased PIAS1 mRNA level and promoted the polarization to M1-phenotypein vitro. Finally, reduced m6A modification by specific downregulation METTL3 in microglia of the spinal dorsal horn contributes to alleviate IBD-associated hyperalgesia. Conclusions The mRNA stabilization of m6A-modified PIAS1-mediated PPARγ SUMOylation as the underlying mechanism through which METTL3 preserved M1-phenotype microglia contributes to IBD-associated hyperalgesia.
Revelation of inherent trends in Mucormycosis resurgence in India: A comparative analysis of past prevalence (pre-Covid-19) and current outbreaks
Authors: Pant Pratibha , Pant Prashant , Rajpal Vijay Rani , Singh Apekshita , Arya Harshit , Sonkar Anand , Chandra Atika , Raina Soom Nath
Published: September 2023

Mucormycosis (MM), commonly referred to as ‘Black Fungus’ was a relatively lesser-known fungal infection until the onset of Covid-19 pandemic. However, amidst the global Covid-19 outbreak, it emerged as a widespread fungal infection causing significant morbidity and mortality. In India, the recorded incidence of MM was approximately 80% higher than in the rest of the world due to a higher prevalence of specific pre-disposing factors, causal organisms, clinical manifestations, and intriguing epidemiological trends. This study compared the MM case-control studies conducted in India before the Covid-19 pandemic and during the current pandemic to comprehend the impact of Covid-19 on the surge in MM cases. Our findings demonstrate that MM is a distinct condition which is not solely dependent on Covid-19. Interestingly, the trends of association of MM with comorbidities like diabetes and its greater prevalence in male gender remains consistent in both study periods. The increased occurrence of MM in India during the current pandemic appears to be more intricately linked to challenges in management and treatment of Covid-19, leading to emergence of novel predisposing factors. The indiscriminate use of steroids, immunosuppressants, and the resultant hyperglycemic condition, especially in a population already burdened with diabetes as comorbidity contributed significantly to the current MM havoc. The study suggests that raising general awareness about preventive measures, diabetes management and the regulation of steroid drug misuse can play a crucial role in curtailing the development and spread of deadly infections like MM in future.
Ginsenoside rb2 regulates tissue autophagy in the ischemic penumbra area and delays BMSC senescence by improving the ischemic-hypoxic microenvironment
Authors: WANG SHIQI , Hui Xiao-shan , Zhang Hao , Zhang Hui , Zhang Chen-ming , Zhang Jin-sheng , Xie Fei
Published: September 2023

Introduction: Ischemic cardiovascular disease (CVD), is associated with high morbidity and mortality. Panax notoginseng (PNS) has some advantages in improving ischemic cardiovascular diseases, but the mechanism of action of its active ingredient ginsenoside Rb2 is not clear.
Methods: In this study, network pharmacology, molecular docking, and LC-MS/MS were used to evaluate the relationship between PNS and its main active constituent and autophagy. In vivo and in vitro investigations were then used to further confirm the results.
Results: In this investigation, we discovered that the primary active component of PNS, ginsenoside Rb2, might increase tissue autophagy in myocardial infarction rat models' ischemic semidark zone. In the cell model, ginsenoside Rb2 boosted the proliferation rate and decreased the apoptosis rate of bone marrow mesenchymal stem cells (BMSCs). And alleviated oxidative stress, delayed aging, raised GATA4mRNA, lowered cTNTmRNA levels, and protected BMSCs from the harm brought on by ischemic-hypoxic injury.
Discussion: Our research initially established an ischemic-hypoxic cell model, which may be provided as a reference for related research. And clarified the functions of ginsenoside Rb2 in the ischemic-hypoxic microenvironment, which may be conducive to the exploration of therapeutic targets of ischemic CVD.
Improvement in methane concentration in the biogas produced through the co-digestion of waste from the seafood restaurant industry and mezcal vinasses.
Authors: Sagrero Kathia Amital Lemus , Carmen Chávez-Parga Ma. Del , Cortés José Apolinar
Published: September 2023

The release of waste by the mezcal and seafood restaurant industries, due to their characteristics, generates adverse effects on soils, bodies of water, and air. An important aspect of anaerobic digestion is having an inoculum whose microbial consortium is in suitable conditions for carrying out the anaerobic process in its four stages. Applying the combined pretreatments (chemical, thermal, and volumetric ratio of waste) modifies its bioavailability and, consequently, its consumption rate by the microorganisms in the anaerobic inoculum. This research focused on evaluating the strategy of having an enriched inoculum, co-digestion of waste, and applying pretreatments to methane production in the biogas produced through the BMP test. The development of the tests was carried out considering a Taguchi L4 orthogonal experimental design for the variables in two levels of pretreatment: by temperature, volumetric ratio of waste from the restaurant industry of seafood waste and mezcal vinasses, and chemical by pH adjustment, for an initial concentration of residue mixture of 18 g VS L-1; the monitoring variables were biogas production, methane concentration, volatile solid, pH, conductivity, and alkalinity. The results show that the enriched inoculum used in the test had a pH of 8.18, a conductivity of 19.24 mS cm-1, an alkalinity of 31 g CaCO3 L-1, and an alpha (α) ratio of 0.75; the time in which the BMP test was carried out was of the order of 29 days. At the best test, with pretreatment at a temperature of 50°C, a residue ratio of 1 VSW/ 2 VMV, and a pH of 6.5, a production of 1420.51 ± 0.038 N mL CH4 and an 82.3 % CH4 concentration in the biogas were reached, with a yield of 175.37 N mL CH4 g-1 VS and a degradation constant of 0.14 d-1.
Role of NLRP3 inflammasomes in monocyte and microglial recruitments in choroidal neovascularization
Authors: Dieckmann Blake W. , Paguaga Marcell E. , McCollum Gary W. , Penn John S. , Uddin Imam
Published: September 2023

Though the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2RFPCx3cr1GFP dual-reporter mice to characterize migration of Ccr2RFP positive monocytes and Cx3cr1GFP positive microglial cells into CNV lesions after laser-induced rupture of Bruch’s membrane. MCC950 was used as NLRP3 inhibitor. Immunostaining was used to confirm localization of NLRP3 inflammasomes in the LCNV lesions. Confocal microscopy was used to image and quantify LCNV volumes. ELISA and qRT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1β protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (-/-) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that RFP positive monocyte-derived macrophages and GFP positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post-laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2RFP positive macrophages, Cx3cr1GFP positive microglia, and other cells resulting in an increase in total lesion size. NLRP3 (-/-) LCNV mice, showed significantly increased lesion size compared to age-matched controls. Inhibition of NLRP3, resulted in decreased IL-1β mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1β.
The anxiety caused by long-term low-dose ketamine, and related metabolomics characteristics change in rat
Authors: Fu Yingqiang , Zou Jing , Zhao Wensong , Yang Hong , Xiao Li , Sun Yiming , Jiang Zihan , Lin Yao , Ye Yi , Ma Chunling , Liao Linchuan
Published: September 2023

Ketamine is a kind of dissociation anesthesia, clinical studies have demonstrated the ability of ketamine to induce rapid and sustained antidepressant actions. However, considering the side effects such as dissociative properties, psychotomimetic effect, neurotoxicity, and abuse potential, the safety profile of prolonged use of ketamine still needs to be investigated. To investigate the effects of repeated administration of low-dose ketamine on locomotor activity, and mood changes in rats. To explore the metabolome and metabolic pathway change in plasma, and prefrontal cortex of rats after chronic administration and withdrawal of low-dose ketamine.To provide evidence for toxicity studies of ketamine as an antidepressant. Rat’s behavior changes induced by ketamine administration and withdrawal were observed by elevated plus-maze experiments. Untargeted metabolomics analysis of rat plasma and prefrontal cortex tissues was performed by UHPLC-QE/MS to screen differential expression metabolites and explore differential metabolic pathways. The number of entries into (0.80 ± 1.17 times, p < 0.05) and duration in (12.48 ± 13.65s, p < 0.01) open-arms were significantly lower than that of the control group (3.40 ± 1.62 times, 59.74 ± 23.32s), showing stronger anxiety degree. After withdrawal, the anxiety of rats was relieved. 74 differential metabolites were screened in the plasma of ketamine group, involving cysteine and methionine metabolism, valine and isoleucine biosynthesis, glutamine and glutamate metabolism. After one week of withdrawal, the cysteine and methionine metabolic pathways were still significantly different with the saline group; 87 metabolites in the prefrontal cortex significantly changed, which involved purine metabolism, ascorbic acid, and aldose metabolism pathways.
RETRACTED: Synergistic Antibioiflm Activity of Probiotic Lactobacillus Acidophilus and Punica Granatum L., Against Pseudomonas Aeruginosa Biofilm
Authors: Khursheed Hadia , Qasim Rimsha
Published: September 2023

The authors have requested that this preprint be removed from Research Square.
Arthrospira maxima hydrolysate as a high value biofertilizer in basil (Ocimum basilicum L.) seedlings
Authors: Marín-Marín Camila Andrea , Estrada José Alberto , Naranjo Juan Martín Delgado , Ocampo Paola Andrea Zapata
Published: September 2023

Continued increase of human populations and use of chemical fertilizers remain a threat to the health and stability of human-ecological systems worldwide. To ameliorate this problem and achieve sustainable agriculture, a variety of ecofriendly technologies have been developed, including the production of cyanobacteria-based biofertilizers. This technology can be optimized through experiments that assess how plant growth is enhanced under different biofertilizer concentrations (g L− 1). Here we assess the biofertilizer potential of hydrolysates derived from the cyanobacteria Arthospira maxima on the growth of basil (Ocimum basilicum) under six different concentrations (0, 2.5, 5, 10, 20, and 40 g L− 1), and an additional treatment where we applied the registered product Optimar ® (4 mL L− 1). For all response variables except stem length, a concentration of 40 g L− 1 yielded significantly higher values. The beneficial effects of the application of Optimar were often surpassed when plants received cyanobacteria concentrations above 10 g L− 1. A chemical composition analysis of A. maxima revealed high concentrations of the phytohormones gibberellic acid (0.19 g L− 1), 6-benzyladenine (0.37 g L− 1), and 1-naphthaleneacetic acid (0.25 g L− 1) that are likely responsible for the cyanobacteria’s biostimulant activity. Further research is required to determine how other crop plants respond to different concentrations of A. maxima and the viability of creating an economically accessible product with a higher concentration of A. maxima using circular economy and biorefinery concepts to obtain high value-added by-products.
Uric acid, high density lipoprotein cholesterol and their ratio are related to microbial enterotypes and serum metabolites in females with blood stasis constitution
Authors: Sun Chen , Liu Yanmin , Huang Wei , Chen Yang , Deng Yusheng , Yuan Jiaming , Deng Lili , Xu Ning , Shang Xiaoxiao , Wang Chuyang , Yang Zhimin , Huang Li , Qiu Qinwei
Published: September 2023

Background
Blood stasis constitution in Traditional Chinese Medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear.
Methods
This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC) and their ratio (UHR), gut microbiota and serum metabolites. Clinical data, fecal and serum samples were collected from 24 individuals with blood stasis constitution and 80 with balanced constitution among healthy subjects from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed.
Results
Females with blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomics analysis identified subtle alterations between groups, including lower phenylalanine and higher trimethylaminoacetone levels in blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation.
Conclusions
Our findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.
Effect of Air Annealing on Structural, Textural, Thermal, Magnetic and Photocatalytic Properties of Ag-Doped Mesoporous Amorphous Crystalline Nanopowders Bi2O3
Authors: Ilves V. G. , Gaviko V. S. , Murzakaev A. M. , Sokovnin S. Y. , Svetlova O. A. , Zuev M. G. , Uimin M.A.
Published: September 2023

Ag doped Bi2O3 nanopowders (NPs) were produced by pulsed electron beam evaporation (PEBE) under vacuum. The solid phase synthesis in an electric furnace on air was used for silver doping of bismuth oxide (addition of - 1 and 5 wt% crystalline silver nitrate). Structural, textural, thermal and magnetic properties of Ag doped Bi2O3 NPs have been studied. The specific surface area of (SSA) Ag- Bi2O3 NPs was 23.7 m2/g, which was almost 2 times bigger than the SSA of the pure Bi2O3 (13.2 m2/g). Air annealing (200 °C) caused decreased crystallinity and growth of SSA in all NPs, without exception. Silver doping reduced the grain size of NPs after they were air annealed compared to the grain size of NPs annealed pure bismuth oxide. The dominant phase in not annealed/annealed Ag doped Bi2O3 NPs at 200 °C and 300 °C was β -phase Bi2O3 with a tetragonal structure. Accordingly, the photocatalytic activity of the Ag doped NPs was higher in the doped Bi2O3. The thermal stability of the pure and Ag-doped Bi2O3 NPs was maintained at 300-350 °C. The phase transition β→α occurred with a further increase in temperature. The annealing temperature could effectively change the physicochemical properties of the Bi2O3 NPs.
Cellulose/graphene nanoplatelets cryogel for adsorption of dyes in an aqueous medium
Authors: Lazzari Lídia K. , Zattera Ademir J. , Santana Ruth M. C.
Published: September 2023

The development of new technologies for the removal of dyes present in industrial effluents has been the subject of great interest in recent years, due to the increase in awareness about environmental preservation and the greater rigor of specific legislation. In this context, adsorption is one of the most promising techniques for color removal, since it has a relatively low cost, in addition to having appreciable efficiency. The use of graphene nanoplatelets (GNP) as a reinforcement for cellulose cryogels brings interesting properties to it, such as increased mechanical strength and adsorption capacity (oils, dyes...). Considering the mentioned aspects, this work aims to evaluate the adsorbent capacity of cellulose/GNP cryogel in the removal of congo red organic dye in an aqueous medium. The differential of the present work will be the use of GNP as a carbonaceous structure to reinforce the cellulose cryogel. Thus, a potential material will be developed for application as an adsorbent in the removal of dyes in an aqueous medium.
Spatio-temporal changes and hydrological forces of wetland landscape pattern in the Yellow River Delta during 1986-2022
Authors: Qiu Mengqi , Liu Yanxu , Chen Peng , He Naijie , Wang Shuai , Fu Bojie
Published: September 2023

Context:
Estuarine wetlands provide valuable ecosystem services but have undergone continuous change under the pressures of climate change and anthropogenic disturbance. The Yellow River Delta (YRD) wetland, which is one of the most vigorous delta areas in the world, has undergone dramatic changes. However, the long-term and high-resolution typical salt marsh vegetation evolution processes and hydrological drivers remain unclear.
Objectives
(1) Generate annual mapping of salt marsh vegetation in the YRD wetland from 1986 to 2022. (2) Analyze the trends of wetland patch area and landscape pattern, and explain the hydrological drivers of landscape pattern evolution.
Methods
Combining Landsat 5‒8 and Sentinel-2 images, vegetation phenology, remote sensing indices, and Random Forest supervised classification to map the typical salt marsh vegetation. We applied piecewise linear regression model to analyze YRD wetland changes, and stepwise multiple linear regression was used for assessing the impact of hydrological factors on landscape pattern.
Results
We identified three stages of landscape pattern evolution with 1997 and 2009 as turning points, including the rapid expansion stage, gradual decline stage, and bioinvasion stage. In the first phase, the wetland area was expanded by 70.45%, while the typical salt marsh vegetation, Phragmites australis area was reduced by 25%. In the second phase, the wetland was reduced by 21.33% and the Phragmites australis area was reduced by 15.96%. The third stage, Spartina alterniflora demonstrated an unstoppable trend of rapid expansion, with an area increase of 68 times relative to 2009, expanding at an average rate of 344 hm2 per year.
Conclusions
Areas of wetland, tidal flat, and Phragmites australis are significantly influenced by cumulative sediment and cumulative runoff, which total explain 61.5%, 75.7% and 63.8% of their variations, respectively. Wetland and tidal flat areas increased with the cumulative sediment, while cumulative runoff had a weak negative effect. As for Phragmites australis, cumulative runoff had a positive effect, whereas cumulative sediment had a negative effect. Water resources regulation measures should be taken to prevent the degradation of wetland ecosystems, and intervention measures can be implemented during the seedling stage to control the invasion of Spartina alterniflora.
BDNF Val66Met moderates increases in CSF t-tau and p-tau181 in early sporadic Alzheimer’s disease: A prospective cohort study
Authors: Thomson Diny , Rosenich Emily , Maruff Paul , Lim Yen Ying
Published: September 2023

Background: Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer’s disease (i.e., Aβ+ older adults), and pre-symptomatic autosomal dominant AD (ADAD). In ADAD, Met66 was also associated with greater increases in CSF levels of total-tau (t-tau) and phosphorylated tau (p-tau181). This study sought to determine the extent to which BDNF Val66Met is associated with changes in episodic memory and CSF t-tau and p-tau181 in Aβ+ older adults in early-stage sporadic AD.
Methods: Aβ+ Met66 carriers (n=94) and Val66 homozygotes (n=192) enrolled in the Alzheimer’s Disease Neuroimaging Initiative who did not meet criteria for AD dementia, and with at least one follow-up neuropsychological and CSF assessment, were included. A series of linear mixed models were conducted to investigate changes in each outcome over 10 years, covarying for CSF Aβ42 (except when examining changes in CSF Aβ42), APOE ε4 status, sex, age, baseline diagnosis and years of education.
Results: Aβ+ Met66 carriers demonstrated significantly faster memory decline (d=0.33; 95% CI [0.08, 0.58]) and significantly greater increases in CSF t-tau (d=0.30; 95% CI [0.05, 0.55]) and p-tau181 (d=0.29; 95% CI [0.04, 0.54]) compared to Val66 homozygotes, despite showing equivalent rates of change in CSF Aβ42.
Conclusions: These findings suggest that reduced neurotrophic support, which is associated with Met66 carriage, may increase vulnerability to Aβ-related tau hyperphosphorylation, neuronal dysfunction and cognitive decline in the early stages of sporadic AD. Additionally, these findings highlight the need for clinicopathological models of AD to account for neurotrophic factors and the genes which moderate their expression.
Interferon-γ and tumor growth
Authors: Ilyushin A. L. , Bogdashin I. V. , Aleksanyan A. Z. , Novikov V. V. , Ashrafyan L. A.
Published: September 2023

Purpose of the study: to analyze published data on the mechanisms of action of interferon gamma (IFN-γ) in tumor growth and to evaluate the possibility of its use in the treatment of solid tumors. Material and Methods. More than 200 publications were found in the Scopus, Pubmed, eLibrary and other databases, the search keywords were: interferon gamma, tumor growth, cancer therapy. This review includes 54 papers. Results. IFN-γ is a pleiotropic cytokine with antiviral, antitumor, and immunomodulatory functions and plays an important role in coordinating the innate and adaptive immune response. The success of immuno-oncology drugs and chemotherapy in the treatment of malignant tumors depends on the stimulation of the production and adequate signaling of IFN-γ. Suppression and loss of IFN-γ receptor and downstream signaling mediators, and amplifcation of molecules that inhibit the IFN-γ signaling pathway are common mechanisms for tumor cells to escape from the immune system. The development of malignant processes is accompanied by a change, more often a decrease, in the secretion of IFN-γ, which attracts the attention of researchers to its exogenous administration. Determination of the IFN-γ signature may be a predictive marker of clinical response to anticancer drug therapy. The antitumor properties of IFN-γ are largely dose-dependent, which has been clearly shown in clinical and experimental studies. Low doses of the drug often promote tumor growth. On the contrary, the use of high doses is usually accompanied by an antitumor effect. IFN-γ or its inducers remain promising agents for cancer therapy. Combinatorial strategies involving IFN-γ may be a rational option to overcome tumor resistance to blockade of immune checkpoints. Conclusion. It is necessary to continue fundamental and applied research to study the feasibility of using interferon gamma as a therapeutic agent in tumor growth.
Features of aminothiol metabolism and progression of breast cancer
Authors: Markovsky A. V.
Published: September 2023

Background. Imbalance of aminothiol metabolism is a potential risk factor for malignant transformation of cells and caner development, including breast cancer, which is the most commonly diagnosed cancer in the world. The purpose of the study was to summarize the available data on the characteristics of thiol metabolism as one of the factors contributing to the progression of breast cancer. Material and Methods. Data were searched from 1999 to 2022 using the Web of Science, Scopus, MedLine, The Cochrane Library, PubMed databases, which made it possible to assess the role of thiol-dependent metabolic disturbances in the regulation of tissue redox balance in breast cancer genesis. Results. The review considers the results of both our own data and international studies on breast cancer, which suggest that an imbalance of thiol compounds necessary to maintain a moderately reducing cellular environment that counteracts oxidative stress during cellular metabolism and detoxifcation under conditions of tumor progression can provoke reprogramming of the leading links of antiblastoma resistance, contributing to cancer progression. Conclusion. A more detailed study of the mechanisms of aminothiol metabolism in breast cancer emphasizes their particular importance for stabilizing the cellular genome and providing antitoxic protection of the cell, as well as understanding the important role of thiols as a coordination center in redox signaling. Disturbances at any stage of thiol metabolism can play an etiological role in oncogenetic pathologies, while the role of thiols as signaling molecules and the regulation of their metabolism should not be generalized for the entire group of diseases. Determination of serum markers of the redox state in patients with breast cancer, especially during antitumor therapy, can serve for an objective assessment of the effectiveness of treatment and the adaptive capabilities of the body, as well as predicting tumor growth and optimizing the program for screening and preventing cancer.
A clinical case of extragastrointestinal tumor in combination with testicular feminization syndrome (Morris syndrome)
Authors: Sidakova Z. A. , Baranova A. A. , Gritsai A. N. , Efremov G. D. , Lyubchenko L. N.
Published: September 2023

Background. According to literature data, errors in the diagnosis of gastrointestinal tumors (GIST) are uncommon, accounting for approximately 6% of cases that results in treatment failure. Case report. Here, we describe a rare case of a 58-year-old female patient with extragastrointestinal stromal tumor (EGIST) in the evidence of testicular feminisation syndrome (TFS) – Morris syndrome. This hereditary pathology is associated with complete insensitivity of target organs to androgens and was described in 1953 by the American gynaecologist John Morris. The patient was referred to the cancer clinic, where she was wrongly diagnosed with uterine leiomyoma. Interdisciplinary approach, cancer alarm, active surgical tactics, additional immunohistochemical (IHC) and molecular genetic studies (MGI) allowed verifcation of the true diagnosis. There are reported cases of EGIST of the bladder, prostate, retroperitoneum, mesentery, omentum, and posterior mediastinum. However, we were not able to fnd publications regarding the cases of EGIST originating from the vaginal wall. Combination of TFS and EGIST is a unique case in our clinical practice. Conclusion. The study of rare cases expands the understanding of the molecular pathogenesis of malignancies. Patients with rare types of malignant tumors should be obligatorily examined and treated in specialized cancer clinics with involvement of certifed oncologists, surgeons, chemotherapists, geneticists.
Sclerosing mucoepidermoid thyroid carcinoma combined with autoimmune thyroiditis
Authors: Ryabchenko E. V.
Published: September 2023

Background. Sclerosing mucoepidermoid thyroid carcinoma (SMTC) is a recently recognized malignant neoplasm of the thyroid. SMTC was frst reported in 1991. It arises in a background of Hashimoto thyroiditis (HT). There are two variants of mucoepidermoid carcinoma of thyroid gland: the conventional and sclerosing variants. SMTC has recently been recognized as a separate disease entity by World Health Organization (WHO). Description of the clinical case. We present the case of a 51-year-old woman with a 2-year history of autoimmune thyroiditis with a thyroid nodule. The patient had no symptoms or signs of compression. The level of thyroid–stimulating hormone (TSH) was 15.8 (range 0.4-4.0), antibodies to peroxidase: 150 Iu/ml. Scintigraphy of the thyroid gland revealed a dominant cold nodule (1.5×2 cm) in the right lobe of the gland. The control ultrasound examination showed negative fndings. Fine needle aspiration cytology of the nodule revealed follicular lesion in a background of TH. Extrafascial thyroidectomy was performed. The patient was followed up for 10 months.
Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus
Authors: Nevolskikh A. A. , Mihaleva Y. Y. , Avdeenko V. A. , Titova L. N. , Berezovskaya T. P. , Gulidov I. A. , Petrov L. O. , Ivanov S. A. , Kaprin A. D.
Published: September 2023

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2  twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2  on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.
Effcacy and toxicity of regorafenib compared to reintrodaction of chemotherapy in metastatic colon cancer: retrospective multicenter study
Authors: Kuzmina E. S. , Fedyanin M. Yu. , Reshetov I. V. , Pokataev I. A. , Galkin V. N.
Published: September 2023

The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer. Material and Methods. Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study. Results. The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p<0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on PFS (HR, 1.9; 95 % CI, 1.3–2.8; p<0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4 %) of 215 patients and signifcantly more frequent in the regorafenib group: 67.4 % (89/132) vs 33.7 % (28/83) in the group with repeated administration of previously effective regimens (p<0.001). Conclusion. Regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was signifcantly higher in the reintroduction group as the 3rd line of treatment, with signifcantly lower toxicity.
Comorbidity in predicting surgical outcomes for gastric cancer
Authors: Suvorov V. A. , Panin S. I. , Kovalenko N. V. , Zhavoronkova V. V. , Postolov M. P. , Tolstopyatov S. E. , Panina A. A. , Suleymanov Sh. R. , Vezirov E. Sh. , Peshkurova I. A.
Published: September 2023

Objective: The present study aimed to analyze the treatment outcomes and develop a predictive model of surgical treatment for gastric cancer, taking into account the comorbidity of patients. Material and Methods. The treatment outcomes were studied in 477 (100 %) gastric cancer patients. Patients were stratifed into two groups according to the Age-Adjusted Charlson Comorbidity Index (ACCI) (0–4 points – 311 (65,2 %), more than 4 points – 166 (34,8 %) patients). Two hundred and seventy six patients (57.9 %) underwent distal or total gastrectomy, 178 (37.3 %) total gastrectomy, 19 (4 %) minimally invasive gastrectomy, and 4 (0.8 %) patients underwent extirpation of the gastric stump. The construction of models for the prognosis of surgical treatment was carried out using binary logistic regression, the comparison of models – by analyzing error curves (ROC-analysis). Results. The incidence rate of postoperative complications (grade III-V) according to the Clavien-Dindo classifcation was signifcantly higher in group 2 (9.9 %, 47/477) compared to group 1 (2.1 %, 10/477) (χ2 =64.79, p<0.001; OR 11.9 [5.82–24.3]). Postoperative mortality rate was 0.2 % (1/477) in group 1 and 1.9 % (9/477) in group 2 (χ2 =13.7, p<0.001; OR 17.8 [2.23–142]). In a comparative analysis, the prognostic model, taking into account the ACCI of the patient, allowed prediction of the development of postoperative grade III–V complications according to the Clavien-Dindo with the greatest accuracy. The area under the curve (AUC) was 0.921 ± 0.01 (95 % CI: 0,96–0,998), sensitivity – 71.9 %, specifcity – 99.8 %, diagnostic accuracy – 96.4 %. Conclusion. The inclusion of comorbidity in gastric cancer patients in the predictive concept makes it possible to improve the accuracy of prediction of postoperative complications of III–V grade according to Clavien-Dindo.
Long-term effects of cytostatic agents on germ cells of testicular tissue (experimental study)
Authors: Borovskaya T. G. , Vychuzhanina A. V. , Shchemerova Yu. A. , Kseneva S. I. , Fomina T. I. , Bokhan E. A. , Goldberg V. E.
Published: September 2023

Currently, cytostatic drugs are widely used not only in cancer treatment, but also in the treatment of autoimmune infammatory diseases. A favorable prognosis of the disease, ability to reproduce, young age and the absence of children serve as an incentive to decide on the need for childbearing. There is concern, that the mutagenic effects of chemotherapy in germ cells, the ability to induce epigenetic changes in them, may have phenotypic manifestations in offspring. Conception in the early stages after treatment (impact on mature and differentiating germ cells) has been proven to increase the risk of defective offspring. Data on the health of the offspring of patients conceived in the long term after treatment (impact on stem spermatogenic cells) are contradictory. The aim of the study was to assess long-term toxic effects of cytostatic drugs in the male rat offspring copulated in terms corresponding to the effect on stem spermatogonial cells (SSCs). Material and Methods. The experiments were carried out on autobred male Wistar rats (n=140), aged 2.5 months, 70 of which made up the group of intact animals. The effect of cytostatic drugs (etoposide, irinotecan, cisplatin, carboplatin, methotrexate, farmorubicin, and paclitaxel) injected 3 and 6 months before mating was assessed on the offspring of intact female and male rats. Results. The male rat offspring treated with cytostatic drugs was found to be viable. Gross external developmental anomalies were detected in 2 cases. In several offspring, a slowdown in physical development, decrease in the rate of formation of sensory-motor refexes and learning ability were observed. The most toxic drugs were etoposide and paclitaxel. Conclusion. The offspring of rats treated with cytostatic drugs in terms corresponding to the effect on the SSCs is at risk. The degree of severity of long-term effects varies signifcantly and depends on the type of the drugs used. A decrease in the ability to learn is the most frequently detected abnormalities in offspring. Judging by the timing of conception after cytostatic exposure, a signifcant increase in the period of time after the administration of the drug before mating is not always justifed.
Differentiated approach to adjuvant neutron therapy in patients with locally advanced breast cancer, taking into account signifcant prognostic factors
Authors: Velikaya V. V. , Startseva Zh. A. , Babyshkina N. N. , Goldberg V. E. , Popova N. O.
Published: September 2023

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ2 =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion. Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.
Soils, Water Quality, and Watershed Size
Authors: Calhoun Frank G. , Baker David B. , Slater Brian K.
Published: September 2023

Soil variability in watersheds accounts for the problem of partitioning downstream water quality data and evaluating sources of nonpoint pollution. This review of previous water quality studies was conducted to examine more closely the influence of soil properties on pollutant export. The approach used in this paper was to start with data from the two largest watersheds (Maumee and Sandusky) and then compare them on a unit area export basis with data from intermediate‐size and smaller watersheds. General relationships between pollutant levels at the river mouth and upstream soil conditions are vague and seemingly contradictory at the large‐watershed scale. With smaller watersheds, it can be determined that soil texture, slope, and internal drainage are controlling factors for pollutant export. Although Paulding (very‐fine, illitic, nonacid, mesic Typic Epiaquept) and Roselms (very‐fine, illitic, mesic Aeric Epiaqualf) soils occupy only 5% of the Maumee basin, they generate more than 10 times as much sediment per unit area as the tile‐drained Hoytville (fine, illitic, mesic Mollic Epiaqualf) soils that occupy 16% of the Maumee basin. Tile drainage of very poorly drained soils that are formed from either glacial till or silty to sandy lake deposits reduces runoff and increases downward movement of soluble nutrients into tile drains. The assumption that sloping moraine areas are the primary source of pollutants should be reexamined based on this review.
EVALUATION OF COMMUNITY OUTREACH PROGRAM OF A HEI ADOPTED COMMUNITY IN MEYCAUAYAN CITY
Authors: Jay C. Dayao Ryan , B. Santos Arren , A. Beluan Ranulfo , G. Gregorio Belen
Published: September 2023

This study evaluates the impact and outcomes of the community outreach program of a Higher Education Institution (HEI) in Meycauayan City Adopted Community. The program aims to promote educational, social, and economic development in the community through various initiatives and activities. The evaluation is based on a survey conducted among the program beneficiaries, including students, parents, and community members. The survey measures the effectiveness of the program in achieving its objectives and identifies areas for improvement. The study also analyzes the programs sustainability and scalability, taking into account the resources and capacity of the HEI and the community. The findings of this study provide insights into the best practices and strategies for community outreach programs in higher education and contribute to the development of a framework for evaluating the impact of such programs.The community also benefited from the program, with improved access to education, health, and social services. The institution also gained from the program, with increased visibility and recognition in the community.The study concludes that the community outreach program is an effective way for HEIs to engage with the local community and contribute to social and economic development. The study recommends that HEIs should continue to invest in community outreach programs and evaluate their impact regularly to ensure continuous improvement.
ORALITY, ORAL PRACTICES AND CHRISTIAN WORSHIP IN WEST AFRICANCULTURES
Authors: Olusola Fasipe (Ph.D.) Emmanuel
Published: September 2023

In West African countries, despite Western education, oral culture still exists, and it is more prevalent in some societies within the region. Oral tradition has been one of the means by which some West African people educate, instruct, and worship. Christian worship services are conducted virtually in oral form in many indigenous churches across the region. This study demonstrates that authentic Christian worship is not made possible only through written materials. Many West African Christians are able to express their faith and worship without being able to read and write. The study examines some of the characteristics of Christian worship done without much use of written materials. It highlights some of the problems and benefits of oral communication in Christian worship.
A CRITICAL REVIEW OF DYE EFFLUENT
Authors:   Associate Professor Department of Botany Post Graduate Govt. College For Girls Sector 11,Chandigarh., Bhattacharjee Madhumita
Published: September 2023

The worldwide increase in fashion , there is mushrooming of textile industry. A number of harmful chemicals including synthetic dyes are used in processing of textile. All synthetic dyes are coal tar dyes. The effluent from textile industry whether partially treated or untreated are discharged in various water bodies or agricultural field causing a major threat to human.