Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms.

This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host-virus interactions.

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines.

In this study, we present the discovery and pharmacological characterization of a new series of 6-piperazinyl-7-azaindoles. These compounds demonstrate potent antagonism and selectivity against the 5-HT6 receptor. Our research primarily focuses on optimizing the lead structure and investigating the structure-activity relationship (SAR) of these compounds. Our main objective is to improve their activity and selectivity against off-target receptors. Overall, our findings contribute to the advancement of novel compounds targeting the 5-HT6 receptor. Compound 29 exhibits significant promise in terms of pharmacological, physicochemical, and ADME (Absorption, Distribution, Metabolism, and Excretion) properties. Consequently, it merits thorough exploration as a potential drug candidate due to its favorable activity profile and successful outcomes in a range of in vivo experiments.

Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu7 Receptor Modulation Activity and Antipsychotic-Like Properties.

Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 activity in the T-REx 293 cell line expressing a recombinant human mGlu7 receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu7 IC50 = 6.14 µM) was selective over other group III mGlu receptors (mGlu4 and mGlu8), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further tested in animal models of antipsychotic-like activity, assessing the positive, negative, and cognitive symptoms. ALX-171 reversed DOI-induced head twitches and MK-801-induced disruptions of social interactions or cognition in the novel object recognition test and spatial delayed alternation test. On the other hand, the efficacy of the compound was not observed in the MK-801-induced hyperactivity test or prepulse inhibition. In summary, the observed antipsychotic activity profile of ALX-171 justifies the further development of the group of quinazolin-4-one derivatives in the search for a new drug candidate for schizophrenia treatment.

New Screening Protocol for Effective Green Solvents Selection of Benzamide, Salicylamide and Ethenzamide.

New protocol for screening efficient and environmentally friendly solvents was proposed and experimentally verified. The guidance for solvent selection comes from computed solubility via COSMO-RS approach. Furthermore, solute-solvent affinities computed using advanced quantum chemistry level were used as a rationale for observed solvents ranking. The screening protocol pointed out that 4-formylomorpholine (4FM) is an attractive solubilizer compared to commonly used aprotic solvents such as DMSO and DMF. This was tested experimentally by measuring the solubility of the title compounds in aqueous binary mixtures in the temperature range between 298.15 K and 313.15 K. Additional measurements were also performed for aqueous binary mixtures of DMSO and DMF. It has been found that the solubility of studied aromatic amides is very high and quite similar in all three aprotic solvents. For most aqueous binary mixtures, a significant decrease in solubility with a decrease in the organic fraction is observed, indicating that all systems can be regarded as efficient solvent-anti-solvent pairs. In the case of salicylamide dissolved in aqueous-4FM binary mixtures, a strong synergistic effect has been found leading to the highest solubility for 0.6 mole fraction of 4-FM.

Smart SDN Management of Fog Services to Optimize QoS and Energy.

The short latency required by IoT devices that need to access specific services have led to the development of Fog architectures that can serve as a useful intermediary between IoT systems and the Cloud. However, the massive numbers of IoT devices that are being deployed raise concerns about the power consumption of such systems as the number of IoT devices and Fog servers increase. Thus, in this paper, we describe a software-defined network (SDN)-based control scheme for client-server interaction that constantly measures ongoing client-server response times and estimates network power consumption, in order to select connection paths that minimize a composite goal function, including both QoS and power consumption. The approach using reinforcement learning with neural networks has been implemented in a test-bed and is detailed in this paper. Experiments are presented that show the effectiveness of our proposed system in the presence of a time-varying workload of client-to-service requests, resulting in a reduction of power consumption of approximately 15% for an average response time increase of under 2%.

Synthesis of amide and sulfonamide substituted N-aryl 6-aminoquinoxalines as PFKFB3 inhibitors with improved physicochemical properties.

In oncology, the "Warburg effect" describes the elevated production of energy by glycolysis in cancer cells. The ubiquitous and hypoxia-induced 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) plays a noteworthy role in the regulation of glycolysis by producing fructose-2,6-biphosphate (F-2,6-BP), a potent activator of the glycolysis rate-limiting phosphofructokinase PFK-1. Series of amides and sulfonamides derivatives based on a N-aryl 6-aminoquinoxaline scaffold were synthesized and tested for their inhibition of PFKFB3 in vitro in a biochemical assay as well as in HCT116 cells. The carboxamide series displayed satisfactory kinetic solubility and metabolic stability, and within this class, potent lead compounds with low nanomolar activity have been identified with a suitable profile for further in vivo evaluation.

Surgical treatment for renal masses in the elderly: analysis of oncological, surgical and functional outcomes.

PURPOSE: Radical treatment in elderly patients with renal tumor remains debatable due to uncertainties regarding the risk of surgical complications, risk of end-stage renal disease (ESRD) and survival benefit. The aim of the study was to assess outcomes of radical treatment for renal cancer in elderly patients. MATERIALS AND METHODS: This retrospective analysis enrolled 507 consecutive patients treated with partial or radical nephrectomy due to renal mass. Patients with upfront metastatic disease (n=46) and patients lost to follow-up (n=110) were excluded from the analysis. Surgical, functional (screen for ESRD development) and survival outcomes were analyzed in patients aged >75 years in comparison to younger individuals. RESULTS: The analyzed group included 55 elderly patients and 296 younger controls. Within the cohort a total of 148 and 203 patients underwent radical and partial nephrectomies respectively. The rate of surgical complications, including grade >3 Clavien- Dindo complications, did not differ between groups (3.6% vs. 4.4%, p=0.63). Median length of hospital stay was equal in both groups (7 days). During a follow-up (median 51.9 months, no difference between groups), ESRD occurred in 3.4% of controls and was not reported in elderly group (p=0.37). Younger patients demonstrated a statistically significant advantage in both overall survival and cancer-specific survival over elderly patients (OS 94.6% vs. 87% p=0.036, CSS 97.3% vs. 89.1% p=0.0008). CONCLUSIONS: Surgical treatment in elderly patients with renal tumor is as safe as in younger individuals and does not increase the risk of ESRD. However, cancer specific survival among these patients remains shorter than in younger patients.

[Pseudoexfoliation syndrom]. / Zespól pseudoeksfoliacji (PEX).

Pseudoexfoliation syndrome (PEX) is systematic microfibrylopathy associated with abnormalities of the accumulation of the extracellular matrix - buildup of protein clumps of abnormal basal membrane of trabecular epithelium, iris, ciliary body and lens capsule. The exfoliation material accumulates in anterior segment of a human eye (anterior lens capsule, ciliary zonule, ciliary body, iris, trabecular, anterior hyaloid membrane, conjunctiva) and other organs such as heart, connective tissue of lungs, vessels, skin, gallbladder, kidneys, liver, urinary bladder and meninges. People with PEX are more likely to develop cardio-vascular diseases, hearing loss and Alzheimer's disease as well.

[Fixed and temporary keratoprosthesis]. / Keratoprotezy stale i czasowe.

Keratoprosthesis is a chance for all patients who have bilateral visual loss due to corneal pathology so serious and extensive that it cannot be removed by graft transplantation. This problem mainly affects less developed countries. The eyesight of these patients could return to normal if corneal transplants were practiced and keratoprosthesis were widely available. Keratoplasty makes great progress and gets better and better results. The future will show whether there will be more reliable and biologically integrated keratoprosthesis, with low risk of complications.

[Visual disorder after visual contact with a geodetic laser]. / Visual disorder after visual contact with a geodetic laser.

Macular edema is a rare complication that can occur under the influence of light. Damage occurs as a result of focusing the light beam on the macula. A 23-year-old patient reported to the hospital due to a sudden reduction in visual acuity of the left eye after visual contact with a geodetic laser at work. After full diagnosis and treatment implementation after 3 weeks, vision improvement was achieved. The case report shows the harmful effects of laser techniques on human vision.

[Infective endocarditis in a patient with vision disorders]. / Infekcyjne zapalenie wsierdzia u chorej z zaburzeniami widzenia.

Roth spots are petechiae of the retina with a white or pale center that corresponds to a bundle of cotton wool or a multinuclear leukocyte aggregate. Often considered a sign of bacterial endocarditis, they are an unspecific symptom, usually more commonly seen in patients with hematopoietic system diseases. A 56-year-old patient reported to the hospital due to sudden visual impairment. The fundoscopy revealed Roth spots in both eyes that aroused the suspicion of infective endocarditis. After confirming the condition at the Department of Cardiology and the implementation of the treatment, there was a significant improvement in visual acuity, including the resolution of retinal changes. The presented case presents an accurate, still rare ophthalmic diagnosis of infective endocarditis.

[Assessment of visual acuity in aphakia patient after bilateral cataract removal]. / Ocena ostrosci wzroku u chorej bezsoczewkowej po obustronnym usunieciu zacmy wrodzonej.

Congenital cataracts are lens opacities that are already present at birth or are developing in the first years of life. Treatment consists of the surgical removal of the lens. Bilateral cataract deeply impairs vision, preventing the development of physiological reflex fixation and causes the development of nystagmus about 3 months of age. This nystagmus persists even after the surgical removal of cataracts without allowing often >0,1 visual acuity despite adequate aperture correction. Intraocular lens implants in children under the age of 1 are subject to discussion. Presents the patient's current visual acuity, in which an artificial intraocular lens was not implanted after a congenital cataract removal, retinal detachment, high myopia, glaucoma and persistent nystagmus. The whole treatment and adaptation mechanisms of the patient allowed to obtain surprising visual acuity for near vision without additional eyeglass correction.

[Ocular symptoms in von Recklinghausen disease]. / Objawy oczne w chorobie Recklinghausena.

Von Recklinghausen disease is a genetic disease with autosomal dominant, belonging to the group phakomatoses. In the clinical picture of the disease are skin lesions, eye, bone, intracranial tumors and other cancers of the extracranial location. Due to the high variability of clinical symptoms often diagnosis is delayed in cases of mild expression. The prognosis depends on the location and extent of the change and only symptomatic treatment have a tendency to change regrowth.

1-Sulfonyl-6-Piperazinyl-7-Azaindoles as potent and pseudo-selective 5-HT6 receptor antagonists.

A series of 1-Sulfonyl-6-Piperazinyl-7-Azaindoles, showing strong antagonistic activity to 5-HT6 receptor (5-HT6R) was synthesized and characterized. The series was optimized to reduce activity on D2 receptor. Based on the selectivity against this off-target and the analysis of the ADME-tox profile, compound 1c was selected for in vivo efficacy assessment, which demonstrated procognitive effects as shown in reversal of scopolamine induced amnesia in an elevated plus maze test in mice. Compound 3, the demethylated version of compound 1c, was profiled against a panel of 106 receptors, channels and transporters, indicating only D3 receptor as a major off-target. Compound 3 has been selected for this study over compound 1c because of the higher 5-HT6R/D2R binding ratio. These results have defined a new direction for the design of our pseudo-selective 5-HT6R antagonists.

PIN2-like proteins may contribute to the regulation of morphogenetic processes during spermatogenesis in Chara vulgaris.

KEY MESSAGE: PIN2-like auxin transporters are expressed, preferentially in a polarized manner, in antheridial cells of freshwater green alga Chara vulgaris , considered to be the closest relative of the present-day land plants. Chara vulgaris represents a group of advanced multicellular green algae that are considered as the closest relatives of the present-day land plants. A highly specialized structure of its male sex organs (antheridia) includes filaments consisting of generative cells, which after a series of synchronous divisions transform into mature sperm, and non-generative cells comprising outer shield cells, cylindrical manubria, and central complex of capitular cells from which antheridial filaments arise. Immunofluorescence observations indicate that PIN2-like proteins (PIN2-LPs), recognized by antibodies against PIN-FORMED2 (PIN2) auxin transporter in Arabidopsis thaliana, are expressed in both types of antheridial cells and, in most of them, preferentially accumulate in a polarized manner. The appearance of PIN2-LPs in germ-line cells is strictly confined to the proliferative period of spermatogenesis and their quantities increase steadily till antheridial filaments reach the 16-celled stage. An enhanced level of PIN2-LPs observed in the central cell walls separating two asynchronously developing parts of antheridial filaments (characterized by the plugged plasmodesmata) is correlated with an enhanced deposition of callose. Intense PIN2-LPs immunofluorescence maintained in the capitular cells and its altering polarity in manubria suggest a pivotal role of these cells in the regulation of auxin transport directionality during the whole time of antheridial ontogenesis. Immunohistochemical staining of IAA revealed a clear-cut correspondence between localization sites of auxins and PIN2-LPs. It seems probable then that a supplementary developmental mechanism has evolved in Chara, by which all antheridial elements may be integrated at the supra-cellular level via plasma membrane-targeted PIN2-LPs and auxin-mediated processes.

Human papillomavirus infection of the fallopian tube as a potential risk factor for epithelial ovarian cancer.

Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV's 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development.

Sustainable management and recycling of anaerobic digestate solid fraction by composting: A review.

The aim of the study was to review and discuss the management and recycling of anaerobic digestate solid fraction by composting process in the context of circular bioeconomy and sustainable development. The conversion of the solid fraction into compost can be recognized as novel process-enhancing supplements for land reclamation. Moreover, the solid fraction of the digestate is a valuable substrate for compost production, both as a monosubstrate and as a valuable additive for other raw materials to enrich in organic matter. These results should serve as reference point to target adjusting screws for anaerobic digestate solid fraction by composting process improvement, its implementation in modern bioeconomy perspective as well as provide a guideline for effective waste management.

Production of compost from logging residues.

The implementation of forest management generates logging residue which can be used in several ways. One of the option is to use of logging residue in the composting process. Therefore, this study determined the possibility of producing compost based on logging residue and the produced fertilizer used to fertilize forest nurseries. Pine chips and sewage sludge were used for carrying out the study. The compost, as well as the leachate produced during composting, were characterized by high NPK content. The leachate collected at the end of the experiment was characterized by nitrogen content of approximately 6500 mg‧dm-3, phosphorus of approximately 450 mg‧dm-3, and potassium of approximately 500-700 mg‧dm-3. In contrast, the compost produced contained approximately 0.57 g‧kg-1 nitrogen, approximately 0.39 g‧kg-1 phosphorus, and approximately 0.24 g‧kg-1 potassium. The disadvantage in terms of the usefulness of the resulting fertilizer in forest nurseries is its pH, which exceeded 9.0.

Different Types of Vasculitis Complicated by Heparin-Induced Thrombocytopenia-Analysis of Four Cases and Literature Review.

Vasculitis and HIT have different etiologies, although both involve autoimmune mechanisms. Treatment of vasculitis often requires the use of an anticoagulant such as heparin, which can lead to the development of HIT and subsequent life-threatening complications. The analysis covered patients hospitalized in the Department of Internal Medicine, Nephrology and Dialysis in the period from September 2020 to March 2023. After analyzing the data, we selected four patients in whom vasculitis treatment was complicated by HIT. These included two patients with ANCA vasculitis and two patients with anti-GBM disease. We also described similar cases reported in the literature.

Pathological changes or technical artefacts? The problem of the heterogenous databases in COVID-19 CXR image analysis.

BACKGROUND: When the COVID-19 pandemic commenced in 2020, scientists assisted medical specialists with diagnostic algorithm development. One scientific research area related to COVID-19 diagnosis was medical imaging and its potential to support molecular tests. Unfortunately, several systems reported high accuracy in development but did not fare well in clinical application. The reason was poor generalization, a long-standing issue in AI development. Researchers found many causes of this issue and decided to refer to them as confounders, meaning a set of artefacts and methodological errors associated with the method. We aim to contribute to this steed by highlighting an undiscussed confounder related to image resolution. METHODS: 20 216 chest X-ray images (CXR) from worldwide centres were analyzed. The CXRs were bijectively projected into the 2D domain by performing Uniform Manifold Approximation and Projection (UMAP) embedding on the radiomic features (rUMAP) or CNN-based neural features (nUMAP) from the pre-last layer of the pre-trained classification neural network. Additional 44 339 thorax CXRs were used for validation. The comprehensive analysis of the multimodality of the density distribution in rUMAP/nUMAP domains and its relation to the original image properties was used to identify the main confounders. RESULTS: nUMAP revealed a hidden bias of neural networks towards the image resolution, which the regular up-sampling procedure cannot compensate for. The issue appears regardless of the network architecture and is not observed in a high-resolution dataset. The impact of the resolution heterogeneity can be partially diminished by applying advanced deep-learning-based super-resolution networks. CONCLUSIONS: rUMAP and nUMAP are great tools for image homogeneity analysis and bias discovery, as demonstrated by applying them to COVID-19 image data. Nonetheless, nUMAP could be applied to any type of data for which a deep neural network could be constructed. Advanced image super-resolution solutions are needed to reduce the impact of the resolution diversity on the classification network decision.