[Efficacy and safety of artificial intelligence-based large language models for decision making support in herniology: evaluation by experts and general surgeons]. / Effektivnost' i bezopasnost' bol'shikh yazykovykh modelei na osnove iskusstvennogo intellekta v kachestve instrumenta podderzhki prinyatiya reshenii v gerniologii: otsenka ekspertami i obshchimi khirurgami.

OBJECTIVE: To evaluate the quality of recommendations provided by ChatGPT regarding inguinal hernia repair. MATERIAL AND METHODS: ChatGPT was asked 5 questions about surgical management of inguinal hernias. The chat-bot was assigned the role of expert in herniology and requested to search only specialized medical databases and provide information about references and evidence. Herniology experts and surgeons (non-experts) rated the quality of recommendations generated by ChatGPT using 4-point scale (from 0 to 3 points). Statistical correlations were explored between participants' ratings and their stance regarding artificial intelligence. RESULTS: Experts scored the quality of ChatGPT responses lower than non-experts (2 (1-2) vs. 2 (2-3), p<0.001). The chat-bot failed to provide valid references and actual evidence, as well as falsified half of references. Respondents were optimistic about the future of neural networks for clinical decision-making support. Most of them were against restricting their use in healthcare. CONCLUSION: We would not recommend non-specialized large language models as a single or primary source of information for clinical decision making or virtual searching assistant.

Multimodal Optical Coherence Tomography for Intraoperative Evaluation of Tumor Margins and Surgical Margins in Breast-Conserving Surgery.

The aim of the study: We compare the effectiveness of multimodal optical coherence tomography (MM OCT) in the traditional structural OCT mode and the OCT elastography (OCE) mode in addressing two clinically important tasks: (1) detecting groups of tumor cells at surgical margins during breast-сonserving surgery (BСS) in breast cancer (BC) and (2) identifying breast tumor margins. The obtained results were correlated with corresponding histological sections. Materials and Methods: The study was performed on 100 surgical margin samples (top, bottom, medial, and lateral - four samples from each patient in total) obtained from 25 patients with BC who underwent BCS (lumpectomy), and on 25 postoperative tumor samples (to determine tumor margins). With MM OCT method, we visually and numerically assessed the scattering (level and depth of OCT signal penetration) and elastic (stiffness values, or Young's modulus (kPa)) properties of the tumor and non-tumor breast tissue and the obtained values were compared with the results of postoperative histological examination. Results: In 4 surgical margin samples (out of 100), with the OCE method we identified groups of histologically confirmed tumor cells ("positive" resection margins) at the distance of about 5 mm from the visible tumor margin. The identified zones were larger than 0.5 mm with stiffness of more than 400 kPa in all these cases. However, the structural OCT could not identify these groups of tumors and they were not distinguishable from the surrounding fibrous tissue.In the areas of tumor into non-tumor tissue transition, structural OCT images detected tumor margins only if they were adjacent to adipose tissue and did not detect them if there were adjacent to non-tumor fibrous tissue. OCE images with high stiffness values (more than 400 kPa) and high contrast showed a clear tumor margin with both adipose and fibrous tissue. Conclusion: The study demonstarets the potential of MM OCT, particularly its OCE mode, as a real-time method for intraoperative tumor margin and surgical margin assessment in BCS. OCE images compared to structural OCT images visualize higher contrast between different types of breast tissue (adipose tissue, fibrous stroma, hyalinized stroma, tumor cell clusters), as well as more accurate identification of the tumor border and detection of small groups of tumor cells at surgical margins. An algorithm for intraoperative MM OCT examination of the state of the resection margin is proposed in accordance with standard clinical guidelines for achieving clean surgical margins in breast cancer patients.

Effect of Vitamin D3 in Composition of Original Rectal Suppositories on Parameter of Protein Oxidative Modification in Large Intestine in Experimental Ulcerative Colitis.

The effect of vitamin D3 in the composition of original rectal suppositories on the content of products of oxidative modification of proteins in mucous membrane of the large intestine was studied in rats with experimental ulcerative colitis provoked by a two-stage administration of 3% oxazolone. The rectal suppositories with vitamin D3 (1500 IU) were administered every 12 h during 5 days. Condition of the rats was assessed according to disease activity index (DAI), while the content of oxidative modification products of proteins in the homogenate of the mucous membrane was assayed with extraction-spectrophotometric method in the lesion focus of large intestine. DAI increased during entire observation period of ulcerative colitis, which correlated with the level of products of spontaneous and induced oxidative modification of proteins in mucous membrane of the colon. The study examined the pharmaceutical and technological features of novel rectal suppositories of original composition weighing 300 mg, which are based on polyethylene glycol supplemented with aqueous solution of vitamin D3 (10%). The use of rectal suppositories with vitamin D3 reduced DAI and inhibited the oxidative modification of proteins.

Hypoxia as a Factor Involved in the Regulation of the apoA-1, ABCA1, and Complement C3 Gene Expression in Human Macrophages.

Hypoxia plays a critical role in progression of atherosclerosis. Local oxygen deficiency in a plaque creates a specific microenvironment that alters the transcriptome of resident cells, particularly of macrophages. Reverse cholesterol transport from plaque to liver is considered a main mechanism for regression of atherosclerosis. Ubiquitously expressed ATP-binding cassette transporter A1 (ABCA1) and liver- and small intestine-derived apolipoprotein A-1 (ApoA-1) are two main actors in this process. We recently reported endogenous apoA-1 expression in human macrophages. While ABCA1 and ApoA-1 have antiatherogenic properties, the role of complement factor C3 is controversial. Plasma C3 level positively correlates with the risk of cardiovascular diseases. On the other hand, C3 gene knockout in a murine atherosclerosis model increases both plaque size and triglycerides level in blood. In the present study, we show for the first time that a hypoxia-mimicking agent, CoCl2, induces the upregulation of the apoA-1 and C3 genes and the accumulation of intracellular and membrane protein ApoA-1 in THP-1 macrophages. The MEK1/2-Erk1/2 and MKK4/7-JNK1/2/3 cascades are involved in upregulation of ABCA1 and C3 via activation of transcription factor NF-κB, which interacts with the HIF-1α subunit of hypoxia-inducible factor 1 (HIF-1). The three major MAP-kinase cascades (Erk1/2, JNK1/2/3, and p38) and the NF-κB transcription factor are involved in the hypoxia-induced expression of the apoA-1 gene in THP-1 macrophages.

Hybrid κ-carrageenan-based polymers showing "schizophrenic" lower and upper critical solution temperatures and potassium responsiveness.

Novel multiresponsive hybrid biocompatible systems of κ-carrageenan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s with unique combination of responsiveness to external stimuli were synthesized and studied. The polymer thermoresponsive behavior proved the existence of both lower and upper critical solution temperatures in aqueous milieu, forming gel at lower temperature, a solution at room temperature and cloudy nanophase-separated dispersion at elevated temperature. The limit temperatures can easily be adjusted by the polyoxazoline graft length and grafting density. Moreover, the polymer behavior is additionally dependent on the concentration of potassium ions. The polymers behave similarly as the original κ-carrageenan, and thus, the poly(2-alkyl-2-oxazoline) grafts do not decrease the ability of the κ-carrageenan to form the self-assembled structures. Molecular principles beyond this multistimuli-responsive behavior were elucidated with the use of dynamic light scattering, magnetic resonance and fluorescence measurements as well as atomic force microscopy. These polymers could be used in a wide range of biological applications demanding thermo- and potassium-responsiveness.

New multispecific array as a tool for electrochemical impedance spectroscopy-based biosensing.

Using electrochemical impedance spectroscopy (EIS) for biosensing applications typically requires repetitive experiments. To address this need, we have designed a multispecific electrochemical array with eight individually addressable 2mm-diameter gold working electrodes for rapid biosensing data accumulation by EIS in the presence of redox agent. The array allows to incorporate multiple negative controls in the course of a single binding experiment, as well as to perform parallel identical experiments to improve reliability of detection. The array is fit with attached electrochemical cell with Ag/AgCl mini reference electrode and can be used to process macro samples of 0.5-1 ml or micro samples of 5 microl in a drop-wise fashion. Eight individual EIS measurements are completed in 15 min. The reported array is disposable, economical and is easy to use. Examples of array use for label-free genetic sensing of 2.7 kb-long target Yersinia pestis DNA and for protein sensing of Ricin Toxin Chain A (RTA) are presented. We suggest the reported array design as a tool for researchers in the area of EIS sensing.

Challenges of electrochemical impedance spectroscopy in protein biosensing.

Electrochemical impedance spectroscopy (EIS) measurement, performed in the presence of a redox agent, is a convenient method to measure molecular interactions of electrochemically inactive compounds taking place on the electrode surface. High sensitivity of the method, being highly advantageous, can be also associated with nonspecific impedance changes that could be easily mistaken for specific interactions. Therefore, it is necessary to be aware of all possible causes and perform parallel control experiments to rule them out. We present the results obtained during the early stages of aptamer-based sensor development, utilizing a model system of human alpha thrombin interacting with a thiolated DNA aptamer, immobilized on gold electrodes. EIS measurements took place in the presence of iron ferrocyanides. In addition to known method limitations, that is, inability to discriminate between specific and nonspecific binding (both causing impedance increase), we have found other factors leading to nonspecific impedance changes, such as: (i) initial electrode contamination; (ii) repetitive measurements; (iii) additional cyclic voltammetry (CV) or differential pulse voltammetry (DPV) measurements; and (iv) additional incubations in the buffer between measurements, which have never been discussed before. We suggest ways to overcome the method limitations.

[Isolation and characteristics of catalytic antibodies to DNA in systemic lupus erythematosis]. / Vydelenie i kharakteristika kataliticheskikh antitel k DNK pri sistemnoi krasnoi volchanke.

A method for purifying DNA-specific catalytic antibodies based on affinity chromatography on protein A Sepharose and on both modified and non-modified DNA-cellulose as well as HPLC has been developed. The elution conditions with high yields of DNA-hydrolyzing activity of antibodies have been optimized. The biochemical and immunological properties of catalytic antibodies have been examined. The kinetic parameters of the enzyme interaction with an oligonucleotide substrate have been determined. The influence of effectors on DNA hydrolysis by antibodies has been investigated.

DNA hydrolyzing autoantibodies.

A DNA-nicking activity was detected in the sera of patients with various autoimmune pathologies and was shown to be a property of autoantibodies. The DNA hydrolyzing activity, which was purified by affinity and high-performance liquid chromatography, corresponded in size to immunoglobulin M (IgM) and IgG and had a positive response to antibodies to human IgG. The DNA hydrolyzing autoantibodies were stable to acid shock and yielded a DNA degradation pattern that was different from that of deoxyribonuclease (DNase) I and blood DNase.

Identification of a sequence-specific protein binding the 5'-transcribed spacer of rat ribosomal genes.

A novel 85-kD protein factor which interacts specifically with the 5'-transcribed spacer of rat ribosomal genes was identified using the gel mobility shift, DNase I protection and UV-crosslinking techniques. The binding site of the factor is located inside the 36 bp Alul-HindIII fragment of transcribed spacer, most probably in the region +94 to +115 with respect to the transcription initiation site. Factors giving very similar gel mobility shift patterns were also found in mouse and human cell extracts. Sequences resembling the binding site of this factor were revealed in corresponding regions of mouse and human ribosomal genes. The biological function of FTS remains to be elucidated.

[Protein factors specifically binding to the regulatory elements of non-transcribed spacer of rat ribosomal genes]. / Belkovye faktory, spetsificheski sviazyvaiushchiesia s reguliatornymi élementami netranskribiruemogo speisera ribosomnykh genov krysy.

Mouse, rat and human protein factors recognizing regulatory elements of nontranscribed spacer of rat ribosomal genes were studied by gel retardation assay. Protein factors bind specifically to the DNA fragments containing the core promoter sequence of RNA-polymerase I, to "spacer" promoter and to a putative enhancer sequence. Factors of mouse, rat and human nuclear extracts that recognize the region containing the core promoter sequence have similar molecular masses and are not identical to the previously described protein factor TIF-1B. Two factors that bind the "spacer" promoter region differ from the factors of the core promoter. "Spacer" promoter factors of mouse and rat nuclear extracts are probably identical, but differ from those of human extract. Protein factors, recognizing the putative enhancer region of rat and human extracts are alike but were not detected in mouse extract. Regions of nontranscribed spacer containing dispersed and tandem repeats do not bind any specific protein factors.

Nucleotide sequence analysis of the spacer regions flanking the rat rRNA transcription unit and identification of repetitive elements.

We investigated the organization of the rat rDNA non-transcribed spacer (NTS) by determining the sequence of large NTS segments located upstream (2501 bp) and downstream (4025 bp) from the rRNA transcription unit. We identified four B2-like and two ID mobile elements. They may be grouped in three pairs with the members of each pair located in the upstream and downstream NTS. The ID sequences are identical to the consensus sequence, while the pairs of B2-like elements show 85% and 50/65% homology to the consensus B2 sequence. The proximal part of the downstream NTS contains a region of widely diverged SalI tandem repeats. A considerable part of the analyzed upstream and downstream NTS sequences is constituted by different types of simple sequences and long poly(purine) X poly(pyrimidine) tracts. These data show that the rat rDNA NTS regions flanking the rRNA transcription unit are characterized by a combination of short interspersed (B2-superfamily) and various simple sequences.