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In 2020, five eurytomid species were found for first time on bark beetles in Pinus sylvestris plantations in Ihtimanska Sredna Gora Mountains in Bulgaria: Eurytoma afra Boheman, 1836, Eurytoma arctica Thomson, 1875, Eurytoma morio Boheman, 1836, Eurytoma sp.1 and Eurytoma sp.2. One of them, E. arctica is a new species for the Bulgarian fauna. The parasitoids were reared from stem and branch samples infested by Ips acuminatus, Pityogenes bistridentatus, Pityophthorus pityographus, Tomicus piniperda and T. minor. All host-parasitoid associations are new for Bulgaria. In parasitoid complex, the most abundant species was E. morio (75.9%), followed by E. arctica (13.8%), Eurytoma sp. (6.9%) and E. afra (3.4%). The parasitism of the hosts varied between 2.6% (E. afra on I. acuminatus, P. bistridentatus and P. pityographus) and 33.3% (E. morio on I. acuminatus).

Abstract Background Many hospitalised patients require rehabilitation during recovery from acute illness. We use routine data from Electronic Health Records (EHR) to report the quantity and intensity of rehabilitation required to achieve hospital discharge, comparing patients with and without COVID-19. Methods We performed a retrospective cohort study of consecutive adults in whom COVID-19 testing was undertaken between March 2020 and August 2021 across three acute hospitals in Scotland. We defined rehabilitation contacts (physiotherapy, occupational therapy, dietetics and speech and language therapy) from timestamped EHR data and determined contact time from a linked workforce planning dataset. Our aim was to clarify rehabilitation required to achieve hospital discharge and so we excluded patients who died during their admission, and those who did not require rehabilitation (fewer than two specialist contacts). The primary outcome was total rehabilitation time. Secondary outcomes included the number of contacts, admission to first contact, and rehabilitation minutes per day. A multivariate regression analysis for identifying patient characteristics associated with rehabilitation time included age, sex, comorbidities, and socioeconomic status. Results We included 11,591 consecutive unique patient admissions (76 [63,85] years old, 56% female), of which 651 (6%) were with COVID-19, and 10,940 (94%) were admissions with negative testing. There were 128,646 rehabilitation contacts. Patients with COVID-19 received more than double the rehabilitation time compared to those without (365 [165, 772] vs 170 [95, 350] mins, p

The endophytic fungus Biscogniauxia mediterranea, a causal agent of charcoal canker disease, was established for the first time on red oak (Quercus rubra) in Bulgaria. Symptomatic trees were found in 2023-2024 in the field protective forest belts planted in the State Hunting Enterprise Balchik (Sokolovo and Trigortsi villages) and State Forest Enterprise Dobrich (Kozloduytsi Village) in northeastern Bulgaria. Water stress during the last growing seasons seems to reduce red oak trees’ resistance and predispose them to be infected with the pathogen B. mediterranea. The disease has caused dieback of infected trees and increased their vulnerability to attacks by xylophagous insect pests.

Background: Osteoarthritis (OA) is a prevalent musculoskeletal disorder, often complicated by comorbid conditions such as cardiovascular diseases, metabolic syndromes, and mental health issues. These comorbidities significantly impact the progression of OA and the effectiveness of its management, posing challenges for comprehensive patient care. Objectives: This review examines the relationship between OA and its common comorbidities, focusing on cardiovascular diseases, metabolic conditions, and mood disorders. We also explore the impact of pharmacological and non-pharmacological treatments in these patients, emphasizing the importance of integrated care strategies. Methods: Data from multiple studies were analyzed to assess the association between OA and comorbid conditions. The studies examined mortality risk, cardiovascular incidents, metabolic syndrome, diabetes, obesity, and mood disorders, while considering the effects of various OA treatment modalities, particularly non-steroidal anti-inflammatory drugs (NSAIDs). Results: Cardiovascular comorbidities, including coronary heart disease, are significantly linked to OA, with functional limitations such as impaired mobility being major contributors to increased cardiovascular risks and mortality. NSAIDs, commonly prescribed for OA, present substantial cardiovascular and renal risks, complicating their use in patients with pre-existing cardiovascular conditions. Metabolic comorbidities, particularly obesity and diabetes, are highly prevalent in OA patients and are associated with reduced quality of life and exacerbation of OA symptoms. Furthermore, mood disorders like depression and anxiety are common among OA patients, leading to a vicious cycle of pain and psychological distress that worsens functional outcomes. Conclusions: OA is closely related to various comorbidities, necessitating a holistic, multimodal approach to treatment. Beyond pharmacologic interventions, lifestyle changes, psychosocial support, and careful management of comorbid conditions are essential for improving outcomes in OA patients.

Chokeberry pomace, rich in polyphenolic compounds, holds potential to be a valuable feed additive for enhancing the antioxidative capacity and overall quality of milk. This study explores the impact of dietary inclusion of chokeberry pomace on oxidative stress parameters and other milk quality parameters in high-producing dairy goats.

Abstract Zic family member ZIC4 is a transcription factor that has been shown to be silenced in several cancers. However, understanding the regulation and function of ZIC4 in pediatric choroid plexus tumors (CPTs) remained limited. This study employed data mining and bioinformatics analysis to investigate the DNA methylation status of ZIC4 in CPTs and its correlation with patient survival. Our results unveiled ZIC4 methylation as a segregating factor, dividing CPT cohorts into two clusters, with hyper-methylation linked to adverse prognosis. Hyper-methylation of ZIC4 was confirmed in a choroid plexus carcinoma-derived cell line (CCHE-45) by bisulfite sequencing. Furthermore, our study demonstrated that demethylating agent and a histone methyltransferase inhibitor could reverse ZIC4 silencing. RNA sequencing and proteomic analysis showed that ZIC4 over-expression influenced genes and proteins involved in immune response, antigen processing and presentation, endoplasmic reticulum stress, and metabolism. Functionally, re-expressing ZIC4 negatively impacted cell proliferation and migration. Ultimately, these findings underscore ZIC4 hyper-methylation as a prognostic marker in CPTs and shed light on potential mechanisms underlying its tumor suppressor role in CPC. This insight paves the way for novel therapeutic targets in treating aggressive CPTs.

This study describes a new species, Nanopsocus ajabu n. sp., discovered on Unguja Island, Zanzibar. The species exhibits unique morphological characteristics and complex colour patterns. Material was collected and examined following standard protocols, with specimen deposited at the National Museum of Natural History, Sofia, Bulgaria. An identification key for all known Nanopsocus species is provided.

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020–April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit β, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.

Abstract Traditional measurements of gait are typically performed in clinical or laboratory settings where functional assessments are used to collect episodic data, which may not reflect naturalistic gait and activity patterns. The emergence of digital health technologies has enabled reliable and continuous representation of gait and activity in free-living environments. To provide further evidence for naturalistic gait characterization, we designed a master protocol to validate and evaluate the performance of a method for measuring gait derived from a single lumbar-worn accelerometer with respect to reference methods. This evaluation included distinguishing between participants’ self-perceived different gait speed levels, and effects of different floor surfaces such as carpet and tile on walking performance, and performance under different bouts, speed, and duration of walking during a wide range of simulated daily activities. Using data from 20 healthy adult participants, we found different self-paced walking speeds and floor surface effects can be accurately characterized. Furthermore, we showed accurate representation of gait and activity during simulated daily living activities and longer bouts of outside walking. Participants in general found that the devices were comfortable. These results extend our previous validation of the method to more naturalistic setting and increases confidence of implementation at-home.

Abstract Fibonacci anyons ε provide the simplest possible model of non-Abelian fusion rules: [1] × [1] = [0] ⊕ [1]. We propose a conformal field theory construction of topological quantum registers based on Fibonacci anyons realized as quasiparticle excitations in the ℤ3 parafermion fractional quantum Hall state. To this end, the results of Ardonne and Schoutens for the correlation function of four Fibonacci fields are extended to the case of arbitrary number n of quasi-holes and N = 3r electrons. Special attention is paid to the braiding properties of the obtained correlators. We explain in details the construction of a monodromy representation of the Artin braid group B $$ \mathcal{B} $$ n acting on n-point conformal blocks of Fibonacci anyons. The matrices of braid group generators are displayed explicitly for all n ≤ 8. A simple recursion formula makes it possible to extend without efforts the construction to any n. Finally, we construct N $$ \mathcal{N} $$ qubit computational spaces in terms of conformal blocks of 2 N $$ 2\mathcal{N} $$ + 2 Fibonacci anyons.

Abstract This paper presents a detailed characterization of the positron beam delivered by the Beam Test Facility at Laboratori Nazionali of Frascati to the PADME experiment during Run III, which took place from October to December 2022. It showcases the methodology used to measure the main beam parameters such as the position in space, the absolute momentum scale, the beam energy spread, and its intensity through a combination of data analysis and Monte Carlo simulations. The results achieved include an absolute precision in the momentum of the beam to within ~1–2 MeV/c, a relative beam energy spread below 0.25%, and an absolute precision in the intensity of the beam at the level of 2%.

Abstract While the simultaneous degradation of muscle composition and postural stability in aging are independently highly investigated due to their association with fall risk, the interplay between the two has received little attention. Thus, the purpose of this study is to explore how age-related changes in muscle composition relate to postural stability. To that aim, we collected posturography measures and ultrasound images of the dominant Vastus Lateralis and Biceps Brachii from 32 young (18–35 year old) and 34 older (65–85 year old) participants. Muscle properties were quantified with echo-intensity and texture-based metrics derived from gray-level co-occurrence matrix analysis, and postural stability with the variability of the center of pressure during bipedal stance tasks. Ultrasound parameters revealed that young muscle possessed lower echo-intensity and higher homogeneity compared to the elderly. Echo-intensity and muscle thickness, and several texture-based parameters possessed outstanding young versus older classification performance. A canonical correlation analysis demonstrated a significant relationship between ultrasound and postural measures only within the young group (r = 0.53, p

During the period 2019-2020, parasitoids of invasive oak lace bug (Corythucha arcuata) were studied in Bulgaria. Biological material (larvae of C. arcuata) was collected from European oak (Quercus robur) or Austrian oak (Quercus cerris) in five localities of the country. Five eulophid specimens (Hymenoptera: Eulophidae) were reared from the host larvae: Tamarixia pubescens, Elasmus sp., Minotetrastichus sp., Pnigalio sp. and Sympiesis sp. The impact of the parasitoids on the host number was very low (0.1-0.3%). The present records in Bulgaria are the first documented case of adaptation of native parasitoids to the host in the newly occupied areas in Europe and Asia.

This study presents novel findings on the Psocoptera (Insecta) fauna of Vietnam, contributing to the understanding of biodiversity in the region. Psocoptera specimens were collected from Tam Dao National Park during October 2023, adding 19 new species to the existing list. These discoveries include species previously unknown to Vietnam and some new to the Indochina Peninsula and continental Asia. Material examination and species identification were conducted following established methodologies, with specimens deposited at the National Museum of Natural History, Sofia, Bulgaria. The findings underscore the importance of continued research efforts in documenting and understanding the psocid fauna of Vietnam, particularly in tropical forest ecosystems.

Abstract The rodent-borne Andes virus (ANDV) causes a severe disease in humans. We developed an ANDV mRNA vaccine based on the M segment of the viral genome, either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Female mice immunized by m1Ψ-mRNA developed slightly greater germinal center (GC) responses than U-mRNA-immunized mice. Single cell RNA and BCR sequencing of the GC B cells revealed similar levels of activation, except an additional cluster of cells exhibiting interferon response in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Similar immunoglobulin class-switching and somatic hypermutations were observed in response to the vaccines. Female Syrian hamsters were immunized via a prime–boost regimen with two doses of each vaccine. The titers of glycoprotein-binding antibodies were greater for U-mRNA construct than for m1Ψ-mRNA construct; however, the titers of ANDV-neutralizing antibodies were similar. Vaccinated animals were challenged with a lethal dose of ANDV, along with a naïve control group. All control animals and two animals vaccinated with a lower dose of m1Ψ-mRNA succumbed to infection whereas other vaccinated animals survived without evidence of virus replication. The data demonstrate the development of a protective vaccine against ANDV and the lack of a substantial effect of m1Ψ modification on immunogenicity and protection in rodents.

Background and aims – Euodia frauenfeldii has the characteristic ‘semi-circular’ or ‘crescent-shaped’ valves found in most species of Euodia, but as it also has a pair of conspicuous transapical costae, it was later transferred to Eunotogramma. Examination of the structure of its valves and girdle has led to a reassessment of its taxonomic position. Material and methods – We discuss various aspects of terminology used for the parts of the valve, their abbreviations used throughout the literature and provide a detailed taxonomic background to both Euodia and Eunotogramma. Key results – A new genus, Moralesonia is described and its relationships discussed.

Purpose – This paper is devoted to the generalized Kadomtsev–Petviashvili I equation. This study aims to propose a new approach for investigation for the existence of at least one global classical solution and the existence of at least two nonnegative global classical solutions. The main arguments in this paper are based on some recent theoretical results. Design/methodology/approach – This paper is devoted to the generalized Kadomtsev–Petviashvili I equation. This study aims to propose a new approach for investigation for the existence of at least one global classical solution and the existence of at least two nonnegative global classical solutions. The main arguments in this paper are based on some recent theoretical results. Findings – This paper is devoted to the generalized Kadomtsev–Petviashvili I equation. This study aims to propose a new approach for investigation for the existence of at least one global classical solution and the existence of at least two nonnegative global classical solutions. The main arguments in this paper are based on some recent theoretical results. Originality/value – This article is devoted to the generalized Kadomtsev–Petviashvili I equation. This study aims to propose a new approach for investigation for the existence of at least one global classical solution and the existence of at least two nonnegative global classical solutions. The main arguments in this paper are based on some recent theoretical results.

Special Purpose Acquisition Company (SPAC) is a special type of public listed company available to investors in financial markets, and was formed with the aim of investing in one or more existing operating companies after raising capital. This paper provides an overview of academic and financial literature on SPACs, describes their characteristics, advantages and risks of using SPAC as a form that does not offer services and does not conduct business operations, but is formed only for the purpose of acquisition of target companies. The paper focuses on the analysis of the impact of these forms of short-term investments on private companies, SPAC managers and investors. The paper further examines whether the impact of SPACs on European financial markets can be expected to grow. Authors’ findings show that, beside limitations for growth of European SPAC number, there is evident interest among European startup companies to go public through SPACs.

Abstract A search for the central exclusive production of top quark-antiquark pairs ( t t ¯ $$ \textrm{t}\overline{\textrm{t}} $$ ) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb −1. The t t ¯ $$ \textrm{t}\overline{\textrm{t}} $$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%.

The present case report aims to describe a postmortem finding of a colloid goiter, without obvious clinical signs of endocrine disease in a 30-year-old American black bear (Ursus americanus) from the “Zoo” in the city of Sofia, Bulgaria. A clinical examination due to a bad general condition was performed under anesthesia and a computed tomography was conducted. After the established irreversible spondylarthrosis changes the bear was euthanized. Postmortem, the thyroid gland was pathologically examined and typical findings for a colloid goiter were observed. Hibernating mammals such as the American black bear have been shown to enter a state of physiological hypothyroidism during hibernation. Hormonal signals from the thyroid gland have been suggested to be a key mediator of hibernation. From the presented case could be assumed that the captive life conditions and the prolonged life of the zoo bears may affect the function of their thyroid gland.

The study presents findings from a survey of terrestrial snails conducted on Unguja Island (Zanzibar). The survey, conducted in March 2024, focused on the eastern coast of the island, specifically around Uroa Village and Kiwengwa Cave. A total of 12 species of terrestrial snails were recorded, including Gulella minutissima (Thiele, 1911), previously unknown for over six decades.

This article presents an innovative approach for developing the mechanical and control systems of humanoid 3D-printed hand with fingers, based on a modular principle. The novelty is in creating the 3D printed fingers as a single assembled component and embedding the actuators and control elements, thus making it a complete independent module. The new approach allows the implementation of the same software and actuating components to be used in finger modules with different individual sizes and joint constraints. The mechanical and control system of the hand is developed and a working prototype is created. It is described how to adjust and control the position of fingers with different sizes and joint constraints. The communication of the modules with the developed software is described. The repeatability of finger movement is studied and the force that each finger is capable of exerting during folding is measured. Functional experiments are performed and discussed.

Background: Fitusiran, a subcutaneous, investigational siRNA therapeutic lowers antithrombin to rebalance hemostasis and enhance thrombin generation in People with Hemophilia (PwH) A or B, regardless of inhibitor status. For the management of perioperative hemostasis, Bleed Management Guidelines (BMG) with reduced dose and/or frequency of Clotting Factor Concentrates (CFC), or Bypassing Agents (BPA) were implemented. Aims: To describe hemostatic outcomes of major surgeries conducted while on fitusiran prophylaxis in PwHA/B aged ≥12-years, regardless of inhibitor status. Methods: All major surgeries in the fitusiran clinical development program until June 2023 were evaluated, including participants on the 80 mg QM and revised antithrombin-based dose regimen. Informed consent and ethics committee approval were obtained for all studies. Procedures conducted during fitusiran prophylaxis and AT activity < 60% were included. Major surgeries included: opening into a major body cavity, operation on a joint, removal of an organ, operative alteration of normal anatomy, crossing of a mesenchymal barrier, dental extraction of molar teeth or ≥3 nonmolar teeth, or tooth implantation. Investigators/surgeon assessed peri-operative hemostatic control based on the ISTH 4-point response scale (excellent/good/moderate/poor). Results and discussion: Sixty major surgeries (24 in inhibitor patients) were performed. In 47 (78.3%) major surgeries, BMG were followed, and reduced doses were used as perioperative prophylaxis. Four major surgeries were conducted without additional CFC/BPA. Hemostatic control on the day of the surgery was rated excellent/good in 30/31 (97%) cases following BMG and 9/10 (90%) cases not following BMG. ATIII concentrate was used to reverse the pharmacodynamic effect of fitusiran in 7 surgeries with an excellent/good hemostatic outcome. No major treatmentrelated safety concerns were identified perioperatively. Postoperative thrombosis occurred only when dosing exceeded BMG recommendations in 2 participants. Conclusions: Major surgeries can be safely and effectively conducted during fitusiran prophylaxis when BMG are followed, irrespective of inhibitor status. Reversal of lowered AT is not necessary.

ABSTRACT Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, antigen-specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large data set mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against 20 viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus-specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B-cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3 identity threshold above which B cells appear to exclusively share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality.IMPORTANCEThe B-cell compartment of the humoral immune system plays a critical role in the generation of antibodies upon new and repeated pathogen exposure. This study provides an unprecedented level of detail on the molecular characteristics of antibody repertoires that are specific to each of the different target pathogens studied here and provides empirical evidence in support of a 70% CDRH3 amino acid identity threshold in pairs of B cells encoded by identical IGHV:IGL(K)V genes, as a means of defining public clonality and therefore predicting B-cell antigen specificity in different individuals. This is of exceptional importance when leveraging public clonality as a method to annotate B-cell receptor data otherwise lacking antigen specificity information. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.

BTB (bric-a-brack, Tramtrack, and broad complex) is a diverse group of protein-protein interaction domains found within metazoan proteins. Transcription factors contain a dimerizing BTB subtype with a characteristic N-terminal extension. The Tramtrack group (TTK) is a distinct type of BTB domain, which can multimerize. Single-particle cryo-EM microscopy revealed that the TTK-type BTB domains assemble into a hexameric structure consisting of three canonical BTB dimers connected through a previously uncharacterized interface. We demonstrated that the TTK-type BTB domains are found only in Arthropods and have undergone lineage-specific expansion in modern insects. The Drosophila genome encodes 24 transcription factors with TTK-type BTB domains, whereas only four have non-TTK-type BTB domains. Yeast two-hybrid analysis revealed that the TTK-type BTB domains have an unusually broad potential for heteromeric associations presumably through a dimer-dimer interaction interface. Thus, the TTK-type BTB domains are a structurally and functionally distinct group of protein domains specific to Arthropodan transcription factors.

Video presentation has become ubiquitous in paradigms investigating the neural and behavioral responses to observed actions. In spite of the great interest in uncovering the processing of observed bodily movements and actions in neuroscience and cognitive science, at present, no standardized set of video stimuli for action observation research in neuroimaging settings exists. To facilitate future action observation research, we developed an open-access database of 135 high-definition videos of a male actor performing object-oriented actions. Actions from 3 categories: kinematically natural and goal-intact (Normal), kinematically unnatural and goal-intact (How), or kinematically natural and goal-violating (What), directed toward 15 different objects were filmed from 3 angles. Psychometric evaluation of the database revealed high video recognition accuracy (Mean accuracy = 88.61 %) and substantial inter-rater agreement (Fleiss' Kappa = 0.702), establishing excellent validity and reliability. Videos' exact timing of motion onset was identified using a custom motion detection frame-differencing procedure. Based on its outcome, the videos were edited to assure that motion begins at the second frame of each video. The videos' timing of category recognition was also identified using a novel behavioral up-down staircase procedure. The identified timings can be incorporated in future experimental designs to counteract jittered stimulus onsets, thus vastly improving the sensitivity of neuroimaging experiments. All videos, their psychometric evaluations, and the timing of their frame of category recognition, as well as our custom programs for performing these evaluations on our, or on other similar video databases, are available at the Open Science Framework (https://osf.io/zexc4/).

Deforming osteoarthritis of the knee joint alters the mechanical axis of the lower limb. This, combined with extra articular deformity of the tibia or femur leads to serious dysfunction of the limb and great disability for the patient. These rare cases present great challenge for the orthopedic surgeon. Most of the cases with mild to moderate deformities can be successfully managed by adjusting intra articular resections, but in those with severe extra articular deformity, an extra articular correctional osteotomy may be required in order to achieve good flexion-extension balance of the knee. We report a case of total knee replacement performed together with correctional osteotomy of the tibia due to extra articular deformity of about 20 degree varus.

During the period of 2022 and 2023, 10 patients with early infection following joint arthroplasty were admitted to the Clinic of Orthopedics and Traumatology at Sofiamed. Among them were 8 women and 3 men, with an average age of 69 years. All patients were readmitted between 18-21 days after the primary joint arthroplasty. Laboratory and microbiological investigations were conducted for all patients, followed by surgical intervention and prolonged antibiotic therapy. At a mean follow-up of 1 year and 2 months, all patients showed excellent results, except for one who died and one who was lost to follow-up.

Summary: During DNA repair, ATM-induced H2AX histone phosphorylation and MDC1 recruitment spread megabases beyond the damage site. While loop extrusion has been suggested to drive this spread, the underlying mechanism remains unclear. Herein, we provide two lines of evidence that loop extrusion is not the only driver of damage-induced γH2AX spread. First, cohesin loader NIPBL and cohesin subunit RAD21 accumulate considerably later than the phosphorylation of H2AX and MDC1 recruitment at micro-IR-induced damage. Second, auxin-induced RAD21 depletion does not affect γH2AX/MDC1 spread following micro-irradiation or DSB induction by zeocin. To determine if diffusion of activated ATM could account for the observed behavior, we measured the exchange rate and diffusion constants of ATM and MDC1 within damaged and unperturbed chromatin. Using these measurements, we introduced a quantitative model in which the freely diffusing activated ATM phosphorylates H2AX. This model faithfully describes the dynamics of ATM and subsequent γH2AX/MDC1 spread at complex DNA lesions.

In this article we discuss achievement badges as a way to motivate students’ learning process. We present an experiment that includes two groups of students, enrolled in an online mathematics course for a one-month period. The article illustrates the results and effects of using badges in e-learning.

In the area of upper extremity lipomas larger than 5 centimeters are considered giant. In the current article, we describe a case of a giant lipoma, which included the muscles of the first extensor compartment before their passing through it, in a woman in her 40s. The patient was successfully treated by excision of this tumor. The diagnosis and treatment options of giant lipomas of the upper extremity are briefly discussed.

The main purpose of the present paper is to prove the existence of periodic solutions of the three-body problem in the 3D Kepler formulation. We have solved the same problem in the case when the three particles are considered in an external inertial system. We start with the three-body equations of motion, which are a subset of the equations of motion (previously derived by us) for any number of bodies. In the Minkowski space, there are 12 equations of motion. It is proved that three of them are consequences of the other nine, so their number becomes nine, as much as the unknown trajectories are. The Kepler formulation assumes that one particle (the nucleus) is placed at the coordinate origin. The motion of the other two particles is described by a neutral system with respect to the unknown velocities. The state-dependent delays arise as a consequence of the finite vacuum speed of light. We obtain the equations of motion in spherical coordinates and split them into two groups. In the first group all arguments of the unknown functions are delays. We take their solutions as initial functions. Then, the equations of motion for the remaining two particles must be solved to the right of the initial point. To prove the existence–uniqueness of a periodic solution, we choose a space consisting of periodic infinitely smooth functions satisfying some supplementary conditions. Then, we use a suitable operator which acts on these spaces and whose fixed points are periodic solutions. We apply the fixed point theorem for the operators acting on the spaces of periodic functions. In this manner, we show the stability of the He atom in the frame of classical electrodynamics. In a previous paper of ours, we proved the existence of spin functions for plane motion. Thus, we confirm the Bohr and Sommerfeld’s hypothesis for the He atom.

Lyazzat Kulembekova,1 David Hailey,2 Maksut Kulzhanov,1 Adlet Tabarov,3 Svetlin Georgiev,4 Magdalena Jaworzynska,5 Antoniya Yordanova Yanakieva,4 Lyazzat Kosherbayeva1,6 1Health Policy and Management Department, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan; 2School of Information Sciences and Computer Technology, University of Wollongong, Wollongong, Australia; 3Deputy Director of the National Center for Health Development, Ministry of Health, Astana, Kazakhstan; 4Department HTA, Faculty of Public Health “prof. Tzecomir Vodenitcharov, MD, PhD, Dsc”, Medical University, Sofia, Bulgaria; 5Faculty of Economics, Maria Curie-Sklodowska University, Lublin, Poland; 6Department of Health Policy and Organization, Al-Farabi Kazakh National University, Almaty, KazakhstanCorrespondence: Lyazzat Kosherbayeva, Asfendiyarov Kazakh National Medical University, 88 Tole Bi Street, Almaty, Kazakhstan, Email lyazzat.k@mail.ru; klk.lyazzat@gmail.comBackground: In recent years, involvement of healthcare stakeholders in health technology assessment (HTA) has been discussed as helping the inclusion of social values in the decision-making process. The aim of our research was to identify and compare details from Kazakhstan, Poland and Bulgaria on their stakeholders’ involvement in the HTA process. Information was sought on their identification, responsibilities, and regulation.Methods: We conducted a survey of seven types of stakeholders in the healthcare systems of Kazakhstan, Poland, and Bulgaria. They included patients and the public, providers, purchasers, payers, policy makers, product makers, and principal investigators. They were questioned on their involvement in the HTA process, and on the objectives of their participation.Results: Levels of involvement of different kinds of stakeholder varied between countries, reflecting political and administrative developments. There was full or partial agreement on the objectives of stakeholder participation. All respondents agreed that representatives of the ministry of health should be involved in selection of stakeholders for HTA.Conclusion: Progress has been made in the involvement of stakeholders, with interest in further development in all three countries.Keywords: health priorities, health policy, stakeholder involvement, Universal health coverage, health technology assessment

Abstract Background A xanthoma is a rare bone condition consisting of a predominant collection of lipid-rich, foamy histiocytes. The central xanthoma of the jaws is a unique benign tumor. Case report A 15-year-old Caucasian male has been presented to our department. He had radiological changes in the area of the left mandibular angle, with an area of diffuse osteolysis of 3.0 cm by 2.0 cm. Computed tomography reveals an area of diffuse osteolysis that starts from the distal root of the lower second molar and reaches the ascending process. A bone biopsy was performed, which revealed a benign proliferative process composed of histiocytic cells involving and infiltrating trabecular bone in a background of loose fibrous connective tissue devoid of any other significant inflammatory infiltrate. The size of the formation was 2.9 cm by 2.0 cm. Immunohistochemical staining for CD68 was strongly positive and negative for S-100 and CD1a. From routine blood tests, cholesterol, triglycerides, and blood sugar are within normal values, which excludes systemic metabolic disease. Subsequent to the surgical intervention, the patient underwent postoperative assessments at intervals of 14, 30, 60 days, and a year later, revealing the absence of any discernible complications during the aforementioned observation periods. Conclusion The diagnosis of primary xanthoma of the mandible is rare and can often be confused with other histiocytic lesions. A differential diagnosis should be made with nonossifying fibroma and Langerhans cell histiocytosis, as in our case. In these cases, immunohistochemistry with CD 68, S-100, and CD1a, as well as blood parameters, are crucial for the diagnosis.

The current study reports the first records of an aphid-like pest and leaf pathogen on oak species in Bulgaria. In 2020-2023, leaf samples presenting characteristic yellow spots and lesions were collected from mature trees of Quercus petraea, Q. cerris, Q. frainetto and Q. robur in different localities of the country. Damage caused by oak obligate leaf pathogen Microstroma album, the leaf phylloxera, Phylloxera glabra, and the oak lace bug, Corythucha arcuata were identified on the lower surface of oak leaves. M. album was identified on all studied Quercus species. Angular white patches, the fruiting stage of the fungus, appeared on the lower surfaces of the leaves. P. glabra caused yellowish mosaic discoloration on the leaf surface of Quercus cerris, Q. frainetto and Q. pertaea. Sucking damage displayed a stippled pattern of yellow, brown, or whitish dots. In places where M. album develops, the invasive oak lace bug was often found as the only sucking species on oak leaves, which is most likely also a vector of the disease. Severe damage caused by established both obligate pathogen (M. album) and sucking insect pests (P. glabra, C. arcuata) could result in a weakening of the oak trees. On sufficiently weakened trees, secondary fungal pathogens or boring insects, commonly infested oak trees, can cause their death.

Rapidly destructive coxopathy (RDC) is a rare type of coxarthritis marked by swift deterioration of the hip joint. Although its cause remains unclear, several pathophysiological mechanisms are proposed. To comprehensively analyze this poorly understood condition, a literature search was conducted focusing on associations of bilateral RDC and rheumatoid arthritis (RA). The problem of long-standing RA, bilateral RDC with a febrile episode that preceded a rapid decline in mobility and severe hip pain, with radiological assessment confirmed bilateral hip destruction, was presented. Rapidly destructive coxopathy, especially when linked to RA, poses diagnostic and therapeutic challenges. Our review confirmed by the clinical picture emphasizes the need for vigilance in RA patients with hip involvement and calls for further research to understand RDC’s mechanisms and enhance clinical care.

Abstract Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.

Abstract Background CTCF is highly likely to be the ancestor of proteins that contain large clusters of C2H2 zinc finger domains, and its conservation is observed across most bilaterian organisms. In mammals, CTCF is the primary architectural protein involved in organizing chromosome topology and mediating enhancer–promoter interactions over long distances. In Drosophila, CTCF (dCTCF) cooperates with other architectural proteins to establish long-range interactions and chromatin boundaries. CTCFs of various organisms contain an unstructured N-terminal dimerization domain (DD) and clusters comprising eleven zinc-finger domains of the C2H2 type. The Drosophila (dCTCF) and human (hCTCF) CTCFs share sequence homology in only five C2H2 domains that specifically bind to a conserved 15 bp motif. Results Previously, we demonstrated that CTCFs from different organisms carry unstructured N-terminal dimerization domains (DDs) that lack sequence homology. Here we used the CTCF attP(mCh) platform to introduce desired changes in the Drosophila CTCF gene and generated a series of transgenic lines expressing dCTCF with different variants of the N-terminal domain. Our findings revealed that the functionality of dCTCF is significantly affected by the deletion of the N-terminal DD. Additionally, we observed a strong impact on the binding of the dCTCF mutant to chromatin upon deletion of the DD. However, chromatin binding was restored in transgenic flies expressing a chimeric CTCF protein with the DD of hCTCF. Although the chimeric protein exhibited lower expression levels than those of the dCTCF variants, it efficiently bound to chromatin similarly to the wild type (wt) protein. Conclusions Our findings suggest that one of the evolutionarily conserved functions of the unstructured N-terminal dimerization domain is to recruit dCTCF to its genomic sites in vivo.

This paper describes Archipsocus michamwiensis n. sp., a new species from the family Archipsocidae collected in Zanzibar, Tanzania. The single female (holotype) is macropterous and exhibits distinct reddish-brown colouration, and equal-length tarsal segments. Morphological measurements highlight features such as short antennae and a V-shaped pigmented area on the subgenital plate.

We present the findings of a Whole Exome Sequencing in a 2-year-old boy, conceived via In Vitro Fertilization with donor sperm, who suffers from an undiagnosed neurological syndrome. The following heterozygous variant in the EPHA4 gene was identified and classified as likely pathogenic: c.1655_1656, p.(Ser552CysfsTer23). Subsequent segregation analysis showed that the variant was not inherited from the mother and the sperm donor is not accessible for genetic testing. The presented results can further expand upon the genetic variants considered when diagnosing complex neurological syndromes and shows the importance of access to biological samples from donor banks in genetically ambiguous cases.

Abstract The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

Background: Palatal rugae, or plicae palatinae, are uniquely designed structures, well-formed, asymmetric, irregular mucosal folds suited in the anterior part of the hard palate. Palatoscopy, or the analysis of the palatal rugae pattern, is a simple, low-cost, non-invasive, innovative, and highly sensitive technique that can be successfully used in stomatology. This study aimed to analyze the palatal rugae pattern among an adolescent sample of the Albanian population in Kosovo, to determine the most prevalent palatal rugae pattern in both genders in association with Class I, II, and III malocclusions according to Angle’s classification. Materials and Methods: In this cross-sectional study, a total of 100 adolescents (50 males and 50 females) aged from 12 to 18 were randomly selected from schools in southeastern Kosovo. All subjects were divided into classes of malocclusion according to Angle’s classification (Class I, Class II, and Class III). The rugae patterns were classified based on shape, unification, and length according to the Thomas and Kotze classification. In the present study, the palatal rugae pattern in Class I, II and III malocclusions show no significant difference between female and male subjects. In Class I malocclusion, the straight pattern was dominant in female subjects, and the wavy pattern was dominant in male subjects. The straight pattern was dominant in males and females with Class II malocclusion. In Class III malocclusion, the wavy pattern was dominant in female subjects, and the curved pattern was dominant in male subjects. The study showed that male subjects were at slightly higher risk for having Class I malocclusion and slightly lower risk for having Class II and Class III malocclusions than female subjects. Conclusion: This study provides essential information regarding the dominant palatal rugae pattern among Albanian adolescents of southeastern Kosovo with Class I, II, and III malocclusions according to Angle’s classification.

The purpose of the present case report was to describe an extremely rare variation of vena cava cranialis in a Pug dog observed during routine dissection. The right cranial vena cava was normally represented, while the left cranial vein was described as an exception and very rarely in mammalian orders with an asymmetric cranial hollow vein, while there are animal classes and orders in which the double, symmetrical cranial hollow vein is normally present. The different end in the right atrium of this extra vein, visualised by imaging methods, can be misinterpreted as pathology of the heart. The left cranial vena cava is an important finding during radiological examination, as well as for specialists dealing with breeding and hereditary anomalies.

This study aimed to determine the effects of low-temperature plasma jet produced in gas helium (LTP-helium) on cariogenic biofilms composedby Streptococcusmutans, Streptococcus sanguinis and Streptococcus gordonii, and also by the combination of Candida albicans, Lactobacillus acidophilus and S. mutans. Biofilms were treated for 1, 3, 5, and 7 minutes. A 0.12% chlorhexidine solution was used as the positive control and sterile physiologic solution was the negative control. Biofilm viability was analyzed by viable cell recovery, scanning electron microscopy, and confocal laser scanning microscopy. All assays were performed intriplicate in three independent experiments. Multispecies biofilms exposed to LTP-helium had a significant reduction in viability when compared to the negative control (p < 0.0001). For biofilm formedby S. mutans, S. sanguinis, and S. gordonii, LTP treatments for 5 and 7 minutes caused similar reduction of morethan 2 log10. Also, a significant reduction in the viability of biofilms formedby C. albicans, L. acidophilus, and S. mutans was detected (p < 0.0001). In conclusion, LTP-helium reduced theviability of cariogenic biofilms with different microbial compositions, which indicates that LTP-helium is a potential tool for developing new protocols for dental caries prevention and treatment.

Mechanisms underlying cognitive impairment after perinatal stroke could be explained through brain network alterations. With aim to explore this connection, we conducted a matched test-control study to find a correlation between functional brain network properties and cognitive functions in children after perinatal stroke. First, we analyzed resting-state functional connectomes in the alpha frequency band from a 64-channel resting state EEG in 24 children with a history of perinatal stroke (12 with neonatal arterial ischemic stroke and 12 with neonatal hemorrhagic stroke) and compared them to the functional connectomes of 24 healthy controls. Next, all participants underwent cognitive evaluation. We analyzed the differences in functional brain network properties and cognitive abilities between groups and studied the correlation between network characteristics and specific cognitive functions. Functional brain networks after perinatal stroke had lower modularity, higher clustering coefficient, higher interhemispheric strength, higher characteristic path length and higher small world index. Modularity correlated positively with the IQ and processing speed, while clustering coefficient correlated negatively with IQ. Graph metrics, reflecting network segregation (clustering coefficient and small world index) correlated positively with a tendency to impulsive decision making, which also correlated positively with graph metrics, reflecting stronger functional connectivity (characteristic path length and interhemispheric strength). Our study suggests that specific cognitive functions correlate with different brain network properties and that functional network characteristics after perinatal stroke reflect poorer cognitive functioning.

This paper introduces multi-use applications to unlock behind-the-meter flexibility by integrating grid-serving capabilities with user-oriented control strategies. We deploy a hierarchical flexibility coordination process in a co-simulation research environment and propose a control strategy prioritizing self-consumption optimization with a secondary focus on grid-serving applications. This approach enhances the viability of behind-the-meter technologies, particularly benefiting battery energy storage systems with high investment costs. It also facilitates active grid operation amid the growing presence of distributed energy resources. The research’s key contribution lies in designing an information architecture to efficiently utilize behind-the-meter flexibility for grid-serving processes. The paper demonstrates the feasibility of a multi-use operation, combining user-oriented optimization and grid-serving flexibility provision for local grid congestion management. The implemented control algorithm in a home energy management system achieves grid-serving objectives while maintaining behind-the-meter asset performance. Co-simulation results show that in less than 2.5% of simulated time steps, transformer utilization exceeds operational limits in both scenarios, indicating the viability of multi-use operation for leveraging new value streams and managing grid congestion simultaneously.

Abstract The hyperdiverse wood‐inhabiting fungi play a crucial role in the global carbon cycle, but often are threatened by deadwood removal, particularly in temperate forests dominated by European beech (Fagus sylvatica) and Oriental beech (Fagus orientalis). To study the impact of abiotic drivers, deadwood factors, forest management and biogeographical patterns in forests of both beech species on fungal composition and diversity, we collected 215 deadwood‐drilling samples in 18 forests from France to Armenia and identified fungi by meta‐barcoding. In our analyses, we distinguished the patterns driven by rare, common, and dominant species using Hill numbers. Despite a broad overlap in species, the fungal composition with focus on rare species was determined by Fagus species, deadwood type, deadwood diameter, precipitation, temperature, and management status in decreasing order. Shifting the focus on common and dominant species, only Fagus species, both climate variables and deadwood type remained. The richness of species within the deadwood objects increased significantly only with decay stage. Gamma diversity in European beech forests was higher than in Oriental beech forests. We revealed the highest gamma diversity for old‐growth forests of European beech when focusing on dominant species. Our results implicate that deadwood retention efforts, focusing on dominant fungi species, critical for the decay process, should be distributed across precipitation and temperature gradients and both Fagus species. Strategies focusing on rare species should additionally focus on different diameters and on the conservation of old‐growth forests.

Abstract Background Autosomal recessive spastic ataxia ofCharlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early‐onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES). Methods Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia. Results Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2‐hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT). Conclusion We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking

Background This article introduces an innovative classification methodology to identify nanowires within scanning electron microscope images. Methods Our approach employs advanced image manipulation techniques in conjunction with machine learning-based recognition algorithms. The effectiveness of our proposed method is demonstrated through its application to the categorization of scanning electron microscopy images depicting nanowires arrays. Results The method’s capability to isolate and distinguish individual nanowires within an array is the primary factor in the observed accuracy. The foundational data set for model training comprises scanning electron microscopy images featuring 240 III-V nanowire arrays grown with metal organic chemical vapor deposition on silicon substrates. Each of these arrays consists of 66 nanowires. The results underscore the model’s proficiency in discerning distinct wire configurations and detecting parasitic crystals. Our approach yields an average F1 score of 0.91, indicating high precision and recall. Conclusions Such a high level of performance and accuracy of ML methods demonstrate the viability of our technique not only for academic but also for practical commercial implementation and usage.

BackgroundParkinson’s disease is associated with increased impulsivity, which can be divided into several domains: motor (consisting of proactive and reactive subdomains), reflection, and cognitive impulsivity. Evidence suggests that both dopaminergic medication and subthalamic nucleus deep brain stimulation can affect impulsivity. Therefore, we set out to investigate the effects of dopaminergic medication and subthalamic nucleus deep brain stimulation on motor, reflection, and cognitive impulsivity in Parkinson’s disease patients.MethodsTwenty Parkinson’s disease patients who underwent subthalamic nucleus deep brain stimulation were tested ON and OFF dopaminergic medication and ON and OFF subthalamic nucleus deep brain stimulation. They performed three different impulsivity tasks: the AX continuous performance task (AX-CPT) to test for motor impulsivity, the Beads task for reflection impulsivity, and the Delay discounting task for cognitive impulsivity.ResultsThe combination of subthalamic nucleus deep brain stimulation and dopaminergic medication led to an increase in motor impulsivity (p = 0.036), both proactive (p = 0.045) and reactive (p = 0.006). There was no effect of either dopaminergic medication or subthalamic nucleus deep brain stimulation on reflection and cognitive impulsivity.ConclusionThe combination of dopaminergic medication and subthalamic nucleus deep brain stimulation leads to increased motor, but not cognitive or reflection, impulsivity in patients with Parkinson’s disease. Both proactive and reactive motor impulsivity were impaired by the combination of dopaminergic medication and subthalamic nucleus deep brain stimulation.