Phenotypic plasticity and inflammation, two well-established hallmarks of cancer, play key roles in local invasion and distant metastasis by enabling rapid adaptation of tumor cells to dynamic micro- environmental changes. Here, we show that in oral squamous carcinoma cell carcinoma (OSCC), the competition between the NuRD and SWI/SNF chromatin remodeling complexes plays a pivotal role in regulating both epithelial-mesenchymal plasticity (EMP) and inflammation. By perturbing these complexes, we demonstrate their opposing downstream effects on inflammatory pathways and EMP regulation. In particular, downregulation of the BRG1-specific SWI/SNF complex deregulates key inflammatory genes such as TNF-α and IL6 in opposite ways when compared with loss of CDK2AP1, a key member of the NuRD complex. We show that CDK2AP1 genetic ablation triggers a pro-inflammatory secretome encompassing several chemo- and cytokines thus promoting the recruitment of monocytes into the tumor microenvironment (TME). Furthermore, CDK2AP1 deletion stimulates their differentiation into M2-like macrophages, as also validated on tumor microarrays from OSCC patient- derived tumor samples. Further analysis of the inverse correlation between CDK2AP1 expression and TME immune infiltration revealed specific downstream effects on CD68+ macrophage abundance and localization. Our study sheds light on the role of chromatin remodeling complexes in OSCC locoregional invasion and points at the potential of CDK2AP1 and other members of the NuRD and SWI/SNF chromatin remodeling complexes as prognostic markers and therapeutic targets.

This paper introduces a simultaneous optimization approach to synthesizing work and heat exchange networks (WHENs). The proposed work and heat integration (WHI) superstructure enables different thermodynamic paths of pressure and temperature-changing streams. The superstructure is connected to a heat exchanger network (HEN) superstructure, enabling the heat integration of hot and cold streams identified within the WHI superstructure. A two-step solution strategy is proposed, consisting of initialization and design steps. In the first step, a thermodynamic path model based on the WHI superstructure is combined with a model for simultaneous optimization and heat integration. This nonlinear programming (NLP) model aims to minimize operating expenditures and provide an initial solution for the second optimization step. In addition, hot and cold streams are identified, enabling additional model reduction. In the second step of the proposed solution approach, a thermodynamic path model is combined with the modified HEN model to minimize the network’s total annualized cost (TAC). The proposed mixed integer nonlinear programming (MINLP) model is validated by several examples, exploring the impact of the equipment costing and annualization factor on the optimal network design. The results from these case studies clearly indicate that the new synthesis approach proposed in this paper produces solutions that are consistently similar to or better than the designs presented in the literature using other methodologies.

Introduction: Patients following the acute stage of Severe Acute Respiratory Syndrome Coronavirus 2 were shown to present with persisting symptoms including fatigue, dyspnea, joint pain, and chest pain. The aim of this study was to investigate the effect of a 6-week home physiotherapy program on the psychological and physical symptoms, as well as the physical abilities to perform activities of daily living in post-COVID-19 patients. Methods: The subjects were 39 adult patients who had been diagnosed with COVID-19 and had been hospitalized at the University Clinical Center of Kosovo. Patients initially underwent a physiotherapy assessment 2-3 weeks after discharge from the hospital, including sociodemographic data, psychological and physical symptoms, and functional performance in daily activities using the Patient-Specific Functional Scale (PSFS). Based on their functional capacity, the patients received two types of brochures for a home physiotherapy program that was carried out over the next 6 weeks. Upon the completion of the physiotherapy program, 23 patients reported for the second physiotherapy assessment. The Mann–Whitney Wilcoxon test was used for comparison of the variables obtained during the first and second assessments. Results: Pre–post analysis showed that the symptoms including excessive fatigue, difficulty breathing, and insomnia were significantly less present following the home physiotherapy program (p = 0.005; p = 0.008; p = 0.034). On the PSFS scale, the mean score increased from 5.2 (2.1) to 7.8 (0.5) for stair climbing, from 5.5 (1.8) to 8.8 (1.6) for walking longer distances, and from 3.7 (3.2) to 4.0 (5.6) for running. Conclusion: Although limited by the absence of a control group, the findings from this study indicate that home physiotherapy intervention can be feasible and effective in enhancing psychological and physical symptoms, as well as activities of daily living in post-COVID-19 patients following hospitalization.

The aim of this study was to determine the frequencies of alleles and genotypes of the single nucleotide polymorphism of the FTO gene (rs17817449) and the intensity of physical activity in relation to the BMI of subjects in the student population. Genotyping was performed using the PCR-RFLP method. 94 subjects stated that they were not physically active, 57 subjects were moderately physically active and 52 were intensely physically active. In the total sample, the risk allele G of the investigated polymorphism rs17817449 of the FTO gene had a lower frequency (41.8%) compared to the normal allele T (58.13%). Although a higher frequency of the risk allele G was found in the group of overweight subjects compared to the group with BMI < 25, the difference was not statistically significant (p > 0.05).

The topic of this research, chronic subdural hematoma (CSH), is one of the most common pathologies in neurosurgery, and it is more frequent in the elderly. Surgical evacuation has been widely considered the gold standard treatment. Despite the excellent outcomes, sometimes some cases require a different approach. The treatment choice depends on the general condition of the patients, as well as the clinical presentation and hematoma volume. Also, preexisting comorbidities in elderly patients, postoperative complications, and the ability to recover must be considered. Consequently, conservative treatment can be effective in carefully selected cases, and can be considered if the patient's neurological and physical conditions allow. Some drugs contribute to CSH resolution by changing the capsule membrane permeability and inhibiting the fibrinolytic and inflammatory systems. Our work is based on the efficacy of dexamethasone as a method of conservative therapy, and it was demonstrated in the case of a 91-year-old patient.

Objectives: To measure and analyze the seroprevalence and risk factors of human brucellosis among clinically suspected patients in the Travnik area, Bosnia and Herzegovina in the period 2018-2023. Methods: A total of 337 samples of clinically suspected brucellosis patients in Travnik, Central Bosnia and Herzegovina were collected between 2018-2023. Rose Bengal agglutination was used for sera testing. Expressive and investigative statistics were considered. Differences between the prevalence of brucellosis according to age, sex, and the seasonal incidence rate were assessed. Results: The prevalence of brucellosis among the suspected patients was 23.30%. The highest prevalence rate 35.71%, was detected during year 2021. Higher rate of brucellosis was observed among males 63.86% than females 36.14%. Most cases were reported during month of June and October, 14.15% and 14.19% respectively. The highest prevalence, 56.76% rate was observed in age group 41–60 years old. Conclusion: Our survey found a high prevalence of human brucellosis among clinically suspected patients in Travnik area strongly indicating that clinical suspicion is a valid criterion, which requires fast laboratory detection and patient treatment. Detecting specific anti-Brucella antibodies using agglutination Rose Bengal test is a fast a reliable diagnostic procedure for clinically suspect individuals. There is a strong association between human brucellosis and age.

Increasingly, and often mutually conflicting requirements for the use of water resources, there is a need for more complex management methods, including the management of the volume of reservoirs. Silt filling of reservoirs is one of the most well-known problems of river hydraulics. Dams and reservoirs, created by damming river flows, cause the retention of river sediment (drag and floating sediment) that comes from the gravitating basins, or sub-basins of the reservoir's tributaries. By analyzing the sediment transport on the tributaries, and the total amount of sediment deposited in the Modrac multi-purpose reservoir, real data are obtained on the amount of sediment introduced into the Modrac multi-pupose reservoir, the dynamics of sediment input, and the degree of pollution of this type of water body. The Modrac multi-purpose reservoir is the only available water resource in the region of Tuzla and its surroundings. Acknowledging the fact that the useful volume of the reservoir is limited, and that over time the reservoir is filled with dragged sediment and coal dust as floating sediment, and that consumers - the population, industry and others must be provided with a water supply with a high degree of safety. Excess water needs to be used to the maximum for the purpose of electricity production, and there is a need to optimize the system, i.e. more efficient management of the water resources of the reservoir, i.e. to prove the maximum utilization of the reservoir while continuously providing all the necessary amounts of water to which the Modrac multi-purpose reservoir is connected.

The auditory brainstem response (ABR) is a measure of subcortical activity in response to auditory stimuli. The wave V peak of the ABR depends on stimulus intensity level, and has been widely used for clinical hearing assessment. Conventional methods to estimate the ABR average electroencephalography (EEG) responses to short unnatural stimuli such as clicks. Recent work has moved towards more ecologically relevant continuous speech stimuli using linear deconvolution models called Temporal Response Functions (TRFs). Investigating whether the TRF waveform changes with stimulus intensity is a crucial step towards the use of natural speech stimuli for hearing assessments involving subcortical responses. Here, we develop methods to estimate level-dependent subcortical TRFs using EEG data collected from 21 participants listening to continuous speech presented at 4 different intensity levels. We find that level-dependent changes can be detected in the wave V peak of the subcortical TRF for almost all participants, and are consistent with level-dependent changes in click-ABR wave V. We also investigate the most suitable peripheral auditory model to generate predictors for level-dependent subcortical TRFs and find that simple gammatone filterbanks perform the best. Additionally, around 6 minutes of data may be sufficient for detecting level-dependent effects and wave V peaks above the noise floor for speech segments with higher intensity. Finally, we show a proof-of-concept that level dependent subcortical TRFs can be detected even for the inherent intensity fluctuations in natural continuous speech. Visual abstract Significance statement Subcortical EEG responses to sound depend on the stimulus intensity level and provide a window into the early human auditory pathway. However, current methods detect responses using unnatural transient stimuli such as clicks or chirps. We develop methods for detecting level-dependent responses to continuous speech stimuli, which is more ecologically relevant and may provide several advantages over transient stimuli. Critically, we find consistent patterns of level dependent subcortical responses to continuous speech at an individual level, that are directly comparable to those seen for conventional responses to click stimuli. Our work lays the foundation for the use of subcortical responses to natural speech stimuli in future applications such as clinical hearing assessment and hearing assistive technology.

In order to ensure the long-term sustainability of the conservation process of Norwegian plum germplasm, as well as to enhance the possibility of its utilization, a central plum heritage cultivar collection was established in 2020. In this study, 40 plum accessions maintained at the Ullensvang plum heritage cultivar collection were genetically characterized using a set of nine microsatellite markers recently approved by the ECPGR Prunus working group. The obtained molecular data were used to investigate the genetic identity, diversity, and structure among the analyzed accessions. No redundancies were detected among the plum accessions, which is in stark contrast to the previous molecular study on plum samples collected through an on-farm inventory of Southern Norway. Furthermore, the obtained data indicate that the Ullensvang collection contains a significant genetic diversity of Norwegian plum germplasm, previously held in decentralized sites. With that in mind, this collection can certainly be considered for the role of the National Clonal Plum Germplasm Repository. The nine microsatellite markers, recommended by ECPGR, revealed a genetic structure not entirely tied to previously proposed pomological groups, possibly indicating a history of hybridization among members of the various groups.

Introduction: There are concerns with rising rates of antimicrobial resistance (AMR) across countries with appreciable impact on morbidity, mortality and costs. Amongst low- and middle-income countries, a key driver of AMR is the excessive use of antibiotics in ambulatory care, with a critical area being the appreciable selling of antibiotics without a prescription often driven by patient demand and limited knowledge. There is currently conflicting evidence in South Africa regarding this practice. Consequently, there is a need to explore these critical issues amongst patients, especially in more rural areas of South Africa. A pilot study was undertaken to address this. Methods: A two-step descriptive approach was undertaken. This involved two questionnaires amongst patients exiting chain and independent community pharmacies followed by cognitive interviews. Results: Overall, 21 patients were approached for an interview, including 11 for Part 1 of the questionnaire with 3 declining, and 10 for Part 2, with 2 declining. Subsequently 8 patients completed each part of the questionnaire.. On average, it took 2 min 13 s to complete both parts. 3 of the 5 patients being dispensed an antibiotic were dispensed one without a prescription, with all 3 patients exiting from independent pharmacies. Key reasons for self-purchasing included money and convenience. There was mixed knowledge regarding antibiotics and AMR amongst the 8 patients interviewed with Part 2. Overall, there was a satisfactory understanding of the Part 1 questions, although some modifications were suggested. Some participants had difficulty with fully understanding the questions in Part 2, with a number of suggestions made to improve this for the main study. Conclusion: There were concerns with the extent of purchasing antibiotics without a prescription in this pilot study as well as the knowledge of patients regarding antibiotics and AMR. Both areas need addressing and will be explored further in the main study.