Germline whole exome sequencing from molecular tumor boards has the potential to be repurposed to support clinical pharmacogenomics. However, accurately calling pharmacogenomics-relevant genotypes from exome sequencing data remains challenging. Accordingly, this study assessed the analytical validity of the computational tool, Aldy, in calling pharmacogenomics-relevant genotypes from exome sequencing data for 13 major pharmacogenes. Germline DNA from whole blood was obtained for 164 subjects seen at an institutional molecular solid tumor board. All subjects had whole exome sequencing from Ashion Analytics and panel-based genotyping from an institutional pharmacogenomics laboratory. Aldy v3.3 was operationalized on the LifeOmic Precision Health Cloud with copy number fixed to two copies per gene. Aldy results were compared to those from genotyping for 56 star-defining variants within CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, NUDT15, SLCO1B1, and TPMT. Read depth was >100x for all variants except CYP3A4*22. For 75 subjects in the validation cohort, all 3,393 Aldy variant calls were concordant with genotyping. Aldy calls for 736 diplotypes containing alleles assessed by both platforms were also concordant. Aldy identified additional star alleles not covered by targeted genotyping for 139 diplotypes. Aldy accurately called variants and diplotypes for 13 major pharmacogenes except for CYP2D6 variants involving copy number variations, thus allowing repurposing of whole exome sequencing to support clinical pharmacogenomics.

Background: Studies suggest that applying probiotic skincare products may have beneficial effects on the skin due to bacteria competitiveness and specific metabolites produced by probiotics. The cream CLS02021 is a postbiotic blend of metabolites, including organic acids, enzymes, and peptides that are a result of the co-fermentation of three proprietary probiotic strains and is specific for its high concentration of the enzyme Sphingomyelinase which plays a significant role in cell signaling pathways and ceramide production. Objective: The aim of this study is to evaluate the cosmetic effects of probiotic-derived Ingredient CLS02021 and its safety in healthy volunteers. Methods: Fifty healthy volunteers between 18 and 69 years old were recruited to participate in this multicentric, randomized, intra-individual, double-blind group study. Following a face-split design, volunteers applied both face cream containing CLS02021 on one side of their face and a placebo cream on the other side of their face for a total duration of four weeks, two times a day. Evaluation of the cosmetic effects included instrument measurements of moisturizing, elasticity, wrinkle depth, sebum production, pore size, melanin production, sensitivity, and side effects. Results: A significant difference of CLS02021 over the placebo group was observed for moisture and elasticity increase (both p<0.001), pore size (p<0.01), and a wrinkle depth decrease (p<0.05). No significant differences were noted in sebum production, melanin level, skin cleanliness, and sensitivity between groups. Conclusion: CLS02021, as a probiotic-derived ingredient, showed strong beneficial effects on skin moisture and elasticity increase, wrinkle depth, and pore size reduction. Face cream containing CLS02021 is well tolerated and could be an organic choice for cosmetic hydrating and antiaging skincare treatment.

We collected 1,671 Dermacentor reticulatus ticks from 17 locations in the Czech Republic, Slovakia, and Hungary. We found 47.9% overall prevalence of Rickettsia species in ticks over all locations. Sequence analysis confirmed that all tested samples belonged to R. raoultii, the causative agent of tick-borne lymphadenopathy.

Simple Summary Oral cavity is the most common site of head and neck cancer which is ranked as the eighth most common cancer worldwide. Oral cancer treatment is often associated with significant morbidity and is sometimes ineffective. These cancers, mainly due to tobacco and alcohol consumption, can develop from oral potentially malignant disorders, the most common of which is oral leukoplakia. Some of these oral potentially malignant disorders disappear, while others will transform to oral cancer. Patients may also develop cancer in the field of cancerization. Unfortunately, except for the surgical excision of lesions with dysplasia, there is no effective intervention to effectively prevent transformation or cancer development in the field of cancerization. Moreover, no standardized biomarker has been clearly identified as sufficient to predict malignant transformation. In this article, several experts discuss the main challenges in oral cancer prevention, in particular the need (i) to define new a new classification system integrating cellular and molecular features aiming (ii) at better identifying patients at high risk of malignant transformation, and (iii) at developing treatment strategies to prevent their malignant transformation of oral potentially malignant disorders. Abstract Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.

Introduction: In Sweden, during specialty training, the nurse anesthetist learns how to ensure patient safety in a health-care setting by implementing the surgical checklist measures during perioperative care. To date, there are still considerable shortcomings when it comes to implementing these patient safety measures in Swedish hospitals. Aim: The purpose of this study is to describe the use of the WHO surgical safety checklist (WHOSSC) by surgical teams, with special emphasis on nurse anesthetists to increase patient safety. Materials and Methods: This descriptive questionnaire-based study was performed between September 2018 and March 2019 and included 196 health-care professionals who completed the questionnaire. The survey was carried out among all the health-care professionals at two surgical units at a university hospital during the data collection period. Results: The results reveal that the majority of health-care staff in this study agree with the need to implement the WHOSSC during surgery and the necessity of doing so to ensure patient safety. However, it is not clear whether this checklist needs to be made a matter of routine at the clinics and whether this is possible in emergency situations. Conclusion: The nurse anesthetists, as members of the surgical team, use the list all the time in emergency situations and conclude, like other members of the team, that the list improves patient safety. Clearer procedures are needed during surgery regarding the usage of the checklist in practice, and there should be a designated person in the surgical team responsible for implementing the checklist.

Objectives. The present study aimed to assess changes in the perception of and willingness to participate in organ donation (OD) among immigrants from Bosnia and Herzegovina living in Sweden from the perspective of gender differences. Materials and Methods. A cross-sectional study with 60 participants born in Bosnia and Herzegovina and living in Sweden was performed. Data were collected using a self-administrative questionnaire, providing demographic characteristics, information about opinions, awareness, and knowledge on the donation process and religious approach to the subject, willingness to donate/receive organs, and possession of a donor card. Results. Our results showed significant differences between genders regarding the definition of transplantation (P<0.0001), information about OD (P<0.0001), knowledge (P<0.0001) and importance of OD (P<0.003), religious permitting (P=0.0001), and religious opposing (P=0.0007) to OD. Furthermore, a significant difference was observed regarding the preferred recipient (P=0.0062) and the possession of the donor card (P<0.0001). Regression analysis showed that female gender and higher income were statistically significant in prediction of positive attitudes toward OD (P=0.0027, P=0.0002, respectively). Conclusion. Change of social background and integration into Swedish society undoubtedly led to change in the attitudes toward OD, regardless of the perspective of gender differences. However, women were found to have more positive attitudes toward OD.

There are activities in viticulture and mariculture that require extreme physical endurance from human workers, making them prime candidates for automation and robotization. This paper presents a novel, practical, heterogeneous, autonomous robotic system divided into two main parts, each dealing with respective scenarios in viticulture and mariculture. The robotic components and the subsystems that enable collaboration were developed as part of the ongoing HEKTOR project, and each specific scenario is presented. In viticulture, this includes vineyard surveillance, spraying and suckering with an all-terrain mobile manipulator (ATMM) and a lightweight autonomous aerial robot (LAAR) that can be used in very steep vineyards where other mechanization fails. In mariculture, scenarios include coordinated aerial and subsurface monitoring of fish net pens using the LAAR, an autonomous surface vehicle (ASV), and a remotely operated underwater vehicle (ROV). All robotic components communicate and coordinate their actions through the Robot Operating System (ROS). Field tests demonstrate the great capabilities of the HEKTOR system for the fully autonomous execution of very strenuous and hazardous work in viticulture and mariculture, while meeting the necessary conditions for the required quality and quantity of the work performed.

Background: Endocrine disrupting air pollutants such as sulphur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), fine particle matter (PM2.5), and ozone (O3) can affect thyroid gland function on the level of synthesis, metabolism, and the action of its hormones. Objective: The aim of this study was to establish whether increased air pollution could contribute to an increased incidence of autoimmune thyroid diseases (AITD). Methods: A retrospective analysis was conducted of the medical records of 82000 patients at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. The target group of this study comprised a total of 174 patients from the Lukavac area. Daily data on concentrations of air pollutants were collected from the air quality monitoring station located in Lukavac. The study covered the period from 2015 to 2020. Results: The results of the monitoring confirmed the presence of air pollutants in concentrations above the permitted limits throughout the entire observed period. Concentrations of PM2.5, SO2, NO2, CO, and O3 were in the range of 1.90–431.40 μg/m3, 3.60-620.50 μg/m3, 3.40-66.20 μg/m3, 48.00-7002.00 μg/m3, and 0.70-89.40 μg/m3, with means of 64.08 μg/m3, 77.48 μg/m3, 22.57 μg/m3, 1657.15 μg/m3, and 31.49 μg/m3, respectively. During the six-year period, 174 cases of AITD were registered, of which 150 (86.21%) were women and 24 (13.79%) men. Hashimoto’s thyroiditis was found in 33 patients (18.97%), whilst 141 patients (81.03%) were diagnosed with atrophic thyroiditis. The highest total incidence of autoimmune thyroiditis was recorded in 2017, when it reached 99.49, 95% CI. Conclusion: The effects of chronic exposure to a mixture of air pollutants on the function of the thyroid gland are still not sufficiently well-known, but the numerical tendency towards a higher incidence of AITD in this study, albeit without statistical significance (p>0.05), still underlines the need for additional research.

Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are indications that vitamin B6 plays a significant role in the process of transsulfuration in homocysteine metabolism, specifically, in a part of the reaction in which homocysteine transfers a sulfhydryl group to serine to form α-ketobutyrate and cysteine. Therefore, an elevated homocysteine concentration (hyperhomocysteinemia) could be a consequence of vitamin B6 and/or folate deficiency. Hyperhomocysteinemia in turn could damage the endothelium and the blood vessel wall and induce worsening of atherosclerotic process, having a negative impact on the mechanisms underlying MI and HF, such as oxidative stress, inflammation, and altered function of gasotransmitters. Given the importance of the vitamin B6 in homocysteine metabolism, in this paper, we review its role in reducing oxidative stress and inflammation, influencing the functions of gasotransmitters, and improving vasodilatation and coronary flow in animal models of MI and HF.

Background: The prevalence of chronic heart failure (CHF) is up to 1-2% of the adult population in developed countries, rising to >10% after the age of 70. Heart failure with reduced ejection fraction (HFrEF) remains a prevalent clinical syndrome associated with significant morbidity and mortality. Objective: The aim of this study was to evaluate the clinical efficacy of sacubitril/valsartan in a group of ambulatory patients with heart failure with reduced ejection fraction (HFrEF) and its effect on the hemodynamic, metabolic, renal, and cardiac remodeling parameters. Methods: From January 2018 to May 2021, 106 patients with chronic heart failure with reduced ejection fraction (HFrEF) were prospectively enrolled. Patients treated with sacubitril/valsartan (ARNI) were compared with an arm of the same size (n = 53) and matched by age and gender who were taking a standard optimal medical therapy for HFrEF. Results: The 106 patients completing the study were characterized by age: 69.5 ± 8.0, 64% are male gender. The mean duration of follow-up in the 2 treatment arms was 12 months. In the ARNI arm, we evaluate the hemodynamic, metabolic, renal, and cardiac remodeling parameters upon the initial evaluation and at the end of the follow-up after 12 months treatment with sacubitril/valsartan. The LVEF values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm, 42.1 % vs. 30.1%. The LVMI decreased from a baseline value of 153.1 g/m2 to 147.8 g/m2 with significant improvement only in the arm treated with ARNI. The eGFR values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm 70.1 vs. 64.9 mL/min/1.73 m2. Initiation and titration of sacubitril-valsartan was associated with a reduction in NT-pro-BNP concentration, the values of NT-pro-BNP improved significantly only in the arm treated with ARNI 3107.1 vs. 5678.2. Mortality and re-hospitalization due to HF were lower in the arm treated with ARNI compared to the control (20.3 vs. 32.4 % and 25.3 vs. 46.6 %, respectively; p < 0.05). Conclusion: Sacubitril/valsartan is an important advancement in the treatment of HFrEF. Sacubitril/valsartan induce “hemodynamic recovery”. This study provides real-world data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan in ambulatory setting.

Extended Abstract Phosphonates possess a great potential for the therapy of bone tumours due to their inhibitory potential for osteoclasts. The delivery of phosphonates via cellulose nanocrystals (CNCs) seems a promising approach for their increased efficacy in target tissues. However, the immunological effects of these conjugates have not been investigated thoroughly. Here we modified used wood-based native (n)CNC, oxidized (ox-CNC) and phosphonate (3-AminoPropylphosphonic Acid (ApA))-conjugated CNC to test their physicochemical properties and immunomodulatory potential. Modification of CNC increased their elasticity module and hardness, which resulted in their reduced internalization by

Objective. The objective of this study was to study the morphometry of the styloid process of the temporal bone and the prevalence of an elongated styloid process in relation to side and gender. Material and Method. The present study included 200 human skulls which were procured from the rich osteological collections of the Department of Anatomy, Faculty of Medicine, University of Sarajevo. The styloid process was observed macroscopically on both sides of all the skulls and elongations, if any, were noted. The lengths of the styloid processes were measured using digital vernier calipers. The measurements were taken from the point of emergence of the process (base) up to the tip. Results. Out of 200 specimens, only 14 cases (7%) exhibited an elongated styloid process. The mean length of the styloid process was 25.8±4.68 mm and 24.2±4.54 mm for the right and left sides, respectively. The size of the styloid process did not different significantly between the two sides (P=0.724). The mean length of the styloid process was 24.05±3.54 mm in females and 25.95±5.68 mm in males, and the difference was statistically significant (P=0.023). Conclusion. The study and knowledge of the anatomical variations of the styloid process in the Bosnian population may help clinicians to diagnose Eagle’s syndrome. Knowledge of this disorder can prevent the worsening of the painful symptoms related to an elongated styloid process.

Introduction: Domestic violence is a threat to human dignity and public health. Mounting evidence shows that domestic violence erodes personal and public health, spawning issues such as lifelong mental health challenges. To further compound the situation, COVID-19 and societies’ poor response to the pandemic have not only worsened the domestic violence crisis but also disrupted mental health services for domestic violence victims. While technology-based health solutions can overcome physical constraints posed by the pandemic and offer timely support to address domestic violence victims’ mental health issues, there is a dearth of research in the literature. To bridge the research gap, in this study, we aim to examine technology-based mental health solutions for domestic violence victims amid COVID-19. Methods: A literature review was conducted to examine solutions that domestic violence victims can utilize to safeguard and improve their mental health amid COVID-19. Databases including PubMed, PsycINFO, and Scopus were utilized for the literature search. The search was focused on four themes: domestic violence, mental health, technology-based interventions, and COVID-19. A reverse search of pertinent references was conducted in Google Scholar. The social ecological model was utilized to systematically structure the review findings. Results: The findings show that a wide array of technology-based solutions has been proposed to address mental health challenges faced by domestic violence victims amid COVID-19. However, none of these proposals is based on empirical evidence amid COVID-19. In terms of social and ecological levels of influence, most of the interventions were developed on the individual level, as opposed to the community level or social level, effectively placing the healthcare responsibility on the victims rather than government and health officials. Furthermore, most of the articles failed to address risks associated with utilizing technology-based interventions (e.g., privacy issues) or navigating the online environment (e.g., cyberstalking). Conclusion: Overall, our findings highlight the need for greater research endeavors on the research topic. Although technology-based interventions have great potential in resolving domestic violence victims’ mental health issues, risks associated with these health solutions should be comprehensively acknowledged and addressed.