Goce Delcev University

Idea generation, as a key component of the Front End of Innovation (FEI), is a critical phase in entrepreneurial endeavors, serving as the foundation for new venture creation and product development. Innovation management and entrepreneurship literature underscores the importance of idea generation, emphasizing its role as an essential precursor to successful ventures and products. While academic research has extensively explored the FEI and idea generation methods, a significant gap remains in developing FEI models for broad use or specific contexts. Especially, there is a lack of action-oriented, performative models that offer detailed, applicable techniques and tools. Existing models often adopt only a corporate perspective, are overly broad, use complex structures or miss the use of new emerging digital tools, which makes these models not accessible or relevant to entrepreneurs or applicable across different industries or product types. To address these issues, employing the Integrative Literature Review Methodology, this study proposes a comprehensive FEI framework designed to facilitate the development of new idea-generation models that cater to different types of users and contexts and incorporate contemporary techniques and tools. The framework focuses on six (6) key dimensions of FEI models: (1) Model Orientation, Scope and Context; (2) Innovation Type and Innovation Drivers; (3) Model Structure and Visualization; (4) Flow of Activities, Flexibility and Adaptability; (5) Core FEI Activities and Granularity; and (6) Toolkit (Tools and Techniques), offering a range of recommendations for each. It aims to provide scholars and practitioners (entrepreneurs, teams, or companies) with a systematic approach to creating usable FEI models that make the Front End of Innovation more structured and predictable.

Bektashism order as a spiritual direction in Sufism has always aroused attention regarding social behavior stemming from its doctrine and ideology. In the Republic of Macedonia, Bektashi dervish order has its roots in the 13th century, before the arrival of the Ottomans, through the activity of the dervishes who traveled and settled in this territory. One of the most important and influential tekkes is Harabati Baba in Tetovo, built during the 16th century, which in the course of history has passed through turbulent social ordeals, but still remains a synonym of Bektashism in the Republic of Macedonia. Hence came our idea to present in this paper the social transformations resulting from the change in the ethnic structure of the followers, and the social and political situation of the country. We view this situation through musical tradition, because it is an important part of the ritual and serves as a fundamental tool in the expression of mystical theosophy. We achieved our goal through field research, by interviews and analysis of audio and printed music materials that are used today and testify to the change of the sound image of the music tradition of Bektashi in Harabati Baba Tekke in Tetovo.

Our research on the music tradition perspectives during the periods similar to the current 21st century conditions in the Republic of Macedonia resulted in findings that reveal significant modifications in the musical expressions. We perceive these changes as an outcome of the individual and collective cultural identities, which are derived from both the ethnicity and domination of the global tendencies. Though these two ongoing and sequential “live” processes are dissimilar in nature, they are also complementary to each other in certain segments to such an extent that the specifics of their music products encompass the most subtle elements of the spiritual tradition. The main objective of this study is to present the cultural identity’s impact on the musical segments in the spiritual mystical tradition in the Republic of Macedonia, where there are four dervish orders active at the moment: Rifai, Halveti, Bektashi, and Melami. Due to the complexity of this phenomenon, we have restricted our field of theoretical and research interest to spiritual music in the rites of the Rifai order. Rifai was considered to be the only dervish order in which there have been alterations in the ethnicity of the followers of the tarikat; hence, we believed this to be the most radiant example for our initial thesis. The qualitative research involved analyses of digitalized music contents that were performed on the occasion of the festive dhikirs during the period 2008–2009. Collected data validate the manifestation of certain modifications in the musical expression, developed by the recognition of particular segments from the global music culture and also as a result of the ethnic–cultural identity.

A highly sensitive ultra-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-TQ-MS) was applied for simultaneous determination of seven biogenic amines (cadaverine, putrescine, histamine, spermine, tyramine, phenyethylamine and tryptamine) in Montenegrin red Vranac and Kratošija ( Vitis Vinifera L.) wines. The method was validated, confirmed the suitability for determination of biogenic amines in red wines and was applied to examine the changes of biogenic amines in three vinification stages: after alcoholic fermentation, malolactic fermentataion and ten months of aging of the wines. The results showed that the total amine levels were low, ranging from 1.27 to 3.26 mg/L, observing increased concentration in the wines after finished malolactic fermentation. Putrescine, which was constituted as a main amine in wines (range: 0.79 to 2.39 mg/L), was observed in a slightly higher content in Vranac wines compared to Kratošija, followed by the aliphatic cadaverine (range: 0.091 to 0.35 mg/L) and the aromatic phenylethylamine (range: 0.119–0.373 mg/L). Histamine and tyramine which are subject of toxicological interest, were present in a very low concentration in wines (on average value: 0.082 and 0.015 mg/L, respectively). Cadaverine and putrescine significantly correlated with the sum of total biogenic amines, even the reached values were below the toxicity threshold. According to the principal component analysis, wines were clearly separated in three groups according to the three vinification stages.

Investigating the impact of textile structure reinforcement on the mechanical characteristics of polymer composites produced by the compression molding technique was the goal of this work. An epoxy resin system served as the matrix, and various woven (plain, twill, basket), nonwoven (mat), and unidirectional (UD) textile structures made from E-glass fibers were employed as reinforcement elements. Compression molding of pre-impregnated textile materials (prepregs) was used to create the composites. The well-impregnated textile structures with resin into prepreg and the good interface between layers of the composites were verified during the manufacture of the polymer–textile composites using DSC thermal analysis and an SEM microscope. For the mechanical behavior, flexural properties were determined. The composite samples with unidirectional prepreg reinforcement have the highest longitudinal flexural strengths at roughly 900 MPa. The woven prepreg-based composite laminates show balanced flexural properties in both directions. Composites based on plane and basket prepregs have a flexural strength of about 450 MPa. Their flexural strength is over 20% lower than that of the samples made using twill prepreg. In both directions, nonwoven prepreg-reinforced composite samples show the least amount of resistance to bending stresses (flexural strength of roughly 150 MPa).

Croup is a common respiratory illness in children under 5 years, primarily caused by viral infections. Symptoms include inspiratory stridor, barking cough, and hoarseness due to inflamed vocal cords. Diagnosis is based on symptoms difficulty breathing, stridor, chest in-drawing voice changes and head nodding. Severity ranges from mild to severe cases. This study aimed to explore variations in croup and factors contributing to its recurrence in children. This retrospective longitudinal study analyzed health records from the Pediatric Practice "Vitalino" in Veles, North Macedonia, from 2016 to 2022. It included children aged 0-5 years who had croup at least once. The sample was substantial and representative, allowing for a thorough examination of potential correlations and trends in croup occurrence. Among 707 studied children, 254 had croup, with a prevalence of 35.9% over seven years or 5.1% per year. Females had lower odds of recurrent croup, while males had higher odds, but the differences were not statistically significant. Atopic dermatitis and bronchiolitis exposure were significantly associated with croup in both genders. The study provides insights into the prevalence, distribution of croup and associated conditions in young children. The significant associations of atopic dermatitis and bronchiolitis suggest a link between these conditions and recurrent croup. Considering these strong associations, we can conclude that bronchiolitis and croup should be included in the trajectory of the atopic march.

Objective To determine the possible role of patent foramen ovale (PFO) as indicated by a right to left shunt and cryptogenic stroke in patients aged ≥ 60 years and to compare the prevalence of patent foramen ovale with stroke of known cause. Methods We prospectively examined the prevalence of PFO using contrast enhanced colour Transcranial Doppler ultrasonography (bubble-cTCD) in 86 consecutive patients aged ≥60 years with transient ischaemic attack (TIA) or stroke and 86 consecutive patients aged <60 years with TIA/stroke as a control group. Patients with cryptogenic stroke were compared to stroke patients with known cause. Results A significantly higher prevalence of PFO in patients with cryptogenic compared to patients with stroke of known cause was registered in the patients aged < 60 years (56.6% vs.18.8%) and in patients aged ≥ 60 years (37.14% vs.11.76%), respectively. Multivariate analysis adjusted for age, hypertension and coronary disease showed that the existence of R-to-L shunt (RLS) was independently associated with cryptogenic stroke in both, in the younger group (odds ratio 4.012; 95% CI1.323 to 12.171, p =0.0143.70) and in the older group (odds ratio 3.197; 95% CI 1.140 to 10.877, p=0.037). Conclusion Our findings suggest that PFO is strongly associated with cryptogenic stroke in patients aged ≥ 60 years. Bubble – cTCD was feasible and suitable as a first-line method for the detection of PFO in older patients.

Introduction Attrition, its prevention and therapy is a complex problem, with a multifactorial etiology. The aim of this paper is to examine the treatment of attrition in everyday dental clinical practice with the help of soft inserts. Material and method In this study, 30 patients were included, divided into two groups of 15 patients, the study and the control group. The examined patients had first degree of attrition diagnosed according to the Bardsley index, after which the condition was noted in four intervals: the initial situation, after 2, 4 and 6 months from the first visit. The research data were processed in Statistica for Windows 7.0 and SPSS version 20, and the same were presented graphically. Results In the study group with I degree of attrition, for p>0.05, no statistically significant difference was determined in the range of the Bardsley index between the four measurement times (Friedman Test: N=15; Chi-Square=7,200; df =3; p=0.0658). In the control group, for p<0.05, a significant difference was determined in the range of the Bardsley index between the four measured times (Friedman Test: N=15; Chi-Square=15.180; df=3; p=0.0017) with a significantly high value after 6 months. Discussion From the results obtained when comparing the study group in patients with I degree of attrition and the control group, a negative change from the parafunction bruxism was observed in 20% of the test group and 47% of the control group. The results of our research indicated that in patients with the first degree of attrition from the study group, soft dental inserts give significantly better results than untreated patients in the control group. This correlates with the research of Khayat N. et al. Conclusions From the results of the subjects in the group with I degree of attrition, we can conclude that the soft inserts has great efficiency as a means of management of this parafunction and therefore its application in daily therapy is recommended.

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

Background Sodium ¹⁸ F-fluoride for injection can be easily cyclotron-produced and purified, as a simple inorganic salt, by adsorption/desorption onto an anion-exchange cartridge and then dispensed for clinical use. Since the clinical demand for this radiopharmaceutical is constantly increasing, this study aimed to design and develop a simple, fully automated method for the in-house, rapid, and efficient processing and dispensing of injectable solutions of Sodium ¹⁸ F-fluoride without the need of a synthesis module and disposable kit, but using only the dispensing unit. Results A new simple method for the efficient routine production of injectable solutions of [ ¹⁸ F]NaF was developed through a straightforward modification of the commercial dispenser Clio (Comecer S.p.A., Italy) and without the need of a synthesis module. The full production, processing and dispensing of [ ¹⁸ F]NaF were entirely carried out on the same batch using only the dispensing module. Process validation was carried according to GMP guidelines to ensure consistency of [ ¹⁸ F]NaF quality with international standards. The final radiopharmaceutical met all quality criteria specified by Ph. Eur. and chemical, radionuclidic and radiochemical impurities were significantly below the required limits.. Conclusion A new simple and reliable procedure developed for the preparation and dispensing of injectable [ ¹⁸ F]NaF in less than 10 minutes with a radiochemical yield > 97% (decay corrected) has been successfully developed. Notably, the proposed method also allows the preparation of [ ¹⁸ F]NaF using the residual fluorine-18 activity remaining after a [ ¹⁸ F]FDG production run, thus making it immediately accessible to patients for further PET imaging investigations. Kew words: GMP Production, [ ¹⁸ F]NaF, cost-effective method, residual activity, validation.

The purpose of this study is to formulate and evaluate amphiphilic cream with meloxicam indicated for topical relief of pain, particularly because there are currently no available topical dosage forms on the market. Thus, the present research is focused on characterization of the capacity of the amphiphilic base, composed of glycerol monostearate, cetyl alcohol, Tagat® S2, Myritol® 318, propylene glycol, and white petrolatum, to be loaded with drug model meloxicam dissolved in propylene glycol. To enhance the solubility and penetration of meloxicam, menthol as a rubefacient was added to the meloxicam solution. The series of three formulations were prepared with variable content of added menthol. Obtained creams were characterized by drug content, pH, spreadability, viscosity, microbial purity, drug release, and stability. Results showed stable cream formulations with good spreadability and viscosity, suitable for topical application.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a significant tick-borne virus causing severe hemorrhagic disease with high fatality rate. This report presents the genomic characterization of CCHFV strain from North Macedonia’s first outbreak in over 50 years, emphasizing the importance of genomic surveillance in tracking virus evolution and spread patterns in this region.

Red blood cell (RBC) antigen matching beyond ABO and RhD is commonly recommended for patients with sickle cell disease (SCD) and thalassaemia. We present an updated systematic literature review to inform evidence‐based guidelines on RBC matching. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool was used to develop recommendations. Six new observational studies (4 prospective, 2 retrospective) were identified. The six studies reported on 583 patients in total, including cross‐over designs, with sample sizes from 10 to 343. Studies were heterogeneous, utilising varying degrees of RBC matching and different definitions for ‘extended’ matching. All reported on alloimmunisation. One study reported on molecular matching. The reported prevalence of alloimmunisation using limited matching was 0%–50% and with extended matching was 0%–24%. Eighty‐two patients were alloimmunised before study entry. The risk of bias across studies was moderate to critical. The guideline panel recommends that ABO, RhDCcEe, and K‐compatible RBCs are selected for individuals with SCD and thalassaemia, even in the absence of alloantibodies, and that RBCs which are antigen‐negative to already existing clinically significant antibodies are chosen. There is a need for comparative research to define the benefit, impact, cost‐effectiveness, and feasibility of extended RBC matching strategies to prevent alloimmunisation.

The conversion of CO2 into formate (HCOO⁻), a techno‐economically feasible product, can be achieved using earth‐abundant CuxS electrocatalysts, but questions remain regarding how catalyst structure, composition, and reaction environment influence product selectivity. A novel synthesis method based on electrodeposition of Cu foam and its subsequent sulfidation via immersion in sulfur saturated toluene solution resulted in CuxS foams. Catalytic activity studies found that HCOO⁻ selectivity is dependent on electrochemical activation at higher overpotentials. To understand the effects of activation, determine the active forms of the catalysts, and identify the role of sulfur, the electrodes are carefully characterized as well as gaseous and sulfur dissolved in electrolyte. This included study of the effects of intentional addition of solution sulfur species, identification of the sulfur loss, determination of the electrode composition and relating sulfur speciation to observed product selectivity. It is found that residual sulfur stabilizes Cu⁺ during electrolysis at potentials favoring HCOO⁻ production, in contrast to pristine Cu that undergoes complete reduction and shows poor HCOO⁻ selectivity. Sulfur in both the catalyst and dissolved in electrolyte are of dynamic nature, and surface residues of SO4²⁻ species are identified in all activated catalysts which correspond with enhanced HCOO⁻ production.

The purpose of this study was to identify new and low‐frequency gene variants using whole exome sequencing (WES) in patients with childhood‐onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low‐frequency variants were identified in 7 patients. One variant was classified as pathogenic ( KMT2D , NM_003482.3:c.8626delC, predicted to truncate the protein p.(Gln2876Serfs*34)) and two as likely pathogenic according to the American College of Medical Genetics and Genomics classification guidelines ( ADAR , NM_001111.3:c.2815A>G, predicted to encode p.(Ile939Val); BLK , NM_001715.2:c.211G>A, predicted to encode p.(Ala71Thr)). The other variants remain of uncertain significance at this point of time. WES is an important diagnostic and research instrument, producing a growing list of likely genes and gene variants that may be of relevance in the pathogenesis of cSLE and potentially point to novel therapeutic targets.

Purpose The objective of this study was to identify the relationship between COVID-19 and lower urinary tract symptoms in patients with benign prostatic hyperplasia. Materials and methods Data from forty outpatients who had recovered from COVID-19 and had previously been diagnosed with and treated medically for benign prostatic hyperplasia were assessed. Pre- and post-COVID-19 assessments were also conducted for prostate volume, total serum PSA concentration, and lower urinary tract symptoms. Hospitalizations related to COVID-19, the time interval between COVID-19 recovery and urologist referrals, and comorbidities were considered. Independent Student’s t-tests or chi-square tests were used to compare changes in all variables. For the Spearman rank correlation analysis, only variables with a univariate analysis of p < 0.10 were included in the multiple regression models, with the significance threshold set at two-tailed p < 0.05. Results After COVID-19, there was an increase in IPSS (12.87 ± 3.76), total serum PSA (1.56 ± 0.87), and prostate volume (10.68 ± 11.73). Multiple linear regression analysis of the independent predictors of IPSS increase revealed pre-COVID-19 IPSS with intermittency and straining as leading symptoms and bladder catheterization during COVID-19. Pre-COVID-19 frequency and nocturia status were found to be independent predictors of increased blood volume, hospital treatment for COVID-19, and bladder catheterization. A weak stream, UTI, and hypertension were found to be independent predictors of a PSA increase. The time from COVID-19 recovery to urologist referral was shorter in patients with post-COVID-19 IPSS increase (p < 0.05). Conclusion Determining the predictors of the effects of COVID-19 on worsening BPH symptoms is essential for continued monitoring and treatment.