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Objectives This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. Materials and methods Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. Results Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673–0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). Conclusion miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients.

Introduction. The reconstruction of columella defects is still regarded as a challenging procedure due to the very specific anatomy of the columella and limited local and regional flap options. Furthermore, the texture and color of columella tissue pose difficulties in choosing the right method of reconstruction. Case report. The report presents a patient who underwent reconstruction of a complex columella defect using a Schmid-Meyer flap. Schmid-Meyer flap represents a tubular flap with an internal supraciliary pedicle which allows the transposition of the temporal skin with the addition of ear cartilage on the tip of the nose or the ala nasi. The integration of the flap was complete. During the five-year follow-up period, the cosmetic and functional results were satisfying. Conclusion. Schmid-Meyer flap may be one of the best options for the reconstruction of complex defects of the columella.

Currently, flight delays are common and they propagate from an originating flight to connecting flights, leading to large disruptions in the overall schedule. These disruptions cause massive economic losses, affect airlines' reputations, waste passengers' time and money, and directly impact the environment. This study adopts a network science approach for solving the delay propagation problem by modeling and analyzing the flight schedules and historical operational data of an airline. We aim to determine the most disruptive airports, flights, flight-connections, and connection types in an airline network. Disruptive elements are influential or critical entities in an airline network. They are the elements that can either cause (airline schedules) or have caused (historical data) the largest disturbances in the network. An airline can improve its operations by avoiding delays caused by the most disruptive elements. The proposed network science approach for disruptive element analysis was validated using a case study of an operating airline. The analysis indicates that potential disruptive elements in a schedule of an airline are also actual disruptive elements in the historical data and they should be considered to improve operations. The airline network exhibits small-world effects and delays can propagate to any part of the network with a minimum of four delayed flights. Finally, we observed that passenger connections between flights are the most disruptive connection type. Therefore, the proposed methodology provides a tool for airlines to build robust flight schedules that reduce delays and propagation., Comment: accepted to Data Science and Management

Objectives: The aim of the study is to evaluate the effectiveness of the surgical and nonsurgical treatment of headache caused by contact points (CPs) between the nasal septum and inferior or middle turbinate. Methods: The research was designed as a prospective clinical case-series study. The patients with CP headaches were offered to choose between 2 treatment options, surgery and medical treatment. Two groups of surgically treated patients (surgery groups 1 and 2, depending on whether there is a contact between nasal septum and inferior turbinate or middle turbinate) were evaluated and compared for headache intensity and frequency. Headache intensity was measured using a visual analog scale value from 0 to 10; the frequency of headache was expressed as the number of days during 1 month with a headache (before surgery, 1 month, and 6 months after surgery). A comparison was also made between surgically and nonsurgically treated patients. Results: We found more intensive and frequent headache in patients who had CP between the nasal septum and the middle turbinate ( P = .038 and P = .003, respectively). A significant reduction in headache intensity and frequency was found in both groups of surgically treated patients 6 months after surgery; however, this reduction was more significant in patients with mucosal contact between nasal septum and middle turbinate. The nonsurgical treatment made a significant reduction of headache intensity and frequency at 1-month follow-up ( P = .012 and P = .031, respectively), but not at 6-month follow-up ( P = .114 and P = .088, respectively). Conclusion: Surgery gave a statistically significant reduction in the intensity and frequency of headache, which was assessed 6 months after surgery. Surgery was found as superior to nonsurgical treatment in the therapy of CP headache.

Uvod/Cilj. Incidencija orofaringealnih karcinoma se povećavala tokom poslednje decenije, a epidemiologija promenila sa pojavom humanog papiloma virusa (HPV) kao bitnog faktora rizika od ovih karcinoma. Potrebno je ustanoviti bolje terapeutske izbore za specifične grupe bolesnika koji se leče od orofaringealnog karcinoma. Cilj ove studije bio je da se procene kvalitet života i funkcionalne performanse, kao i uticaj različitih demografskih faktora, stadijuma bolesti i tipa terapija na te parametre kod bolesnika sa orofaringealnim karcinomom kod kojih je postignuta uspešna lokoregionalna kontrola, godinu dana posle sprovedene terapije. Metode. Studija je uključila 87 bolesnika koji su odgovorili na upitnike o kvalitetu života i funkcionalnim performansama: European Organization for Research and Treatment of Cancer Quality-of Life-Questionnaire-C30 - EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of-Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) i Karnofsky Performance Scale (KPS), 12 do 14 meseci posle završenog onkološkog tretmana. Rezultati. Specifične grupe bolesnika značajno su se razlikovale u skorovima na upitnicima za kvalitet života posle lečenja. Faktori koji su bili povezani sa slabijim rezultatima su bili ženski pol, život bez partnera, nivo obrazovanja, zaposlenost i HPV status. Zaključak. Kliničari bi trebali da uzmu u obzir socioekonomske faktore i HPV status u planiranju postoperativnog oporavka kod bolesnika lečenih od orofaringealnog karcinoma. Pol bolesnika, nivo obrazovanja i zaposlenost su faktori koji nose određen nivo rizika koji je povezan sa nižim nivoom kvaliteta života kod ovih bolesnika. Backround/Aim. Considering the distinct increase in the incidence of oropharyngeal cancer over oral cavity cancers and changing epidemiology with human papilloma virus (HPV) infection emerging as an important risk factor, there is a need to establish better treatment choices in specific groups of patients with oropharyngeal cancer. The aim of this study was to assess the quality of life (QOL) and functional performance and the impact of different demographical data, stage of disease, and treatment type on these parameters in patients with oropharyngeal cancer with successfully achieved locoregional control a year after the treatment. Methods. Study included 87 patients who underwent QOL and functional impairment assessment 12 to 14 months after finished oncological treatment with the following questionnaires: the European Organization for Research and Treatment of Cancer Quality-of Life-Questionnaire-C30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of-Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) and the Karnofsky Performance Scale (KPS). Results. Specific groups of patients had significantly different post-treatment QOL scores. The factors associated with the worse QOL scores were female gender, not being in a partnership, level of education and HPV status. Conclusion. Clinicians should consider socioeconomic factors and HPV status in planning the recovery after treatment of patients with oropharyngeal carcinoma. Gender, education level and employment are the variables that form a certain risk profiles associated with the lower QOL.

Surgical and orthodontic treatment of a teenage cleft patient.Authors describe the case of a 13 year old female cleft patient presented with class III malocclusion RESULT: The patient underwent comprehensive surgical secondary bone grafting and orthodontic treatment. Stable skeletal and occlusal class I relationship was achived and maintained in the post treatment observation period till the age of 16.Although several authors suggests primary gingivoperiosteoplasty, other advocates that such early intervention can cause later restrictions in maxillary growth. For alveolar reconstruction, maxillary growth and dental age were the main considerations in determining the timing of surgical intervention.This case showed that borderline cases of complex dentoalveolar and skeletal anomaly in cleft patients could be successfully treated with comprehensive secondary bone grafting and orthodontic treatment thus avoiding the need for orthognatic surgery.Alveolar bone grafting, Cleft, Malocclusion.

This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski’s rule of five for good permeability (absorption) potential.

C-C bond formation reactions between (benzamidomethyl)triethylammonium chloride (1) and some carbon nucleophiles (2a-f) were performed smoothly in aqueous media, under mild reaction conditions and ambient temperature. Mono-C-alkyl (3a, 3b, 3c) and di-C-alkyl (3d, 3e, 3f) derivatives were obtained without using a catalyst. Crystals of the products were easily isolated by simple filtration, in moderate yields and with no apparent contamination due to the formation of O-alkyl products.

The protonation of some meta and para substituted benzamides in sulfuric acid solutions was studied by UV spectroscopy in the 190-350 nm region. Principal component analysis was applied to separate the effect of protonation from the medium effect. The spectral region 200-350nm was used for the calculation of the ionization ratio from coefficient of the first principal component, which explains about 95-98% of the total variability. The dissociation constants as well as the solvation parameters m* and ? were calculated using the excess acidity method and the Bunnett-Olsen method. The pK BH + values obtained with the H A function (defined by the average m* - values) are in satisfactory agreement with those calculated with the previously mentioned methods. The pK BH + values were correlated with structure using the Hammett (?=-0.91) and Taft approach. It was found that the inductive effect is more relevant than the resonance one for both substituted benzamides (meta and para). .

Although airlines plan aircraft routes and crew schedules in advance, perturbations occur everyday. As a result, flight schedules may become infeasible and would need to be updated. This Day of Operations Scheduling problem impacts the entire system of an airline as the decisions enforced are final. When perturbations are relatively small, the airline may be able to at least preserve the planned aircraft and crew itineraries. We propose a model that determines new flight schedules based on planned crew transfers, rest periods, passenger connections, and maintenance. Its dual is shown to be a network model, hence solvable in a real-time environment. In addition, it can be used in more sophisticated operational and planning systems.

The protonation of 3-methylindole, D-tryptophan, 3-formylindole, 3-acetylindole and indolyl-2-carboxylic acid in sulfuric acid media was studied by UV spectroscopy. The measurement of the absorbance at four selected wavelengths enabled the calculation of the corresponding molar absorptivities. The results were used to calculate the pKa value of the protonated form of the indole derivatives by the Hammett Method. The Hammett postulate (the slope of the plot log [c(BH+)/c(B)]vs. H should be equal to 1) was tested. The dissociation constants and solvent parameter m* were also obtained by applying the Excess Acidity Method. The position of the additional protons in the protonated compounds is discussed.

A wide variety of factors result in disturbances in carrying out planned airline schedules. Technical failures in the aircraft, meteorological conditions, crew delay, crews not showing up for flights, breakdowns in aircraft ground servicing equipment, and bottlenecks at airports lead to cancelation and/or delay of some flights. This paper develops a model to reduce airline schedule disturbances. The heuristic model that is developed [using the first in, first out (FIFO) principle and a sequential approach based on dynamic programming] can greatly facilitate the work of the dispatcher when making decisions regarding traffic management. The developed models and corresponding software package were tested on a large number of hypothetical numerical examples. The software package provides the dispatcher with an active role in choosing the final solution. Relying on his or her experience and intuition, the dispatcher can change the type of aircraft on a specific flight, departure times of individual flights, or...

One of the early successes of cost-cutting decision support systems in the airline industry was in crew management. Due to high crew costs incurred by the airlines, deploying efficient crew management information systems became a necessity to thrive. For decades, research and development groups have been developing sophisticated algorithms and solution methodologies for solving complex crew management problems. We overview the early developments and the recent state-of-the-art algorithms. These algorithms form optimization engines behind modern crew management information systems. Common components of commercial systems are detailed and we discuss key software vendors.

This paper is concerned with the problem of determining seat reservations on flights with several legs and different types of fares on each leg. The aim is to find some reservation levels that maximize the air carrier's revenue. The nonlinear integer programming model developed is solved by using simulated annealing techniques with an initial “satisfactory” point obtained by a Monte‐Carlo approach.

Perturbations in carrying out a schedule are occurrences which happen from time to time and there are numerous factors behind them. Cancelled or delayed flights can be caused by meteorological reasons, technical reasons, late or absent crew members, etc. One or more aircraft from an airline fleet might be taken out of operation due to technical reasons and the airline has to operate with a reduced number of planes. This paper presents the results of an effort to define a new daily airline schedule in this situation so that the total number of cancelled flights is minimized. Should there be several airline schedules with an equal total number of cancelled flights, the schedule with the minimum total passenger delay on flights to be performed is chosen. A heuristic algorithm is developed to solve this lexicographic optimization problem and is tested on numerical examples.