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Background and Objectives: This study aimed to evaluate the frequency of multidrug-resistant (MDR) bacteria in biliary samples, MDR-bacteria risk factors, and the relationship between MDR-bacteria positivity and some clinical outcomes. Materials and Methods: The study was conducted between May 2018 and May 2023, including patients over the age of 18 who had positive culture results in biliary samples. The frequency of MDR-bacteria in biliary samples was evaluated. Risk factors for MDR bacteria were assessed using univariate and multivariate analyses. MDR and non-MDR groups were compared inappropriate empirical antibiotic treatment, total antibiotic treatment duration, length of stay, and in-hospital mortality. Results: 342 microorganisms were isolated from 202 patients. Escherichia coli was the most commonly (37.2%) isolated Gram-negative microorganism, and Enterococcus spp. was the most commonly (70.2%) isolated Gram-positive microorganism. The incidence of MDR microorganisms was 42.3%. Gastrointestinal malignancy (OR: 1.96; 95% CI, 1.03-3.71) and previous antibiotic use (OR: 2.26; 95% CI, 1.09-4.68) were independent risk factors for MDR-bacteria. In the MDR group, inappropriate empirical antibiotic treatment (56.6% vs. 41%, p = 0.091), total antibiotic treatment duration (13 vs. 8 days, p = 0.054), length of stay (24 vs. 15 days, p = 0.001), and in-hospital mortality (27.3% vs. 22.3%, p = 0.416) were higher compared to the non-MDR group. Conclusion: MDR-bacteria positivity is associated with inappropriate antibiotic treatment, prolonged hospitalization, and increased mortality. Screening, antibiotic prophylaxis, and empirical treatment approaches should be carefully performed in patients with malignancy and recent antibiotic use, which are significant risk factors for MDR-bacteria.

Advergames represent a novel product placement strategy that surpasses traditional advertising methods by fostering interaction between brands and their target audiences. This study investigates the unique engagement opportunities provided by video games, focusing mainly on the ‘flow experience’, an intensified state of immersion frequently encountered by players of computer games. Such immersive experiences have the potential to significantly influence a player’s perception, offering a new avenue for advertisements to impact and engage audiences effectively. The primary objective of this research was to examine the influence of advergames on players who are deeply immersed in the gaming experience, with a specific focus on the subsequent effects on brand recognition over time. The study involved 44 software developers, who were evenly divided into two groups for the experiment. Both groups were exposed to an identical gaming environment with the task of locating a designated product within the game. However, one group interacted with an enhanced version of the game, which included additional stimuli—such as dynamic music, an engaging narrative, time constraints, a competitive leaderboard, and immersive voice acting—to intensify the gaming experience. The experiment strategically placed various products within the game, and their detectability was assessed using eye-tracking technology. Following gameplay, participants completed questionnaires that measured their experience with flow state and brand recall. The data were analyzed using the Mann–Whitney U test and correlation analysis to facilitate comparisons. The findings indicated that the product associated with the primary task achieved the highest recall rate between both groups. Furthermore, eye-tracking technology identified the areas in the game that attracted the most attention, revealing a preference for mid- and high-level placements over lower-level ones.

Abstract Software development is a complicated process that requires experienced human resources to produce successful software products. Although this process needs experience from the individuals, it is hard to provide this experience without encountering real incidents during the software development process. To fill this gap, this study proposes a Virtual Reality Based Software Development Framework (VR‐SODEF), which provides an interactive virtual reality experience for individuals learning about the tasks of software development starting from requirement analysis through software testing. In the VR‐SODEF, the participant takes on the role of a novice software developer being recruited into a virtual software development organisation who should work alongside five virtual characters, played by artificial intelligence. This exclusive viewpoint draws participants from the 2D separation of the classical experience and virtually into the world of the software development itself. Participants experience the intense dramatic elements created for simulation and confront the challenges of virtual software practitioners in a somewhat uncompromising virtual simulation environment. To examine the efficiency of the VR‐SODEF, it was tested on 32 computing students, with results indicating that virtual reality can be an effective educational medium, especially for skills that might traditionally be acquired through experience rather than traditional classroom‐based teaching.

Avrupa Birliği’ne ancak insan haklarına saygılı devletler ve AB Hukuku’nun yüklediği yükümlülükleri üstlenebilecek devletler üye olabilmektedir. Türkiye’nin Avrupa kurumları ile olan güçlü ilişkileri ve AB üyeliği perspektifi, dolayısıyla Avrupa İnsan Hakları Mahkemesi ve Avrupa Birliği Adalet Divanı kararları, gerek Türkiye gerek KKTC üzerinde Kıbrıs’taki mülkiyet sorunu bakımından hukuki vesiyasi sıkıntılar ortaya çıkarmaktadır. AİHM kararlarında, KKTC’nin devlet olarak tanınmadığına işaret ederek, 1974’ten sonra Kıbrıslı Rumların terk ettiği gayrimenkuller üzerinde KKTC’nin yaptığı devletleştirme işlemlerini tanımayı reddetmiş, Kıbrıslı Rumların mülkiyet haklarının ihlal edildiğine ve bu ihlallerden Türkiye’nin sorumlu olduğuna karar vermiştir. Avrupa Birliği Adalet Divanı da,Kıbrıs Rum Kesimi’nde oturum yapan mahkemelerin, Kuzey Kıbrıs’taki gayrimenkuller ile ilgili olan davalarda yargı yetkisine sahip olduğuna karar vermiştir. Bu gelişmeler KKTC’nin konuya ilişkin siyasi görüşlerini ve hukuki düzenlemelerini değiştirmesine sebebiyet vermiştir.

Avrupa Birliği, üretim faktörlerinin serbestçe dolaştığı ve rekabetin korunduğu bir İç Pazar oluşturmayı hedeflemektedir. Serbest dolaşım önündeki en büyük engellerden biri de, üye devletlerin kendi üreticilerine sağladığı devlet yardımlarıdır. Üye devletler, kendi üreticilerine çeşitli şekillerde ve yardım yaparak, onların rekabet gücünü artırmakta, bu da dolaylı olarak üye devletler arasındaki ticareti etkilemektedir. İç Pazar’ın etkin bir şekilde çalışabilmesi için gerekli olan devlet yardımlarının denetimi, Komisyon, Avrupa Birliği Adalet Divanı ve ulusal mahkemelerden oluşan bir mekanizma ile sağlanmaktadır. Bu mekanizma hem İç Pazar’daki rekabetin korunması hem de ekonomik kalkınma hedefleri arasında bir denge yaratmayı hedeflemektedir

Cutaneous allergic reactions due to drug intake may be triggered by many types of drugs such as atropine, anticonvulsants and benzodiazepines. But allergic reactions due to benzodiazepines are extremely rare. Alprazolam is a benzodiazepine which may be useful for refractory idiopathic urticaria due to antihistaminergic effect. Although antihistaminergic effect of alprazolam, a cold urticaria case and an angioedema case induced by alprazolam are known in the literature. In the case, we present a child suffering from cutaneous allergic reaction due to alprazolam at the first dose taken. [Cukurova Med J 2016; 41(2.000): 400-402]

Cutaneous allergic reactions due to drug intake may be triggered by many types of drugs such as atropine, anticonvulsants and benzodiazepines. But allergic reactions due to benzodiazepines are extremely rare. Alprazolam is a benzodiazepine which may be useful for refractory idiopathic urticaria due to antihistaminergic effect. Although antihistaminergic effect of alprazolam, a cold urticaria case and an angioedema case induced by alprazolam are known in the literature. In the case, we present a child suffering from cutaneous allergic reaction due to alprazolam at the first dose taken.

Graduation projects play an important role in computer engineering careers in which students are expected to draw upon their knowledge and skills that were acquired since admission. To manage the activities of graduation projects, an iterative and incremental approach which aims continuous improvement is proposed as an alternative to a controversial delivery model. However, such integration brings up a set of challenges to be taken into account: e.g. multiple project deliveries, more labor-intensive effort from instructors, and ultimately continuous learning for all participants. One promising way to achieve such an integrated and continuous deployment velocity is to eliminate potential bottlenecks by giving student teams to receive early and continuous feedback. To this end, we propose a continuous feedback and delivery mechanism for managing the life-cycle of a graduation project through draft proposal, literature review, requirements gathering, design, implementation and testing which should produce intermediate outputs at predefined intervals. Most importantly, our approach makes it possible to quantify most of the activities involved in life-cycle process with various rubrics (i.e. measurement scales) that have been purposefully developed. The proposed model promotes the fact that all improvements should be monitored, evaluated and documented. The results of this study indicate that students who were managed using this approach produced better project deliverables and ultimately have delivered better and successful projects.

Ingrown toenail is an often painful clinical condition that usually affects the big toe. Chemical matricectomy with phenol has a low recurrence rate and good cosmetic results. However, it produces extensive tissue destruction that can result in drainage and delayed healing. Alternatives such as sodium hydroxide and trichloroacetic acid (TCA) have therefore come into vogue. A total of 39 patients with 56 ingrown toenail edges underwent chemical matricectomy with 90% TCA after partial nail avulsion. In most of the patients, adverse effects such as postoperative pain and drainage were minimal. One patient who underwent matricectomy had recurrence in a single nail edge (1.8%) at 12 months follow-up. No recurrence was observed among 38 patients during the mean follow-up period. This was considered to be statistically significant (P < 0.001). Partial nail avulsion followed by TCA matricectomy is a safe, simple, and effective method with low rates of postoperative morbidity and high rates of success.

Somehow in analogy with the European Union, 10 Southeast Asian countries are in the process of forming a political and economic union which is (ASEAN) Association of Southeast Asian Nations for decades. This process of regional integration goes in tandem with the regional media associations such as Asia News Network (ANN) which is an Asian-German initiative that consists of daily newspapers from various Asian countries. As a regional association covering not only all ASEAN countries, but also ASEAN neighbors; ANN may serve a significant role for regional collaboration and integration. The network is instrumental to the promotion of freedom of speech which is not always easy to propound in some of these countries. This article analyzes news coverage and publication policy of ANN and discusses challenges and opportunities of regional journalism in SEA as a case for international and intercultural communication.

Avrupa Birliği tarafından akdedilmiş uluslararası anlaşmalar ve andlaşmalar acquis communautaire yani AB müktesebatının bir parçasını teşkil etmektedir. AB’nin akdettiği bu anlaşma ve andlaşmalardan doğan yükümlülüklerini yerine getirebilmesi için, üye devletler gerekli tüm tedbirleri almak zorundadırlar. Birleşmiş Milletler Deniz Hukuku Sözleşmesi BMDHS gibi bazı uluslararası andlaşmalar, AB’nin yetkisinin karmaşık karakteri nedeniyle, hem AB hem de üye devletler tarafından birlikte akdedilmekte, bu nedenle karma andlaşmalar olarak nitelendirilmektedirler. Karma andlaşmalar da AB müktesebatının bir parçasını teşkil etmektedir. AB üyeliğinin gerçekleşebilmesi için, Türkiye gibi aday devletlerin müktesebatı kabul etmeleri gerekmektedir. Ege Denizi’nde, Yunanistan ile Türkiye arasında mevcudiyetini koruyan hukuki uyuşmazlıklar nedeniyle, Türkiye BMDHS’ne taraf olmamış, hatta bu sözleşmenin bazı hükümleri için ısrarlı redci konumuna gelmiştir. AB üyeliği perspektifi, Türkiye’nin müktesebatı tam anlamıyla kabul etmiş sayılması için, BMDHS’ne taraf olma zorunluluğunun olup olmadığı konusunu gündeme getirmektedir

Plasma membrane rupture (PMR) is the final cataclysmic event in lytic cell death. PMR releases intracellular molecules known as damage-associated molecular patterns (DAMPs) that propagate the inflammatory response 1-3 . The underlying mechanism of PMR, however, is unknown. Here we show that the cell-surface NINJ1 protein 4-8 , which contains two transmembrane regions, has an essential role in the induction of PMR. A forward-genetic screen of randomly mutagenized mice linked NINJ1 to PMR. Ninj1 -/- macrophages exhibited impaired PMR in response to diverse inducers of pyroptotic, necrotic and apoptotic cell death, and were unable to release numerous intracellular proteins including HMGB1 (a known DAMP) and LDH (a standard measure of PMR). Ninj1 -/- macrophages died, but with a distinctive and persistent ballooned morphology, attributable to defective disintegration of bubble-like herniations. Ninj1 -/- mice were more susceptible than wild-type mice to infection with Citrobacter rodentium, which suggests a role for PMR in anti-bacterial host defence. Mechanistically, NINJ1 used an evolutionarily conserved extracellular domain for oligomerization and subsequent PMR. The discovery of NINJ1 as a mediator of PMR overturns the long-held idea that cell death-related PMR is a passive event.

Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors are employees of, and/or hold equity in BioElectron Technology Corporation, Inc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel-Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.

Protein motions are ubiquitous and are intrinsically coupled to catalysis. Their specific roles, however, remain largely elusive. Dynamic loops at the active center of the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex are essential for several catalytic functions starting from a predecarboxylation event and culminating in transfer of the acetyl moiety to the E2 component. Monitoring the kinetics of E1 and its loop variants at various solution viscosities, we show that the rate of a chemical step is modulated by loop dynamics. A cysteine-free E1 construct was site-specifically labeled on the inner loop (residues 401-413), and the EPR nitroxide label revealed ligand-induced conformational dynamics of the loop and a slow "open <--> close" conformational equilibrium in the unliganded state. An (19)F NMR label placed at the same residue revealed motion on the millisecond-second time scale and suggested a quantitative correlation of E1 catalysis and loop dynamics for the 200,000-Da protein. Thermodynamic studies revealed that these motions may promote covalent addition of substrate to the enzyme-bound thiamin diphosphate by reducing the free energy of activation. Furthermore, the global dynamics of E1 presumably regulate and streamline the catalytic steps of the overall complex by inducing an entirely entropic (nonmechanical) negative cooperativity with respect to substrate binding at higher temperatures. Our results are consistent with, and reinforce the hypothesis of, coupling of catalysis and regulation with enzyme dynamics and suggest the mechanism by which it is achieved in a key branchpoint enzyme in sugar metabolism.

[reaction: see text] The Kishner reduction of 2-furylhydrazone gives 2-methylene-2,3-dihydrofuran as the major abnormal reduction product. 2-Methylene-2,3-dihydrofuran is an excellent ene in the carbonyl-ene reaction, reacting with a variety of aldehydes. Most notable was the asymmetric carbonyl-ene reaction of 2-methylene-2,3-dihydrofuran and decanal using Ti(OCH(CH3)2)4/(S)-BINOL to give the corresponding alcohol in 66% yield and 94% ee. The reaction of 2-methylene-2,3-dihydrofuran with 2 equiv of 1,4-benzoquinone unexpectedly gave a monoalkylated 1,4-hydroquinone/1,4-benzoquinone electron donor-acceptor complex.