Abstract Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non‐ albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first‐choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP 51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in‐house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP 51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP 51. Finally, molecular dynamics simulations of the C. albicans CYP 51 ( CACYP 51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.
The use of waste materials in concrete design draws the attention of researchers. Studies on the use of these materials both as binders and aggregates accelerate. In this study, ground granulated blast furnace slag (GGBFS) based geopolymer concrete was produced. 0, 25, 50, 75 and 100% recycled concrete aggregate (RCA) was used instead of river aggregate in the mixtures. These samples were exposed to temperatures at 100, 200, 400, 600 and 800 °C. The cooling process of these samples exposed to temperature was in 3 different forms: air, oven and water. Compressive strength, ultrasonic pulse velocity (UPV), weight loss, sorptivity and water absorption values of the samples were determined. At the same time, the changes in the microstructure of the samples under the elevated temperature were examined. Compressive strengths of the samples decreased with increasing RCA ratio in the mixture. Samples were severely affected due to elevated temperature, properties of the samples decreased. As the temperature degree increased, the weight loss and sorptivity values of the samples increased. As the temperatures to which the samples were exposed increased, there was a decrease in Ca/Si ratio and an increase in Si/Al ratio. The microstructure of the samples deteriorated at elevated temperatures.
The temperature change, internal pressure and corrosion are main reason of cracksin pipes. Removal of damaged pipes with new ones gives rise to major disruptionduring operation. This causes loss of time and cost. This study aims to prevent crackpropagation and to obtain fast repair in damaged area, at the beginning of the dam-age. Repair of small cracks in steel pipes using composite patches has been studiedin this work. The aim of the study is to repair small cracks less than 8 mm length.For this purpose, holes with 8 mm diameters were drilled in 170 mm long pipes andcomposite patches with 2, 2.6 and 3.2 mm thickness and 35, 40 and 45 mm overlaplengths with 60, 90 and 120o overlap angles were attached with an adhesive of0.2 mm thickness. The repaired pipes were subjected to internal pressure until dam-age occurred. A finite element model was developed and the numerical results wereverified based on experiments. The repair of steel pipe with adhesive bonding wassuccessfully achieved under high pressure with composite patches.The results show that the increase in overlap angle results in an increased sur-face area, and consequently an increase in failure load. Furthermore, the failure loadincreased with an increase in patch thickness. Additionally, it is seen that the failureload does not change significantly with increasing patch thickness.
Introduction: Saphenous vein graft (SVG) failure remains a key limitation in coronary artery bypass grafting (CABG). The no-touch harvesting technique aims to improve graft durability by preserving perivascular tissue and preventing endothelial injury caused by mechanical trauma during conventional harvesting. Purpose: To assess whether the no-touch SVG harvesting technique offers superior graft patency and acceptable safety outcomes compared to conventional SVG harvesting in patients undergoing CABG. Methods: A systematic search was conducted in PubMed, Cochrane CENTRAL, Ovid Medline, and Web of Science databases through May 5, 2025. Randomized controlled trials (RCTs) comparing no-touch versus conventional SVG harvesting in CABG were included. The primary outcome was SVG occlusion per graft at the end of follow-up. Secondary outcomes included SVG occlusion per patient, all-cause mortality, total surgery time, and wound complications. Data were pooled using an inverse variance–weighted random-effects model. Analyses were conducted using the “meta” package in R (version 4.4.3). Results: Eight RCTs comprising 4,234 patients (mean age: 62.6 ± 8.5 years) were included. No-touch SVGs were associated with significantly decreased risk of SVG occlusion by 31% compared to conventional SVGs (RR: 0.69; 95% CI: 0.60–0.80; I2 = 0%, p < 0.0001). A similar benefit was observed at the patient level (RR: 0.68; 95% CI: 0.56–0.83; I2 = 0%, p = 0.0002). All-cause mortality was comparable among the techniques (RR: 1.04; 95% CI: 0.63–1.71; I2 = 0%, p = 0.88). The no-touch technique was associated with a statistically significant but clinically negligible increase in operative time (MD: 9.69 minutes; 95% CI: 2.48–16.90; I2 = 62%, p = 0.0084). However, wound complications occurred more frequently in the no-touch group (RR: 2.03; 95% CI: 1.67–2.47; I2 = 0%, p < 0.0001). Conclusion: The no-touch SVG harvesting technique provides superior graft patency at both the graft and patient levels compared to conventional methods. Although associated with a modest prolongation in operative time and a higher risk of wound complications, these drawbacks may acceptable in patients with low risk for wound morbidity and can potentially be improved upon by increased operator experience with this technique.
The aim of this project is to compare the performance of LSTM and Linear Kalman Filter in the presence of a multipath noise. The Kalman filter approach is based on an intuitively defined process and dynamically changing matrices. Using the past data, the next point of the system is tried to be predicted. This filter may not represent the time correlation between data very well because it uses a user-specified dynamic model. In addition, although the Kalman filter is known to be ideal in the presence of Gaussian noise, its performance in the presence of non-Gaussian noise is not good.RNN's are used to model time series, sequential data. LSTM is a special type of RNN with memory. LSTM aims to overcome these problems by learning noisy and dynamic models. This is an area where the Kalman filter is expected to perform poorly. Instead of testing this approach in sensor data, randomly generated 1 and 2 dimensional trajectory data were used. Although LSTM was trained with little data, it was concluded that it provided better performance than Kalman filter when appropriate hyper-parameters were provided.
Sanayi ve teknolojinin gelişmesiyle birlikte, üretim süreçlerinde otomasyona geçişle ilgili son derece önemli ilerlemeler olmuştur. Bu ilerlemeler sonunda, büyük ölçüde insandan bağımsız sistemlerin kurulması aşamasına kadar gelinmiştir. Ancak bu ilerlemeler iş sağlığı ve güvenliği (İSG) açısından yaşanan sorunları ortadan kaldırmamıştır. Sorunlar, bazı işletmelerde emek yoğun dönemdekine benzer şekilde yaşanmakta olup bazı işletmelerde de biçim değiştirmiş durumdadır. Bu çerçevede, İSG’nin halen işletmeler için hayati öneme sahip bir konu olduğunu ifade etmek mümkündür. Bu çalışmada, işletmelerde İSG sorunlarının çözümüne yönelik uygulamalı bir araştırma gerçekleştirilmiştir. Araştırma, mobilya sektöründe faaliyet gösteren bir fabrikada bütün üretim süreçlerini kapsayacak şekilde yapılmıştır. Bu kapsamda, araştırma iki aşamalı olarak planlanmıştır. Birinci aşamada, üretim süreçleri içerisinde etkin olmayan bölümlerin tespit edilmesi amaçlanmıştır. Bu amaç doğrultusunda Veri Zarflama Analizi (VZA) tekniği kullanılmıştır. VZA için gerekli olan veriler, ergonomik ölçüm cihazları ve anket yöntemi kullanılarak elde edilmiştir. Veriler,VZA modellerinden girdi odaklı Charnes Cooper Rhodes (CCR) modeli ile teknik ölçüm yapılarak analiz edilmiştir. Analiz sonucunda, demir atölyesi ve mobilya üretim bölümü fabrikada iyileştirilmesi gereken birimler olarak tespit edilmiştir. İSG açısından etkin olmayan birimler belirlendikten sonra, ikinci aşamada, Kısıtlar Teorisi (KT) tekniği ile sorunların çözümüne yönelik çalışmalar yapılmıştır. Etkin olmayan birimlerdeki ana problemin işletmede İSG kültürünün eksik olmasından kaynaklandığı Mevcut Gerçeklik Ağacı (MGA) ile gösterilmiştir. Buharlaşan Bulut (BB) ile eksiklerin giderilmesine yönelik çözüm önerileri sunulmuş ve Gelecek Gerçeklik Ağacı (GGA) ile de sorunların çözümüyle gerçekleşecek durum ifade edilmiştir.
Background: Thoracic aortic aneurysm (TAA) poses a significant risk of aortic dissection and mortality. Angiotensin receptor blockers (ARBs) have been proposed as a potential therapeutic intervention to mitigate these risks but their effects are uncertain. Aim: To evaluate the efficacy of ARBs in patients with TAA. Methods: A comprehensive search of Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science yielded 2563 records, from which 8 unique randomized controlled trials (RCTs) (including 7 Marfan and 1 bicuspid aortic valve+TAA populations) comprising 1575 patients were included in the analysis. The primary outcome measures were aortic dissection and all-cause mortality. Pooled risk ratios (RR) or mean differences (MD) in an inverse variance random-effects model were generated and analyses were performed with “meta” package in R (version 4.3.2). Results: Our analysis reveals no significant beneficial effect of ARBs on aortic dissection (RR 0,62 [95%CI, 0,20; 1,92], I 2 :0%) and all-cause mortality (RR 0,61 [95%CI, 0,18; 2,05], I 2 :0%), irrespective of specific ARB agents (including losartan, irbesartan, and telmisartan), comparators (beta blocker, placebo, or no treatment), disease condition (Marfan syndrome or bicuspid aortic valve), and patient demographics (children or adults). Additionally, there were no significant differences observed between ARB and control groups in changes in ascending aorta and aortic annulus diameter, as well as aortic Z-score at the 3-year mark, including the annual change in ascending aorta (MD 0.04 mm/year [95% CI, -0.07 to 0.15], I 2 :0%) and aortic root diameter (MD -0.06 mm/year [95% CI, -0.22 to 0.10], I 2 :81%) by echocardiography. However, there was a significant reduction in aortic root diameter as assessed by MRI (MD -0.48 mm/year [95%CI, -0.89 to -0.08]) and echocardiography (MD -0.51 mm/3year [95%CI, -0.85 to -0.17]), with low heterogeneity when compared with control. Risk of aortic surgery and severe adverse events were also comparable. Conclusion: We found no significant beneficial effect of ARBs in reducing the risk of aortic dissection or all-cause mortality in patients with TAA. Despite observing a significant reduction in the aortic root diameter by MRI and echocardiography with ARB therapy, other imaging outcomes were comparable between ARB and control groups.
Bu çalışmada lif katkılı kerpiç tuğla üretimi gerçekleştirmek için kullanılan killi toprak ile boyları 6 mm, 12 mm ve 19 mm olan polipropilen lif kullanılmıştır. Killi toprağa ağırlıkça % 0 (katkısız), % 0,5 , % 1 ve % 1,5 oranlarında polipropilen lif katılmıştır. Katkısız karışımdan 1, polipropilen katkılı karışımlardan 9 farklı karışım toplam 10 adet farklı karışım oluşturularak kerpiç tuğla üretimi gerçekleştirilmiştir. Her bir karışım için 3 adet kerpiç tuğla numunesi üretilmiştir. Üretilen bu örneklerin hacim kayıpları, birim hacim ağırlıkları, basınç dayanımları ve eğilme hasar yükleri araştırılmıştır. Çalışma sonucunda polipropilen lif katkılı numunelerin katkı oranı ve lif boyu arttıkça hacim kaybının katkısız numunelere göre %8,57 ile %37,25 aralığında azaldığı, birim hacim ağırlığının ise %1,54 ile %7,25 aralığında azaldığı görülmüştür. Basınç dayanımlarının katkısız numunelere göre lif oranı ve boyu arttıkça %11,67 ile %44,93 aralığında arttığı görülmüştür. Eğilme hasar yüklerinin ise katkısız numunelere göre %43,19 ile %250,05 aralığında arttığı tespit edilmiştir.
Abstract Objective Sickle cell anaemia (SCA), an inherited chronic hematological disease affecting hundreds of thousand people worldwide, causes significant morbidity and reduced life expectancy about two or three decades. This study aimed to conduct a meta‐analysis of the efficacy of voxelotor, 900 mg in patients with SCA. Methods The research protocol was registered at the International Register of Prospective Systematic Reviews (PROSPERO), under the registration number: CRD42020147796. ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Conference Abstracts, Google Scholar, Ovid Medline, Scopus, Web of Science, and Wiley Online Library from 2015 through July 25, 2019, and bibliographies of review articles and eligible studies. Eleven eligible studies that evaluated the effectiveness of voxelotor, 900 mg in SCA. Based on pre‐specified inclusion and exclusion criteria, 2 randomized, placebo‐controlled studies were included in the meta‐analysis. Results The primary outcome measured was hemoglobin elevation, assessed in a highly similar fashion in both trials. There was a significant difference between voxelotor and placebo in haemoglobin change from baseline (mean difference [MD]: 0.87, 95% confidence interval [CI]: 0.67‐1.06). Voxelotor also reduced markers of haemolysis, MD: −36.79, 95% CI: (−75.05) to 1.48 for unconjugated bilirubin that changes from baseline; MD: −19.09, 95% CI: (−44.06) to 5.88 for the percentage of reticulocytes that change from baseline and MD: −23.29, 95% CI: (−65.14) to 18.55 for LDH that change from baseline) but the difference was not statistically significant. Conclusions As a conclusion, voxelotor, 900 mg use significantly increased hemoglobin levels which of 1 g/dL elevation predicts a reduced risk of stroke (41%), albuminuria (53%), pulmonary arterial hypertension (57%), and mortality (64%) in recent studies. Voxelotor also reduced markers of hemolysis but failed to reach statistically significance in current evidence. Multicenter, randomized, placebo‐controlled studies are on the way and will provide more evidence to see the potential of disease‐modifying effects of voxelotor.
Background/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a–k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 μg/mL and 0.619 μg/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 μg/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 μg/mL and 1.23 μg/mL, MIC of ciprofloxacin = 31.49 and 125.99 μg/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14α-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.
Cisplatin (CIS)-induced nephrotoxicity is associated with oxidative stress, apoptosis, inflammation, and fibrogenesis. In this study, we investigated the therapeutic effects of ranolazine (RAN), a current antianginal drug known to experimentally reduce oxidative damage in CIS-induced nephrotoxicity. We randomly assigned thirty-two Sprague Dawley rats to one of four groups (Control, CIS, CIS+RAN, and RAN+CIS). We evaluated kidney function parameters including blood urea nitrogen (BUN), creatinine (Cre), electrolytes, and albumin, as well as tissue biochemical parameters including malondialdehyde (MDA) and antioxidant enzymes. Histopathological parameters were also assessed. We observed a significant increase in BUN and Cre values in the CIS group compared to the control group (p<0.05). However, there was a significant decrease in BUN values (p<0.05) in the CIS+RAN and RAN+CIS groups compared to the CIS group. In contrast, the decrease in Cre values did not reach statistical significance (p>0.05), and serum electrolytes were comparable among groups. Furthermore, a statistically significant increase in albumin levels was observed in the CIS+RAN group compared to the CIS group (p<0.05). MDA levels were significantly decreased in the CIS+RAN group compared to the CIS group, indicating the antioxidant activity of RAN (p<0.05). Histopathological analysis revealed that necrosis and dilatation in epithelial cells of cortical and medullary tubules were more prominent in the CIS group (p<0.0001). However, in the RAN+CIS group, the histopathological changes observed in the CIS group were found to be significantly reduced (p<0.0001). Degenerative changes in tubules were observed in the CIS+RAN group (p>0.05). Our findings suggest that the beneficial effects of RAN on CIS-induced nephrotoxicity may be related to its antioxidant activity.
Abstract Studies investigating the efficacy of β-blocker agents on patients with thoracic aortic aneurysm have produced heterogeneous and conflicting results. This study was aimed to assess protective effects of β-blockers in terms of aortic events (dissection, rupture) and mortality in patients with thoracic aortic aneurysm. A systematic literature search was performed through Ovid MEDLINE, EMBASE, Web of Science, Pubmed and The Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), all from inception to May 10, 2022. Randomized controlled trials exploring the efficacy of β-blocker agents in patients with thoracic aortic aneurysm were considered for inclusion with no population restriction. Two independent reviewers performed the literature search. Two reviewers independently extracted all available prespecified relevant data in accordance with the International Prospective Register of Systematic Reviews protocol. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. The overall risk of bias assessment was conducted by using the Cochrane Risk of Bias 2 tool A sensitivity analysis was performed regarding whether the conclusions reached might differ substantially if a single study was omitted. The primary outcome was aortic events (aortic dissection/rupture). Secondary outcomes were death (all-cause mortality) and aortic dissection. Two independent reviewers identified 4 RCTs presented in 5 reports from 1494 unique studies screened. Three trials involving 129 eligible participants compared β blockers (propranolol and celiprolol) with no treatment. One trial involving 32 eligible participants compared β blocker (atenolol) with placebo. This systematic review and meta-analysis included 161 patients with thoracic aortic aneurysm (mean age, 27.6 years; 80 [49.7%] male, mean follow-up 6.7 years). The pooled risk ratio in the β-blocker arm for aortic events was 0.74 [95% CI (0.20; 2.71), I2: 0%, p=0.64] when comparing to the placebo or no treatment in patients with thoracic aortic aneurysm. The pooled risk ratio for death (all-cause mortality) and aortic dissection in the β-blocker arm were 0.45 [95% CI (0.10; 1.98), I2: 0%, p=0.29] and 0.58 [95% CI (0.15; 2.24), I2: 0%, p=0.43], respectively. The risk of aortic dissection, rupture, or death were essentially identical, regardless of treatment group and subgroup analysis. A sensitivity analysis revealed that none of the studies significantly influenced the pooled risk estimate to any great extent. We found no evidence of benefit from β-blocker treatment. More robust data regarding β-blocker use in patients with thoracic aortic aneurysms from randomized controlled trials are needed to establish evidence based recommendations and to determine whether current evidence comes from absense of evidence or evidence of absense.Forest plot for death (all-cause)
The aim of this scoping review is to evaluate the impact of smartphone application (SPA) technology in patients undergoing elective colonoscopy to measure compliance with appointments, cost-effectiveness, bowel preparation, and quality of life. The scoping review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Ovid Medline, Web of Science, Science Direct, Scopus, Cochrane Library, and PubMed were screened up to Oct 14, 2020, and bibliographies of the retrieved articles were included. Based on pre-specified inclusion and exclusion criteria, 8 primary studies were included in the final analysis from a total of 3,979 non-duplicate articles. Seven out of eight studies measured the bowel preparation quality. In six of these studies, patients in the smartphone group had a successful bowel preparation when compared with the control arm; on the other hand, one study did not find any differences between groups. Adherence to colonoscopy screening was assessed by one study. Patients in the digital intervention arm were significantly more likely to complete a screening test. Patient satisfaction during the periprocedural period of colonoscopy was assessed by five studies which reported significantly higher patient satisfaction in the intervention arm compared to the control arm. None of the studies measured cost-effectiveness. We came to the conclusion that a well-designed, user-friendly SPA can help and guide patients undergoing colonoscopy through the process of following up on their appointments, adhering to bowel preparation, and better understanding their disease condition. Future trials investigating SPAs should include cost-effectiveness and adherence to appointments as an endpoint.
