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The aim of the study is to determine the structural characteristics of sheep and goat farm in Çorum province, the problems faced by breeders and to offer solutions to these problems. The material for the study consisted of data obtained through personal interviews in 140 sheep and goat farms in the districts of Çorum province. In the study, it was determined that the breeders were mostly between 41-50 years old, their education level was secondary school (55.7%), the number of family members was 3-4 and their experience in the profession was 21-30 years. In the study, it was determined that females were used for breeding for 4-5 years and males for 3 years. It was determined that animal records were generally not kept on the farm and the need for shepherds in the family was met from the family (64.3%). In conclusion in addition to the problems of marketing and insufficient pastures, breeders also lack knowledge about cultivation and health protection and the potential in the region is not adequately reflected in production. In order to overcome these problems, it is necessary to increase and continue the support for the development of sheep and goat husbandry, improve health protection and social rights and encourage young people in particular.

Abstract Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65–69 years old, 70–79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3–22.3) months. There was no significant difference in mPFS between age groups (p = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9–54.1) months and there was no significant difference between age groups (p = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3–4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.

Purpose – This study aims to empirically examine the effects of smart cities on sustainable development for the period 1990–2019 for Türkiye. Design/methodology/approach – The relationship between smart cities and sustainable development was analyzed with the help of the ARDL Bounds Test. In addition, the consistency of the model was tested with the FMOLS estimator. The indicators of the smart city were selected following the literature to represent smart cities, and the author created the smart city index. The study used other variables thought to impact sustainable development as secondary data. Findings – The results show that smart cities positively and significantly impact sustainable development in Turkiye in both models during the sampling period. In addition, while real GDP, population density, and financial development variables positively affect sustainable development, population density has a negative effect on sustainable development, according to the results obtained from FMOLS estimators. Originality/value – The first novelty of this study is the creation of the smart city index. The second novelty is that there are almost no studies on the effects of smart cities on sustainable development, especially for Türkiye.

Disasters are events that disrupt normal life and cause physical, economic, and social losses to people. Due to its location, Turkey is exposed to many disasters. This makes it important to successfully carry out the disaster management process. Planning what to do before and after a disaster and taking the necessary precautions are of great importance in the disaster management process. Strategies to be implemented in the first 72 hours, which is the most critical time period for search and rescue activities, are one of the most important parts of the process. Activities to be carried out within the first 72 hours represent a critical period for the management and commencement of the recovery process after a disaster. Resolving situations such as rapid rescue and first aid, ensuring communication infrastructure, meeting emergency needs, damage assessment and evaluation, ensuring community safety, and establishing a coordination center are vital within the first 72 hours after a disaster. This study encompasses the determination of strategies to be implemented in the critical first 72 hours after a disaster occurs. Multi-criteria decision-making methods were utilized in this study. The criteria influencing the determination of intervention strategies were weighted using the Analytic Hierarchy Process (AHP) method. The strategies developed in line with the weighted criteria were then prioritized using the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method. As a result of weighting the criteria with the AHP method, disaster severity ranked first, followed by the type of disaster in second place. In the ranking of strategies with the TOPSIS method, rapid rescue and first aid ranked first, and establishing a coordination center ranked second. In this way, we aim to achieve effective results in the shortest time by determining the priority order of activities.

ÖZ:Alman edebiyatında 18 ve 19. yüzyıllarda sık görülen bir tür olan Bildungsroman, başka ulusların edebiyatlarında da örnekleri sergilenen ve günümüze kadar etkisini sürdürebilmiş bir roman türüdür. Genel olarak bir kahramanın, çocukluk döneminden başlayarak nasıl olgunlaştığını kronolojik bir şekilde anlatan otobiyografik anlatımlı romanlardır. Eğitim, gelişim ve sanatçı romanları gibi alt türleri bulunan Bildungsromanda, kahramanın gelişimi diyalektik bir şekilde gerçekleşir. Kahramanın gelişmesinin kıstası toplumla uzlaşmayı öğrenmesidir. Dolayısıyla Bildungsromanlar genel olarak mutlu bir sonla biter. Bu çalışmada, Alman edebiyatının Nobel ödüllü yazarı Hermann Hesse’nin ‘Gençlik Güzel Şey’ isimli uzun öyküsü, Bildungsroman özellikleri çerçevesinde incelenmiştir. Hesse, ‘Gençlik Güzel Şey’ eserinde çocukluk döneminde çevresi tarafından onaylanmayan tavırlara sahip olan ve yıllar sonra evine ideal kimliğine kavuşarak dönen bir gencin hikâyesini anlatır. Çalışmanın amacı, edebi eserin okumasını Bildungsroman çerçevesinde yapabilmek ve geleneksel Bildungsromanın dışında gelişmiş bir Bildungsroman versiyonunu göstermektir. Nitekim bu edebi eserin, bazı özellikler açısından Bildungsromanın geleneksel çizgisinde olduğu; fakat bazı özellikler açısından da Bildungsromanın modern versiyonlarına dahil edilebileceği görülmüştür. ABSTRACT:Bildungsroman, a genre frequently seen in German literature in the 18th and 19th centuries, is a type of novel whose examples are also exhibited in the literature of other nations and has maintained its influence until today. In general, they are autobiographical novels that tell chronologically how a hero matures, starting from his childhood. In Bildungsroman, which has subgenres such as education, development and artist novels, the development of the hero takes place in a dialectical manner. The criterion of the hero's development is that he learns to compromise with society. Therefore, Bildungsromans generally have a happy ending. In this study, the long story ‘Youth is a Beautiful Thing’ by Hermann Hesse, the Nobel Prize-winning author of German literature, was examined within the framework of Bildungsroman features. In his work 'Youth is a Beautiful Thing', Hesse tells the story of a young man who had attitudes that were not approved by those around him during his childhood, and who returns home years later with his ideal identity. The aim of the study is to read the literary work within the framework of Bildungsroman and to show a developed version of Bildungsroman other than the traditional Bildungsroman. As a matter of fact, this literary work is in the traditional line of Bildungsroman in terms of some features; however, it has been seen that it can be included in the modern versions of Bildungsroman in terms of some features.

Abstract Background Infectious diseases not only cause severe health problems but also burden the healthcare system. Therefore, the effective treatment of those diseases is crucial. Both conventional approaches, such as antimicrobial agents, and novel approaches, like antimicrobial peptides (AMPs), are used to treat infections. However, due to the drawbacks of current approaches, new solutions are still being investigated. One recent approach is the use of AMPs and antimicrobial agents in combination, but determining synergism is with a huge variety of AMPs time-consuming and requires multiple experimental studies. Machine learning (ML) algorithms are widely used to predict biological outcomes, particularly in the field of AMPs, but no previous research reported on predicting the synergistic effects of AMPs and antimicrobial agents. Results Several supervised ML models were implemented to accurately predict the synergistic effect of AMPs and antimicrobial agents. The results demonstrated that the hyperparameter-optimized Light Gradient Boosted Machine Classifier (oLGBMC) yielded the best test accuracy of 76.92% for predicting the synergistic effect. Besides, the feature importance analysis reveals that the target microbial species, the minimum inhibitory concentrations (MICs) of the AMP and the antimicrobial agents, and the used antimicrobial agent were the most important features for the prediction of synergistic effect, which aligns with recent experimental studies in the literature. Conclusion This study reveals that ML algorithms can predict the synergistic activity of two different antimicrobial agents without the need for complex and time-consuming experimental procedures. The implications support that the ML models may not only reduce the experimental cost but also provide validation of experimental procedures.

Abstract Background The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. Methods In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. Results Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p =

This study aims to college students' healthy nutrition attitude, sleep status, and musculoskeletal disorders during the COVID-19 pandemic. In total, 165 university students participated in this research. The students filled out the Attitude Scale for Healthy Nutrition, Pittsburgh Sleep Quality Index (PSQI), and Cornell Musculoskeletal Discomfort Questionnaire. The attitude toward healthy eating of 34 (20.6%) students was found to be moderate, 100 (60.6%) high, and 31 (18.8%) very high. There was no meaningful difference between groups according to having COVID-19 disease (p>0.05). Among the participants, 43 (26.06%) students were found to be good and 122 (73.94%) to be poor in terms of sleep quality. The global PSQI and sleep duration subgroup scores of those who had COVID-19 were statistically higher (p=0.010 and 0.043, respectively). The five regions with the most musculoskeletal symptoms were the upper back (78.18%), lower back (70.91%), neck (69.09%), right shoulder (55.76%) and left shoulder (49.09%). Significant differences were observed in the scores of the right wrist (p=0.009), left wrist (p=0.007), right lower leg (p=0.024), left lower leg (p=0.026), right foot (p=0.001), and left foot (p=0.009). The COVID-19 pandemic partially affected university students in terms of healthy eating attitudes and, to a greater extent, in terms of sleep and musculoskeletal disorders.

When assessing the quality of a system or product, it is necessary to take all responses into account and optimize them in a concurrent manner to find the factor levels that satisfy the overall system, process, or product properties to solve the robust design problem. This problem can be solved as a multi-response optimization problem. There are many methods suggested to solve this problem based on different disciplines like multi-objective optimization. In this study, we improve the theory of nondifferentiable desirability functions' optimization for which the so-called gradient-based methods are not useful. In this study, we propose an infinite programming approach for nondifferentiable desirability functions including more than one nondifferentiable point. We employed DNLP model of GAMS/BARON which is a nondifferentiable solver, however, the solution of more than one nondifferentiable point problem is resulted as infeasible. We also tested MATLAB/NOMAD which is a derivative-free solver for MINLP problems, however, MATLAB/NOMAD also did not succeed and could not solve this nondifferentiable problem. Lastly, we use a genetic algorithm that is implemented under MATLAB and it also cannot find a feasible solution. We use an example that is solved by different desirability functions approaches before and show that the desirability functions approach with more than one nondifferentiable point is a good alternative to the ones in the literature. We present the conclusion and future studies at the end of the paper.

Without democracy and the alternative channels it brings, it is challenging to guarantee sustainable development. The lack of a democratic dimension of sustainable development research enables citizens and institutions to realize their development visions. In this context, the study aims to investigate the effects of democracy on sustainable development empirically. The relationship between democracy and sustainable development was investigated with the help of the annual data for the period 1990-2019 and the Han and Phillips (2010) method for the E-7 countries. According to the findings, democracy has a statistically significant and positive effect on sustainable development. On the other hand, the variables of GDP, innovation, and renewable energy consumption discussed in the study also have a positive and statistically significant effect on sustainable development. The study's findings show that democracy is a significant factor in promoting sustainable development in E-7 countries.

Social constructivism theory, one of the theories of the field of international relations, deals with the current problems of modern life and offers solutions to them. Identity structuring in the nation-building process and the elements that make up identity constitute one of the main working subjects of social constructionists. In this study, Islam, Wahhabism, Bedouinism, regional leadership, energy geopolitics, which are effective in the foreign policy determination process of Saudi Arabia, will be tried to be explained through the constructivism theory as the main factors that determine the Saudi identity. Along with the semantic changes that Saudi identity has expressed for Saudi Arabia from the past, its effect on current politics is determined, and the geopolitical position of Saudi Arabia and the strategic orientations caused by this position are discussed. In addition, the policies that Saudi Arabia started to follow in the post-Arab Spring period are examined, especially with an emphasis on its relationship with the Islamic identity. A holistic framework for Saudi Arabia's foreign policy will be drawn by listing various approaches to the identities mentioned in the article. It will also focus on the internal dynamics that are important in the formation of Saudi Arabia's foreign policy identities.

Abstract Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

For a wide range of service requirements, the 5G-NR offers significant flexibility based on OFDM with numerous numerologies. However, OFDM is recognized to have a significant disadvantage due to a high PAPR. On the other hand, the PAPR reduction for mixed-numerology OFDM has received little attention compared to single-numerology OFDM, despite there being possible challenges and advantages such as computational complexity and new structure opportunity, respectively. In this paper, the phase rotation PAPR reduction approach on mixed-numerology OFDM is proposed for the first time. Unlike the single-numerology approach, the need for additional IFFT and side information overhead is eliminated, and the mixed-numerology transmitter structure is exploited to provide three novel approaches, namely proposed numerology-based (Proposed-NB), proposed symbol-based (Proposed-SB), and proposed location-based (Proposed-LB). Proposed-NB has the same PAPR performance with a lower complexity compared to the partial transmit sequence (PTS) method for single-numerology OFDM. Moreover, the new ability to use multiple phase factors for the same numerology symbols in the defined largest symbol length enhances the PAPR reduction performance further using Proposed-SB. While all symbols are jointly optimized in the Proposed-SB, Proposed-LB drives a sub-optimal solution developed by optimizing the selected symbols. Due where the presence of different symbols duration between numerologies and also consecutive symbols in the same numerology, PAPR reduction performance in Proposed-LB almost reaches the optimum Proposed-SB performances with a lower computational complexity compared to Proposed-SB. The conducted numerical results validate the superiority of the proposed methods for 5G and beyond compared to PTS and numerology scheduling methods.

Divorce is a stressful life transformation process that includes the post-divorce stage as well as the stages of decision making and divorce proceedings. This process affects almost all areas of life and causes many changes in living conditions. On the one hand, the divorced individual confronts the reality of the divorce and realizes the intense emotions and changes to deal with. On the other hand, the individual focuses on his/her transition to a new identity and lifestyle. Current statistics reveal the increase in divorce rates both in the world and in our country. Therefore, it seems important to consider the divorce process in terms of adjustment. There are many approaches to examine divorce and post-divorce adjustment process. Although these models differ in explaining post-divorce adjustment, all of them consider adjustment as a part of the divorce process. Thus, this review study has several purposes. First of all, current divorce rates and effects of divorce in legal, economic, social terms and in terms of psychological and physiological health will be included. Then, divorce and post-divorce adjustment models and assessment of adjustment will be explained. It is believed that a comprehensive review of divorce and post-divorce adjustment would facilitate divorced individuals to access appropriate information and support. Besides, correct understanding of the process regarding divorce and divorce-adjustment will be useful for further studies.

Today, the world is in the middle of an energy transformation. On the one hand, consumers demand clean energy, and on the other hand, manufacturers are willing to invest in this field. In this context, this study aims to empirically examine the impact of financial development on renewable energy investments in E−7 countries in the 2000–2017 period with the panel threshold regression model developed by Hansen (1999). In addition, the study examined the effects of GDP, patent applications, carbon emissions, inflation, fossil fuel consumption, and the policy index created by the Author as control variables on renewable energy investments. As a result of the analysis, strong evidence was found that the relationship between financial development and renewable energy investments is nonlinear, and there is a single threshold value for financial development (0.3602). However, when looking at the size of the coefficients showing the marginal effects, the positive effect of the increase in financial development on renewable energy investments was found to be above the threshold value (0.8573) and below the threshold value (1.3125). This result shows that the positive marginal effect of financial development on renewable energy investments tends to decrease above the threshold value. This result is thought to be because although the amount of funds in the financial system increased in the later stages of financial development, these funds remained idle and could not be directed to renewable energy investments at the same rate as the level of increase in financial development. In other words, with the development of the financial system, an imbalance may occur among renewable energy investments in the E−7 country group. Kao Panel Cointegration, FMOLS, and DOLS methods were also used in the study to investigate the consistency of the results obtained in the Panel Threshold Regression model. The Panel Threshold Regression analysis concluded that GDP, patent applications, carbon emissions, inflation, and policy index had a significant and positive impact. At the same time, fossil fuel consumption negatively affected renewable energy investments. FMOLS and DOLS results used as alternative models also gave similar results to the panel threshold value model, except for carbon emissions and fossil fuel consumption.

Background: Proton pump inhibitor (PPI) induced hypomagnesemia is a completely unexplained issue and cases are still being reported. Long-term use is the main factor, but there are a few articles stating that it may also emerge with short-term use. We aimed to evaluate the changes of serum and urine magnesium levels during short-term high dose pantoprazol treatment. Methods: The serum and 24-hour urine magnesium levels of 58 patients were evaluated during the course of 2 days. Of 58 patients, 25 were allowed oral intake on the 3rd day of hospitalization and thus, 24-hour urine for 3 days was collected from 33 patients. Results: There were no significant differences in the mean levels of serum magnesium and the median levels of urine magnesium. When the magnesium levels were evaluated by age over and under 60 years, the baseline serum magnesium level was significantly higher than the 1st level in patients aged ≥ 60 years (p = 0.029). The 3rd day serum magnesium level was significantly higher than the baseline and 1st day levels in those aged < 60 years (p = 0.049). Conclusions: We showed that plasma levels and urinary excretion of magnesium did not change significantly during high-dose pantoprazol treatment. It can be hypothesized that magnesium levels are not affected by PPIs in short-term usage. Age and other contributing factors ma y have more impact on PPI induced hypomagnesemia. Patients aged over 60 years might be handled carefully under proton pump inhibitors treatment. [ABSTRACT FROM AUTHOR]

One of the most used artificial intelligence techniques for maximum power point tracking is artificial neural networks. In order to achieve successful results in maximum power point tracking, the training process of artificial neural networks is important. Metaheuristic algorithms are used extensively in the literature for neural network training. An important group of metaheuristic algorithms is swarm-intelligent-based optimization algorithms. In this study, feed-forward neural network training is carried out for maximum power point tracking by using 13 swarm-intelligent-based optimization algorithms. These algorithms are artificial bee colony, butterfly optimization, cuckoo search, chicken swarm optimization, dragonfly algorithm, firefly algorithm, grasshopper optimization algorithm, krill herd algorithm, particle swarm optimization, salp swarm algorithm, selfish herd optimizer, tunicate swarm algorithm, and tuna swarm optimization. Mean squared error is used as the error metric, and the performances of the algorithms in different network structures are evaluated. Considering the results, a success ranking score is obtained for each algorithm. The three most successful algorithms in both training and testing processes are the firefly algorithm, selfish herd optimizer, and grasshopper optimization algorithm, respectively. The training error values obtained with these algorithms are 4.5 × 10−4, 1.6 × 10−3, and 2.3 × 10−3, respectively. The test error values are 4.6 × 10−4, 1.6 × 10−3, and 2.4 × 10−3, respectively. With these algorithms, effective results have been achieved in a low number of evaluations. In addition to these three algorithms, other algorithms have also achieved mostly acceptable results. This shows that the related algorithms are generally successful ANFIS training algorithms for maximum power point tracking.

The acceleration of capital transfers between countries after globalization has increased the importance of foreign direct investments in developing countries. Lack of capital in developing countries such as Turkey, constitute obstacles to investment. In this context, foreign direct investments that will come to the country are important in terms of eliminating the negativities caused by the lack of capital. Foreign direct investments are affected by many factors. One of them is the country's geopolitical risk. In this study, it is aim to investigate the impact of geopolitical risk on foreign direct investment in Turkey by using ARDL Bound Test for the 1998-2018 period. In addition to the geopolitical risk, real exchange rate, labor force, real GDP and savings that affect foreign direct investments were also included in the study. According to the analysis re-sults obtained, while geopolitical risk and labor force had a negative effect on FDI; real GDP, real exchange rate and savings have and positive effect on FDI.

Despite the high prevalence of lung cancer among other primary tumors, metastasis of this particular malignancy in the breast is very rare. We report three new cases of lung cancer with breast metastases and discuss radiological and clinical findings. Radiologically, each case displayed different characteristics. First, one of them had bilateral superficially and deeply located irregular lesions. Second, the patient presented with findings similar to inflammatory breast cancer. The third case had a circumscribed mass, resembling a benign complicated cyst. To guide clinicians for proper patient management, radiologists should be aware of the scope of typical and atypical imaging findings of metastatic involvement of the breast.

Polybutylene adipate terephthalate (PBAT) is a biodegradable alternative to polyethylene and can be broadly used in various applications. These polymers can be degraded by hydrolases of terrestrial and aquatic origin. In a previous study, we identified tandem PETase-like hydrolases (Ples) from the marine microbial consortium I1 that were highly expressed when a PBAT blend was supplied as the only carbon source. In this study, the tandem Ples, Ple628 and Ple629, were recombinantly expressed and characterized. Both enzymes are mesophilic and active on a wide range of oligomers. The activities of the Ples differed greatly when model substrates, PBAT-modified polymers or PET nanoparticles were supplied. Ple629 was always more active than Ple628. Crystal structures of Ple628 and Ple629 revealed a structural similarity to other PETases and can be classified as member of the PETases IIa subclass, α/β hydrolase superfamily. Our results show that the predicted functions of Ple628 and Ple629 agree with the bioinformatic predictions, and these enzymes play a significant role in the plastic degradation by the consortium.

The degradation of plastics by marine microbes is not well understood. Here, Meyer-Cifuentes et al. use a meta-omics approach to study the biodegradation of an aromatic-aliphatic copolyester blend by a marine microbial enrichment culture, showing that different degradation steps are performed by different microorganisms.

ABSTRACT Objective This study was designed to investigate the role of visceral adiposity along with other clinical parameters in predicting poor coronary collateral circulation (CCC) among patients with severe obstructive coronary artery disease (CAD). Subjects and methods A total of 135 patients with severe obstructive CAD and good (n = 70) or poor (n = 65) CCC were included. Data on angiographically detected CCC, the quality criteria for CCC (Rentrop scores) and visceral fat index (VFI) obtained via bioelectrical impedance were compared between good and poor CCC groups. Independent predictors of poor CCC, the correlation between VFI and Rentrop score and the role of VFI in the identification of CCC were analyzed. Results A significant negative correlation was noted between VFI and Rentrop scores (r = -0.668, < 0.001). The presence of hypertension (OR 4.244, 95% CI 1.184 to 15.211, p = 0.026) and higher VFI (OR 1.955, 95% CI 1.342 to 2.848, p < 0.001) were shown to be independent predictors of an increased risk for poor CCC. ROC analysis revealed a VFI > 9 (AUC [area under the curve] (95% CI): 0.898 (0.834-0.943), p < 0.0001) to be a potential predictor of poor CCC with a sensitivity of 95.38% and specificity of 85.71%. Conclusion In conclusion, our findings revealed comorbid hypertension and higher VFI to significantly predict the risk of poor CCC in patients with severe obstructive CAD.

Background:The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood.Aims:To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed.Study Design:Multicenter retrospective observational cohort study.Methods:In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer.Results:The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%).Conclusion:The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Type 1 diabetes (T1D) increases the risk for pregnancy complications. Increased time in the pregnancy glucose target range (63-140 mg/dL as suggested by clinical guidelines) is associated with improved pregnancy outcomes that underscores the need for tight glycemic control. While closed-loop control is highly effective in regulating blood glucose levels in individuals with T1D, its use during pregnancy requires adjustments to meet the tight glycemic control and changing insulin requirements with advancing gestation. In this paper, we tailor a zone model predictive controller (zone-MPC), an optimization-based control strategy that uses model predictions, for use during pregnancy and verify its robustness in-silico through a broad range of scenarios. We customize the existing zone-MPC to satisfy pregnancy-specific glucose control objectives by having (i) lower target glycemic zones (i.e., 80-110 mg/dL daytime and 80-100 mg/dL overnight), (ii) more assertive correction bolus for hyperglycemia, and (iii) a control strategy that results in more aggressive postprandial insulin delivery to keep glucose within the target zone. The emphasis is on leveraging the flexible design of zone-MPC to obtain a controller that satisfies glycemic outcomes recommended for pregnancy based on clinical insight. To verify this pregnancy-specific zone-MPC design, we use the UVA/Padova simulator and conduct in-silico experiments on 10 subjects over 13 scenarios ranging from scenarios with ideal metabolic and treatment parameters for pregnancy to extreme scenarios with such parameters that are highly deviant from the ideal. All scenarios had three meals per day and each meal had 40 grams of carbohydrates. Across 13 scenarios, pregnancy-specific zone-MPC led to a 10.3 ± 5.3% increase in the time in pregnancy target range (baseline zone-MPC: 70.6 ± 15.0%, pregnancy-specific zone-MPC: 80.8 ± 11.3%, p < 0.001) and a 10.7 ± 4.8% reduction in the time above the target range (baseline zone-MPC: 29.0 ± 15.4%, pregnancy-specific zone-MPC: 18.3 ± 12.0, p < 0.001). There was no significant difference in the time below range between the controllers (baseline zone-MPC: 0.5 ± 1.2%, pregnancy-specific zone-MPC: 3.5 ± 1.9%, p = 0.1). The extensive simulation results show improved performance in the pregnancy target range with pregnancy-specific zone MPC, suggest robustness of the zone-MPC in tight glucose control scenarios, and emphasize the need for customized glucose control systems for pregnancy.

The main objective of selection studies is to select genotypes with superior properties from hybrid combinations. In this study, seedling and first clonal generation stages were carried out with the variation obtained by using hybrid seeds from three different hybrid potato combinations. The research was carried out in cloth greenhouse (seedling generation) and field (first clonal generation) in Tokat/Kazova conditions between 2017 and 2018. In the study, 5500 hybrid true potato seeds were used from three combinations (A3/15×Bafana, T5/4×Bafana, Başçiflik Beyazı×Lady Olympia) created by using five different parents. These hybrid true potato seed were planted in 13x8 vials and then seedlings were transplanted to appropriate sized pots (15×24 cm) when they reached to 10-15 cm length. The hybrid clones obtained from the seedlings were selected according to the breeder preference and the first clonal generation stage was started with the clones (1380 clones) which were suitable to be continued. The plantings were constructed with 70×50 distance in the field conditions. After harvest, each of the 1380 clones was examined separately and 1100 clones were selected as a result of negative selection made by considering the phenotypic characteristics of the tubers.

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.

In this study, graft compatibility between almond cultivar Lauranne and almond seedling and Rootpac R, Rootpac 90, Rootpac 70 and Rootpac 40 clonal rootstocks was anatomically investigated. The anatomical analysis of scion/ rootstock combinations was performed by taking cross sections for 30 days and 12 months after T-budding in June, 2017. It was determined that, 30 days after grafting, the callus cells developed but cambial continuity has not occurred between the rootstock and scion tissues in all scion/rootstock combinations. 12 months after grafting, cambial relation was established, vascular differentiation was observed, regular parenchymatic tissue properties and scleroid (petrosal cell) cells and sclerenchyma bundles were seen in the graft union. There was no problem in terms of rootstock- scion compatibility in Lauranne almond cultivar which was grafted on almond seedling and some Rootpac clonal rootstocks.

Accumulation of plastics in the oceans presents a major threat to diverse ecosystems. The introduction of biodegradable plastics into the market aims to alleviate the ecological burden caused by recalcitrant plastics. Poly (butylene adipate-co-terephthalate) (PBAT) is a biodegradable commercial plastic that can be biodegraded similarly to polyethylene terephthalate (PET) by PETase-like enzymes and MHETases. The role of MHETases is to hydrolyze the intermediate degradation product of PET, mono-2-hydroxyethyl terephthalate (MHET) to its monomers. We recently identified a homolog of the MHETase of the PET-degrading bacterium Ideonella sakaiensis, Mle046, from a marine microbial consortium. In this consortium, Mle046 was highly expressed when a PBAT-based blend film (PF) was supplied as the sole carbon source. In this study, we recombinantly expressed and biochemically characterized Mle046 under different conditions. Mle046 degrades MHET but also 4-(4-hydroxybutoxycarbonyl) benzoic acid (Bte), the intermediate of PF degradation. Mle046 is a mesophilic enzyme adapted to marine conditions, which rapidly degrades MHET to terephthalate and ethylene glycol at temperatures between 20 and 40°C. Mle046 degradation rates were similar for Bte and MHET. Despite its mesophilic tendency, Mle046 retains a considerable amount of activity at temperatures ranging from 10 to 60°C. In addition, Mle046 is active at a range of pH values from 6.5 to 9. These characteristics make Mle046 a promising candidate for biotechnological applications related to plastic recycling.

Phenyl urea herbicides are being extensively used for weed control in both agricultural and non-agricultural applications. Linuron is one of the key herbicides in this family and is in wide use. Like other phenyl urea herbicides, it is known to have toxic effects as a result of its persistence in the environment. The natural removal of linuron from the environment is mainly carried through microbial biodegradation. Some microorganisms have been reported to mineralize linuron completely and utilize it as a carbon and nitrogen source. Variovorax sp. strain SRS 16 is one of the known efficient degraders with a recently sequenced genome. The genomic data provide an opportunity to use a genome-scale model for improving biodegradation. The aim of our study is the construction of a genome-scale metabolic model following automatic and manual protocols and its application for improving its metabolic potential through iterative simulations. Applying flux balance analysis (FBA), growth and degradation performances of SRS 16 in different media considering the influence of selected supplements (potential carbon and nitrogen sources) were simulated. Outcomes are predictions for the suitable media modification, allowing faster degradation of linuron by SRS 16. Seven metabolites were selected for in vitro validation of the predictions through laboratory experiments confirming the degradation-promoting effect of specific amino acids (glutamine and asparagine) on linuron degradation and SRS 16 growth. Overall, simulations are shown to be efficient in predicting the degradation potential of SRS 16 in the presence of specific supplements. The generated information contributes to the understanding of the biochemistry of linuron degradation and can be further utilized for the development of new cleanup solutions without any genetic manipulation.

Objective: Hepatocyte growth factor is a pleiotropic cytokine with potent mitogenic activity in many organs and tissues. The receptor for hepatocyte growth factor is c-Met, a transmembrane glycoprotein with tyrosine kinase activity. We investigated the relationships between hepatocyte growth factor and c-Met expression levels on sperm motility and male infertility. Methods: The study was designed as a prospective cohort, single-center clinical trial and was conducted between March 2015 and June 2016. The control group consisted of 31 healthy male volunteers with children, while the study group consisted of 61 men who were diagnosed with male infertility after presenting to the In Vitro Fertilization Unit of our Institute. All participants in the study were aged 18–60 years. Sperm samples were taken from each participant and divided in two. The fresh sample was examined immediately for expression of c-Met, while the other was stored frozen and evaluated later for hepatocyte growth factor. Primary outcome measures were the levels of hepatocyte growth factor and c-Met expression, while secondary outcome measures were the correlation of these levels with sperm count, morphology and motility. Results: The c-Met expression level in the control group (26.53 ± 3.50, 19.43–32.73) was significantly lower than in the infertile group (27.95 ± 2.86, 21.58–33.07) (p = 0.039). HGF expression was also significantly lower in the control group (3.25 ± 1.76, 0.83–8.25) than in the infertile group (4.87 ± 4.11, 1.01–21.58) (p = 0.043). In the overall group, c-Met expression showed a positive correlation with sperm motility percentage and a negative correlation with sperm count and sperm morphology percentage. Conclusions: The c-Met receptor and its ligand, hepatocyte growth factor, appear to be fundamental regulators of spermatogenesis, sperm motility and fertilization capacity.

ABSTRACT: Objective: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. Methods: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. Results: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. Conclusion: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.

PromA plasmids are broad host range (BHR) plasmids, which are often cryptic and hence have an uncertain ecological role. We present three novel PromA γ plasmids which carry genes associated with degradation of the phenylurea herbicide linuron, two of which originated from unrelated Hydrogenophaga hosts isolated from different environments (pPBL-H3-2 and pBPS33-2), and one (pEN1) which was exogenously captured from an on-farm biopurification system (BPS). Hydrogenophaga sp. plasmid pBPS33-2 carries all three necessary gene clusters (hylA, dca, ccd) determining the three main steps for conversion of linuron to Krebs cycle intermediates, while pEN1 only determines the initial linuron hydrolysis step. Hydrogenophaga sp. plasmid pPBL-H3-2 exists as two variants, both containing ccd but with the hylA and dca gene modules interchanged between each other at exactly the same location. Linuron catabolic gene clusters that determine the same step were identical on all plasmids, encompassed in differently arranged constellations and characterized by the presence of multiple IS1071 elements. In all plasmids except pEN1, the insertion spot of the catabolic genes in the PromA γ plasmids was the same. Highly similar PromA plasmids carrying the linuron degrading gene cargo at the same insertion spot were previously identified in linuron degrading Variovorax sp. Interestingly, in both Hydrogenophaga populations not every PromA plasmid copy carries catabolic genes. The results indicate that PromA plasmids are important vehicles of linuron catabolic gene dissemination, rather than being cryptic and only important for the mobilization of other plasmids.

Bacteria produce a diverse array of antagonistic compounds to restrict growth of microbial rivals. Contributing to this warfare are bacteriocins: secreted antibacterial peptides, proteins and multi-protein complexes. These compounds typically eliminate competitors closely related to the producer. Lectin-like bacteriocins (LlpAs) constitute a distinct class of such proteins, produced by Pseudomonas as well as some other proteobacterial genera. LlpAs share a common architecture consisting of two B-lectin domains, followed by a short carboxy-terminal extension. Two surface-exposed moieties on susceptible Pseudomonas cells are targeted by the respective lectin modules. The carboxy-terminal domain binds D-rhamnose residues present in the lipopolysaccharide layer, whereas the amino-terminal domain interacts with a polymorphic external loop of the outer-membrane protein insertase BamA, hence determining selectivity. The absence of a toxin-immunity module as found in modular bacteriocins and other polymorphic toxin systems, hints toward a novel mode of killing initiated at the cellular surface, not requiring bacteriocin import. Despite significant progress in understanding the function of LlpAs, outstanding questions include the secretion machinery recruited by lectin-like bacteriocins for their release, as well as a better understanding of the environmental signals initiating their expression.

Son yıllarda gösterdiği çarpıcı kalkınma hamlesiyle Orta Doğu’nun yükselen yıldızı olan Dubai küreselleşme kavramının bölgedeki en başarılı örneğidir. Bu makalede bedevi kültürünün hüküm sürdüğü kurak bir çöl coğrafyasında yer alan bu küçük yerleşim yerinin, Orta Doğunun ticaret ve turizm merkezi haline dönüşmesini sağlayan ilgi çekici gelişimi incelenecektir. Ayrıca Dubai örneğinde İbn Haldun’un toplum yaşamında ilkel bir durumdan, badawa'dan,(kırsal toplumdan) asabiyet adını verdiği ve bir tür toplum sözleşmesi olarak görülebilecek dayanışma ile zamanla uygar topluma, yani hazara'ya dönüşmesindeki açıklamaların ne derece örtüştüğüne de bakılacaktır. Dubai’nin başarısındaki sosyolojik, tarihsel ve ekonomik faktörlerin analizi yapılırken İbn Haldun’un umran ve asabiyet kavramları üzerinde de durulacaktır.

Kimyasal maddelerin güvenli kullanımı ile ilgili toplumda genel bilgi eksikliği olması, özellikle çocukları kimyasal maddeler konusunda bilinçlendirmenin gerekliliğini ortaya koymaktadır. Bu amaçla Avrupa Birliği Yaşam boyu Öğrenme Programı Leonardo da Vinci (LdV) Ortaklık Projeleri kapsamında “Đç ve dış ortam kimyasal maddelerin zararları konusunda çocukların farkındalıklarını arttırmak” adlı bir proje hazırlanmıştır. Proje için üç ülkedeki (Türkiye, Polonya, Đsveç) sekiz kurumdan oluşan disiplinler arası bir ekip oluşturulmuştur. Hazırlanacak eğitim materyalinin temel kavramlar, evimizdeki ilaçlar, ev içi temizlik ürünleri, pestisitler, plastikler, çevresel sigara dumanı ve karbonmonoksit başlıklarını içermesi planlanmış ve DVD ile öğretmenlere yönelik bir el kitabı hazırlanmıştır. Çalışmada ilköğretim 4. ve 5. sınıfa devam eden yaşları yaklaşık 10-12 arasında olan çocuklardan oluşan iki deney ve iki kontrol grubu yer almıştır. Araştırma sonucunda, ele alınan kimyasallar ve bunların kullanımına ilişkin, deney grubundaki öğrencilerin kontrol grubundaki öğrencilere göre son testte daha fazla doğru yanıt verdikleri elde edilmiştir. Etkileşimli bir süreçte kullanılacak bu öğretim materyalinin Fen ve Teknoloji dersi öğretim programlarındaki boşluğu doldurması ve çocukların daha bilinçli bireyler olarak gelişmelerine katkıda bulunması beklenmektedir.

Objective: Aim of the study was to evaluate sleep quality in a small sample of patients with gastro-esophageal reflux disease (GERD) comparing them with the patients under treatment in oncology department. Method: Forty-eight patients were included in the study, 22 of them were recruited from the oncology department (oncology patients: OnPs) and 26 from the gastroenterology department (gastroenterology patients: GEPs) at a university hospital. By senior psychology students, the Hospital Anxiety and Depression Scale and the Pittsburg Sleep Quality Index were administered to the patients. Results: There was no significant difference between the two groups regarding anxiety and depression scores of the patients and their total sleep quality scores. Nevertheless, it has been found that GEPs had higher anxiety scores than OnPs. Conclusion: The regression analysis demonstrated that sleep quality scores are determined only by anxiety scores and that being an oncology or gastroenterology patients, being at a certain age, or gender have no effect on total sleep quality scores. [Med-Science 2012; 1(4.000): 315-22]

Purpose. NSAIDs and ASA may cause upper gastrointestinal bleeding (UGIB) both in adults and in elderly. There is no study that compares this increased bleeding risk between adult and elderly subjects. Methods. A total of 524 patients with UGIB were included in this study. The data of patients were, respectively, analyzed. Results. NSAIDs and ASA-associated UGIB rates were similar between

Purpose. In this study we tried to determine the association between body-mass index (BMI), survival rate, and the stage of tumor at the time of diagnosis in patients with gastric cancer. Methods. A total of 270 gastric cancer patients’ hospital records were retrospectively evaluated. Patients were grouped according to their BMI at the time of tumor diagnosis. Tumor stages at admission were compared according to their BMI values. Results. There were no differences in OS among BMI subgroups (p=0.230). The percent of patients with stage III tumor was significantly higher in nonobese while the percent of stage IV tumor was surprisingly higher in obese patients (p was 0.011 and 0.004, resp.). Percent of patients who did not have any surgical intervention was significantly lower in overweight and obese patients than normal and/or underweight patients. Conclusions. At the time of diagnosis, obese patients had significantly higher percent of stage IV tumor than nonobese patients. Despite of that, there were no differences in survival rates among BMI subgroups. Our study results are consistent with “obesity paradox” in gastric cancer patients. We also did not find any relationship between BMI and localization of gastric tumor.

Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft progression was determined as follows: cleft cell contractility, cleft region cell-cell adhesion strength, epithelial cell mitosis rate, and cell-matrix adhesion strength.

Background/Aim. To identify the etiological role of Helicobacter pylori (Hp) and nonsteroidal anti-inflammatory drugs (NSAIDs) in endoscopically diagnosed duodenal ulcers (DUs). Methods. Patients undergoing esophagogastroduodenoscopy in two major hospitals in Antalya and Adiyaman were included in this study and assigned as duodenal ulcer (n=152; median age: 41.0 (16–71) years; 58.6% males) or control group (n=70; median age: 41.0 (18–68) years; 57.1% males). Patient demographics, risk factors, and NSAID/acetylsalicylic acid (ASA) use were recorded. Results. HP was more commonly located in the corpus (75.0 versus 50.0%; odds ratio [OR] = 3.00; 95% confidence interval [CI]: 1.66–5.44; P