Search

Abstract Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate‐glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug–drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically‐based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration‐time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7‐fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non‐wild‐type variants for both isoforms. This study is a first cornerstone to qualify the PK‐Sim platform for use of UGT‐mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.

Environmental degradation is a dynamic issue that requires ongoing monitoring to ensure ecological repair and environmental management for sustainable development. This study employed remote sensing techniques to ascertain the desertification sensitivity areas in the Niger River Basin (NRB) using the MEDALUS Model. The indicators for the model were divided into three categories: vegetation quality, climate quality, and soil quality index. The net primary productivity, estimated by the Carnegie Ames Stanford Approach model was substituted in the vegetation quality index. Each quality index was computed by calculating the geometric mean of selected sub-indices, while the geometric mean of the three quality indicators was utilized to determine the Environmental sensitivity to desertification in the study area. A total of 26.10% of the study area had low soil quality, while 26.16% and 17.41% of the study area had low vegetation and climate indicators, respectively. The study revealed that about 36.56% of the study area is highly sensitive while 27.65% and 35.78% are moderately and less sensitive respectively, to desertification in the NRB. The desertification-sensitivity index map shows that the northern part of the study area is highly susceptible to desertification and is encroaching southwards. The findings reveal that climate variables are major influencers in the study area. Our research is of importance to the Niger Basin Authority, planners, and other government agencies in charge of protecting the environment, to ascertain the sensitive areas to desertification, and to help cushion the effect of land degradation in the NRB.

Aim. To investigate the effect of the triggering method on the results of fresh embryo transfer in patients who underwent gonadotropin-releasing hormone antagonist cycles. Methods. The study was conducted retrospectively at a university-based tertiary reproductive center. The sample consisted of a total of 295 patients, of whom 111 were in the human chorionic gonadotropin (hCG) trigger group and 184 were in the dual trigger group. The main outcome measure of this study was the live birth rate, and secondary outcomes were the implantation rate, clinical pregnancy rate, miscarriage rate, and good-quality embryo rate. Results. Patient demographics and baseline characteristics did not significantly differ between the dual and hCG trigger groups. The results also indicated statistically nonsignificant differences between the two groups in terms of the number of oocytes retrieved (p>0.05), the number of mature oocytes (p>0.05), and the fertilization rate (p>0.05). The number of good-quality embryos (p=0.002) was higher in the dual trigger group compared with the hCG trigger group. However, the rates of clinical pregnancy and live births did not significantly differ between the groups (p>0.05). Conclusions. Although the number of total and high-quality embryos obtained was higher in the dual trigger group, there were no significant differences between the two groups in terms of pregnancy outcomes. The fresh embryo transfer yielded similar rates of implantation and live births in both trigger groups.

Category: Ankle Arthritis Introduction/Purpose: Total ankle arthroplasty and ankle arthrodesis are both first line options for end stage arthritis. Both have good outcomes in terms of patient reported outcome measures, complications, and revision rate. Despite efforts to determine a superior option, results are inconsistent. It may be better to take a patient-specific approach in deciding which procedure to use based on risk factors such as BMI, age, and co-morbidities. This scoping review aims to identify and summarise all literature on total ankle arthroplasty and risk factors to guide a patient-specific decision making process, helping clinicians refine selection criteria and identify patients who are likely to respond well to the procedure. Methods: A scoping review was performed using the Preferred Reporting Items for Systematic Reviews an Meta-Analyses (PRISMA) guidelines. Computer based literature searching was performed in PubMed, Embase, Cochrane trials and ISI Web of science. Two reviewers independently performed title/abstract and full text screening according to pre-determined selection criteria. English-language original research studies reporting patient related factors associated with a poorer outcome following total ankle arthroplasty were included. Outcomes were defined as patient reported outcome measures (PROMs), peri-operative complications and failure. Results: A total of 94 studies reporting 101,552 cases of total ankle arthroplasty in 101,177 patients were included. The most common patient-related risk factor associated with poorer outcomes were younger age (21 studies), rheumatoid arthritis (17 studies) and diabetes (16 studies). Of the studies using multivariate regression specifically, the most frequently described risk factors were younger age (12 studies), rheumatoid arthritis (8 studies) and diabetes (8 studies). Conclusion: When controlling for cofounding factors, the most commonly reported risk factors are younger age, rheumatoid arthritis and co-morbidities such as diabetes and smoking. These patient-related risk factors reported may be used to facilitate the refinement of patient selection criteria for total ankle arthroplasty and inform patient expectations.

Category: Other Introduction/Purpose: Optimising clinical practice requires emphasis on patient-orientated care and therefore patient reported outcome measures (PROMs) play a key role in shaping evidence-based clinical guidelines. As such, it is crucial that we use appropriate, valid and reliable PROMs to quantify outcomes in orthopaedic research. A previous systematic review evaluating evidence published between 2002-2011 identified 139 different PROMs used in the foot and ankle literature and found the most common PROM was The American Orthopaedic Foot and Ankle Society (AOFAS) score. However, in 2011, AOFAS issued a position statement outlining the lack of reliability and validity of the AOFAS score, describing it as a ‘less than ideal’ measure. This systematic review aims to provide an updated analysis of the PROMS used in the foot and ankle literature. Methods: This systematic review was performed according to PRIMSA guidelines. An electronic title/abstract screen of every article published between January 2012- December 2022 in Foot and ankle international, Clinical Orthopaedics and Related Research, Knee Surgery Sports Traumatology and Arthroscopy, The Bone and Joint Journal and The American Journal of Sports Medicine was performed by two reviewers. Articles with a foot and ankle focus were selected for full text screening and papers reporting at least one PROM were included in the final review. The following data was extracted from each article: journal of publication, month/year of publication, pathology/intervention described, PROMS reported and use of the minimally clinically important difference (MCID) to evaluate post intervention changes in PROMs. The number of studies using each individual PROM was calculated and a subgroup analysis was performed to investigate variation in PROM selection according to year of publication, journal of publication and the condition being investigated. Results: A total of 3,174 foot and ankle articles were identified, of which 1,168 (36.8%) articles reporting at least one PROM were included. The most common PROM was the AOFAS score, reported in 50.3% of studies, followed by visual analogue scale (VAS) pain score (44.4%) and 36-item short form survey (SF-36) (15.3%). Use of the AOFAS score declined across the review period. Between 2012-2016 AOFAS was the most common PROM, whilst VAS pain was most common in four of the last six years. Although some variation in PROMs according to clinical pathology exists, AOFAS score is featured in the top 3 most common PROMs for every analysed condition. Only 8/1,168 (0.7%) articles reported the number of patients achieving a minimally clinically important difference (MCID) post-intervention. Conclusion: Whilst use of the AOFAS score declined over the review period, it remains the most common PROM overall across all included journals and many conditions. There exists a lack of consensus regarding the most suitable alternative PROMs, with multiple validated instruments including FAOS, FAAM and FFI used inconsistently with relatively low frequency. There is a heavy reliance on statistical significance to evaluate and compare post-intervention PROM changes. However, it is important to quantify PROMs according to the patient perspective. Reporting the proportion of patients achieving MCID will allow clinicians to interpret PROMs and develop management guidelines in a patient-focused manner.

In this paper, we introduce a membership function used to form the fuzzy Mandelbric set and investigate the structural effects of additive and multiplicative dynamic noises on it. The newly defined membership function of this fuzzy set and its perturbations is a generalization of the indicator function for the classical Mandelbric set. We present an algorithm for detecting each complex number’s fuzzy membership degree. Through the use of the membership degrees of each complex number and experimental mathematics based on the visualizations of a variety of versions by utilizing computer-aided design, we gain a deep foresight for the structure characteristics of the additive and multiplicative perturbed fuzzy Mandelbric sets. Our novel approach allows us to identify the symmetry states of the Mandelbric set and its perturbations by the membership degrees of complex numbers, unlike the existing methods described in the literature.

Objectives:To determine the demographic, etiological, microbiological, and clinical characteristics and present treatment results of contact lens (CL)-associated microbial keratitis (CLAMK).Materials and Methods:Medical records of patients who were followed in our clinic for CLAMK between January 2014 and May 2020 were retrospectively analyzed. Demographic characteristics, symptom duration, CL and usage characteristics, risk factors, isolated microorganisms, lesion characteristics, hospital stay, recovery and follow-up times, and best corrected visual acuities (BCVA) at first and last examination were recorded.Results:The 22 patients (16 females, 6 males; 22 eyes) had a mean follow-up time of 13.0±18.3 months and mean age of 26.9±14.3 years. Most of the female patients (13/16) were under 35 years old. At least one risk factor associated with improper CL usage was identified in 21 patients (95.4%). The most common risk factor was sleeping with CL (n=15, 68.1%). Causative microorganisms were detected on microbiological examination in 15 cases (68.1%). The most common microorganism was Pseudomonas aeruginosa (n=8). Causative pathogens were sensitive at rates of 84.2%, 95% and 94.7% to combined vancomycin/amikacin, combined vancomycin/ceftazidime, and moxifloxacin, respectively. Mean BCVA was 0.9±1.1 logMAR in the first examination and increased to 0.59±1.1 at last examination (p=0.006). There was a negative correlation between BCVA at presentation and length of hospital stay (p=0.014).Conclusion:Mistakes in CL use are a frequent predisposing factor in patients with CLAMK. Informing CL users in detail about CL usage and cleaning may reduce the frequency of these mistakes and thus infections. Current antibiotic options that should be preferred in empirical treatment remain largely effective against likely pathogens. Favorable visual outcomes can be obtained in most cases with detailed diagnostic examination and appropriate treatment approaches.

Abstract Rivaroxaban is approved in various regions for the treatment of acute venous thromboembolism (VTE) in children aged between 0 and 18 years and was recently investigated for thromboprophylaxis in children aged between 2 and 8 years (with body weights

This study uses Panadero et al.'s (2021) Deep Learning Strategies Questionnaire to discover EFL learners' strategies from a new perspective. The questionnaire is a newly designed self-report instrument with ground-breaking features constructed with validity and reliability to measure students' actual strategies in real situations. The current study is the first in an EFL context to use this innovative tool. It investigates self-regulation strategies for learning English as a foreign language (EFL) among 430 male EFL college students in Saudi Arabia. The questionnaire enabled us to adopt a micro-level inspection of strategy functions based on an innovative model that can help identify possible avenues for strategy interventions. The results mostly showed a high use of deep language learning strategies in all four questionnaire categories: basic learning, visual elaboration and summarizing, deep information processing, and social learning. Consequently, all the categories had a strong, positive, and significant correlation. In addition, the most used strategies were basic learning strategies, whereas the least used were visual elaboration and summarizing. Our findings provide useful pedagogical implications for promoting EFL learning strategies and strategy instruction. Successfully replicating the Deep Learning Strategies Questionnaire scrutinizes this methodological instrument's validity and reliability and encourages other researchers to use it.

This article aims to simplify and facilitate the process of practical teaching of enzyme kinetics by utilizing minimal teaching laboratory requirements. Simultaneously, it ensures that students comprehend the enzyme kinetics experiment effectively. The focus is on teaching students how to estimate the maximum velocity (Vmax) and Michaelis constant (Km) of [beta]-fructofuranosidase enzyme (also known as invertase) isolated from dry yeast. The invertase enzyme catalyzes the hydrolysis of sucrose substrate into glucose and fructose, employing the Michaelis-Menten approach of evaluating invertase enzyme kinetics as well as Lineweaver-Burk linear graphic approach of evaluating the Michaelis-Menten enzyme kinetics. The practical experiment seeks to reinforce the concepts of initial velocity dependence on substrate concentration. The data presented in the work were generated from a genuine practical biochemistry course enrolled by second-year undergraduate students in the Department of Pharmacy and the Department of Medical Laboratory Science. While there were minor variations in the invertase enzyme kinetic parameters among students, they successfully carried out the experiment. The students accurately estimated the Vmax and Km of the invertase enzyme in the sucrose hydrolysis chemical reaction. Moreover, they demonstrated an understanding of the meanings of the kinetic parameters (Km and Vmax) and the utility of the Lineweaver-Burk plot.

Objectives:To present the demographic, etiological, clinical, and mycological characteristics and treatment results of fungal keratitis patients admitted to our clinic.Materials and Methods:The medical records of patients diagnosed with fungal keratitis between October 2012 and 2018 were reviewed. The diagnosis of fungal keratitis was confirmed mycologically and/or cytologically. Treatment response was defined as complete infiltrate resolution and re-epithelization with medical treatment and minor surgical interventions. Patients who underwent penetrating keratoplasty or evisceration due to clinical deterioration despite treatment were classified as treatment nonresponders and were compared with responders in terms of demographic, etiological, and clinical characteristics.Results:Seventy-two (12.8%) of 559 patients diagnosed with microbial keratitis in the 6-year period were fungal keratitis. Of these, 38 cases (38 eyes) without polymicrobial etiology were included in the study. The patients’ mean age was 44.9±19.0 years (range: 2-80) and males predominated (14 females [36.8%], 24 males [63.2%]). Trauma (63.6%) was the most common predisposing factor in patients younger than 40 years old, whereas pathologies impairing ocular surface immunity were the leading risk factor (48.1%) in patients older than 40 years. Filamentous fungi were detected in 34 (89.5%) cases, while yeasts were found in 4 (10.5%) cases. Among 26 cases with positive cultures, Aspergillus species were the most common pathogens (42.3%). Infiltrate size before treatment was larger in nonresponders (14/38, 36.8%) compared to treatment responders (19/38, 50%) (p=0.049). In addition, rates of treatment response were higher in cases in which the infiltrate was located paracentrally compared to other cases (p=0.036).Conclusion:Fungal keratitis is an important public health problem in our region. Ocular trauma is a leading etiology in men under the age of 40 years. In the 6-year period, we observed that the main causes of fungal keratitis were filamentous fungi, and most commonly Aspergillus species. In cases presenting with large and central lesions, aggressive treatment options should be considered and these patients should be followed up more closely.

Abstract Tuberculosis (TB) primarily affects the lungs, but some of its most devastating clinical consequences arise because of its ability to spread from the lungs to other organs. Extrapulmonary TB (EPTB) constitutes 15–20% of all TB cases. Imaging findings are not always specific and can mimic many diseases; therefore, EPTB should be considered in the differential diagnosis, particularly in patients with immune system disorders (AIDS, patients receiving chemotherapy, etc.) and those in other high-risk groups including people with diabetes. The bacterium's passage to the regional lymph nodes is essential for developing a protective T-cell-mediated immune response, but the bacterium can spread hematologically and via the lymphatic system, leading to extrapulmonary involvement. Diagnosis of EPTB in high-risk patients is made based on suspected clinical and radiological findings, but further positive culture and histopathological confirmation may be required in some instances. Radiological evaluations are critical for diagnosis and crucial in planning the treatment and follow-up. This paper aims to review the typical and atypical imaging features and the differential diagnosis of EPTB.

Amaç: Bu çalışmanın amacı farklı endikasyonlar için terapötik amaçlı yumuşak kontakt lens (TKL) uygulanan olgularda tedavi etkinliğini ve komplikasyonları incelemektir. Gereç ve Yöntem: Aralık 2011 – Haziran 2020 tarihleri arasında TKL uygulanan olguların tıbbi kayıtları retrospektif olarak incelendi. Demografik özellikler, klinik endikasyonlar, tedavi öncesi ve sonrası en iyi düzeltilmiş görme keskinlikleri (EİDGK), tedavi sonrası klinik bulgularda iyileşme ve TKL ile ilişkili komplikasyonlar kaydedildi. Bulgular: Yaşları 10-90 yıl arasında (ort. 56,08±21,18) değişen 86 olgunun (36 kadın, 50 erkek) 95 gözü çalışma kapsamına alındı. Tüm olgulara yumuşak silikon hidrojel kontakt lens (KL) uygulandı. Olguların ortalama TKL kullanım süresi 40±70,2 hafta idi (1 gün-416 hafta). TKL uygulaması için en sık endikasyonlar; büllöz keratopati (39 göz, %41,1), epitel defektleri (15 göz, %15,8) ve filamenter keratit (14 göz, %14,7) idi. TKL ile 45 gözde (%47,4) klinik bulgularda iyileşme, 30 gözde (%35,3) EİDGK’de artış saptandı. Komplikasyon olarak 8 gözde (%8,4) TKL kaybı ve 4 gözde (%4,2) mikrobiyal keratit gelişimi gözlendi. Nörotrofik kornea ülserli 10 gözde (%90,9), filamenter keratitli 11 gözde (%78,6) ve epitel defektli 10 gözde (%66,7) klinik bulgularda iyileşme saptandı. Kornea bulgularındaki iyileşmeyle paralel olarak filamenter keratitli 10 gözde (%71,4), epitel defektli 6 gözde (%40) ve nörotrofik kornea ülserli 3 gözde (%30) EİDGK’de artış saptandı. Sonuç: Uygun endikasyonlarda TKL kullanımı klinik iyileşmeye yardımcı, cerrahi girişim gereksinimini azaltabilen başarılı bir uygulamadır.

Purpose: Evaluation of ganglion cell complex measurement and the use of parameters of lamina cribrosa depth in early diagnosis and progression of patients with suspected glaucoma. Materials and Methods: Measurements were taken with Heidelberg Spectralis Spectral Domain Optical Coherence Tomography from patients in both groups. Ganglion cell complex thicknesses measured with segmentation analysis. Lamina cribrosa depths were measured by using optic nerve head images of the glaucoma suspected group and the control group. Results: Thirty-one glaucoma suspect patients and 42 healthy individuals were included in the study. The thickness of the ganglion cell layer was 11.46  in the glaucoma suspect group, and it was 12.19  in the control group. Mean lamina cribrosa depth was 579.3  in the glaucoma suspected group and 399.62  in the control group. Conclusion: Optical coherence tomography helps ophthalmologists for the diagnosis and follow-up of glaucoma patients, and non-invasively measured ganglion cell layer and lamina cribrosa depth may be a guide for early diagnosis. In this study, lamina cribrosa depth difference is more significant in the glaucoma suspect group so this parameter can be used in early diagnosis.

Amaç: Bu çalışmanın amacı farklı glokom tiplerinde korneanın biyomekanik özelliklerinin incelenmesi ve kornea biyomekaniği ile demografik ve klinik parametreler arasındaki ilişkinin araştırılmasıdır. Gereç ve Yöntem: Bu retrospektif gözlemsel çalışmaya primer açık açılı glokom (PAAG), psödoeksfoliatif glokom (PEG) ve pigmenter glokom (PG) olguları ve kontrol grubu olarak sağlıklı olgular dahil edildi. Tüm olgulara kapsamlı oftalmolojik muayene yapıldı, bilgisayarlı perimetri incelemesi ve optik koherens tomografi (OKT) verileri kaydedildi. Korneal biyomekanik özellikler Corvis ST® (Oculus, Wetzlar, Almanya) ile değerlendirildi. Bulgular: Çalışmaya yaş ortalaması 61,4±11,4 olan 48 glokom olgusu (25 PAAG, 15 PEG, 8 PG; 48 göz) ve 45,2±9,9 olan 51 sağlıklı gönüllü (51 göz) dahil edildi. Birinci aplanasyon hızı (A1V) ve deformasyon amplitüdü (DA) PAAG olgularında diğer gruplara göre daha düşük bulundu. Ayrıca PAAG grubunda 1. aplanasyondaki sertlik parametresi (SP-A1), kontrol grubu ve PEG grubuna kıyasla daha yüksek bulundu. Glokom olgularında, yaş ile stres gerinim indeksi arasında aynı yönlü glokom süresi ile SP-A1 arasında ise ters yönlü bir ilişki bulundu.. Sonuç: Çalışmamızda korneanın PAAG olgularında PEG ve PG olguları ve sağlıklı kornealara kıyasla deformasyona daha dirençli olduğu bulundu. Psödoeksfoliatif glokom ve PG olguları arasında ve bu olgular ile kontrol grubu arasında kornea biyomekaniği açısından bir fark saptanmadı..

Amaç: Bu çalışmada bir üçüncü basamak sağlık merkezinde uygulanan penetran keratoplasti (PK) ameliyatlarının endikasyon dağılımının ve çalışma periyodu içerisinde bu dağılımda görülen değişimlerin incelenmesi amaçlanmıştır. Gereç ve Yöntem: PK ameliyatı geçiren hastaların tıbbi kayıtları retrospektif olarak incelendi. Endikasyonlar; korneal skar, korneal distrofi, keratokonus, büllöz keratopati, regreft ve akut enfeksiyöz keratit olmak üzere altı ana kategori altında incelendi. Endikasyonların zaman içerisindeki değişimini inceleyebilmek amacıyla çalışma periyodu iki eşit zaman dilimine ayrıldı ve bu iki periyottaki veriler karşılaştırıldı. Bulgular: İki yüz altmış üç hastanın (117 kadın [%44,5], 146 erkek [%55,5]) 303 gözü çalışmaya dahil edildi. Penetran keratoplastinin en sık endikasyonu korneal skarlar (76 göz, %25,1) idi. Enfeksiyöz keratit sekelleri (38/76, %50) korneal skar etyolojisi içerisinde ilk sırayı alırken, etkenlere göre dağılım incelendiğinde herpetik keratite bağlı sekeller (21/38, %55,2) en büyük alt grubu oluşturmaktaydı. Çalışma periyodunun 2. yarısında korneal distrofi nedeniyle uygulanan cerrahilerin oranının azaldığı, regreft uygulanan olguların oranının ise artış gösterdiği saptandı. Sonuç: Çalışmamızda PK’nın en sık nedeni korneal skar olarak bulunmuştur.. Enfeksiyöz keratit ve korneal travma olguları açısından sağlık hizmetlerinin iyileştirilmesi; korneal distrofiler açısından ise akraba evliliklerinin önlenmesine yönelik sosyal projelerin ve genetik danışmanlık hizmetlerinin yaygınlaştırılması, bölgemizde korneal patolojiler kaynaklı görme kayıplarını azaltabilecektir.

Proteases are closely associated with many pathological conditions. Efficient detection of protease activity may be useful for diagnosis, prognosis, and the development of new therapeutic biomolecules. Fluorescent Resonance Energy Transfer (FRET) is defined as the non-radioactive energy transfer that occurs between two fluorophores. Fluorescent proteins are widely used in FRET biosensors because they can be genetically encoded and compatible with cells. Fluorescent Protein based FRET (FP-FRET) biosensors are used to monitor biological processes such as enzyme activity, intracellular ion concentration, conformational changes, protein-protein interactions. In this study, it was aimed to detect protease activity using an FP-FRET biosensor and TEV protease was chosen as a model enzyme. The plasmid encoding the mNeonGreen-mRuby3 fluorescent protein-based FRET biosensor was constructed. The gene of the designed FP-FRET biosensor was expressed in Escherichia coli DH5α cells using recombinant DNA techniques and purified using Ni-NTA affinity chromatography. As a result, the activity of the TEV protease enzyme was determined by emission measurements performed in the spectrofluorometer using the produced FP-FRET biosensor. The usability of the designed FP-FRET biosensor in the determination of protease enzyme activity was demonstrated.

Abstract Rivaroxaban has been investigated in the EINSTEIN‐Jr program for the treatment of acute venous thromboembolism (VTE) in children aged 0 to 18 years and in the UNIVERSE program for thromboprophylaxis in children aged 2 to 8 years with congenital heart disease after Fontan‐procedure. Physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling were used throughout the pediatric development of rivaroxaban according to the learn‐and‐confirm paradigm. The development strategy was to match pediatric drug exposures to adult exposure proven to be safe and efficacious. In this analysis, a refined pediatric PopPK model for rivaroxaban based on integrated EINSTEIN‐Jr data and interim PK data from part A of the UNIVERSE phase III study was developed and the influence of potential covariates and intrinsic factors on rivaroxaban exposure was assessed. The model adequately described the observed pediatric PK data. PK parameters and exposure metrics estimated by the PopPK model were compared to the predictions from a previously published pediatric PBPK model for rivaroxaban. Ninety‐one percent of the individual post hoc clearance estimates were found within the 5th to 95th percentile of the PBPK model predictions. In patients below 2 years of age, however, clearance was underpredicted by the PBPK model. The iterative and integrative use of PBPK and PopPK modeling and simulation played a major role in the establishment of the bodyweight‐adjusted rivaroxaban dosing regimen that was ultimately confirmed to be a safe and efficacious dosing regimen for children aged 0 to 18 years with acute VTE in the EINSTEIN‐Jr phase III study.

Artificial intelligence (AI) has become an integral component of human existence, with individuals employing AI tools in various facets of life. Among the most significant applications of AI is its role in facilitating communication among humans. The present study focuses on the use of AI in translating a crucial type of text that falls within the realm of geography specifically, geopolitical texts. This study investigates the influence of geography on the politics and economy of different countries. To this end, the research utilises the ChatGPT and Google Translate applications for translating geopolitical texts. A total of 84 geopolitical news headlines have been selected for analysis. The researcher adopts an eclectic model for analysing English-Arabic translations in order to address the study's key questions: What strategies are employed in rendering English geopolitical news headlines into Arabic? Furthermore, how accurate are AI tools in conveying geopolitical texts from English to Arabic?

Mathematical creative thinking skill often becomes the orientation of mathematics learning, aiming to enhance students' creativity in mathematics. Recognizing that creativity encompasses the capacity for thinking creatively and creativity disposition is essential. Building on this conceptual foundation, the primary objective of this study is to develop a comprehensive model illustrating the relationship between students' aptitude for mathematical creative thinking and their creative disposition. The research methodology employed in this study aligned with the framework of cause-and-effect analysis. The study cohort consisted of 36 students, carefully selected by a cluster random sampling technique. The research instruments included a mathematical creative thinking ability assessment and a creative disposition scale. The data was analyzed using the Non-Recursive Structural Equation Modeling. The results showed the reciprocal cause-and-effect dynamic between mathematical creative thinking ability and creative disposition, exhibiting a mutually influential relationship with determination coefficients of 21.83% and 21.05%. This shows that mathematical creative thinking ability is better at explaining mathematical creative disposition than mathematical creative disposition explaining mathematical creative thinking ability, with a relatively small difference (0.78%). This study also concluded that an optimal approach to mathematics pedagogy entails a balanced and simultaneous focus on nurturing mathematical creative thinking ability and disposition.

Objective: There are multiple risk factors, such as individual features, parenting behaviours, and peer influences associated with the development of conduct problems. The Alabama Parenting Questionnaire-Child Form (APQ-CF) is a commonly used instrument to measure parenting behaviours. The study aimed to examine the factor structure of the instrument report in the Turkish context. Method: The psychometric properties of the Turkish translation of the APQ-CF was examined with a sample of 357 high school students (M[subscript age] = 15.68, SD = 1.07, 54.1% female). Confirmatory factor analyses were conducted to examine the factor structure of the APQ. In addition, criterion-related validity and reliability coefficients for the scale were investigated. Gender differences were examined with independent samples t-tests. Results: Confirmatory factor analyses with a five-factor solution (involvement, positive parenting, poor monitoring/supervision, inconsistent discipline, and corporal punishment) showed good fit. Criterion-related validity indicated that the monitoring subscale is positively correlated with conduct problems and prosocial behaviours; mother involvement and father involvement were positively associated with prosocial behaviours. Significant gender differences emerged; while girls received more mother involvement and positive parenting, boys received less monitoring behaviours. Conclusions: These findings are indicative of acceptable psychometric properties for the Turkish version of the APQ-CF. Researchers and practitioners can use the instrument to measure parenting behaviours regarding conduct problems for various purposes such as diagnosis, treatment and intervention, and relation to behavioural and mental health outcomes.

This study employed a single-case design with an AB structure to examine the effect of implementing a Response to Intervention (RTI) model on a fourth-grade elementary school student with reading difficulties. The participant in the study was Deniz, a fourth-grade elementary school student. The pretest measures revealed that Deniz was at the frustration level in both word recognition and reading comprehension skills. Consequently, an eight-week reading intervention program was designed to address and remediate Deniz's reading difficulties. Through the intervention program, Deniz's word recognition improved from the frustration level to the instructional level, and her reading comprehension progressed from the frustration level to the independent level, accompanied by a significant decrease in reading miscues.

Abstract The success of applications of physiologically‐based pharmacokinetic (PBPK) modeling in drug development and drug labeling has triggered regulatory agencies to demand rigorous demonstration of the predictive capability of the specific PBPK platform for a particular intended application purpose. The effort needed to comply with such qualification requirements exceeds the costs for any individual PBPK application. Because changes or updates of a PBPK platform would require (re‐)qualification, a reliable and efficient generic qualification framework is needed. We describe the development and implementation of an agile and sustainable technical framework for automatic PBPK platform (re‐)qualification of PK‐Sim® embedded in the open source and open science GitHub landscape of Open Systems Pharmacology. The qualification approach enables the efficient assessment of all aspects relevant to the qualification of a particular purpose and provides transparency and traceability for all stakeholders. As a showcase example for the power and versatility of the qualification framework, we present the qualification of PK‐Sim® for the intended purpose of predicting cytochrome P450 3A4 (CYP3A4)–mediated drug–drug interactions (DDIs). Several perpetrator PBPK models featuring various degrees of CYP3A4 modulation and different types of mechanisms (competitive inhibition, mechanism‐based inactivation, and induction) were coupled with a set of PBPK models of sensitive CYP3A4 victim drugs. Simulations were compared to a comprehensive data set of 135 observations from published clinical DDI studies. The platform's overall predictive performance showed reasonable accuracy and precision (geometric mean fold error of 1.4 for both area under the plasma concentration‐time curve ratios and peak plasma concentration ratios with/without perpetrator) and suggests that PK‐Sim® can be applied to quantitatively assess CYP3A4‐mediated DDI in clinically untested scenarios.

The COVID-19 pandemic kick-started a new paradigm shift in the way and manner teaching and learning takes place on the global scale due to the lockdown that succeeded in shutting down school activities. As a result, most institutions turned to technology supported e-learning as against the traditional face-to-face teaching and learning in order to cover for lost time. This study therefore tested the effectiveness of game-based learning on students' performance in educational technology. Using a simple repeated measures design, 24 students participated in this study. Using an Educational Technology Achievement Test (ETAT), which was validated and pilot-tested to obtain data, the students were given two separate pre-tests before the commencement of the treatment as well as two different post-tests after the treatment. Data were computed using a mixed design repeated-measures ANOVA. Findings revealed that game-based learning significantly improved students' performance to a large extent (F[subscript (3, 69)] = 170.960; p < 0.05) with an effect size ([partial eta-squared]) of 0.881. The study has some implications for Nigerian teachers and researchers in Educational Technology and Science-related fields on the need to incorporate game-based learning given that it has what it takes to improve students' performance.

Changes in construction projects are inevitable. As a result of changes, construction projects experience time and cost overruns, as well as non-conformance to set quality standards leading to poor performance. Despite several studies that have been conducted on project change management systems, not enough has been done to determine its impacts on project performance. The aim of this study is to assess the impacts of change management practices on the performance of construction projects in Bauchi State, Nigeria, with a view to improving construction project delivery in the area. The study opted for an explanatory research design. A questionnaire survey was conducted in which 190 questionnaires were administered to construction professionals using the purposive sampling technique. One hundred and forty-seven (147) were returned completed representing a 77% response rate. The data obtained were analysed by means of descriptive statistics, factor analysis and multiple regression analysis. Findings from the survey revealed that the extent of Change Management (CM) practices in the construction project in the study area was low. In addition, the impacts of CM practices on time and cost performance as well as on end users’ satisfaction was positive and significant. Similarly, its impacts on the overall project performance were also positive and significant. The CM activities identified in this study can serve as a framework for effective CMS that can be used by construction professionals in managing changes at project level.

Abstract Breast tuberculosis is a rare form of extrapulmonary tuberculosis which tends to affect females of reproductive age, and is much rarer in males, postmenopausal women, and pre-pubescent girls. It is difficult to diagnose because it can mimic benign conditions such as a fibroadenoma, as well as malignant diseases like a carcinoma. It is also particularly difficult to distinguish breast tuberculosis from granulomatous mastitis, so other possible diagnoses should be ruled out first. The diagnosis of breast tuberculosis has three essential pillars: clinical examination, radiological evaluations, and histopathological sampling. Radiological evaluations are not only critical in diagnosis but are also important in the planning of the treatment and during the follow-up. This paper aims to review the imaging findings and the differential diagnosis of breast tuberculosis.

Aim:The aim of this study was to evaluate the diagnostic performance of non-contrast rapid sequences (RAMRI) visualization on cases who were clinically diagnosed as having acute abdominal pain (AAP).Materials and Methods:Forty-six patients were chosen from 2850 patients who were admitted to the emergency service between January 2016 - January 2019 because of sudden onset abdominal pain and could not get a computerized tomography analysis. A 1.5 Tesla magnetic resonance (MR) device (GE Signa Hi-Speed, Milwaukee) was used for analysis. Coronal and axial T2-weighted single-shot fast spin-echo series were used as scan protocol. No intravenous, oral or rectal contrast material was used. The cases were identified as positive (+) or negative (-) by MRI. The cases who had symptoms related with AAP, were considered as positive (+), and the cases who did not have symptoms or had symptoms which were not related with AAP, were considered as negative (-).Results:Of the patients, 26 (56.5%), were female and 20 (43.5%) were male. The median age was 38.65 (18-86) years. The treatment methodology was surgery for 25 cases (54%) and conservative for 21 (46%) cases. The operative group (surgically treated) included 24 MR (+) and one MR (-) cases. There was a harmony between the clinic and MRI data of all members in non-surgical group. The accuracy of the study was calculated as 95.6% (44/46). The sensitivity of RAMRI was calculated as 96% for operative group and 100% for non-operative group.Conclusion:A successful diagnostic performance was achieved by non-contrast RAMRI in cases with AAP.

As technology advances, AI, like ChatGPT, has become a pivotal tool in improving educational practices, particularly in special education (SE). These tools support the fourth Sustainable Development Goal (SDG), which concerns quality education for all, and the tenth SDG addresses reducing disparities. The purpose of this study is to explore the ChatGPT's role in achieving Council for Exceptional Children (CEC) standards among preservice special education teachers (SET) and the challenges they confront while using this tool. The study employed a descriptive quantitative approach with purposive sampling. The data were collected through an online questionnaire, and the study sample comprised 166 preservice SETs. The data analysis was conducted using descriptive statistics of means and standard deviations to understand the participants' perceptions comprehensively. The results indicated that the preservice SET assessed ChatGPT as a valuable tool that assisted them in meeting the CEC standards (M=3.39). The highest benefit was observed in achieving CEC Standard 2 (M= 3.87), highlighting meeting individual learning and developmental needs. Additionally, they face moderate challenges (M=2.7), primarily regarding concerns about the validity of generated data and a tendency to over-rely on the tool. These insights posit the vitality of integrating ChatGPT with SE programs while guiding students on its effective use.

The purpose of this study is to provide students with a 21st century training that can be easily applied to industrial automation training, both online and in person, and that goes beyond traditional learning methods. It involves creating and programming a training package that is compatible with the Ministry of National Education (MEB) curriculum, using the project-based learning (PBL) method and a curriculum that focuses on skills acquisition. Two different brands of programmable logic controllers (PLC) have been integrated into the manufactured training set so that the set can be used to conduct various PLC trainings. In the training set, product separation can be carried out using the electro-pneumatic system with a turntable and two conveyor belts. Motor controls, sensor applications, electro-pneumatics, touch panel and various PLC controls can also be carried out with the training set. The set focuses on the grafcet diagram method and can show how to program the same scenarios in different PLC models. By using PLC software components in the training set, students also get the opportunity to develop and experience their own unique SCADA (supervisory control and Data Acquisition) software with visual programming. This study also includes a sample curriculum prepared for PBL. In this way, all on-set training can be done using the PBL method and students get a 21st century experience. They also get the opportunity to improve their skills. PBL is an innovative and process-oriented learning method and is supported by the Ministry of Education (MoE). The prepared curriculum also includes the learning plan and measurement and assessment scales (rubrics). We anticipate that this package will be effective and useful in providing students with 21st century job skills and abilities in the field of industrial automation engineering, both online and face-to-face.

Background/purpose: In the literature, favoritism is often discussed as a form of corruption and an unethical practice. Studies related to favoritism in educational organizations have found that favoritism negatively impacts educational institutions. This study aims to investigate how teachers defined and perceived favoritism at school as well as their views on preventing such acts by the school principal. Materials/methods: A qualitative, phenomenological approach was used in the study. Data was collected from forty-five teachers who had previously been exposed to acts of favoritism using a semistructured interview form. Participants were selected using a purposive, criterion-based sampling method. Data was analyzed using descriptive and content analysis. Results: The results indicated that teachers defined favoritism as preferential and unfair treatment of people based on personal interests, friendship, gender, kinship, political views, union affiliation, teaching subject, professional experience, or race. The participants reported that school principals practiced favoritism through their choice of adjustments to class schedules and duty days, unfair distribution of extra duties, unfair response to leave requests, being unfair in tolerating mistakes, allowing for flexible class entry and exit times, or modifications to class assignments. To prevent such practices, the teachers suggested that the criteria for becoming a principal be regulated to ensure merit-based appointments and democratic management in addition to providing in-service training and supervision. They also suggested that school principalship should be subject to rotation to avoid acts of favoritism. Conclusion: These results indicate that school principals should be appointed using more objective criteria so that factors such as union affiliation and political views are not prioritized over merit. Teachers and school principals' awareness of favoritism and its negative results could also be raised by providing in-service training and explicit norms to support justice in schools.