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In this paper, an attempt has been taken to develop a method to solve the neutrosophic multiobjective linear fractional programming (NMOLFPP) problem. In the first step of our method, the problem is linearized based on some transformations. Then, the linearized model is reduced to a crisp multi-objective programming problem with the help of the accuracy function for each objective. In the following, we extend Zimmerman’s approach to maximize the truth membership and minimize the indeterminacy and falsity membership functions in the solution pro- cedure. Finally, to illustrate the proposed approach, a numerical example is included. [ABSTRACT FROM AUTHOR]

This study attempts to develop a regression model when both input data and output data are quasi type-2 fuzzy numbers. To estimate the crisp parameters of the regression model, a linear programming model is proposed based on goal programming. To handle the outlier problem, an omission approach is proposed. This approach examines the behavior of value changes in the objective function of proposed model when observations are omitted. In order to illustrate the proposed model, some numerical examples are presented. The applicability of the proposed method is tested on a real data set on soil science. The predictive performance of the model is examined by cross-validation. [ABSTRACT FROM AUTHOR]

Background: For the treatment of bone defects that exceed the critical size of the injury, several therapies have been investigated. Thermal decomposition method is suggested for extraction of natural hydroxyapatite bioceramic (HA). This technique in comparison with other methods of producing HA, has less complexity and greater economic efficiency. Objective: In the present study, a thermal decomposition method is suggested for extraction of natural HA from bovine femur bones. Methods: In this experiment, to extract the ceramic material, the bone samples were first de-fatted and ground to particles less than 420 μm, and also 420-500 μm, respectively. Prepared powders were heated at 170 °C for 24 h, and then divided into two groups for 6 h. The first group was heated at 750 °C; the second group was heated at 850 °C. The calcium phosphate compounds were obtained with complete elimination of the organic phase of the bone. These bioceramic compounds were characterized physiochemically by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), and scanning electron microscopy (SEM). Results: We found that the powder heated at 750 °C in two dimensional scales was rich in carbonated hydroxyapatite, and therefore, eminently suitable for using in hard tissue replacements. However, increasing the temperature up to 850 °C reduced the Ca/P ratio to 1.5 in the powder sample sizes less than 420 μm. Consequently, the obtained composition became rather similar to the chemical formula of tricalcium phosphate (TCP) that is appropriate in tissue engineering and drug delivery applications. Conclusion: The observations affirmed that by eliminating the collagen and other organic materials existing in the bovine bones, the mineral phase of the bone had the potential of transformation to nanoparticles. To investigate the repair of critical-size bone defects and bone augmentation, cylindrical blocks were fabricated by applying different pressures of 150, 160 and 170 MPa. The structure and compressive strength of the pressed samples after sintering at 1200 °C were characterized by SEM and compressive strength test. [ABSTRACT FROM AUTHOR]

Background and Objectives: Comprehending the research dataset is crucial for obtaining reliable and valid outcomes. Health analysts must have a deep comprehension of the data being analyzed. This comprehension allows them to suggest practical solutions for handling missing data, in a clinical data source. Accurate handling of missing values is critical for producing precise estimates and making informed decisions, especially in crucial areas like clinical research. With data's increasing diversity and complexity, numerous scholars have developed a range of imputation techniques. To address this, we conducted a systematic review to introduce various imputation techniques based on tabular dataset characteristics, including the mechanism, pattern, and ratio of missingness, to identify the most appropriate imputation methods in the healthcare field., Materials and Methods: We searched four information databases namely PubMed, Web of Science, Scopus, and IEEE Xplore, for articles published up to September 20, 2023, that discussed imputation methods for addressing missing values in a clinically structured dataset. Our investigation of selected articles focused on four key aspects: the mechanism, pattern, ratio of missingness, and various imputation strategies. By synthesizing insights from these perspectives, we constructed an evidence map to recommend suitable imputation methods for handling missing values in a tabular dataset., Results: Out of 2955 articles, 58 were included in the analysis. The findings from the development of the evidence map, based on the structure of the missing values and the types of imputation methods used in the extracted items from these studies, revealed that 45% of the studies employed conventional statistical methods, 31% utilized machine learning and deep learning methods, and 24% applied hybrid imputation techniques for handling missing values., Conclusion: Considering the structure and characteristics of missing values in a clinical dataset is essential for choosing the most appropriate data imputation technique, especially within conventional statistical methods. Accurately estimating missing values to reflect reality enhances the likelihood of obtaining high-quality and reusable data, contributing significantly to precise medical decision-making processes. Performing this review study creates a guideline for choosing the most appropriate imputation methods in data preprocessing stages to perform analytical processes on structured clinical datasets., (© 2024. The Author(s).)

Background: Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF., Materials and Methods: The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy., Results: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02)., Conclusion: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF.

Background: When treating aortic aneurysm patients with complex anatomical features, preprocedural planning aided by 3D-printed models offers valuable insights for endovascular intervention. This study highlights the use of stereolithographic (SLA) 3D printing to fabricate a phantom of a challenging aortic arch aneurysm with a complex neck anatomy., Clinical Case: A 75-year-old female presented with a 58 mm descending thoracic aortic aneurysm (TAA) extending to the distal arch, involving the left subclavian artery (LSA) and the left common carotid artery (LCCA). The computed tomography (CT) scans underwent scrutiny by radiology and vascular teams. Nevertheless, the precise spatial relationships of the ostial origins proved to be challenging to ascertain. To address this, a patient-specific phantom of the aortic arch was fabricated utilizing an SLA printer and a biomedical resin. The thoracic endovascular aortic repair (TEVAR) procedure was simulated using fluoroscopy on the phantom to enhance procedural preparedness. Subsequently, the patient underwent a right carotid-left carotid bypass and a right carotid-left subclavian bypass. After a 24-hour interval, the patient underwent the TEVAR procedure, during which a 37 mm × 150 mm stent graft (CTAG, WL Gore and Associates, Flagstaff, AZ, USA) and a 40 mm × 200 mm stent graft (CTAG, WL Gore and Associates, Flagstaff, AZ, USA) were deployed, effectively covering the LSA and LCCA. Notably, the aneurysm exhibited complete sealing, with no indications of endoleaks or graft infoldings. At the 12-month follow-up, the patient remains in good health, with no evidence of endoleaks or any other surgery-related complication., Conclusion: This report showcases the successful use of a 3D-printed endovascular phantom in guiding the decision-making process during the preparation for a TEVAR procedure. The simulation played a pivotal role in selecting the appropriate stent graft, ensuring an intervention protocol optimized based on the patient-specific anatomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An ideal vascular phantom should be anatomically accurate, have mechanical properties as close as possible to the tissue, and be sufficiently transparent for ease of visualization. However, materials that enable the convergence of these characteristics have remained elusive. The fabrication of patient-specific vascular phantoms with high anatomical fidelity, optical transparency, and mechanical properties close to those of vascular tissue is reported. These final properties are achieved by 3D printing patient-specific vascular models with commercial elastomeric acrylic-based resins before coating them with thiol-based photopolymerizable resins. Ternary thiol-ene-acrylate chemistry is found optimal. A PETMP/allyl glycerol ether (AGE)/polyethylene glycol diacrylate (PEGDA) coating with a 30/70% AGE/PEGDA ratio applied on a flexible resin yielded elastic modulus, UTS, and elongation of 3.41 MPa, 1.76 MPa, and 63.2%, respectively, in range with the human aortic wall. The PETMP/AGE/PEGDA coating doubled the optical transmission from 40% to 80%, approaching 88% of the benchmark silicone-based elastomer. Higher transparency correlates with a decrease in surface roughness from 2000 to 90 nm after coating. Coated 3D-printed anatomical replicas are showcased for pre-procedural planning and medical training with good radio-opacity and echogenicity. Thiol-click chemistry coatings, as a surface treatment for elastomeric stereolithographic 3D-printed objects, address inherent limitations of photopolymer-based additive manufacturing., (© 2024 Wiley‐VCH GmbH.)

Background: There is no agreement on which of the 2 gonadotropin-releasing hormone (GnRH) agonist protocols are the most efficient, neither there is any consensus on which one yields a better clinical pregnancy percentage., Objective: The present study aims to compare the effectiveness of reduced dosages of long- and short-acting GnRH agonists on pregnancy outcomes., Materials and Methods: In this randomized controlled clinical trial, 400 women were randomly assigned to 2 groups (n = 200/group): the reduced dosage of long-acting GnRH agonist group (group 1, 1.25 mg Decapeptyl) and the short-acting GnRH agonist group (group 2, 0.5 mg/day Buserelin Acetate). The study was conducted at Mehr Medical Institute, Rasht, Iran between July 2019 and July 2020. Biochemical and clinical pregnancy were compared between groups., Results: No significant differences were observed in the endometrial lining, the total number of retrieved and metaphase-II oocytes, progesterone, and serum estradiol levels on human chorionic gonadotropin day, fertilization rate, and top-quality embryos between the groups. The duration of induction (10.8 ± 1.7 vs. 10 ± 2.1, p < 0.001) and the total dosage of gonadotropins (2939.4 ± 945.9 vs. 2441 ± 1247.1, p < 0.001) were significantly greater in group 2 than in group 1. No significant differences were observed between the 2 groups in terms of implantation rate, chemical pregnancy rate, and clinical pregnancy rate. A higher percentage of ovarian hyperstimulation syndrome was observed in group 2 (p = 0.005)., Conclusion: Due to a lower percentage of ovarian hyperstimulation syndrome in group 1 and similar assisted reproductive technology outcomes in both groups, the long protocol was found to be superior to the short protocol., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2023 Kabodmehri et al.)

Objectives: To investigate the added diagnostic value of delayed imaging at 3 and 4 h compared to 2 h imaging as well as scanning up to 4 h compared to 3, and by this means, diagnosis reclassification or changes in diagnosis across various time points., Methods: Seventeen patients clinically suspected of gastroparesis, 8 (47.1%) men and 9 (52.9%) women, according to the standard procedural guidelines, underwent gastric emptying scintigraphy after ingesting a standard meal. One-minute static images in anterior and posterior projections were acquired immediately after ingestion and then at 1-, 2-, 3- , and 4 h time points. For image analysis, a manual region-of-interest was drawn, and then, count of stomach in each projection was used to calculate geometric mean for each time point. Decay correction was applied. At 2-, 3- and 4 h time points, percentage of retained activity was compared to standard values; therefore, each patient was labeled as normal or delayed., Results: Pairwise correlation between time points was statistically significant. Value of hour 3 shows an extremely strong correlation with the value of hour 4 (r=0.951, p<0.001). In hour 2, of 17 participants, 11 (64.7%) were diagnosed as normal and 6 (35.3%) as delayed. In hour 3, the diagnosis made as delayed rose to 9 (52.9%), whereas normal was 8 (47.1%). Finally, in hour 4, results were 10 (58.8%) as delayed and 7 (41.2%) as normal. All subjects who were labeled as delayed in hour 3 remained with the same diagnosis and 1 out of 8 subjects categorized as normal in hour 3 changed to delayed. For testing agreement, coefficient of kappa was computed between each pair. Agreement between diagnosis in hour 2 with hours 3 or 4 was not strong (kappa <0.6 for both pairs). However, a strong agreement was found between diagnosis in hours 3 and 4 (kappa: 0.881)., Conclusion: Because of excellent correlation between values of hours 3 and 4 and strong agreement between the diagnosis in those time points, extending acquisition from 3 to 4 h adds little to the final dai gnosis and may not be noticeably meaningful, especially in the clinical setting., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the Turkish Society of Nuclear Medicine / Molecular Imaging and Radionuclide Therapy published by Galenos Publishing House.)

Tyrosine protein kinases (TKs) have been proved to play substantial roles on many cellular processes and their overexpression tend to be found in various types of cancers. Therefore, over recent decades, numerous tyrosine protein kinase inhibitors particularly epidermal growth factor receptor (EGFR) inhibitors have been introduced to treat cancer. Present study describes a novel series of imidazo[1,2-a]quinazolines 18 as potential -inhibitors. These imidazoquinazolines (18a and 18o, in particular) had great anti-proliferative activities with IC 50 values in the micromolar (µM) range against PC3, HepG2, HeLa, and MDA-MB-231 comparing with Erlotinib as reference marketed drug. Further evaluations on some derivatives revealed their potential to induce apoptotic cell death and cell growth arrest at G0 phase of the cell cycle. Afterwards, the kinase assay on the most potent compounds 18a and 18o demonstrated their inhibitory potencies and selectivity toward EGFR (with EGFR-IC 50 values of 82.0 µM and 12.3 µM, respectively). Additionally, western blot analysis on these compounds 18a and 18o exhibited that they inhibited the phosphorylation of EGFR and its downstream molecule extracellular signal-regulated kinase (ERK1/2). However, the level of B-Actin phosphorylation was not changed. Finally, density functional theory calculations, docking study, and independent gradient model (IGM) were performed to illustrate the structure-activity relationship (SAR) and to assess the interactions between proteins and ligands. The results of molecular docking studies had great agreement with the obtained EGFR inhibitory results through in vitro evaluations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

An important role has been considered for the vascular endothelial growth factor receptor 2 (VEGFR-2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC 50 values of 4.5-15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR-2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Objective: To investigate if combination therapy with clomiphene citrate (CC) plus letrozole (L) was associated with a higher efficacy than L and CC alone in patients undergoing ovarian induction plus intrauterine insemination., Methods: The present multicenter randomized controlled clinical trial was performed between 2018 and 2020. Participants were randomized into three groups: L (n = 167; 5 mg/day), CC (n = 167; 100 mg/day), and L + CC (n = 167) (2.5 mg/day + 50 mg/day) from day 3. Ovarian stimulation was continued with the appropriate dose of gonadotropins daily starting from day 8 and continued until follicular size was 20 mm or more followed by administration of human chorionic gonadotropin (10 000 IU). Semen samples were prepared by direct swim-up technique., Results: In the CC group, gonadotropin dose was significantly higher but endometrial thickness was significantly lower compared with other groups. Number of follicles of 18 mm or more was significantly lower in the L group compared with the other two groups. Number of follicles less than 15 mm was meaningfully higher in the CC group compared with the other groups. In the L + CC group, total and largest follicular size, and the rates of chemical, clinical, and ongoing pregnancy, and live birth were significantly higher compared with other groups., Conclusion: Combination therapy with L + CC was superior to either L or CC for achieving pregnancy in women undergoing ovarian induction plus intrauterine insemination., (© 2021 International Federation of Gynecology and Obstetrics.)

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC 50 = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC 50 = 9-123 nM) compared to donepezil as the standard drug (IC 50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC 50 = 2 nM) showed acceptable BuChE inhibition activity (IC 50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H 2 O 2 -induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce β-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MS declared a shared affiliation with the authors EH, SM, MS, MK at the time of review., (Copyright © 2022 Babaei, Küçükkılınç, Jalili-Baleh, Nadri, Öz, Forootanfar, Hosseinzadeh, Akbari, Ardestani, Firoozpour, Foroumadi, Sharifzadeh, Mirjalili and Khoobi.)

Developing isothermal bio-analyzers for amplified detection of multi-factor diseases like cancer biomarkers (nucleic acid and protein) has facilitated the early diagnosis and clinical theranostics. In light of that, a sensitive detection system was developed assisted by the recognition capability of a functional aptamer followed by cyclic self-assembly of three auxiliary hairpins via branched hybridization chain reaction (b-HCR) performance. In the downstream process, in the presence of hemin, split sequences of a DNAzyme brought in close proximity to facilitate the color alteration of the solution to a green appearance. By ingenious exerting multi-level amplification, the assay empowered sensitive detection of miR-21 and PDGF-BB related cancer biomarkers with LOD values of 10 pM and 40 nM, respectively. Taken together, simplicity, enzyme-free nature, excellent generality, affordable cost without any washing steps and immobilization makes the presented system a promising analytical tool in synthetic biology, designing nanomachines and point-of-care detection in resource-constrained settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds 8b and 8c displayed broad-spectrum activity and superior in vitro antifungal capabilities compared to the standard drug FLC against sensitive and resistant Candida albicans ( C. albicans ). The highly active compounds 8b and 8c had potent antibiofilm properties against FLC-resistant C. albicans species. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure-activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally, in vivo results represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along with in vitro and in silico studies, demonstrating the therapeutic efficiency of compounds 8b and 8c as novel leads for candidiasis drug discovery., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Introduction: Renal transplantation is the gold standard treatment for chronic kidney disease. Renal scintigraphy has been performed widely to evaluate postsurgical complications of transplantation, but there are little data regarding 99mTc-EC scintigraphy in kidney transplantation., Methods and Materials: This was a prospective descriptive study. All patients who underwent kidney transplantation and passed an uneventful postoperative period entered the study. Demographic characteristics, including age, gender, biochemical parameters before and after the transplantation and 99mTc-EC parameters including time to max, time to ½ max, slope from max to ½ max, upslope time interval and time to 2/3 max as well as episodes of rejection, were recorded. Patients were then followed up for 1 year at 3-, 6-, 9- and 12-month intervals., Results: Forty-one patients who underwent renal transplantation entered the study. Mean ± SD age of patients was 40.65 ± 12.84 years (min 17 and max 74 years). In total, 25% (10) of patients experienced one or two episodes of rejection and were hospitalized. Time of max, time of 1/2 max, time from max to 1/2 max, time of 2/3 max, time from max to 2/3 max and upslope time interval had a significant association with transplant rejection using a Cox regression model. With 1-min increase in time of max, the risk of rejection increased by 27% (hazard ratio = 1.27; CI, 1.03--1.56) and with 1-min increase in time of 1/2 max, the risk of rejection increased by 28% (hazard ratio = 1.28; CI, 1.14-1.45)., Discussion: 99mTc-EC renal scintigrahpy was able to predict kidney transplantation rejection in our patients. 99mTc-EC renal scintigrahpy is beneficial to evaluate transplant kidney function to prevent complications and helps close follow-up., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The epiphyseal tubercle, the corresponding metaphyseal fossa, and peripheral cupping are key stabilizers of the femoral head-neck junction. Abnormal development of these features in the setting of supraphysiologic physeal stress under high forces (for example, forces that occur during sports activity) may result in a cam morphology. Although most previous studies on cam-type femoroacetabular impingement (FAI) have mainly focused on overgrowth of the peripheral cupping, little is known about detailed morphologic changes of the epiphyseal and metaphyseal bony surfaces in patients with cam morphology., Questions/purposes: (1) Does the CT-based bony morphology of the peripheral epiphyseal cupping differ between patients with a cam-type morphology and asymptomatic controls (individuals who did not have hip pain)? (2) Does the CT-based bony morphology of the epiphyseal tubercle differ between patients with a cam-type morphology and asymptomatic controls? (3) Does the CT-based bony morphology of the metaphyseal fossa differ between patients with a cam-type morphology and asymptomatic controls?, Methods: After obtaining institutional review board approval for this study, we retrospectively searched our institutional database for patients aged 8 to 15 years with a diagnosis of an idiopathic cam morphology who underwent a preoperative CT evaluation of the affected hip between 2005 and 2018 (n = 152). We excluded 96 patients with unavailable CT scans and 40 patients with prior joint diseases other than cam-type FAI. Our search resulted in 16 patients, including nine males. Six of 16 patients had a diagnosis of bilateral FAI, for whom we randomly selected one side for the analysis. Three-dimensional (3-D) models of the proximal femur were generated to quantify the size of the peripheral cupping (peripheral growth of the epiphysis around the metaphysis), epiphyseal tubercle (a beak-like prominence in the posterosuperior aspect of the epiphysis), and metaphyseal fossa (a groove on the metaphyseal surface corresponding to the epiphyseal tubercle). A general linear model was used to compare the quantified anatomic features between the FAI cohort and 80 asymptomatic hips (aged 8 to 15 years; 50% male) after adjusting for age and sex. A secondary analysis using the Wilcoxon matched-pairs signed rank test was performed to assess side-to-side differences in quantified morphological features in 10 patients with unilateral FAI., Results: After adjusting for age and sex, we found that patients with FAI had larger peripheral cupping in the anterior, posterior, superior, and inferior regions than control patients who did not have hip symptoms or radiographic signs of FAI (by 1.3- to 1.7-fold; p < 0.01 for all comparisons). The epiphyseal tubercle height and length were smaller in patients with FAI than in controls (by 0.3- to 0.6-fold; p < 0.02 for all comparisons). There was no difference in tubercle width between the groups. Metaphyseal fossa depth, width, and length were larger in patients with FAI than in controls (by 1.8- to 2.3-fold; p < 0.001 for all comparisons). For patients with unilateral FAI, we saw similar peripheral cupping but smaller epiphyseal tubercle (height and length) along with larger metaphyseal fossa (depth) in the FAI side compared with the uninvolved contralateral side., Conclusion: Consistent with prior studies, we observed more peripheral cupping in patients with cam-type FAI than control patients without hip symptoms or radiographic signs of FAI. Interestingly, the epiphyseal tubercle height and length were smaller and the metaphyseal fossa was larger in hips with cam-type FAI, suggesting varying inner bone surface morphology of the growth plate. The docking mechanism between the epiphyseal tubercle and the metaphyseal fossa is important for epiphyseal stability, particularly at early ages when the peripheral cupping is not fully developed. An underdeveloped tubercle and a large fossa could be associated with a reduction in stability, while excessive peripheral cupping growth would be a factor related to improved physeal stability. This is further supported by observed side-to-side differences in tubercle and fossa morphology in patients with unilateral FAI. Further longitudinal studies would be worthwhile to study the causality and compensatory mechanisms related to epiphyseal and metaphyseal bony morphology in pathogenesis cam-type FAI. Such information will lay the foundation for developing imaging biomarkers to predict the risk of FAI or to monitor its progress, which are critical in clinical care planning., Level of Evidence: Level III, prognostic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Each author certifies that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2020 by the Association of Bone and Joint Surgeons.)

Aim of the Study: Some cancerous patients have hip prosthesis of metal elements when they undergo radiation therapy. Metal implants are a cause of metal artifacts in computed tomography (CT) images due to their higher density compared to normal tissues. The aim of this study is to evaluate the quantitative effects of metal artifacts on dose distribution of the pelvic region., Materials and Methods: Seven patients with metal implants in the pelvic region were scanned and CT images were exported to the Monaco treatment planning system. Based on the diagnosis of each patient, three-dimensional plans were implemented on CT images and dose distributions were extracted. At the next step, metal artifacts were contoured and electron densities of these new structures were modified to the extent of soft tissue. Finally, dose distributions and the differences were investigated by VeriSoft software., Results: The results of this study showed that if the electron density to metal artifacts is not assigned properly, it will increase the calculated monitor units (MUs) by almost 3.78 MUs/fraction which will significantly affect total dose distribution of treatment., Conclusion: For the precise implementation of the treatment and in order to minimize the systematic errors related to the calculated MUs, necessary corrections on the electron density of metal artifacts should be considered before the treatment planning. The issue will be more critical in advanced treatment modalities where dose escalation is needed., Competing Interests: None

As a novel cause of pneumonia, coronavirus disease 2019 (COVID-19) has rapidly progressed worldwide. Previous studies have indicated COVID-19 patients with diabetes show higher mortality rates and more severe COVID-19 infection with an increased requirement for intensive care and hospital length of stay (LOS) compared to non-diabetic patients. The present study aimed to investigate the association of diabetes and COVID-19 outcome with severity of disease in hospitalized patients. The present case-control study included 268 patients diagnosed with COVID-19 who were hospitalized in Ayatollah Khoyi Hospital, Khoy, Iran. Diabetes was identified based on medical history and/or criteria of published documents. Out of 268 patients (median age of 59 years; 53.4 % male), 127 patients had diabetes (47 %). Diabetic patients had remarkably higher mortality rates (adjusted odds ratio, aOR: 3.36; confidence interval, CI: 1.17-9.66), requirement for invasive mechanical ventilation (IMV) (aOR: 4.59; CI: 1.38-15.25), and LOS (aOR: 1.13; CI: 1.06-1.24) compared to patients without diabetes. Inflammatory biomarkers including C-reactive protein (CRP), lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) were increased in patients with diabetes compared to non-diabetic patients (P < 0.05 for all the comparisons). In hospitalized patients with COVID-19, diabetes was correlated with increased disease severity and mortality., (Copyright © 2021 Moghaddam Tabrizi et al.)

Over recent years, in-depth understanding of the mechanism of oxidative N-heterocyclic carbene (NHC) catalyzed reactions in the presence of a mild oxidant and the structure of key radical intermediates have been considered as an important challenge in organic chemistry. Furthermore, the role of using a mixture of bases with different strengths is unclear in NHC-catalyzed reactions. In this paper, the detailed competing oxidative mechanisms, origin of stereoselectivity, and role of the NHC-organocatalyst in the NHC-catalyzed reactions of dioxindoles with enals were studied using the density functional theory method. In addition, the roles of newly produced Brønsted acids of the applied bases, i.e.DBU·H+ and DABCO·H+, are examined. The computational results indicated that the oxidation of the Breslow intermediate by nitrobenzene (NB) occurs first through a hydrogen atom transfer (HAT) pathway from the Breslow intermediate, and then it is oxidized into acyl azolium by single electron transfer (SET). We found that the energy barrier of the proton transfer processes is remarkably reduced by the conjugated Brønsted acid of the weaker base in the solution. Further, the calculated results revealed that the NHC catalyst has different behavior before and after the oxidation of the Breslow intermediate in these reactions. Before oxidation, the nucleophilicity of R1 increased by adding R1 to NHC, while, after the oxidation process, the electrophilicity of R1 increases, and as a result the product of oxidation, α, β unsaturated acyl azolium, acts as an electrophile. This mechanistic study paves the way for the rational design of oxidative NHC-catalyzed reactions.

Background: There is conflicting evidence regarding the impact of season on the assisted reproductive technology outcome., Objective: To retrospectively compare three year outcome of women undergoing their first intracytoplasmic sperm injection cycle, across seasons., Materials and Methods: In this descriptive cross-sectional study, 3,670 women who underwent their first intracytoplasmic sperm injection cycle in Mehr Medical Institute, Rasht, Iran between April 2010 and May 2014 were studied. Women were divided into four groups according to the day of oocyte retrival as: spring (n = 808), summer (n = 994), autumn (n = 1066), and winter (n = 802). Basal and stimulation charecteristics were compared among groups., Results: While sperm concentration and motility were significantly lower during summer, the total number of retrieved and metaphase II oocytes were significantly higher (p = 0.0001, p = 0.0001, p = 0.004, p = 0.02, respectively). Fertilization rate were significantly higher during autumn (p = 0.0001). Also, the number of high- quality transferred embryos were significantly higher during summer and winter (p = 0.03). A similar pattern was observed in implantation rate and pregnancy over the four seasons., Conclusion: Despite the fact that intracytoplasmic sperm injection minimize the seasonal effect on pregnancy outcome, changes in pregnancy rate still occur among different seasons without particular pattern. It seems that performing assisted reproductive technology procedures in a particular season should be considered as an effective factor., Competing Interests: The authors declare that there is no conflict of interest in the present study., (Copyright © 2020 Mehrafza et al.)

Fluctuation of nucleic acid expression and ultrasensitive and specific detection of these variations in expression is a crucial subject in molecular medicine and clinical theranostics. A novel DNAzyme-coupled branched hybridization chain reaction (b-HCR) assay is reported for efficient signal-amplified detection of miRNA in this study. This assay was composed of a translator (T) hybridized with miR-21 to initiate the first HCR by hairpin 1 (H 1 ) and hairpin 2 (H 2 ). The primary HCR provided a backbone chain for numerous branches budding through hairpin 3 (H 3 ) and hairpin 4 (H 4 ) assembles. In the presence of hemin, the G-rich domains embedded in H1 and H4 produce an active G-quadruplex DNAzyme upon exposure to a target that could catalyze the oxidation of colorless substrate to colored product. The present approach has the potential to be used for quantitative detection of miR-21 with a sensitivity and a dynamic range of 1 pM and 1 pM to 1 nM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

According to aptamer-mediated hairpin DNA cascade amplifier and gold nanoparticles aggregation, an optical platform for cancer cells determination has been proposed. High-affinity chimeric aptamers were used for cancer cell detection and also as an initiator for beginning hairpin assembly to construct three-way junction (3WJ) nanostructures. These three hairpins were modified at 3' ends with biotin. In the presence of target cell, chimeric aptamer binds to its ligand on cell surface and initiates 3WJ nanostructures formation. These 3WJ nanostructures interact with streptavidin-modified gold nanoparticles (AuNPs) via non-covalent biotin-streptavidin interactions and create a crossover lattice of nanoparticles. This event leads to AuNPs aggregation and red-shifting. The results were confirmed by gel electrophoresis and UV-visible spectrophotometry. The dynamic range of this assay is 25 to 10 7 cells with a detection limit of 10 cells which is respectively 9 and 4 times more significant than the sensitivity of AuNP-based approaches without amplification and enzyme-mediated signal amplification. Graphical abstract.

Aim: Rheumatoid arthritis (RA) is a prevalent inflammatory, autoimmune diseases characterized by inflammation and destruction of joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can have modulatory interference in disease process. In this study, the effect of Guluronic Acid (G2013) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunomodulatory effects was evaluated on IL-17 , RORγt , IL-4 and GATA-3 gene expression in RA patients. Methods: Fourteen patients with RA who had an inadequate response to conventional treatments were included in this clinical trial. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. G2013 was administered orally at dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the gene expression levels of IL-4 , GATA-3 , IL-17 and RORγt . Results: Primary and secondary efficacy endpoints and Disease Activity Score (DAS) 28 showed an improvement after 12 weeks of treatment. G2013 has a potent efficacy on gene expression of these molecules, so that it could decrease IL-17 and RORγt levels and increase IL-4 and GATA-3 levels after 12 weeks of treatment. Reduction of IL-17 was statistically non-significant whereas for its transcription factor (RORγt ) was statistically significant. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. Conclusion: G2013 as a natural novel drug showed a significant increase on IL-4 and GATA-3 and a significant decrease on RORγt gene expression after 12 weeks oral administration of this drug in RA patients. (Clinical trial identifier: IRCT2016092813739N5).