The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Corrigendum: Applications and techniques for fast machine learning in science.

[This corrects the article DOI: 10.3389/fdata.2022.787421.].

The Effect of Lower Limb Position on Anterior Cruciate Ligament Reconstruction on Uncommon Complications after Surgery.

Background: To reduce the complications of orthopedic surgery, the desire for less invasive procedures, such as, knee arthroscopy to repair the anterior cruciate ligament, has increased. There are, currently, two common positions for limbs that are used during surgery depending on the surgeon's experience. Therefore, our aim was to investigate the effect of limb position on complications after anterior cruciate ligament reconstruction surgery. Materials and Methods: From April 2016 to July 2020 at our orthopedic-sports trauma center, 688 patients between the ages of 18 and 50 with anterior cruciate ligament rupture underwent reconstruction surgery with a hamstring graft. Patients were divided into two groups in terms of limb position at the time of surgery. For three months, patients were evaluated for surgical complications, basic demographic information, and information during surgery. Results: There was no statistically significant difference between the two groups in terms of demographic information, side of injury, preparation time, tourniquet time, operation time, and duration of hospitalization. At quarterly follow-up, there was no significant difference between the two groups in terms of postoperative complications (P = 0.976). Conclusions: There is no difference between compartment syndrome and deep vein thrombosis in different situations, therefore, the surgeon should operate in any position he is skilled in. Also, surgeons should always pay special attention to these complications and provide necessary training to patients in order to prevent them.

Epigenetic drugs as new emerging therapeutics: What is the scale's orientation of application and challenges?

Epigenetics is the study of heritable changes in gene expression or function without altering the DNA sequence. Important factors are part of epigenetic events, such as methylation, DNA histone rearrangements, nucleosome transposition, and non-coding RNAs. Dysregulated epigenetic mechanics are associated with various cancers' initiation, development, and metastasis. It is known that the occurrence and development of cancer can be controlled by regulating unexpected epigenetic events. Epi-drugs are used singly or in combination with chemotherapy and enhance antitumor activity, reduce drug resistance, and stimulate the host immune response. Despite these benefits, epigenetic therapy as a single therapy or in combination with other drugs leads to adverse effects. This review article introduces and compares the advantages, disadvantages, and side effects of using these drugs for the first time since their introduction. Also, this article describes the mechanism of action of various epigenetic drugs. Recommendations for future use of epigenetic drugs as cancer therapeutics are suggested as an overall conclusion.

Cellular and molecular basis of therapeutic approaches to breast cancer.

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer.

Specific pattern of bone scan as a result of unintentional-intraarterial injection into the ulnar artery.

Background: Bone scintigraphy with 99mTc labeled radiopharmaceuticals is a valuable method in nuclear medicine for assessing the bony structure. In clinical setting, bone scintigraphy is accomplished after the injection of 99mTc labeled diphosphonate complexes into a peripheral vein. Inadvertent intra-arterial injection on the antecubital region may cause a special form of artifacts leading to problems inaccurately interpreting these studies as functional images. Case Presentation: We present a 44-year-old man with history of chest wall pain for bone scintigraphy as part of a work-up for determining the pain source. The patient received an injection of 740MBq 99mTc-methylene diphosphonate (MDP) into a blood vessel at the right forearm. Two hours later, an increased uptake of activity was observed on the right forearm and ulnar half of the wrist-hand in the whole body and spot images. The scan findings were consistent with the anatomical and physiological expectations of the ulnar arterial perfusion range. This case displays that an incidental injection with a 99mTc labeled diphosphonate into the ulnar artery results in a hot ulnar half of the palm and ulnar-sided three digits, because these areas are directly exposed to radiopharmaceutical, therefore more radiopharmaceutical is deposited. Conclusion: It is important for the physician, and especially for the nuclear medicine technician, to know the specific appearance created in the bone scan due to such an event so that they do not make a diagnostic mistake.

Applications and Techniques for Fast Machine Learning in Science.

In this community review report, we discuss applications and techniques for fast machine learning (ML) in science-the concept of integrating powerful ML methods into the real-time experimental data processing loop to accelerate scientific discovery. The material for the report builds on two workshops held by the Fast ML for Science community and covers three main areas: applications for fast ML across a number of scientific domains; techniques for training and implementing performant and resource-efficient ML algorithms; and computing architectures, platforms, and technologies for deploying these algorithms. We also present overlapping challenges across the multiple scientific domains where common solutions can be found. This community report is intended to give plenty of examples and inspiration for scientific discovery through integrated and accelerated ML solutions. This is followed by a high-level overview and organization of technical advances, including an abundance of pointers to source material, which can enable these breakthroughs.

The efficacy of melatonin against radiotoxicity of iodine-131 and its response to treatment in hyperthyroid patients: a randomized controlled trial.

BACKGROUND: Since melatonin is a non-toxic compound with proven radioprotective effects, we aimed to investigate its efficacy in an in-vivo setting in hyperthyroid patients who are treated with iodine-131. This double-blind placebo-controlled study was conducted on hyperthyroid patients referred to nuclear medicine centers in Babol, Iran. We excluded patients suffering from hypertension treated with warfarin, autoimmune diseases, genetic diseases, cancers, smokers, chemical wounded, radiology and radiotherapy workers, and those who were treated with chemotherapy agents. Patients were randomly assigned to receive a capsule containing 300 mg of melatonin powder or a placebo. Just before receiving iodine-131, blood samples were taken from individuals. All 52 female patients received 10 to 20 mCi iodine-131 for treating hyperthyroidism. A second blood sample was taken one hour after the administration of iodine-131. MATERIAL AND METHODS: To determine the chromosomal damages before and after receiving radioiodine, we performed the cytokinesis- block micronucleus assay. Also, at phase 2, 6 months follow-up was performed, in which patients' positive responses to treatment were compared. RESULTS: The findings of this study indicate that the difference in micronucleus formation between the placebo and melatonin groups is not significant. However, a significant difference in the 6 months follow-up revealed that 61.5% and 85.7% of patients had a positive response to treatment in the placebo and melatonin groups, respectively. CONCLUSIONS: As one of the first studies dealing with the human in-vivo assessment on the radioprotective effects of melatonin, it was concluded that melatonin has a non-significant positive impact on reducing the rate of chromosomal damages in hyperthyroid patients treated with iodine-131. Nevertheless, the outcome of treatment was significantly higher by melatonin compared to the placebo group.

Successful intracoronary thrombolysis in a patient with anterior myocardial infarction and large thrombus burden associated with coronary artery ectasia.

Although ectatic coronary arteries with high thrombus burden, leading to acute coronary events, can be difficult to manage, intracoronary thrombolytics and glycoprotein IIb/IIIa inhibitors can act as potential successful treatment options.

Coupling brain-tumor biophysical models and diffeomorphic image registration.

We present SIBIA (Scalable Integrated Biophysics-based Image Analysis), a framework for joint image registration and biophysical inversion and we apply it to analyze MR images of glioblastomas (primary brain tumors). We have two applications in mind. The first one is normal-to-abnormal image registration in the presence of tumor-induced topology differences. The second one is biophysical inversion based on single-time patient data. The underlying optimization problem is highly non-linear and non-convex and has not been solved before with a gradient-based approach. Given the segmentation of a normal brain MRI and the segmentation of a cancer patient MRI, we determine tumor growth parameters and a registration map so that if we "grow a tumor" (using our tumor model) in the normal brain and then register it to the patient image, then the registration mismatch is as small as possible. This "coupled problem" two-way couples the biophysical inversion and the registration problem. In the image registration step we solve a large-deformation diffeomorphic registration problem parameterized by an Eulerian velocity field. In the biophysical inversion step we estimate parameters in a reaction-diffusion tumor growth model that is formulated as a partial differential equation (PDE). In SIBIA, we couple these two sub-components in an iterative manner. We first presented the components of SIBIA in "Gholami et al., Framework for Scalable Biophysics-based Image Analysis, IEEE/ACM Proceedings of the SC2017", in which we derived parallel distributed memory algorithms and software modules for the decoupled registration and biophysical inverse problems. In this paper, our contributions are the introduction of a PDE-constrained optimization formulation of the coupled problem, and the derivation of a Picard iterative solution scheme. We perform extensive tests to experimentally assess the performance of our method on synthetic and clinical datasets. We demonstrate the convergence of the SIBIA optimization solver in different usage scenarios. We demonstrate that using SIBIA, we can accurately solve the coupled problem in three dimensions (2563 resolution) in a few minutes using 11 dual-x86 nodes.

Simulation of glioblastoma growth using a 3D multispecies tumor model with mass effect.

In this article, we present a multispecies reaction-advection-diffusion partial differential equation coupled with linear elasticity for modeling tumor growth. The model aims to capture the phenomenological features of glioblastoma multiforme observed in magnetic resonance imaging (MRI) scans. These include enhancing and necrotic tumor structures, brain edema and the so-called "mass effect", a term-of-art that refers to the deformation of brain tissue due to the presence of the tumor. The multispecies model accounts for proliferating, invasive and necrotic tumor cells as well as a simple model for nutrition consumption and tumor-induced brain edema. The coupling of the model with linear elasticity equations with variable coefficients allows us to capture the mechanical deformations due to the tumor growth on surrounding tissues. We present the overall formulation along with a novel operator-splitting scheme with components that include linearly-implicit preconditioned elliptic solvers, and a semi-Lagrangian method for advection. We also present results showing simulated MRI images which highlight the capability of our method to capture the overall structure of glioblastomas in MRIs.

CLAIRE: A DISTRIBUTED-MEMORY SOLVER FOR CONSTRAINED LARGE DEFORMATION DIFFEOMORPHIC IMAGE REGISTRATION.

With this work we release CLAIRE, a distributed-memory implementation of an effective solver for constrained large deformation diifeomorphic image registration problems in three dimensions. We consider an optimal control formulation. We invert for a stationary velocity field that parameterizes the deformation map. Our solver is based on a globalized, preconditioned, inexact reduced space Gauss‒Newton‒Krylov scheme. We exploit state-of-the-art techniques in scientific computing to develop an eifective solver that scales to thousands of distributed memory nodes on high-end clusters. We present the formulation, discuss algorithmic features, describe the software package, and introduce an improved preconditioner for the reduced space Hessian to speed up the convergence of our solver. We test registration performance on synthetic and real data. We Demonstrate registration accuracy on several neuroimaging datasets. We compare the performance of our scheme against diiferent flavors of the Demons algorithm for diifeomorphic image registration. We study convergence of our preconditioner and our overall algorithm. We report scalability results on state-of-the-art supercomputing platforms. We Demonstrate that we can solve registration problems for clinically relevant data sizes in two to four minutes on a standard compute node with 20 cores, attaining excellent data fidelity. With the present work we achieve a speedup of (on average) 5× with a peak performance of up to 17× compared to our former work.

The assessment of radio-adaptive response in graves' hyperthyroidism patients following radioactive iodine uptake.

Low doses of radiation affect the response of cells to higher doses; this phenomenon is called radio-adaptive response, which leads to increased resistance to subsequent higher doses. We have investigated the adaptive response using 0.37 MBq priming dose of I-131 followed by 296-444 MBq challenging dose in peripheral human lymphocyte cells. The study was performed on 42 patients with Graves' disease and 29 healthy adult persons as a control group. The patients were divided into two groups. In the first group, patients were referred for radioactive iodine therapy with a specific dose, and iodine was given to them on the day of referral. In the second group, patients were referred for radioactive iodine uptake and radioactive iodine therapy, and iodine uptake was initially performed, then 24 h later, iodine therapy was done. In both groups, 1 month after treatment, blood samples were taken to cytokinesis-block micronucleus (MN) assay. The number of MN in binuclear lymphocyte cells was counted as an end point test. The mean frequency of MN in first, second, and control groups was 75.86 ± 12.68, 71.45 ± 12.56, and 20.06 ± 7.30, respectively. Our results showed that the frequency of total chromosome aberration in both radiation groups was higher than controls. However, in the first group was higher than another group, but their difference was not statistically significant. According to the results, we cannot approve the hypothesis that 0.37 MBq I-131 administration before iodine therapy could induce a radio-adaptive response in lymphocytes of Graves' patients.

Development of 153Sm-DTPA-SPION as a theranostic dual contrast agents in SPECT/MRI.

OBJECTIVES: This study describes the preparation, biodistribution of 153Sm-DTPA-SPION after intravenous injection in rats. MATERIALS AND METHODS: The chelator DTPA dianhydride was conjugated to SPION using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1: 4 (SPION:ccDTPA) molar ratio. Conjugation reaction was purified with magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked. RESULTS: The RTLC showed that labeling yield was above 99% after purification and the compound have good in vitro stabilities until 48 hr post injection in the presence of human serum. The biodistribution of 153Sm-DTPA-SPION in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. Biodistribution results show that after 30 min post injection more than 84% of injected activities were taken up by the liver and spleen (about 64% and 20%, respectively). CONCLUSION: Due to magnificent uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be a potential candidate for RES theranostic purposes.

Estimating the population dose from nuclear medicine examinations towards establishing diagnostic reference levels.

PURPOSE OF THE STUDY: This study conducted a review on nuclear medicine (NM) services in Mazandaran Province with a view to establish adult diagnostic reference levels (DRLs) and provide updated data on population radiation exposure resulting from diagnostic NM procedures. MATERIALS AND METHODS: The data were collected from all centers in all cities of Mazandaran Province in the North of Iran from March 2014 to February 2015. The 75(th) percentile of the distribution and the average administered activity (AAA) were calculated and the average effective dose per examination, collective effective dose to the population and annual effective dose per capita were estimated using dose conversion factors. The gathered data were analyzed via SPSS (version 18) software using descriptive statistics. RESULTS: Based on the data of this study, the collective effective dose was 95.628 manSv, leading to a mean effective dose of 0.03 mSv per capita. It was also observed that the myocardial perfusion was the most common procedure (50%). The 75(th) percentile of the distribution of administered activity (AA) represents the DRL. The AAA and the 75(th) percentile of the distribution of AA are slightly higher than DRL of most European countries. CONCLUSIONS: Myocardial perfusion is responsible for most of the collective effective dose and it is better to establish national DRLs for myocardial perfusion and review some DRL values through the participation of NM specialists in the future.

An inverse problem formulation for parameter estimation of a reaction-diffusion model of low grade gliomas.

We present a numerical scheme for solving a parameter estimation problem for a model of low-grade glioma growth. Our goal is to estimate the spatial distribution of tumor concentration, as well as the magnitude of anisotropic tumor diffusion. We use a constrained optimization formulation with a reaction-diffusion model that results in a system of nonlinear partial differential equations. In our formulation, we estimate the parameters using partially observed, noisy tumor concentration data at two different time instances, along with white matter fiber directions derived from diffusion tensor imaging. The optimization problem is solved with a Gauss-Newton reduced space algorithm. We present the formulation and outline the numerical algorithms for solving the resulting equations. We test the method using a synthetic dataset and compute the reconstruction error for different noise levels and detection thresholds for monofocal and multifocal test cases.

Anaesthetic management and outcomes after noncardiac surgery in patients with hypoplastic left heart syndrome: a retrospective review.

CONTEXT: Noncardiac surgery in patients with hypoplastic left heart syndrome has been associated with significant morbidity and mortality in case reports and small series. OBJECTIVE: A retrospective study to review the anaesthetic care and outcomes of patients with hypoplastic left heart syndrome undergoing noncardiac surgery. DESIGN: The medical records of patients undergoing anaesthesia for noncardiac surgery were reviewed, including anaesthesiology records, operative notes, admission history, physical examination records and discharge summaries. Data were collected on patient characteristics, co-morbidities, surgical procedure, anaesthetic and monitoring techniques, intraoperative and postoperative complications and admission status. SETTING: A tertiary medical centre with a high volume of congenital heart disease. PARTICIPANTS: Seventy-three procedures performed in 40 patients with hypoplastic left heart syndrome undergoing noncardiac surgery between July 2002 and May 2008. RESULTS: Thirty-three procedures were performed on an outpatient basis without invasive monitoring or complications. Adverse events occurred in 11 (15%) cases, including cardiovascular and respiratory instability, airway obstruction and postoperative stridor, with 13 (18%) patients admitted to the ICU postoperatively. CONCLUSION: Given the high incidence of adverse events in this patient population, it is imperative that perioperative care be individualised based on the presence of known risk factors such as the stage of palliation, residual cardiac disease and severity of planned surgery.

Predictors of abnormal renal cortical scintigraphy in children with first urinary tract infection: the importance of time factor.

INTRODUCTION: We evaluated different factors predicting the development of acute pyelonephritis in Iranian children, with special attention to time factor. METHODS: One hundred nineteen patients (93 females and 26 males; age = 32.6 ± 30.8 months) with first urinary tract infection (UTI) were evaluated. None had previous urological problems. Prior to antibiotic therapy blood samples were gathered for laboratory evaluation. Vital signs on admission were measured. Clinical and laboratory indices, including therapeutic delay time (TDT) and therapeutic response time (TRT), were measured. Most patients were evaluated with renal ultrasound in the first three days following admission. All patients underwent dimercaptosuccinic acid (DMSA) renal scintigraphy and 71 were assessed for vesicoureteral reflux (VUR). RESULTS: DMSA scans were abnormal in 77 cases, of which 11 cases had bilateral renal involvement. Mean values for TDT, TRT, leukocyte count (LC), absolute neutrophil count (ANC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were 74.1 h, 39.6 h, 15725 ± 6682 mm(-3), 10772 ± 6458 mm(-3), 51.9 ± 32.5 mm, and 27.3 ± 25.1 mg l(-1), respectively. VUR was present in 29 of 142 evaluated renal units. CONCLUSION: TDT ≥ 48 h, TRT ≥ 24 h, axillary temperature ≥ 39°C, LC ≥ 13500 mm(-3), and age ≥ 18 months predicted abnormal DMSA scan in patients with first episode of UTI. Considerably higher TDT and TRT values of the current study compared to previous ones suggests the more important role of time factor in predicting abnormal DMSA findings in a developing country than in developed ones.