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Abstract Background Leishmaniasis, an illness caused by protozoa, accounts for a substantial number of human fatalities globally, thereby emerging as one of the most fatal parasitic diseases. The conventional methods employed for detecting the Leishmania parasite through microscopy are not only time-consuming but also susceptible to errors. Therefore, the main objective of this study is to develop a model based on deep learning, a subfield of artificial intelligence, that could facilitate automated diagnosis of leishmaniasis. Methods In this research, we introduce LeishFuNet, a deep learning framework designed for detecting Leishmania parasites in microscopic images. To enhance the performance of our model through same-domain transfer learning, we initially train four distinct models: VGG19, ResNet50, MobileNetV2, and DenseNet 169 on a dataset related to another infectious disease, COVID-19. These trained models are then utilized as new pre-trained models and fine-tuned on a set of 292 self-collected high-resolution microscopic images, consisting of 138 positive cases and 154 negative cases. The final prediction is generated through the fusion of information analyzed by these pre-trained models. Grad-CAM, an explainable artificial intelligence technique, is implemented to demonstrate the model’s interpretability. Results The final results of utilizing our model for detecting amastigotes in microscopic images are as follows: accuracy of 98.95 1.4%, specificity of 98 2.67%, sensitivity of 100%, precision of 97.91 2.77%, F1-score of 98.92 1.43%, and Area Under Receiver Operating Characteristic Curve of 99 1.33. Conclusion The newly devised system is precise, swift, user-friendly, and economical, thus indicating the potential of deep learning as a substitute for the prevailing leishmanial diagnostic techniques.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Abstract COVID-19 is a highly communicable respiratory illness caused by the novel coronavirus SARS-CoV-2, which has had a significant impact on global public health and the economy. Detecting COVID-19 patients during a pandemic with limited medical facilities can be challenging, resulting in errors and further complications. Therefore, this study aims to develop deep learning models to facilitate automated diagnosis of COVID-19 from CT scan records of patients. The study also introduced COVID-MAH-CT, a new dataset that contains 4442 CT scan images from 133 COVID-19 patients, as well as 133 CT scan 3D volumes. We proposed and evaluated six different transfer learning models for slide-level analysis that are responsible for detecting COVID-19 in multi-slice spiral CT. Additionally, multi-head attention squeeze and excitation residual (MASERes) neural network, a novel 3D deep model was developed for patient-level analysis, which analyzes all the CT slides of a given patient as a whole and can accurately diagnose COVID-19. The codes and dataset developed in this study are available at https://github.com/alrzsdgh/COVID . The proposed transfer learning models for slide-level analysis were able to detect COVID-19 CT slides with an accuracy of more than 99%, while MASERes was able to detect COVID-19 patients from 3D CT volumes with an accuracy of 100%. These achievements demonstrate that the proposed models in this study can be useful for automatically detecting COVID-19 in both slide-level and patient-level from patients’ CT scan records, and can be applied for real-world utilization, particularly in diagnosing COVID-19 cases in areas with limited medical facilities.

Abstract Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system’s power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract

The present research was an endeavor to examine and compare the effects of digitally self-regulated and guided discovery learning instructions on Iranian EFL learners’ vocabulary acquisition. To this end, by conducting the Oxford Placement Test, 60 out of 140 Iranian EFL male and female learners from three language institutes in Isfahan, Iran, were randomly selected, and divided into three equal groups (i.e. two experimental groups and one control group). Prior to the instructions, a vocabulary pretest, designed and validated by the researchers, was conducted. Then, the experimental groups received two types of instruction, separately. The first experimental group was taught via digitally self-regulated learning (SRL) instruction based on Santangelo, Harris, and Graham’s (2008) six-stage model. The second experimental group was instructed via guided discovery learning instruction based on Brown and Campione’s (2011) stages. In contrast, the control group received the traditional method of teaching vocabulary such as word lists, dictionary use, and word translation. After conducting eight-session instructions, a posttest was administered. The data were analyzed via ANOVAs and post hoc analysis using the Tukey test. The findings of the study revealed that both digitally self-regulated and guided discovery promoted Iranian EFL learners’ vocabulary acquisition. Additionally, the findings indicated that digitally self-regulated instruction was more effective than guided discovery instruction regarding vocabulary acquisition. Eventually, the theoretical and pedagogical implications regarding language learners, teachers, and curriculum designs are also provided.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B–cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

This work presents the design, fabrication, and measured results of a fully integrated miniature rectenna using a novel tunnel diode known as the Asymmetrical Spacer Layer Tunnel (ASPAT). The term rectenna is an abbreviation for a rectifying antenna, a device with a rectifier and antenna coexisting as a single design. The ASPAT is the centrepiece of the rectifier used for its strong temperature independence, zero bias, and high dynamic range. The antenna is designed to be impedance matched with the rectifier, eliminating the need for a matching network and saving valuable real estate on the gallium arsenide (GaAs) substrate. The antenna is fully integrated with the rectifier on a single chip, thus enabling antenna miniaturisation due to the high dielectric constant of GaAs and spiral design. This miniaturisation enables the design to be fabricated economically on a GaAs substrate whilst being comparable in size to a 15-gauge needle, thus unlocking applications in medical implants. The design presented here has a total die size of 4 × 1.2 mm2, with a maximum measured output voltage of 0.97 V and a 20 dBm single-tone 2.35 GHz signal transmitted 5 cm away from the rectenna.

In this paper, the flashlight (FL) algorithm, which is categorized as a heuristic method, has been suggested to determine the ultimate pit limit (UPL). In order to apply the suggested algorithm and other common algorithms, such as the dynamic programming, the Korobov, and the floating cone, and to validate the capability of the proposed method, the ultimate pit limit was determined in a cross-section of the Korkora reserve, which is located in Kurdistan province, northwestern of Iran and consists of 3080 blocks. The comparison of the FL algorithm and other methods revealed that same as high accuracy dynamic programming methods, the proposed algorithm could find the optimum value, while the Korobov and the floating cone algorithms failed to determine the optimum limit.

Background: The aim of this study was to develop a prognostic model to identify a subgroup of high-risk patients for non-healing after femoral neck fracture fixation among young adults. The model was implemented by presenting graphically as a nomogram that could be easily used in every day clinical cases. Methods: Data on a total of 129 patients were included in the current study. The mean [standard deviation (SD)] age of the participants was 42 (13) years and 28% of the patients were women. Harrell’s C statistic was used as a measure of discrimination predictive power. We calculated the Nam-D’Agostino χ2 to examine calibration for prediction models. Results: Approximately, 83% of fractures united uneventfully, with avascular necrosis (AVN), fixation nonhealing, non-union, infection, arthroplasty, and death being observed. Body mass index (BMI) and head acetabular trabecular angle (HATA) were inversely associated with the risk of all-cause nonhealing. The final model showed excellent discriminatory power [Harrell’s C statistic: 0.820, 95% confidence interval (CI) (0.680-0.960)] and it was well-calibrated [Nam-D’Agostino χ2: 10.1, (P = 0.3456)]. A nomogram developed by incorporating significant predictors modelled without discretizing continuous variables. Conclusion: Using readily available clinical and radiological data, we developed a parsimonious, simple, accurate yardstick to measure the 5-year risk of nonhealing after femoral neck fractures among young adults. In order to add ease-of-use and to promote its integration into clinical practice, the prognostic model was demonstrated visually as a statistic nomogram.

Background and Objectives: Occupational traumas are known as work-related disorders, associating with some sorts of factors such as repetitive tasks, body postures, workstations, and hand tools. These traumas cause various problems for both workers and employers. Due to occupational hygiene considerations, problems such as cumulative trauma disorders, occupational trauma, low back pain (LBP), and work-related musculoskeletal disorders should be controlled. In this regard, ergonomic interventions can have efficient outcomes toward controlling occupational traumas. In this study, the focus was on working at some walnut gardens in the city of Tuyserkan in Iran, to reach an ergonomic analysis base, in which hand tools were assessed. The main objective was to develop a new ergonomic design for workers using hand tools. Subjects and Methods: In this cross-sectional study, 19 workers participated and filled out the Nordic Musculoskeletal Questionnaire (NMQ). Their body postures during harvesting walnuts were evaluated by the Ovako Working Posture Analysis System method. Hand tool analysis was also performed by ergonomic risk assessments. Results: The results showed that 15% of the farmers experienced some sorts of trauma during the harvest while using traditional hand tools. The results also emphasized that 61.5% of the workers' body postures should be modified. In addition, according to the NMQ, the most common problems among workers were wrist disorders, LBP, and knees' and shoulders' disorders. Conclusions: Considering experimental data, a new device was developed in which the weight, adjustability, and form of hand tools were modified under ergonomic considerations. The benefits of the new design were confirmed by SOLIDWORKS software. Since this new device helps farmers to decrease extra force exertion in awkward postures, it is expected to improve farmers' condition while using it.

Abstract Background In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. Methods Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. Results Median age of the patients was 83 years (range 76–90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a CRP value over 80 mg/l (P

Development of next-generation sequencing and metagenomics has revolutionized detection of novel viruses. Among these viruses are 3 human protoparvoviruses: bufavirus, tusavirus, and cutavirus. These viruses have been detected in feces of children with diarrhea. In addition, cutavirus has been detected in skin biopsy specimens of cutaneous T-cell lymphoma patients in France and in 1 melanoma patient in Denmark. We studied seroprevalences of IgG against bufavirus, tusavirus, and cutavirus in various populations (n = 840), and found a striking geographic difference in prevalence of bufavirus IgG. Although prevalence was low in adult populations in Finland (1.9%) and the United States (3.6%), bufavirus IgG was highly prevalent in populations in Iraq (84.8%), Iran (56.1%), and Kenya (72.3%). Conversely, cutavirus IgG showed evenly low prevalences (0%–5.6%) in all cohorts, and tusavirus IgG was not detected. These results provide new insights on the global distribution and endemic areas of protoparvoviruses.

In recent years, the increased incidence of natural disasters with irreparable damage to people has led to various efforts to reduce its destructive effects and consequences. Hence, humanitarian aid logistics are aimed at preserving life and reducing the suffering of people in crises. Facility location is a strategic issue in humanitarian logistics and has a planning role before the crisis. Finding the right place for establishment of the facilities can help relieve the disaster. This research is also based on the principles of non-operational defense and the design of a multi-objective mathematical model for seeking a suitable location for the facility. In this mathematical model based on four population density indexes, user appropriateness, access to the road and enclosure of the appropriate location for the establishment of a hospital, temporary care centers, shelters and warehouses is selected. The designed model is solved using Lexicographic method and via GAMS software.

Abstract Background In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs – KIPyV, WUPyV, MCPyV and TSPyV – were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses. We developed a Luminex-based multiplex assay for simultaneous detection of all 13 HPyVs known, and explored their occurrence in tonsillar tissues of children and adults mostly with tonsillitis or tonsillar hypertrophy. Methods We set up and validated a new Luminex-based multiplex assay by using primer pairs and probes targeting the respective HPyV viral protein 1 (VP1) genes. With this assay we tested 78 tonsillar tissues for DNAs of 13 HPyVs. Results The multiplex assay allowed for simultaneous detection of 13 HPyVs with high analytical sensitivity and specificity, with detection limits of 100–102 copies per microliter, and identified correctly all 13 target sequences with no cross reactions. HPyV DNA altogether was found in 14 (17.9%) of 78 tonsils. The most prevalent HPyVs were HPyV6 (7.7%), TSPyV (3.8%) and WUPyV (3.8%). Mixed infection of two HPyVs occurred in one sample. Conclusions The Luminex-based HPyV multiplex assay appears highly suitable for clinical diagnostic purposes and large-scale epidemiological studies. Additional evidence was acquired that the lymphoid system plays a role in HPyV infection and persistence. Thereby, shedding from this site during reactivation might take part in transmission of the newly found HPyVs.

Increasing sequence information indicates that RNA viruses constitute a major fraction of marine virus assemblages. However, only 12 RNA virus species have been described, infecting known host species of marine single-celled eukaryotes. Eight of these use diatoms as hosts, while four are resident in dinoflagellate, raphidophyte, thraustochytrid, or prasinophyte species. Most of these belong to the order Picornavirales, while two are divergent and fall into the families Alvernaviridae and Reoviridae. However, a very recent study has suggested that there is extraordinary diversity in aquatic RNA viromes, describing thousands of viruses, many of which likely use protist hosts. Thus, RNA viruses are expected to play a major ecological role for marine unicellular eukaryotic hosts. In this review, we describe in detail what has to date been discovered concerning viruses with RNA genomes that infect aquatic unicellular eukaryotes.

News has played a vital role in peoples’ and governments’ decision making. As such, the source and reliability of the news are of equal or even more significance than the news itself and that makes reporting the news a challenging and critical profession. Accordingly, investigating how news is reported is essential and further it would be illuminating to see how different news reporting organizations and cultures report their news for their readers. This study compared the Persian and English news to explore the similarities and differences between two languages. Utilizing Schematic Structure of Editorials (Based on van Dijk, 1992, 1995) to analyze the data, the researcher found significant similarities and differences between Persian and English in terms of genre of news.

[This corrects the article DOI: 10.1371/journal.pone.0139096.].

We used comprehensive serodiagnostic methods (IgM, IgG, and IgG avidity) and PCR to study Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus infections in children observed from infancy to adolescence. Comparing seroconversion intervals with previous and subsequent intervals, we found that primary infections with these 2 viruses were asymptomatic in childhood.

The main goal in this paper is to propose an optimization model for determining the structure of a series-parallel system. Regarding the previous studies in series-parallel systems, the main contribution of this study is to expand the redundancy allocation parallel to systems that have repairable components. The considered optimization model has two objectives: maximizing the system mean time to first failure and minimizing the total cost of the system. The main constraints of the model are: maximum number of the components in the system, maximum and minimum number of components in each subsystem and total weight of the system. After establishing the optimization model, a multi objective approach of Imperialist Competitive Algorithm is proposed to solve the model.

Societies’ change from traditional to knowledge-based ones and the need to use the new communicative conditions leads in universal movement in the developed and developing countries to change the educational structure. The country’s authorities understood the change in global circumstances well and this is realized in the ministry of education’s approved documents. The authorities are completely aware that in a knowledge -based society, it is worth to produce science and knowledge. Smart schools can be considered as an educational setting which makes the fulfillment of knowledge-based society possible. In this paper, using the survey research method, the smart schools’ development challenges in Iran would be investigated and some strategies would be offered to meet these challenges.

To determine whether 5-methylenetetrahydrofolate (MTHF) is more effective than folic acid supplementation in treatment of recurrent abortion in different MTHFR gene C677T and A1298C polymorphisms.A randomized, double blind, placebo-controlled trial conducted April 2011-September 2014 in recurrent abortion clinics in Tehran, Iran. The participants were women with three or more idiopathic recurrent abortion, aged 20 to 45 years. Two hundred and twenty eligible women who consented to participate were randomly assigned to receive either folic acid or 5-MTHF according to the stratified blocked randomization by age and the number of previous abortions. Participants took daily 1 mg 5-methylentetrahydrofolate or 1 mg folic acid from at least 8 weeks before conception to the 20th week of the pregnancy. The primary outcome was ongoing pregnancy rate at 20th week of pregnancy, and the secondary outcomes were serum folate and homocysteine at the baseline, after 8 weeks, and at the gestational age of 4, 8, 12, and 20 weeks, MTHFR gene C677T and A1298C polymorphisms.There was no significant difference in abortion rate between two groups. Serum folate increased significantly in both groups over time; these changes were significantly higher in the group receiving 5-MTHF than the group receiving folic acid (value = 2.39, p

Human bocaviruses (HBoVs) 1-4 are recently discovered, antigenically similar parvoviruses. We examined the hypothesis that the antigenic similarity of these viruses could give rise to clinically and diagnostically important immunological interactions. IgG and IgM EIAs as well as qPCR were used to study ~2000 sera collected from infancy to early adolescence at 3-6-month intervals from 109 children whose symptoms were recorded. We found that HBoV1-4-specific seroprevalences at age 6 years were 80%, 48%, 10%, and 0%, respectively. HBoV1 infections resulted in significantly weaker IgG responses among children who had pre-existing HBoV2 IgG, and vice versa. Furthermore, we documented a complete absence of virus type-specific immune responses in six viremic children who had pre-existing IgG for another bocavirus, indicating that not all HBoV infections can be diagnosed serologically. Our results strongly indicate that interactions between consecutive HBoV infections affect HBoV immunity via a phenomenon called "original antigenic sin", cross-protection, or both; however, without evident clinical consequences but with important ramifications for the serodiagnosis of HBoV infections. Serological data is likely to underestimate human exposure to these viruses.

Merkel Cell Polyomavirus (MCV) is a common infectious agent likely to be involved in the pathogenesis of most Merkel cell carcinomas (MCC). Trichodysplasia spinulosa-associated polyomavirus (TSV), which exhibit high seroprevalence in general population, has been detected in trichodysplasia spinulosa (TS) skin lesions suggesting an etiological role for this disease. Previous studies have shown strong MCV-specific T-cell responses, while no data exist on T-cell immunity against TSV. In order to characterize Th-cell immunity against TSV, and to allow comparisons with the MCV-specific Th-cell immunity, we studied TSV-specific proliferation, IFN-γ, IL-10 and IL-13, and MCV-specific IFN-γ and IL-10 responses in 51 healthy volunteers, and in one MCC patient. Recombinant TSV and MCV VP1 virus-like particles (VLPs) were used as antigens. A significant correlation was found between virus-specific Th-cell and antibody responses with TSV; with MCV it proved weaker. Despite significant homology in amino acid sequences, Th-cell crossreactivity was not evident between these viruses. Some subjects seronegative to both TSV and MCV exhibited Th-cell responses to both viruses. The agent initially priming these Th-cells remains an enigma. As CD8(+) cells specific to MCV T-Ag oncoprotein clearly provide an important defense against established MCC, the MCV VP1-specific Th-cells may, by suppressing MCV replication with antiviral cytokines such as IFN-γ, significantly contribute to preventing the full process of oncogenesis.