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Abstract Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: “Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature”. Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of “a globally coordinated diagnostic and research pipeline”. To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient’s diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.

Abstract Excessive use of pesticides against pests has contaminated agricultural crops and raised global concerns about food safety. This research investigates the alleviation effects of 24-epibrassinolide (EBL) seed priming on diazinon (DZ) pesticide toxicity. The experiment was conducted with eight groups including control, DZ, EBL (10 µM), EBL (0.1 µM), EBL (0.01 µM), EBL (10 µM) + DZ, EBL (0.1 µM) + DZ, and EBL (0.01 µM) + DZ. Plants grown with the lowest concentration of EBL (0.01 µM) exhibited an upward increase in the activity of SOD, CAT, POD, APX, GR, and GST enzymes under DZ toxicity stress. In contrast, higher concentrations of EBL showed some inhibitory effects on the activity of antioxidant enzymes. In addition, low concentrations of EBL elevated the free radical scavenging capacity (DPPH), iron-reducing antioxidant power (FRAP), photosynthesis rate (Pn), stomatal conductance (Gs) and proline, and protein contents. EBL also reduced lipid peroxidation (MDA levels) in the DZ-exposed plants, leading to membrane integrity. The favorable effects of EBL were more evident when plants were exposed to pesticides than normal growth conditions. The results indicated that EBL seed priming intensifies the antioxidant enzymes system activity, and helps maize plants against toxic effects of DZ under proper concentration.

Abstract Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease. These findings provide a beginning to new avenues and pan-ethnic therapeutic approaches, as well as to potential genetic screening protocols. The causative virus, SARS-CoV-2, is still in the spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance and further research is warranted. We also note emphatically that to prevent future pandemics and other world-wide health crises, it is imperative to capitalize on what we have learnt from COVID-19: specifically, regarding its origins, the world’s response, and insufficient preparedness. This requires unprecedented international collaboration and timely data sharing for the coordination of effective response and the rapid implementation of containment measures.

Abstract COVID-19, which is caused by the SARS-CoV-2, has ravaged the world for the past 2 years. Here, we review the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase. We are particularly concerned by the lack of solid information from the initial phases of the pandemic that highlighted the necessity for better preparation to face similar future threats. On the other hand, we are gratified by the progress into human genetic susceptibility investigations and we believe now is the time to explore the transition from the pandemic to the endemic phase. The latter will require worldwide vigilance and cooperation, especially in emerging countries. In the transition to the endemic phase, vaccination rates have lagged and developed countries should assist, as warranted, in bolstering vaccination rates worldwide. We also discuss the current status of vaccines and the outlook for COVID-19.

Abstract COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.

Background and Aim: Pulmonary tuberculosis (TB) infection is common in patients infected with the Human immunodeficiency virus (HIV). In this study, we evaluated thoracic CT scan findings of HIV/TB co-infection, before and after anti-TB treatment. Materials and Methods: In this retrospective cross-sectional study, pre-and post-treatment thoracic CT scans of patients diagnosed with HIV and definite pulmonary TB infection were evaluated. Results: A total of 101 patients (64 male, 37 female, mean age of 43±3.4) were included. The most common findings before treatment of TB were mediastinal or hilar lymphadenopathy with hypodense center (41.58%) and free pleural effusion (32.67%). The prevalence of these findings decreased to half after anti-TB treatment (P= 0.009 and P= 0.003 respectively). Loculated pleural effusion showed increased prevalence after treatment (P= 0.031) with no significant change in the prevalence of bronchiectasis, solitary pulmonary nodule, and lymphadenopathy without a hypodense center. Conclusion: The most prevalent thoracic CT scan findings in patients with HIV/TB co-infection before anti-TB treatment were lymphadenopathy with the hypodense center, pleural effusion, and ground-glass opacities. After treatment, numerous changes in imaging manifestations might be seen. The remaining residual CT scan findings (including bronchiectasis, lymphadenopathy with a hypodense center, and solitary pulmonary nodule) require more attention for accurate interpretation of thoracic CT scans in HIV patients.

Abstract The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.

Abstract It is crucial to use the wealth of information emerging from the ongoing SARS-CoV-2 pandemic and confront COVID-19 with a rational approach. There are proactive steps to prevent and fight COVID-19. Management of the disease should be according to clinical features and laboratory test markers and personalized therapeutic targets.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today we are facing a global epidemic. Fever, cough, fatigue, breathlessness, and smell or taste loss are the most frequent clinical symptoms. In most cases, the symptoms are mild. However, it may occasionally progress to widespread thrombosis, septic shock, or acute respiratory disease syndrome (ARDS). The incubation period is usually about 5 days, but can vary from 2 to 14 days. Early quarantine is vital for preventing the complications and rapid spread of the disease. Real-time reverse transcription-polymerase chain reaction (RT-PCR) of a nasopharyngeal sample is the standard diagnostic test. However, this method is expensive and unavailable in many parts of the country, and has delayed results. On the other hand, computerized tomography scan (CT-scan) is widely available and low-cost throughout the country, and provides immediate results with high sensitivity. Indeed, in some cases, CT-scan is capable of providing evidence for the disease before detection of viral RNA from upper respiratory samples. CT-scan exhibits higher sensitivity, but lower specificity for diagnosis of COVID-19, compared to RT-PCR (sensitivity of 59-78% and 95-98% as well as specificity of approximately 100% and 96% for RT-PCR and chest CT-scan, respectively). Low sensitivity for diagnosis of COVID-19 and ionizing radiation exposure are two major disadvantages of CT-scan, which can be resolved to a large extent by clinical and laboratory correlations and utilizing low-dose CT protocols. It seems that CT-scan can be ordered for diagnosis of COVID-19 when PCR test is not feasible, or in case of high clinical suspicion in spite of negative PCR. In addition, CT-scan plays a major role in assessing the severity, extent and prognosis of the disease in monitoring the response to treatment, and in diagnosis of complications.

Hypersensitivity pneumonitis (HP) is an immune-mediated diffuse parenchymal lung disease induced by inhaled antigens. High-resolution computed tomography (HRCT) is widely used in the diagnosis and follow-up of patients and determining the progression and prognosis of the disease. In this retrospective study, 45 consecutive patients with the final diagnosis of HP, seen at a large tertiary care center during a period of 4 years, were included and their HRCT findings were evaluated. The most common HRCT findings were ground glass opacity and reticulation. Some HRCT patterns were detected more severely in bird fanciers in comparison with other etiologies. There is no “gold standard” for the diagnosis of HP. HRCT findings play an important role in hypersensitivity pneumonitis diagnosis and CT scan also help to define the severity of hypersensitivity pneumonitis injuries. In our study, reticulation and ground glass opacity were the most common findings in HRCT of patients with HP. We also find that patients with avian contacts had a significantly higher rate of fibrosis.

Synovial sarcoma is an uncommon soft tissue tumor occurring mainly in the periarticular region of the extremities in young adults. It happens less frequently in the head and neck, mediastinum, lungs, heart, and digestive tract. A 28-year-old man two months after total esophagectomy with final diagnosis of esophageal synovial sarcoma was referred to our Positron Emission Tomography (PET-CT) department for the evaluation of treatment response and further treatment planning. To our knowledge this case is the 11th case of esophageal synovial sarcoma, being reported in the literature. We presented the 11th case of esophageal synovial sarcoma. Synovial sarcomas are very rare tumor entities, particularly in the gastrointestinal tract and are likely to be mistaken with other more common tumors such as gastrointestinal stromal tumors.

In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification induced by toxic beta-amyloid oligomers (oAbeta). To identify immediate molecular targets downstream of oAbeta binding, we prepared synaptoneurosomes from prefrontal cortex of control and incipient AD (IAD) patients, and isolated mRNAs for comparison of gene expression. This novel approach concentrates synaptic mRNA, thereby increasing the ratio of synaptic to somal mRNA and allowing discrimination of expression changes in synaptically localized genes. In IAD patients, global measures of cognition declined with increasing levels of dimeric Abeta (dAbeta). These patients also showed increased expression of neuroplasticity related genes, many encoding 3'UTR consensus sequences that regulate translation in the synapse. An increase in mRNA encoding the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) was paralleled by elevated expression of the corresponding protein in IAD. These results imply a functional impact on synaptic transmission as GluR2, if inserted, maintains the receptors in a low conductance state. Some overexpressed genes may induce early deficits in cognition and others compensatory mechanisms, providing targets for intervention to moderate the response to dAbeta.