Alternative Method For Diagnosis Research Articles

CELIAC DISEASE: NEW POSSIBILITIES FOR DIAGNOSIS AND MANAGEMENT

Вackground. Celiac disease is an autoimmune disease that occurs in genetically predisposed individuals and is characterized by damage to the mucous membrane of the small intestine due to exposure to gluten. The interest of researchers in gluten-associated diseases is growing every year. The true prevalence of celiac disease is not sufficiently studied due to the rarity of "classic" cases and the higher frequency of atypical and various clinical manifestations of this disease. Manifestation of celiac disease is possible at any age, the disease is more often diagnosed in adults. All this dictates the need to develop new algorithms for examining patients for timely detection and treatment of сеliacia. Aim: To review updated key consensus documents on the diagnosis and treatment of celiac disease. Matherials and methods. The results of scientific research related to celiac disease were searched. The studies that are included were selected based on searches in the online databases PubMed, Web of Science, Scopus, Google Scholar and others and relate to the basic methods of diagnosis and management of celiac disease. 110 sources were selected for analysis, of which were used that met the search criteria. Results. Based on the analysis of experimental and clinical studies, difficulties were identified in diagnosing celiac disease associated with a greater prevalence of extraintestinal manifestations and a rarity of "classical" cases. Methods of approach to the diagnosis of celiac disease in children and adults have been developed, taking into account invasiveness and accessibility. The basic approach in the treatment of celiac disease is a observed gluten-free diet. Regarding the selection of products, the individual characteristics of each patient are taken into account. Conclusion. To verify the diagnosis, adults and children with suspected celiac disease are recommended to perform esophagogastroduodenoscopy with biopsy of the duodenal mucosa at several points. An alternative method of diagnosis can be a combination of a very high level of antibodies of the imonoglobulin (Ig) A class to tissue transglutaminase (TGAs) and positive antibodies to endomysium (anti EMA) in two blood samples, however, no single analysis is 100% specific for celiac disease, and the diagnostic accuracy varies significantly between different laboratories. The only proven effective treatment for celiac disease is a lifelong gluten-free diet. In the absence of a complete clinical and serological response to diet, treatment goals are determined individually for each patient. The development of new treatments for celiac disease continues.

(18)F-fluorodeoxyglucose uptake by positron emission tomography in patients with IPAH and CTEPH.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG (p = 0.006), right lung FDG (p = 0.004), right atrial (RA) FDG (p < 0.001) and RV FDG (p < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) (r = 0.7, p = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) (r = 0.5, p = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension.

Reversible strengthening behaviour of subsurface layers in sandy soils – understanding variable response to strategic deep tillage

Deep sandy soils cover more than 10 M ha of Australia's southern dryland cropping lands. Farming these soils is inherently challenging, and yield gaps are often wide due to multiple cropping constraints. Physical constraints that limit rooting depth are commonplace and often attributed to traffic-induced soil compaction. However, recent observations draw attention to a reversible hardsetting behaviour in response to soil water content. This hardsetting phenomenon is poorly understood and it may explain inconsistent crop responses to deep ripping in sandy soils. We examined the dynamic behaviour of soil strength under different soil water contents in deep ripped and unripped sands from four South Australian sites. We analyzed the elemental, mineralogical, chemical and physical compositions to differentiate the nature of hardened subsurface layers. Soil compaction and cementation were ruled out due to the soil's bulk density (<1.6 g cm−3) encountered and the rapid slaking that occurred when a hardened pan was submerged in water. The hardsetting behaviour was confirmed by the abrupt change in soil strength in response to the soil water content, measured using intact samples in a laboratory-based penetrometer. This significant increase in soil strength was also observed for soils collected from the ripped plots and for repacked soil samples, with penetration resistance ranging from 0.4 to 5.7 MPa depending on soil content. In contrast to our hypotheses, the hardsetting layer could not be distinguished from the layers above or below it by any analytical method. Given soil strength is typically measured on field moist soil, and standard chemical analysis did not differentiate hardsetting behaviour, alternative methods of diagnosis are needed to understand where deep tillage is likely to have the desired long-term effect. Identifying the nature of potential binding agents responsible for increased strength upon drying would be valuable. Our results confirmed reversible hardsetting in deep sandy soils is driven by small changes in soil water content, from 0.08 g g−1 to 0.05 g g−1 upon drying. Given that rapid re-consolidation of the soil matrix after expensive deep ripping interventions are reported, there is a strong imperative to improve diagnosis, and to identify if soil ameliorants could improve longevity by disrupting hardsetting behaviour.

A Modified Corona Score Using Lung Ultrasound to Identify COVID-19 Patients.

COVID-19 continues to circulate around the world with multiple different strains being active at once. While diagnosis with antigen and molecular testing is more readily available, there is still room for alternative methods of diagnosis, particularly in out-of-hospital settings, e.g., home or nursing homes, and in low-medium income countries, where testing may not be readily available. To evaluate the performance of two modified corona score methods compared with a traditional corona score approach to identify patients with COVID-19. This was a retrospective multicenter study performed to compare the ability to predict SARS-CoV-2 test results on a nasopharyngeal swab between the corona scores and two novel corona scores (modified 1 corona score (M1CS) and modified 2 corona score (M2CS)). The M1CS included lung ultrasound (LUS) and chest X-ray (CXR) results, while the M2SC only utilized LUS findings without CXRs. Emergency physicians performed point-of-care LUS and a physical examination upon admission to the emergency department. Subjects positive for SARS-CoV-2 were older and had higher ferritin levels and temperature and lower diastolic blood pressure and oxygen saturation. The two groups differed on corona score and modified corona scores (p < 0.001 for all). SARS-CoV-2-positive patients had fewer pleural line irregularities (p = 0.025) but presented more frequently with an interstitial pattern on CXRs (p < 0.001). In our study, LUS alone provided a valuable contribution to the corona score and improved its performance more than when CXR results were included. These results suggest that resource-limited areas where CXRs may be unavailable or prohibitively expensive can utilize an ultrasound as the sole imaging modality without a loss of diagnostic performance for SARS-CoV-2 pneumonia diagnosis.

High-Sensitivity Detection toward SARS-CoV-2 S1 Glycoprotein by Parallel Reaction Monitoring Mass Spectrometry.

The outbreak of coronavirus disease 2019 (COVID-19) has overwhelmed the global economy and human well-being. On account of the sharp increase in test demand, there is a need for an accurate and alternative diagnosis method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, with the aim to specifically identify the trace SARS-CoV-2 S1 glycoprotein, we developed a high-sensitivity and high-selectivity diagnostic method based on the targeted parallel reaction monitoring (PRM) assay of eight selected peptides. This study emphasizes the outstanding detection sensitivity of 0.01 pg of the SARS-CoV-2 S1 glycoprotein even in the interference of other structural proteins, which to our knowledge is the current minimum limit of detection for the SARS-CoV-2 S1 glycoprotein. This technology could further identify 0.01 pg of the SARS-CoV-2 S1 glycoprotein in a spike pseudovirus, revealing its practical effectiveness. All our preliminary results throw light on the capability of the mass spectrometry-based targeted PRM assay to identify SARS-CoV-2 as a practicable orthogonal diagnostic tool. Furthermore, this technology could be extended to other pathogens (e.g., MERS-CoV S1 protein or SARS-CoV S1 protein) by quickly adjusting the targeted peptides of MS data acquisition. In summary, this strategy is universal and flexible and could be quickly adjusted to detect and discriminate different mutants and pathogens.

A Decision Support System for Diagnosis of COVID-19 from Non-COVID-19 Influenza-like Illness Using Explainable Artificial Intelligence.

The coronavirus pandemic emerged in early 2020 and turned out to be deadly, killing a vast number of people all around the world. Fortunately, vaccines have been discovered, and they seem effectual in controlling the severe prognosis induced by the virus. The reverse transcription-polymerase chain reaction (RT-PCR) test is the current golden standard for diagnosing different infectious diseases, including COVID-19; however, it is not always accurate. Therefore, it is extremely crucial to find an alternative diagnosis method which can support the results of the standard RT-PCR test. Hence, a decision support system has been proposed in this study that uses machine learning and deep learning techniques to predict the COVID-19 diagnosis of a patient using clinical, demographic and blood markers. The patient data used in this research were collected from two Manipal hospitals in India and a custom-made, stacked, multi-level ensemble classifier has been used to predict the COVID-19 diagnosis. Deep learning techniques such as deep neural networks (DNN) and one-dimensional convolutional networks (1D-CNN) have also been utilized. Further, explainable artificial techniques (XAI) such as Shapley additive values (SHAP), ELI5, local interpretable model explainer (LIME), and QLattice have been used to make the models more precise and understandable. Among all of the algorithms, the multi-level stacked model obtained an excellent accuracy of 96%. The precision, recall, f1-score and AUC obtained were 94%, 95%, 94% and 98% respectively. The models can be used as a decision support system for the initial screening of coronavirus patients and can also help ease the existing burden on medical infrastructure.

Diagnosis of ultrafast ultraintense laser pulse characteristics by machine-learning-assisted electron spin

The rapid development of ultrafast ultraintense laser technology continues to create opportunities for studying strong-field physics under extreme conditions. However, accurate determination of the spatial and temporal characteristics of a laser pulse is still a great challenge, especially when laser powers higher than hundreds of terawatts are involved. In this paper, by utilizing the radiative spin-flip effect, we find that the spin depolarization of an electron beam can be employed to diagnose characteristics of ultrafast ultraintense lasers with peak intensities around 1020–1022 W/cm2. With three shots, our machine-learning-assisted model can predict, simultaneously, the pulse duration, peak intensity, and focal radius of a focused Gaussian ultrafast ultraintense laser (in principle, the profile can be arbitrary) with relative errors of 0.1%–10%. The underlying physics and an alternative diagnosis method (without the assistance of machine learning) are revealed by the asymptotic approximation of the final spin degree of polarization. Our proposed scheme exhibits robustness and detection accuracy with respect to fluctuations in the electron beam parameters. Accurate measurements of ultrafast ultraintense laser parameters will lead to much higher precision in, for example, laser nuclear physics investigations and laboratory astrophysics studies. Robust machine learning techniques may also find applications in more general strong-field physics scenarios.

2119. Predictive Value of the Immunodeficiency Scoring Index for COVID-19 Related Outcomes in Hematopoietic Transplant Recipients

Abstract Background The Coronavirus Disease 2019 (COVID-19) has significantly impacted cancer patients with some reported mortality as high as 25%. The Immunodeficiency Scoring Index (ISI) was developed as a prognostic tool in allogeneic hematopoietic cell transplant (allo-HCT) recipients with respiratory syncytial virus but also for other respiratory viruses to predict severe infections and mortality. The purpose of our study was to correlate the ISI in HCT recipients with COVID-19 and associated complications such as hospitalization, supplemental oxygen use, and mortality. Methods We performed a cohort study of HCT recipients of all ages with COVID-19 between March 2020 and October 2021. We included only patients who were diagnosed by a PCR-based assay. We excluded patients for whom an ISI score, as previously described, could not be calculated. Outcomes of interest included 60-day mortality, hospital and ICU admission due to COVID-19, and supplemental oxygen requirements. A univariate analysis using Fischer exact testing for nominal variables was performed. Results Out of the 219 HCT with COVID-19, 101 were excluded due to alternative methods of diagnosis (13), lack of laboratory values needed to calculate an ISI at time of COVID-19 diagnosis (79), or COVID-19 diagnosed prior to transplant (9). Out of the remaining 118 patients, the median age was 60 years (range 6-85), most were male (56%), Caucasian (57%), and had no smoking history (64%). Most patients had an alloHCT (66%) with matched related donor [MRD] (25%), or matched unrelated donor [MUD] (21%) (Table 1). Median time from transplant to COVID-19 was 615 days (range 2-5692), median ISI was 3 (range 0-11), and 92% of patients were unvaccinated prior to COVID-19 (Table 1). On univariate analysis, an ISI of moderate to high (score ≥3) was associated with COVID-19 related hospitalization [p=0.0147] and an ISI ≥ 4 was associated with 60-day all-cause (p=0.045) and COVID-19-related (p-0.019) mortality (Table 2). Table 1: Patient Characteristics Abbreviations: Hematopoietic Cell Transplant (HCT); Chronic Obstructive Pulmonary Disease (COPD); Chronic Kidney Disease (CKD); End-Stage Renal Disease (ESRD); Acute Lymphocytic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Lymphocytic Leukemia (CLL); Chronic Myelogenous Leukemia (CML) Myeloproliferative Disorder (MDS); Matched Related Donor (MRD); Matched Unrelated Donor (MUD); Mismatched Unrelated Donor (MMUD); Graft versus Host Disease (GvHD); Lower Respiratory Tract Infection (LRI); White Blood Cell (WBC); Absolute Neutrophil Count (ANC); Absolute Lymphocyte Count (ALC). Table 2: Univariate Analysis of Outcomes due to COVID-19 in HCT Recipients Abbreviations: Immunodeficiency Scoring Index (ISI); Hematopoietic Cell Transplant (HCT); Allogenic (Allo); Autologous (Auto); Lower Respiratory Infection (LRI); High-Flow Nasal Cannula (HFNC) Figure 1: Survival Curve (Kaplan-Meier Curve) Comparing Time to Death in Patients with an ISI Score of 4 or Greater. (Log-rank 0.0295) Conclusion An ISI of 4 or greater was a prognostic marker for worse outcomes such as COVID-related and all-cause mortality in HCT recipients. Whether an aggressive and prompt management of high-risk patients with COVID-19 may impact these outcomes needs to be determined in future studies. Disclosures Gabriella Rondon, MD, Omeros: Advisor/Consultant Ella Ariza-Heredia, MD, MERCK: Grant/Research Support Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Meeting an un-MET need: Targeting MET in non-small cell lung cancer.

The MET pathway can be activated by MET exon 14 skipping mutations, gene amplification, or overexpression. Mutations within this pathway carry a poor prognosis for patients with non-small cell lung cancer (NSCLC). MET exon 14 skipping mutations occur in 3-4% of patients with NSCLC, while MET amplifications are found in 1-6% of patients. The most effective method for detection of MET amplification is fluorescent in situ hybridization (FISH) and of MET exon 14 skipping mutations is RNA-based next generation sequencing (NGS). Immunohistochemistry (IHC) is an alternative method of diagnosis but is not as reliable. Early studies of MET tyrosine kinase inhibitors (TKIs) demonstrated limited clinical benefit. However, newer selective MET TKIs, such as capmatinib and tepotinib, have improved efficacy. Both drugs have an acceptable safety profile with the most common treatment-related adverse event being peripheral edema. One of the most frequent resistance mechanisms to EGFR inhibition with osimertinib is MET amplification. There is interest in combining EGFR inhibition plus MET inhibition in an attempt to target this resistance mechanism. Additional ways of targeting MET alterations are currently under investigation, including the bi-specific antibody amivantamab. Additional research is needed to further understand resistance mechanisms to MET inhibition. There is limited research into the efficacy of immune checkpoint inhibition for MET-altered NSCLC, though some data suggests decreased efficacy compared with wild-type patients and increased toxicity associated with the combination of immunotherapy and MET TKIs. Future directions for research will include combination clinical trials and understanding rational combinations for MET alterations.

A Novel Approach to Detect COVID-19: Enhanced Deep Learning Models with Convolutional Neural Networks

The novel coronavirus (COVID-19) is a contagious viral disease that has rapidly spread worldwide since December 2019, causing the disruption of life and heavy economic losses. Since the beginning of the virus outbreak, a polymerase chain reaction has been used to detect the virus. However, since it is an expensive and slow method, artificial intelligence researchers have attempted to develop quick, inexpensive alternative methods of diagnosis to help doctors identify positive cases. Therefore, researchers are starting to incorporate chest X-ray scans (CXRs), an easy and inexpensive examination method. This study used an approach that uses image cropping methods and a deep learning technique (updated VGG16 model) to classify three public datasets. This study had four main steps. First, the data were split into training and testing sets (70% and 30%, respectively). Second, in the image processing step, each image was cropped to show only the chest area. The images were then resized to 150 × 150. The third step was to build an updated VGG16 convolutional neural network (VGG16-CNN) model using multiple classifications (three classes: COVID-19, normal, and pneumonia) and binary classification (COVID-19 and normal). The fourth step was to evaluate the model’s performance using accuracy, sensitivity, and specificity. This study obtained 97.50% accuracy for multiple classifications and 99.76% for binary classification. The study also got the best COVID-19 classification accuracy (99%) for both models. It can be considered that the scientific contribution of this research is summarized as: the VGG16 model was reduced from approximately 138 million parameters to around 40 million parameters. Further, it was tested on three different datasets and proved highly efficient in performance.

Carotid intima media as predictor of liver fibrosis in type 2 diabetes mellitus with NAFLD

Background and aimsNon Alcoholic Fatty Liver Disease (NAFLD) is common in type 2 Diabetes Mellitus (DM) that might progress to advance liver fibrosis. Early recognition of liver fibrosis may have clinical implication. Non invasive assessment tool for severity of liver fibrosis in NAFLD is expensive fibroscan. An alternate method of diagnosis will be very useful innovation. We aimed to evaluate Carotid Intima Media Thickness (CIMT) and its association with severity of liver fibrosis in patients with type 2 DM and NAFLD. MethodsTreatment naïve patients with type 2 DM were enrolled. Measurement of CIMT, hepatic ultrasound and fibroscan were done. Liver function tests included hepatic transaminases. The data obtained was subjected to statistical analysis using IBM SPSS version 20.0 software. ResultPrevalence of NAFLD was 76% including 12% with moderate to advance liver fibrosis in patients with type 2 DM. CIMT was significantly higher in patients with NAFLD than with normal liver. CIMT positively correlated with severity of liver fibrosis measured by fibroscan. ROC curve analysis showed right CIMT value of 0.575 mm predicting liver fibrosis with sensitivity of 91.7% and specificity of 78.9%. ConclusionThree fourth of patients with type 2 DM had NAFLD but small proportion had moderate to advance liver fibrosis. CIMT increased more in patients with NAFLD than with normal liver in T2DM. CIMT value of 0.575 mm has a good sensitivity to predict liver fibrosis and therefore, it can be a reliable marker of severity of Non Alcoholic Steato Hepatitis (NASH) in diabetes with NAFLD.

Considerations on Classification of the Main Components of the Vehicles By their Vibroacoustic Fingerprint

Abstract The modern car industry is evolving under new premises, such as new propulsion technology, which imply offering to the customer the completed new solutions (charging station, service contract and remote diagnosis). Proven diagnostic technology is reaching its limits because is generally based on detecting the electrical faults and the mechanical, hydraulic and pneumatic failures have a slight degree of detection by this method. An alternative method of diagnosis could be the study of actual noise and vibration parameters of the main components of the vehicle subject to major faults and compare them to that specific to good status of operation. This paper deals with the classification of the main components of the vehicles by their vibroacoustic fingerprint. Those components of the vehicle grouped by vehicle category and their common patterns of vibroacoustic fingerprints must be permanently overseen and compare with those assigned to the status of good health for diagnosis.

YIELD OF INDUCED SPUTUM IN CLINICALLY DIAGNOSED PULMONARY TUBERCULOSIS

Background:- Direct sputum smear examination is used as a basic diagnostic tool in the diagnosis of pulmonary tuberculosis. But difficulty in obtaining adequate sputum is the main cause of failure of bacteriological diagnosis. Alternative methods of obtaining sputum specimens are frequently needed in those patients with clinicoradiological suspicion of TB who are unable to expectorate or are smear negative. Aim:- To assess the yield of smear positivity of induced sputum (SI) with hypertonic saline nebulisation, broncho-alveolar lavage fluid and Rifampicin resistance in clinically diagnosed pulmonary TB who have no/inadequate sputum. Materials and Methods:- In the present cross-sectional observational study, we analysed the smear positivity of AFB in induced sputum of patients at Veer Surendra Sai Institute of Medical Science &amp; Research, Burla, Odisha, India, from November 2018 to October 2020. A total of 100 patients with clinically diagnosed pulmonary TB who were unable to produce adequate sputum fulfilling inclusion criteria were included in the study. 10 ml of 3% hypertonic saline was injected into the nebulizer reservoir device. The assembly was connected to the jet nebulizer. The patients were instructed to inhale and exhale the mist of the nebulized solution through the mouth piece only. The inhalation of hypertonic saline was interrupted every 5 min, so that the patient could expectorate the sputum into a clean sterile sputum container. The sputum samples were stained with auramin-rhodamin stain and examined for AFB, also same samples were subjected for CBNAAT(cartridge based nucleic acid amplification test). Selected sputum induction(SI) CBNAAT negative patients are also underwent bronchoscopy and BAL fluid was subjected for CBNAAT. Results:- Out of 100 clinically diagnosed tuberculosis patients, 49% of cases had only infiltration, 45% cases had consolidation,17% had infiltration with fibrosis,16% cases with cavitary lesions and 6% had miliary lesions in chest X -ray. 17(17%) cases became induced sputum smear positive, 30(30%) cases became induced sputum CBNAAT positive. All induced sputum CBNAAT positive cases were rifampicin sensitive. No rifampicin resistance was detected. Out of 70 patients with SI CBNAAT negative, 21 patients with highly clinico radiological suspicion underwent bronchoscopy and 4(19%) patients become post bronchoscopy sputum AFB positive. Out 21 patients 8(38%) patients become BAL CBNAAT positive and all are rifampicine sensitive. Conclusion:- Induced sputum and BAL fluid are better alternative methods for diagnosis in patients with clinico-radiological suspicion of TB who are unable to expectorate or are smear negative and no rifampicin resistant cases were detected throughout this study.

Epidermolysis Bullosa With Congenital Absence of Skin: Congenital Corneal Cloudiness and Esophagogastric Obstruction Including Extended Genotypic Spectrum of PLEC, LAMC2, ITGB4 and COL7A1.

Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of COL7A1 are responsible for EB with CAS in the vast majority of cases. Type and subtype diagnosis of EB with CAS generally requires specific immunohistological examinations that are not widely available plus targeted gene analysis. The present study aimed to determine the clinical features of five patients affected by EB with CAS and to identify the underlying genetic defects using whole exome sequencing (WES) followed by focused analysis of the target genes. Four patients had generalized skin involvement and one had localized defects. Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. In the WES analysis, the average coverage of the target exons was 99.05% (726 of 733 exons), with a range of 96.4–100% for individual genes. We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: PLEC:c.2536G > T (p.Glu846Ter); LAMC2:c.3385C > T (p.Arg1129Ter); KRT5:c.429G > A (p.Glu477Lys); ITGB4:c.794dupC (p.Ala266SerfsTer5); COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG. All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding. The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes. The data confirm that WES provides very high coverage of coding exons/genes and support its use as a reasonable alternative method for diagnosis of EB. The present data from an underrepresented population in Southeast Asia could further broaden the knowledge and research on EB.

Ideal predictor studies

We have read the article titled “Evaluation of Covid-19 cases that applied to the hospital at the first peak of the pandemic” prepared by Akdoğan et al. with great interest. Firstly, we thank authors for their research from Turkey that aims create an alternative diagnosis method by using some laboratory parameters in the early phase of COVID-19. Although the study resulted in negative results, these studies of academics from Turkey for humanity at a time when the whole world was affected by the pandemic are commendable. Secondly, we thank the authors and the editorial board for their courage in publishing this negative article that is informative and successful manuscript. As mentioned in an article published in nature, highlighting negative results will improve science. We also would like to mention a few important points about ideal predictor studies in the early phase of COVID-19.

Trends in Diagnosing Obstructive Sleep Apnea in Pediatrics.

Obstructive sleep apnea in children has been linked with behavioral and neurocognitive problems, impaired growth, cardiovascular morbidity, and metabolic consequences. Diagnosing children at a young age can potentially prevent significant morbidity associated with OSA. Despite the importance of taking a comprehensive sleep history and performing thorough physical examination to screen for signs and symptoms of OSA, these findings alone are inadequate for definitively diagnosing OSA. In-laboratory polysomnography (PSG) remains the gold standard of diagnosing pediatric OSA. However, there are limitations related to the attended in-lab polysomnography, such as limited access to a sleep center, the specialized training involved in studying children, the laborious nature of the test and social/economic barriers, which can delay diagnosis and treatment. There has been increasing research about utilizing alternative methods of diagnosis of OSA in children including home sleep testing, especially with the emergence of wearable technology. In this article, we aim to look at the presentation, physical exam, screening questionnaires and current different modalities used to aid in the diagnosis of OSA in children.

SPONTANEOUS HEMOPERITONEUM BY UTERINE VARICOSE VEIN RUPTURE IN PREGNANCY: A CASE REPORT

A 34-year-old pregnant woman, second gravida with previous vaginal delivery, was referred to our hospital at 34 weeks of gestation complaining severe pain abdomen. She was diagnosed with hemoperitoneum with intrauterine foetal demise in ultrasonography. An emergency laparotomy was performed, and intraoperatively it was found that bleeding was caused by ruptured of uterine variceal veins on posterior surface. Lower segment caesarean section was performed and patient delivered a fresh still born male child. Hemostasis with sutures was successfully performed. Spontaneous hemoperitoneum during pregnancy caused by rupture of uterine blood vessels is very rare. Difcult to diagnose and it is a life threatening condition with poor foetal and maternal outcome. It requires rapid and accurate diagnosis and surgical treatment. In most incidences of spontaneous hemoperitoneum during pregnancy, a caesarean delivery is performed along with a simultaneous emergency laparotomy. Alternative methods of diagnosis and management options need to be discussed to improve foetal and maternal outcome.

THE PULMONARY MICROBIOME AS A RISK FACTOR FOR LUNG CANCER DEVELOPMENT AND PROGRESSION. REVIEW

Lung cancer, being one of the leading causes of mortality among cancer patients, is a global medical and social problem. The number of studies devoted to the etiology, molecular pathology and methods of early detection of lung neoplasms has been steadily increasing. Recently, the great efforts are made to search for alternative methods of diagnosis, therapy and prevention of neoplasms of the respiratory system. So the study of the influence of the quantitative and qualitative microbiome characteristics on the growth and tumor development has become increasingly relevant. This review is devoted to the association between the composition of the pulmonary microbiome and the development of malignant neoplasms of the lungs. We used the analysis of the available literature data to perform this review.

Evaluation of Covid-19 cases that applied to the hospital at the first peak of the pandemic

Early diagnosis in COVID-19 is essential in terms of treatment and prevention of contagiousness. In this study, we aimed to find an alternative diagnosis method by using fewer laboratory parameters in the early diagnosis of COVID-19 disease by creating a fast, easily accessible, cost-effective index and has a diagnostic accuracy rate of over 90%. All patients over the age of 18 who applied to Hitit University Erol Olçok Training and Research Hospital Emergency COVID Outpatient Clinic with a pre-diagnosis of COVID-19 between March and April 2020 were evaluated retrospectively. Patients were divided into two groups as COVID-19 positive and COVID-19 negative. It was aimed to create a HITIT-19 index by evaluating the cases according to the clinical and laboratory results. Between March and April 2020 (in the first peak of the pandemic), 1586 patients were applied to the Emergency COVID-19 outpatient clinic with a pre-diagnosis of COVID-19. According to COVID-19 RT-PCR, card test, and CT involvement, 285 (13%) patients were diagnosed with COVID-19. PCR was positive in 285 (18%) of 1586 patients, and PCR was negative in 1301 (82%). While 153 (53.7%) of the patients diagnosed with COVID-19 were male and the median age was 45 (28-62.75), 883 (55.7%) of the patients not diagnosed with COVID-19 were male, and the median age was 43 (31-65). Hypertension (HT) was the most common underlying disease in 10.5% of patients applied to the emergency room with a diagnosis of COVID-19, while 38.9% dyspnea and 35.1% fever were the most common symptoms. While 76% of Plaquenil and 58% azithromycin were the most frequently started treatments, 31.4% (28.4% of them were hospitalized in the service, 3% in the intensive care unit) of them hospitalized. It was to create a HITIT-19 index that is fast, easily accessible, cost-effective, and has a diagnostic accuracy rate of over 90% by using laboratory tests. However, we could not achieve this goal due to the low accuracy of the diagnostic tests and the lack of significant change in the laboratory levels of the patients at admission. Considering that the pandemic is continuing rapidly, there is still a need to develop practical diagnostic methods that are easier and cheaper in diagnosis. In this sense, we believe that our study will be a guiding study for other studies that will be designed for diagnostic index studies.

CRISPR-Cas12a combined with reverse transcription recombinase polymerase amplification for sensitive and specific detection of human norovirus genotype GII.4

Human norovirus (NOV) is a common and serious virus that accounts for sporadic cases and outbreaks of gastroenteritis. This study aimed to develop rapid, reliable and portable detection systems by coupling reverse transcription recombinase polymerase amplification (RT-RPA) with CRISPR-Cas12a (RT-RPA-Cas12a) for NOV genotype GII.4. Here, three primers for RNA-dependent RNA polymerase gene of NOV were designed and screened. Then, RT-RPA products were detected using CRISPR-Cas12a system by combing with fluorescence or lateral flow (LF). RT-RPA-Cas12a-based fluorescence or LF assay can be completed within 40 min, with the detection limit of up to 9.65 × 102copies/mL and no cross-reactivity with metapneumovirus, bocavirus, seoul virus, and respiratory syncytial virus. Furthermore, the detection coincidence rates of RT-RPA-Cas12a-based fluorescence and LF with qRT-PCR were 98.3%. Therefore, the present study suggests that both RT-RPA-Cas12a-based fluorescence and LF are promising sensitive, specific and alternative method for diagnosis of NOV genotype GII.4 without ancillary equipment.