It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. Besides, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

Considering the age of the dogs, it was expected that elderly animals would have stiffer thyroids than adults. The aim of this study was to evaluate the thyroid glands of healthy dogs using 2D shear wave elastography in order to establish qualitative and quantitative parameters of tissue stiffness in dogs of different age groups. The B-mode ultrasound and elastography findings were correlated with the weight and sex of the patients, allowing a reference range to be established for different groups of dogs. 31 dogs of different breeds, sexes and sizes were evaluated. Animals with clinical signs or ultrasound findings indicative of endocrine disease or thyroid lesions were not included in the study. Using QelaXtoTM 2D software, shear wave velocity data in m/s and color elastograms were evaluated and calculated. A healthy thyroid has a blue color elastogram, indicative of low stiffness, and there was no distinction between adult and elderly dogs, genders or sizes. The reference range for the shear wave velocity of thyroid tissue assessed by 2D shear wave elastography can be between 1.6 and 2.0 m/s with a variation of ±0.889 in adult and elderly dogs.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Background: Online survey-based observational cross-sectional study aimed at elucidating experience and attitudes of unstructured population regarding diagnostic imaging. Methods: Invitations to participate were distributed using mixed-mode design to deidentified residents aged 18 years and older. Main outcome measures included morbidity structure and incidence of diagnostic imaging administrations. Results: Respondents (n = 1069) aged 44.3 ± 14.4 years; 32.8% suffered from cardiovascular diseases (CVD); 9.5% had chronic respiratory pathology; 28.9% considered themselves healthy. Respondents with COVID-19 history (49.7%) reported higher rates of computed tomography (CT) (p < .0001), magnetic resonance imaging (MRI) (p < .001), and ultrasound (p < .05). COVID-19 history in CVD respondents shifted imaging administrations towards CT and MRI (p < .05). Every tenth respondent received MRI, CT, and ultrasound on paid basis; 29.0% could not pay for diagnostic procedures; 13.1% reported unavailable MRI. Professional status significantly affected the pattern of diagnostic modalities (p < .05). MRI and CT availability differed between respondents in urban and rural areas (p < .0001). History of technogenic events predisposed responders to overestimate diagnostic value of fluorography (p < .05). Conclusions: Preparedness to future pandemics requires development of community-based outreach programs focusing on people's awareness regarding medical imaging safety and diagnostic value.

Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

The “red code” (RD) represents the highest levels of emergency in the emergency department (ED). The study retrospectively analyzed RDs in the Regina Margherita Children’s Hospital ED, a regional referral center in north Italy, between 1 July 2020 and 30 June 2023. The aim was to describe RD characteristics and to identify significant correlations between presenting complaints and clinical management. The study includes 934 RDs (0.9% of overall ED admissions); 64% were assigned based on the Pediatric Assessment Triangle alteration. Most patients, 86.5%, followed the medical pathway, while 13.5% were surgical cases. Admission complaints were respiratory (46.9%), neuropsychiatric (26.7%), traumatic (11.8%), cardiologic (9.3%), metabolic (3.8%), and surgical (1.5%). Seventy-six per cent of patients received vascular access, and intraosseous access was obtained in 2.2% of them. In one-third of RDs, an urgent critical care evaluation was necessary, and 19% of cases required admission to the intensive care unit. The overall mortality rate was 3.4% (0.4% in ED setting). The study identified six distinct diagnostic pathways, each associated with specific characteristics in clinical presentation, management, therapeutic interventions, and outcomes: this underscored the significance of a systematic approach in improving outcomes in pediatric RD management.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Primary care pediatricians encounter a wide range of complex conditions in their daily clinical practice. It is not uncommon for their patients to get exposed to medical errors. Diagnostic errors, defined as missed, delayed, or wrong diagnosis, are of great importance as they may cause significant harm to the pediatric patient with severe disease. These errors often occur when the symptoms and signs of a disease are atypical or missing. Data on the most frequent misdiagnosed situations in pediatrics is scarce. One of these groups of conditions is that regarding cardiac diseases. The pediatric cardiology field has met rapid development over the past few decades. Primary care providers play a key role in diagnosis, management, and referral of children with heart disease, both congenital and acquired, because many common cardiac complaints are first addressed in the primary care setting. The scope of this review is to investigate the cardiac entities that are often missed by the general pediatricians. In particular, it aims to spot the most common of them, to describe their clinical presentation, their diagnostic options, red flags, and tips, and to provide the ways to avoid erroneous, delayed, or missed diagnosis.

The coronavirus pandemic was declared by the World Health Organization (WHO) in 2020, and a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, many countries around the world have reported that so-called genetic vaccines, such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular damage, as well as a wide variety of diseases involving all organs and systems, including the nervous system. In this article, based on these circumstances and the volume of evidence that has recently come to light, we call the attention of medical professionals to the various risks associated with blood transfusions using blood products derived from people who have suffered from long COVID and from genetic vaccine recipients, including those who have received mRNA vaccines, and we make proposals regarding specific tests, testing methods, and regulations to deal with these risks. We expect that this proposal will serve as a basis for discussion on how to address post-vaccination syndrome and its consequences following these genetic vaccination programs.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

Intestinal parasitic infections pose a significant public health challenge in Northern Nigeria, with prevalence rates ranging from 20% to 70%. Traditional diagnostic methods, primarily microscopic examination of stool samples, face limitations such as low sensitivity and high costs. This research addresses these challenges by proposing an Artificial Intelligence (AI)-based platform for the identification and counting of intestinal parasites. Leveraging the You Only Look Once (YOLO) V8 model, trained on a dataset of 360 pre-processed and annotated images, the AI model demonstrated promising performance metrics. The precision-recall curve, average precision, mean average precision, and F1 score indicated reliable detection and classification across various parasite classes. The model exhibited a well-balanced trade-off between precision and recall, showcasing its potential as a cost-effective and accessible tool for improving the diagnosis and treatment of intestinal parasitic infections in resource-limited settings.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Background: The bacterium Capnocytophaga spp. is a part of the oral microbiome of dogs, which has zoonotic potential. This study aimed to assess factors that influence the prevalence of Capnocytophaga cynodegmi and Capnocytophaga canimorsus in Wrocaw’s dog population. Methods: Molecular detection (PCR) involved 105 swabs, examining parameters such as oral cavity condition, underlying health issues, recent antibiotics, age, medications, material collection, and dog chews. Results: The study highlighted significant associations between the presence of Capnocytophaga cynodegmi and oral cavity condition, material collection method, and use of dog’s chews. Conclusions: Correlations obtained in this study between the oral health of Wroclaw's dog population and the presence of Capnocytophaga cynodegmi suggest its significance in the oral microbiome of dogs. Limitations, including the small sample size, highlight the need for more research to comprehensively understand additional factors that affect the prevalence of Capnocytophaga spp. in dogs

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P<0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) exist in the atmosphere in the vapor and particulate phases, as well as in the solubilized form in fog/rain/cloud waters. They are abundant pollutants and are known for their acute and chronic toxicity. In the current paper, fogwater samples are collected during 42 events between 2015 and 2021 at four sites (Strasbourg, Geispolsheim, Erstein, Cronenbourg) in the Alsace region with different topological characteristics. PAHs and PCBs are extracted using the liquid-liquid extraction (LLE) supported on a solid cartridge (XTR Chromabond), and then analyzed by gas-chromatography tandem mass spectrometry (GC-MS/MS). Total PAHs and PCBs concentration in fog samples varied between 0.58 and 6.7 µg L-1 (average of 2.70 µg L-1), and 0.14 and 15.5 µg L-1 (average of 2.75 µg L-1). Low molecular weight (LMW) predominant and highly detectable over high molecular weight PAHs by at least 1.6 times, while pentachloro-biphenyls are the dominant PCB congener accounting for at least 50% of the total fraction. PAHs and PCBs concentrations have increased over sampling years at all sites, except a slight decrease in PCBs level at Geispolsheim. Diagnostic ratio analysis suggested that diesel and fossil fuel combustion are the dominant contributors to PAHs in Alsace

Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guide-lines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ES-GO-ESTRO-ESP recommendations was performed furtherly confirming this statement. Trans-vaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumour delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insuffi-cient sensitivity to detect small-volume metastases, as any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, con-trast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography in combination with CT (PET-CT) are recommended to assess extrapelvic spread. The aim of this paper is to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer.

This study examined the efficiency of a combined diagnostic approach in which bioamplification of Arizona 861 S1 citron was integrated with RT‒PCR to detect Citrus tristeza virus (CTV) and Hop Stunt Viroid (HSVd) in Citrus plants. The capacity of the combined method to diagnose mixed infections of CTV and HSVd, along with early single infections of both pathogens, was assessed by evaluating the incubation periods and differential detection capabilities between the combined and direct methods. The bioamplification method exhibited high sensitivity (100%) and specificity (100%) for CTV, enabling early detection even in patients with low-titer infections compared to direct RT‒PCR. However, for HSVd, the combined method achieved 50% sensitivity in early infections, highlighting the need for additional replicates to enhance diagnostic reliability. The relative concentrations of pathogens in mixed and simple infections were evaluated; the analysis revealed no significant differences, suggesting minimal interference between CTV and HSVd. This approach allows early detection of CTV but requires further refinement for HSVd diagnosis. These findings underscore the complementary roles of the cost-effectiveness of direct RT‒PCR and the sensitivity of the combined method in implementing effective disease control strategies in citrus crops.

We performed urine cytology analysis of a pharmacologically induced diuresis for diagnostics of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, a first cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated with radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as follow-up procedure, a second cohort of 1250 patients who underwent radical cystectomy for bladder cancer was selected. In the first cohort, sensitivity of cytology of pharmacologically forced diuresis in patients with invasive, high-grade, low-grade, and concomitant carcinoma in situ was 8%, 9%, 0% and 14%, respectively. In the second cohort, cytology of pharmacologically forced diuresis was positive in 30/689 (4.3%) of patients, in whom upper urinary tract recurrence was present in 21/30 (70%) and urethral recurrence in 8/30 (26%) of cases. As a follow-up tool, cytology of pharmacologically forced diuresis showed a sensitivity, specificity, and positive and negative predictive value of 60%, 99%, 70% and 98%, respectively. Summarized, as diagnostic tool, sensitivity of cytology of pharmacologically forced diuresis is slightly better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As follow-up method, positive cytology of pharmacologically forced diuresis is strongly related to cancer recurrence and can reveal urethral recurrence. cytology of pharmacologically forced diuresis might be useful in patients with contraindications for imaging or with difficult endoscopic access to the upper urinary tract.

Autism spectrum disorder (ASD) is a common condition with lifelong implications. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes (P=0.0002), validating that most are indeed disease related. Sequence reanalysis increased diagnostic yield from 28% to 68%, mostly by inclusion of de novo PDVs in genes not yet reported as ASD associated. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

Chest trauma is a critical medical condition that encompasses a range of injuries and can result from various causes. Prompt and accurate diagnosis is crucial in managing chest trauma patients and radiology plays a pivotal role in this aspect. Imaging modalities in chest trauma aid in precise diagnosis and treatment planning. Especially, X-rays remain the initial imaging modality of choice due to their accessibility, speed, and ability to detect acute life-threatening conditions. Computed Tomography (CT) Scan offers detailed cross-sectional images allowing for comprehensive evaluation of chest trauma and surgical planning when necessary. Ultrasound (US) is increasingly valuable tool due to its portability and real-time imaging capabilities, aiding in rapid assessment at the bedside. Magnetic Resonance Imaging (MRI) is less commonly used due to time constraints and limited availability. Radiological imaging serves various purposes in the diagnosis and management of chest trauma such as early detection and triage, characterization and severity assessment, surgical planning, follow-up and monitoring of chest trauma. Reduction of radiation exposure, advancements in imaging technology (dual-energy CT, contrast-enhanced imaging) and Artificial Intelligence (AI) algorithms are crucial challenges and deserve attention. A multidisciplinary approach integrating radiological expertise remains fundamental in ensuring optimal outcomes for patients with chest trauma.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

The study of paraneoplastic syndromes in humans has a long history, whereas for domestic animals – only since the beginning of the 21^th century. There are various forms of paraneoplastic syndromes; many classifications based on pathogenetic, organ-system principles are described. In accordance with the modern classification, paraneoplastic syndromes are divided into endocrinopathies, hematological paraneoplastic syndromes, gastrointestinal, renal, dermatological, neurological, ophthalmological. The purpose of this study was to develop a scientifically based algorithm for diagnosing ophthalmopathies against the background of paraneoplastic syndrome in dogs, including a multifactorial system of “hormonal-drug treatment” of paraneoplastic ophthalmopathies. The work used a comprehensive methodological approach, including the collection of anamnestic data, clinical examination of the animal, examination of the area of the pathological process, hematological studies, cytomorphological studies, visual diagnostic methods with complete oncological and ophthalmological examinations using the necessary equipment. Treatment for cancer included surgical removal of the tumor, chemotherapy and radiotherapy. The choice of treatment protocol depended on the location of the disease, tumor phenotype (if present) and stage of the malignancy. The only chemotherapy was applied using complex protocols in the treatment of dog lymphomas. Treatment of melanoma in dogs was carried out using an integrated approach which combined methods of surgery, chemotherapy, and radiotherapy. The obtained results can be recommended for use in the diagnosis and treatment of paraneoplastic ophthalmopathies in dogs.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including virulence factors and host interactions, are discussed in detail. Diagnostic methods, ranging from traditional techniques to advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.

In the literature, the question of the amount of data necessary and sufficient to validate different models of the occurrence of risk of adverse events for patients or the classification of the presence or absence of pathological features has been repeatedly raised. In the presented study, we propose a new approach to determine the necessary and enough studies for validation of medical software based on artificial intelligence technology, whose main task is to classify medical X-rays according to the presence of normality and pathology. It is shown that for several studies in a dataset, when AUC ROC has maximum heterogeneity, it varies depending on the balance of "norm"/"pathology" classes. Thus, for a balance of "normal"/"abnormality", where 90% is "normal" and 10% is "abnormality", maximum heterogeneity is achieved for 190 studies, for a balance of 80% ("normal")/20% ("abnormality") for 80 studies, for a balance of 70% ("norm")/30% ("abnormality") - 120 trials, for a balance of 60% ("norm")/40% ("abnormality") the maximum heterogeneity is reached at 110 trials, and for a balance of 50% ("norm")/50% ("abnormality") - at 70 trials. The obtained data are in good agreement with the previous results. They allow us to determine a sufficient (necessary) number of studies in the dataset to perform an unbiased assessment of AUC ROC.

Artificial intelligence (AI) tools, such as OpenAI's Chat Generative Pre-trained Transformer (ChatGPT), have great potential in various fields, such as healthcare, education, and industry. This review highlights the applications and challenges of the ChatGPT versions 3.5 and 4.0 in radiology. ChatGPT can process medical texts, analyze medical images, and generate reports and summaries for different audiences. ChatGPT can also answer patients' questions and translate complex medical information into a plain language. ChatGPT has shown impressive results in medical tests and quizzes, indicating its potential to enhance diagnostic accuracy and medical education. These models show promise for reducing diagnosis times and healthcare costs. However, ChatGPT also faces challenges and limitations, such as a lack of visual content, ethical and legal issues, data quality, and error detection. This review highlights the benefits and future directions of ChatGPT and artificial intelligence (AI) in radiology.

Intrauterine growth restriction (IUGR) and being born small for gestational age (SGA) are two distinct conditions with different implications for child development. IUGR is associated with greater perinatal morbidity and mortality and can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnios, lack of growth in the interval, estimated weight <3rd percentile). IUGR may also be present in neonates with birth weights above the 10th percentile. Recognizing fetuses being “at risk” of a higher perinatal mortality and morbidity rate in order to monitor them accordingly and deliver them in good time is still challenging. This review article summarizes approaches to increase the diagnostic accuracy of IUGR and presents current concepts of pathophysiology with a focus on oxidative stress and consecutive inflammatory and metabolic changes. Since prenatal influences affect the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood and look at future scientific challenges. It should be emphasized that prenatal and postnatal care of IUGR neonates should be regarded as a continuum.

To analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection.

The lack of accurate and feasible diagnostic tests poses a significant challenge to visceral leish-maniasis (VL) healthcare services in endemic areas. To date, various VL diagnostic tests have been or are being developed, and their diagnostic performance needs to be assessed.. In the present study, the diagnostic performance of rk39RDT, Direct Agglutination Test (DAT), Microscopy, Loop Mediated Isothermal Amplification (LAMP), and miniature direct-on-blood polymerase chain reaction - nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) was assessed using quantitative polymerase chain reaction (qPCR) as reference test in an endemic region of Ethiopia. In this study, 235 patients VL suspected patients and 104 non-endemic healthy controls (NEHC) were recruited. Among the VL-suspected patients, 144(61.28%) tested positive with qPCR. Sensi-tivities for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA were 88.11%, 96.50%, 76.58%, 94.33%, and 95.80%, respectively. Specificities were 83.33%, 97.96%, 100%, 97.38%, and 98.92% for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA, respectively. In conclusion, Rk39 RDT and microscopy exhibited lower sensitivity, while DAT demonstrated excellent performance. LAMP and mini-dbPCR-NALFIA showed excellent perfor-mance with feasibility to implement in remote endemic areas, although the latter requires further evaluation in such regions.

Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYA) with sarcoma are a unique and under-studied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYA with sarcoma who underwent comprehensive molecular profiling (CMP) using either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following the Molecular Tumour Board evaluation. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range 37-57). Potentially actionable variants were detected for 14 patients (56%) and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change of diagnosis. Implementation for CMP for AYA with sarcoma is clinically valuable, feasible and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune mediated liver disease which progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance for young women but may be seen in children and elderly. Diagnosis requires integration of clinical, biochemical and serologic parameters along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a pre-requisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the Original Scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH with their limitations and utility, with an emphasis on the role of liver histology in diagnosis and management of AIH.

Chronic Kidney Disease is a medical condition that causes the decrease in the kidney function and can eventually derive in a total cessation of the work of the organ. It currently affects >10% of the global population, and the number is expected to grow within the next few years, since the correlated diabetes condition is escalating too. Diagnosing the disease on its early stages is crucial to improve life quality, and to increase the chances of survival. The traditional diagnostic methods, which include a biopsy, are invasive, expensive and dangerous. With the use of machine learning algorithms like neural networks, random forest and genetic algorithms, this paper seeks to discover an algorithm with high accuracy, whose selected attributes will be the most optimal combination aiming to reduce the cost, level of invasiveness, and easiness to obtain.

Background: First-line biological diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT), which detect in the blood the Histidin Rich Protein 2 antigen, specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold-standard diagnosis, aims to evaluate the performance of RDTs used in Mali and to describe the distribution of Plasmodium species in each administrative regions of Mali; Methods: We collected RDT cassettes in 47 sites of the nine regions of Mali. We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs from each regions. DNA was extracted from the RDTs’ nitrocellulose strip and then assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with qPCRs specific for P. falciparum, P. malariae, P. vivax, and P. ovale; Results: Of the 1,389 tested by qPCR RDTs, 258 (18.6%) were positive for Plasmodium spp. P.falciparum was the most predominant (97.3%). However, the prevalence of P.vivax reach 21.1% in the Ménaka region in the north; Conclusion: Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. Our finding support the adjustment of RDTs to the local epidemiology.

Introduction Cone Beam Computed Tomography (CBCT) scans should be digitally oriented using a reference plane before being evaluated for patient growth and treatment outcome. Current orientation planes are usually dependent on the Porion points. Using more reliable landmarks than the Porion, we introduce the Acta plane and investigate its reliability as an alternative reference plane for cases in which the Porion point is inaccessible. Methods To test its reliability, a dental student and an orthodontist located sixteen skeletal and dental landmarks in sixteen CBCT scans, before and after reorientation. Also, four measurements were calculated based on these landmarks’ coordinates. The reorientation of these CBCT scans with the Acta plane was done by another dental student. Intraclass Correlation Coefficient (ICC) was calculated before and after orientation, intra- and inter-examiner. The data were tested for significance through the Shapiro Wilk test with a threshold set at 0.05. Through the ICC variation of the points’ coordinates, this article also evaluated the reliability of this plane with the t-paired and exact-sign tests. Results: The identification of landmarks was more reliable in the reoriented CBCT images than in the original images, with a significant increase of 0.012 in the median of the ICC. Linear and angular measures showed no significant differences between groups. Conclusion This plane is a reliable alternative for the orientation of CBCT images. The design of the Acta plane might allow the use of a smaller field of view and, consequently, a reduction in the radiation dose.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

Human pulmonary paragonimiasis, an emerging concern in North East India, frequently masquerades as pulmonary tuberculosis due to clinical and radiological similarities, leading to diagnostic challenges. This research was aimed to harness the immunoblotting technique to discern immunodiagnostic protein antigens from both adult worm and excretory-secretory (ES) extracts of the prevalent Paragonimus westermani type 1 in Arunachal Pradesh, North East India. We studied the time kinetics of immunoreactive patterns in relation to the duration of infection in rodent models. Immunoblot analyses were also conducted using sera from ELISA positive patients confirmed with paragonimiasis, facilitating the selection of antigenic extracts with diagnostic potential. Further, ES proteins antigens were subjected to 2D- immunoblot analysis and immunoreactive protein spots identified by MALDI-TOF MS. Immunoreactivity patterns of ES antigens with sera of paragonimiasis positive patients were detailed, and specific immunoreactive protein antigens were pinpointed using peptide mass fingerprinting (MALDI-TOF). This work underscores the enhanced diagnostic accuracy when combining ELISA with immunoblotting for pulmonary paragonimiasis in regions like North East India, marked by co-existing helminth infections.

Background. ADHD is a neurodevelopmental disorder that is accompanied by executive deficits. Objectives. To obtain evidence of the usefulness of the BRIEF-P and to analyse the possible ceiling and floor effect of its scores in the assessment of executive function in preschoolers with signs compatible with a possible diagnosis of ADHD. Methods. Seven articles were selected from 2538 potentially eligible articles from different databases. We included studies assessing samples of individuals with symptoms compatible with ADHD, with age range 2-6 years, published in English or Spanish, during the period 2012-2022. References published in: Science Direct, NCBI (PubMed), ProQuest Education Journals in the last decade. Risk of bias was assessed using the QUADAS-2 questionnaire. The main variables were: age and executive functioning. Conclusions. Executive deficits in early-life individuals with ADHD-compatible symptoms are more extensive than deficits in working memory. BRIEF-P is an instrument that facilitates obtaining a sensitive and discriminative executive profile. It should be used in combination with other neuropsychological performance tests, finding a floor effect in tests associated with warm executive functions and a ceiling effect in cold executive functions. This requires using a variety of tests to assess executive performance in preschoolers with symptoms compatible with ADHD and designing intervention proposals in line with them...

In food industry, there is a growing demand for cost-effective methods for inline inspection of food items able to non-invasively detect small foreign bodies which may have contaminated the product during the production process. Microwave imaging may be a valid alternative to the existing technologies, thanks to its inherently low-cost and its capability of sensing low-density contaminants. In this paper, a low-complexity microwave imaging system specifically designed to enable the inspection of a large variety of food products is presented. The system consists of two Circularly Loaded Antipodal Vivaldi Antennas, having a very large operative band, from 1 to 15 GHz, thus allowing a suitable spatial resolution for different food products from mostly fatty to high water-content ones. The antennas are arranged in such a way to collect the signal useful to exploit a recently proposed real-time microwave imaging strategy, leveraging the inherent symmetries usually characterizing food items. The system is experimentally characterized, and the achieved results compare favorably with the design specifications and the numerical simulations. Relying on these positive results, a first experimental proof of the effectiveness of the whole system is presented, which confirms its efficacy.

This study aimed to investigate the potential correlations and differences between patients with Acute Coronary Syndrome (ACS) and controls. Emphasis was placed on examining the relationship between arterial blood gas PH value and arterial blood gas lactate value as well as assessing the utility of the Peripheral Perfusion Index (PI) in ACS management. Materials and Methods: A prospective observational study was conducted between January 1, 2023, and July 1, 2023, involving 60 ACS patients and 30 control subjects in an emergency department. The diagnosis of ACS was confirmed by experienced emergency physicians, and various parameters, such as peripheral perfusion index, blood gas values, and cardiac biomarker values, were collected. The statistical analyses included Pearson’s chi-square test, Mann-Whitney U test, Student’s t-test, and others, using SPSS version 18.0. There were significant differences in the mean age, perfusion index, and lactate levels between the patient and control groups. A robust negative correlation was found between age and PI, and a moderate negative correlation was observed between pH and lactate levels (r = -0.301, p=0.004). The perfusion index in the patient group was significantly lower, indicating its potential diagnostic utility. The findings demonstrate the importance of arterial blood gas pH and lactate values in understanding ACS patient profiles, emphasizing the potential of PI as a noninvasive diagnostic method. The negative correlation between pH and lactate levels may offer valuable insights into risk stratification and treatment strategies for patients with ACS.

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

Background. Ovarian cysts are common in premenopausal women but can present with vague, non-specific symptoms, making discovery more challenging. Most are benign and resolve spontaneously; however, they can present, as in this case, as ovarian torsions, which is a gynecological emergency. Case presentation. A twenty-year-old female had presented over 3–4 times per year for the last 6 years to her primary doctor citing intermittent abdominal pain, irregular menstruation, dyspnea, and an enlarging abdomen circumference. The doctor stated, she was “just fat” and could, benefit from a “special camp to lose weight”, so she stopped mentioning her concerns. Upon presenting to the emergency department with acute onset abdominal pain, a computed tomography scan showed a large cyst lesion filling the abdominal and pelvic cavity. Its origin appeared to be from the left adnexa. Surgery was performed, and an acute ovarian torsion caused by a 36 cm craniocaudal left ovarian cyst was found and removed along with the left fallopian tube and 16 L of fluid. Conclusions. The value of respecting the “third presentation” rule indicates to health care providers that any patient who presents with any /or other symptoms or complaint needs to be thoroughly investigated. In this case the patient presented recurring pelvic/abdominal concerns, irregular menstruation, which warranted further investigation to safeguard fertility and prevent errors of omission. It is important to consider the differentials and be aware of vague symptoms that may lead to early recognition and effective management to prevent adverse consequences, complications, or even death.

This study investigated clinical nurses’ knowledge and visual differentiation ability of the pressure injury classification system (PICS) and incontinence-associated dermatitis (IAD), additionally analyzing possible influencing factors. A convenience sample of 248 nurses took the PICS and IAD knowledge test (KT) and completed the visual differentiation ability test (VDAT), consisting of 21 photographs with clinical information. The overall mean score for correct answers was 12.65±2.90 points in PICS & IAD KT and 11.43±4.57 points in VDAT. Incorrect responses were most common for statements related to stage Ⅱ, Ⅲ, IAD for PICS & IAD KT, and deep tissue pressure injury (DTPI), unstageable, and stage Ⅲ for VDAT. Significant correlations were found between PICS & IAD KT and VDAT (r=.252, p<.001). Factors affecting scores for VDAT were the scores of PICS & IAD KT, debridement experience in nursing patients with PI, and the management frequency of PI and IAD. Results indicate that nurses have an overall understanding of PICS and IAD, but low visual differentiation ability regarding stage Ⅲ, DTPI, and unstageable PI. Continuing education is needed to further improve knowledge and visual differentiation ability for PICS and IAD.

Background: This prospective study assesses the use of Rapid Remote Online Cytological Evaluation analysis for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved a total of 314 Rapid Remote Online Cytological Evaluations (17 brush, 143 fine needle aspirations and 154 imprint cytologies) analyses performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was determined and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of Rapid Remote Online Evaluation, 86 cytological benign and 190 malignant and 38 findings of unclear diagnosis were recorded (Ø assessment time 100 sec., range 11 - 370sec.). In 27 of the 38 cases with unclear diagnosis, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another five of these 38 cases remained unclear. Excluding these 38 findings, the Rapid Remote online cytology achieved a sensitivity of 78.6% with a specificity of 99.5% and a correct classification rate of 93.1% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived.

This study aimed to assess the diagnostic accuracy of a mobile application by comparing its diagnoses to those of Orofacial Pain and Oral Medicine specialists and further imaging results (TMJ CBCT and MRI) in 500 patients with temporomandibular disorder (TMD). The research focused on three diagnostic categories: initial specialist diagnoses, final diagnoses after imaging, and the mobile app's diagnoses. The concordance rate, sensitivity, specificity, and positive predictive value of the diagnoses were examined, with further imaging serving as the gold standard. The mobile app demonstrated a high concordance rate compared to both final (0.93) and initial specialist diagnoses (0.86). Sensitivity, specificity, and positive predictive values also indicated strong reliability, affirming the app's diagnostic validity. Although the concordance rate was slightly lower when comparing the app's diagnoses to imaging results (CBCT and MRI), specialist diagnoses yielded similar results. The study suggests that user-friendly diagnostic mobile applications, based on the Diagnostic Criteria for Temporomandibular Disorders, could enhance the clinical management of TMD. Given the reliability of mobile applications for diagnostic purposes, their wider implementation could facilitate the provision of appropriate and timely treatments for patients with TMD.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, Sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

Introduction: The serological support to early diagnosis and differential diagnosis of inflammatory bowel diseases (IBD) is actually very limited. In this study we evaluated the performance of a promising multiparametric method including either well established and newly developed biomarkers. Methods: This multicenter retrospective observational study finally enrolled 156 patients with IBD, 100 affected by Crohn’s disease (CD) and 56 by ulcerative colitis (UC) recruited at the Gastroenterology Units of Udine (Italy), Rijeka (Croatia) and Belgrade (Serbia). Twently age-sex matched blood donors (BD) were included as controls. Autoantibody profiles were determined using a mosaic cell and tissue-based indirect immunofluorescence (IIF) method simultaneously investigating: anti-saccharomyces cerevisiae antibodies (ASCA), anti-atypical perinuclear neutrophilic antibodies (P-ANCA), anti-pancreatic antigens antibodies (PAB) and anti-goblet cells antibodies (GAB). Results: PAB (anti-CUZD1 and/or anti-GP2 antibodies) were present in 24 CD patients versus none of UC patients or BD (24% sensitivity, 100% specificity). As regards CD patients, combined positivity of PAB and ASCA (sensitivity 84%, specificity 71.4%) performed better than ASCA alone. Colon involvement (87.5% vs. 60.5%; p=0.014), deep mucosal lesions (58.3% vs. 25.0%; p=0.002) and need for biologic therapies (79.2% vs. 46.1%; p=0.005) were significantly more prevalent in PAB-positive than in PAB-negative CD patients. Multivariate analysis identified PAB positivity (OR=3.67; 95%CI=1.29-10.46) and anti-CUZD1 in particular (OR=3.54; 95%CI=1.08-11.63) as significant risk factors for deep mucosal lesions development in CD. Conclusion: A multiparametric diagnostic approach appears very useful to better characterize IBD patients. PAB, isolated or combined with other autoantibodies, may support both differential diagnosis and selection of CD patients at risk for more severe disease.

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

A recently proposed single image parasite quantification (SIMPAQ) platform based on a Lab-On-a-Disc (LOD) device has been earlier successfully tested in field conditions demonstrating the efficiency in soil-transmitted helminths (STH) egg detection and analysis. A related study (Micromachines 2021, 12, 1032) revealed the effects that can limit the performance of a SIMPAQ method due to the action of the Euler and Coriolis forces, and the interaction of the moving eggs with the walls of the LOD chamber. Here we propose a new improved design that allows to overcome those limitations and enhance the yield of the SIMPAQ LOD device which is demonstrated in the experiments with synthetic particle model system and real parasite eggs.

Aims: To date, precision medicine plays a pivotal role in the clinical administration of solid tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently investigated in clinical trials. A pitfall in the molecular tests is the diagnostic routine sample available to analyze predictive biomarkers; scant tissue sample often represents the only diagnostical source of nucleic acids to assess molecular analysis. At the sight of these critical issues, Next Generation Sequencing (NGS) platforms emerged as referral testing strategy for molecular analysis of predictive biomarkers in routine practice but high-skilled personnel, extensive working-time drastically impact on the widespread diffusion of this technology in diagnostic setting. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with NGS based diagnostic workflow by a referral institution. Methods: A retrospective series of n=64 samples (n=32 DNA, n=32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion) were retrieved from internal archive of University of Naples Federico II. Each sample was tested by adopting Oncomine Precision Assay (OPA), able to detect 2769 molecular actionable alterations [hot spot mutations, copy number variations (CNV) and gene fusions on fully integrated NGS platform (Genexus, Thermofisher Scientifics. (26,27) Concordance rate between these technical approaches was carried out. Results: Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between OPA and SiRe™ panel both for DNA and RNA based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) was assessed. Conclusions: Fully automatized Genexus system combined with OPA (Thermofisher Scientifics) may be considered a technically valuable, saving time sequencing platform to test predictive biomarkers in diagnostic routine practice.

SARS-CoV-2, influenza A/B virus (IAV/IBV) and respiratory syncytial virus (RSV) are among the common viruses causing acute respiratory infections. Clinical diagnosis to differentiate these viruses is challenging due to similar clinical presentations, thus laboratory-based real-time RT PCR is the gold standard for diagnosis. The study aimed to evaluate the diagnostic performance of STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor Inc, Seoul, Korea). This retrospective study was conducted with archived respiratory samples positive and negative for SARS-CoV-2, IAV, IBV or RSV. The evaluation study involved a total of 322 respiratory samples comprising 215 positive samples (49 SARS-CoV-2, 48 IAV, 53 IBV, 65 RSV) and 107 negative samples. All samples were tested with both STANDARD M10 and either Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV (Cepheid, USA). The sensitivity, specificity, positive predictive value and negative predictive value rates of STANDARD M10 were very similar to Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV ranges for each virus (98-100%). The overall agreement was 99.4% with 99.1% agreement for positive samples and 100% agreement for negative samples. In conclusion, the STANDARD M10 point-of-care test is suitable for rapid simultaneous detection of SARS-CoV-2, IAV, IBV and RSV.

Introduction: Determination of radiological bone age (BA) is a diagnostic method that consists of estimating chronological age (CA) from the bone maturation of children. Although environmental and hormonal factors can interfere with bone ossification, the process is essentially dependent on ancestral inheritance. These ethnic backgrounds are not usually considered, which can lead to biased interpretations and inadequate decision-making by pediatricians or forensic experts. The objective of this study was to determine the precision and accuracy of these radiological procedures among different ethnic groups. Methods: A qualitative systematic review carried out following MOOSE statement and previously registered in the International Prospective Registry of Systematic Reviews PROSPERO (CRD42023449512). Search was performed in MEDLINE (PubMed) (n=561), Cochrane Library (n=261), CINAHL (n=103), Web of Science (WOS) (n=181) and public institutional repositories (n=37) from inception to 31st December 2022 using Mesh as “Diagnostic Techniques and Procedures”, “Diagnostic imaging”, “Radiography”, “Age Determination by Skeleton” and free terms combining with booleans “AND” and “OR”. PEDro scale, and Risk of Bias in non-randomized Studies of Exposure (ROBINS-E) were used to assess methodological quality and risk of bias of included studies respectively. Results: 51 articles (n=19,531) were included according to the inclusion criteria previously established. There was a good to moderate methodological quality and a high to very high risk of bias. Skeletal methods for determining BA were precised in terms of intra-observer and inter-observer reliability in all ethnic groups. Regarding to accuracy of Skeletal methods in Caucasians and Hispanic children, GPA was accurate at all ages, but in youths, TW3 RUS could be a consistent alternative. In Asian and Arab, GPA and TW3 overestimated BA in adolescents near adulthood. In African youths, GPA overestimated BA while TW3 was more accurate in estimating CA. Dental and Cervical radiographic methods are equally precise but lesser accurate than Skeletal BA determination. Conclusion: Skeletal radiographic methods GPA and TW3 are both precise for BA determination among all ethnical groups, but their accuracy in estimating CA can be altered by racial bias.

Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). Numerous techniques have been devised to detect prion seeding activity, each with limitations. Here, we developed a technology for in vitro amplification of abnormal prion proteins (PrPSc), thereby enabling their sensitive detection. Using the real-time quaking-induced conversion (RT-QuIC) PrPSc amplification assay, we could detect ≥1 fg of PrPSc in diluted human prion disease brain homogenate. Although RT-QuIC assay is suitable for detecting prion seeding activity in a variety of specimens, its accuracy in whole blood, blood plasma, or blood-contaminated tissues is reduced. To circumvent this issue and move toward developing a blood test for prions, we introduced an immunoprecipitation step at the beginning of the RT-QuIC reaction. We refer to this enhanced method as “eQuIC”. eQuIC utilizes three types of human monoclonal antibodies, which significantly increased its sensitivity—making it approximately 1000 times more sensitive than the original RT-QuIC assay. Nevertheless, when we tested the blood (serum, plasma, and whole blood) of six patients with sporadic human prion disease using eQuIC, we were unable to detect prion activity. Therefore, we concluded that the detection of prion seeding activities in blood samples from patients with sporadic prion disease remains challenging; thus, alternative methods beyond RT-QuIC and eQuIC will be necessary for future research.

Blood gas analysis plays a central role in modern medicine. Advances in technology have expanded the range of available parameters and increased the complexity of their interpretation. By applying user-centered design principles, it is possible to reduce the cognitive load associated with interpreting blood gas analysis. In this international, multicenter study, we explored anesthesiologists' perspectives on Visual Blood, a novel visualization technique for presenting blood gas analysis results. We conducted interviews with participants following two computer-based simulation studies: the first utilizing Virtual Reality (VR) (50 participants) and the second without VR (70 participants). Employing the template approach, we identified key themes in the interview responses and formulated six statements, which were rated using Likert scales: from 1 (strongly disagree) to 5 (strongly agree) in an online questionnaire. The most frequently mentioned theme was the positive usability features of Visual Blood. The online survey revealed that participants found Visual Blood to be an intuitive method for interpreting blood gas analysis (median 4, IQR 4-4, p<0.001). Participants noted that minimal training was required to effectively learn how to interpret Visual Blood (median 4, IQR 4-4, p<0.001). However, adjustments are necessary to reduce visual overload (median 4, IQR 2-4, p<0.001). Overall, Visual Blood received a favorable response. The strengths and weaknesses derived from these data will help optimize future versions of Visual Blood to improve the presentation of blood gas analysis results.

Natural killer cells are associated with the pathogenesis of ulcerative colitis (UC), but their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated genes (ANAGs) in UC. Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, 92 differentially expressed genes (DEGs) were screened out by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT, which revealed a higher abundance of activated NK cells in noninflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2) and establish an activated NK-associated gene score (ANAG score). The ANAG score demonstrated excellent diagnostic value and was validated in three external datasets. The expression of the 4 key ANAGs was validated in UC patients and healthy controls (HC) samples. Through scRNA-seq data analysis, higher expression levels of SELP, TIMP1, MMP7, and ABCG2 were observed in post-capillary venules, inflammatory fibroblasts, enterocytes, and immature enterocytes. The cell scores based on the ANAGs showed enrichment in endothelial cells and fibroblasts. In conclusion, we established and validated an ANAG score with the ability to precisely diagnose UC. The 4 key ANAGs have the potential to serve as therapeutic targets in UC.

Stem cells can be used in cellular therapy. This happended in order to replace damaged cells or having aim to regenerate organs. The definition of stem cells can be extended. From this point of view, we can mention taking in consideration the idea in which it is known that these cells form the base of the building body. More than, we can mention that stem cells are characterized by two knowing properties namely differentiation and selfrenewal. Based on the observation that differentiation of adult stem cells into specific derivativescan be controlled by laboratory techniques, it is anticipated that adult stem cells may become the basis of therapies for many, and various types of medical conditions. Taking on stem cells, regenerative medicine (RM) it is known as being one of the hottest topics in biotechnology nowadays. From this purpose, stem cells can be used in regenerative medicine (RM). The principles of regeneration are found in different types of cultures, from long time ago, centuries etc.

Transportation authorities aim to boost road safety by identifying risky locations and applying suitable safety measures. The Highway Safety Manual (HSM) is a vital resource for US transportation professionals, aiding in the creation of Safety Performance Functions (SPFs), which are predictive models for crashes. These models rely on Negative Binomial distribution-based regression and misinterpreting them due to unmet statistical assumptions can lead to erroneous conclusions, including inaccurately assessing crash rates or missing high-risk sites. The Florida Department of Transportation (FDOT) has introduced context classifications to HSM SPFs, complicating assumption violation identification. This study, part of an FDOT-sponsored project, investigates established statistical diagnostic tests to identify model violations and proposes a novel approach to determine optimal spatial regions for Empirical Bayes adjustment. This adjustment aligns HSM-SPFs with regression assumptions. The study employs a case study involving Florida roads. Results indicate that a 20-mile radius offers an optimal spatial sample size for modeling crashes of all injury levels, ensuring accurate assumptions. For severe injury crashes, which are less frequent and harder to predict, a 60-mile radius is suggested to fulfill statistical modeling assumptions. This methodology guides FDOT practitioners in assessing the conformity of HSM-SPFs with intended assumptions and determining appropriate region sizes.

Dyes, as indigo carmine have become indispensable to modern life being widely used in food, textile, pharmaceutical, medicine and cosmetic industries. Although indigo carmine is considered toxic and presents many adverse effects, it is heavily used in the food industry because the blue pigment is difficult to obtain from natural sources and is one of the most used dyes in the textile industry, especially for dyeing denim. Also, indigo carmine is one of the dyes used in medicine as diagnostic agent because it has impressive applicability in terms of diagnostic methods and surgical procedures. In the literature it is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, corneal and conjunctival disorders or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine, its use in various industries and medicine, the adverse effects of its ingestion, injection or skin contact, the effects on environmental pollution and its toxicity testing.

This study aimed to investigate the diagnostic potential of circulating microRNAs (miRNAs) for detecting early myocardial fibrosis development in HFpEF patients. This observational study used a case-control research design. Peripheral blood samples were isolated from 25 HFpEF patients and 25 normal patients. They were measured for NTproBNP levels using ELISA, as well as MicroRNA-1, 21, and 29 levels using RT-PCR. All patients also underwent echocardiography for global longitudinal strain (GLS) to measure the myocardial fibrosis progression. Data were analyzed using SPSS 25.0. HFpEF patients had significantly higher GLS compared to the normal patients (-13±2.4% vs -19±3.2%; p &lt; 0.05), suggesting HFpEF patients tended to have myocardial fibrosis. HFpEF patients also had significantly higher microRNA-1 and microRNA-21 compared to the normal patients (p &lt; 0.05), but they had lower microRNA-1 (p &lt; 0.05). There was a positive correlation between microRNA-1 (r = 0.753; p &lt; 0.05) and microRNA-21 (r = 0.675; p &lt; 0.05) and an inverse correlation with microRNA-29 (r = -0.653; p &lt; 0.05) based on the GLS findings. By using a GLS cutoff of -15% for myocardial fibrosis, microRNA-1, microRNA-21, and microRNA-29 were found to be able to predict myocardial fibrosis based on GLS with a specificity of 78% and sensitivity of 75%. Increasing microRNA-1 and microRNA-21 followed by decreasing microRNA-29 in HFpEF patients suggest early myocardial fibrosis.

Animal viruses are a significant threat to animal health and are easily spread across the globe with the rise of globalization. The limitations in diagnosing and treating animal virus infections have made the transmission of diseases and animal deaths unpredictable. Therefore, early diagnosis of animal virus infections is crucial to prevent the spread of diseases and reduce economic losses. To address the need for rapid diagnosis, electrochemical sensors have emerged as a promising tool. Electrochemical methods present numerous benefits, including heightened sensitivity and selectivity, affordability, ease of use, portability, and rapid analysis, making them suitable for real-time virus detection. This paper focuses on the construction of electrochemical biosensor, as well as promising biosensor models, and expounds its advantages in virus detection, which is a promising research direction.

Spinal deformity refers to a range of disorders that are defined by anomalous curvature of the spine and may be classified as scoliosis, lordosis, or kyphosis. Among these, scoliosis stands out as the most common type of spinal deformity in human beings, and it can be distinguished by abnormal lateral spine curvature accompanied by axial rotation. Accurate identification of spinal deformity is crucial for a person's diagnosis, and numerous assessment methods have been developed by researchers. Therefore, the present study aims to systematically review recent works on spinal deformity as-assessment for scoliosis diagnosis, utilizing image processing techniques. To gather relevant studies, a search strategy was conducted on three electronic databases (Scopus, ScienceDirect, and PubMed) between 2012 and 2022, using specific keywords and focusing on scoliosis cases. A total of 17 papers fully satisfied the established criteria and were extensively evaluated. Despite variations in methodological designs across the studies, all reviewed articles obtained quality ratings higher than satisfactory. Various diagnostic approaches have been employed, including artificial intelligence mechanisms, image processing, and scoliosis diagnosis systems. These approaches have the potential to save time and, more significantly, can reduce the incidence of human error. While all assessment methods have potential in scoliosis diagnosis, they possess several limitations that can be ameliorated in forthcoming studies. Therefore, the findings of this study may serve as guidelines for the development of a more accurate spinal deformity assessment method that can aid medical personnel in the real diagnosis of scoliosis.

Although jojoba (Simmondsia chinensis) has been cultivated for years, information on its N re-quirements is limited. A 6-year study of mature jojoba plants grown under field conditions with an intensive management regime evaluated the effect of N-application rate on plant nutrient status, growth and productivity, and nitrate accumulation in the soil. Five levels of N application were tested: 50, 150, 250, 370 and 500 kg N ha-1. The fertilizers were provided all along the growing season via subsurface drip irrigation system. Leaf N concentration, in both spring and summer, reflected the level of N applied. Diagnostic leaf (youngest leaf that has reached full size) concentration of 1.3% N was identified as the threshold for N deficiency. Increasing rates of N application resulted in higher P levels in young leaves. Plant K status, as reflected by leaf analysis, was not affected by N treatment but was strongly affected by fruit load. Vegetative growth was inhibited when only 50 kg N ha-1 was applied. Soil analysis at the end of the fertilization season showed substantial accumulation of nitrate for the two highest application rates. Considering productivity, N costs, and environmental risk, 150 kg N ha-1 is the recommended dosage for in-tensively grown jojoba. N deficiencies can be identified using leaf analysis and excess N can be detected by soil sampling toward the end of the growing season. These results and tools will fa-cilitate precise N fertilization in intensive jojoba plantations.

Live cell imaging is a powerful technique to study the dynamics and mechanics of various biological molecules like proteins, organelles, DNA, and RNA. With the rapid evolution of optical microscopy, our understanding of how these molecules is implicated in the cells’ most critical physiological roles deepens. Here in this review, we focus on how spatiotemporal nanoscale live cell imaging on a single molecule level allows for profound contributions towards new discoveries in life science. This review will start by summarizing how single molecule tracking has been used to analyze membrane dynamics, receptor ligand interactions, protein-protein interactions, inner- and extracellular transport, gene expression/transcription, and whole organelle tracking. We then move on to how current authors are trying to improve single molecule tracking and overcome current limitations by offering new ways in labeling protein of interests, multi-channel/color detection, improvements in time laps imaging, and new methods and programs to analyze colocalization and movement of targets. We later discuss how single molecule tracking can be a beneficial tool used for medical diagnosis. Finally wrapping up with limitation and future perspective of single molecule tracking and total internal refection microscopy.

This study aimed to evaluate the diagnostic roles of various immunohistochemical markers in urothelial carcinoma in situ (uCIS) through a meta-analysis and review of diagnostic test accuracy. Immunohistochemical markers CK20, CD44, AMACR, and p53 were evaluated in the present study. We analyzed the expression rates of immunohistochemical markers and compared their diagnostic accuracies. The estimated expression rates were 0.803 (95% confidence interval [CI]: 0.726–0.862), 0.142 (95% CI: 0.033–0.449), 0.824 (95% CI: 0.720–0.895), and 0.600 (95% CI: 0.510–0.683) for CK20, CD44, AMACR, and p53, respectively. In the comparison between uCIS and reactive/normal urothelium, the expression of CK20, AMACR, and p53 in uCIS was significantly higher than in reactive/normal urothelium. CD44 showed significantly lower expression in uCIS than in the reactive/normal urothelium. Among the markers, AMACR had the highest sensitivity, specificity, and diagnostic odds ratio. The AUC on SROC was the highest for CK20. In conclusion, immunohistochemical markers, such as CK20, CD44, AMACR, and p53, can be useful in differentiating uCIS from reactive/normal urothelium.

Lipidomics provides comprehensive study of all lipid components in cells, serum, plasma or tissues of organisms, aiming to the discovery of diagnostic, prognostic and predictive biomarkers of diseases such as malignancies. This systematic review evaluates studies, where lipidomics applies to the diagnosis, prognosis, prediction of ovarian cancer (OC) and the discrimination between malignant and benign ovarian masses. Literature search was conducted in PubMed, Science Direct and SciFinder. Only publications written in English language after 2012 were included. From the reference lists of primary included studies, relevant citations were identified and were also added in our list. All studies included referred to the application of lipidomics in serum/plasma samples of human cases with OC, whereby few of them included also tumor tissue samples. In some of the included studies metabolomic analysis was also involved where other metabolites besides lipids were identified. Qualitative data were assessed and risk of bias was determined using the ROBINS-I tool. In total, 29 studies were included, 15 of which applied non-targeted, 7 targeted lipidomics and 7 were reviews relevant to our aim. Most studies concerned the possible application of lipidomics in OC diagnosis, exhibiting phospholipids and sphingolipids as the most significantly altered during development of the disease. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.

Hepatitis B e antigen (HBeAg) is a marker of wild-type hepatitis B virus replication. In resource-limited countries where access to enzyme-linked immunosorbent assay (ELISA) remains a challenge, rapid diagnostic tests (RDT) constitute a good alternative. The HBeAg status is employed to evaluate eligibility for antiviral therapy and to prevent the transmission of hepatitis B from mother to child (PMTCT). The objective of this study was to assess the diagnostic performance of the SD-Bioline®HBeAg RDT commonly used for detecting HBeAg in laboratories in Burkina Faso. The sample panel used was collected from HBsAg positive patients received in the laboratory for the detection of HBeAg with the rapid test. The samples were retested for HBeAg using the VIDAS HBe/Anti-HBe enzyme-linked fluorescent assay (ELFA) (Gold standard). Then, the viral load (VL) of HBV DNA was determined using the GENERIC HBV CHARGE VIRLAE kit (GHBV-CV). The diagnostic performances of the SD-Bioline®HBeAg and its agreement with the gold standard were calculated with their 95% confidence intervals. 340 sera obtained from HBsAg positive patients were included in this evaluation Compared to the VIDAS HBe/Anti-HBe ELFA test, the sensitivity (Se) and specificity (Sp) of the SD-Bioline®HBeAg test were 33.3% and 97.9% respectively. The concordance between the two tests was 0.42. Depending on the viral load, the Se and Sp varied from 8.8% and 98.3% for a VL &lt; 2,000 IU/mL to 35.5% and 98.4% for a VL &gt; 2,000,000 IU/mL. The results showed a low Sensibility of the SD-Bioline®HBeAg RDT test, indicating that its use is inappropriate for the clinical management of HBV-infected patients. They also highlight the urgent need to develop HBeAg rapid tests with better sensitivities.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes (buffaloes 01 to 05) in the amazon biome are described. Epidemiological data were obtained during the clinical visit in which the animals with clinical signs compatible with polioencephalomalacia were submitted to a general and specific clinical examination of the nervous system. During the necropsy of the five animals, the intensity and location of the lesions were evaluated and fragments from different organs were collected and fixed in 10% buffered formalin and sent to the Pathological Anatomy Sector of the Federal Rural University of Rio de Janeiro for histopathological examination. Of the five studied animals, all were of the Murrah breed, four male and one female, with ages ranging from two months to one year. Two buffaloes (buffalo 01 and 02) were from the municipality of Castanhal, Pará, kept in an extensive breeding system on Urochloa brizantha pasture. Buffaloes 03 and 04 belonged to a property located in the municipality of Cachoeira do Arari, Marajó Island, Pará, and buffalo 05 was from a property located in the municipality of Itaubal, state of Amapá, all of them were raised in an extensive system in flooded of native pasture. At the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), and there was noted decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding to the corral structures, head pressing and circumduction of the hindquarters when supported on the forelimbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. Histopathological examination showed laminar necrosis of the cerebral cortex. The diagnosis of polioencephalomalacia was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. The cause of polioencephalomalacia in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, mainly in the Amazon region.

Rikenella microfusus is an essential intestinal probiotic with great potential. The latest research shows that its imbalance in the intestinal flora is related to the occurrence of various diseases, such as intestinal diseases, immune diseases, and metabolic diseases. Rikenella may be a target or biomarker for some diseases, providing a new possibility for preventing and treating these diseas-es by monitoring and changing the abundance of Rikenella in the intestine. However, the current detection methods have disadvantages such as long detection time, complicated operation, and high cost, which seriously limit the possibility of clinical application of this new treatment method. Therefore, developing rapid and low-cost detection methods has become an urgent problem to be solved. In this study, we used Rikenella as the target bacterium, meanwhile including five other prominent gut bacteria Akkermansia muciniphila, Allobaculum stercoricanis, Blautia producta, Rose-buria intestinalis and Parabacteroides distasonis as control organisms. The aptamer library R.m-R13 was evolved with high specificity and strong affinity (Kd = 9.597 nM) in an iterative Cell-SELEX process after 13 rounds of selection. R. microfusus can efficiently be discriminated from other major gut bacteria in complex mixtures in different analysis techniques including fluorescence micros-copy or fluorometric suspension assays and even in human stool samples. These preliminary re-sults open new avenues towards the development of aptamer-based microbiome bio-sensing ap-plications for fast and reliable R. microfusus monitoring.

Background: Neurosarcoidosis is a great mimic, and its distinction from multiple sclerosis and other disorders can be particularly troublesome. We investigated whether cerebrospinal fluid (CSF) examination could help distinguish these two conditions and propose new diagnostic criteria. Methods: Stringent hierarchical diagnostic criteria were formulated. These were then applied prospectively to 531 neurological patients in whom neurosarcoidosis entered the differential diagnosis. The CSF total protein (TP), white cell count (WCC) and angiotensin-converting enzyme (ACE) levels were measured. The CSF and serum IgG patterns after isoelectric focusing were compared. Not all CSF parameters were measured in every patient. Results: 85/531 (16%) cases examined were diagnosed with neurosarcoidosis. Only 22 of these 85 (26%) met stringent diagnostic criteria. Intrathecal synthesis of oligoclonal IgG was evident in only 1/19 (5%) who fulfilled these criteria compared to 19/59 (32%) cases who did not (p = 0.03). CSF TP levels > 1g/L were more common in patients meeting the stringent criteria compared to the remainder of the patients, i.e. 11/22 (50%) vs 14/58 (24%) (p<0.05). Eleven out of 20 cases (55%) fulfilling stringent criteria had elevated CSF WCCs, and 6/12 cases (50%) had raised CSF ACE, neither significantly different from the remaining cases. Mean CSF TP, WCC, and ACE levels did not differ significantly between any groups of patients. Interpretation: Large elevations in CSF total protein, white cell count, and ACE occur in neurosarcoidosis but are rare in multiple sclerosis. However, the diagnostic use of these tests is limited since minimal changes may occur in both conditions. In contrast, intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is very uncommon in neurosarcoidosis whilst occurring in 95-98% of cases of multiple sclerosis. This observation implies that the immunopathogenesis of the two disorders is quite different. We suggest caution in diagnosing neurosarcoidosis when intrathecal oligoclonal IgG synthesis is detected. We propose new diagnostic criteria for neurosarcoidosis for future research.

Tomato brown rugose fruit virus (ToBRFV) is a causal agent of severe emergent diseases in Solanaceae hosts with agronomic relevance, such as tomato and pepper. Herein, we analyzed the seed transmission rate and efficacy of different seed disinfection treatments and performed a comparison of molecular biology techniques seeking rapid and sensitive detection in seed lots. We evaluated several total RNA extraction and RT-PCR protocols using a distinct combination of PCR primers to test for the presence of the ToBRFV Mexican strain in tobacco host. Our results showed that the percentage of seed and seedlings transmission was less than 1% and that a 3% sodium hypochlorite solution was effective as a seed disinfection treatment. Finally, the most sensitive molecular method identified for virus detection consisted of a CTAB-Trizol RNA extraction followed by nested PCR using primers reported by Dovas et al. (2004). Additionally, we tested potential natural hosts in selected Cucurbitaceae and Solanaceae species. Our results showed that the ToBRFV Mexican strain is capable of experimentally infecting eggplant (Solanum melongena), tomatillo (Physalis ixocarpa), and tobacco (Nicotiana rustica).

Breast cancer is the foremost common in women, and its early diagnosis will help treat and increase patients' survival. This review article aims to studies on recent findings of standard imaging techniques and their characteristics for breast cancer diagnosis and recent nanoparticles (NPs) which are used for breast cancer detection. Herein, The search was performed in the literature through scientific citation websites, including Google Scholar, PubMed, Scopus, and Web of Science until May 2023. A comprehensive study on different imaging modalities and NPs for breast cancer diagnosis is reviewed, and their successes, challenges, and limitations are discussed.

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

Uncontrolled and fast cell proliferation is the cause of brain tumors. Early cancer detection is vitally important in order to save many lives. Brain tumors can be divided into several categories depending on the kind, place of origin, pace of development, and stage of progression; as a result, tumor classification is crucial for targeted therapy. The aim of brain tumor segmentation is to accurately delineate the areas of the brain. A specialist with a thorough understanding of brain illnesses must manually identify the proper type of brain tumor. Additionally, processing a lot of images takes time and is tiresome. Therefore, automatic segmentation and classification techniques are required to speed up and enhance the diagnosis of brain tumors. Tumors can be quickly and safely detected by brain scans using imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and others. Machine learning (ML) and artificial intelligence (AI) have shown promise in the development of algorithms that aid in automatic classification and segmentation utilizing various imaging modalities. This review discussed various types of brain tumors, publicly accessible datasets, enhancement methods, segmentation, feature extraction, classification, machine learning techniques, and deep learning, learning through transfer, for the study of brain tumors.

The paper presents the methods of assessing the technical condition of varistor surge arresters used in laboratory tests and in operation - performed without disconnecting the arresters from the network. The analysis of diagnostic methods was supplemented with the results of measurements of the leakage current of arresters coming directly from production and used in the power industry. Among the available methods of evaluating the technical condition of arresters, mainly indicator solutions (temperature, operation counter) and using the measurement of selected parameters of the leakage current are used. In the latter, the method of determining the resistive component of the leakage current, determined on the basis of the analysis of voltage and current waveforms, or only the arrester current, has become widespread. In this type of measurements, current clamps are used in operation, and additionally in voltage measurements from voltage transformers, where you have to take into account the fundamental, additional sources of errors discussed in the article. These errors and dispersion resulting from the production technology may fundamentally hinder the proper assessment of the technical condition, hence it is so important to properly recognize the listed basic sources of measurement uncertainty. In addition, the analysis should take into account three factors related to external conditions - temperature, voltage applied to the arrester and the content of higher harmonics in the supply voltage for which appropriate methods have been provided to determine the active component of the leakage current for reference conditions.

Epigenetic alterations are heritable and enduring modifications in gene expression that play a pivotal role in immune evasion. These include alterations to noncoding RNA, DNA methylation, and histone modifications. DNA methylation plays a crucial role in normal cell growth and development but alterations in methylation patterns such as hypermethylation or hypomethylation can enable tumor and viral cells to evade host immune responses. Histone modifications can also inhibit immune responses by promoting the expression of genes involved in suppressing normal immune function. In the case of T-cell lymphoma, adult T-cell Lymphomas (ALT) also undergo immune evasion through the exceptional function of its accessory and regulatory genes. Epigenetic therapies are emerging as a promising adjunct to traditional immunotherapy and chemotherapy regimens. Clinical trials are currently investigating the use of epigenetic therapies in combination with immunotherapies and chemotherapies for more effective treatment of ATL and other cancers. This review highlights epigenetic alterations that are widely found in T cell malignancies.

Tick-borne diseases are a growing concern worldwide, affecting both human and animal populations. Ticks are known to harbor a wide range of pathogens and are considered one of the most important vectors of disease. Lyme disease, caused by Borrelia burgdorferi sensu lato, is the most common tick-borne disease in the US and Europe. However, accurate diagnosis of Lyme disease can be challenging due to the complex immune evasion strategies employed by Borrelia species and the limitations of existing diagnostic tests. To address this issue, researchers are exploring novel approaches, including the use of bacteriophages as diagnostic tools. Bacteriophages are highly specific and offer advantages over traditional methods for detecting bacteria, including Borrelia. In particular, the use of multicopy bacteriophages as molecular markers for Borrelia detection is a promising approach that may provide greater sensitivity than targeting single-copy bacterial genes. Nonetheless, the task of identifying trace amounts of bacteriophages in blood samples necessitates attention, and scientists are devising innovative techniques to surmount this hurdle. In summary, employing bacteriophages as a diagnostic tool for tick-borne diseases, such as Lyme disease, by specifically targeting free circulating bacteriophages in blood samples, offers significant potential for enhancing patient outcomes and public health.

The unprecedented COVID-19 pandemic posed major challenges to local, regional, and global economies and health systems, and fast clinical diagnostic workflows were urgently needed to contain the spread of SARS-CoV-2. Here, we describe the platform and workflow established at the Cornell COVID-19 Testing Laboratory (CCTL) for high-throughput testing of clinical samples from the university and the surrounding community. This workflow enabled efficient and rapid detection, and successful control of SARS-CoV-2 infection on campus and its surrounding communities. Our cost-effective and fully automated workflow enabled testing of over 8,000 pooled samples per day and provided results for over 2 million samples. Automation of time- and effort-intensive sample processing steps such as accessioning and pooling increased laboratory efficiency. Customized software applications were developed to track and store samples, deconvolute positive pools, track and report results and for workflow integration from sample receipt to result reporting. Additionally, quality control dashboards and turn-around time tracking applications were built to monitor assay and laboratory performance. As infectious disease outbreaks pose a constant threat to both human and animal health, the highly effective workflow implemented at CCTL could be modeled to establish regional high-capacity testing hubs for infectious disease preparedness and emergency response.

Background and Objectives: The relevance of red flags in serious spinal pathology (SSP) evolved throughout the last years. Recently, new considerations have been proposed to expand the consideration of red flags. The purpose of this study was to determine, approve and test a model for the triage and manage-ment process of SSP based on the latest data available in the literature. Materials and Methods: The SSP model was initially built on the basis of a literature re-view. The model was further determined and approved by an expert panel us-ing a Delphi process. Finally, clinical scenario were used to test the applicabil-ity of the model. Results: After three rounds of Delphi process, panellists reached a consensus on a final version of the model. The use of clinical scenari-os by experts bring about reflexive elements both on the determined model and on the evocative SSP of the clinical cases. Conclusions: The validation of the model and its implementation in the clinical field could help assess the skills of first-line practitioners managing spinal painful patients. To this end, the devel-opment of additional clinical scenarios fitting with the determined model should be further considered.

Classifying spinal tumors can be challenging due to nonspecific clinical and radiological qualities, and a precise biopsy is crucial for an accurate diagnosis and treatment planning. This study aimed to enhance the accuracy and efficiency of spinal biopsies integrating Cone Beam Computed Tomography (CBCT) and magnetic resonance imaging (MRI) modalities using an O-arm CT navigation system. Eighteen patients with diverse spinal lesions underwent 18 biopsies following the Stealth Station navigation system Spine 8 protocol. Preoperative MRI scans were merged with intraoperative CT navigation systems for continuous monitoring during the biopsy process. The combined imaging technique accurately identified the diseased lesion type in all biopsies, demonstrating 100% sensitivity and specificity. In conclusion, combining MRI and CT imaging modalities significantly improved spinal biopsy accuracy and efficiency, differentiating between pathological entities. However, large-scale studies are desired to validate these findings and investigate potential benefits in different clinical scenarios. Although this method requires general anesthesia, its potential profits in avoiding misdiagnosed lesions and decreasing the need for further invasive procedures make it a promising approach for improving spinal biopsy accuracy and efficiency.

Negative work behavior (NWB) threatens employee well-being. There are numerous constructs that reflect NWBs, such as bullying, aggression, and discrimination and they are often examined in isolation of each other, limiting scientific integration of these studies. We aim to contribute to this research field by developing a diagnostic tool with content validity on the full spectrum of NWBs. First, we provide a full description of how we tapped and organized content from 44 existing NWB measurement instruments and 48 studies. Second, we discussed our results with experts (N = 3) in this research field to check for missing studies and to discuss our integration results. This two-stage process yielded a questionnaire measuring physical, material, psychological, sociocultural, and digital NWB. Furthermore, the questions include a range of potential actors of NWB, namely internal (employees, managers) and external actors (clients, customers, public, family members) at work and their roles (i.e., target, perpetrator, perpetrator's assistant, target's defender, outsider, and witness of NWBs). Finally, the questionnaire measures what type of harm is experienced (i.e., bodily, material, mental, and social harm).

Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.

Abstract Background. There is an inherent limit in the accuracy of our measurements, set by nature itself and predicted by Heisenberg's uncertainty principle, which defines the properties of nature in the microcosmos. There is a fundamental limit to the accuracy with which complementary phys-ical quantities of a particle can be predicted from their initial conditions. As classical physics is essentially considered at borderline of quantum mechanics, so the power of uncertainty princi-ple is limited in describing everyday life perceived or managed phenomena. Method. In this study, we apply Heisenberg's uncertainty principle to children under diagnostic uncertainty re-garding appendicitis. We analyze this phenomenon in clinical practice. Results. Medical practice is full of uncertainty. False negative decisions correlate with delays in treatment and adverse outcomes in children with atypical appendicitis. On the other hand, false-positive surgery deci-sions result in negative appendectomies. With improvement of technology, the incidence of complicated appendicitis or negative appendectomies due to diagnostic uncertainty has de-creased but cannot be ignored or eliminated. Conclusion. According to the principle, there is a fundamental limit to the accuracy with which the complementary variables of negative appen-dectomy and complicated appendicitis can be observed or measured simultaneously. What does all this mean for the physician?

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (nuclear magnetic resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine (F.C. = 0.8, p = 0.002), lysine (FC = 0.8, p &lt; 0.001), leucine (FC=0.7, p &lt; 0.001) but higher levels of formic acid (FC=1.6, p ≤ 0.001) when compared to controls. However, metabolic profiling of MM patients compared to controls exhibited decreased levels of total Apolipoprotein-A1 (FC =0.6, p&lt;0.001), HDL-4 Apolipoprotein-A1 (FC = 0.5, p ≤ 0.001), HDL-4 Apolipoprotein-A2 (FC = 0.6, p &lt; 0.001), HDL Free Cholesterol (FC = 0.7, p &lt; 0.001), HDL-3 Cholesterol (FC = 0.5, p ≤ 0.001) and HDL-4 Cholesterol (FC = 0.5, p ≤ 0.001). Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol (FC = 0.6, p ≤ 0.001), HDL Cholesterol (FC = 0.7, p ≤ 0.001), HDL Free Cholesterol (FC = 0.4, p ≤ 0.001), Total Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL-4 Apolipoprotein-A1 (FC = 0.6, p ≤ 0.001) and HDL-4 Phospholipids (FC = 0.6, p ≤ 0.001). This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.

This article presents the results of technical and technological studies of the oil painting by the artist of German origin Werner Tübke “Hiroshima I" (1958). The creative heritage of the author has been little studied and represents scattered data on the technology of painting and artistic techniques. The aim of the work was to determine the artistic materials and painting technolo-gy described in his diaries, using the example of his only painting in Russia – “Hiroshima I". For this purpose, an integrated approach was used using non–invasive control methods - photo in the light of visible luminescence, infrared reflectography (IRR), radiography, portable X-ray fluorescence (XRF), as well as infrared-Fourier spectroscopy (FT-IR) and polarizing microsco-py using microprobes. As a result, the pigment composition of the painting layers was deter-mined, the painting technology was refined, and a previously unknown hidden portrait of Werner Tübke's father was revealed.

Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes depending mainly on timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.

1) Background: Genomic medicine harbors the real potential to improve the health and healthcare jour-ney of patients, care provider experiences, and improve health system efficiency – even reducing health care costs. There is expected to be an exponential growth in medically necessary new genome- based tests and test approaches in coming years. Testing can also create scientific research and commercial opportu-nities beyond healthcare decision-making. The purpose of this research is to generate a better under-standing of Canada’s state of readiness for genomic medicine, and to provide some insights for other healthcare systems; (2) Methods: a mixed-methodsapproach of literature review and key informant in-terviews with a purposive sample of experts was used. Health system readiness was assessed using a pre-viously published set of conditions. (3) Results: Canada has created some of the established conditions but more needs to be done to improve the state of readiness for genome-based medicine. Important gaps are the need for linked information systems and data integration; evaluative processes that are timely, and transparent; navigational tools for care providers; dedicated funding to facilitate rapid onboarding and supports test development and proficiency testing; and broader engagement with a broader set of inno-vation stakeholders. These findings highlight the known role of organizational context, social influence, and other factors that are known to affect the diffusion of innovation within health systems

The identification of biomarkers is crucial for cancer diagnosis, understanding the underlying biological mechanisms, and developing targeted therapies. In this study we propose a machine learning approach to predict the outcome and platinum resistance status of ovarian cancer patients using public available gene expression data. Six classical machine learning algorithms are compared on their predictive performance. Those with the highest score are analyzed by their feature importance using the SHAP algorithm. We were able to select multiple genes that were correlating with the outcome and platinum resistance status of the patients and validated those using Kaplan-Meier plots. In comparison to similar approaches the performance of the models were higher and different genes using feature importance analysis were identified. The most promising identified genes that could be used as biomarkers are: TMEFF2, ACSM3, SLC4A1 and ALDH4A1.

1) Background: Northwest Syria (NWS), is a conflict-affected and unstable area. Due to its limited health infrastructure, accessing advanced COVID-19 testing services is challenging. COVID-19 antigen rapid diagnostic tests (Ag-RDTs) have the potential to overcome this barrier. Therefore, a pilot project was implemented to introduce Ag-RDTs in this setting aiming to a) describe the feasibility, uptake, and results of Ag-RDTs; and b) identify facilitators and barriers to Ag-RDTs testing. 2) Methods: A cross-sectional study design involving secondary analysis of data collected during the project’s monitoring was developed. A local NGO implemented 25,000 Ag-RDTs cross boarder through trained community health workers. 3) Results: A total of 27,888 persons were found eligible and enrolled, of which 24,956 (89.5%) consented to test and 121 (0.5%) were found positive. Highest positivity was observed among those with severe COVID-19 symptoms (12.7%), those with respiratory illnesses (2.5%), persons enrolled at Afrin Hospitals (2.5%), and healthcare workers (1.9%). A non-random sample of 236 people underwent confirmatory rt-PCR test. Accordingly, observed sensitivity, specificity, positive and negative predictive values, were 80.0%, 96.1%, 91.4% and 90.3%, respectively. Key encountered challenges included obtaining informed consent and conducting confirmatory rt-PCR testing. 4) Conclusion: This project demonstrated great feasibility utilizing Ag-RDTs as a screening/diagnostic tool for COVID-19 infections with nearly 90% uptake. Considering the high specificity and negative predictive values and the higher positivity rates among severe COVID-19 symptomatic, embedding Ag-RDTs into COVID-19 testing strategies for ruling out and in COVID-19 infections would hold a great advantage.

The makeup of human microbiota has been linked to a number of autoimmune disorders. Recent developments in whole metagenome sequencing and 16S rRNA sequencing technology have considerably aided research into the microbiome and its relationship to disease. Due to the inherent high dimensionality and complexity of data generated by high-throughput platforms, conventional bioinformatics techniques could only provide an inadequate explanation for the most relevant changes and seldom provide correct predictions. Machine learning, on the other hand, is a subset of artificial intelligence applications that enable the untangling of high-dimensional systems and intricate knots in correlation by learning complex patterns and improving automatically from training data without being explicitly programmed. Machine learning is increasingly being utilized to research the influence of microbes on the onset of illness and other clinical features since computer power has increased dramatically in the last few decades. In this review paper, we focused on emerging methodological approaches of supervised machine learning algorithms for identification of autoimmune disorders utilizing metagenomics data, as well as the potential benefits and limitations of machine learning models in clinical applications.

Background: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder that has no curative treatment. Diagnosis is based on a set of criteria established by Gilman (1998 and 2008) and recently updated by Wenning (2022). We aim to determine the effectiveness of [123I]Ioflupane SPECT in MSA, especially at the initial clinical suspicion. Methods: Cross-sectional study of patients at initial clinical suspicion of MSA, referred for [123I]Ioflupane SPECT. Results: 139 patients (68 men, 71 women) were included, 104 being MSA-probable and 35 MSA-possible. MRI was normal in 89.2% while SPECT was positive in 78.45%. SPECT showed high sensitivity (82.46%) and positive predictive value (86.24), reaching maximum sensitivity in MSA-P (97.26%). Significant differences were found when relating both SPECT assessments in the healthy-sick and inconclusive-sick groups. We also found an association when relating SPECT to the subtype (MSA-C or MSA-P), as well as to the presence of parkinsonian symptoms. Lateralization of striatal involvement was detected (left side). Conclusions: [123I]Ioflupane SPECT is a useful and reliable tool for diagnosing MSA, with good effectiveness and accuracy. Qualitative assessment shows a clear superiority when distinguishing between the healthy-sick categories, as well as between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes at initial clinical suspicion.

Background Cancer is one of the most concerning public health issues in the world. One of cancer hallmarks wildly accepted is sustaining proliferative signaling, which involved most of the cell cycle biological activities. Centromeric histone, Centromere Protein A (CENPA), a variant of canonical histone H3, plays an essential role in selective chromosome segregation in the cell cycle. However, so far, a systematic pan-cancer bioinformatic analysis has not been done yet. Methods We accessed genome, transcriptome, and clinical information from open databases. The genetic alteration, mRNA expression, functional enrichment, stemness, mutation association, expression in cell populations and cellular locations, cell cycle association, survival association of CENPA, and immune association were analyzed. A prognostic model for glioma patients was constructed as an example application of CENPA as a biomarker. Drugs targeting CENPA in cancer cells were also screened and predicted by the CENPA correlation of drug sensitivity and protein-ligand docking. Results CENPA had low gene mutation in cancers. CENPA was overexpressed in almost all cancer types in TCGA compared to their normal control. CENPA was highly expressed in the nucleus of malignant cells. CENPA was associated with the cell cycle of cancer cells. CENPA is a biomarker for the cell cycle G2 phase in cancer cells. CENPA was a diagnostic and prognostic biomarker across multiple cancer types. The prognosis of glioma with CENPA was reliable and can be applied with other prognostic factors. CENPA was associated with the immune microenvironment. Drugs CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. Conclusion CENPA was a cell cycle biomarker in cancers with diagnostic and prognostic value.

Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency, to evaluate the diagnostic performance of serum ferritin in polycythemia vera and to describe the mechanisms of this association. This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR=115; 95% CI [14.4-918.2], p<0.000). The sensitivity and specificity of serum ferritin were 52.63% and 100% respectively. Assessment of iron deficiency should be part of the initial evaluation of polycythemia. The presence of iron deficiency is specific for polycythemia vera.

Introduction: Tuberculosis (TB) is one of the most prevalent respiratory diseases in the world. In 2020 there were at least 9.9 million new infections, with 1.5 million deaths. Approximately 10% of people infected with Mycobacterium tuberculosis (LTBI) develop the disease during the first 2 to 5 years after infection. Currently in South America, the diagnosis of LTBI continues to be per-formed through the Mantoux tuberculin skin test (TST). Objective: The objective of our study was to compare the sensitivity of a new immunofluorescence IGRA test against a widely available IGRA kit on the market. Material and method: Close contact to infectious patients with TB, or HIV patients or immunocompromised for another cause were recruited. Two interferon gamma release assay (IGRA) diagnostic kits were used and compared with TST. Results: 76 patients were recruited. 93.42% were Chilean nationality, 98.68% of the patients did not have immunosuppres-sion. The sensitivity of the new technique was 88.89% and specificity 92.50% in the study popula-tion compared to the IGRA previously used. In the subgroup older than 36 years, the sensitivity was 95.65% and the specificity 89.47%. Conclusion: IGRA techniques are a new resource in clini-cal laboratories to be able to make an accurate diagnosis in LTBI in the region of the Americas. In our population, the greatest benefit of this new IGRA would be observed in people over 36 years of age, where the sensitivity of the technique was like that of the currently available test.

Background: Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in NeNT have been described using various ap-proaches, a comprehensive list of its antigenic determinants that are involved with immunity have not been elucidated. To that end, a high resolution analysis of the linear B-cell epitopes in NeNT was performed using antibodies generated in vaccinated children. Methods: Two hundred sixty-four peptides that cover the entire coding sequence of TeNT protein were prepared in situ on a cellulose membrane by SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes that were further characterized and validated by immunoassays. Results: Forty-three IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as Multiple Antigen Peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). Conclusions: The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the ef-ficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-40/G and TT-42/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines

Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from 2 independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant Prx3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.

The sandwich format immunoassay is generally more sensitive and specific than more common assay formats, including direct, indirect, or competitive. A sandwich assay, however, requires two receptors to bind non-competitively to the target analyte. Typically, pairs of antibodies (Abs) or antibody fragments (Fabs) capable of forming a sandwiching with the target are identified through a slow, guess-and-check method with panels of candidate binding partners. Additionally, sandwich assays reliant on commercial antibodies can suffer from changes to reagent quality outside the researchers’ control. This report presents a reimagined and simplified phage display selection protocol that directly identifies sandwich binding peptides and Fabs. The approach yielded two sandwich pairs, one peptide-peptide and one Fab-peptide sandwich for the cancer and Parkinson’s disease biomarker DJ-1. Requiring just a few weeks to identify, the sandwich pairs delivered apparent affinity comparable to other commercial peptide and antibody sandwiches. The results reported here could expand the availability of sandwich binding partners for a wide range of clinical biomarker assays.

The disease COVID-19 is brought on by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) First appeared in China in December 2019 and quickly spread around the world after being declared a worldwide pandemic by the World Health Organization in March 2020. COVID-19, Medical Laboratory Professionals, SARS-COV-2, Diagnostic, Importance and difficulties for testing were the selected terms to search the databases of PubMed and Google Scholar for previously published material. Many diagnostic tests are applied in corona virus detection like Droplet Digital PCR (ddPCR), Multiplex PCR, Loop-mediated Isothermal Amplification (LAMP) and more. There is a lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies. Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.