The difficulty in the clinical diagnosis of labor is due to an evolutionary mismatch. The ability to hide the signs and symptoms of labor is an evolutionary trait that was once advantageous, but became maladaptive due to environmental changes. Prospective diagnosis of labor is not possible with certainty using only clinical criteria; however, by analyzing the urinary metabolome of women in labor, this diagnosis is likely possible in all cases. In this review, we explain why the two methods (clinical and metabolomic) differ in efficacy and sensitivity, and we try to fit this difference into an evolutionary framework that explains these discrepancies considering evolutionary mismatch. The study of metabolomics allows the truth to emerge from the past, and the diffusion of metabolomic techniques and their application to clinical reality in the form of POC (Point of Care) could change the management of labor and childbirth in the future.

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

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.

Elevated resting heart rate is frequently observed in cancer patients, and is associated with increased mortality. Although specific chemotherapeutic agents can induce cardiotoxicity, the presence of sinus tachycardia in chemotherapy-naive patients suggests other factors likely contribute to this clinical presentation. Despite its prevalence, cancer-associated resting sinus tachycardia has not been fully recognized and comprehensively described as a separate clinical entity. Secondary effects of cancer, especially structural cardiac changes, secretory factors (inflammatory cytokines), and thromboembolic disease can cause resting tachycardia. Alternatively, rapid heart rate may reflect compensatory mechanisms responding to increased metabolic demands, raised cardiac output states, and even pain. Hence, cancer-associated tachycardia presents a clinical dilemma; acute life-threatening conditions (such as sepsis, pulmonary embolism, etc.) must be ruled out, but cancer itself can explain resting sinus tachycardia and more conservative management can avoid unnecessary testing, cost and patient stress. Furthermore, identification and management of cardiac conditions associated with cancer may improve survival and the quality of life of cancer patients.

Superior mesenteric artery (SMA) syndrome or Wilkie’s syndrome is a vascular compression disorder that causes abnormal compression of the third portion of the duodenum by the SMA. It has a low incidence rate, higher in young women, and is rarely associated with the Nutcracker phenomenon: a condition of compression of the left renal vein between the SMA and the aorta, which manifests as pain in the left flank and pelvis. Here we report the case of a 54-year-old woman with a history of repeated episodes of abdominal pain caused by the Nutcracker syndrome and Wilkie's syndrome.

Due to the host immunological disease brought on by infection is sepsis, multiple organ dysfunction syndrome (MODS), which has a high morbidity and mortality rate, could be the result. With advances in pathogen detection technologies, breakthroughs in anti-infection drugs, and the creation of organ function support, the clinical diagnosis and treatment of sepsis have advanced significantly. Pathogen-induced abnormal immunological responses, which can range from excessive inflammation to immunosuppression, are recognized to play a significant role in the high death rate. Unfortunately, no medications that are specifically intended to treat sepsis have been licensed. In order to offer a theoretical foundation for the management of sepsis, we will now discuss current advancements in research on immunological responses in sepsis. The prognosis of sepsis patients may be improved by developing and optimizing a dynamic immune system treatment plan based on anti-infection therapy, fluid replacement, support for organ function, and timely application of immunomodulatory therapies

Pancreatic cancer (PC) is the most lethal type of cancer, it has the lowest 5-year survival rate among all other types of cancers. More than half of PC cases are diagnosed at an advanced stage due to PC’s insidious and non-specific symptoms. Surgery remains the most efficacious treatment option currently available, but only 10-20% of PC cases are resectable upon diagnosis. As of now, the sole biomarker approved by the United States Food and Drug Administration (US-FDA) for PC is carbohydrate antigen 19-9 (CA19-9); however, its use is limited use for early diagnosis. An in-creasing number of studies have investigated a combination of biomarkers. Lately, there has been considerable interest in the application of a liquid biopsy, including the utilization of microRNAs (miRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Screening for PC is indicated for high-risk patients; studies on new diagnostic models combined with biomarkers for early detection have also shown promising results for the ability of these models and biomarkers to aid clinicians in deciding on whether to start screening. This review seeks to provide a concise overview of the advancements in existing biomarkers and explore novel strategies for the early detection of PC.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Purpose: This study analysed the impact of the COVID-19 pandemic on the diagnosis of malignant neoplasia of the bronchus and lung. Cases diagnosed in the Burgos region in the year prior to the official declaration of the pandemic were compared with those in the year after the pandemic. The research sought to identify whether there was a decrease in the number of cases during the pandemic, and whether this may have led to a delay in diagnosis, reflected in more advanced stages of the disease. Mortality and survival time in each of the periods were also analysed.

Smartphone-based fundus camera and telemedicine are an opportunity for accessing ocular health inequalities in underresourced areas. The objective of this study is to evaluate the prevalence of retinal findings in a community in the Amazon and propose strategies to enhance ocular health. A cross-sectional study was conducted in a river side community. Retinal photos from the posterior pole and optic disc were captured using a portable fundus camera. All photos and data were analyzed remotely by a retina specialist. The final sample was 107 participants, aged 52±17. Retinal findings were detected in 37.4% (95%CI 28.7–46.8) of the sample, the three main retinal findings were epithelial changes (10.3%, 95%CI 5.6–17.1), chorioretinal scars (8.4%, 95%CI 4.2–14.8), and dry Age-related Macular Degeneration (7.5%, 95%CI 3.6–13.6). This study detected retinal alterations in similar prevalence of other underresourced areas. Telemedicine is an opportunity to address health inequities, especially in ophthalmology, through relatively low-cost portable devices, supporting clinical decisions in areas with low health access, however, maintaining assistance after implementation is a challenge. Enhancing medical education and training local non-specialized health professionals for risk assessment, device handling, and data base use is reasonable to ensure follow-up.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Monkeypox virus belongs to the Orthopoxvirus genus, which belongs to the Poxviridae family. The Monkeypox virus is responsible to cause monkeypox, a developing zoonotic disease that has been identified as the most common orthopoxvirus infection in humans in the post-eradication era of smallpox. The virus can be transmitted by a variety of animals, including monkeys and rodents as well as person-to-person. Monkeypox has a clinical presentation that is quite similar to smallpox but mortality is low, in that the febrile prodrome is followed by a period of skin eruption. Monkeypox cases have extended outside the forests of central Africa, where they were first discovered, to other regions of the globe, where they have been imported. This pattern of transmission is most likely related to a global reduction in orthopoxvirus immunity following the discontinuation of smallpox vaccination in 1980, when smallpox was proclaimed eliminated. As a result, monkeypox might become the very common orthopoxvirus infection that affect humans. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of monkeypox cases are critical tools for gaining a better knowledge of the disease's ever-changing epidemiology.

Background/Objectives: To evaluate incidental findings in the mandible after the placement of dental implants using a new cone-beam computed tomography (CBCT) software. Methods: The initial sample consisted of 2,872 CBCT scans of patients of both sexes. The parameters evaluated in this study were the location of the implants in the mandible, implant length, anatomical relationship of the implant with the mandibular canal, presence or absence of damage to the adjacent teeth, presence or absence of implant fractures, and presence or absence of bone support. Fisher's exact test was performed to compare the variables. The significance level was set at p = 0.05. Results: Out of 2,872 CBCT scans, 214 images of patients with an average age of 44.5 years were included. The most frequent location of the implants was the posterior region (93.5%), with 54% of the implants having a length between 9 and 14 mm. It was found that 92% of the implants were positioned above the mandibular canal. Three damage to adjacent teeth was observed, with no correlation with the implant positioning (p = 0.999). In 100% of cases of implants in the anterior region, there was bone support. Fracture was observed in 1.7% of implants with a length between 9- and 14-mm. Conclusions: The installation of implants in the mandible occurs more frequently in the posterior region, with a high presence of bone support and a low incidence of damage to adjacent teeth, anatomical structures, and fractures.

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a heterogeneous group of cancers with distinct molecular characteristics in each anatomic and pathological subtype. The pathological classification of BTC includes grossly classifiable growth patterns, such as mass-forming, periductal infiltrating, and intraductal growing. The small duct and large duct types of intrahepatic cholangiocarcinoma have been recently introduced in the WHO classification. Typical clinical presentations and various radiological, endoscopic, and molecular modalities for diagnosis are described in detail. To overcome the limitations of traditional tissue acquisition, new diagnostic modalities are being investigated. In fact, the treatment landscape is evolving rapidly owing to the emergence of distinct subgroups harboring unique molecular alterations with corresponding targeted therapies. In addition, we highlight the key points in the diagnostic process in real-world clinical practice for biliary tract cancer.

This critical review revisited the new classification system for periodontitis, specifically for staging, suggesting modifications, and introducing a new flowchart for a better clinical evaluation. It evaluated articles published between 2018 and 2024 in the English language, which had an educational motivation focused on staging periodontitis. PubMed/MEDLINE, Web of Science, and Embase databases were used to retrieve the articles. The focus questions involved the analysis of all parameters for staging periodontitis. A total of 836 articles were initially found; 388 duplicated were excluded; 448 were evaluated by title and abstract; 26 articles followed for full-text reading, and 6 articles were included in this critical review (k=0.98). All articles included detailed parameters and steps about how to diagnose periodontitis. Therefore, it was possible to observe instability and “gray zones” in the staging step, which was due to a lack of priority and an organized order sequence. This review suggests the severity parameters cannot be overcome by complexity parameters, following a cumulative sequence: CAL (1^st), RBL (2^nd), TLP (3^rd), and, after, complexity parameters. An exception must be permitted only for complexity factors between Stages III and IV that can change the initial Stage (III or IV) obtained through the severity analysis, but only between themselves. Moreover, for patients without tooth loss or with TLP of ≤4 teeth (without need for complex rehabilitation) and presenting any type of drifting or flaring or a secondary traumatic occlusion, it cannot be a justification for moving the diagnosis from Stage III to Stage IV.

Our target point within this following steps, is prostate cancer. Prostate cancer is classified structurally, by its Gleason Score. Phosphatases are implicated in differents cell alterations, including proliferation, differentiation and carcinogenesis. In specific life circumstances, proteins are regulators with implications in intracellular signaling pathways. Alterations in phosphatases functionality represent a key point in malignancy development. We try within our description, to focus on an important process refering to dysregulation of phosphatase activity. More than, we will discuss therapeutic key points refering to compounds that inhibits phosphatase proteins with implications in carcinogenesis. Researchers try to investigate and to conclude on prostate cancer using also genomic analyses, clinically useful biomarkers and imagistic methods. So finally after folowing describtion steps, purposed aim is to conclude on prostate cancer and different key points abordation.

HIV infection is a nowadays pathology that affect persons from all of the world. Pathogenesis of the HIV-infection and cancer is a great problem, with a complexity directions in research. More important in HIV infection to patients, is also to take into consideration others things, such as prevention, diagnosis, monitoring, treatment, including control measures. This previously mentioned, should be supported by statistical studies that report on restricted or extended geographical areas, to the level of social class and age. In our written text we try to describe from our opinion, strategies in HIV, infection, status knowing as a social and as a healthcare problem.

Background: Differentiating essential tremor (ET) and functional tremor (FT) remains challenging due to their overlapping clinical presentations. Objective: In this study, we aimed to elucidate the demographic and psychometric differences between the aforementioned tremor types to enhance the diagnostic accuracy and therapeutic strategies. Methods: In this prospective study, we included 96 patients diagnosed with ET or FT and analysed their related demographic data, clinical symptoms, and psychometric evaluation scores. Our statistical analysis involved Pearson’s chi-square tests, Fisher’s exact tests, and logistic regression to assess how the different variables impact tremor diagnosis. Results: Our study demonstrated a higher ET prevalence in males (p = 0.015). Furthermore, we demonstrated that patients with ET displayed a significantly lower body mass index and a lower age of onset compared to those with FT (p = 0.050 and p = 0.023, respectively). Our psychometric assessments revealed higher cognitive and body image scores in patients with ET, whereas those with FT scored higher on depression and anxiety scales. The misdiagnosis rate was 14.5%, emphasising the need for improved diagnostic criteria. Conclusions: We established specific demographic and psychometric distinctions between ET and FT, which could potentially benefit clinicians in making accurate diagnoses and tailoring treatment approaches. These findings support the inclusion of comprehensive psychometric evaluations into standard diagnostic procedures to better differentiate tremor types.

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo wheat allergen-specific skin prick test (SPT), blood test for serum immunoglobulin E (sIgE) levels or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its novel diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis and basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability and safety of related clinical trials will then be discussed.

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 self renewal. Based on the observation that differentiation of adult stem cells into specific derivative scan 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. As an interdisciplinary field of research, regenerative medicine, play a great role in tissues and organs damaged reparation with a higher potential in transplantation if necessary.

Vibration signal analysis is regarded as a fundamental approach in diagnosing faults in rolling bearings, and recent advancements have shown notable progress in this domain. However, the presence of substantial background noise often results in the masking of these fault signals, posing a significant challenge for researchers. In response, an Adaptive Denoising Autoencoder (ADAE) approach is proposed in this paper. The data representations are learned by the encoder through convolutional layers, while the data reconstruction is performed by the decoder using deconvolutional layers. Both the encoder and decoder incorporate adaptive shrinkage units to simulate denoising functions, effectively removing interfering information while preserving sensitive fault features. Additionally, dropout regularization is applied to sparsify the network and prevent overfitting, thereby enhancing the overall expressive power of the model. To further enhance ADAE's noise resistance, shortcut connections are added. Evaluation using publicly available datasets under scenarios with known and unknown noise demonstrates that ADAE effectively enhances the signal-to-noise ratio in strongly noisy backgrounds, facilitating accurate diagnosis of faults in rolling bearings.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

The aim of this article is to identify the best available evidences analyzing liver samples, normall and pathological. In the study were used liver samples, collected during necropsy, from healthy patients and from patients diagnosed with cirrhosis .This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. Were made permanent preparations and used Hematoxylin–Eosin staining and other special stainings for structural observations at optical microscope using lens with differents magnifications, such us x10 and x40.

Classifying network flow subsequences in an Industrial IoT gateway is an effective method for identifying Industrial IoT faults. This paper proposes a subsequence classification algorithm SSGBUL-IKNN based on unsupervised learning encoding to address the problem of low classification accuracy. Firstly, we built a network module based on unsupervised learning to encode the flow sequence of the Industrial IoT gateway. In the encoding module, a subsequence calibration algorithm controls the increasing error during the coding process. Then, the specific fault type is obtained through an improved KNN classification algorithm based on the indication distance source from the integrated coding sequences converted by multi-dimensional network flow sequences. The test result on three Industrial IoT datasets of a sewage treatment plant shows that the accuracy of SSGBUL-IKNN in this paper exceeds 92%, significantly higher than the algorithm DTW and TSF. It reaches the classification requirements of Industrial IoT fault diagnosis.

Intelligent fault diagnosis techniques have replaced the time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning model can improve the accuracy of intelligent fault diagnosis with the help of its multilayer nonlinear mapping ability. This paper has proposed a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in first convolutional layer for extracting feature and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform state of the art DNN model which is based on frequency features under different working load and noisy environment.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. Postmortem confirmation of rabies traditionally involves invasive brain tissue testing, a process met with resistance from deceased patients' families, impeding consent. This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. This method preserves the cadaver's integrity, potentially easing family reluctance towards autopsies. The limited testing of both human and animal rabies in Ghana highlights the challenges in diagnosing this fatal disease. Scarce diagnostic resources and the complexity of obtaining brain tissue samples exacerbate the issue. Cultural and religious beliefs surrounding autopsies contribute to familial hesitation, viewing these procedures as disruptive and disfiguring, further complicating consent. The transnasal technique involves approaching the brain tissue through the nostrils and cribriform plate without any superficial manipulation of the patient's head and face, thereby preserving aesthetics and natural features of the person. Technological advancements and seamless One Health collaboration among governmental, non-governmental, and research entities locally and globally culminated in Ghana's first confirmed rabies diagnosis using this method of brain tissue collection. This success emphasizes the efficiency and feasibility of transnasal brain collection approach and the invaluable role of the One Health approach and collaborative efforts in overcoming diagnostic challenges in rabies control.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

Ensuring optimal performance and reliability in rotor-bearing systems is crucial for industrial applications. Imbalance and shaft bow in these systems can lead to decreased efficiency and increased vibrations. Early detection and mitigation of a rotor’s faults are essential, and model-based fault identification has gained much attention in the manufacturing industry for years. Over the past two decades, however, the development of fault diagnosis rules with data-driven and artificial intelligence (AI) has become a trend, and in the foreseeable future, AI combined with big data will become mainstream. Nevertheless, the critical role of rotating machinery in manufacturing introduces a challenge, as the availability of fault data is often insufficient. This limitation renders the establishment of diagnostic rules using data-driven methods and AI technologies impractical. In light of these challenges, this study proposes a novel hybrid approach, that combines a physical model with machine learning (ML) techniques for the diagnosis of multi-faults (imbalance and shaft-bow demonstrated) in a Jeffcott rotor. To overcome the lack of real-world faulted, labeled datasets, a physics-based Jeffcott rotor model is first derived and then used to generate abundant fault datasets for ML. Subsequently, simulated data are employed for the training of an artificial neural network (ANN), enabling the network to learn from and analyze the vast array of generated data. The results prove that a well-trained feed-forward neural network (FNN) can accurately isolate and diagnose the imbalance and shaft-bow faults using the simulated data and the real data from the Jeffcott rotor experiment. These physics-based and ML approaches prove effective particularly for multi-fault, offering new possibilities for advanced rotor system monitoring and maintenance strategies in industrial applications.

Objective: Evaluation of patients with prosthetic valves who developed infective endocarditis by comparing treatment outcomes in both early- and late-onset IE episodes following prosthetic valve replacement surgery. This study sought to conduct a comprehensive assessment of the efficacy of these methodologies. The insights derived from this assessment will be utilized to enhance the quality of care for individuals with infective endocarditis who have received prosthetic valve replacement surgery. Results: During the period of investigation (January 2018 - December 2022), 78 patients diagnosed with infective endocarditis (IE) on prosthetic valve were admitted to the Infectious Diseases Department of the "Dr. Carol Davila" Central Military Emergency University Hospital in Bucharest. In 28 cases (35.8%), the onset of PVE occurred within 12 months of surgery (early onset), whereas in 50 patients (64.2%), the onset occurred more than 12 months after surgery (late onset). The mortality rate was 35.9% (53.6% among the early onset patients and 26% among the late-onset patients). Among patients who received surgical and medical therapy, the mortality rate was 29.6%, whereas among those who underwent only medical therapy, a 39.2% mortality rate was reported. According to the extracted data, antibiotic therapy was successful in 72.6% of patients. In contrast, a combination of surgical and drug-based approaches resulted in a cure in 76.1% of the patients. The most common etiological agent was Staphylococcus aureus (38.5%), followed by Enterococcus faecalis (26.9%), and Streptococcus mitis (10.3%). The mortality rate of patients with S. aureus was 29.2%, indicating the severity of this infectious agent. Conclusions: Prosthetic valve endocarditis (PVE) is a serious condition associated with a high mortality rate both in the short and long term. Regardless of the therapy used, the risk of death remains high. All patients with PVE who survived received effective early treatment, highlighting the need for prophylactic measures.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

Rocky Mountain or Brazilian spotted fever, caused by Ricketsia ricketssi, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Rapid detection are essential for a better prognosis and survival rate of the infected individual. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. Therefore, this review aimed to identify methods for antibody or antigen detection, its gaps, and evolution over time. A search was conducted to find all studies in the Pubmed database that described antibody or antigen detection for Ricketsia ricketsii infection. Initially, a total of 403 articles were screened. Of these articles, only 19 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as low specificity using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective Ricketsia ricketssi infection diagnosis.

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

This work presents a Fault-Tolerant Model Predictive Control (FTMPC) algorithm applied to a simulation model for sewer networks. The control system will aim to prevent contaminated water from escaping the network, especially during periods of heavy rainfall, that can cause combined sewer overflows (CSO), while maintaining the flow of water towards the wastewater treatment plant (WWTP) as close as possible to its nominal value. The main purpose of the work is to preserve the operation of the predictive controller as much as possible, in accordance with its operational objectives, when there may be anomalies affecting the elements of the control system, mainly sensors and actuators. Comparing the results obtained considering various types of faults, with situations of normal controlled operation and with the behavior of the sewer network when no control is applied, will allow some conclusions to be drawn at the end.

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries resulting either in pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, while timely diagnosis is challenging due to the nonspecific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about the abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions and is important for the radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis.

Objective: The aim of our study was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Results: There was a statistically significant age difference between the two study periods, both by the average age of patients and by age group. The mean difference was 32 years before the pan-demic and 35 years during the pandemic (p-value >0.05). The majority of patients presenting for investigations before and during the pandemic were in the 30-39-year-old age group (31.95%, respectively; 34.2% (p-value = 0.003). The biggest patient loss ratio identified by age group was in the 50–59 years: 14,53% in the pre-pandemic period and 9,1% in the pandemic period. In the pan-demic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the prepandemic period, with an increase in more severe lesions in the pandemic period, has a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusion: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervicorrhagia as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

An increasing need for better agricultural practices that are sustainable to provide increased yields of crops for the ever increasing food demand to be met for the growing world population is a current necessity. It is estimated by the UN that in 2050 the world’s populace may be as much as 9.8 billion global, yet, farmers still face several obstacles, which includes soil degradation, extreme temperatures, and drought which as increasingly becoming more severe with climate changes. Plant health monitoring is a method that will help to increase awareness about plant enhancing by studying how to increase crop yields while decreasing the environmental impacts. The use of low-cost, controlled environments, soil quality, water levels, and pathogenic and pests attacks can be regularly monitored. Currently, several diagnostic technologies and portable point-of-use methods and technologies are employed for detection of diseases, although, the current available lab-based methods used for plant’s diagnostics test are inadequate for plant point-of-use monitoring. The promotion of use of these point of use methods will enable pathogen detection, poor plant growth, unsuitable environmental conditions and nutrient use efficiency allowing for immediate and timely corrective actions to ensure minimal damage to the plants with maximal yield. Increase in the use of sustainable agri practices are required for ensuring higher yields with minimal inputs and that are non-destructive to the land and the use of improved methodologies and technologies will be useful tools for achieving sustainable agriculture.

Keywords: domain adversarial; channel reconstruction; transfer learning; fault diagnosis

Breast cancer stands as a predominant health concern for women globally. As mammography is the primary screening tool for breast cancer detection, improving the detection of breast cancer at screening could save more lives. This mammography re-view paper provides a systematic review of computer-aided techniques during a specific time frame for the segmentation and classification of microcalcification, evaluating image processing, machine learning, and deep learning techniques. The systematic review is meticulously carried out, adhering closely to the preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This article focuses on mammographic breast cancer detection approaches based on automated systems, discussed chronologically from 1970 through 2023. This article encompasses the breadth of artificial intelligence-based methods from the most primitive to the most sophisticated models. Image processing and machine learning-based methods are compre-hensively reviewed. The evaluation of a deep learning architecture based on self-extracted features for classification tasks demonstrated outclass performance. Large-scale datasets required for a broader and in-depth analysis of novel methods for breast cancer detection are also discussed in this article. This research work is aligned with the United Nations' sustainability de-velopment goals.

Splenic rupture and hematoma are significant complications that can arise in patients with non-Hodgkin lymphoma (NHL). Understanding these associations is essential for optimal patient management and patients' enhancing outcomes. Histopathological and immunohistochemistry analyses are crucial in diagnosing NHL and assessing splenic involvement. A judicial autopsy was requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from the gurney, reporting a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. Abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy, but the patient showed signs of hemodynamic shock and subsequently died. The evidence emerging from the autopsy allowed us to diagnose a Mantle Cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess splenic rupture's diagnosis and time estimation. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering underlying hematological malignancies when investigating delayed splenic rupture. Immunohistochemical study of spleen samples allowed the assessment of the timing of splenic hematoma and rupture, leading to establishing a causal relationship with trauma.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there is no data on cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, recombinant OHFV NS1 protein was produced using Escherichia сoli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. Western blot analysis and ELISA of recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown not to be cross-reactive to OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to OHFV NS1 protein were not detected in the sera of TBE patients whereas the sera contained antibodies to TBEV NS1 protein.

(Background) Canine mammary tumors (CMT) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) and their protein cargo have recently gained attention as potential tools for disease screening and monitoring. (Objectives) This study aimed to isolate SEVs from canine patients and analyze their proteomic profile to assess their diagnostic and prognostic potential. (Methods) Plasma samples were collected from female dogs grouped into CMT (malignant and benign), healthy controls, relapse, and remission groups. SEVs were isolated and characterized using ultracentrifugation (UC), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Proteomic analysis of circulating SEVs was conducted using Liquid Chromatography–Mass Spectrometry (LC–MS). (Results) While no significant differences were observed in the concentration and size of exosomes among the studied groups, proteomic profiling revealed important variations. Mass spectrometry identified exclusive proteins that could serve as potential biomarkers for mammary cancer. These included Inter-alpha-trypsin inhibitor heavy chain (ITIH2 and ITI4), phosphopyruvate hydratase or alpha enolase (ENO1), eukaryotic translation elongation factor 2 (eEF2), actin (ACTB), transthyretin (TTR), beta-2-glycoprotein 1 (APOH) and gelsolin (GSN) found in female dogs with malignant tumors. Additionally, Vitamin D-binding protein (VDBP), also known as group-specific component (GC), was identified as a protein present during remission. (Conclusion) The results underscore the potential of proteins found in SEVs as valuable biomarkers in CMT. Despite the lack of differences in vesicle concentration and size between the groups, the analysis of protein content revealed promising markers with potential applications in CMT diagnosis and monitoring. These findings suggest a novel approach in the development of more precise and effective diagnostic tools for this challenging clinical condition.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

Abstract Introduction: Although ankle fractures and Achilles tendon injuries are among the most common traumatic presentations when they occur individually, concomitant Achilles tendon rupture and ipsilateral ankle fractures are quite unusual. To our knowledge this is the first report of acute Achilles tendon rupture associated with missed ipsilateral closed bimalleolar ankle fracture. Case Presentation: A 34 years old male patient presented with a traumatic right Achilles tendon rupture after sustaining road traffic accident one day prior. There was an open wound over the tendon substance with absent active plantaflexion of the involved leg. After confirming complete Achilles tendon rupture with positive Thompson test, the patient was prepared for emergency debridement and possible tendon repair differing imaging studies, which missed ipsilateral closed bimalleolar ankle fracture. Conclusion: Routine anteroposterior and lateral X-rays should be used in conjunction with a complete history and physical examination to detect any concomitant fracture with open Achilles tendon rupture.

System level diagnosis is an abstraction of high level and, thus, its practical implementation to particular cases of complex systems is the task which requires additional investigations, both theoretical and modeling. Mostly, diagnosis at system level intends to identify only permanently faulty units. In the paper, we consider the case when both permanently and intermittently faulty units can occur in the system. Identification of intermittently faulty units has some specifics which we have considered in this paper. We also suggest the method which allows distinguishing among different types of intermittent faults. Diagnosis procedure was suggested for each type of intermittent faults.

Tuberculosis (TB) is an infectious disease of global public health importance, caused by the Mycobacterium tuberculosis complex. Despite advances in diagnosis and treatment, this disease has worsened with the emergence of multidrug-resistant strains of tuberculosis We aim to present and review the history, progress, and future directions in the diagnosis of tuberculosis by evaluating the current methods of laboratory diagnosis of tuberculosis, with a special emphasis on microscopic examination, cultivation on solid and liquid medium, as well as an approach to molecular assays. The microscopic method, although widely used, has its limitations, and the use and evaluation of other techniques are essential for a complete and accurate diagnosis. Bacterial culture, both in solid and liquid mediums, are essential methods in the diagnosis of TB. Culture on solid medium provides specificity and accuracy, while culture on liquid medium brings rapidity and increased sensitivity. Molecular tests such as LPA and Xpert MTB/RIF have been found to offer significant benefits in the rapid and accurate diagnosis of TB, including drug-resistant forms. These tests allow the identification of resistance mutations and provide essential information for choosing the right treatment. We conclude that combined diagnostic methods, using several techniques and approaches, provide the best result in the laboratory diagnosis of TB. Improving the quality and accessibility of tests, as well as the implementation of advanced technologies, is essential to help improve the sensitivity, efficiency, and accuracy of TB diagnosis.

Autoimmune hemolytic anemias (AIHAs) are conditions whereby a person produces an antibody to their own red blood cells (RBCs). These conditions can be primary with unknown cause or secondary, associated with diseases or infections. There are seven different categories of AIHA, warm-antibody AIHA (wAIHA); cold-antibody AIHA that includes cold agglutinin syndrome (CAS) and cold agglutin disease (CAD); mixed AIHA, also called combined cold and warm AIHA; paroxysmal cold hemoglobinuria (PCH) also termed Donath-Lansteiner test-positive AIHA; direct antiglobulin test-negative AIHA (DAT-neg AIHA); drug-induced immune hemolytic anemia (DIIHA); and passenger lymphocyte syndrome. This review will discuss each of these AIHAs and provide information on diagnosis and treatment.

Microwave radiation diagnosis technology can detect thermal changes in skin tissue earlier than anatomical changes, but its detection accuracy is limited by non-target radiation interference in the measurement environment, additional measurement errors of system units, and energy scattering and transmission between skin tissues. This paper aims to address the scientific challenges of analyzing the forward and inversion modelling detection mechanism of layered accurate temperature measurement of human skin tissue based on multi-band. The study focuses on the construction of a pencil beam antenna optimization system, the optimization strategy of high-sensitivity correlated radiometer architecture, and the high-precision multi-band forward and inversion modelling detection algorithm. The key technologies include: (1) A new method of integrated modeling and multi-index optimization of antenna with high directivity and small aperture is proposed, and a priori knowledge-guided neural network of pencil beam distribution is constructed to realize the inversion model of antenna structural parameters; (2) The influence mechanism of high sensitivity correlated radiometer architecture error is analyzed, and a periodic phase shift error correction algorithm based on uniform polar circle is designed; (3) Combining deep learning theory and hyperparameter optimization framework, an iterative model is established, and the objective function modified by the penalty factor is defined to realize a new detection method combining forward and inversion. This paper presents a theoretical foundation for the industrialization of microwave radiation diagnostic technology.

Many physiotherapy treatments begin with a diagnosis process. The patient describes symptoms, upon which the physiotherapist decides which tests to perform until a final diagnosis is reached. The relationships between the anatomical components are too complex to keep in mind and the possible actions are abundant. A trainee physiotherapist with little experience naively applies multiple tests to reach the root cause of the symptoms, which is a highly inefficient process. This work proposes to assist students in this challenge by presenting three main contributions: (1) A compilation of the neuromuscular system as components of a system in a Model-Based Diagnosis problem; (2) The PhysIt is an AI-based tool that enables an interactive visualization and diagnosis to assist trainee physiotherapists; and (3) An empirical evaluation that comprehends performance analysis and a user study. The performance analysis is based on evaluation of simulated cases and common scenarios taken from anatomy exams. The user study evaluates the efficacy of the system to assist students in the beginning of the clinical studies. The results show that our system significantly decreases the number of candidate diagnoses, without discarding the correct diagnosis, and that students in their clinical studies find PhysIt helpful in the diagnosis process.

Volunteering has many social, emotional and health benefits and could be an option for people with younger/early onset dementia to engage in stage/age-appropriate, personally meaningful activity within their local community. Audio data of people with young onset dementia discussing their volunteering experiences were taken from the Dementia Diaries and co-analysed. This study explored how people with dementia volunteer in the UK, the benefits and barriers, and how we can improve access to volunteering opportunities. The findings suggest that stigma is the overarching concept (or net) which influences people’s experiences of volunteering with dementia. Within the stigma net, three themes were developed that employed a lifespan approach to challenging said stigma: 1) Valuing the past, 2) Valuing the present and 3) Valuing the future, each with additional subthemes. This research contributes to the limited pool of literature that highlights the clear benefits of volunteering for people with young onset dementia, while also considering how dementia stigma can create practical and institutional barriers to accessing volunteering. Guidance is provided for how to deliver meaningful and accessible volunteering opportunities.

Tuberculosis (TB) is an infectious disease declared a global emergency by the World Health Organization and continues as one of the world’s top ten causes of death. TB diagnosis is more critical in developing countries where demanded infrastructure for detection, and treatment complicates the efforts against the disease. These aspects related to limited resources are significant, especially in areas away from the main cities, with few mechanisms to make a timely diagnosis that contributes to successfully addressing the possible patients. Artificial intelligence has begun to be essential in providing additional strategies in the diagnosis processes for health professionals’ support. This paper uses natural language processing (NLP) and machine learning (ML) techniques to create models that can supply TB diagnosis when the needed infrastructure is unavailable. Two different sources were explored: text extracted from electronic medical records (EMR) and patient clinical data (CD). Four proposals using five different machine learning models were implemented. The first two models employed ML and each data source independently. Then, two additional approaches developed a data fusion from both sources. This strategy’s employment was analyzed with physicians according to their pertinence in the process and understanding of the EMR. Finally, the results of the data fusion were compared to each source, obtaining better performance at using only the CD, where an area under the ROC curve of 69.9±2.3% was obtained. However, the advantage of analyzing physician’s reports is the availability of this information contrasted to clinical-specific data, which can be more useful in places far from the main cities without enough basic structure for its obtaining.

Advances in gastric cancer screening and endoscopic technology have made it possible to detect and treat gastric cancer at an early stage. As a result, about 40% of all gastric cancers have now been resected by endoscopic treatment in Japan. In endoscopic diagnosis, magnifying endoscopic observation using band-limited light such as narrow band imaging (NBI) has significantly improved the accuracy of gastric cancer diagnosis. At the same time, in endoscopic treatment, endoscopic submucosal dissection (ESD) has contributed to increase explosively the number of gastric cancers which could be resected endoscopically. In recent years, the construction of algorism for endoscopic diagnosis and treatment with a view to personalized medicine has been explored, and endoscopic use for gastric cancer managements is expected to develop further in the future. Keywords (5 words):

This study examined ways to prevent failures in the front-end of forklifts by addressing the center of gravity of heavy objects carried by forklifts, predicting the remaining useful lifetime (RUL), and the fault diagnosis based on alarm rules. In the research process, acceleration signals were acquired from the outer beam of the front-end of the forklift. A one-second window was applied to extract the time-domain statistical features, which were then set as variables. An exponentially weighted moving average was used to smooth the noise in the feature data set. The AWGN and LSTM autoencoders were used for data augmentation. Based on them, random forest and lightGBM models were used to develop classification models for the weight center of heavy objects carried by a forklift. In addition, contextual diagnosis performed by applying exponentially weighted moving averages to the classification probabilities of the machine learning models showed that random forest achieved an accuracy of 0.9563 and lightGBM achieved an accuracy of 0.9566. In addition, the acceleration data were collected through experiments to predict forklift failure and RUL because of the repeated forklift use when the center of heavy objects carried by the forklift was skewed to the right. The time-domain statistical features of the acceleration signals were extracted and set as variables by applying a 20-second window. Subsequently, logistic regression and random forest models were used to classify the failure stages of the forklifts. The f1-score (macro) obtained were 0.9790 and 0.9220 for logistic regression and random forest, respectively. In addition, the random forest probabilities for each stage were combined and averaged to generate a degradation curve and derive the failure threshold. The coefficient of the exponential function was calculated using the least squares method on the degradation curve, and the RUL prediction model was developed to predict the failure point. In addition, the SHAP algorithm was used to identify the significant features in classifying the stage. The alarm rule-based fault diagnosis was performed using the threshold of the normal stage distribution of the significant features.

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

Bearing component damage contributes significantly to rotating machinery failures. It is vital for the rotor-bearing system to be in good condition to ensure proper functioning of the machine. Over recent decades, extensive research has been devoted to the condition monitoring of rotational machinery, with a particular focus on bearing health. This paper provides a comprehensive literature review of recent advancements in intelligent condition monitoring technologies for rolling element bearings. Fundamental monitoring strategies are introduced, covering various sensing, signal processing, and feature extraction techniques for detecting defects in rolling element bearings. While vibration-based monitoring remains prevalent, alternative sensor types are also explored, offering complementary diagnostic capabilities or detecting different defect types compared to accelerometers alone. Signal processing and feature extraction techniques, including time domain, frequency domain, and time-frequency domain analysis, are discussed for their ability to provide diverse perspectives for signal representation, revealing unique insights relevant to condition monitoring. Special attention is given to information fusion methodologies and the application of intelligent algorithms. Multisensor systems, whether homogeneous or heterogeneous, integrated with information fusion techniques, hold promise in enhancing accuracy and reliability by overcoming limitations associated with single sensor monitoring. Furthermore, the adoption of AI techniques, such as machine learning and metaheuristic optimisation, has led to significant advancements in condition monitoring, yielding successful outcomes in various studies. Finally, avenues for further advancements to improve monitoring accuracy and reliability are identified, offering insights into future research directions.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, we present a comprehensive approach utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets are based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH Dataset, we deployed an ensemble strategy incorporating VGG16 and ResNet50 architec-tures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique, to preprocess a high-resolution image, which facilitates focused analysis of localized regions of interest. The annotated BACH dataset encompasses 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, we employed the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify mi-croscopic images into eight distinct categories (four benign and four malignant). For both models we leveraged a five-fold cross-validation approach for rigorous training and testing. Preliminary ex-perimental results indicate a Patch classification accuracy of 95.31% (on BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to on-going endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

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.

With recent focus on deep neural network architectures for development of algorithms for computer-aided diagnosis (CAD), we provide a review of studies within the last 3 years (2015-2017) reported in selected top journals and conferences. 29 studies that met our inclusion criteria were reviewed to identify trends in this field and to inform future development. Studies have focused mostly on cancer-related diseases within internal medicine while diseases within gender-/age-focused fields like gynaecology/pediatrics have not received much focus. All reviewed studies employed image datasets, mostly sourced from publicly available databases (55.2%) and few based on data from human subjects (31%) and non-medical datasets (13.8%), while CNN architecture was employed in most (70%) of the studies. Confirmation of the effect of data manipulation on quality of output and adoption of multi-class rather than binary classification also require more focus. Future studies should leverage collaborations with medical experts to aid future with actual clinical testing with reporting based on some generally applicable index to enable comparison. Our next steps on plans for CAD development for osteoarthritis (OA), with plans to consider multi-class classification and comparison across deep learning approaches and unsupervised architectures were also highlighted.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Lung cancer is one of the leading causes of cancer-related mortality globally. Pulmonary nodules are one of the risk factors and their discovery rate has been increasing. Based on the nodule size and growth rate, their malignancy propensity is determined; however, it is very challenging to distinguish between benign and cancerous nodules. Many tumour-associated antigens (TAA) have been studied as blood biomarkers for lung cancer, most commonly the Cytokeratin 19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC Ag), carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA). Due to their low sensitivity, TAAs are not recommended as tools for the early detection of lung cancer. However, cancer testis antigens (CTAs) are highly specific for carcinomas but their expression is more commonly associated with advanced stages of cancer and poor prognosis. Despite the fact that TAAs may provide useful insights for the diagnosis and prognosis of early lung cancer, their potential to do so has yet to be demonstrated.

The number of XLPE cables being used near or beyond their designed lifespan is increasing. The importance of timely cable replacement is increasing. Therefore, research is actively being conducted using VLF Tan δ diagnostic technology to assess the insulation condition of cables. There is a lack of studies measuring and analyzing VLF Tan δ of service aged XLPE cables. Additionally, there is a lack of research considering the operating environment. Therefore, research is needed to diagnose and analyze the insulation condition of the same serviced aged cable when it is operated in a different environment. This paper evaluates and analyzes the insulation condition of cables installed in the BFP, cooling tower, and deaerator booster pump of a combined heat and power plant. Each cable was analyzed by measuring VLF Tan δ, dielectric breakdown test of the cable, and tensile strength, elongation at break, crystallinity, and dielectric strength of XLPE specimens. Additionally, the correlation between VLF Tan δ and other characteristics was also analyzed. It was found that degradation progressed in the order of BFP, cooling tower, and deaerator booster pump. Therefore, it was confirmed that even for the same cable, deterioration varies depending on the installation location.

The patellofemoral joint (PFJ) is a complex articulation between the patella and the femur, in-volved in the extensor mechanism of the knee. Patellofemoral disorders can be classified into ob-jective patellar instability, potential patellar instability, and patellofemoral pain syndrome. An-atomical factors such as trochlear dysplasia, patella alta, and tibial tuberosity-trochlear groove (TT-TG) distance contribute to instability. Patellofemoral instability can result in various types of dislocations, and the frequency of dislocation can be categorized as recurrent, habitual, or per-manent. Primary patellar dislocation requires diagnostic framing, including physical examina-tion and imaging. Magnetic resonance imaging (MRI) is essential for assessing the extent of damage, such as bone bruises, osteochondral fractures, and medial patellofemoral ligament (MPFL) rupture. Treatment options for primary dislocation include urgent surgery for oste-ochondral fragments or conservative treatment for cases without lesions. Follow-up after treat-ment involves imaging screening and assessing principal and secondary factors of instability. Detecting and addressing these factors is crucial for preventing recurrent dislocations and opti-mizing patient outcomes.

SARS-CoV 2 also known as COVID-19 is a fast spreading coronavirus related disease that emerged from China in December 2019 and is currently attained the status of a pandemic. There are currently no drugs/ vaccines against the same and moreover limited diagnostic tests to identify the infection. Additionally, these tests are expensive and hence are exclusive for very highly suspected cases of the disease especially in developing countries. This is causing an under-diagnosis which is an alarming state of affairs, as even a single missed SARS-CoV 2 case would spread the disease exponentially and keep it in the community. Through this entirely in silico study, we have developed a cheaper and faster diagnostic method based on simple PCR and restriction enzyme digestion, commonly used in restriction fragment length polymorphism (RFLP) tests. Through comparative genomics, we found the closest neighbours of SARS-CoV 2 then found the highly conserved regions of the genome which were absent in SARS-CoV 1, its closest neighbour. Then we found restriction sites for various enzymes followed by designing of PCR primers flanking those sites. We have found the primer pair to produce a 401 bp amplicon and when digested by SwaI enzyme, it produces two fragments of lengths 216 bp and 185 bp. As an internal control, GAPDH primers are pooled with the SARS-CoV 2 primers as the patient sample will also include human RNA mixed with the viral RNA. This primer pair gives an amplicon of 131 bp and hence a negative sample should show a single band of 131 bp while a positive digested sample will give three bands of 401 bp, 216 bp and 131 bp. The primers are specific to SARS-CoV 2 only and can additionally be used for SYBR green based real time quantification of viral load. The developed tests have not yet been tested in vitro due to stressed out working hours in the only pathogenic virus handling laboratory in our institute. Nonetheless, this study works as a head start for other laboratories to rapidly test the suggested protocols in vitro and make available a cheaper alternative test for SARS-CoV 2 which would especially be beneficial for the lower to middle income countries.

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram) and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests such as RT-QuIC is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain among others) to try to universalize access to early diagnosis in the case of prion diseases.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

Background: Esophageal cancer was hardly diagnosed in early stage, and more potential biomarkers should be found. Methods: 252 patients and normal controls which recruited in Renmin Hospital of Wuhan University, were divided into esophageal carcinoma group (105 cases), disease control group (75 cases) and the control group of healthy people (72 cases). Moreover, TISIDB and GEPIA databases were used to investigate the different expression of EC and normal tissues, and explore the roles of C1q in tumor-immune system interactions in EC. Results: The concentration of serum C1q in EC group is 196.8(180~219.4) mg/L, which is higher than the level of DC [178.10(153.70~200.85) mg/L]and HC [183.00(167.75~201.00) mg/L] (P<0.05). A higher expression level of C1q was observed in Ⅲ and Ⅳ grades [214(192~237.3) mg/ml] than grades Ⅰ and Ⅱ [180.95(172.03~193.85) mg/L] (P<0.05). C1q was positively correlated with eosinophils, active CD8 T cells, myeloid derived suppressor cells, natural killer cells, monocytes and macrophages (r = 0.373; r = 0.659; r = 0.846; r = 0.760; r = 0.499; r = 0.757; P<0.05). Conclusion: The concentrations of C1q increased in EC and related to the severity of EC, which had potential value of diagnosis of EC. There were correlations in C1q and tumor-infiltrating lymphocytes.

Properties of time domain parameters of the vibration signal have been extensively studied for the fault diagnosis of rolling element bearings (REB). Parameters like kurtosis and Envelope Harmonic-to-Noise Ratio are most widely applied in this field and some important progress has been made. However, since only one-sided information is contained in these parameters respectively, problems still exist in practice when the signals collected are of complicated structure and/or contaminated by strong background noises. A new parameter, named Shock pulse index (SPI), is proposed in this paper. It integrates the mutual advantage of both parameters above and can help effectively identify fault related impulse components under the interference of strong background noises, unrelated harmonic components and random impulses. The SPI optimizes the parameters of Maximum Correlated Kurtosis Deconvolution (MCKD), which is used to filter the signals under consideration. Finally, the interested transient information contained in the filtered signal can be highlighted through demodulation with Teager Energy Operator (TEO). Fault related impulse components can therefore be extracted accurately. Simulations and experiment analyses verify the effectiveness and correctness of the SPI.

A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This narrative collects most of them from a clinical and pathologic perspective offering urologists and general pathologists their most salient definitory features. Together with classical, well-known, entities such as urothelial papillomas (conventional and inverted), nephrogenic adenoma, polypoid cystitis, fibroepithelial polyp, prostatic-type polyp, verumontanum cyst, xanthogranulomatous inflammation, reactive changes secondary to BCG instillations, schistosomiasis, keratinizing desquamative squamous metaplasia, post-radiation changes, vaginal-type metaplasia, endocervicosis/endometriosis (müllerianosis), malakoplakia, florid von Brunn nest proliferation, cystitis/ureteritis cystica and glandularis, among others, still other cellular proliferations with concerning histological features and poorly understood etiopathogenesis like IgG4-related disease, PEComa, and pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodule, inflammatory myofibroblastic tumor), are reviewed. Some of these diagnoses are problematic for urologists, other for pathologists, and still others for both. Interestingly, the right identification of their definitory features will allow their correct diagnoses thus avoiding overtreatment. The literature selected for this review also focuses on the immunohistochemical and/or molecular data useful to delineate prognosis.

Acute pancreatitis (AP) is an inflammatory condition of the pancreas and is one of the most common ailments of the gastrointestinal system that results in significant morbidity and mortality. The main etiologic causes of AP are alcohol consumption, gallstones, hypertriglyceridemia, and biliary stones. The clinical signs and symptoms, and diagnostic criteria of AP are well established in the literature and multiple studies. Multiple scoring systems have been used to predict the severity, prognosis, and mortality associated with AP. The present review of the literature brings to light the significant and recent contributions in the etiology, risk factors, epidemiology, diagnosis, complications, prognosis and newest modalities in treatment that could be beneficial in the management of AP.

Background Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aims to better investigate the performance of NurugoTM. Objectives i) verify whether the NurugoTM can be a communication tool between the General Practitioner (GP) and dermatologist in the first assessment of skin lesions; ii) analyze the degree of diagnostic-therapeutic agreement between dermatologists; iii) estimate the number of potentially serious diagnostic errors. Methods One hundred forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies such as the current pandemic context.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Distinguishing the level of pathology in the lungs through the sound of a cough is a complicated process that includes many factors. This paper explores the challenges of diagnosing lung pathology based solely on cough sounds. It emphasizes that while cough type can offer initial clues, it is just one piece of a complex diagnostic puzzle. For example, the differentiation of dry, productive, barking, hacking, and wheezing coughs provides initial insights into potential pathologies, which can range from respiratory infections to chronic diseases. The examination of cough characteristics, such as frequency, strength, and persistence, aids in identifying the severity of underlying conditions. Moreover, associated respiratory and systemic symptoms further contribute to the diagnostic landscape, with manifestations such as dyspnea, wheezing, chest pain, and hemoptysis offering valuable clinical information. Diagnostic tests, such as imaging studies and laboratory analyses, play a pivotal role in confirming diagnoses. However, challenges in diagnosis based solely on cough sounds require a more holistic approach, taking into consideration the complexity of lung pathologies. The paper concludes that accurately diagnosing lung pathologies based on cough sounds alone is difficult and requires careful consideration of multiple factors and stresses on contextualizing cough characteristics with other clinical features and diagnostic tests for an accurate assessment and comprehensive treatment planning.

Since first described by Dr. Tomisaku Kawasaki in 1967, the clinical diagnosis of Kawasaki disease (KD) has remained relatively unchanged. However, studies since then have suggested that diagnoses using only that original clinical criteria may lead to underdiagnosis. In this review, updated KD diagnostic methods, diagnostic methods for “atypical” KD, diagnostic pitfalls, and other differential diagnoses are discussed. Peripheral blood eosinophil showed important in distinguishing KD from febrile children. We review herein the current literature regarding new biomarkers, scoring systems, and microRNA panels that may aid in the diagnosis of KD, the importance of eosinophil and treatment updates.

Study objective Since December 2019, the coronavirus disease (COVID-19) pandemic has caused over a million deaths and resulted in adverse socio-economic impacts worldwide. However, predictability and prognostication of clinical features vary among different populations. Methods We search PubMed, EMBASE, Cochrane Library, Google Scholar, and WHO Global Health Library from December 2019 to April 2020 for studies reporting the risk factors, clinical features, and outcomes. The random-effect models for transformed prevalence (single-arm) or bivariate random-effect models (sensitivity and specificity) for correlated performance indicators. Results Among the 189 included studies representing 53,659 patients, the most sensitive predictor for COVID-19 infection was fever in adults (83%, 95% confidence interval [CI]:73–90%), and the most specific predictor was fatigue (96%, 95% CI: 80–99%). Fever was the most sensitive symptom in predicting the severity (89%, 95% CI:83–92%), followed by cough (71%, 95% CI:63–78%). The most specific predictor of severe COVID-19 was a chronic obstructive pulmonary disease (99%, 95% CI:98–99%). The stage of the outbreak and age significantly affect the prevalence of fever, fatigue, cough, and dyspnea. Fever, cough, fatigue, hypertension, and diabetes mellitus combined have a 3.06 positive likelihood ratio (PLR) and a 0.59 negative likelihood ratio (NLR) in the diagnosis. Additionally, fever, cough, sputum production, myalgia, fatigue, and dyspnea combined have a 10.44 PLR and a 0.16 NLR in predicting severe COVID-19. Conclusions Understanding the different distribution of predictors essential for screening potential COVID-19 infection and severe outcomes and the combination of symptoms could improve the pre-test probability.

Background: Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are accurately detected late in the progressive form of the disease. Methods: Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. Results: In the apparently macroscopically unchanged tegument, photon microscopy revealed both progressive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. Conclusions: The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help in defining patients’ prognosis and stratification. Beyond neurofilaments, chitinases are a promising family of possible biomarker, which correlate with neuroinflammatory status. We evaluated plasmatic levels of CHI3L1 in MNDs, MND mimics and healthy controls (HCs); (2) Methods: We used Sandwich ELISA to quantify CHI3L1 in plasma samples from 44 MNDs, 7 HSP, 9 MND mimics and 19 HCs. We collect also ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, neuropsychological evaluation; (3) Results: Plasma levels of CHI3L1 resulted to be different among groups (p= 0.005). Particularly, MND mimics showed higher CHI3L1 levels compared to MNDs and HCs. CHI3LI levels did not differ among PMA, PLS and ALS and we do not find correlation among CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, red blood cells count and haemoglobin correlated with CHI3L1 levels (respectively, p&lt;0.001, r=0.63; p= 0.022, r=0.52); (4) Conclusions: CHI3L1 plasma levels resulted to be increased in the MND mimics cohort when compared to MNDs. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that CHI3L1 plasma levels did not differentiate between ALS and HCs and nor correlate with neuropsychological impairment.

Algologists and neurologists play a significant role in management of headache. The study aimed to compare the headache management approaches of algologist and neurologists and evaluate the impact of telehealth education on their practices. A questionnaire was developed and sent to algologists and neurologists through social media and email. Demographic information, diagnostic and treatment approaches to a headache case, and the impact of telehealth education were evaluated 82 algologists and 97 neurologists completed the survey. There was no significant difference between diagnosis. However, the examination methods differed, with the neurologists relying on history and the algologists suggesting further investigations. Both groups agreed on the application of prophylaxis treatment, with botulinum toxin administration and classical prophylactic agents being accepted in both groups. The newest preventive treatment method was used more frequently in the Neurologists. Participants reported that online meetings had a positive impact on their daily practices, with 48% stating that they were reflected in their practice. Those who attended online meetings marked more up- to-date treatment options such as CGRP antagonists and Botulinum toxin. The study showed that algologists and neurologists had similar approaches to headache management, with differences in examination methods and the use of newer preventive treatment methods. Telehealth education had a positive impact on the participants, improving their knowledge of up-to-date treatment options.

Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and their carcasses. As the endemic areas have expanded, so has the need for rapid, sensitive, and cost effective diagnostic tests – especially those which take advantage of samples collected antemortem. Over the past two decades, strategies have evolved from the recognition of microscopic spongiform pathology and associated immunohistochemical staining of the misfolded prion protein to enzyme-linked immunoassays capable of detecting the abnormal prion conformer in postmortem samples. In a history that parallels the diagnosis of more conventional infectious agents, both qualitative and real-time amplification assays have recently been developed to detect minute quantities of misfolded prions in a range of biological and environmental samples. With these more sensitive and semi-quantitative approaches has come a greater understanding of the pathogenesis and epidemiology of this disease in the native host. Because the molecular pathogenesis of prion protein misfolding is broadly analogous to the misfolding of other pathogenic proteins, including Aβ and α-synuclein, efforts are currently underway to apply these in vitro amplification techniques towards the diagnosis of Alzheimer’s disease, Parkinson’s disease, and other proteinopathies. Chronic wasting disease – once a rare disease of Colorado mule deer – now represents one of the few naturally occurring protein misfolding disorders which might allow continued development and implementation of novel diagnostic strategies in an animal model.

Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: a) breast/chest radiation exposure, b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. And randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

Background and Objectives: Overuse and inappropriate use of testing and hospital admission are common in syncope evaluation and management. Though guidelines are available to optimize syncope care, study suggested that the current clinical guidelines have not significantly impacted resource utilization surrounding emergency department (ED) evaluation of syncope. Matching implementation strategies to barriers and facilitators and tailoring strategies to local context hold significant promise for a successful implementation of clinical practice guideline (CPG). Our team applied implementation science principles to develop a stakeholder-based implementation strategy. Methods and Materials: We partnered with patients, family caregivers, frontline clinicians and staff, and health system administrators at four health systems to conduct quantitative surveys and qualitative interviews for context assessment. The identification of implementation strategies was done by applying the CFIR-ERIC Implementation Strategy Matching Tool and soliciting stakeholders’ inputs. We then co-designed with patients and frontline teams, developed and tested specific strategies. Results: 114 clinicians completed surveys and 32 clinicians and stake-holders participated in interviews. Results from the surveys and interview indicated low awareness of syncope guidelines, and communication challenges with patients, lack of CPG protocol integration into ED workflows, and organizational process to change were recognized as major barriers. Thirty-one patients and their family caregivers participated in interviews and ex-pressed their expectations: clarity regarding their diagnosis, context surrounding care plan and diagnostic testing, and a desire to feel cared about. After identifying change methods to address those barriers, the multilevel, multicomponent implementation strategy, MISSION, included pa-tient educational materials, mentored implementation, academic detailing, Syncope Optimal Care Pathway and corresponding Mobile App, and Lean quality improvement methods. The pilot of MISSION demonstrated feasibility, acceptability and initial success on appropriate testing. Con-clusions: Effect multifaceted implementation strategies that target individuals, teams, and healthcare systems can be employed to plan successful implementation and promote adherence to syncope CPGs.

An outbreak of novel coronavirus(2019-nCoV) that began in Wuhan, China, is rapidly spreading to all over China, and gradually to multiple countries. Regarding to put the epidemic prevention and spread under the control, early identification and diagnosis play a critical role. Patients with initially no or mild symptoms of Novel Coronavirus Pneumonia (2019-nCoV), namely “stealth” infection, often lack of typical clinical evidence to establish the diagnosis. Based on the clinical analysis of 4 cases in stealth infection, the results of this study highlight that early diagnosis requires a combination of epidemiological history, clinical manifestations, early chest CT examination, and 2019-nCoV RNA test (nucleic acid test), with particular emphasis on definite epidemiological history and early chest CT findings when positive nucleic acid tests lag behind.

Handwriting is a complex perceptual-motor task that requires years of training and practice before complete mastering. Its acquisition is crucial since handwriting is the basis, together with reading, for the acquisition of higher-level skills such as spelling, grammar, syntax, and text composition. Despite correct learning and practice of handwriting, some children never master this skill to a sufficient level. These handwriting deficits, referred to as developmental dysgraphia, can seriously impact the acquisition of other skills and thus the academic success of the child if they are not diagnosed and handled early. In this review, we present a non-exhaustive listing of the tools which are the most reported in the literature for the analysis of handwriting and the diagnosis of dysgraphia. Tools focusing on both the final handwriting product and the handwriting process will be considered. We will then discuss the pros and cons of the existing tools, and the perspectives for the development of future tools.

Malaria remains an important cause of death, especially in sub-Saharan Africa with about 228 million malaria cases worldwide and an estimated 405,000 deaths in 2019. Currently, malaria is diagnosed in the health facility using a microscope (BS) or rapid malaria diagnostic test (MRDT) and with area where these tools are inadequate the presumptive treatment is performed. Apart from that self-diagnosis and treatment is also practiced in some of the households. With the high-rate self-medication on malaria drugs, this study aimed at computing the most significant features using feature selection methods for best prediction of malaria in Tanzania that can be used in developing a machine learning model for malaria diagnosis. A malaria symptoms and clinical diagnosis dataset were extracted from patients’ files from four (4) identified health facilities in the regions of Kilimanjaro and Morogoro. These regions were selected to represent the high endemic areas (Morogoro) and low endemic areas (Kilimanjaro) in the country. The dataset contained 2556 instances and 36 variables. The random forest classifier a tree based was used to select the most important features for malaria prediction. Regional based features were obtained to facilitate accurate prediction. The feature ranking as indicated that fever is universally the most influential feature for predicting malaria followed by general body malaise, vomiting and headache. However, these features are ranked differently across the regional datasets. Subsequently, six predictive models, using important features selected by feature selection method, were used to evaluate the features performance. The features identified complies with malaria diagnosis and treatment guideline provided with WHO and Tanzania Mainland. The compliance is observed so as to produce a prediction model that will fit in the current health care provision system in Tanzania.

Laboratory diagnosis of leishmaniasis remains a major challenge, demonstrating variable efficacy in detecting infected mammalian hosts. Thus, there is a great need for the accuracy of the identification of appropriate antigens to also improve diagnostic tests. This review brings to the fore the sensitivity of the balance in canine and human leishmaniasis, which greatly influences the progression of the disease and especially the diagnostic methods. The problem of diagnosis arises in asymptomatic leishmaniasis, since in these conditions the methods considered as reference in the diagnosis of leishmaniasis no longer show certainty, being influenced for the most part by the immune response of the host, which is different according to the presence of other associated diseases or even according to the breed, when we talk about dogs. Consequently, the diagnosis and surveillance of leishmaniasis cases remains an open topic, with the need for new methods adapted to the immunological status of the host.

We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).

Pattern analysis of salivary metabolic profile has been proven accurate to discriminate generalized periodontitis (GP) patients from healthy individuals (HI) as disease modifies the salivary concentrations of specific metabolites. Due to the scarcity of data in the literature, the aim of this study was to determine whether non-surgical periodontal therapy (NST) could change salivary metabolomic profile in GP to one more similar to HI. Unstimulated whole saliva of 11 HI and 12 GP patients were obtained prior to and 3 months after NST. Metabolic profiling was performed using Nuclear Magnetic Resonance (NMR) spectroscopy, followed by supervised multivariate statistical approach on entire saliva spectra and partial least square (PLS) discriminant analysis. In GP group, periodontal treatment improved all clinical parameters, but not all the diseased sites were eradicated. PLS revealed an accuracy of 100% in discriminating the metabolomic profile of each GP patient before and after NST. OPLS was able to discriminate the 3 groups of subjects with an accuracy of 85.6%. However the post-NST metabolic profile of GP patients could not be completely assimilated to that of HS. Although NST may produce significant changes in the metabolic profile, GP patients maintained a distinctive fingerprint compared to HI.

To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

Since its 2013 emergence in the Americas, chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a Ct cutoff of 22. As the Ct value increased from 22, ELISA sensitivity decreased. We then developed and validated two lateral flow tests using independent antibody pairs. The sensitivity and specificity reached 100% for both lateral flow tests using 39 samples from Colombia and Honduras at Ct cutoffs of 20 and 27, respectively. For both lateral flow tests, sensitivity decreased as the Ct increased after 27. Because CHIKV E1/E2 are exposed in the virion surfaces in serum during the acute infection phase, these sensitive and specific assays demonstrate opportunities for early detection of this emerging human pathogen.

Precise HDV-RNA detection and quantification are pivotal for accurate diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three assays: Hepatitis Delta RT-PCR system, EurobioPlex HDV assay, and the RoboGene HDV RNA Quantification kit 2.0, testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. Finally, all HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well between tests, r2=0.703 (Vircell-vs-Eurobio), r2=0.833 (Vircell-vs-RoboGene), r2=0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results in terms of correlation and bias. The three assays demonstrate promising performance. Their accuracy, reflected in concordance rates and quantitative analysis, makes them suitable for clinical practice. However, in the absence of assay harmonization, quantitative HDV RNA monitoring should be performed in the same laboratory and assay to avoid variability.

The viral nervous necrosis virus (VNNV) is the causative agent of an important disease affecting fish species cultured worldwide. Early and accurate diagnosis is at present the most effective control and prevention tool, and the molecular techniques have been strongly introduced and accepted by official organizations. Among those, real time quantitative polymerase chain reaction (rt-qPCR) is nowadays displacing other molecular techniques. However, another PCR-based technology, the droplet digital PCR (ddPCR), is on the increase. It has many advantages over qPCR, such as higher sensitivity and more reliability of the quantification. Therefore, we decided to design and validate a protocol for diagnosis and quantification of SJ and RG type VNNV, using reverse transcription-ddPCR (RT-ddPCR). We obtained an extremely low limit of detection, 10 to 100-folds lower than with RT-qPCR. Quantification by RT-ddPCR, with a dynamic range of 6.8 – 6.8 x 104 (SJ type) or 1.04 x 101 – 1.04 x 105 (RG) cps/rctn, was more reliable than with RT-qPCR. The procedure was tested and validated in field samples, providing the high clinical sensitivity and negative predictive values. In conclusion, we propose this method to substitute RT-qPCR protocols because it exceeds the expectations of qPCR in the diagnosis and quantification of VNNV.