The purpose of the study is to analyse and to identify specific structural characteristics of melanocytic nevi. Using the optical microscope, could be possible a proper describtion related melanocytic nevi, reffering to youth pacients. In this study direction play a significant role, different factors, such as genetic, epigenetic, microbiomic, and proteomic factors. Future directions refers to preventive and prophylactic methods. Disease diagnostic and management directions are also important.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

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.

Purpose: The purpose of this study is to apply the Composite Radiographic Index modified (CRIm) in CBCT scans of patients with Medication related osteonecrosis of the jaws (MRONJ) in order to detect its validity, and corelate the radiologic findings with the clinical staging of the disease. Methods: This study included 43 patients with MRONJ diagnosis and CBCT scans performed in the School of Dentistry and approved by the Research Ethics Committee. Clinical staging for every patient (0-3) was provided according to AAOMS 2022 guidelines. In cases of patients with both jaws affected, each jaw was evaluated independently resulting to 52 CBCT scans. The 52 CBCT scans were assessed under standardized viewing conditions by 2 observers who evaluated independently the following 8 radiologic features: lytic changes, sclerosis, periosteal reaction, sequestration, non-healing extraction sockets and other findings (sinus implication, inferior alveolar canal involvement, jaw fracture). The CRIm index was constructed to assess the extent of osseous changes. The radiologic features were scored as absent (0), localized/single (1), extensive/multiple (2), yielding a theoretical range of 0–12. For statistical analysis Fisher’s exact test and Spearman’s correlation coefficient were performed. Results: A statistically significant association of clinical stage with lytic changes, sequestration and inferior alveolar canal involvement was found. Also, a statistically significant correlation of clinical stage with CRIm index classification was obtained. Conclusions: The CRIm index tends to increase as the clinical stages of MRONJ advance, suggesting a correlation between the clinical stage of MRONJ and the CRIm index.

Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus while less common, tetanus is a serious disease following contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is this disease primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, malignant edema can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causing sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

The diagnosis and the pathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. In this work, we took advantage of a large public dataset on the IgG antibodies to 3,054 EBV peptides to understand whether these immune responses could be used as putative biomarkers for disease diagnosis and triggers of pathological autoimmunity in ME/CFS patients using healthy controls (HCs) as a comparator cohort. We then aimed at predicting disease status of study participants using a Super Learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. When we compared data of all ME/CFS patients or data of a subgroup of these patients with non-infectious or unknown disease trigger to the dataset of HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. In contrast, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from HCs with 100% and 90% accuracies on the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis of a subset of patients, but they are less likely to trigger pathological autoimmune responses that could explain the pathogenesis of ME/CFS.

Incidental findings (IFs) depicted in imaging tests during diagnostic evaluation of patients with cleft lip and/or palate (CL/P) can guide clinicians during treatment-planning procedures for effective, comprehensive cleft care. Evidence regarding IFs in different anatomical regions distant from the dentition are scarce. The aim of this study was to compare the prevalence of IFs in various anatomical areas between patients with non-syndromic CL/P and unaffected subjects. Orthopantomographs (OPT), lateral cephalometric (LC) radiographs and cone-beam computed tomography (CBCT) scans of 120 subjects (case group: n = 40, 18 females, age 14.5 ± 5.0 years; control group: n = 80, 36 females, age 14.6 ± 4.9 years) were examined and IFs were assessed by four observers. Significantly higher prevalence of IFs (p < 0.001) was reported in the case group (97.5%) compared with the control group (62.5%). The most prevalent location of IFs in the case group was the maxilla (92.5%), followed by the nasal cavity (75.8%) and the mandible (63.2%), while in the control group, the highest rates of IFs occurred in the maxilla (43.8%), mandible (41.3%) and temporomandibular joint (TMJ) (14.7%). No gender-dependent pattern for IF occurrence was detected overall. Orofacial clefts may affect the mandible. However, the reported IFs were limited compared to those in the maxilla. In conclusion, individuals with CL/P are more likely to present with a range of IFs than their unaffected peers. Understanding the association between CL/P and IFs is critical for successful interdisciplinary treatment, raising awareness of the potential need for future dental care for cleft patients, and managing extra-dental aberrations. A systematic assessment of diagnostic records is required to eliminate the risk of overlooking clinically significant IFs.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLME-Resnet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial and spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3\%) and Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and adjustment of treatment, by providing physicians with insights into the underlying pathological organization of gliomas.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

Immunohistochemistry (IHC) helps identify different types of tissues and provides important information about the pattern, shape, and structure of cells in a tissue sample. It is a very useful tool and widely used to uncover histology and pathology diagnosis uses. The IHC is a very useful tool to conduct research in the developmental biology area. Some insects, like butterflies, bees, beetles, ants, wasps, and moths, undergo a unique life cycle called complete metamorphosis, which has four distinct stages: egg, larva, pupa, and adult. Larvae are often wingless and have different habits and forms than adults, which are better suited for growth and development. During the metamorphosis, how does the insect legs change is a really an interesting issue.To better understand insect development, agriculture pest control, and insect pathogen interaction, here we use an insect Bombyx mori (domestic silk moth) as a model to detail how to conduct the IHC assays, such as HE staining, TUNEL to see the cell apoptosis, pH3 and BrdU staining to check cell division. The reagents can be easily found, and this step-by-step protocol is easily reproduced.

Degnala is one of the main mycotoxicoses that affects buffaloes, and the fungus Fusarium spp. is the main causative agent. This disease is strongly related to the supply of rice straw to buffaloes and is considered endemic to regions where this crop is cultivated. Cases of the disease are concentrated in the winter, when conditions favour fungal growth in inadequately stored rice straw. Degnala is characterized by necrosis and gangrene of the extremities, including the tail, lower limbs, ears, tongue, muzzle and teats. The pelvic limbs are more affected than the thoracic limbs. A tortuous appearance of the tail is very common, and cracks or corneal loss of the hooves may occur, with exposure of the blades and even the bones. There is no diagnostic method for identifying the disease in animals other than the clinical and epidemiological criteria associated with fungal culture of rice straw samples. There is no treatment that neutralizes the effects of the toxins, and the treatment currently used is a palliative and supportive method consisting of pentasulfate solution, anti-Degnala liquid, 2% nitroglycerin ointment and broad-spectrum antibiotics for secondary infections. In addition, the management of drying straw and proper storage are essential for controlling this disease.

Multiple Sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves the intricate interplay of different immune cells going awry leading to inflammation, demyelination, and neurodegeneration. Its diagnosis is quite arduous because of the baffling number of symptoms it elicits and the varied clinical manifestation it presents. The simplified criteria (in form of Macdonald’s Criteria) which have got modified several times is now the single most important criteria accepted by neurology bodies for diagnosing MS. Biomarkers from time to time have been explored to simplify the diagnosis and prognosticate MS along with anecessity to monitor treatment outcome. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and rapidly measured, their specificity, safety, and their ability to yield precise results. Biomarkers are classified into various categories including predictive, diagnostic, prognostic, related to disease activity, and monitoring treatment outcome. Each representative of the disease activity category reflects a variety of pathological processes of MS such as neuroaxonal loss, gliosis, demyelination, disability progression, remyelination, etc. This review discusses several promising serum and cerebrospinal fluid biomarkers and imaging biomarkers used in clinical practice. Myelin oligodendrocyte glycoprotein antibody disease which is recently recognized as a definite disease will also be discussed. Furthermore, it sheds light on the criteria and the challenges a biomarker faces to be considered as a standard one.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

Candidiasis is a significant fungal infection caused by various species of the genus Candida, posing health challenges to a wide range of animals, including Choloepus species (two-toed sloths). This review article aims to provide a comprehensive understanding of candidiasis in Choloepus sp., highlighting the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention strategies.The article begins by examining the causative agents, primarily focusing on Candida albicans, which is the most commonly implicated species in candidiasis. The epidemiological aspects are discussed, emphasizing the prevalence of candidiasis in wild and captive Choloepus populations and identifying predisposing factors such as immunosuppression, stress, poor nutrition, and environmental conditions. Pathogenesis is explored, detailing the mechanisms through which Candida species invade host tissues and evade immune responses. Clinical manifestations in Choloepus sp. are described, including oral thrush, cutaneous lesions, and gastrointestinal infections, and their impact on the health and behavior of affected individuals. Diagnostic methods, including culture techniques, histopathology, and molecular assays, are reviewed to highlight their roles in accurately identifying Candida infections. The article also covers treatment options, focusing on antifungal therapies and supportive care tailored to the unique physiology of Choloepus sp. Finally, prevention and management strategies are discussed, emphasizing the importance of maintaining optimal husbandry practices, regular health monitoring, and early intervention to reduce the incidence and impact of candidiasis in Choloepus populations. This review underscores the need for further research to enhance our understanding of candidiasis and improve health outcomes for these unique and vulnerable animals.

Pathological Brain Detection (PBD) is a crucial field aimed at identifying and diagnosing structural or functional abnormalities in the brain related to neurological, neurodegenerative, or psychiatric disorders. This detection process typically employs medical imaging technologies such as MRI, CT, or PET scans, along with neurological evaluations, blood tests, and other diagnostic tools. Early detection is essential for effective treatment, improving prognosis, and enhancing the quality of life for affected individuals. Each common computational method provides unique insights into brain pathologies. Despite significant advancements in technology and methodology, PBD faces challenges such as variability in brain anatomy, the complexity of disorders, data quality, standardization issues, interpretability of models, and ethical concerns. Addressing these challenges necessitates collaboration among researchers, clinicians, and policymakers to develop robust and ethical methods for improving the detection and diagnosis of brain disorders.

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Epigenetic changes are changes in gene expression that do not involve alterations to the basic DNA sequence. These changes lead to establishing a so-called epigenetic code that dictates which and when genes are activated, thus orchestrating gene regulation and playing a central role in development, health, and disease. The brain, being for the most formed by cells that do not undergo a renewal process through life, is highly prone to the risk of alterations leading to neuronal death and neurodegenerative disorders, mainly at late age. Here we review the main epigenetic modifications that have been described in the brain, with particular attention to those related to the onset of developmental anomalies or neurodegenerative conditions and/or occurring in old age. DNA methylation and several types of histone modifications (acetylation, methylation, phosphorylation, ubiquitination, sumoylation, lactylation, and crotonylation) are major players in these processes. They are directly or indirectly involved in the onset of neurodegeneration in Alzheimer’s or Parkinson’s disease. Therefore, this review briefly describes the role of these epigenetic changes in the mechanisms of brain development, maturation, and aging and some of the most important factors dynamically regulating or contributing to these changes such as oxidative stress, inflammation, and mitochondrial dysfunction.

Cognitive functions are based on neuronal plasticity, which is provided by various mechanisms involving numerous bioactive molecules, the most important of which are endocannabinoids (eCBs). Over the past three decades, a lot of data have been accumulated on the involvement of eCBs in the mechanisms of memory and other cognitive functions. These functions are impaired in neurodegenerative diseases such as Alzheimer's disease (AD) and temporal lobe epilepsy (TLE). The main pathological feature of neurons in AD and TLE is increased excitability; therefore, an activation of the endocannabinoid system, which controls cellular excitation, may be a promising approach in their therapy. The available information about the effect of (endo)cannabinoids on cognitive functions is contradictory, which may depend on the drugs used, their dose, and the experimental conditions. There is an extensive literature indicating a protective effect of cannabinoids in the treatment of neurodegenerative diseases in humans and in animal models of cognitive deficits. This review, focusing on the recent researches, is devoted to the analysis of the effects of endocannabinoid system activation on cognitive functions in norm and in the brain with neurodegeneration that occurs in AD and TLE diseases. Possible reasons for inconsistencies in the available data are discussed.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age >18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p<0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p>0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of >99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

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

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion (“post-exertional malaise”) and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is largely comprised of disturbances to immunological and inflammatory pathways, autonomic and neurologic systems, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiome disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a far-reaching homeostatic shift affecting each of these systems. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, which underpins methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

This study aimed to learn disturbance information to effectively control multiple small unmanned surface vehicles (USVs) for marine research purposes at sea. The learned disturbance information was used to investigate the control of multiple USV swarms based on the leading–following formation technique. Numerous studies have already been conducted on swarm control using drones in the air; however, there has been a paucity of studies on swarm control in the sea. Contrary to swarm control in aviation, the fluid density of the sea is high, and the environment is constantly changing; thus, a robot system would be significantly affected by disturbances. This ultimately influences the maintenance of swarm formations and the accomplishment of missions [1,2]. Therefore, it is difficult to control numerous moving objects while maintaining a formation at sea by using the existing aerial drone swarm control technology. To solve this problem, we learned a long short-term memory (LSTM) model with time-series marine environmental data to predict maritime disturbances. Thereafter, the model was applied to a mission-based position control algorithm of each USV constituting the swarm to design a marine unmanned floating vessel swarm control system that can be applied to various marine environments. Specifically, to effectively control numerous small USVs for marine research purposes, ocean currents are learned using the LSTM algorithm, and the predicted ocean currents are used to generate a swarm USV control system for USV formations. In this study, a control system model of several small USVs equipped with two rear thrusters and a front lateral thruster was designed. The LSTM algorithm was learned using the previous ocean current data, and the velocity of the following ocean currents was predicted. The predictions were then used as a system disturbance to determine the thrust of the controller. To measure ocean currents in the sea when each USV moves, the velocity, azimuth, and position (latitude, longitude) data from the GPS mounted on the USV were used to measure the velocity and direction of the hull's movement. Further, the flow rate was measured using a flow rate sensor on a small USV. The USV movement and position were controlled using an artificial neural network-PID (ANN-PID) controller. This study entailed a comparative analysis of the designed USV model results and those generated by the simulator, including the behavior control rule of the USV swarm and the path of the actual USV swarm at sea. It was verified that the effectiveness of the USV mathematical model and behavior control rules. By comparing the movement path of the swarm USV with and without the disturbance learning algorithm and ANN-PID control algorithm applied to the designed simulator, the position error and maintenance performance of the swarm formation were analyzed, and the application results were compared.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Cancer is one of the leading causes of death, making timely diagnosis and prognosis very important. Utilization of AI (artificial intelligence) enables providers to organize and process patient data in a way that can lead to better overall outcomes. This review paper aims to look at the varying uses of AI for diagnosis and prognosis and clinical utility. PubMed and EBSCO databases were utilized for finding publications from January 1, 2013, to December 22, 2023. Articles were collected using key search terms such as “artificial intelligence” and “machine learning.” Included in the collection were studies of the application of AI in determining cancer diagnosis and prognosis using multi-omics data, radiomics, pathomics, clinical and laboratory data. The resulting 89 studies were categorized into eight sections based on the type of data utilized and then further subdivided into two subsections focusing on cancer diagnosis and prognosis, respectively. 8 studies integrated more than one form of omics, namely genomics, transcriptomics, epigenomics, and proteomics. Incorporating AI into cancer diagnosis and prognosis alongside omics and clinical data represents a significant advancement. Given the considerable potential of AI in this domain, ongoing prospective studies are essential to enhance algorithm interpretability and to ensure safe clinical integration.

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).

Mitochondria play a significant role in the functioning of the cell, acting both as an intracellular energy source and a signaling organelle. In the heart, mitochondria produce more than 95% of the ATP in addition to regulating the redox state, calcium homeostasis, apoptosis, and lipid synthesis. However, there is also evidence that mitochondria exist outside of cells where they have been observed to mediate cell-to-cell communication, repair, and participate in the immune response. Cardiometabolic disease (CMD) has a complex pathogenesis closely associated with mitochondrial dysregulation, inflammation, and metabolic abnormalities. Because of this metabolic interdependence between the myocardium and the intracellular mitochondria, circulating extracellular mitochondria (CEMI) are being identified as possible regulators of CMD. Outside of the cell, mitochondrial functions are determined by the mitochondrial form, either as whole functional structures (e.g., small extracellular mitochondria) or as mitochondrial components with or without membrane encapsulation. Here, we explore the different forms of CEMI, their role in CMD pathogenesis, their potential therapeutic utility in treating diseases, and their role as biomarkers.

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.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Introduction: The concept of hypersexuality belongs to modern parlance, according to a predominantly clinical meaning, understood as a psychological and behavioural alteration as a result of which sexually motivated stimuli are sought in inappropriate ways, often experienced in a way that is not completely satisfactory. Methods: Literature up to February 2023 was reviewed. Results: Forty-two articles were included in the review. Conclusion: Hypersexuality is a potentially clinically relevant condition, consisting of one or more dysfunctional and pathological behaviours of one's sexual sphere and graded according to the severity of impairment of subjective acting out; for this reason, the Perrotta Hypersexuality Global Scale (PH-GS) is suggested, which distinguishes high-functioning forms (pro-active and dynamic hypersexuality) from those of attenuated and corrupted functioning (dysfunctional and pathological hypersexuality of grade I and II). Future research is hoped to address the practical needs of this condition, such as the exact etiopathology, the role of oxytocin in dopaminergic hypotheses (and its ability to attenuate the symptomatology suffered by the patient in terms of manic drive), the best structural and functional personality framing of the subject, and the appropriate therapy to pursue.

Myeloperoxidase (MPO) belong to the family of heme containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kD) is the product of MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications like removal of introns and signal peptide and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing active proMPO by the insertion of heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into extracellular fluid after oxidative stress and different inflammatory responses. MPO is the only type of peroxidase using H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation that can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and pathogenesis of several other major chronic diseases like rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes and cancer have been reported to be linked with myeloperoxidase derived oxidants. So the enhanced level of MPO activity is one of the best diagnostic tool of inflammatory and oxidative stress biomarkers among these commonly occurring diseases.

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.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

Type 2 Diabetes Mellitus and Alzheimer's disease are two diseases with a high incidence today that share similar pathophysiological mechanisms suggesting a potential causal relationship between them. In fact, Alzheimer-associated Mellitus Diabetes is also known as Type 3 Diabetes Mellitus and constitutes a diabetes intricately linked to Alzheimer's disease. Central to this association is insulin resistance, a key factor leading to decreased insulin sensitivity, hyperglycemia, and impaired glucose uptake. Because of this, the brain is altered resulting in energy deficits and neuronal damage associated with neurodegenerative disorder characteristic of Alzheimer's disease. Both diseases exhibit common biochemical and physiological characteristics such as inflammation, mitochondrial dysfunction, oxidative stress, and the formation of advanced glycation end products. Understanding the complex pathophysiology of Type 3 Mellitus Diabetes and identifying common features shared with Diabetes and Alzheimer's disease are essential steps towards potential therapeutic interventions targeting the insulin resistance pathway. The authors of this review on the relationships between type 2 diabetes and Alzheimer's disease have developed two works. In the first (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. I. Common pathogenic mechanisms), authors explore the shared (physiological, genetics and molecular) pathological changes occurring in Type 2 Mellitus Diabetes and Alzheimer's disease as well as pathways such as AMPK, PPARγ, cAMP, and PI3K/Akt as potential targets for managing Type 3 Diabetes Mellitus. By exploring these intricate mechanisms, the goal is to uncover their interdependencies and facilitate the discovery of innovative pharmacological and nutritional (epigenetics) strategies. In the second paper (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. II Potential therapies) we describe possible nutritional intervention, particularly dietary patterns and phytochemicals that can enhance the effects of pharmaceutical drugs designed against pathological mechanisms involved in the complex dual disease Type 2 Diabetes Mellitus and Alzheimer's disease (or in Type 3 Diabetes Mellitus as other authors consider).

The implementation of systems condition monitoring is of utmost importance in ensuring effective maintenance, optimal efficiency, and adherence to established design criteria. This research presents a novel and economically efficient Digital Twin Model (DTM) designed for the purpose of Live Condition Monitoring (LCM) and Predictive Lifecycles. This study discusses the enhancement of DTs modelling by decreasing the number of dimensions from five to three: Physical, Digital, and Connection entities. The resulting model exhibits a notable improvement in accuracy and efficiency. The suggested Dynamic Time Model (DTM) enhances the empirical pre-set average load for both simulation and experimentation by 35.7%, which is equivalent to a 1.6-fold increase. The DTM demonstrates a significant enhancement in the empirical predefined average lifecycles of the system, as shown in the real-life case study. Specifically, the DTM achieves a 12-fold improvement compared to the simulated results and a nine-fold improvement compared to the experimental findings. The suggested Dynamic Time Management (DTM) demonstrates a significant enhancement in the average lifecycles of the system, with a 19.7% improvement (equivalent to 1.2 times greater) compared to the wireless DTM results obtained through the application of the real system load. The suggested Dynamic Time Warping (DTW) method's accuracy and efficiency are shown via a practical case study using the suspension system of a Peugeot 3008 vehicle.

The KCNA1 gene encodes Kv1.1 voltage-gated potassium channel α subunits, which are crucial for maintaining healthy neuronal firing and preventing hyperexcitability. Mutations in the KCNA1 gene can cause several neurological diseases and symptoms, such as episodic ataxia and epilepsy, which may occur alone or in combination, making it challenging to establish simple genotype-phenotype correlations. Previous analyses of human KCNA1 variants have shown that epilepsy-linked mutations tend to cluster in regions critical for the channel’s pore, whereas EA1-associated mutations are evenly distributed across the length of the protein. In this review, we examine 17 recently discovered pathogenic or likely pathogenic KCNA1 variants to gain new insights into the molecular genetic basis of KCNA1 channelopathy. We provide the first systematic breakdown of disease rates for KCNA1 variants in different protein domains, uncovering potential location biases that influence genotype-phenotype correlations. Our examination of the new mutations strengthens the proposed link between the pore region and epilepsy and reveals new connections between epilepsy-related variants, genetic modifiers, and respiratory dysfunction. Additionally, the new variants include the first two gain-of-function mutations ever discovered for KCNA1, the first frameshift mutation, and the first mutations located in the cytoplasmic N-terminal domain, broadening the functional and molecular scope of KCNA1 channelopathy. Moreover, the recently identified variants highlight emerging links between KCNA1 and musculoskeletal abnormalities and nystagmus, conditions not typically associated with KCNA1. These findings improve our understanding of KCNA1 channelopathy and promise to enhance personalized diagnosis and treatment for individuals with KCNA1-linked disorders.

AbstractWe investigated the effect of cigarette smoking on pathological staging in clinically low-risk patients. Data of 59 patients who were diagnosed with bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated retrospectively. 33 patients who smoked were classified as Group I, and 26 patients who did not smoke were classified as Group II. Pathological diagnoses of the patients in both groups were compared. The mean age of the patients were 64.8 (20–86) years. In Group II, 5 (19.2%) were female and 21 (80.8%) were male (p < 0.05). Nine patients (27.3%) in Group I and 18 patients (69.2%) in Group II had Ta disease (p < 0.05). Nineteen patients (57.6%) in Group I and 5 patients (19.2%) in Group II had T₁ disease (p < 0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in Group I and in Group II, respectively (p < 0.05). The number of patients with high grade(HG) tumor were 25 (75.8%) and 7 (26.9%) in Group I and in Group II, respectively (p < 0.05). TaHG was detected in 9 (27.3%) patients in Group I. In contrast, no patients in Group II had TaHG disease (p < 0.05). The number of patients with T₁HG was 17(51.5%) patients in Group I and 2 (7.69%) patients in Group II (p < 0.05). Smoking is associated with pathologically HG and stage in patients with first time bladder tumor which is single and smaller than 3 cm.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has executed 6.9 million people and infected over 765 million. It’s become a major worldwide health alarm and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower res-piratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse out-comes. Prophylactic anticoagulation is essential to prevent complication and death rate associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation exhibits some similarities to DIC induced by sepsis. LDH, D-dimer, ferritin, and CRP biomarker are often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

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

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

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.

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.

Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.

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.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Background. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p&lt;0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

The blood brain barrier (BBB) is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system (CNS). During the occurrence and development of glioblastoma (GBM), BBB is pathologically disrupted with markedly increased permeability. Due to the obstruction imposed by the BBB, strategies currently employed for GBM therapeutics still obtain a very low success rate and lead to systemic toxicity. Moreover, chemotherapy could promote pathological BBB functional restoration, accompanied with a prominent decrease of intracerebral therapeutics transportion during GBM multiple administration, resulting in chemotherapy failure for GBM treatment. The effective delivery of therapeutics into the brain still faces with severe challenges. Regulation of pathological BBB for enhanced transporting of therapeutics across the barrier may provide new opportunities for effective and safe treatment of GBM. This article reviews the structure and function of BBB in physiological state, the mechanisms underlying BBB pathological fenestration during the development of GBM, and the therapeutic strategies of GBM based on BBB intervention and therapeutic drugs transporting across the BBB.

Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extra-mitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP-synthase (E55A mutation), indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca2+ handling, which resulted in sarcoplasmic reticulum Ca2+ overloading. The effects of IF1 on Ca2+ handling were associated with the cytosolic activation of CaMKII and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF-1 induced pathological hypertrophy. Conclusions IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase independent, role for IF1 in mitochondrial Ca2+ handling and mitochondrial- to nuclear crosstalk involving CaMKII.

Globally, the COVID-19 pandemic has brought the world to a standstill with the infected cases surpassing millions. The causative agent of COVID-19, the SARS-CoV-2 is a novel coronavirus that emerged from the wet animal market in Wuhan, China in early December 2019. Soon after, human-to-human transmission increased the rate of infection making the disease widespread with new hotspots emerging around the world.The epidemiological reports based on clinical characteristics including age, gender, symptoms (both severe and non-severe), and the conditions requiring intensive medical care, along with case fatality revealed that people with co-existing health conditions like diabetes, hypertension, cigarette smoking, and others with cardiovascular and kidney diseases were more susceptible to COVID-19 infection with poor prognosis in cases related to the severity of symptoms and requiring ICU, medical ventilators with a high fatality rate. Even people with immunosuppressed conditions like HIV and cancer, alongwith old age and pregnant women are vulnerable to COVID-19 infection and can cause severe health complications.It is extremely important to have a comprehensive idea of the underlying pathophysiology related to these health conditions which makes them more susceptible to contract SARS-CoV-2 infection in correlation with the development of severe symptoms. This review will provide an extensive viewpoint related to COVID-19 patients having coexisting health conditions together with the association between the prognosis of the disease and the pathogenesis of the SARS-CoV-2 infection, based on the current information available.

Biophoton emission has been experimented for decades. The photo-genic origin of biophoton has also been attributed to the oxidative stress or free radical production. However, there are considerable gaps in quantitative understanding of biophoton emission. In this work, I propose an analytical hypothesis for interpreting a few patterns of steady-state biophoton emission of human, including the dependency on age, the diurnal variation, and the geometric asymmetry associated with serious asymmetrical pathological conditions. The hypothesis is based on an alternative form of energy state, termed vivo-nergy, which is associated with only metabolically active organisms that are also under neuronal control. The hypothesis projects a decrease of the vivo-nergy in human during growth beyond puberty. The hypothesis also proposes a modification of the vivo-nergy by the phases of systematic or homeostatic physiology. The hypothesis further postulates that the deviation of the physiology-modified vivo-nergy from the pre-puberty level is deteriorated by acquired organ-specific pathological conditions. A temporal differential change of vivo-nergy is hypothesized to proportionally modulate oxidative stress that functions as the physical source of biophoton emission. The resulted steady-state diffusion of the photon emitted from a photo-genic source in a human geometry simplified as a homogeneous spherical domain is modeled by photon diffusion principles incorporating an extrapolated zero-boundary condition. The age and systematic physiology combined determines the intensity of the centered physiological steady-state photo-genic source. An acquired pathology sets both the intensity and the off-center position of the pathological steady-state photo-genic source. When the age-commemorated, physiology-commanded, and pathology-controlled modifications of the steady-state photo-genetic sources are implemented in the photon diffusion model, the photon fluence rate at the surface of the human-representing spherical domain reveals the patterns on age, the temporal variation corresponding to systematic physiology, and the geometric asymmetry associated with significant asymmetric pathological condition as reported for spontaneous biophoton emission. The hypothesis, as it provides conveniences for quantitative estimation of biophoton emission patterns, will be extended in future works towards interpreting the temporal characteristics of biophoton emission under stimulation.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p&lt;0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle, a respiratory form, and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus whereas the gastroenteric form causes neonatal diarrhea or calf scour in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscores the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. Research data so far have shown that the viral structure or strain is not a determinant of tissue tropism and clinical form of the disease. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. The virus is classified under Coronaviridae family, Betacoronavirus genus and Betacorovirus 1 species. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have also been used increasingly in recent years for the detection and identification of BCoV. Loop-mediated isothermal amplification, helicase-dependent amplification, recombinase polymerase amplification, and multienzyme isothermal rapid amplification are some examples of the isothermal amplification assays for used BCoV. Point-of-care testing has gained some popularity recently as they can offer user-friendly testing on the farm (barn-side). The present study reviewed literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

We describe an interesting case report about a patient with hemophilia A with severe chronic elbow arthropathy who underwent multiple surgical because of his condition. We collected all the clinical and imaging findings, and we compared the decision-making flow chart and the surgery performed with the most recent indications, treatments and complications reported in the literature. The aim of this case report is to show how usually the hemophilic patient even if young usually comes to our attention from the beginning with complex and advance musculoskeletal disease. Elbow hemophilic arthropathy is a complex disease and the management in these patients could be more difficult than others because of the higher risk of complications rate after all surgical procedures, for this reason it’s very important to treat these patients in hub centers with expertise in well-coordinated multidisciplinary teams. The path from diagnosis to surgical treatment of hemophilic elbow arthropathy can be a risky one, as it happened in this case.

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.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Abstract: Infectious bronchitis virus (IBV) induces respiratory and urogenital disease in chickens. Although IBV replicates in the gastrointestinal tract, enteric lesions are uncommon. We have reported a case of runting-stunting syndrome in commercial broilers from which an IBV variant was isolated from the intestines. The isolate, CalEnt, demonstrated an enteric tissue tropism in chicken embryos and SPF chickens experimentally. Here, we determined the full genome of CalEnt and compared it to other IBV strains, in addition to comparing the pathobiology of CalEnt and M41 in commercial broilers. Despite the high whole-genome identity to other IBV strains, CalEnt is rather unique in nucleotide composition. The S gene phylogenetic analyses showed great similarity between CalEnt and Cal 99. Clinically, vent staining was slightly more frequent in CalEnt-infected birds than those challenged with M41. Furthermore, IBV IHC detection was more evident and the viral shedding in feces was overall higher with the CalEnt challenge compared with M41. Despite underlying intestinal lesions caused by coccidiosis and salmonellosis vaccination, microscopic lesions in CalEnt-infected chickens were more severe than in M41-infected chickens or controls, supporting the enteric tropism of CalEnt. Further studies in SPF chickens are needed to determine the pathogenesis of the virus, its molecular mechanisms for the enteric tropism, and its influence in intestinal health.

Introduction: We investigated the potential effect of smoking on pathological staging in clinically low-risk patients. Material-Methods: Data of 59 patients who were diagnosed with a bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated, retrospectively. A total of 33 patients who currently smoke or smoked were classified as ever smokers group and 26 patients who did not ever smoke were classified as never smokers group. Pathological diagnoses of the patients in both groups were compared. Results: A total of 9 patients (27.3%) in ever smokers group and 18 patients (69.2%) in never smokers group had Ta disease (p<0.05). Morover, 19 patients (57.6%) in ever smokers group and 5 patients (19.2%) in never smokers group had T1 disease (p<0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in ever smoking and never smoking groups, respectively (p<0.05). The number of patients with high grade (HG) tumor were 25 (75.8%) and 7 (26.9%) in ever smoking and never smoking groups, respectively (p<0.05). Ta HG was detected in 9 (27.3%) patients in ever smoking group. In contrast, no patients in never smoking group had Ta HG disease (p<0.05). The number of patients with T1 HG was 17 (51.5%) in ever smoking group and 2 (7.69%) in never smoking group (p<0.05). Conclusion:Smoking seems to associate with pathologically worse stage and grade in patients with primary, single, < 3cm bladder cancer.

Understanding the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that herpesviruses' infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment – symptoms consistent with ME/CFS and Long COVID. The paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within ECs of ME/CFS patients. This review offers a conceptual advance by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research towards potentially unexplored avenues in understanding and treating this complex syndrome.

Aims: To report on the clinico-pathological features of a series of 12 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Methods and methods: All mucoepidermoid carcinomas diagnosed in the period 1990-2012 were retrieved, the original histological preparations were reviewed to confirm the diagnosis, and from selected cases, showing exclusive intra-cystic neoplastic component, additional sections were cut at 3 subsequent 200m intervals and stained with Hematoxylin-Eosin, PAS and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Also, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of 5 years. The neosplasm were located in the hard palate (9 cases), the soft palate (2), the cheeck (2) and the retromolar trigone (1). In all instances histological examination was revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue and no solid areas or infiltrating tumour clusters were detected. Conservative surgical resection was performed in all cases and no recurrences or nodal metastases were observed during the follow up period. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumours. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic fashion and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues or metastasize.

(1) Background: The aim of this study was to investigate the circadian rhythms of tongue features according to the effects of physiological phases over a 24-hour period. (2) Methods: Fifteen healthy participants aged 20 to 69 years were recruited. The participants did not have current chronic diseases or past diseases and had to meet the inclusion and exclusion criteria. The participants stayed at the Gil Hospital for a duration of 2 nights and 3 days. On the first day, at 18:00, they consumed their allocated portions of food and water and then completed a questionnaire. At approximately 21:00, their tongue images were acquired using a computerized tongue image acquisition system, following which they slept for 8 hours, commencing at 23:00. Measurements were taken from 07:00 through 21:00 on the second day, and the final acquisition was taken at 07:00 on the following morning, resulting in a total of eight images. The circadian rhythm was authenticated and quantified utilizing the single cosinor analysis, a technique for periodic regression analysis for fitting a 24-hour cosine curve. (3) Results: Cosinor analysis revealed that all tongue features were significantly related to circadian rhythm. (4) Conclusions: The results of this study may be important for considering the time of day at which the tongue is observed and tongue status is evaluated.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

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.

Purpose The gradual increase in geriatric issues and global imbalance of the ratio between patients and healthcare professionals has created a demand for intelligent systems with the least error-prone diagnosis results to be used by less medically trained persons and save clinical time. This paper aims at investigating the development of an image-based colourimetric analysis. The purpose of recognising such tests is to support wider users to begin a colourimetric test to be used at homecare settings, telepathology, etc. Design/methodology/approach The concept of an automatic colourimetric assay detection is delivered by utilising two cases. Training Deep Learning (DL) models on thousands of images of these tests using transfer learning, this paper i) classifies the type of the assay, and ii) classifies the colourimetric results. Findings This paper demonstrated that the assay type can be recognised using DL techniques with 100% accuracy within a fraction of a second. Some of the advantages of the pre-trained model over the calibration-based approach are robustness, readiness and suitability to deploy for similar applications within a shorter period of time. Originality/value To the best of our knowledge, this is the first attempt to provide Colourimetric Assay Type Classification (CATC) using DL. Humans are capable to learn thousands of visual classifications in their life. Object recognition may be a trivial task for humans, due to photometric and geometric variabilities along with the high degree of intra-class variabilities it can be a challenging task for machines. However, transforming visual knowledge into machines, as proposed, can support non-experts to better manage their health and reduce some of the burdens on experts.

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in GBA1, characterized by glucocerebrosidase dysfunction and glucocerebroside and glucosylsphingosine accumulation. Since phenotypes of murine models of GD often differ from those in patients, careful characterization of Gba1 mutant mice is necessary to establish their ability to model GD. We performed side-by-side comparative biochemical and pathologic analyses of four murine Gba1 models with genotypes L444P/L444P (p.L483P/p.L483P), L444P/null, D409H/D409H (p.D448H/p.D448H), and D409H/null, along with matched wildtype mice, all with the same genetic background and cage conditions. All mutant mice exhibited significantly lower glucocerebrosidase activity (p < 0.0001) and higher glucosylsphingosine levels than wildtype, with the lowest glucocerebrosidase and highest glucosylsphingosine levels in mice carrying a null allele. Although glucocerebrosidase activity in L444P and D409H mice was similar, D409H mice showed more lipid accumulation. No Gaucher or storage-like cells were detected in any of the Gba1 mutant mice. Quantification of neuroinflammation, dopaminergic neuronal loss, alpha-synuclein levels and motor behavior revealed no significant findings, even in aged animals. Thus, while the models may have utility for testing the effect of different therapies on enzymatic activity, they did not recapitulate the pathological phenotype of patients with GD, and better models are needed.

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

Recent advancements in mass spectrometry have significantly enhanced our understanding of complex lipid profiles, opening new avenues for oncological diagnostics. This review highlights the importance of lipidomics in the comprehension of certain metabolic pathways and its potential for the detection and characterization of various cancers, in particular melanoma. Through detailed case studies, we demonstrate how lipidomic analysis has led to significant breakthroughs in the identification and understanding of cancer types and its potential for detecting unique biomarkers that are instrumental in its diagnosis. Additionally, the review addresses the technical challenges and future perspectives of these methodologies, including their potential expansion and refinement for clinical applications. The discussion underscores the critical role of lipidomic profiling in advancing cancer diagnostics, proposing a new paradigm in how we approach this devastating disease, with particular emphasis on its application in comparative oncology.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.

Intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominant basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%) and basal-like immune-activated (IHC-BLIA, 10.9%). The pathological complete response (pCR) rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes. Although, IHC-BLIA demonstrated a trend toward better survival and IHC-mesenchymal worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

This article investigates the effectiveness of feature extraction and selection techniques for enhancing the performance of classifiers accuracy in Type II Diabetes Mellitus (DM) detection using microarray gene data. To address the inherent high dimensionality of the data by employing three Feature Extraction (FE) methods are used namely, Short-Time Fourier Transform (STFT), Ridge Regression (RR), and Pearson Correlation Coefficient (PCC). To further refine the data, meta-heuristic algorithms like Bald Eagle Search Optimization (BESO) and Red Deer Optimization (RDO) are utilized for feature selection. The performance of seven classification techniques such as Non-Linear Regression - NLR, Linear Regression - LR, Gaussian Mixture Model - GMM, Expectation Maximization - EM, Logistic Regression - LoR, Softmax Discriminant Classifier - SDC, and Support Vector Machine with Radial Basis Function kernel - SVM-RBF are evaluated with and without feature selection. The analysis reveals that the combination of PCC with SVM-RBF achieved a promising accuracy of 92.85% even without feature selection. Notably, employing BESO with PCC and SVM-RBF maintained this high accuracy. However, the highest overall accuracy of 97.14% was achieved when RDO was used for feature selection alongside PCC and SVM-RBF. These findings highlight the potential of feature extraction and selection techniques, particularly RDO with PCC, in improving the accuracy of DM detection using microarray gene data.

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.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.

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.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

Background: Neonatal cholestasis (NC) initiates in the first trimester of a newborn, comprising extra and intrahepatic medical conditions, with a high risk of fatality warranting early diagnosis and treatment to prevent morbimortality. The differential diagnosis of NC is a challenge demanding an accurate diagnosis for disease detection. The current study evaluates NC's clinical symptoms and differential diagnosis using ultrasound, liver biopsy, histopathology, and biochemistry. Methods: Infant registry data from Hevi Pediatric Teaching Hospital (January 2016 - January 2022) were obtained and screened for subject selection. The inclusion criteria include infants with direct hyperbilirubinemia within an onset of 1 to 90 days of birth. As indicated, the recruited subjects underwent liver ultrasound, blood biochemistry, and liver biopsy. Results: Seventy-two children presented with the criteria for inclusion in the study. The study found that ultrasound helped diagnose 43.1% of subjects for BA compared to 34.7% through histopathology. The histopathology confirmed 13 children (18.1%) having neonatal hepatitis. Test sensitivity of the ultrasound method for BA and NH was 60% (40.74, 76.6) and 38.46% (17.71, 64.48), respectively. Conclusion: The study found both ultrasound and liver biopsy to be critical diagnostic methods to differentiate the etiology of NC. Ultrasound has a higher specificity and sensitivity for diagnosing BA than NH. Histopathology and blood biochemistry should be considered, too, for effective diagnosis. In the future, larger sample and multicenter studies should be conducted to develop practically implementable strategies.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

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.

Immunology is a branch of medicine that studies the immune system and its pathology. There are known scientific informations, that in medical immunology specific tests performed in the laboratory for diagnosis. In addition good to mention that allergies include medical diagnostic methods such as blood tests. Also there are used for detection the presence and the levels of IgE antibodies. These antibodies are produced by the human immune system in contact with certain allergens. Examples of allergens include for example pollen, house dust, some herbs or molds, some animals and certain foods. If a person has an allergy, their immune system overreacts to an allergen by producing antibodies, called Immunoglobulin E (IgE). Currently within the present describtion aim to discuss some aspects reffering to fungal allergen and mold allergy diagnosis, in a briefly following steps of our purposed shortly review.

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

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

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.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

Previous research has already examined the relationship between Future Anxiety, a construct recently introduced in Italy, and mental health in young adults, although possible mediating variables in this relationship have so far never been investigated. The present study attempts to fill this gap by exploring the incidence of Future Anxiety on psychological distress in a group of 302 young Italian adults (18 - 30 years; M = 21.9; SD = 2.6), presenting and evaluating the simultaneous mediating effect of Intolerance of Uncertainty and Non-Pathological Worry.Findings highlighted how Future Anxiety had a positive and significant direct effect on Stress and Depression, but not on Anxiety. In the three serial mediation models proposed, Intolerance of Uncertainty and Non-Pathological Worry mediated the relationship between Future Anxiety and mental health outcomes. The results also confirmed the hypothesized serial mediation effect by highlighting how young adults with greater Future Anxiety experienced more Intolerance of Uncertainty, which positively affected Non-Pathological Worry levels and, in turn, exacerbated psychological distress. Finally, results indicated that female participants experienced more Stress, Anxiety, and Depression in relation to Future Anxiety compared to males. Starting from the review of main references on this subject, the results discussed provide new insights for understanding youth psychological distress. Finally, practical implications for the design of supportive interventions for this study’s target group are proposed.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.