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AbstractThis comprehensive review delves into the advancements and challenges in biosensing, with a strong emphasis on the transformative potential of CRISPR technology for early and rapid detection of infectious diseases. It underscores the versatility of CRISPR/Cas systems, highlighting their ability to detect both nucleic acids and non-nucleic acid targets, and their seamless integration with isothermal amplification techniques. The review provides a thorough examination of the latest developments in CRISPR-based biosensors, detailing the unique properties of CRISPR systems, such as their high specificity and programmability, which make them particularly effective for detecting disease-associated nucleic acids. While the review focuses on nucleic acid detection due to its critical role in diagnosing infectious diseases, it also explores the broader applications of CRISPR technology in detecting non-nucleic acid targets, thereby acknowledging the technology’s broader potential. Additionally, the review identifies existing challenges, such as the need for improved signal amplification and real-world applicability, and offers future perspectives aimed at overcoming these hurdles. The ultimate goal is to advance the development of highly sensitive and specific CRISPR-based biosensors that can be used widely for improving human health, particularly in point-of-care settings and resource-limited environments. [ABSTRACT FROM AUTHOR]

Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients. [ABSTRACT FROM AUTHOR]

Objective: There exists a paucity of data regarding the mechanism and manometric findings in retrograde cricopharyngeal dysfunction (RCPD). In this study, we aimed to compare esophageal physiologic findings between patients with RCPD compared to an asymptomatic cohort. Study Design: Case‐control study. Setting: Tertiary Care Center. Methods: Esophageal high‐resolution impedance manometry was completed preoperatively in patients diagnosed with RCPD. Manometric data were compared between the RCPD and asymptomatic cohorts. A 2:1 age‐sex‐matched asymptomatic cohort was used as the control group. Treatment response was assessed among the RCPD cohort. Results: Thirty‐nine patients are included: 13 RCPD [mean age: 31.1 (SD: 12.6) years, female sex: 11 (85%)] and 26 asymptomatic [mean age: 32.1 (SD: 1.5) years, female sex: 22 (85%)]. The RCPD cohort, compared to the asymptomatic cohort, exhibited significantly greater upper esophageal sphincter (UES) length [4.5 (SD: 0.7) vs 3.7 (0.9) cm, P =.01] and higher UES basal pressures [91.9 (35.0) vs 49.7 (25.5) mm Hg, P =.002]. Patients with RCPD demonstrated higher rates of ineffective swallows [70.0% (31.6%) vs 15.4% (21.6%), P <.001] and incomplete bolus clearance [81% (22.0%) vs 21.8% (30.0%), P <.001]. All patients who underwent cricopharyngeal botulinum injections experienced initial improvement of symptoms with 3 patients requiring repeat intervention. Conclusion: RCPD is associated with a longer UES, elevated UES basal pressures, and an increased incidence of ineffective esophageal motility. This study is the first to compare preoperative manometry results among patients with RCPD to those of an asymptomatic cohort, providing insights into the mechanism of RCPD. [ABSTRACT FROM AUTHOR]

Infertility affects a significant proportion of the reproductive‐aged population, with male‐associated factors contributing to over half of the cases. However, current diagnostic tools have limitations, leading to an underestimation of the true prevalence of male infertility. While traditional semen parameters provide some insights, they fail to determine the true fertility potential in a substantial number of instances. Therefore, it is crucial to investigate additional molecular targets responsible for male infertility to improve understanding and identification of such cases. Seminal plasma, the main carrier of molecules derived from male reproductive glands, plays a crucial role in reproduction. Amongst its multifarious functions, it regulates processes such as sperm capacitation, sperm protection and maturation, and even interaction with the egg's zona pellucida. Seminal plasma offers a non‐invasive sample for urogenital diagnostics and has shown promise in identifying biomarkers associated with male reproductive disorders. This review aims to provide an updated and comprehensive overview of seminal plasma in the diagnosis of male infertility, exploring its composition, function, methods used for analysis, and the application of emerging markers. Apart from the application, the potential challenges of seminal plasma analysis such as standardisation, marker interpretation and confounding factors have also been addressed. Moreover, we have also explored future avenues for enhancing its utility and its role in improving diagnostic strategies. Through comprehensive exploration of seminal plasma's diagnostic potential, the present analysis seeks to advance the understanding of male infertility and its effective management. [ABSTRACT FROM AUTHOR]

Dermatological conditions and skin cancers are common health concerns that require early detection and intervention. Primary care physicians play a crucial role in recognizing these conditions and serving as the first line of defense against skin cancers. This guide provides a systematic approach to conducting thorough skin examinations and enhancing understanding of common presentations of precancerous and cancerous lesions. We emphasize the importance of performing annual full-body skin exams to facilitate early detection and management of skin conditions, including a step-by-step, systematic protocol for conducting these exams, comprising preparing the patient, documenting findings, educating the patient, and considering biopsy or referral for suspicious lesions. Furthermore, we explore the atypical features of skin lesions that raise clinical suspicion and warrant further investigation. We describe the characteristics of common skin cancers, such as basal cell carcinoma, squamous cell carcinoma, and melanoma. We stress the importance of patient education on self-skin checks and sun protection measures. By incorporating the knowledge and skills presented in this guide, primary care physicians can confidently perform thorough full-body skin checks, identify common dermatological findings and early signs of skin cancers, and provide comprehensive care to patients. This will help ensure optimal outcomes in dermatological health. [ABSTRACT FROM AUTHOR]

Aims: Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods: In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results: A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion: These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373.

Abstract Lung cancer is one of the most common type of cancer and, despite significant advances in screening and diagnosis approaches, a large proportion of patients at diagnosis still present advanced stages of the disease with distant metastasis and bad prognosis. Finding and validating biomarkers of lung cancer is therefore essential. Such studies are often conducted on European, American and Asian populations and the relevance of these biomarkers in other populations remains less clear. In that prospect, we investigated the expression level of seven microRNAs, chosen from the medical literature (miR-16-5p, miR-92a-3p, miR-103a-3p, miR-375-3p, miR-451a, miR-520-3p and miR-let-7e-5p), in the blood of Tunisian lung cancer patients, treated or not by chemotherapy, and healthy control individuals. We found that high expression levels of circulating miR-16-5p, miR-92a-3p and miR-451a in the plasma of untreated patients discriminate them from healthy control individuals. In addition, miR-16-5p and miR-451a expression levels are significantly reduced in the plasma of chemotherapy-treated patients compared to untreated patients. Our results confirmed previous work in other populations worldwide and provide further evidence that circulating miR-16-5p, miR-92a-3p and miR-451a potentially regulate key pathways involved in the initiation and progression of cancer.

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells--all indicative of disease progression--before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the wide-ranging applications of Next-Generation Sequencing (NGS) techniques in veterinary medicine for companion animals. It addresses the need for advanced diagnostic and treatment approaches in veterinary care. The aims include understanding parasitic transmission, infectious disease dynamics, metabolic disorders, autoimmune diseases, oncological processes, and genetic predispositions in animals. The article demonstrates NGS's efficacy in comprehensive parasite profiling, rapid pathogen identification, personalized tumor analysis, and genetic disease elucidation. Conclusions highlight the transformative potential of NGS in enhancing veterinary diagnostics, treatment planning, and disease management for companion animals. The review's insights promise to revolutionize veterinary care, enabling precise and tailored treatments, improving animal health outcomes, and advancing overall societal well-being through healthier and happier companion animals. Next-Generation Sequencing (NGS) techniques have revolutionized veterinary medicine for cats and dogs, offering insights across various domains. In veterinary parasitology, NGS enables comprehensive profiling of parasite populations, aiding in understanding transmission dynamics and drug resistance mechanisms. In infectious diseases, NGS facilitates rapid pathogen identification, characterization of virulence factors, and tracking of outbreaks. Moreover, NGS sheds light on metabolic processes by elucidating gene expression patterns and metabolic pathways, essential for diagnosing metabolic disorders and designing tailored treatments. In autoimmune diseases, NGS helps identify genetic predispositions and molecular mechanisms underlying immune dysregulation. Veterinary oncology benefits from NGS through personalized tumor profiling, mutation analysis, and identification of therapeutic targets, fostering precision medicine approaches. Additionally, NGS plays a pivotal role in veterinary genetics, unraveling the genetic basis of inherited diseases and facilitating breeding programs for healthier animals. Physiological investigations leverage NGS to explore complex biological systems, unraveling gene–environment interactions and molecular pathways governing health and disease. Application of NGS in treatment planning enhances precision and efficacy by enabling personalized therapeutic strategies tailored to individual animals and their diseases, ultimately advancing veterinary care for companion animals. [ABSTRACT FROM AUTHOR]

Communication disorders in children are multifaceted and often difficult to diagnose accurately due to their complex nature. The Children’s Communication Checklist (CCC) is a widely used diagnostic instrument for identifying and diagnosing children with and without communication disorders. This review aimed to conduct a thematic examination of existing literature that applies the CCC and CCC-2 in the diagnosis of communication disorders. It sought to explore the nuances of CCC’s deployment, its diagnostic traits, and its capability to accurately distinguish individuals with or without communication disorders. A comprehensive literature search was conducted across multiple databases, yielding studies that apply the CCC and CCC-2 in diagnosing communication disorders. The 39 selected studies were subjected to a thematic analysis to identify patterns and themes concerning the use of CCC in diagnosing communication disorders. The review identified seven major themes related to the use of the CCC, such as the evolution and development of the CCC, its application and effectiveness, limitations and strengths, use in specific populations, translation and adaptation, use in different formats, and role in identifying pragmatic language impairments (PLIs). The CCC and CCC-2 have proven invaluable in assessing and diagnosing communication disorders in children. Despite some limitations, their strengths, including their versatility across diverse populations, languages, and contexts, and their ability to identify PLIs, make them effective tools in the field of pediatric communication disorders. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are small lipid bilayer–enclosed vesicles that mediate vital cellular communication by transferring cargo between cells. Among these, tissue-derived extracellular vesicles (Ti-EVs) stand out due to their origin from the tissue microenvironment, providing a more accurate reflection of changes in this setting. This unique advantage makes Ti-EVs valuable in investigating the intricate relationship between extracellular vesicles and cancer progression. Despite considerable research efforts exploring the association between Ti-EVs and cancers, a comprehensive clustering or grouping of these studies remains lacking. In this review, we aim to fill this gap by presenting a comprehensive synthesis of the mechanisms underlying Ti-EV generation, release, and transport within cancer tissues. Moreover, we delve into the pivotal roles that Ti-EVs play in cancer progression, shedding light on their potential as diagnostic and therapeutic tools. The review culminates in the construction of a comprehensive functional spectrum of Ti-EVs, providing a valuable reference for future research endeavors. By summarizing the current state of knowledge on Ti-EVs and their significance in tumor biology, this work contributes to a deeper understanding of cancer microenvironment dynamics and opens up avenues for harnessing Ti-EVs in diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

In this review, we examine the current landscape of point-of-care testing (POCT) diagnostic tools designed for poverty-related infectious diseases (PRIDs) in sub-Saharan Africa (sSA) while delineating key avenues for future advancements. Our analysis encompasses both established and emerging diagnostic methods for PRIDs, addressing the persistent challenges in POCT tool development and deployment, such as cost, accessibility, and reliability. We emphasize recent advancements in POCT diagnostic tools as well as platforms poised to enhance diagnostic testing in sSA. Recognizing the urgency for affordable and widely accessible POCT diagnostic tools to detect PRIDs in sSA, we advocate for a multidisciplinary approach. This approach integrates current and emerging diagnostic methods, explicitly addressing challenges hindering point-of-care (POC) tool development. Furthermore, it recognizes the profound impact of misdiagnosis on public and global health, emphasizing the need for effective tools. To facilitate the successful development and implementation of POCT diagnostic tools in sSA, we propose strategies including the creation of multi-analyte detection POCT tools, the implementation of education and training programs, community engagement initiatives, fostering public-private collaborations, and the establishment of reliable supply chains. Through these concerted efforts, we aim to accelerate the development of POCT in the sSA region, ensuring its effectiveness and accessibility in addressing the diagnostic challenges associated with PRIDs. [ABSTRACT FROM AUTHOR]

Purpose: Despite the robust expansion of research surrounding artificial intelligence (AI) and machine learning (ML) and their applications to medicine, these methodologies often remain opaque and inaccessible to many otolaryngologists. Especially, with the increasing ubiquity of large-language models (LLMs), such as ChatGPT and their potential implementation in clinical practice, clinicians may benefit from a baseline understanding of some aspects of AI. In this narrative review, we seek to clarify underlying concepts, illustrate applications to otolaryngology, and highlight future directions and limitations of these tools. Methods: Recent literature regarding AI principles and otolaryngologic applications of ML and LLMs was reviewed via search in PubMed and Google Scholar. Results: Significant recent strides have been made in otolaryngology research utilizing AI and ML, across all subspecialties, including neurotology, head and neck oncology, laryngology, rhinology, and sleep surgery. Potential applications suggested by recent publications include screening and diagnosis, predictive tools, clinical decision support, and clinical workflow improvement via LLMs. Ongoing concerns regarding AI in medicine include ethical concerns around bias and data sharing, as well as the "black box" problem and limitations in explainability. Conclusions: Potential implementations of AI in otolaryngology are rapidly expanding. While implementation in clinical practice remains theoretical for most of these tools, their potential power to influence the practice of otolaryngology is substantial. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments. [ABSTRACT FROM AUTHOR]

Background The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. Methods We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. Results In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. Conclusions The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE. [ABSTRACT FROM AUTHOR]

Between 1 to 2 of every 1,000 children are born deaf or hard of hearing (DHH) and, of those, 30–50% have additional disabilities, including Autism Spectrum Disorder (ASD). Most measures assessing ASD characteristics rely on some degree of behavioral response to sound (e.g., responding to name, listening response), and may not be appropriate for use with children who are DHH. Further, ASD specific measures do not provide information on a child's functional abilities across developmental domains. We conducted a cross-sectional analysis comparing mean T-scores on a standardized multidimensional measure, the Behavior Assessment System for Children, Third Edition, Parent Rating Scale (BASC-3 PRS), across three groups matched for age and sex: children who are DHH and diagnosed with ASD (DHH + ASD; n = 16); children who are DHH without ASD (DHH-ASD; n = 16); and children who are typically hearing with ASD (H + ASD; n = 16). Analyses revealed statistically significant differences across scales of Attention Problems, Atypicality, Withdrawal, Behavioral Symptoms Index, Social Skills, Leadership, Functional Communication, Activities of Daily Living, Adaptive Skills, Autism Probability Indices, and Developmental Social Disorders. Pairwise comparisons showed DHH + ASD and H + ASD mean T-scores were statistically similar and distinct from DHH-ASD mean T-scores on all these scales except for Withdrawal, Leadership, Functional Communication, and Activities of Daily Living, where pairwise comparisons varied. The findings add to the literature on ASD and DHH children and call for further exploration of the BASC-3 as a tool for both evaluation of ASD and the development of individualized treatment plans in this unique population. [ABSTRACT FROM AUTHOR]

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations. [ABSTRACT FROM AUTHOR]

This article is an editorial published in Frontiers in Veterinary Science that discusses the pathogenesis, diagnosis, prognosis, and treatment of canine lymphoma. The authors highlight the heterogeneity of canine lymphoma and the importance of molecular techniques in its classification. They also discuss advancements in diagnosis, staging, and treatment, as well as the potential of canine lymphoma as a model for human disease. The article includes a summary of nine manuscripts that explore various aspects of canine lymphoma, including early diagnostic biomarkers, RNA biomarkers, microRNAs, next-generation sequencing, Raman spectroscopy, DNA damage response, and new therapeutic protocols. The authors conclude by emphasizing the current research activities and trends in canine lymphoma and their implications for comparative oncology. [Extracted from the article]

Introduction: Pulse harmonic analysis is a quantitative and objective methodology within traditional Chinese medicine (TCM) used to evaluate pulse characteristics. However, interpreting pulse wave data is challenging due to its inherent complexity. This study aims to provide a comprehensive review and comparison of existing human pulse wave harmonic analysis methods to elucidate their patterns and characteristics. Methods: A systematic review of clinical research reports published from 1990 to 2021 was conducted, focusing on variations in harmonic characteristics across different medical conditions and physiological states. Keyword searches included terms related to analysis methods (e.g., ''Pulse Spectrum,'' ''harmonic analysis,'' ''harmonic index'') and measured indicators (e.g., ''vascular response,'' ''PPG,'' ''Photoplethysmography,'' ''aortic,'' ''arterial,'' ''blood pressure''). Supplementary research using PubMed's Mesh terms specifically targeted ''Pulse wave analysis'' within the methods and statistical analysis domain. Articles were filtered based on predefined criteria, including human participants and research related to pulse pressure or vascular volume changes. Conference papers, animal studies, and irrelevant research were excluded, with literature evaluation scales selected based on the retrieved research reports. Results: Initially, 6487 research reports were identified, and after screening, 50 reports were included in the review. The analysis revealed that low-frequency harmonics increase following vigorous activity or sympathetic excitation but decrease during rest or parasympathetic excitation. Cardiovascular patients exhibited elevated first harmonics associated with the liver meridian, while diabetes patients displayed weakened third harmonics related to the spleen meridian. Liver dysfunction was linked to changes in the first harmonic, and cancer patients showed signs of liver and kidney yin deficiency in the first and second harmonics. These findings underscore the potential of harmonic analysis for TCM disease diagnosis and organ assessment. Moreover, individuals with conditions such as liver dysfunction, cancer, and gynecological disorders displayed distinct intensity patterns across harmonics one through ten compared to healthy controls, albeit with some variations. Heterogeneity in these studies mainly stemmed from differences in measurement methods and study populations. Additionally, research suggested that factors like blood circulation and cognitive activity influenced harmonic intensity. Conclusions: In summary, this report consolidates prior research on pulse wave harmonics analysis, revealing unique patterns associated with various physiological conditions. Despite limitations, such as limited sample sizes in previous studies, the observed associations between physiological states and harmonics hold promise for potential clinical applications. This study lays a solid foundation for future applications of arterial wave harmonics analysis, promoting wider adoption of this analytical approach.

As the largest human organ, the skin is continuously exposed to various external and internal triggers that affect body homeostasis. Psoriasis is a persistent inflammatory skin condition that has a major bearing on patients' physiological functioning as well as their mental well-being. It is an autoimmune disorder and has been the focus of extensive research efforts in recent years. Cells secrete exosomes into the environment surrounding them, which comprises a lipid bilayer. The movement of cellular components like microRNAs, mRNAs, DNA, lipids, metabolites, and cell-surface proteins is mediated by exosomes. Exosomes are crucial for inducing communication between cells. There has been extensive study of exosomes, both preclinical and clinical, looking at their potential role in autoimmune diseases. Besides the role that they play in the body's basic processes, exosomes are also considered an increasingly essential part as diagnostic and therapeutic agents. In the following article, we conduct a literature review of current studies related to molecular and structural aspects of exosomes. We emphasis on the function of exosomes in pathogenesis, as well as the possibility of their usage in medicinal applications and as biomarkers. [ABSTRACT FROM AUTHOR]

This paper aimed at devising an intelligence-based method to select compounds that can distinguish between open-angle glaucoma patients, type 2 diabetes patients, and healthy controls. Taking the concentration of 188 compounds measured in the aqueous humour (AH) of patients and controls, linear discriminant analysis (LDA) was used to identify the right combination of compounds that could lead to accurate diagnosis. All possibilities, using the leave-one-out approach, were considered through ad hoc programming and in silico massive data production and statistical analysis. Our proof of concept led to the selection of four molecules: acetyl-ornithine (Ac-Orn), C3 acyl-carnitine (C3), diacyl C42:6 phosphatidylcholine (PC aa C42:6), and C3-DC (C4-OH) acyl-carnitine (C3-DC (C4-OH)) that, taken in combination, would lead to a 95% discriminative success. 100% success was obtained with a non-linear combination of the concentration of three of these four compounds. By discarding younger controls to adjust by age, results were similar although one control was misclassified as a diabetes patient. Methods based on the consideration of individual clinical chemical parameters have limitations in the ability to make a reliable diagnosis, stratify patients, and assess disease progression. Leveraging human AH metabolomic data, we developed a procedure that selects a minimal number of metabolites (3–5) and designs algorithms that maximize the overall accuracy evaluating both positive predictive (PPV) and negative predictive (NPV) values. Our approach of simultaneously considering the levels of a few metabolites can be extended to any other body fluid and has potential to advance precision medicine. Artificial intelligence is expected to use algorithms that use the concentration of three to five molecules to correctly diagnose diseases, also allowing stratification of patients and evaluation of disease progression. In addition, this significant advance shifts focus from a single-molecule biomarker approach to that of an appropriate combination of metabolites. [ABSTRACT FROM AUTHOR]

Extraskeletal osteosarcoma (EOS) is a malignant tumor producing bone matrix and/or chondroid material, without direct attachment to bone or periosteum. In humans and dogs, EOS is highly infiltrating, rapidly growing, often characterized by osteoid deposition and variable ossification, similar to primary skeletal osteosarcoma (SOS). In dogs, EOS arises from visceral and soft tissue locations, occasionally in trauma or foreign body sites, or in granulomas. Few data are currently available on the phenotype of these tumors. The present study aims to assess the expression RUNX2 and Karyopherin alpha-2 in EOS, comparing it with SOS and the data available from the human counterpart. Seventeen cases of canine osteosarcoma (13 EOS and 4 SOS) were retrospectively selected and submitted to immunohistochemistry for RUNX2 and Karyopherin alpha-2. Our results showed that, in EOS, RUNX2 is expressed in a mean of 73.07 ± 5.36 neoplastic cell nuclei, in face of a mean 36.15 ± 6.25 of Karyopherin alpha-2 positive nuclei. Osteoclasts, when present, were negative for both markers. No correlation was observed among the two markers (p > 0.05), nor statistically significant difference in quantitative expression was assessed comparing EOS and SOS groups. RUNX2 is expressed in canine EOS similarly to SOS and could be used as a diagnostic marker in a larger panel. Karyopherin alpha-2 is expressed in canine EOS and SOS similarly to human SOS and could be validated in future studies as an additional diagnostic marker. Further studies should be planned to evaluate the expression of these proteins as prognostic predictive parameters. [ABSTRACT FROM AUTHOR]

At an early stage, esophageal cancer can be removed surgically or endoscopically. T1a tumors are removed by endoscopic resection, whereas T1b tumors are preferably surgically removed (esophagectomy) due to possible lymph node involvement. However, the diagnostic tools (endoscopic ultrasonography (EUS) and CT/PET-CT) used to distinguish between T1a and T1b tumors and to detect malignant lymph nodes are imprecise. This study aimed to review the accuracy of preoperative locoregional staging in superficial esophageal cancer in a Danish setting. This was a retrospective, multicenter study including patients with a cT1 esophageal tumor, both adenocarcinoma and squamous cell carcinoma. Patients receiving neoadjuvant treatment were excluded. Results from the preoperative diagnostics tools were compared with the pathology report to determine the diagnostic accuracy. Sixty-eight patients were included, 34 patients underwent esophagectomy, and 34 patients underwent endoscopic resection. The positive predictive value (PPV) of PET-CT (or CT) (when staged as a T1 tumor) was 77% (95%CI: 0.59–0.88), and the PPV of EUS (when staged as a T1a or T1b tumor) was 52% (95%CI: 0.32–0.72) and 60% (95%CI: 0.36–0.82), respectively. Six patients had malignant lymph nodes in the surgical specimen; none of them was identified before surgery. In conclusion, neither CT/PET-CT nor EUS is a precise tool to distinguish mucosal from submucosal esophageal tumors. Furthermore, in superficial malignant lesions, lymph node involvement is rare, but when present, it is rarely detected before surgery. To improve staging accuracy, all patients with cT1 tumors could be referred for a diagnostic endoscopic resection prior to possible other treatments. [ABSTRACT FROM AUTHOR]

Introduction: Visual disturbances are the most common symptoms of migraine aura. These symptoms can be described systematically by subdividing them into elementary visual symptoms. Since visual symptoms of migraine aura are not easy to describe verbally, we developed a collection of images illustrating previously reported elementary visual symptoms. Objectives: To test a standardised visual migraine aura iconography in a large population of migraine with aura patients and to improve it based on the participants' feedback. Methods: We created a set of images representing 25 elementary visual symptoms and a web-based survey where participants could report whether they recognised these images as part of their visual aura. Elementary visual symptoms could also be recognised via a corresponding text description or described in a free text by participants. Individuals with migraine aura recruited from four tertiary headache centres (in Switzerland, Denmark, Norway and Italy) were invited to complete the survey. Results: Two hundred and fifteen participants completed the study (78.9% women, median age 36). They recognised a total of 1645 elementary visual symptoms from our predefined list. Of those, 1291 (78.4%) where recognised via standardised iconography images. A new type of elementary visual symptom was reported by one participant. Conclusion: Most elementary visual symptoms experienced by participants were recognised via the standardised iconography. This tool can be useful for clinical as well as research purposes. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP. [ABSTRACT FROM AUTHOR]

Biomaterials embody a groundbreaking paradigm shift in the field of drug delivery and human applications. Their versatility and adaptability have not only enriched therapeutic outcomes but also significantly reduced the burden of adverse effects. This work serves as a comprehensive overview of biomaterials, with a particular emphasis on their pivotal role in drug delivery, classifying them in terms of their biobased, biodegradable, and biocompatible nature, and highlighting their characteristics and advantages. The examination also delves into the extensive array of applications for biomaterials in drug delivery, encompassing diverse medical fields such as cancer therapy, cardiovascular diseases, neurological disorders, and vaccination. This work also explores the actual challenges within this domain, including potential toxicity and the complexity of manufacturing processes. These challenges emphasize the necessity for thorough research and the continuous development of regulatory frameworks. The second aim of this review is to navigate through the compelling terrain of recent advances and prospects in biomaterials, envisioning a healthcare landscape where they empower precise, targeted, and personalized drug delivery. The potential for biomaterials to transform healthcare is staggering, as they promise treatments tailored to individual patient needs, offering hope for improved therapeutic efficacy, fewer side effects, and a brighter future for medical practice. [ABSTRACT FROM AUTHOR]

The article outlines the actual issue of development and approbation of the Ukrainian diagnostic visual measures examining social intelligence in pre-schoolers having intellectual difficulties of a mild degree and in preschoolers having normative development. Currently, special psychology needs tools examining socio-personal and emotional development of children with mild intellectual disabilities from the standpoint of the intersubjectivity principle. The article substantiates the emotional peculiarities in socially deprived pre-schoolers with such disabilities. The psychological diagnostic toolkit developed by the article authors is aimed at researching the intersubjective and intrasubjective bases of emotion recognition in the structure of emotional intelligence, which is considered as a component of a broader category - social intelligence. The article presents the examining measure, consisting of portrait pictures depicting certain social situations with corresponding emotions: 1) joy; 2) anger; 3) sadness; 4) fear; 5) surprise; 6) calmness (separate sets for boys and girls); 12 story pictures in which some characters express a certain emotional state (1 picture for each of the above emotional states); and 12 stories for the story pictures. The specifics of emotion recognition by pre-schoolers with mild intellectual disabilities and by children with normal, typical development were determined. Basing on performed theoretical justification, the prospects of further scientific studies will include the theoretical substantiation and development of diagnostic visual measures studying the moral-behavioural component of social intelligence in pre-schoolers with normative typical development and pre-schoolers with mild intellectual disabilities. [ABSTRACT FROM AUTHOR]

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

In this review, we examine the current landscape of point-of-care testing (POCT) diagnostic tools designed for poverty-related infectious diseases (PRIDs) in sub-Saharan Africa (sSA) while delineating key avenues for future advancements. Our analysis encompasses both established and emerging diagnostic methods for PRIDs, addressing the persistent challenges in POCT tool development and deployment, such as cost, accessibility, and reliability. We emphasize recent advancements in POCT diagnostic tools as well as platforms poised to enhance diagnostic testing in sSA. Recognizing the urgency for affordable and widely accessible POCT diagnostic tools to detect PRIDs in sSA, we advocate for a multidisciplinary approach. This approach integrates current and emerging diagnostic methods, explicitly addressing challenges hindering point-of-care (POC) tool development. Furthermore, it recognizes the profound impact of misdiagnosis on public and global health, emphasizing the need for effective tools. To facilitate the successful development and implementation of POCT diagnostic tools in sSA, we propose strategies including the creation of multi-analyte detection POCT tools, the implementation of education and training programs, community engagement initiatives, fostering public-private collaborations, and the establishment of reliable supply chains. Through these concerted efforts, we aim to accelerate the development of POCT in the sSA region, ensuring its effectiveness and accessibility in addressing the diagnostic challenges associated with PRIDs.

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells—all indicative of disease progression—before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, Huntington’s disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.

The emergence of smart and nanobiosensor (NB) technologies has transformed the monitoring and management of bacterial infections. These developments offer remarkable accuracy and precision for detecting infectious pathogens. Smart artificial intelligence (AI)-assisted and NB-based methods are used as powerful tools in biomedicine for bacterial detection, combatting multidrug resistance, and diagnosing infections. In this study, we delve into the advancements in these technologies, focusing on AI-based techniques for NBs in detecting bacterial infections from 2019 to 2024. We analyze the contributions of machine learning and deep learning techniques to enhance performance and reliability. The new approaches to improve the effectiveness and versatility of antibacterial treatments are critically analyzed. Our study includes the observations of carbon nanoparticles that selectively target bacteria using photothermal properties and the production of hybrid hydrogel composites with capabilities. Furthermore, the study emphasizes the crucial significance of NBs in propelling the progress of diagnostic methods, biosensing technologies, and treatments, thereby transforming the healthcare industry and the way diseases are managed. In addition, we explore pathogen-based infections, bacterial diagnosis, and treatment using engineered NBs enhanced with various modalities such as electrochemistry, acoustics, electromagnetism, and photothermal resonance. Our comprehensive review highlights the potential and throws light on future research directions for effective management and control of bacterial infections.

Extraskeletal osteosarcoma (EOS) is a malignant tumor producing bone matrix and/or chondroid material, without direct attachment to bone or periosteum. In humans and dogs, EOS is highly infiltrating, rapidly growing, often characterized by osteoid deposition and variable ossification, similar to primary skeletal osteosarcoma (SOS). In dogs, EOS arises from visceral and soft tissue locations, occasionally in trauma or foreign body sites, or in granulomas. Few data are currently available on the phenotype of these tumors. The present study aims to assess the expression RUNX2 and Karyopherin alpha-2 in EOS, comparing it with SOS and the data available from the human counterpart. Seventeen cases of canine osteosarcoma (13 EOS and 4 SOS) were retrospectively selected and submitted to immunohistochemistry for RUNX2 and Karyopherin alpha-2. Our results showed that, in EOS, RUNX2 is expressed in a mean of 73.07 ± 5.36 neoplastic cell nuclei, in face of a mean 36.15 ± 6.25 of Karyopherin alpha-2 positive nuclei. Osteoclasts, when present, were negative for both markers. No correlation was observed among the two markers (p > 0.05), nor statistically significant difference in quantitative expression was assessed comparing EOS and SOS groups. RUNX2 is expressed in canine EOS similarly to SOS and could be used as a diagnostic marker in a larger panel. Karyopherin alpha-2 is expressed in canine EOS and SOS similarly to human SOS and could be validated in future studies as an additional diagnostic marker. Further studies should be planned to evaluate the expression of these proteins as prognostic predictive parameters.

Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the in vitro IgG-EC50 values and S-IgG values. Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC50), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC50 and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC50. Results: A high correlation was observed between S-IgG and IgG-EC50 with a Spearman's ρ value of −0.748 (95 % confidence interval [CI]: −0.804–0.678). Using an IgG-EC50 of 50 μg/mL and 20 μg/mL as the cut-off values for moderate and high in vitro neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823–0.946) and 0.920 (95 % CI: 0.681–0.979), respectively. Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating in vitro virus-neutralizing activity, with a high correlation with IgG-EC50 when the rational cut-off value is carefully determined.

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP.

Next-Generation Sequencing (NGS) techniques have revolutionized veterinary medicine for cats and dogs, offering insights across various domains. In veterinary parasitology, NGS enables comprehensive profiling of parasite populations, aiding in understanding transmission dynamics and drug resistance mechanisms. In infectious diseases, NGS facilitates rapid pathogen identification, characterization of virulence factors, and tracking of outbreaks. Moreover, NGS sheds light on metabolic processes by elucidating gene expression patterns and metabolic pathways, essential for diagnosing metabolic disorders and designing tailored treatments. In autoimmune diseases, NGS helps identify genetic predispositions and molecular mechanisms underlying immune dysregulation. Veterinary oncology benefits from NGS through personalized tumor profiling, mutation analysis, and identification of therapeutic targets, fostering precision medicine approaches. Additionally, NGS plays a pivotal role in veterinary genetics, unraveling the genetic basis of inherited diseases and facilitating breeding programs for healthier animals. Physiological investigations leverage NGS to explore complex biological systems, unraveling gene–environment interactions and molecular pathways governing health and disease. Application of NGS in treatment planning enhances precision and efficacy by enabling personalized therapeutic strategies tailored to individual animals and their diseases, ultimately advancing veterinary care for companion animals.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations.

This paper aimed at devising an intelligence-based method to select compounds that can distinguish between open-angle glaucoma patients, type 2 diabetes patients, and healthy controls. Taking the concentration of 188 compounds measured in the aqueous humour (AH) of patients and controls, linear discriminant analysis (LDA) was used to identify the right combination of compounds that could lead to accurate diagnosis. All possibilities, using the leave-one-out approach, were considered through ad hoc programming and in silico massive data production and statistical analysis. Our proof of concept led to the selection of four molecules: acetyl-ornithine (Ac-Orn), C3 acyl-carnitine (C3), diacyl C42:6 phosphatidylcholine (PC aa C42:6), and C3-DC (C4-OH) acyl-carnitine (C3-DC (C4-OH)) that, taken in combination, would lead to a 95% discriminative success. 100% success was obtained with a non-linear combination of the concentration of three of these four compounds. By discarding younger controls to adjust by age, results were similar although one control was misclassified as a diabetes patient. Methods based on the consideration of individual clinical chemical parameters have limitations in the ability to make a reliable diagnosis, stratify patients, and assess disease progression. Leveraging human AH metabolomic data, we developed a procedure that selects a minimal number of metabolites (3–5) and designs algorithms that maximize the overall accuracy evaluating both positive predictive (PPV) and negative predictive (NPV) values. Our approach of simultaneously considering the levels of a few metabolites can be extended to any other body fluid and has potential to advance precision medicine. Artificial intelligence is expected to use algorithms that use the concentration of three to five molecules to correctly diagnose diseases, also allowing stratification of patients and evaluation of disease progression. In addition, this significant advance shifts focus from a single-molecule biomarker approach to that of an appropriate combination of metabolites.

Biomaterials embody a groundbreaking paradigm shift in the field of drug delivery and human applications. Their versatility and adaptability have not only enriched therapeutic outcomes but also significantly reduced the burden of adverse effects. This work serves as a comprehensive overview of biomaterials, with a particular emphasis on their pivotal role in drug delivery, classifying them in terms of their biobased, biodegradable, and biocompatible nature, and highlighting their characteristics and advantages. The examination also delves into the extensive array of applications for biomaterials in drug delivery, encompassing diverse medical fields such as cancer therapy, cardiovascular diseases, neurological disorders, and vaccination. This work also explores the actual challenges within this domain, including potential toxicity and the complexity of manufacturing processes. These challenges emphasize the necessity for thorough research and the continuous development of regulatory frameworks. The second aim of this review is to navigate through the compelling terrain of recent advances and prospects in biomaterials, envisioning a healthcare landscape where they empower precise, targeted, and personalized drug delivery. The potential for biomaterials to transform healthcare is staggering, as they promise treatments tailored to individual patient needs, offering hope for improved therapeutic efficacy, fewer side effects, and a brighter future for medical practice.

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

Chemokine receptors are important components of cellular signaling and play a critical role in directing leukocytes during inflammatory reactions. Their importance extends to numerous pathological processes, including tumor differentiation, angiogenesis, metastasis, and associations with multiple inflammatory disorders. The necessity to monitor the in vivo interactions of cellular chemokine receptors has been driven the recent development of novel positron emission tomography (PET) imaging agents. This imaging modality provides non-invasive localization and quantitation of these receptors that cannot be provided through blood or tissue-based assays. Herein, we provide a review of PET imaging of the chemokine receptors that have been imaged to date, namely CXCR3, CXCR4, CCR2, CCR5, and CMKLR1. The quantification of these receptors can aid in understanding various diseases, including cancer, atherosclerosis, idiopathic pulmonary fibrosis, and acute respiratory distress syndrome. The development of specific radiotracers targeting these receptors will be discussed, including promising results for disease diagnosis and management. However, challenges persist in fully translating these imaging advancements into practical therapeutic applications. Given the success of CXCR4 PET imaging to date, future research should focus on clinical translation of these approaches to understand their role in the management of a wide variety of diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose. [ABSTRACT FROM AUTHOR]

Background: Diabetes and prediabetes are diagnosed differentially by Western and Chinese medicine. While Western medicine uses objective laboratory analysis of biochemical parameters to define the severity of diabetes and prediabetes, Chinese medicine uses a comprehensive approach that integrates observation, inquiry, pulse palpation, and tongue diagnosis. The medical information collected is then categorized into different syndromes. However, traditional methods of pulse and tongue diagnoses used to determine syndrome differentiation are highly subjective and skill dependent., Objective: This study aims to identify the gap in conventional traditional Chinese medicine (TCM) diagnostic techniques for syndrome differentiation analysis using contemporary diagnostic devices. We devised a protocol for a nonrandomized, exploratory, observational case-control study with equal allocations in 5 arms to investigate the syndrome differentiation of diabetes and prediabetes. We hypothesize that the TCM syndrome differentiation of diabetes and prediabetes in the tropical climate may differ from that defined based on the Chinese demographic. We also speculate that the high-frequency spectral energy may reflect a difference in pulse wave intensity and density between the healthy and diabetes groups., Methods: A total of 250 eligible participants will be equally assigned to 1 of 5 arms (healthy or subhealthy, prediabetes, diabetes, prediabetes with hypertension and dyslipidemia, and diabetes with hypertension and dyslipidemia). Participants aged 21-75 years, of any sex or race, and have been diagnosed with diabetes (fasting plasma glucose [FPG] of 7 mmol/L, or 2-hour plasma glucose [2hPG] of 11.1 mmol/L) or prediabetes (impaired FPG of 6.1-6.9 mmol/L, or impaired glucose tolerance with an 2hPG of 7.8-11 mmol/L) will be included. The Health Evaluation Questionnaire, Physical Activity Questionnaire, sugar intake assessment, Constitution in Chinese Medicine Questionnaire, radial pulse diagnosis, and tongue diagnosis will be performed in a single visit. ANOVA for continuous data and chi-square tests of independence will be used for categorical data assessments, with a level of P<.05 considered significant., Results: The recruitment is in progress. We anticipate that the study will conclude in June 2025. As of July 15, 2024, we have enrolled 140 individuals., Conclusions: To the best of our knowledge, this is the first study to use contemporary TCM diagnostic instruments to map expert and empirical knowledge of TCM to its scientific equivalents for the purpose of evaluating the syndrome differentiation of diabetes. We designed this protocol with the exploratory goal to examine objectively the syndrome differentiation of patients with diabetes and those with prediabetes using TCM diagnostic technologies. The data collected and evaluated under standardized conditions using these contemporary diagnostic devices will exhibit a higher degree of stability, hence yielding dependable and unbiased results for syndrome differentiation. Thus, our findings may potentially increase the accuracy of identification, diagnosis, treatment, and prevention of diabetes and prediabetes through a system of targeted treatment., Trial Registration: ClinicalTrials.gov NCT05563090; https://clinicaltrials.gov/ct2/show/NCT05563090., International Registered Report Identifier (irrid): DERR1-10.2196/56024., (©Hui Ping Ng, Shu Yun Chong, Yi Huan Li, Tong Hwee Goh, Ka Yii Pang, Michelle Jessica Pereira, Chin-Ming Huang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.09.2024.)

Background : The incidence of Legionnaires' disease (LD) is increasing steadily in Europe. Its early diagnosis by general practitioners (GPs) is crucial for better patient outcomes. Study objectives : This study assessed Belgian GPs' knowledge about LD and the accessibility of diagnostic tests in their practices. Methods : A specifically designed questionnaire was distributed to actively practicing GPs, including primary care trainees, between 31 January 2022 and 13 March 2022. This survey targeted approximately 4200 GPs with an estimated population catchment of 30% of the actively working Belgian GPs. Results : The response rate was estimated at 3%. Over 70% of the GPs correctly identified the LD occurrence peak, major risk factors, and clinical manifestations. While 62% of participants preferred the Legionella pneumophila urinary antigen test (UAT) as a primary diagnostic method, 75% were unsure about its availability within their laboratories and 82% had not prescribed it in the last year. Finally, 76% expressed a desire for additional information on this topic. Conclusions : Belgian GPs should evaluate the possibility of conducting UAT testing in their laboratories to enhance LD case management and improve their preparedness. Furthermore, initiatives should be implemented to improve communication between specialists and GPs and develop educational programs directed at Belgian GPs.