Advanced Diagnostics Research Articles

Modified Delphi Study to Establish Consensus About Child Neurology Residency Education: Next-Gen Training.

Rapid advances in diagnostics and treatments are shifting child neurology practice, but child neurology training requirements have been much slower to change. Previous literature confirms strong support for modernization, but no formal consensus exists regarding maintaining or changing training. We aimed to develop a holistic consensus regarding the optimal training pathway and requirements using a modified Delphi process. The authors invited 48 child neurologists as panelists, intentionally selecting to represent the diverse geography, practice type, subspecialties, and other demographics of child neurologists practicing in the United States. Panelists participated in an anonymized modified Delphi study with 4 rounds evaluating statements regarding current training requirements, core rotation durations, and mandatory subspecialty rotations with the option to agree or disagree. Statements were derived from current Accreditation Council of Graduate Medical Education, American Board of Psychiatry and Neurology, and American Board of Pediatrics requirements for child neurology training and recent literature. Statements that did not reach a predefined level of consensus (≥75% agreement or disagreement on a 7-point Likert scale) were re-queried or modified for subsequent rounds. Panelists had access to all previous anonymized results and comments. The final modifications were presented in round 4 as a comprehensive training proposal. Twenty-seven panelists agreed to participate, with most completing all 4 rounds. In round 1, consensus was reached on 45 of 118 (38%) items; round 2, 28 of 87 (32%); round 3, 16 of 25 (64%); and round 4, 1 of 1 (100%). There was consensus regarding the age scope of practice and certain subspecialties that should be required, but no initial consensus regarding time-based requirements. By round 4, consensus emerged for the following rotations-months: neonatal and pediatric intensive care-4, adolescent medicine-0.5, emergency medicine-1.5, inpatient pediatrics-3, outpatient pediatrics-3.5, inpatient child neurology-9.5, outpatient child neurology-6, inpatient adult neurology-3, outpatient adult neurology-2, genetics-2, EEG/neurophysiology-2, neuroimaging-1, child psychiatry-1, and electives-7.5. The consensus schedule consists of 46.5 total months of requirements. This study suggests that, despite diverging views prevalent among child neurologists, a diverse panel can, through a multiround Delphi process, arrive at consensus regarding many core features of the child neurology training structure and certification requirements.

Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.

Tandem repeat disorders (TRDs) are genetic conditions characterized by the abnormal expansion of repetitive DNA sequences within specific genes. The growing number of identified TRDs highlights their complexity, with varied molecular mechanisms ranging from toxic protein production and repeat-associated non-AUG translation to RNA toxicity and epigenetic modifications. TRDs also exhibit unique clinical features such as reduced penetrance, anticipation, and repeat motif changes. Advances in molecular diagnostics such as long-read sequencing have significantly improved the detection of TRDs, especially for large or complex repeat expansions. Additionally, emerging therapeutic strategies, particularly antisense oligonucleotides (ASOs) and gene editing technologies, are showing great promise. ASOs in particular have demonstrated success through mechanisms like allele-specific knockdown and splice modulation. In this review, we explore the classification of TRDs, advances in diagnostics, molecular mechanisms, clinical features, and innovative therapeutic strategies, highlighting the need for further research to refine treatments and improve outcomes.

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients. Underdiagnosis and misdiagnosis are common, response assessment remains challenging, and the prognosis associated with this disease of whole neuroaxis remains extremely poor. The dearth of effective therapies is further challenged by the difficulties in studying this dynamic disease state. In this Review, a multidisciplinary group of experts describe the emerging evidence and areas of active investigation in LMD and provide directed recommendations for future research. Drawing upon paradigm-changing advances in mechanistic science, computational approaches, and trial design, the authors discuss domain-specific and cross-disciplinary strategies for optimizing the clinical and translational research landscape for LMD. Advances in diagnostics, multi-agent intrathecal therapies, cell-based therapies, immunotherapies, proton craniospinal irradiation and ongoing clinical trials offer hope for improving outcomes for patients with LMD.

Advancements in Artificial Intelligence-Enhanced Imaging Diagnostics for the Management of Liver Disease—Applications and Challenges in Personalized Care

Liver disease can significantly impact life expectancy, making early diagnosis and therapeutic intervention critical challenges in medical care. Imaging diagnostics play a crucial role in diagnosing and managing liver diseases. Recently, the application of artificial intelligence (AI) in medical imaging analysis has become indispensable in healthcare. AI, trained on vast datasets of medical images, has sometimes demonstrated diagnostic accuracy that surpasses that of human experts. AI-assisted imaging diagnostics are expected to contribute significantly to the standardization of diagnostic quality. Furthermore, AI has the potential to identify image features that are imperceptible to humans, thereby playing an essential role in clinical decision-making. This capability enables physicians to make more accurate diagnoses and develop effective treatment strategies, ultimately improving patient outcomes. Additionally, AI is anticipated to become a powerful tool in personalized medicine. By integrating individual patient imaging data with clinical information, AI can propose optimal plans for treatment, making it an essential component in the provision of the most appropriate care for each patient. Current reports highlight the advantages of AI in managing liver diseases. As AI technology continues to evolve, it is expected to advance personalized diagnostics and treatments and contribute to overall improvements in healthcare quality.

Case report: Giant meningioma of the left hemisphere

Meningiomas are some of the most prevalent primary brain tumors in adults, and are typically non-neuroglial in nature. A variety of symptoms may be observed, including headaches, fluctuations in mental status, ataxia, muscle weakness, nausea and vomiting, seizures, visual changes, speech disorders, and sensory abnormalities. The World Health Organization (WHO) has a grading system for meningiomas based on histological criteria, which is as follows: Grade 1 meningiomas are considered benign; Grade 2 meningiomas have a moderately aggressive nature and usually present with histological atypia; and Grade 3 meningiomas exhibit aggressive malignant behavior. Grade 3 meningiomas are distinguished by aberrant and accelerated cellular proliferation, which increases the probability of invasion and recurrence within the central nervous system relative to the other grades. Malignant meningiomas are further classified by tumor size. For example, WHO grade 3 meningiomas with diameter >5 cm are designated giant meningiomas. Giant meningiomas are complicated by their potential for compression of the brain tissue, which can lead to increased intracranial pressure and hemodynamic changes. In many cases, these changes induce vasogenic edema in the adjacent brain tissue. This article details a rare case of rapidly growing atypical giant meningioma that progressed to an anterior-posterior diameter of 13 cm within 3 years, occupying the majority of the left hemisphere of the brain and encroaching upon the right intracranial structures. Through recent advances in medical diagnostics and heightened public awareness of health issues, cases with such large meningiomas have become exceedingly rare. Fortunately, the tumor in the present case was successfully resected using advanced surgical techniques that employed microscopy in conjunction with sodium fluorescein, resulting in complete removal of the tumor and restoration of the patient’s muscle strength postoperatively. The value of fluorescence-guided surgery in this type of procedure is support in the present case report.

Prenatal imaging - role of fetal MRI.

Congenital abnormalities occur in about 3 in 100 fetuses. Prenatal ultrasound is the standard technique to detect these fetal abnormalities. In Germany, three ultrasound examinations are provided in the first, second, and third trimesters, respectively. Fetal magnetic resonance imaging (MRI) can be used as an adjunct technique to provide further information in cases of congenital abnormalities.A literature search was performed on PubMed focusing on publications that used fetal MRI as a secondary approach after prenatal ultrasound.MRI is a safe imaging method that does not harm the fetus when used during pregnancy. Some publications with experts in radiology show a very clear diagnostic advantage with respect to performing MRI on fetuses with brain abnormalities, while other publications with experts in neurosonography do not find the advantage to be that evident. Both techniques are clearly user-dependent.Fetal MRI can supplement the information obtained by fetal ultrasound and can provide additional information or exclude others. Diagnosis made by an interdisciplinary cooperation based on all available ultrasound and MRI findings is the key to optimal imaging and advice for expectant parents. · Fetal MRI poses no risk for the fetus.. · MRI aids prenatal ultrasound in the evaluation of prenatal findings.. · Tavares de Sousa M, Schönnagel BP, Denecke J et al. Prenatal imaging - role of fetal MRI. Fortschr Röntgenstr 2024; DOI 10.1055/a-2357-6997.

Implementing New Dementia Care Models in Practice.

Care for patients with Alzheimer disease and related neurodegenerative causes of dementia is in the midst of a transformation. Recent advancements in diagnostics and therapeutics reflect a rapidly evolving knowledge base and represent positive steps for patients and clinicians facing these progressive diseases; however, the complexities of emerging biomarkers and treatment options present challenges that will require systematic adaptations to routine care to facilitate effective incorporation of these options. This article reviews ongoing updates in the assessment and management of neurodegenerative causes of dementia, focusing on practical models for innovation that practices and health care systems can use to implement these new tools. In particular, sustainable adaptation in the field will benefit from a comprehensive approach implemented at local levels, including (1) education of clinicians and communities to refine perceptions about dementia care, (2) multifaceted stakeholder engagement to optimize infrastructure and workflows to the new era, and (3) investments in personnel to address existing and exacerbated gaps.

Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients.

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients. Our study also revealed complex interactions among inflammation-related genes, including increased CXCL10 and IL1R2 expression and decreased IL-1b expression in the acute phase. The diminished expression of HLA class II genes indicates impaired antigen presentation. These findings highlight the delicate balance of immune responses in YF pathogenesis and lay the groundwork for future therapeutic and diagnostic advancements.

Rational Design and Development of Phenazine-based Electron Mediators for Enzyme-based Biosensors: Advancing Clinical Diagnostics Through Computational Exploration

The advancement of clinical diagnostics critically depends on the development of efficient and reliable electron mediators. These mediators are pivotal in biosensors, facilitating electron transfer (ET) reactions between the redox-active centers of immobilized enzymes and a conductive electrode support, thus enhancing the sensitivity and selectivity of biosensor devices. In this study, we specifically investigate phenazine as innovative electron mediators with promising diagnostic potential. Through meticulous computational predictions, we identify candidates exhibiting not only high solubility and favorable enzyme binding energies, but also appropriate redox potentials conducive to efficient electron transfer processes. Subsequently, these selected candidates undergo rigorous validation processes to assess their performance in blood glucose test strips, demonstrating a wide linear range from 1.00mM to 32.49mM (R2=0.9976) in whole blood tests, and a strong selectivity of glucose over other interfering substances such as ascorbic acid, uric acid, xylitol and hemoglobin.

A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study

New paradigms of diagnosis and treatment have changed the neurodegenerative trajectory for individuals with spinal muscular atrophy (SMA). Registries are a critical tool to provide real-world data on treatment patterns, their effects and health care provision within this evolving paradigm of care. This study aimed to evaluate the phenotypic and genotypic landscape, treatment patterns and health impact of SMA in Australia through the national registry. This cross-sectional study investigated demographic, clinical and genetic information, sequelae of weakness, treatment patterns and patient-reported outcomes amongst individuals with SMA enrolled in the Australian Neuromuscular Disease Registry (ANMDR) from 1st January 2020 to 30th April 2023. Descriptive statistics were used for analysis and Chi-Squared or Fisher's exact tests for associations. 195 individuals with SMA enrolled into the ANMDR. 5/195 (2.6%) were deceased by censor date. Of (n=190) individuals living with SMA, 104/190 (54.7%) were children. Minimum Australian prevalence was 0.73/100,000. SMN2 copies were inversely associated with phenotype in those with homozygous SMN1 deletions (p<0.0001)). Treatment was utilised in 154/190 (81%) of the population, with 65/137 (47.6%) of individuals perceiving improvements with therapeutic intervention on Patient/Parent Global Impression of Improvement scale (p<0.0001). Engagement with multidisciplinary care practitioners was significantly higher among children with SMA than adults (93% versus 12%, p<0.0001). Despite diagnostic and therapeutic advances, mortality and the multi-systemic health impact of SMA continue to be experienced within the Australian population. Healthcare provision must align with patient-centred outcomes, adapting to meeting their changing but ongoing care requirements. The study identified the considerable unmet need for multidisciplinary care, not only for adults with SMA but also for the emerging cohort of treated children, emphasising the imperative for comprehensive healthcare provision to address their evolving needs. No funding was received for this study.

A Novel and Advanced Diagnostic Approach toward Paracidovorax citrulli Causing Bacterial Fruit Blotch in Watermelon by Direct SYBR Green Real-Time PCR Assay.

Bacterial fruit blotch (BFB) caused by Paracidovorax citrulli is a devastating disease in cucurbit hosts such as watermelon. P. citrulli is a seed-borne pathogen, and contaminated seeds are the primary inoculum. Because it is difficult to control BFB after the emergence of the disease, it is essential to detect the pathogen and remove infected plant materials, including seeds, in the early stages. In this study, we developed a direct SYBR Green real-time polymerase chain reaction (PCR) method using a new species-specific marker for detecting P. citrulli with high specificity and sensitivity. The genome information of P. citrulli and related species was collected and compared to retrieve the P. citrulli-specific gene. The primer set RS01560-164 was designed based on the selected gene and tested for specificity and sensitivity using cloned DNA, genomic DNA, cell suspension, and suspensions obtained from infected watermelon cotyledons. Our primer set detected only P. citrulli from the closely related species with a detection limit of cloned DNA at 1.46 × 103 copies/µl, gDNA at 500 fg/µl, and cell suspension at 1.4 × 104 cfu/ml by real-time PCR. Our method also detected P. citrulli from diseased plants without the need for a DNA extraction phase. Therefore, the primer set and real-time PCR methods newly developed in this study could be applied for the specific detection of P. citrulli in plants or seeds with high sensitivity and robustness, providing the potential to manage BFB in cucurbits.

Diagnostic advances in sepsis: A comparative analysis of syndromic approaches and molecular biology techniques in clinical bacteremia

Sepsis remains a leading cause of morbidity and mortality. This retrospective study, conducted at Avicenne Military Hospital in Marrakech over ten years, analyzed 3721 blood cultures, identifying 420 cases of bacteremia (11.3% positivity rate). The predominant isolates included Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Klebsiella spp., and Acinetobacter baumannii, with significant resistance patterns observed. Notably, 50% of S. aureus were methicillin-resistant (MRSA), while extended-spectrum beta-lactamase (ESBL) production was found in 30% of E. coli and Klebsiella pneumoniae isolates. The FilmArray multiplex PCR system was utilized to enhance rapid pathogen identification, reducing turnaround time from 72 hours to under 2 hours, and demonstrated high concordance with conventional cultures. The molecular diagnostics identified various resistant strains, including carbapenemase-producing organisms in K. pneumoniae and multidrug-resistant A. baumannii, underscoring the critical need for effective antimicrobial stewardship. Overall, this study emphasizes the evolving epidemiology of bacteremia, the rising antimicrobial resistance, and the utility of rapid molecular diagnostics in guiding timely and appropriate treatment, ultimately aiming to improve patient outcomes in sepsis management.

A Comprehensive Review of Pfu DNA Polymerase: Extraction, Production and Applications

Pfu DNA Polymerase, a thermostable enzyme derived from the hyperthermophilic archaeon Pyrococcus furiosus, is widely recognized for its high fidelity and strong processivity. Its 3'-5' exonuclease activity makes it indispensable for the correct amplification of both short and complex DNA strands. These biochemical properties of Pfu DNA Polymerase have encouraged considerable advancements in its extraction and production methods. This review covers some of the traditional approaches for purification, including protein purification and affinity chromatography, and updates on recent advances in recombinant gene expression, automated systems of production, and membrane-based technologies. New ways of engineering enzymes have recently been developed, such as CRISPR-Cas9-mediated gene optimization, which raised the bar on extraction efficiency to meet emerging demand. Once challenging, Pfu DNA Polymerase production has been significantly streamlined through recombinant expression in E. coli both at a laboratory and commercial scale. The optimization techniques that are involved with IPTG concentration and Response Surface Methodology have increased the yield by up to 30%. Auto-induction means even higher biomass outputs are allowed. Today, applications of Pfu DNA Polymerase span from standard PCR up to advanced clinical diagnostics in the fields of molecular biology, forensic analysis, clinical microbiology, and biotechnology.

Consensus of the Italian Primary Immunodeficiency Network on the use and interpretation of genetic testing for the diagnosis of inborn errors of immunity (IEI)

BackgroundInborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the interpretation of genetic testing produced by the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) do not cover specificities for the application to IEIs. ObjectiveThe aim of this consensus study is to define the best approach to genetic testing for IEIs. MethodsA panel of experts in the context of the Italian Primary Immunodeficiency Network (IPINet) composed a list of statements that were evaluated using Delphi method. ResultsThe experts recommend that genetic testing for IEIs should be offered to selected patients with warning signs for IEIs and highlight the crucial role of thorough phenotyping and functional tests for the conclusive diagnosis of IEI. Comprehensive educational programs targeted to health care professionals and the public should be developed to increase IEIs awareness and reduce the diagnostic delay. Ethical issues should be pondered over the diagnostic advantages of genetic tests requested for diagnostic purposes. ConclusionAdherence to the guidelines on the use and interpretation of genetic testing for the diagnosis of IEIs should help limiting the inappropriate use of these techniques and reduce the risk of misdiagnosis and apprehension for inconclusive genetic results.

RNA binding protein RBM22 suppresses non-small cell lung cancer tumorigenesis by stabilizing LATS1 mRNA.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. Despite advancements in diagnostics and therapeutics, the prognosis for NSCLC remains poor, highlighting the urgent need for novel treatment options. RNA binding proteins, particularly RBM22, have emerged as significant contributors to cancer progression by influencing RNA splicing and gene expression. This study investigates the role of RBM22 in NSCLC and its potential as a therapeutic target. We focus on the effects of RBM22 on cell proliferation, invasion, stemness, and its interaction with LATS1 mRNA. RBM22 expression was assessed in samples and cell lines of NSCLC through techniques such as real-time PCR and western blot analysis. To modify RBM22 levels, overexpression and knockdown methods were employed utilizing vectors and siRNAs. We conducted assays for cell proliferation, invasion, and stemness to evaluate the effects of altering RBM22. The interaction between RBM22 and LATS1 mRNA was investigated using RNA immunoprecipitation. In addition, in vivo studies involving subdermal tumor and lung metastasis models in athymic mice were carried out to evaluate how changes in RBM22 influence the tumorigenic and metastatic characteristics of NSCLC. Our analysis revealed a significant underexpression of RBM22 in NSCLC tissues compared to adjacent healthy tissues. Increasing RBM22 expression in NSCLC cell lines led to a marked decrease in cellular proliferation, invasiveness, and stemness, while silencing RBM22 produced opposing effects. Further investigations confirmed that RBM22 directly interacts with LATS1 mRNA, thereby stabilizing and enhancing its expression. In vivo studies validated that elevated RBM22 expression substantially reduced tumor formation and pulmonary metastases, as evidenced by decreased tumor size, mass, and Ki-67 proliferation marker expression, along with a significant reduction in the number of metastatic nodules in the lungs. Our study demonstrates that RBM22 suppresses NSCLC by stabilizing LATS1 mRNA, which in turn reduces tumor growth and metastasis. Consequently, RBM22 emerges as a valuable therapeutic target for NSCLC, offering new strategies for addressing this challenging condition.

Comparative evaluation of BacT/ALERT VIRTUO and BACTEC FX400 blood culture systems for the detection of bloodstream infections.

Bloodstream infections (BSI) pose significant threats to patient health, necessitating timely and accurate diagnostics to reduce mortality and morbidity. This study aimed to evaluate the clinical performance of the BacT/ALERT VIRTUO blood culture system with FANPlus bottles compared to the BACTEC FX400 system in detecting bloodstream pathogens. A total of 1,772 blood specimens were collected from various hospital wards. Specimen selection criteria were based on clinical suspicion of bloodstream infections, ensuring the inclusion of relevant and representative patient samples. These blood samples, collected from the same suspected sepsis patients, were cultured in parallel using both the BacT/ALERT VIRTUO and BACTEC FX400 systems. The diagnostic efficiency of both systems, including detection rates, time to detection (TTD), and sensitivity across different bacterial species, was assessed. In various application scenarios, the VIRTUO system demonstrates a higher positive detection rate, whether in the intensive care unit (ICU) (8.5% vs 6.4%, P = 0.028) or in general wards. Additionally, for different types of bacteria, the TVIRTUO system exhibits superior detection rates for anaerobic bacteria (5.9% vs 3.2%, P < 0.001) and aerobic bacteria (9.1% vs 7.2%, P = 0.043). Furthermore, it boasts a shorter median TTD of 14 hours compared to 16 hours, and a higher sensitivity for Gram-positive bacteria (2.8% vs 1.6%, P < 0.001). These findings emphasize VIRTUO's effectiveness in enhancing diagnostic accuracy, achieving faster time to detection, and expanding the spectrum of detected organisms, thereby facilitating the quicker initiation of appropriate therapies, supporting precise clinical decision-making, and ultimately improving patient outcomes.IMPORTANCEOur study conducted a critical evaluation of advanced blood culture technologies for managing bloodstream infections (BSI). A distinctive strength of our research is the large sample size and the concurrent testing of the same patients with two systems, a methodology rarely achieved in other studies. BSIs present severe health threats, necessitating prompt and accurate diagnostics to mitigate morbidity and mortality. The BacT/ALERT VIRTUO system, in comparison to the BACTEC FX400 system, demonstrated superior detection capabilities, emphasizing the critical role of advanced diagnostics in clinical settings.

Preface

It is both an honor and a privilege to introduce this inaugural issue of Biomaterials Connect. Biomaterials Connect is a newly established journal that intends to be an inclusive forum for all researchers, scientists, engineers, and professionals working within the various fields of biomaterials science. The purpose is to encourage the contribution to multi-disciplinary interaction, the diffusion of new ideas, and contributing to biomaterials research and applications, but in particular those related to medicine and dentistry. Biomaterials Connect is based on the belief that biomaterials would continue to form the foundation of healthcare advances. In collaboration with Scifiniti, we are committed to delivering a premier, peer-reviewed journal to fulfill the multi-faceted and changing biomaterials community needs. Now more than ever, it is critical to remove the barriers among disciplines and provide the fertile ground on which cutting-edge research will flourish to enhance health and improve quality of life. It is a matter of great pride to present a collection of articles that really highlights the breadth and depth of biomaterial research. This issue features two state-of-the-art review articles; one focused on the biofunctional applications of chitosan in dentistry, and another examining the role of MEMS and nanomaterials in the advancement of diagnostics and therapeutics in healthcare. In addition, this issue presents three experimental studies addressing current challenges in medicine and dentistry. These include an investigation into the effects of surface treatment of hemp fibers on the properties of polyethylene composites, a study on the synthesis and characterization of laurate ester of acetate cellulose, and research on the translucency and polymerization efficiency of contemporary resin composites. Finally, we shortly discuss the disruptive potential of 3D printing in the biomaterials field. Biomaterials Connect will cover a broad scope including, but not limited to, tissue engineering, medical devices, dental implants, biocompatibility, nanotechnology, and 3D printing. Original research articles, reviews, perspectives, and commentaries that contribute to the development of biomaterials science are invited. We aim to create a forum for an interactive and creative community that challenges established dogma through facilitating research across disciplinary boundaries. I feel very privileged to stand as Editor-in-Chief of this journal, having such an enthusiastic Editorial Board and such an extended network of renowned reviewers. We have one common goal, which is to maintain standards of scientific stringency and integrity as high as possible. I now call on all researchers from the international community to join this exciting journey and share valuable inputs and results with Biomaterials Connect. Thank you for your support, and I hope you find this first issue both informative and inspiring.

Integrating Diagnostic Approaches in Infant Bacterial Meningitis Caused by a Non-K1 Escherichia coli: A Case Report

Background: Infant meningitis, particularly caused by Escherichia coli, remains a life-threatening condition, especially in premature and low-weight infants. Infections of the central nervous system can be fatal, necessitating prompt diagnosis and appropriate treatment. Acute infections caused by various pathogens, including E. coli, often present with similar clinical symptoms. The rapid identification of pathogens and their antimicrobial resistance mechanisms is critical for timely and effective treatment. We report the case of an 8-month-old patient who presented with fever, diarrhea, and convulsive seizures and was subsequently diagnosed with meningitis. Despite initial empirical treatment with ceftriaxone, the patient’s condition worsened. Methods: At Bambino Gesù Children’s Hospital, molecular diagnostic tools, including the FilmArray Meningitis/Encephalitis and Blood Culture Identification panels, were employed. Results: Although the Meningitis panel did not detect any pathogens due to the lack of the specific bacterial target, the off-label use of the Blood Culture Identification panel identified a non-K1 Escherichia coli strain carrying the CTX-M resistance gene, an extended-spectrum beta-lactamase (ESBL). Despite the rapid diagnostic approach and adjustment of antibiotic therapy, the patient succumbed to the infection due to the strain’s high virulence and multidrug resistance. Whole-genome sequencing further characterized the strain, revealing that it belonged to the ST131 group, a highly resistant and virulent strain associated with sepsis. Conclusions: This case highlights the importance of integrating advanced molecular diagnostics, such as whole-genome sequencing, with traditional methods to improve pathogen detection, especially in cases of emerging resistant strains that are not covered by standard diagnostic panels. It also emphasizes the need for the continuous adaptation of diagnostic tools to include non-K1 E. coli strains for more comprehensive and timely meningitis diagnosis.

Lesiondiff: enhanced breast cancer classification via dynamic lesion amplification using diffusion models

ABSTRACT Breast cancer is a leading cause of mortality among women, underscoring the critical need for accurate and early diagnosis to enhance treatment efficacy. Traditional imaging techniques are limited in their ability to differentiate between benign and malignant lesions, particularly in the early stages, for there are very few images available for the lesion area and the resolution of these images is poor. This paper introduces a novel lesion diffusion model that dynamically amplifies lesion areas, providing a multi-frame analysis to improve classification accuracy. By integrating time-aware motion modeling, the proposed method tracks temporal changes in lesions, Generating a sequence of magnified frames highlighting subtle lesion features. Tested on the BUSI breast ultrasound dataset, our model achieved a 10.269% improvement in classification accuracy over baseline methods, with an average gain of 4.645% across multiple frames. The results demonstrate the model’s ability to enhance the claim and diagnostic utility of breast cancer images after magnification This dynamic lesion amplification approach presents a significant advancement in computer-aided breast cancer diagnostics, offering new possibilities for improving early-stage detection.

Chronic eosinophilic leukaemia-Not otherwise specified: Clinical features, genomic insight and therapeutic strategies.

Chronic eosinophilia leukaemia-not otherwise specified (CEL-NOS) is a rare myeloproliferative neoplasm characterized by persistent clonal hypereosinophilia. Recent advances in genetics have refined diagnostic criteria, leading to the identification of CEL subtypes with specific cytogenetic and molecular abnormalities now classified as myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, which may benefit from targeted therapies. In contrast, CEL-NOS lacks specific genetic drivers and intervention points to halt leukemogenesis. Molecular techniques have also enabled the definition of clonality in a considerable percentage of cases otherwise classified as idiopathic hypereosinophilic syndrome. CEL-NOS poses a significant therapeutic challenge due to limited treatment options, poor prognosis and the risk of progression to acute leukaemia. Patients, often elderly and with comorbidities, face restricted access to transplantation, the only potentially curative treatment. Unfortunately, the prognosis remains poor even post-transplant, with a 5-year survival rate of only one-third of patients. Other therapies, including steroids, cytoreductive and immunomodulatory treatments, offer limited and temporary responses with significant side effects. This review aims to consolidate current knowledge on CEL-NOS, covering diagnostic approaches, genetic advancements and therapeutic challenges. It seeks to provide a comprehensive overview and highlight critical areas for future research.