NeuroIGN: Explainable Multimodal Image-Guided System for Precise Brain Tumor Surgery.

Precise neurosurgical guidance is critical for successful brain surgeries and plays a vital role in all phases of image-guided neurosurgery (IGN). Neuronavigation software enables real-time tracking of surgical tools, ensuring their presentation with high precision in relation to a virtual patient model. Therefore, this work focuses on the development of a novel multimodal IGN system, leveraging deep learning and explainable AI to enhance brain tumor surgery outcomes. The study establishes the clinical and technical requirements of the system for brain tumor surgeries. NeuroIGN adopts a modular architecture, including brain tumor segmentation, patient registration, and explainable output prediction, and integrates open-source packages into an interactive neuronavigational display. The NeuroIGN system components underwent validation and evaluation in both laboratory and simulated operating room (OR) settings. Experimental results demonstrated its accuracy in tumor segmentation and the success of ExplainAI in increasing the trust of medical professionals in deep learning. The proposed system was successfully assembled and set up within 11 min in a pre-clinical OR setting with a tracking accuracy of 0.5 (± 0.1) mm. NeuroIGN was also evaluated as highly useful, with a high frame rate (19 FPS) and real-time ultrasound imaging capabilities. In conclusion, this paper describes not only the development of an open-source multimodal IGN system but also demonstrates the innovative application of deep learning and explainable AI algorithms in enhancing neuronavigation for brain tumor surgeries. By seamlessly integrating pre- and intra-operative patient image data with cutting-edge interventional devices, our experiments underscore the potential for deep learning models to improve the surgical treatment of brain tumors and long-term post-operative outcomes.

Timely diagnosis of multiple endocrine neoplasia 2B by identification of intestinal ganglioneuromatosis: a case series.

BACKGROUND: Medullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. In patients with multiple endocrine neoplasia type 2B (MEN2B), MTC can occur already before the age of 1 year. Recognition of non-endocrine features of MEN2B may lead to timely diagnosis. PURPOSE: To describe how early recognition of non-endocrine features can lead to a timely diagnosis of MEN2B as well as the effect of recognition of premonitory symptoms on prognosis. METHODS: A retrospective case series from the University Medical Center Utrecht/Wilhelmina Children's Hospital, a Dutch national expertise center for MEN patients. All eight MEN2B patients in follow-up between 1976 and 2020 were included and medical records reviewed. RESULTS: Intestinal ganglioneuromatosis (IGN) as the cause of gastrointestinal (GI) symptoms was detected in seven patients. In three of them within months after birth. This led to early diagnosis of MEN2B, which allowed subsequent curative thyroid surgery. On the contrary, a MEN2B diagnosis later in childhood-in three patients (also) triggered by oral neuromas/neurofibromas-led to recurrent, persistent, and/or progressive MTC in five patients. CONCLUSIONS: Neonatal GI manifestations offer the most important window of opportunity for early detection of MEN2B. By accurate evaluation of rectal biopsies in patients with early onset severe constipation, IGN can be timely detected, while ruling out Hirschsprung's disease. MEN2B gene analysis should follow detection of IGN and-when confirmed-should prompt possibly still curative thyroid surgery.

Antibody-Drug Conjugates with Indolinobenzodiazepine Dimer Payloads: DNA-Binding Mechanism of Indolinobenzodiazepine Dimer Catabolites in Target Cancer Cells.

DNA-targeting indolinobenzodiazepine dimer (IGN) payloads are used in several clinical-stage antibody-drug conjugates. IGN drugs alkylate DNA through the single imine moiety present in the dimer in contrast to the pyrrolobenzodiazepine dimer drugs, such as talirine and tesirine, which contain two imine moieties per dimer and cross-link DNA. This study explored the mechanism of binding of IGN to DNA in cells and to synthetic duplex and hairpin oligonucleotides. New, highly sensitive IGN-DNA binding enzyme-linked immunosorbent assay methods were developed using biotinylated IGN analogues (monoimine, diimine, and diamine IGNs) and digoxigenin-labeled duplex oligonucleotides, which allowed the measurement of drug-DNA adducts in viable cells at concentrations below IC50. Furthermore, the release of free drug from the IGN-DNA adduct upon treatment with nuclease ex vivo was tested under physiological conditions. The monoimine IGN drug formed a highly stable adduct with DNA in cells, with stability similar to that of the diimine drug analogue. Both monoimine and diimine IGN-DNA adducts released free drugs upon DNA cleavage by nuclease at 37 °C, although more free drug was released from the monoimine compared to the diimine adduct, which presumably was partly cross-linked. The strong binding of the monoimine IGN drug to duplex DNA results from both the noncovalent IGN-DNA interaction and the covalent bond formation between the 2-amino group of a guanine residue and the imine moiety in IGN.

The Use of Image-Guided Navigation Systems During Spine Surgeries in Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: We used a cross-sectional study design (questionnaire) to investigate the use of image-guided navigation (IGN) in Saudi Arabia and explore possible differences in implementing IGN for daily practice. METHODS: An internet-based survey was sent to all spine surgeons who are practicing in Saudi Arabia (orthopedics or neurosurgery). The survey is composed of 12 items that collected demographic and academic data. RESULTS: Ninety-nine answered the questionnaire from 197; 80% were from Riyadh, the capital, and 50% were consultants (attending physicians). Orthopedic surgeons were almost 60% of responders compared to 40% neurosurgeons. The use of navigation in Saudi hospitals was high (76.8%). There was a significant difference between specialties in the preference of using navigation (23.2% for orthopedics versus 81.4% for neurosurgery, P < .001) and routine use in surgical spine cases (88.4% for neurosurgery versus 50.0% orthopedics, P < .001). The majority of responders from neurosurgery learned to use navigation during residency compared to orthopedics responders (51.2% versus 28.6%, P = .001). More than 30% of orthopedics responders expressed they never learned navigation compared to only 4% of neurosurgery responders. The comfort level of > 75% with performing surgery using navigation was significantly different between specialties (25% for orthopedics versus 46.5% for neurosurgery, P < .001). CONCLUSION: Saudi spine surgeons are among the highest users of IGN systems. The strong healthcare infrastructure and the availability of these devices across the country are among the most important factors for its prevalence. Enhancing surgical exposure and education of postgraduate trainees to use these tools, especially within orthopedics, could increase use and comfort level rates.

Probiotics, prebiotics, synbiotics and insulin sensitivity.

Animal studies indicate that the composition of gut microbiota may be involved in the progression of insulin resistance to type 2 diabetes. Probiotics and/or prebiotics could be a promising approach to improve insulin sensitivity by favourably modifying the composition of the gut microbial community, reducing intestinal endotoxin concentrations and decreasing energy harvest. The aim of the present review was to investigate the effects of probiotics, prebiotics and synbiotics (a combination of probiotics and prebiotics) on insulin resistance in human clinical trials and to discuss the potential mechanisms whereby probiotics and prebiotics improve glucose metabolism. The anti-diabetic effects of probiotics include reducing pro-inflammatory cytokines via a NF-κB pathway, reduced intestinal permeability, and lowered oxidative stress. SCFA play a key role in glucose homeostasis through multiple potential mechanisms of action. Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release of glucagon-like peptide-1 and peptide YY resulting in increased insulin and decreased glucagon secretion, and suppressed appetite. SCFA can decrease intestinal permeability and decrease circulating endotoxins, lowering inflammation and oxidative stress. SCFA may also have anti-lipolytic activities in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation of 5'-AMP-activated protein kinase signalling in muscle and liver tissues. Resistant starch and synbiotics appear to have favourable anti-diabetic effects. However, there are few human interventions. Further well-designed human clinical studies are required to develop recommendations for the prevention of type 2 diabetes with pro- and prebiotics.

Role of the Iodine Global Network in Elimination of Iodine Deficiency.

BACKGROUND: Iodine deficiency (ID) is a major cause of brain damage if not corrected in early pregnancy. Even mild ID leads to measurable neurointellectual impairment. The iodine global network (IGN), previously the international council for the control of iodine deficiency disorders (ICCIDD), has achieved remarkable progress in facilitating iodine nutritional sufficiency in about 70-80% of countries in the world during the past 3 decades or so. RESULTS: At present there are 25 countries with documented iodine deficiency. However, there are still many countries, especially in Europe, with mild iodine deficiency which require active interventional strategies to ensure adequate iodine nutrition. In this context, rigorous monitoring of iodine status is essential to ensure adequate iodisation. CONCLUSION: The IGN, with 10 world-wide regional coordinators and 100 national coordinators is well placed to implement appropriate strategies to achieve these goals. The recent award of a Horizon 20/20 grant to European stakeholders to harmonise iodine supply in Europe emphasises the commitment of the EU to make improvement in the global iodine health. There are no relevant recent patents for this report.

The multifactorial interplay of diet, the microbiome and appetite control: current knowledge and future challenges.

The recent availability of high-throughput nucleic acid sequencing technologies has rapidly advanced approaches to analysing the role of the gut microbiome in governance of human health, including gut health, and also metabolic, cardiovascular and mental health, inter alia. Recent scientific studies suggest that energy intake (EI) perturbations at the population level cannot account for the current obesity epidemic, and significant work is investigating the potential role of the microbiome, and in particular its metabolic products, notably SCFA, predominantly acetate, propionate and butyrate, the last of which is an energy source for the epithelium of the large intestine. The energy yield from dietary residues may be a significant factor influencing energy balance. This review posits that the contribution towards EI is governed by EI diet composition (not just fibre), the composition of the microbiome and by the levels of physical activity. Furthermore, we hypothesise that these factors do not exist in a steady state, but rather are dynamic, with both short- and medium-term effects on appetite regulation. We suggest that the existing modelling strategies for bacterial dynamics, specifically for growth in chemostat culture, are of utility in understanding the dynamic interplay of diet, activity and microbiomic organisation. Such approaches may be informative in optimising the application of dietary and microbial therapy to promote health.