University of Pikeville

Radiation necrosis (RN) presents a significant challenge in the treatment of pediatric central nervous system tumors. This narrative review synthesizes current evidence on the use of bevacizumab (BEV) for managing pediatric RN, drawing from case reports, retrospective reviews, and prospective clinical trials. While high-quality prospective data remain limited, emerging evidence suggests that BEV may be effective in alleviating both clinical symptoms and radiographic manifestations of RN in pediatric patients. This review explores the pathophysiology of RN, BEV’s mechanism of action, and existing evidence on the use of BEV in pediatric RN. Emerging evidence suggests that bevacizumab may provide symptomatic relief and radiographic improvement in pediatric patients with RN. By addressing current knowledge gaps, the aim is to provide insight into the potential role of BEV in improving outcomes for pediatric patients with RN.

BackgroundMicroRNAs (miRNAs), small molecules that fine-tune gene activity, are consistently disrupted in cancer. Found stably in blood and other fluids, their unique cancer-associated patterns offer a promising route for non-invasive detection and monitoring. Merging artificial intelligence (AI) with miRNA analysis could revolutionize our understanding and treatment of cancer; however, reliably integrating these tools into clinics remains challenging.MethodsA multi-database search was executed until July 2025 using integrated miRNA-related descriptors and AI/ML ontologies such as support vector machine (SVM), random forest (RF), artificial neural network (ANN), logistic regression (LR), principal component analysis (PCA), and hierarchical clustering (HC), to interpret complex miRNA data in cancer. Our focus was on considering research article related to early cancer detection, prediction of patient outcomes, and guiding personalized treatments.FindingsAI models analysing miRNA signatures demonstrate remarkable accuracy [area under the curve (AUC) often exceeding 0.90] in diagnosing various cancers, such as gastric, breast, and lung cancer (LC). For example, SVM proved highly effective for breast cancer (BC) detection. Crucially, AI helps identify small miRNA sets linked to cancer progression, such as a 3-miRNA combination (hsa-let-7i-3p, miR-362-3p, and miR-3651) that predicts disease stage across eight cancers. RF models achieved near-perfect AUCs (1.00) in some validation studies. AI also identifies miRNAs, such as a specific 5-miRNA group in BC, that signal resistance to chemotherapy. However, significant roadblocks persist: fragmented and non-standardized data, AI tools that exhibit disparate performance across demographic groups (evidenced by racial bias in mammography algorithms), and unaddressed validation gaps.InterpretationThe powerful combination of AI and miRNA biology is reshaping oncology. It enables earlier cancer detection, more accurate forecasts of disease course, and therapies tailored to the individual. Realizing this potential demands AI models that clinicians can understand and trust, diverse datasets to ensure tools work fairly for all patients, and close teamwork across disciplines to integrate these advances into real-world care. This convergence marks a pivotal shift towards proactive, precise, and accessible cancer management globally.

BackgroundProsthetic joint infections (PJIs) are a major concern in total knee arthroplasty (TKA). One recent measure of interest has been the use of intraosseous vancomycin (IOV). This systematic review aims to evaluate the efficacy of IOV to prevent infection in TKA.MethodsA search was conducted across MEDLINE/Pubmed, Wiley Central, Google Scholar, Web of Science, and Embase databases. Demographics and results of the studies were extracted from the articles that met inclusion criteria. Meta-analysis was conducted on primary TKA studies.ResultsEight studies were included in this systematic review. IOV correlated with decreased odds of infection in primary TKA (odds ratio: 0.31, P = .02) when compared with controls of intravenous antibiotic and no regional IOV. IOV showed no increase in AKI or creatinine concentration in primary TKA when compared with controls. IOV and increased concentration of vancomycin in fat and subcutaneous tissues had a strong correlation (Cohen’s d = 0.9, P = .01). IOV and increased concentration of vancomycin in bone had a moderate correlation (Cohen’s d = 0.59, P = .01). No patients where IOV was used across all studies developed Red Man Syndrome.ConclusionsIOV is an effective adjunctive treatment for preventing infection in primary TKA, with this study showing a 69% decreased odds of infection when compared with controls of intravenous antibiotic and no regional IOV. IOV also appears to be a safe treatment, and with limited data there seems to not be an increase in AKI or creatinine concentration.Level of EvidenceLevel IV; Therapeutic.

HISTORY: A 21-year-old male amateur jiu-jitsu athlete presented with a 3-day history of fever, chills, and malaise. He noticed a pimple-like lesion near his face a week prior, which has since grown in size and number in surrounding area. The patient reported multiple recurrent abscesses and cellulitis over the past year, disrupting his training and competition. His most recent infection occurred a month ago which was cellulitis on his face that spread into his ear requiring an extensive coarse of oral antibiotics. PHYSICAL EXAMINATION: Numerous painful pustular lesions noted on the face with surrounding areas of erythema. Multiple tender palpable lymph nodes identified in the parotid and submandibular areas. DIFFERENTIAL DIAGNOSIS: Group A bacterial infection Herpes gladiatorum Traumatic injury of the skin TESTS AND RESULTS: Patient was febrile with mildly elevated tachycardia. Lab tests was remarkable for leukocytosis with neutrophilia and elevated inflammatory markers. Culture taken from the lesion grew MRSA and a nasal swab confirmed MRSA colonization. FINAL WORKING DIAGNOSIS: MRSA skin infections likely due to colonization and exposure to high-contact athletic environments. TREATMENT AND OUTCOMES: The athlete was treated with an extended coarse of oral antibiotics (sulfamethoxazole and trimethoprim). He was referred for a decolonization regimen with chlorhexidine washes, nasal mupirocin ointment. He received guidance on hygiene and environmental controls, such as frequent equipment sanitization. The athlete returned to training two weeks later but had another infection six months later, requiring additional antibiotics.

Nattokinase is a potent fibrinolytic enzyme widely used in the treatment of cardiovascular diseases for its ability to directly degrade fibrin and plasmin substrates, effectively dissolving blood clots. In this study, both full-length and mature forms of the nattokinase coding sequence were transiently expressed in Nicotiana benthamiana using a modified Bean Yellow Dwarf Virus (BeYDV) replicon system. Overexpression of the full-length (pre-pro) construct resulted in severe leaf necrosis within 2.5 days post-infiltration (dpi), with electrolyte leakage analysis indicating an 83.5% loss of membrane integrity by 3 dpi. In contrast, the mature form of nattokinase was successfully expressed without early cytotoxicity and exhibited strong caseinolytic and fibrinolytic activity, reaching 22,500 FU/g—comparable to commercial standards. These findings demonstrate the feasibility of producing biologically active nattokinase in plants and highlight the potential of plant-based expression systems as scalable, cost-effective platforms for therapeutic enzyme production.

Hypothalamic hamartomas are rare brain tumors that primarily affect children and adolescents. While several surgical approaches exist for resection, there is no consensus on the optimal technique. This study analyzes three approaches: supraorbital translamina terminalis (SO TLT), anterior interhemispheric (AIH), and pterional transsylvian (PTS). The SO TLT approach offers several advantages, including direct access to the hypothalamus, minimal brain retraction, and shorter hospital stays. It also utilizes a minimally invasive “keyhole” craniotomy, often combined with endoscopy for enhanced visualization. While potential complications such as frontal sinus opening and supraorbital nerve damage exist, careful preoperative planning and intraoperative techniques can mitigate these risks. Data analysis of case reports revealed that the SO TLT approach achieved gross total resection in 81% of cases, significantly higher than AIH (68%) and PTS (28%). In addition, SO TLT demonstrated fewer postoperative complications and a lower overall rate of negative outcomes compared with the other approaches. These findings suggest that the SO TLT approach may be the most effective and safest option for hypothalamic hamartoma resection, offering optimal outcomes with minimal morbidity.

Abstract Multisensory object discrimination is essential in everyday life, yet the neural mechanisms underlying this process remain unclear. In this study, we trained rats to perform a two-alternative forced-choice task using both auditory and visual cues. Our findings reveal that multisensory perceptual learning actively engages auditory cortex (AC) neurons in both visual and audiovisual processing. Importantly, many audiovisual neurons in the AC exhibited experience-dependent associations between their visual and auditory preferences, displaying a unique integration model. This model employed selective multisensory enhancement for the auditory-visual pairing guiding the contralateral choice, which correlated with improved multisensory discrimination. Furthermore, AC neurons effectively distinguished whether a preferred auditory stimulus was paired with its associated visual stimulus using this distinct integrative mechanism. Our results highlight the capability of sensory cortices to develop sophisticated integrative strategies, adapting to task demands to enhance multisensory discrimination abilities.

We develop benchmarks for resonant discalar production in the generic complex singlet scalar extension of the Standard Model (SM) with no additional symmetries, which contains two new scalars. These benchmarks maximize discalar resonant production modes at future pp colliders: pp→h2→h1h1, pp→h2→h1h3, and pp→h2→h3h3, where h1 is the observed SM-like Higgs boson and h2,3 are new scalars. The decays h2→h1h3 and h2→h3h3 may be the only way to discover h3, leading to a discovery of two new scalars at once. Current LHC and projected future collider (HL-LHC, FCC-ee+HL-LHC, ILC500+HL-LHC) constraints on this model are used to produce benchmarks at the HL-LHC for h2 masses between 250 GeV and 1 TeV and a future pp collider (FCC-hh) for h2 masses between 250 GeV and 12 TeV. We update the current LHC bounds on the singlet-Higgs boson mixing angle for these benchmarks. As the mass of h2 approaches the multi-TeV region, certain limiting behaviors of the maximum rates are uncovered due to theoretical constraints on the parameters. These limits, which can be derived analytically, are BR(h2→h1h1)→0.25, BR(h2→h3h3)→0.5, and BR(h2→h1h3)→0. It can also be shown that the maximum rates of pp→h2→h1h1 and pp→h2→h3h3 approach the same value. Hence, all three h2→hihj decays are promising discovery modes for h2 masses at and below O(1 TeV), while above O(1 TeV) the decays h2→h1h1 and h2→h3h3 are more encouraging. We choose benchmark masses for h3 to produce a large range of decay signatures including multi-b, multivector boson, and multi-SM-like Higgs production. As we will show, the behavior of the maximum rates leads to the surprising conclusion that in the multi-TeV region this model may be discovered in the Higgs quartet production mode via h2→h3h3→4h1 decays before Higgs triple production is observed. The maximum di- and four Higgs production rates are similar in the multi-TeV range. Published by the American Physical Society 2024