Search Results (1,412)

Epilepsy is a complex neurological disorder characterized by abnormal neural synchronization and interactions between local foci and global brain networks during seizures. Understanding seizure mechanisms across multiple scales is essential for advancing our understanding of epileptic network dynamics and guiding personalized treatment strategies. However, neural recording technologies are limited by insufficient spatial resolution, signal fidelity, and the inability to simultaneously capture network- and cellular-level dynamics. To address these limitations, we developed a high-density, flexible deep-brain probe with excellent mechanical compliance and wideband recording capabilities, enabling high-fidelity recordings of high-frequency oscillations (HFOs, 80–500 Hz) and action potentials (APs). Using a pentylenetetrazol (PTZ)-induced epilepsy model, we identified distinct spatiotemporal dynamics of HFOs and APs across epileptic stages, indicating that CA3 plays a key role in seizure onset, while CA1 is crucial for propagation. AP-HFO coupling analysis further uncovered neuronal heterogeneity, offering insights into the diverse roles of neurons in epileptic networks. This study highlights the potential of a flexible deep-brain probe for advancing epilepsy research and guiding personalized therapeutic interventions. Full article

Background/Objectives: Biportal endoscopic spine surgery (BESS) is one of the minimally invasive spine surgery techniques. BESS has several advantages, such as better visualization, less muscle injury, early rehabilitation, etc. Due to its clear visualization, delicate intraoperative hemostasis of the bleeding foci, including cancellous bone and small epidural vessels, can be achieved. Therefore, some authors have reported that BESS resulted in less intraoperative visible blood loss (VBL) compared to conventional open surgery. However, it is difficult to analyze the exact amount of intraoperative blood loss because of the continuous normal saline irrigation. In addition, hidden blood loss (HBL) tends to be overlooked, and the amount of HBL might be larger than expected. We aim to calculate the amount of HBL during BESS and to compare our findings with convention open surgery. Methods: We retrospectively obtained the clinical data of patients that underwent lumbar central decompression from July 2021 to June 2024. Patients were divided into two groups: the BESS group that underwent biportal endoscopic lumbar decompression, and the open surgery group that underwent open decompression. Both groups used unilateral laminotomy and bilateral decompression techniques. Total blood loss (TBL) using preoperative and postoperative change in hematocrit (Hct) was measured using Gross’s formula and the Nadler equation. Since TBL consists of VBL and HBL, HBL was calculated by subtracting the VBL measured intraoperatively from TBL. Results: A total of sixty-six patients in the BESS group and seventeen patients in the open surgery group were included in the study. The TBL was 247.16 ± 346.88 mL in the BESS group and 298.71 ± 256.65 mL in the open surgery group, without significant difference (p = 0.569). The calculated HBL values were 149.44 ± 344.08 mL in the BESS group and 171.42 ± 243.93 mL in the open surgery group. The HBL in the BESS group was lower than the HBL in the open surgery group, without significant difference (p = 0.764). Conclusions: The TBL and HBL during lumbar central decompression were smaller in patients who underwent BESS compared to those who underwent open surgery. While TBL was significantly lower in BESS, HBL did not show statistical significance between the two groups. HBL during BESS should not be neglected, and related hemodynamics should be considered postoperatively. Full article

Radical chemoradiotherapy has been used as a frontline treatment for squamous cell cancer of the anus for the last 30–40 years. Considerable acute and chronic adverse effects have been observed following radiotherapy using 2D and 3D techniques. A case of very late-onset severe chronic toxicity in a patient 26 years after radiotherapy is presented. The patient underwent radical chemoradiotherapy for squamous anal cancer stage T3N3M0 in 1998. In the anal region, cumulative doses up to 77.6 Gy (including electron boost) were administered. Durable complete regression of the disease was achieved. Fourteen years after treatment, the patient developed vast fibroatrophy of the anus and perineum, progressing within the subsequent four years to necrosis and sphincter loss. Twenty years after treatment, the asymptomatic osteonecrotic foci in the left femur appeared on MRI scans. Despite two courses of hyperbaric oxygen treatment, the fibroatrophy and subsequent necrosis of soft tissues remained progressive, but the osteonecrosis was stable. Twenty-six years after treatment, the progressive changes induced symptomatic osteomyelitis of the ischium and pubic bone. The patient now requires permanent supportive treatment. The presented case is exceptional in the very late-onset typical chronic adverse effects developing after non-conformal radiotherapy administered at high doses as part of contemporary treatment protocols. There is little evidence regarding the late onset of chronic adverse effects, since the follow-up period is usually shorter than that of the case presented. Moreover, a significant portion of patients do not survive to reach the late-onset period of adverse effects. The presented case shows that there may be long-term survivors of anal cancer in the population who were treated with outdated techniques and who still carry a risk of late-onset severe, progressive adverse effects. Full article

Background: Emerging and re-emerging infectious diseases (EIDs and Re-EIDs) cause significant economic crises and public health problems worldwide. Epidemics appear to be more frequent, complex, and harder to prevent. Early warning systems can significantly reduce outbreak response times, contributing to better patient outcomes. Improving early warning systems and methods might be one of the most effective responses. This study employs a bibliometric analysis to dissect the global research hotspots and evolutionary trends in the field of infectious disease early warning, with the aim of providing guidance for optimizing public health emergency management strategies. Methods: Publications related to the role of early warning systems in detecting and responding to infectious disease outbreaks from 1999 to 2024 were retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace software was used to analyze the datasets and generate knowledge visualization maps. Results: A total of 798 relevant publications are included. The number of annual publications has sharply increased since 2000. The USA produced the highest number of publications and established the most extensive cooperation relationships. The Chinese Center for Disease Control & Prevention was the most productive institution. Drake, John M was the most prolific author, while the World Health Organization and AHMED W were the most cited authors. The top two cited references mainly focused on wastewater surveillance of SARS-CoV-2. The most common keywords were “infectious disease”, “outbreak”, “transmission”, “virus”, and “climate change”. The basic keyword “climate” ranked the first and long duration with the strongest citation burst. “SARS-CoV-2”, “One Health”, “early warning system”, “artificial intelligence (AI)”, and “wastewater-based epidemiology (WBE)” were emerging research foci. Conclusions: Over the past two decades, research on early warning of infectious diseases has focused on climate change, influenza, SARS, virus, machine learning, warning signals and systems, artificial intelligence, and so on. Current research hotspots include wastewater-based epidemiology, sewage, One Health, and artificial intelligence, as well as the early warning and monitoring of COVID-19. Research foci in this area have evolved from focusing on climate–disease interactions to pathogen monitoring systems, and ultimately to the “One Health” integrated framework. Our research findings underscore the imperative for public health policymakers to prioritize investments in real-time surveillance infrastructure, particularly wastewater-based epidemiology and AI-driven predictive models, and strengthen interdisciplinary collaboration frameworks under the One Health paradigm. Developing an integrated human–animal–environment monitoring system will serve as a critical development direction for early warning systems for epidemics. Full article

Background/Objectives: MBNL1 is an RNA-binding protein involved in RNA metabolism, including splicing. It colocalizes with RNA foci, a pathological hallmark of myotonic dystrophy, and plays a central role in its disease mechanism. Moreover, MBNL1 has been implicated in other neuromuscular disorders and cancers. In these pathological and biochemical studies, the detection of MBNL1 using antibodies is essential. Given that MBNL1 has multiple splicing-derived isoforms, different antibodies may recognize distinct isoforms. This study aims to compare six commercially available antibodies regarding their specificity in Western blotting, colocalization with RNA foci, and suitability for immunoprecipitation. Methods: Western blot analysis was performed using MBNL1 isoforms and deletion mutants expressed in HEK293 cells, as well as endogenous MBNL1 from various cell lines. RNA fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were conducted in DM1 model cells and patient-derived fibroblasts to assess MBNL1 colocalization with RNA foci. Immunoprecipitation experiments were performed in HEK293 cells to evaluate antibody suitability for protein isolation. Results: Western blot analysis revealed that different antibodies target distinct regions of MBNL1, with three recognizing exon 3 and the remaining antibodies recognizing exon 4, exon 5, and exon 6, respectively. In the FISH-IF experiments, the clarity of RNA foci colocalization varied depending on the antibody used, with some antibodies failing to detect colocalization. The immunoprecipitation analysis showed that four antibodies were able to isolate endogenous MBNL1. Conclusions: This study clarifies the recognition properties and application suitability of MBNL1 antibodies, providing a valuable resource for research on MBNL1-related diseases and RNA metabolism. Full article

In this report, we document and analyze a case in which the Irkut virus (IRKV) (Mononegavirales: Rhabdoviridae) caused a fatal human case following a bat bite in June 2021. Unfortunately, the available data did not permit a detailed taxonomic classification of the carrier bat (Chiroptera). The event occurred in the southwestern part of the Sikhote-Alin mountain region (Russian Far East) covered by the Ussuri taiga forest. The symptoms of the illness began with the following: fever; pronounced psychomotor and motor agitation; tremor of the lower jaw and tongue; aphasia; dyslexia; and dysphagia. These rapidly developed, leading to a severe and fatal encephalitis. The patient was not vaccinated for rabies and did not receive rabies immunoglobulin. Using brain sections prepared from the deceased, molecular diagnostics were performed: immunofluorescence (polyclonal anti-rabies immunoglobulin) indicating the presence of the lyssavirus antigen; and RT-PCR indicating traces of viral RNA. Sectional material (brain) was used for whole-genome sequencing, resulting in a near-complete sequence of the lyssavirus genome. The obtained genomic sequence was identified as the Irkut virus. A comparative analysis of the new sequence and other currently available IRKV sequences (NCBI) revealed differences. Specifically, amino acid differences between antigenic sites in the isolate and those of the rabies vaccine strain used regionally were noted. The patient history and subsequent analysis confirm human IRKV infection following bat contact. Like other fatal cases of IRKV infection described earlier, this case occurred in the southern part of the Russian Far East. Two have occurred in the southwestern part of the Sikhote-Alin mountain region. This indicates the possible existence of an active, natural viral focus. Full article

Transcranial focused ultrasound (TcFUS) neuromodulation is hindered by skull-induced acoustic limitations. To enable synergistic multi-region brain stimulation, we designed non-coaxial multi-focal composite Fresnel acoustic lenses, including an overlapping Fresnel lens (OFL) and an alternating-segmented Fresnel lens (ASFL). These lenses convert planar ultrasound into multiple foci. Based on Fresnel theory, acoustic fields were analyzed via simulations and experiments, validating the generation of four non-coaxial foci (10/30 mm focal lengths) from a 1 MHz planar wave using both OFL and ASFL. The influence of lens parameters on focal pressure distribution was investigated, and morphology was quantified using a linear least-squares method. Significant differences in focal morphology and intensity between OFL and ASFL provide crucial guidance for optimizing multi-target TcFUS strategies. Full article

Background/Objectives: To investigate the association between MRI features of primary breast cancers with axillary status, aiming to identify possible imaging biomarkers. Methods: Patients diagnosed with breast cancer between 2021 and 2023 in our clinic were retrospectively evaluated, and those that presented as mass lesions on preoperative MRI examinations (n: 123) were included in the study. Patients with and without metastatic axillary lymph nodes (mALN) were compared in terms of breast density, background parenchymal enhancement, tumor size, location in the breast, distance from the skin, patient age, presence of edema, multiple foci, histopathological type and molecular subtype of tumors. In multifocal/multicentric cases, the largest lesion was taken into consideration. Prepectoral and subcutaneous edema were considered diffuse edema, while perilesional edema was considered focal edema. MannWhitney U/Student-t test, Chi- square/Fischer Exact tests and logistic regression analysis were used for statistical analyses as appropriate. Results: Axilla was positive in 88 patients. There was a statistically significant difference in terms of edema, age, molecular subtype, Ki-67 index, number of lesions, tumor size, and laterality between the two groups (p < 0.05). Univariate logistic regression analysis showed that all included variables were statistically significant (p < 0.05). Multivariate logistic regression analysis revealed that presence of edema (OR: 2.46 CI; 1.11–5.48, p = 0.027) and multiple lesions (OR: 1.86 CI; 1.01–3.43, p = 0.046) were significantly associated with mALN. There was no significant difference between peritumoral edema and diffuse edema. Conclusions: Our study showed a statistically significant relationship between the axillary status and the presence of edema and multiple tumoral lesions on MRI. These findings have a potential to serve as prognostic imaging biomarkers for predicting the presence of mALN. Further studies with larger case series are needed to support our findings. Full article

Background: Diabetic macular edema (DME) is the most common cause of vision loss among diabetic patients. The first-line treatments for DME are anti-vascular endothelial growth factor (VEGF)-drugs, while intravitreal steroids are generally reserved for second-line treatment. Limited data exist on the role of optical coherence tomography (OCT) biomarkers as predictors of success in non-responders to anti-VEGF treatment undergoing simultaneous cataract surgery and dexamethasone intravitreal implant (DEX-I). Methods: This study was designed as a retrospective analysis of patients with DME who were refractory to anti-VEGF treatment but underwent cataract surgery and received a DEX-I at the time of surgery. All procedures were performed between May 2021 and February 2024. The best-corrected visual acuity (BCVA) and central subfoveal thickness (CST) were recorded at baseline and at 1 week, 1 month, and 3 months. The following OCT-based biomarkers were also collected: ellipsoid zone (EZ) integrity, disorganization of the retinal inner layers (DRIL), CST, and hyperreflective foci (HRF). Correlations between the baseline biomarkers and the anatomical outcome were analyzed using linear mixed models (LMMs). Results: Eleven patients (eighteen eyes) met the inclusion criteria. The mean CST decreased significantly from 469.4 ± 53.8 µm at baseline, to 373.1 ± 34.7 µm at 1 week (p = 0.002) and 354.4 ± 24.1 µm at 1 month (p = 0.011). The mean BCVA improved significantly from 0.47 LogMAR to 0.33 LogMAR at 1 week (p = 0.001), 0.23 LogMAR at 1 month (p < 0.001), and 0.25 LogMAR at 3 months (p < 0.001). Baseline predictors significantly influencing CST included the presence of DRIL, a disrupted/absent EZ, and a higher CST. Conclusions: The administration of DEX-I for DME refractory to anti-VEGF treatment in patients undergoing cataract surgery promoted functional improvements persisting longer than the anatomical ones. Patients presenting with DRIL, disrupted EZ, and higher CST at baseline may be better candidates for the combination of DEX-I and cataract surgery. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

In many types of embodied skills instruction, the learnables—that is, the local and jointly negotiated foci of instruction—emerge from a combination between a pre-existing lesson plan and the spontaneous interaction between teacher and student. Through the analytical lens of Conversation Analysis, this paper investigates the interspecies instruction setting of horse-riding lessons and shows how here, it is not only the human teachers and learners that determine the emergence of new learnables but also the horses. Horses’ actions can initiate new courses of action in a lesson, and horses can thus become interactional partners in the instructional project. Horse-led learnables can be initiated in at least three ways: through horses’ displays of mental or physical states that pre-date the instruction sequence; through actions that respond to local contingencies of the instruction sequence; and through actions that respond specifically to the rider’s actions. In the last case, their responses become diagnostic of the rider’s mistakes. In all three cases, the human participants take their cue from the horse and base new learnables on horses’ actions. Human-led learnables can be adjusted, changed, replaced, or abandoned completely in response to horses. The study broadens the emerging field of interspecies pragmatics to include instructional interactions involving the triad of human–human–horse triad. Full article

C1QBP (Complement Component 1 Q Subcomponent-Binding Protein) plays a critical role in maintaining cellular metabolism, but its function in radiation-induced damage remains unclear. In this study, we generated C1QBP-deficient Huh-7 hepatocellular carcinoma (HCC) cells using CRISPR/Cas9 technology and observed that C1QBP deficiency significantly enhanced radiation-induced damage, as indicated by reduced cell proliferation, impaired colony formation, and increased γ-H2AX foci, a marker of DNA double-strand breaks. Additionally, C1QBP deficiency resulted in elevated phosphorylation of key DNA damage response (DDR) molecules, ATM and CHK2, and caused pronounced S phase cell cycle arrest. Mechanistic investigations revealed that C1QBP modulates NF-κB nuclear activity via the AMPK signaling pathway. The loss of C1QBP reduced NF-κB nuclear translocation, further exacerbating radiation-induced damage. Reintroducing C1QBP alleviated DNA damage, enhanced cell proliferation, and improved survival following radiation exposure. These findings highlight the critical role of C1QBP in modulating HCC cells radiosensitivity and underscore its potential as a therapeutic target to enhance radiotherapy outcomes. Full article

Platinum-based radiochemotherapy is associated with hematologic side effects, impacting patient outcomes. However, the clinical mechanisms of cisplatin and its interaction with ionizing radiation (IR), including in biodosimetry for radiotherapy, have not yet been fully clarified. For this purpose, healthy donors’ peripheral blood lymphocytes (PBLs) were pretreated with cisplatin in a pulse (1–4 h) or continuous (24 h) regimen followed by X-rays. DNA damage was assessed as DNA double-strand breaks using repair foci of γH2AX and 53BP1 after 0.5 h and 24 h in G1 PBLs and a proliferation-based cytokinesis-block micronucleus assay. Additionally, cell death and proliferation activity were measured. Unlike a 1 h pulse, a 24 h cisplatin pretreatment caused a concentration-dependent increase in cisplatin-induced foci while decreasing IR-induced foci, especially 24 h after irradiation. This was accompanied by increased apoptosis, with cisplatin and IR having additive effects. Both genotoxins alone caused a dose-dependent increase in micronuclei, while cisplatin significantly reduced binuclear cells, especially after the 24 h treatment, leading to lower micronuclei frequencies post-irradiation. Our results show that prolonged cisplatin exposure, even at low concentrations, impacts the vitality and division activity of PBLs, with significantly stronger effects post-irradiation. This has major implications and must be considered for the detection of DNA damage-associated biomarkers in PBLs used in clinical prediction or biodosimetry during radiotherapy. Full article

Understanding environmental governance empowers researchers and practitioners alike to work towards solutions that improve both environmental and human well-being outcomes. Collaborative, iterative approaches to governance use bridging approaches such as translational ecology, boundary work, and ecosystem services. The US Environmental Protection Agency’s Office of Research and Development worked with a variety of collaborators to implement six multi-year coordinated case study research projects. The research projects were designed to support agency collaborators spanning different geographies, ecosystems, and environmental management decision contexts, and to demonstrate that different tools, approaches, and ecosystem service foci can enhance coastal and other water resource sustainability. To better understand the iterative and collaborative nature of the cases and collaborations, researchers conducted an analysis of the comparative case studies based on Williams’ (2018) and Ostrom’s (1994, 2009) frameworks. The team identified (1) who participated in the processes; (2) what the programs and goals were; (3) where programs worked and their resources; and (4) the resulting outcomes. We demonstrate that stakeholder participation and outcomes look different within different projects, and we conclude that relationships, focus on place, and common goals produce the most impactful results. Full article

Background and Clinical Significance: Pellagra is caused by a chronic deficiency of niacin (vitamin B3 or nicotinic acid): it is rare in developed countries, where the major risk factors are chronic alcoholism and intestinal malabsorption. Although it typically presents three main symptoms, dermatitis, diarrhea, and dementia, some cases do not show these classic symptoms. Case Presentation: We report a case of a malnourished patient with seizure and multiple cerebrovascular foci, in whom a postmortem autopsy revealed the findings of pellagra. The patient had atypical symptoms of seizure as pellagra and the multiple cerebrovascular lesions, which made the diagnosis difficult. Conclusions: The aim of this paper is to recognize the importance of suspecting pellagra as a treatable disease, especially when patients with eating disorder present atypical symptoms. Full article