Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome.

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09-0.19) for MCD, 0.33 (0.23-0.40) for FSGS, and 0.20 (0.14-0.30) for MN. FENa were 0.24 (0.09-0.68), 1.03 (0.50-2.14), and 0.78 (0.41-1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97-3.81] and HR 1.93 [95% CI 1.46-2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Impact of microvascular decompression on wall shear stress in responsible arteries in trigeminal neuralgia and hemifacial spasm.

Microvascular decompression (MVD) has proven efficacy in trigeminal neuralgia (TN) and hemifacial spasm (HFS). This study utilized computational fluid dynamics (CFD) to investigate the impact of MVD on wall shear stress (WSS) of responsible arteries (RAs) at the neurovascular contact (NVC). A total of 21 cases (10 TN, 11 HFS) were analyzed, involving RAs at NVC validated through intraoperative photographs. Hemodynamic parameters (WSS, vessel diameter, flow rate, pressure drop) was calculated using CFD for the RAs based on 3D silent-magnetic resonance angiograms. The NVC was segmented into NVC-proximal, NVC-site, and NVC-distal portions using simulated 3D CFD images that correlated with surgical observations. WSS ratios of NVC-site to NVC-proximal (NVC-site/proximal) was calculated both before and after MVD. Prior to MVD, WSS in the RA at the NVC displayed a peaked curve with a maximum at NVC-site; however, post MVD, it presented a smooth curve without peaks. The WSS ratio exhibited a significant decrease after MVD. The impact of MVD on WSS of RAs at NVC was evaluated in both TN and HFS cases. Analyzing the hemodynamics of RAs through CFD and identifying WSS peaks at NVC portions before MVD provided a more detailed and localized understanding of the morphologically depicted NVC.

Observation of the Liquid-Liquid Phase Separation of FUS-LC Using Vacuum-Ultraviolet Circular Dichroism Spectroscopy.

To reveal the structural mechanism by which the low-complexity domain of the fused in sarcoma protein (FUS-LC) mediates liquid-liquid phase separation (LLPS), we conducted a vacuum-ultraviolet circular dichroism (VUV-CD) spectroscopic study, a technique to analyze the secondary structures of proteins. The VUV-CD measurements were performed at the BL12 VUV-CD station at the Hiroshima Synchrotron Radiation Center (HiSOR) in Japan. CD spectra were measured between 180 and 260 nm while controlling the temperature of samples from 37°C to 5°C to obtain the LLPS of FUS-LC. The CD spectrum obtained at 37°C exhibited a large negative peak at 195 nm and a small negative shoulder near 220 nm. The peak intensity around 195 nm decreased as the sample temperature decreased. The spectral changes originated from the LLPS formation.

[Relapsed primary central nervous system lymphoma treated with CD19 chimeric antigen receptor T-cell therapy and allogeneic hematopoietic stem cell transplantation].

Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.

Assessment of morphology and hemodynamics in a surgically clipped neck of a cerebral aneurysm: illustrative case.

BACKGROUND: Silent magnetic resonance angiography reduces metal artifacts, enabling clear visualization of the clipped neck following surgical clipping of cerebral aneurysms. This study aimed to delineate the morphology of the clipped neck complex in cerebral aneurysms using three-dimensional (3D) multifusion imaging of silent magnetic resonance angiography and fast spin echo magnetic resonance cisternography. Additionally, computational fluid dynamics analysis was utilized to evaluate the hemodynamics of the parent vessel at the clipped neck, allowing for a detailed assessment of hemodynamics at the clipped neck. OBSERVATIONS: The 3D multifusion image enabled visualization of the orientation and shape of the clip within the clipped neck complex, alongside the morphology of the parent vessel. In the hemodynamic analysis of the parent vessel at the clipped neck, areas of high-intensity magnitude of wall shear stress (WSSm) variation corresponding to the clip's contour, along with significant vector of wall shear stress (WSSv) variation related to vector directionality, were visualized in 3D. The intentional residual neck, coated with muscle grafts, was depicted as an area with low WSSm variation values and high WSSv variation values. LESSONS: Three-dimensional multifusion imaging, along with computational fluid dynamics analysis of the parent vessels, facilitated both the morphological and hemodynamic visualization and assessment of the clipped neck complex following neck clipping surgery for cerebral aneurysms. https://thejns.org/doi/10.3171/CASE24194.

Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma.

Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.

Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.

Ab initio molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR2+, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei. These patterns differ for the two isomers studied. To compare thermal and electronic excitation effects, Ehrenfest dynamics are also performed, allowing to remove the two electrons from selected molecular orbitals. Two intermediate-energy orbitals, localized on the carbon chain, were selected. The dissociation pattern corresponds to the most frequent pattern obtained when adding thermal excitation. On the contrary, targeting the four deepest orbitals, localized on the oxygen atoms, leads to selective ultrafast C-O and/or O-H bond dissociation. To probe the role of environment, a system consisting of a DR molecule embedded in liquid water is then studied. The two electrons are removed from either the DR or the water molecules directly linked to the sugar through hydrogen bonds. Although the dynamics onset is similar to that of isolated DR when removing the same deep orbitals localized on the sugar oxygen atoms, the subsequent fragmentation patterns differ. Sugar damage also occurs following the Coulomb explosion of neighboring H2O2+ molecules due to interaction with the emitted O or H atoms.

Periportal macrophages protect against commensal-driven liver inflammation.

The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1-5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco+ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco+ macrophages. Functional ablation of Marco+ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco+ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.

Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base.

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

Resistive Pulse Sensing on a Capillary-Assisted Microfluidic Platform for On-Site Single-Particle Analyses.

Capillary-assisted flow is valuable for utilizing microfluidics-based electrical sensing platforms at on-site locations by simplifying microfluidic operations and system construction; however, incorporating capillary-assisted flow in platforms requires easy microfluidic modification and stability over time for capillary-assisted flow generation and sensing performance. Herein, we report a capillary-assisted microfluidics-based electrical sensing platform using a one-step modification of polydimethylsiloxane (PDMS) with polyethylene glycol (PEG). As a model of electrical sensing platforms, this work focused on resistive pulse sensing (RPS) using a micropore in a microfluidic chip for label-free electrical detection of single analytes, and filling the micropore with an electrolyte is the first step to perform this RPS. The PEG-PDMS surfaces remained hydrophilic after ambient storage for 30 d and assisted in generating an electrolyte flow for filling the micropore with the electrolyte. We demonstrated the successful detection and size analysis of micrometer particles and bacterial cells based on RPS using the microfluidic chip stored in a dry state for 30 d. Combining this capillary-assisted microfluidic platform with a portable RPS system makes on-site detection and analysis of single pathogens possible.

Five-Fraction Radiosurgery Using a Biologically Equivalent Dose of a Single Fraction of 24 Gy for a 3-cm Parasagittal Para-Central Sulcus Brain Metastasis From Adenocarcinoma of the Cecum.

An isolated single brain metastasis (BM) is an extremely rare manifestation of failure in patients with cecal adenocarcinoma (CAC). Total en bloc resection (while preserving function) of a 3-cm BM involving both the primary motor and sensory cortexes presents a conundrum: achieving long-term local control and safety of such a BM is also challenging for stereotactic radiosurgery (SRS). We describe the case of a 3.1-cm BM from CAC in the left parasagittal para-central sulcus region, which was treated using five-fraction SRS with a biologically effective dose (BED) of 81.6 Gy. In the SRS, the gross tumor volume (GTV, 7.14 cm3) was defined based on computed tomography (CT)/T1/T2 matching (enhancing lesion 11.66 cm3), and 98.7% of the GTV (CT/T2 mass) was covered with 43.6 Gy (58% isodose) using volumetric-modulated arcs. The maximum tumor response was partial (19.7% of the prior GTV) and sustained for 15.2 months, leaving minor neurological symptoms. However, the patient developed neurological worsening at six months, attributed to adverse radiation effects with a CT/T1/T2 mismatch, for which medical management, including the addition of bevacizumab (BEV), was effective for one year. Multi-fraction SRS with a high marginal and internal BED and sequential systemic therapy, including BEV, can be a minimally invasive, efficacious, and durable treatment option for a large CAC-BM involving the central sulcus. Early co-administration of BEV following SRS, dose escalation to the GTV boundary, and more than five fractions of SRS may be considered to improve the efficacy and safety further.

Chryseobacterium indologenes Peritonitis in a Peritoneal Dialysis Patient: A Case Report and Review of Literature.

Peritonitis is one of the most important complications in patients with peritoneal dialysis (PD). Appropriate antibiotic treatment against PD-associated peritonitis is necessary to prevent PD catheter removal and withdrawal from PD. Chryseobacterium indologenes is a Gram-negative rod that occurs in the natural environment. C. indologenes is thought to acquire resistance to ß-lactam drugs through the production of metallo-ß-lactamase and to become resistant to antibiotic therapy through the formation of biofilms. Only a few cases of PD-associated peritonitis caused by C. indologenes have been reported to date, and appropriate treatment strategies have not been clarified. In the past, 5 cases of PD-associated peritonitis caused by C. indologenes have been reported and 2 patients required catheter removal because of recurrence or refractoriness. In this case, a 51-year-old man with PD-associated peritonitis caused by C. indologenes was treated with 2 susceptible antibiotics, including fluoroquinolones to prevent acquired resistance and biofilm formation. There was no recurrence, and catheter removal was not necessary in this case. Collectively, the present case highlighted that PD-associated peritonitis caused by C. indologenes should be treated with 2 susceptible antibiotics including fluoroquinolones for 3 weeks.

Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma.

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient.

An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices.

Intermittent Fasting Sustainably Improves Glucose Tolerance in Normal Weight Male Mice Through Histone Hyperacetylation.

To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), followed by 4 weeks of ad libitum feeding, focusing on expression of genes for lipid metabolism in the skeletal muscle and histone acetylation in the promoter region. The 72hIF regimen resulted in metabolic remodeling, characterized by enhanced lipid utilization and mitochondrial activation in the muscle. This long-term IF (72hIF) caused stronger metabolic effects than alternate day fasting (24hIF) wherein fasting and refeeding are repeated every 24 hours. Upregulation of lipid oxidation genes and an increase in oxygen utilization were sustained even at 4 weeks after discontinuation of 72hIF, associated with histone hyperacetylation of the promoter region of uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) genes. An increase in leucine owing to fasting-induced muscle degradation was suggested to lead to the histone acetylation. These findings support the previously unappreciated notion that sustainable promotion of histone acetylation in lipid oxidation genes of the muscle and adipose tissues during and after IF may contribute to sustained metabolic effects of IF.

Incorporation of a bromine atom into DNA-related molecules changes their electronic properties.

To understand the mechanism underlying the high radio-sensitisation of living cells possessing brominated genomic DNA, X-ray photoelectron spectroscopy (XPS) using synchrotron X-rays with energies of 2000 or 2500 eV was used to study brominated and nonbrominated nucleobases, nucleosides and nucleotides. The bromine atom significantly reduced the energy gap between the valence and conduction states, although the core level states were not greatly affected. This finding was supported by quantum chemical calculation for the nucleobases and nucleosides. Our findings strongly indicate that the energy gaps between the valence and conduction levels of the molecules are significantly reduced by bromination. Furthermore, the brominated molecules are more likely to produce inelastic scattering low energy electrons upon exposure to 2000 or 3000 eV X-rays. This modification of electronic properties around the brominated group may both facilitate electron transfer to the brominated site in DNA and increase the probability of reaction with low energy electrons. These processes can induce DNA damage, presumably resulting in debromination of the uracil moiety and a subsequent cytotoxic effect.

Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy.

PURPOSE: To investigate the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, a protein involved in DNA double-strand break repair. MATERIALS AND METHODS: XRCC4 with a HisTag were expressed by E. coli harboring plasmid DNA and purified. Phospho-mimicking mutants in which one phosphorylation site was replaced with aspartic acid were also prepared in order to reproduce the negative charge resulting from phosphorylation. The proteins were separated into dimers and multimers by gel filtration chromatography. Circular dichroism (CD) spectroscopy was performed in the region from ultraviolet to vacuum-ultraviolet. The CD spectra were analyzed with two analysis programs to evaluate the secondary structures of the wild-type and phospho-mimicked dimers and multimers. RESULT AND DISCUSSION: The proportion of ß-strand in the wild-type dimers was very low, particularly in their C-terminal region, including the five phosphorylation sites. The secondary structure of the phospho-mimic hardly changed in the dimeric form. In contrast, the ß-strand content increased and the α-helix content decreased upon multimerization of the wild-type protein. The structural change of multimers slightly depended on the phospho-mimic site. These results suggest that the ß-strand structure stabilizes the multimerization of XRCC4 and it is regulated by phosphorylation at the C-terminal site in living cells. CONCLUSION: An increase in the ß-strand content in XRCC4 is essential for stabilization of the multimeric form through C-terminal phosphorylation, allowing the formation of the large double-strand break repair machinery.

Nature of the physicochemical process in water photolysis uncovered by a computer simulation.

In this work, we investigate the physicochemical process of water photolysis to bridge physical and chemical processes by a newly developed first-principles calculation code. The deceleration, thermalization, delocalization, and initial hydration of the extremely low-energy electrons ejected by water photolysis are sequentially tracked in the condensed phase. We show herein the calculated results for these sequential phenomena during 300 fs. Our results indicate that the mechanisms heavily depend on the intermolecular vibration and rotation modes peculiar to water and the momentum transfer between the electrons and the water medium. We suggest that using our results for the delocalized electron distribution will reproduce successive chemical reactions measured by photolysis experiments using a chemical reaction code. We expect our approach to become a powerful technique for various scientific fields related to water photolysis and radiolysis.

Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas.

Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.