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Abstract Various anomalies occurring before earthquakes are currently being studied to predict seismic events, with one of them being the radioactive element radon (222Rn). Radon concentrations in the soil, water, and atmosphere fluctuate in response to crustal movement. Recent research has statistically detected anomalies by analyzing the fluctuations in radon concentrations before earthquakes and conducting quantitative evaluations of radon. However, the method used to determine the parameters in the analysis was problematic. Therefore, in this study, we compared observed atmospheric radon concentration data with predicted values based on typical annual patterns using Random Forest analysis. We conducted a more objective analysis by employing this method and statistically determining anomalies using thresholds. This analysis was conducted using atmospheric radon concentration observation data obtained at Kobe Pharmaceutical University (KPU) before the 1995 Kobe Earthquake, and ionization currents emitted when radon decays were obtained at Fukushima Medical University (FMU) before the 2011 Tohoku-oki Earthquake. Consequently, before the major earthquakes occurred at both locations, the difference between the predicted and observed values exceeded the standard deviation by a factor of three. These results indicate the potential of Random Forest analysis to identify anomalies in atmospheric radon concentrations before earthquakes occur.

Objective The application of the da Vinci Surgical System in neurosurgery is limited due to technical difficulties requiring precise maneuvers and small instruments. This study details the advantages and disadvantages of robotics in neurosurgery and the reachable range of the transoral approach to lesions of the skull base and upper cervical spine. Methods In a cadaver study, the da Vinci Xi robot, lacking haptic feedback, was utilized for sagittal and coronal approaches on 5 heads, facilitating dura suturing in 3, with a 30°-angled drill for bone removal. Results Perfect exposure of all the nasopharyngeal sites, clivus, sellar, and choana, including the bilateral eustachian tubes, was achieved without any external incisions using this palatal split approach of transoral robotic surgery. The time required to perform a single stitch, knot, and complete single suture in robotic suturing of deep-seated were significantly less compared to manual suturing via the endonasal approach. Conclusion This is the first report to show the feasibility of suturing the dural defect in deep-seated lesions transorally and revealed that the limit of reach in the coronal plane via a transoral approach with incision of the soft palate is the foramen ovale. This preclinical investigation also showed that the transoral robotic approach is feasible for lesions extending from the sellar to the C2 in the sagittal plane. Refinement of robotic instruments for specific anatomic sites and future neurosurgical studies are needed to further demonstrate the feasibility and effectiveness of this system in treating benign and malignant skull base lesions.

Objective Practical applications of nerve decompression using neurosurgical robots remain unexplored. Our ongoing research and development initiatives, utilizing industrial robots, aim to establish a secure and efficient neurosurgical robotic system. The principal objective of this study was to automate bone grinding, which is a pivotal component of neurosurgical procedures. Methods To achieve this goal, we integrated an endoscope system into a manipulator and conducted precision bone machining using a neurosurgical drill, recording the grinding resistance values across 3 axes. Our study encompassed 2 core tasks: linear grinding, such as laminectomy, and cylindrical grinding, such as foraminotomy, with each task yielding unique measurement data. Results In linear grinding, we observed a proportional increase in grinding resistance values in the machining direction with acceleration. This observation suggests that 3-axis resistance measurements are a valuable tool for gauging and predicting deep cortical penetration. However, problems occurred in cylindrical grinding, and a significant error of 10% was detected. The analysis revealed that multiple factors, including the tool tip efficiency, machining speed, teaching methods, and deflection in the robot arm and jig joints, contributed to this error. Conclusion We successfully measured the resistance exerted on the tool tip during bone machining with a robotic arm across 3 axes. The resistance ranged from 3 to 8 Nm, with the measurement conducted at a processing speed approximately twice that of manual surgery performed by a surgeon. During the simulation of foraminotomy under endoscopic grinding conditions, we encountered a -10% error margin.

Abstract Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.

Objective The impact of adjuvant radiotherapy on overall survival (OS) and progression-free survival (PFS) of patients with grade II spinal cord astrocytomas remains controversial. Additionally, the relationship between progression and clinical deterioration after radiotherapy has not been well investigated. Methods This study included 53 patients with grade II intramedullary spinal cord astrocytomas treated by either subtotal, partial resection or open biopsy. Their clinical performance status was assessed immediately before operation and 1, 6, 12, 24, and 60 months after surgery by Karnofsky Performance Scale (KPS). Patients with and without adjuvant radiotherapy were compared. Results The groups with and without radiation comprised 23 and 30 patients with a mean age of 50.3 ±22.6 years (range, 2–88 years). The mean overall disease progression rate was 47.1% during a mean follow-up period of 48.4 ±39.8 months (range, 2.5–144.5 months). In the radiation group, 11 patients (47.8%) presented with progressive disease, whereas 14 patients (46.7%) presented with progressive disease in the group without radiation. There were no significant differences in OS or PFS among patients with or without adjuvant radiotherapy. KPS in both groups, especially radiation group, gradually decreased after operation and deteriorated before the confirmation of disease progression. Conclusion Adjuvant radiotherapy did not show effectiveness regarding PFS or OS in patients with grade II spinal cord astrocytoma according to classical classification based on pathohistological findings.

Objective The characteristics, imaging features, long-term surgical outcomes, and recurrence rates of primary spinal pilocytic astrocytomas (PAs) have not been clarified owing to their rarity and limited reports. Thus, this study aimed to analyze the clinical presentation, radiological features, pathological findings, and long-term outcomes of spinal PAs. Methods Eighteen patients with spinal PAs who were surgically treated between 2009 and 2020 at 58 institutions were included in this retrospective multicenter study. Patient data, including demographics, radiographic features, treatment modalities, and long-term outcomes, were evaluated. Results Among the 18 consecutive patients identified, 11 were women and 7 were men; the mean age at presentation was 31 years (3–73 years). Most PAs were located eccentrically, were solid or heterogeneous in appearance (cystic and solid), and had unclear margins. Gross total resection (GTR), subtotal resection (STR), partial resection (PR), and biopsy were performed in 28%, 33%, 33%, and 5% of cases, respectively. During a follow-up period of 65 ± 49 months, 4 patients developed a recurrence; however, the recurrence-free survival did not differ significantly between the GTR and non-GTR (STR, PR, and biopsy) groups. Conclusion Primary spinal PAs are rare and present as eccentric and intermixed cystic and solid intramedullary cervical tumors. The imaging features of spinal PAs are nonspecific, and a definitive diagnosis requires pathological support. Surgical resection with prevention of neurological deterioration can serve as the first-line treatment; however, the resection rate does not affect recurrence-free survival. Investigation of relevant molecular biomarkers is required to elucidate the regrowth risk and prognostic factors.

A 63-year-old woman had a history of neoadjuvant chemotherapy, mastectomy, and adjuvant endocrine therapy for 5 years before being diagnosed with recurrent lesions involving the right anterior chest wall, multiple lymph nodes, and pulmonary metastases. The patient was subsequently initiated on a paclitaxel and bevacizumab regimen. During this treatment, the patient complained of palpitations and malaise. Chest radiography revealed a left pneumothorax. Despite attempts at conservative treatment, the pneumothorax did not improve and a thoracoscopic approach was required. One of the metastatic tumors in the left lower lobe appeared to rupture, and this area was estimated to be the cause of air leak. The tumor was covered with a tissue seal sheet, and the patient’s condition improved with no recurrence of pneumothorax. This case highlights the importance of early conversion to surgical treatment when conservative treatment for pneumothorax is unresponsive due to the potential side effects of bevacizumab. The findings of this case report may be of interest to oncologists, pulmonologists, and other healthcare professionals involved in the care of patients with breast cancer and pulmonary metastases who are undergoing bevacizumab chemotherapy.

Abstract The 2011 Tohoku-oki earthquake produced the most well-recorded postseismic deformation of any megathrust earthquake in the world. Over the last decade, researchers have used a dense and widespread geodetic network of more than 1300 Global Navigation Satellite System (GNSS) stations inland, as well as the about 50 stations on the seafloor, to investigate the various deformation sources responsible for the observed crustal deformation. One of the contributing mechanisms to this crustal deformation is the stress relaxation of the viscoelastic mantle beneath the Japanese arc. As evident in experimental rock physics and geophysical observations, ambient mantle conditions and related rheology are expected to be heterogeneous in space. However, the contribution of such rheological heterogeneities to the postseismic deformation is still poorly understood. Here, we piece together several rheological heterogeneities inferred from the decade-long postseismic deformation of the 2011 Tohoku-oki earthquake. We reviewed more than twenty postseismic models to understand how viscoelastic earth can influence the postseismic surface deformation observed after the Tohoku-oki earthquake. Besides, we employed several synthetic models to tease out the contribution of individual rheological heterogeneities such as depth-dependent rheology of mantle wedge, oceanic asthenosphere, and low-viscosity zone beneath the volcanic front. We demonstrate that the vertical postseismic observation is the key to unravel rheological complexity beneath northeastern Japan. The broader vertical deformation pattern reveals the major viscosity contrast between backarc and forearc, and small-scale subsidence detects the presence of low-viscosity bodies related to arc magmatism. In short, this review paper provides a vista of three-dimensional heterogeneous rheology of viscoelastic earth. These rheological heterogeneities may play a crucial role in bridging the gap between our understanding of different phase of subduction zone earthquake cycle.

Highly concentrated trehalose induces beneficial senescence-like state in fibroblasts and accelerates the proliferation of keratinocytes and angiogenesis to promote optimal wound repair, demonstrating its therapeutic potential in modulating fibroblast functions.

Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33−mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways.

Abstract The postseismic Global Navigation Satellite System (GNSS) time series after the 2011 Tohoku‐oki earthquake is often empirically explained by one or more logarithmic and exponential decay functions. However, a function model with these decay functions struggles to illuminate various deformation mechanisms. Here, we propose a new function model incorporating laboratory‐derived constitutive laws (power‐law flow and velocity‐strengthening friction) utilized in mechanical postseismic models of the last decade. We demonstrated that our function model accurately predicts the decade‐long time series of inland GNSS stations, including coastal areas where significant postseismic uplift continues now. Moreover, it decomposes them into displacements due to viscoelastic relaxation and afterslip, similar to results produced by previous stress‐dependent postseismic models of the 2011 Tohoku‐oki earthquake. This physics‐based function model is an effective tool to ease the process of forecasting long‐term GNSS time series by dividing them into two dominant mechanisms at the plate interface and the surrounding viscoelastic mantle.

Abstract Cutaneous arteritis (CA) is a rare limited form of polyarteritis nodosa (PAN), which usually has a benign prognosis and requires less aggressive therapy. Here, we present a case of CA localized to both skin and muscle limited to the same area as skin lesions. We propose CA with muscle disorders as a severe subtype of CA and present a literature review of CA with muscle disorders, which may require treatment with intravenous pulse methylprednisolone, immunosuppressive therapy, and below‐the‐knee amputation. Our case presented here demonstrates a severe case of CA associated with compartment syndrome, leading to a highly elevated serum concentration of procalcitonin.

Abstract Despite the challenges in identifying earthquake precursors in intraplate (inland) earthquakes, various hydrological and geochemical measurements have been conducted to establish a possible link to seismic activities. Anomalous increases in radon (222Rn) concentration in soil, groundwater, and atmosphere have been reported prior to large earthquakes. Although the radon concentration in the atmosphere is lower than that in groundwater and soils, a recent statistical analysis has suggested that the average atmospheric concentration over a relatively wide area reflects crustal deformation. However, no study has sought to determine the underlying physico-chemical relationships between crustal deformation and anomalous atmospheric radon concentrations. Here, we show a significant decrease in the atmospheric radon concentration temporally linked to the seismic quiescence before the 2018 Northern Osaka earthquake occurring at a hidden fault with complex rupture dynamics. During seismic quiescence, deep-seated sedimentary layers in Osaka Basin, which might be the main sources of radon, become less damaged and fractured. The reduction in damage leads to a decrease in radon exhalation to the atmosphere near the fault, causing the preseismic radon decrease in the atmosphere. Herein, we highlight the necessity of continuous monitoring of the atmospheric radon concentration, combined with statistical anomaly detection method, to evaluate future seismic risks.

Abstract The presence of anomalous geochemical changes related to earthquakes has been controversial despite widespread, long time challenges for earthquake prediction. Establishing a quantitative relationship among geochemical changes and geodetical and seismological changes can clarify their hidden connection. Here we determined the response of atmospheric radon (222Rn) to diurnal tidal (K1 constituent) loading in the reported 11-year-long variation in the atmospheric radon concentration, including its anomalous evolution for 2 months before the devastating 1995 Kobe earthquake in Japan. The response to the tidal loading had been identified for 5 years before the occurrence of the earthquake. Comparison between these radon responses relative to crustal strain revealed that the response efficiency for the diurnal K1 tide was larger than that for the earthquake by a factor of 21–33, implying the involvement of crustal fluid movement. The radon responses occurred when compressional crustal stress decreased or changed to extension. These findings suggest that changes in radon exhaled from the ground were induced by ascent flow of soil gas acting as a radon carrier and degassed from mantle-derived crustal fluid upwelling due to modulation of the crustal stress regime.

The ProGrip™ laparoscopic self-fixating mesh provides advantages such as low cost and reduced pain following tack-free fixation in laparoscopic hernia repair through a transabdominal preperitoneal approach. Obturator hernia repair needs adequate fixation around the hernial orifice without the use of tacking, and ProGrip™ mesh provides options for secure fixation. However, it is often difficult to adequately adjust the mesh placement to cover the obturator hernia orifice with a ProGrip™ mesh, due to adhesion of the grips to the surrounding tissues. We introduce our technique to avoid unintentional adhesion during ProGrip mesh repair and discuss its utility in the treatment of obturator hernias. We repaired seven obturator hernia lesions in five patients using this technique without any complications. The biggest advantage of our technique is that the position of the mesh can be adjusted after it is expanded, unless the sheet is completely removed, allowing the surgeons to fix the mesh without any unintended adhesion to surrounding tissue.

Background: Lateral mass screw (LMS) and transpedicular screw (TPS) techniques are the two major options for performing posterior cervical fusion of the subaxial cervical spine. Although these two techniques can cover the vast majority of patients who require posterior fixation of the cervical spine, they are not without their limitations. Objective: The objective of this study is to introduce a novel technique, lateral mass intrapedicular screw (LMIS) fixation, for posterior subaxial cervical spine (C3–C6) fixation. Materials and Methods: The starting point of the screw is defined as the midpoint of the lateral mass. In the axial plane, the screw is angled at 20°–25° with respect to the midline of the spinous process. In the sagittal plane, the screw is directed toward the rostral quarter (zone 1) of the vertebral body and placed within the pedicle. A preliminary, proof-of-concept experiment was performed using a bone model created with synthetic bone and computed tomography images before performing the operation on a patient. Results: During the preliminary experiment, insignificant breaching of the inner cortex of the pedicle was observed with one of the screws. However, no other screws breached the inner cortex in the same manner during the preliminary experiment or during the operation, and the intraoperative fixation was strong. Conclusion: LMIS is a relatively simple and safe technique that can be performed for the fixation of subaxial cervical spines with screws that are longer than those used in LMS. We believe that this technique may join the two existing techniques to become a common alternative technique, particularly for patients with poor bone quality.

Meningiomas are a common pathology in the central nervous system requiring complete surgical resection. However, in cases of recurrence and post-irradiation, accurate identification of tumor remnants and a dural tail under bright light remains challenging. We aimed to perform real-time intraoperative visualization of the meningioma and dural tail using a delayed-window indocyanine green (ICG) technique with microscopy. Fifteen patients with intracranial meningioma received 0.5 mg/kg ICG a few hours before observation during the surgery. We used near-infrared (NIR) fluorescence to identify the tumor location. NIR fluorescence could visualize meningiomas in 12 out of 15 cases. Near-infrared visualization during the surgery ranged from 1 to 4 h after the administration of ICG. The mean signal-to-background ratio (SBR) of the intracranial meningioma in delayed-window ICG (DWIG) was 3.3 ± 2.6. The ratio of gadolinium-enhanced T1 tumor signal to the brain (T1BR) (2.5 ± 0.9) was significantly correlated with the tumor SBR (p = 0.016). Ktrans, indicating blood–brain barrier permeability, was significantly correlated with tumor SBR (p < 0.0001) and T1BR (p = 0.013) on dynamic contrast-enhanced magnetic resonance imaging (MRI). DWIG demonstrated a sensitivity of 94%, specificity of 38%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 75% for meningiomas. This is the first pilot study in which DWIG fluorescence-guided surgery was used to visualize meningioma and dural tail intraoperatively with microscopy. DWIG is comparable with second-window ICG in terms of mean SBR. Gadolinium-enhanced T1 tumor signal may predict NIR fluorescence of the intracranial meningioma. Blood–brain barrier permeability as shown by Ktrans on dynamic contrast-enhanced MRI can contribute to gadolinium enhancement on MRI and to ICG retention and tumor fluorescence by NIR.

Abstract Background Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment. Case presentation A 62-year-old man was treated by pembrolizumab for PD-L1 highly expressed lung adenocarcinoma, with multiple metastasis (small intestinal, lymph nodes, and bone). The treatment was stopped owing to drug-induced pneumonitis. One month after drug withdrawal, the patient visited the emergency department of our hospital with the complaint of severe stomachache. He had a rigid abdomen and generalized tenderness, and computed tomography scans showed free air within the abdomen. We diagnosed bowel perforation and performed emergency surgery. Surgical findings revealed multiple small intestine metastasis and mesenteric lymph node metastasis. Perforation was found in the metastatic site in the jejunum located around 40 cm anal to Treitz’s ligament. This perforated part was resected, and functional end-to-end anastomosis was performed using linear staplers. The post-operative course was uneventful. Pathological examination revealed lung adenocarcinoma metastasis at the perforation site, and the effectiveness of pembrolizumab was grade 1b (Japanese Classification of the Colorectal Carcinoma, seventh edition). Conclusions This is the first report of perforation of small intestinal metastasis of lung adenocarcinoma after pembrolizumab treatment. Because pembrolizumab causes some side effects, particularly autoimmune side effects, careful attention during treatment is warranted.

Abstract Slow earthquakes, including low‐frequency earthquakes and tremor, occur in the brittle‐ductile (plastic) transition zone on plate boundary faults. To understand how transitions in deformation mechanisms can influence seismic behavior, we conducted stick‐slip experiments on halite gouge at normal stresses (σn) of 8 to 113 MPa. In the brittle regime (σn ≤ 18 MPa), the halite gouge showed fast and regular stick‐slip associated with velocity‐weakening behavior. In contrast, increasing the normal stress within the semibrittle regime (σn ≥ 27 MPa) led to a significant decrease in slip velocity and stress drop, which was associated with a transition from velocity‐weakening to velocity‐strengthening behavior. Local stress measurements along the simulated faults, made using strain gauges, revealed that the critical nucleation length (Lc) increased with increasing normal stress. Macrostructural and microstructural observations showed that the transition from fast dynamic slip to slow quasi‐static slip could be attributed to an increasing contribution from semibrittle/plastic deformation occurring within domains that are heterogeneously distributed within the gouge layer. Our findings suggest that brittle‐plastic fault heterogeneity, which may be generated by spatial variations in pore fluid pressure and/or lithology, contributes to the emergence of slow earthquakes.

Introduction and aim. Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients.Material and methods. DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalently-closed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI.Results. HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies.Conclusions. OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.

Abstract We performed two axial deformation experiments on synthetic polycrystalline anorthite samples with a grain size of ~ 3 μm and 5 vol% Si–Al-rich glass at 900 °C, a confining pressure of 1.0 GPa, and a strain rate of 10−4.8 s−1. One sample was deformed as-is (dry); in the other sample, two half-cut samples (two cores) with 0.15 wt% water at the boundary were put together in the apparatus. The mechanical data for both samples were essentially identical with a yield strength of ~ 700 MPa and strain weakening of ~ 500 MPa by 20% strain. The dry sample appears to have been deformed by distributed fracturing. Meanwhile, the water-added sample shows plastic strain localization in addition to fracturing and reaction products composed of zoisite grains and SiO2 materials along the boundary between the two sample cores. Infrared spectra of the water-added sample showed dominant water bands of zoisite. The maximum water content was 1500 wt ppm H2O at the two-core boundary, which is the same as the added amount. The water contents gradually decreased from the boundaries to the sample interior, and the gradient fitted well with the solution of the one-dimensional diffusion equation. The determined diffusion coefficient was 7.4 × 10−13 m2/s, which agrees with previous data for the grain boundary diffusion of water. The anorthite grains in the water-added sample showed no crystallographic preferred orientation. Textural observations and water diffusion indicate that water promotes the plastic deformation of polycrystalline anorthite by grain-size-sensitive creep as well as simultaneous reactions. We calculated the strain rate evolution controlled by water diffusion in feldspar aggregates surrounded by a water source. We assumed water diffusion in a dry rock mass with variable sizes. Diffused water weakens a rock mass with time under compressive stress. The calculated strain rate decreased from 10−10 to 10−15 s−1 with an increase in the rock mass size to which water is supplied from

Plate subduction initiation requires weak boundaries between tectonic plates, but how weaknesses develop is unclear. Here, using high-pressure friction experiments on peridotite gouge material, the authors show that hydration reactions contribute to the weak mantle shear zones leading to subduction initiation.

Study Design: Technical note. Objectives: To show microsurgical technique, considering the meticulous anatomy of the ligamentum flavum (LF). Background: Different methods are available for treating lumbar spinal canal stenosis (LSCS). A minimally invasive surgery, namely, space shuttle laminotomy, has recently been proposed. Here, we describe the surgical method for this novel technique. To conduct this surgery accurately, surgeons must have perfect knowledge of anatomy, especially regarding the LF. Materials and Methods and Results: We use this interlaminectomy technique for all cases of LSCS. All patients with LSCS recovered from their neurological deficits in shorter hoslital stays than regular laminectomy. Conclusion: Minimally invasive space shuttle laminotomy (MISSL), which involves a microsurgical technique, is a safe, complication-free procedure.

This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell–related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE. We elaborate on histopathological differences, especially intraepidermal vesicle formation in PPP linked to IL–1–mediated pathways and the absence of hyaluronan expression, contrasting with Th2 cytokines-driven spongiosis in DPE. By addressing IL-4, hyaluronan synthases, and keratinocyte adhesion molecules, this correspondence aims to deepen understanding of PPP and DPE pathophysiology.

Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, in vivo they encounter multiple signals that control their varied functions in homeostasis, immunity, and disease. Here, we identify roles of Rev-erb nuclear receptors in regulating responses of mouse macrophages to complex tissue damage signals and wound repair. Rather than reinforcing a specific program of macrophage polarization, Rev-erbs repress subsets of genes that are activated by TLR ligands, IL4, TGFβ, and damage-associated molecular patterns (DAMPS). Unexpectedly, a complex damage signal promotes co-localization of NF-κB, Smad3, and Nrf2 at Rev-erb-sensitive enhancers and drives expression of genes characteristic of multiple polarization states in the same cells. Rev-erb-sensitive enhancers thereby integrate multiple damage-activated signaling pathways to promote a wound repair phenotype.

Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein.Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction.

The release of endogenous molecules from the skin after injury has been proposed to influence inflammation. Recent studies have found that pro-inflammatory signals can be generated by damaged endogenous self-RNA, and this event is detected by TLR3. Conversely, release of endogenous fragments of hyaluronic acid (HA) after injury has been proposed to inhibit LPS induced inflammation driven by TLR4. In this study we investigated if HA oligomers could also influence inflammation mediated by TLR3. A tetramer form of HA (oligo-HA) was added to MH-S cells (mouse alveolar macrophage cell line) that were then activated by poly(I:C). ELISA analysis of culture supernatants showed that the presence of oligo-HA suppressed the poly(I:C) induced release of IL-6 and TNFα. IL-6 mRNA expression was also suppressed as measured by quantitative RT-PCR. To determine the mechanism of action for oligo-HA to inhibit poly(I:C), macrophages derived from wild-type (WT), Tlr2-/- or Tlr4-/- mice were treated with oligo-HA and poly(I:C). Similar to WT cells, Tlr2-/- macrophages were inhibited by oligo-HA and retained suppression of cytokine release. In contrast, Tlr4-/- macrophages lost the capacity to be suppressed by oligo-HA. An increase in Traf1 (TLR negative regulator) mRNA was observed after oligo-HA treatment of WT but not in Tlr4-/- macrophages, and oligo-HA did not suppress cytokine responsiveness in Traf1-/- macrophages. These results show that oligo-HA acts through TLR4 and TRAF1 to inhibit TLR3-dependent inflammation. This observation illustrates the complex immunomodulatory action of endogenous products released after injury.

Musashi1 (MSI1) is an RNA-binding protein that plays critical roles in nervous-system development and stem-cell self-renewal. Here, we examined its role in the progression of glioma. Short hairpin RNA (shRNA)-based MSI1-knock down (KD) in glioblastoma and medulloblastoma cells resulted in a significantly lower number of self renewing colony on day 30 (a 65% reduction), compared with non-silencing shRNA-treated control cells, indicative of an inhibitory effect of MSI1-KD on tumor cell growth and survival. Immunocytochemical staining of the MSI1-KD glioblastoma cells indicated that they ectopically expressed metaphase markers. In addition, a 2.2-fold increase in the number of MSI1-KD cells in the G2/M phase was observed. Thus, MSI1-KD caused the prolongation of mitosis and reduced the cell survival, although the expression of activated Caspase-3 was unaltered. We further showed that MSI1-KD glioblastoma cells xenografted into the brains of NOD/SCID mice formed tumors that were 96.6% smaller, as measured by a bioluminescence imaging system (BLI), than non-KD cells, and the host survival was longer (49.3±6.1 days vs. 33.6±3.6 days; P

As C-Xyloside has been suggested to be an initiator of glycosaminoglycan (GAG) synthesis, and GAGs such as Dermatan sulfate (DS) are potent enhancers of fibroblast growth factor (FGF)--10 action, we investigated if a C-Xylopyranoside derivative, (C-β-D-xylopyranoside-2-hydroxy-propane, C-Xyloside), could promote DS production by cultured normal human keratinocytes, how this occurs and if C-Xyloside could also stimulate FGF-dependent cell migration and proliferation. C-Xyloside-treated keratinocytes greatly increased secretion of total sulfated GAGs. Majority of the induced GAG was chondroitin sulfate/dermatan sulfate (CS/DS) of which the major secreted GAG was DS. Cells lacking xylosyltransferase enzymatic activity demonstrated that C-Xyloside was able to stimulate GAG synthesis without addition to core proteins. Consistent with the observed increase in DS, keratinocytes treated with C-Xyloside showed enhanced migration in response to FGF-10 and secreted into their culture media GAGs that promoted FGF-10-dependent cellular proliferation. These results indicate that C-Xyloside may enhance epithelial repair by serving as an initiator of DS synthesis.

Antimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocuity of the cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to host defense. Here we show that S. epidermidis delta-toxin (PSMgamma) is normally present in the epidermis and sparsely in the dermis of human skin using immunohistochemistry. Synthetic delta-toxin interacted with neutrophil extracellular traps (NETs) and colocalized with cathelicidin while also inducing NET formation in human neutrophils. In antimicrobial assays against Group A Streptococcus (GAS), delta-toxin cooperated with CRAMP, hBD2, and hBD3. In whole blood, addition of delta-toxin exerted a bacteriostatic effect on GAS, and in NETs, delta-toxin increased their killing capacity against this pathogen. Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of delta-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally, in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine levels) when the wounds were pretreated with delta-toxin. Thus, these data suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen.

The article presents a case study of adult epidermal nevus syndrome (ENS) with hypophosphatemic osteomalacia treated successfully with burosumab, an anti-FGF23 antibody. Topics include the clinical presentation of ENS, the diagnostic challenges, and the efficacy of burosumab as a first-line therapy in improving hypophosphatemia, skeletal deformities, and intense pain associated with the condition.