[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].

This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.

Regulation of photosystems II and I depending on N partitioning to Rubisco in rice leaves: a study using Rubisco-antisense transgenic plants.

We have previously suggested that in rice (Oryza sativa L.) leaves of different ages and N nutrition statuses, photosystems II and I (PSII and PSI, respectively) are regulated depending on N partitioning to Rubisco, which can determine the magnitude of unutilized light energy. The robustness of this mechanism was tested using Rubisco-antisense transgenic rice plants, in which reduced N partitioning to Rubisco markedly increases unutilized light energy. In wild-type plants, N partitioning to Rubisco tended to be smaller in the leaves at lower positions owing to leaf senescence. In the transgenic plants, N partitioning to Rubisco was generally smaller than in the wild-type plants and was relatively constant among leaf positions. The quantum efficiency of PSII [Y(II)] and quantum yield of non-photochemical quenching [Y(NPQ)] correlated positively and negatively, respectively, with N partitioning to Rubisco irrespective of leaf position or genotype. The oxidation levels of the reaction center chlorophyll of PSI (P700) [Y(ND)] negatively correlated with N partitioning to Rubisco. However, in mature and early senescent leaves of the transgenic plants, Y(ND) was markedly lower than expected from N partitioning to Rubisco. These results suggest that in the transgenic plants, the regulation depending on N partitioning to Rubisco is robust for PSII but fails for PSI in mature and early senescing leaves. In these leaves, the magnitudes of P700 oxidation were found to be less than expected from the Y(II) and Y(NPQ) values. The mechanistic reasons and physiological implications of these phenomena are discussed.

Identification of APPB1 as a substrate for anaplastic lymphoma kinase.

Anaplastic lymphoma kinase (ALK) is a well-known oncogene involved in various malignancies such as anaplastic large cell lymphoma, lung cancer and neuroblastoma. Several substrates for fused ALK have been identified and their biological functions have been described. However, the lack of a comprehensive identification of ALK substrates limits our understanding of the biological roles of receptor ALK. Thus, this study aimed to identify novel ALK substrates and characterize their biological functions. We screened the interactors of the kinase domain of receptor ALK using proximity-dependent biotin identification and identified 43 interactors. We narrowed down the candidates by evaluating whether these interactors were downstream of ALK in a neuroblastoma cell line, NB-1. Among these, we identified amyloid beta precursor protein binding family B member 1 (APBB1) as an ALK downstream molecule involved in NB-1 cell viability. Finally, we assessed the kinase-substrate relationship between ALK and APBB1 and found that ALK phosphorylated multiple tyrosine residues in APBB1 both in-cell and in-tube assays, with tyrosine 269 as a major target. In conclusion, we successfully identified a new substrate for receptor ALK. Our results may help further elucidate the molecular mechanism of ALK downstream signaling in neuroblastoma.

Evaluation of thrombomodulin/thrombin activatable fibrinolysis inhibitor function in plasma using tissue-type plasminogen activator-induced plasma clot lysis time.

Background: Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain. Objectives: Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis. Methods: Since thrombin is required to generate activated TAFI (TAFIa) that targets the C-terminal lysine of partially digested fibrin, a clot lysis assay is suitable for evaluating its function. Using tissue-type plasminogen activator-induced plasma clot lysis time (tPA-PCLT) together with TAFIa inhibitor and recombinant sTM (rsTM), we evaluated the specific function of TM/TAFI in the plasma milieu. Results: tPA-PCLT values were significantly shortened by the TAFIa inhibitor. rsTM supplementation prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor to a time similar to that obtained without rsTM and with the TAFIa inhibitor. Plasma obtained from patients treated with rsTM showed prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor but not further prolonged by rsTM. However, no significant correlation was observed between tPA-PCLT and parameters of TM/TAFI system in the plasma. Conclusion: The role of the TM/TAFI system in regulating fibrinolysis was successfully evaluated using TAFIa inhibitor and rsTM. Trace amounts of soluble TM in normal plasma appeared sufficient to activate TAFI and inhibit fibrinolysis. Further, a therapeutic dose of rsTM appeared sufficient to activate TAFI and regulate fibrinolysis in the plasma milieu.

Interstitial fluid flow decreases with age, especially after 50 years.

Physiological age-related alterations in the interstitial flow in the brain, which plays an important role in waste product removal, remain unclear. Using [15O]H2O positron emission tomography (PET), water dynamics were evaluated in 63 healthy adult participants aged between 20 and 80 years. Interstitial flow was assessed by influx ratio (IR) and drain rate (DR), using time-activity concentration data. Participants were divided into four age groups with 15-year ranges, to evaluate age-related functional alterations. At least one of the indices declined significantly with age across all groups. A significant linear negative correlation between age and both indicators was found in the scatter plots (IR: R2 = 0.54, DR: R2 = 0.44); both indicators were predominantly lower after age 50 years. These results suggest interstitial flow decreases with age, especially after 50 years. These important findings can contribute to devising therapeutic interventions for neurological diseases characterized by abnormal accumulation of waste products, and suggest the need for taking measures to maintain interstitial flow starting around the age of 50 years.

Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats.

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 µM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 µM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 µM), and a P2Y receptor antagonist, cibacron blue F3GA (200 µM), inhibited the ATP (100 µM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 µM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 µM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 µM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.

ATP-Induced Contractile Response of Esophageal Smooth Muscle in Mice.

The tunica muscularis of mammalian esophagi is composed of striated muscle and smooth muscle. Contraction of the esophageal striated muscle portion is mainly controlled by cholinergic neurons. On the other hand, smooth muscle contraction and relaxation are controlled not only by cholinergic components but also by non-cholinergic components in the esophagus. Adenosine triphosphate (ATP) is known to regulate smooth muscle contraction and relaxation in the gastrointestinal tract via purinergic receptors. However, the precise mechanism of purinergic regulation in the esophagus is still unclear. Therefore, the aim of the present study was to clarify the effects of ATP on the mechanical responses of the esophageal muscle in mice. An isolated segment of the mouse esophagus was placed in a Magnus's tube and longitudinal mechanical responses were recorded. Exogenous application of ATP induced contractile responses in the esophageal preparations. Tetrodotoxin, a blocker of voltage-dependent sodium channels in neurons and striated muscle, did not affect the ATP-induced contraction. The ATP-evoked contraction was blocked by pretreatment with suramin, a purinergic receptor antagonist. RT-PCR revealed the expression of mRNA of purinergic receptor genes in the mouse esophageal tissue. The findings suggest that purinergic signaling might regulate the motor activity of mouse esophageal smooth muscle.

Glypican-1-targeted antibody-drug conjugate inhibits the growth of glypican-1-positive glioblastoma.

Glioblastoma is the deadliest form of brain tumor. The presence of the blood-brain barrier (BBB) significantly hinders chemotherapy, necessitating the development of innovative treatment options for this tumor. This report presents the in vitro and in vivo efficacy of an antibody-drug conjugate (ADC) that targets glypican-1 (GPC1) in glioblastoma. The GPC1-ADC was created by conjugating a humanized anti-GPC1 antibody (clone T2) with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl linkers. Immunohistochemical staining analysis of a glioblastoma tissue microarray revealed that GPC1 expression was elevated in more than half of the cases. GPC1-ADC, when bound to GPC1, was efficiently and rapidly internalized in glioblastoma cell lines. It inhibited the growth of GPC1-positive glioma cell lines by inducing cell cycle arrest in the G2/M phase and triggering apoptosis in vitro. We established a heterotopic xenograft model by subcutaneously implanting KALS-1 and administered GPC1-ADC intravenously. GPC1-ADC significantly inhibited tumor growth and increased the number of mitotic cells. We also established an orthotopic xenograft model by intracranially implanting luciferase-transfected KS-1-Luc#19. After injecting Evans blue and resecting brain tissues, dye leakage was observed in the implantation area, confirming BBB disruption. We administered GPC1-ADC intravenously and measured the luciferase activity using an in vivo imaging system. GPC1-ADC significantly inhibited tumor growth and extended survival. In conclusion, GPC1-ADC demonstrated potent intracranial activity against GPC1-positive glioblastoma in an orthotopic xenograft model. These results indicate that GPC1-ADC could represent a groundbreaking new therapy for treating glioblastoma beyond the BBB.

Equisetum praealtum and E. hyemale have abundant Rubisco with a high catalytic turnover rate and low CO2 affinity.

The kinetic properties of Rubisco, a key enzyme for photosynthesis, have been examined in numerous plant species. However, this information on some plant groups, such as ferns, is scarce. This study examined Rubisco carboxylase activity and leaf Rubisco levels in seven ferns, including four Equisetum plants (E. arvense, E. hyemale, E. praealtum, and E. variegatum), considered living fossils. The turnover rates of Rubisco carboxylation (kcatc) in E. praealtum and E. hyemale were comparable to those in the C4 plants maize (Zea mays) and sorghum (Sorghum bicolor), whose kcatc values are high. Rubisco CO2 affinity, estimated from the percentage of Rubisco carboxylase activity under CO2 unsaturated conditions in kcatc in these Equisetum plants, was low and also comparable to that in maize and sorghum. In contrast, kcatc and CO2 affinities of Rubisco in other ferns, including E. arvense and E. variegatum were comparable with those in C3 plants. The N allocation to Rubisco in the ferns examined was comparable to that in the C3 plants. These results indicate that E. praealtum and E. hyemale have abundant Rubisco with high kcatc and low CO2 affinity, whereas the carboxylase activity and abundance of Rubisco in other ferns were similar to those in C3 plants. Herein, the Rubisco properties of E. praealtum and E. hyemale were discussed regarding their evolution and physiological implications.

Tumor cell-expressed lipolysis-stimulated lipoprotein receptor negatively regulates T-cell function.

Lipolysis-stimulated lipoprotein receptor (LSR) is known as a lipoprotein receptor. LSR is expressed in various solid tumors, including epithelial ovarian, gastric, and colon cancers. High LSR expression is significantly associated with poor prognosis, but its role in cancer has not been fully elucidated. LSR belongs to the Ig protein superfamily, which is conserved in B7 family. Here, we assessed LSR as a novel immune checkpoint molecule. We developed a novel anti-LSR antibody (#27-6 mF-18) that defects antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. The #27-6 mF-18 cross-reacts with both human and mouse LSR. We found that LSR was expressed on 4T1 murine breast cancer cell line. The #27-6 mF-18 exhibited antitumor effects against the 4T1 syngeneic tumor model, a poor immunogenic model refractory to treatment with anti-PD-1 or anti-CTLA-4 antibodies. Compared with control antibody-treated mice, mice treated with #27-6 mF-18 showed significantly increased numbers of CD8+ T cells and a ratio of activated CD8+ T cells infiltrated in the tumor tissue. This antitumor effect was abrogated by CD8+ T-cell depletion through anti-CD8 antibody treatment, indicating that LSR negatively regulates tumor immunity by repressing CD8+ T cells. These findings show that LSR negatively regulates T-cell immune activity. LSR targeting could provide immune checkpoint inhibitors for cancer immunotherapy.

Characteristics of compounds with strong or weak nitrification inhibition in sewage.

To clarify the characteristics of compounds with strong or weak nitrification inhibition in sewage, 64 organic compounds including compounds registered in Pollutant Release and Transfer Register (PRTR) were evaluated in terms of their chemical structures and molecular weights. Nineteen compounds showed strong nitrification inhibition by testing with Nitrosomonas europaea. Compounds with thioamide structures had the lowest median value of EC50 (0.017 mg/L), followed by those with alkyne structures (0.121 mg/L), chlorophenol structures (0.300 mg/L), and then azole structures (0.365 mg/L). In contrast, 33 of the 64 compounds showed weak nitrification inhibition at a concentration of 10 mg/L, 27 of which were categorized into three main groups: long-chain alcohol structures, alkyne structures with a phenyl group, and aromatic structures. Most compounds with strong nitrification inhibition had a low molecular weight (MW) from 50 to 200. Meanwhile, the proportion of compounds with weak nitrification inhibition tended to be greater with increasing MW and such compounds were predominant at higher molecular weights above 300. The correlations of results derived from tests of nitrification inhibition based on ISO 9509 and N. europaea showed that 24 out of 30 compounds provided results that were highly correlated between these tests (R = 0.85), while 4 compounds with chlorophenol structures and 2 compounds with alkyne structures showed weaker inhibition rates in the ISO 9509 test than in the N. europaea test. Our results indicate that the magnitude of nitrification inhibition depends on MW in addition to the chemical structure, which is helpful in the search for the cause of nitrification inhibition in wastewater treatment plants.

Removal of calciprotein particles from the blood using an adsorption column improves prognosis of hemodialysis miniature pigs.

Hyperphosphatemia is a major risk for poor prognosis in patients with end-stage renal disease. However, the molecular mechanism behind this link remains elusive. We and others have demonstrated that serum phosphorus levels correlate positively with circulating levels of calciprotein particles (CPPs). CPPs are colloidal mineral-protein complexes containing insoluble calcium-phosphate precipitates and have been reported to induce calcification in cultured vascular smooth muscle cells and inflammatory responses in cultured macrophages. Hence, we hypothesize that CPPs may be responsible for disorders associated with hyperphosphatemia. Using hyperphosphatemic miniature pigs receiving hemodialysis, here we show that removal of CPPs from the blood with a newly developed CPP adsorption column improves survival and alleviates complications including coronary artery calcification, vascular endothelial dysfunction, metastatic pulmonary calcification, left ventricular hypertrophy, and chronic inflammation. The present study identifies CPPs as an effective therapeutic target and justifies clinical trials to determine whether the CPP adsorption column may be useful as a medical device for improving clinical outcomes of hemodialysis patients.

Age-Dependent Changes in Regulation of Water Inflow Into the Vitreous Body.

Purpose: Water inflow into the vitreous body regulated by retinal aquaporin-4 distributed within Müller cells has been observed in mice; however, the changes in this phenomenon with age remain unknown. This study aimed to evaluate whether intravenously injected H2O also flows into the vitreous body of human subjects and to investigate whether water dynamics in the human posterior eye change with age using [15O]H2O positron emission tomography (PET). Methods: Forty-six normal adult volunteers underwent [15O]H2O PET, and the standard uptake value (SUV) in the center of the vitreous body after 1000-MBq [15O]H2O administration was assessed. The SUV was fitted to an exponential curve, and y0, the steady state of the SUV, and b, the speed of increase in the SUV, were calculated. The results for patients ranging from in age from 20 to 39, 40 to 59, and 60 to 79 years were compared using analyses of variance followed by Games to Howell tests. Results: For the parameter y0, statistical analysis revealed no statistically significant differences among the three groups. For parameter b, statistical analysis revealed statistically significant differences between the 20 to 39 and 60 to 79 age groups (P = 0.000), the 40 to 59 and 60 to 79 age groups (P = 0.025), and the 20 to 39 and 40 to 59 age groups (P = 0.037). Conclusions: The present study revealed that H2O injected into the vein flows into the human vitreous body and that the speed of increase in water flow into the vitreous body decreases with aging. This study suggests that water dynamics in the posterior eye, or the retinal glymphatic pathway, change significantly with aging.

Changes in functional connectivity among vestibulo-visuo-somatosensory and spatial cognitive cortical areas in persistent postural-perceptual dizziness: resting-state fMRI studies before and after visual stimulation.

Introduction: Persistent postural-perceptual dizziness (PPPD) is a functional chronic vestibular syndrome with symptom exacerbation by upright posture, motion, and complex visual stimuli. Among these exacerbating factors, visual exacerbation is the most specific characteristic of PPPD requiring further investigation. We hypothesized that stimulus-induced changes occur in the functional connectivity (FC) rather than simple neural activation that is involved in visual stimulation. The present study aimed to identify the neural basis of PPPD by investigating FC before and after visual stimulation. Methods: Eleven patients with PPPD and 11 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI (rs-fMRI) before and after task-based fMRI with visual stimuli. Results: At pre-stimulus, FC between the vestibular cortex and visual areas was low, while that between the somatosensory and visual areas was high in PPPD compared with that in HCs. FC between the visuospatial (parahippocampal gyrus) and spatial cognitive areas (inferior parietal lobule) was elevated in PPPD even in the pre-stimulus condition, which no longer increased at post-stimulus as observed in HCs. In the post-stimulus condition, FC between the visual and spatial cognitive areas and that between the visual and prefrontal areas increased compared with that in the pre-stimulus condition in PPPD. Task-based fMRI demonstrated that no brain regions showed different activities between the HC and PPPD groups during visual stimulation. Discussion: In PPPD, vestibular inputs may not be fully utilized in the vestibulo-visuo-somatosensory network. Given that the FC between visuospatial and spatial cognitive areas increased even in HCs after visual stimuli, elevated status of this FC in combination with the high FC between the somatosensory and visual areas would be involved in the visual exacerbation in PPPD. An increase in FC from the visual areas to spatial cognitive and prefrontal areas after visual stimuli may account for the prolonged symptoms after visual exacerbation and anxious status in PPPD.

AI-Driven Discovery of Amorphous Fluorinated Polymer Electret with Improved Charge Stability for Energy Harvesting.

Electret materials are promising dielectric materials with trapped charges for various applications such as vibration energy harvesters and acoustic transducers. In the present work, ionization potential is discovered as the descriptor to quantify the charging performance for amorphous fluorinated polymer electrets. Using this descriptor, high-throughput computations, and graph neural network models, 1 176 591 functional groups are screened on the cyclic transparent optical polymers (CYTOP), and 3 promising electrets are identified. The electrets are synthesized experimentally as 15 µm-thick films. The films are able to keep their both bipolar surface potentials above ±3.1 kV for over 1500 h and are estimated to have longevity of 146 years under 80 °C, achieving significant improvements on charging stability among CYTOP-based polymer electrets. The excellent bipolar charging performance can greatly enhance power generation capacity of electret-based vibration energy harvesters. This work also demonstrates the use of deep learning as a new paradigm for accelerating practical materials discovery.

Circulating Cell-Free DNA as a Biomarker for Prognosis and Response to Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Systemic therapy provides clinical benefits to a subset of patients with advanced unresectable hepatocellular carcinoma (HCC). However, few biomarkers are available for predicting prognosis and treatment response in patients with advanced HCC undergoing treatment with systemic therapies. This study aimed to examine whether circulating cell-free DNA (cfDNA) containing circulating tumor DNA can act as a therapeutic response and prognostic biomarker in patients with advanced HCC. METHODS: We analyzed longitudinally collected plasma cfDNA of patients with advanced HCC who were naïve to systemic therapy, and assessed their prognostic and predictive values to determine treatment responses. RESULTS: cfDNA concentration positively correlated with entire tumor volume on computed tomography before (p = 0.0231) and at the end (p < 0.0001) of the first-line systemic therapy. The overall survival rate was higher in patients with cfDNA concentrations lower than the median cfDNA level at baseline compared to patients with higher cfDNA concentrations (hazard ratio, 0.2765; 95% confidence interval, 0.08-0.81; p = 0.0197). The ratio of cfDNA at 4 weeks to that at baseline was predictive of radiographic disease response. In patients with progressive disease, cfDNA concentration at 4 weeks increased significantly (p = 0.0245), whereas the concentration remained unchanged in patients with other disease courses (p = 0.9375). CONCLUSION: The baseline plasma cfDNA concentration can be used as a prognostic biomarker in patients with advanced HCC. cfDNA kinetics may also predict the tumor response to therapy and disease progression.

The Effectiveness of Washing Clothing Contaminated With Cyclophosphamide: A Pilot Study.

BACKGROUND: Measures to prevent exposure to anticancer drugs mitigate health hazards for caregivers, family members, and healthcare workers caring for patients with cancer. Previous studies have reported that anticancer drugs were detected on the linens of patients receiving chemotherapy. OBJECTIVES: This pilot study investigated the effectiveness of the washing methods recommended by Japanese guidelines for linens contaminated with cyclophosphamide (CTX). METHODS: This study used 15 shirts contaminated with 10 mg of CTX divided into three study groups washed with or without detergent, with or without an additional clean shirt. The CTX level on each shirt was measured after washing. Residual CTX levels on the shirts were compared to the measurable level of 1 ng/cm2 as a criterion for evaluating efficacy. FINDINGS: Washing a garment twice, as recommended in the Japanese guidelines, is effective in removing CTX contamination from clothing with or without detergent. However, contaminated garments should be washed separately from uncontaminated clothing.

Thromboelastography with platelet mapping to guide anesthetic management of emergency cesarean delivery in a patient with thrombasthenia: a case report.

BACKGROUND: Perinatal management of congenital platelet dysfunction represents a challenge. One of the major concerns is whether neuraxial anesthesia can be applicable for cesarean delivery. We present a patient with thrombasthenia who underwent emergency cesarean delivery. CASE PRESENTATION: A 34-year-old primipara was diagnosed with autosomal dominant thrombasthenia, which was not classified as any known type. A thorough examination revealed that adenosine diphosphate aggregation and collagen aggregation were suppressed. Platelet mapping of viscoelastic testing was used to observe the trajectory of platelet function during pregnancy, which was found to be normal to hypercoagulable until 38 weeks of gestation. On the basis of the results of testing and physiological status, we commenced spinal anesthesia and avoided prophylactic platelet transfusion. CONCLUSION: The platelet mapping of viscoelastic testing was rapid and simple, allowing repeated examinations. We could choose the appropriate anesthesia method and determine the necessity of blood transfusion for a pregnant patient with thrombasthenia.