Pediatric leukemia and maternal occupational exposure to anticancer drugs: the Japan Environment and Children's Study.

ABSTRACT: Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms.

Carrier Transport Switching of Ferroelectric BTBT Derivative.

Alkylamide-substituted [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivative of BTBT-NHCOC14H29 (1), which has ferroelectric N-H···O= hydrogen-bonding network of alkylamide group and two-dimensional (2D) electric structure of BTBT π-cores, was prepared to design the external electric field-responsive organic semiconductors. The short-chain derivative of BTBT-NHCOC3H7 (1') revealed the coexistence of a 2D electronic band structure based on the herringbone BTBT arrangement and the one-dimensional (1D) hydrogen-bonding chain. 1 formed a smectic E (SmE) liquid crystal phase above 412 K and showed ferroelectric hysteresis in the electric field-polarization (P-E) curves at 403-433 K. The remanent polarization (Pr) and coercive electric field (Ec) of 1 at 408 K, 0.1 Hz were 24.0 µC cm-2 and 5.54 V µm-1, respectively. By thermal annealing of thin-film 1 at 443 K, the molecular assembly structure of 1 changed from a monolayer to a bilayer structure with high crystallinity, resulting in conducting layers of BTBT parallel to the substrate surface. The organic field-effect transistor (OFET) device with thermally annealed thin-film 1 showed p-type semiconducting behavior with the hole mobility of 1.0 × 10-3 cm2 V-1 s-1. Furthermore, device 1 showed switching behavior of semiconducting properties by electric field poling and thermal annealing cycle. The electric field response of ferroelectrics modulated the molecular orientation and conduction properties of organic semiconductors, resulting in external electric field control of carrier transport properties.

Operando NMR electrochemical gating studies of ion dynamics in PEDOT:PSS.

Although organic mixed ionic-electronic conductors are widely proposed for use in bioelectronics, energy generation/storage and neuromorphic computing, our fundamental understanding of the charge-compensating interactions between the ionic and electronic carriers and the dynamics of ions remains poor, particularly for hydrated devices and on electrochemical cycling. Here we show that operando 23Na and 1H nuclear magnetic resonance (NMR) spectroscopy can quantify cation and water movement during the doping/dedoping of films comprising the widely used mixed conductor poly(3,4-ethylene dioxythiophene) poly(styrene sulfonate) (PEDOT:PSS). A distinct 23Na quadrupolar splitting is observed due to the partial ordering of the PSS chains within the PEDOT:PSS-rich domains, with respect to the substrate. Operando 23Na NMR studies reveal a close-to-linear correlation between the quadrupolar splitting and the charge stored, which is quantitatively explained by a model in which the holes on the PEDOT backbone are bound to the PSS SO3- groups; an increase in hole concentration during doping inversely correlates with the number of Na+ ions bound to the PSS chains within the PEDOT-rich ordered domains, leading to a decrease in ions within the ordered regions and a decrease in quadrupolar splitting. The Na+-to-electron coupling efficiency, measured via 23Na NMR intensity changes, is close to 100% when using a 1 M NaCl electrolyte. Operando 1H NMR spectroscopy confirms that the Na+ ions injected into/extracted from the wet films are hydrated. These findings shed light on the working principles of organic mixed conductors and demonstrate the utility of operando NMR spectroscopy in revealing structure-property relationships in electroactive polymers.

Multiemission of Ce3+ from a Single Crystallographic Site Induced by Disordering of Ions.

White-light emission with a single activator is an attractive function of phosphors. In this work, we investigated the photoluminescence properties of Ca5.7Y1.3Si7O16.7N3.3, which is a compound denoted as Ca4+xY3-xSi7O15+xN5-x discovered by our group, with Ce-activation using optical measurements and density functional theory (DFT) calculation. Samples showed a tunable emission from purple to white under ultraviolet (UV) light. In this compound, Ca and Y as well as anions are distributed disorderly, and Ca/Y ions occupy two crystallographically distinct sites; those sites are possible sites for Ce substitution. DFT calculation and structural refinement revealed that the tunable emission was generated by Ce at the crystallographically equivalent site but with distinct local structures caused by the disordering of cations and anions. As far as we know, this is the first report about a white-light-emitting phosphor with only Ce activation.

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria.

BACKGROUND: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. METHODS: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. RESULTS: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test). CONCLUSIONS: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria.

[Rectal cancer with multiple metastases complicated by Crohn's disease 5 years after surgery:a case report].

In recent years, with the rising incidence of patients having long-term Crohn's disease, there has been an increase in the number of reports of carcinogenesis from dysplasia with chronic inflammation as the primary pathogenic factor. We hereby report a case of multiple metastases that appeared 5 years after surgery, in a patient with rectal cancer who had Crohn's disease. A man in his 50s was diagnosed with Crohn's disease which affected his small and large intestines 21 years back. The patient was being treated with oral steroids, 5-aminosalicylic acid, and modified nutrition. Infliximab was added to the treatment after it was introduced 11 years ago. He also had a history of rectal cancer and had undergone surgery for the same 5 years back. He was diagnosed with stage II cancer, and had not received any adjuvant chemotherapy. However, 5 years after surgery, multiple metastases recurred, and chemotherapy with mFOLFOX6 was administered. Additionally, for treating his Crohn's disease, which was also active, infliximab was changed to vedolizumab;however, the patient died a year later. Colorectal cancer accompanied with Crohn's disease has a higher risk of developing metastasis and is associated with poorer prognosis as compared to the noncomplicated colorectal cancer. Regarding treatment modalities, while searching for multidisciplinary treatment methods centered on surgical treatment in collaboration with medical oncologists and radiologists, the safety of treatment for Crohn's disease in patients with cancer must be borne in mind. The rising prevalence of cases of colorectal cancer with Crohn's disease is expected to lead to the formulation of specialized diagnostic and treatment strategies for these patients.

pH-Responsive Ultrathin Nanoporous SiO2 Films for Selective Ion Permeation.

Ultrathin nanoporous (NP) films are an emerging field for selective and effective ion/molecular separation and electrochemical sensing applications. We describe selective ion permeation in surface-functionalized ultrathin NP SiO2 films (NP SiO2-NH2). The ultrathin NP SiO2 films with ca. 8 nm thickness were prepared from silsesquioxane-containing blend polymer Langmuir-Blodgett films (nanosheets) using the photo-oxidation method. The porous SiO2 surface was modified with a pH-responsive amine-containing silane coupling agent. Selective ion permeation was demonstrated under acidic pH conditions (pH ≤ 6) using two equally sized redox probes: negative (Fe(CN)63-/4-) and positive (Ru(NH3)62+/3+) ions. The current density for Fe(CN)63-/4- decreased as the pH value increased to pH = 6, whereas it increased for Ru(NH3)62+/3+. Control measurements revealed that the probes can penetrate the pores of nonfunctionalized SiO2 films irrespective of pH values, indicating that both the size and the surface charge response contributed to selective ion permeation. Results obtained from this study pave the way for new applications in molecular separation and sensing applications based on ultrathin nanoporous films (<10 nm) and tailored surfaces.

Infantile neuroblastoma and maternal occupational exposure to medical agents.

BACKGROUND: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study aimed to examine whether such occupational exposure increased the risk of childhood cancer in offspring. METHODS: We used the dataset of the Japan Environment and Children's Study, a nationwide birth cohort involving over 100,000 mother-child pairs. Information was obtained via successive questionnaires that were completed until the child turned 1 year of age. The parents were asked whether they occupationally handled medical agents during pregnancy. RESULTS: A total of 26 infants developed neoplasms: neuroblastoma, leukemia, and brain tumor. The incidence of neuroblastoma was significantly higher in infants whose mothers were exposed to radiation (3/2142: 140.1 per 100,000 population) than in those who were not (12/90,384: 13.3 per 100,000 population). Multivariable regression analyses revealed a close association between maternal irradiation and the development of neuroblastoma (adjusted incident rate ratio: 10.68 [95% confidence interval: 2.98‒38.27]). CONCLUSIONS: The present study demonstrated, for the first time, a potential association between maternal occupational exposure and the occurrence of neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results. IMPACT: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study examined the association between such occupational exposure and offspring's cancers that developed until the age of 1 year. Maternal exposure to ionizing radiation was associated with infantile neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results.

Differences in phosphatidylcholine profiles and identification of characteristic phosphatidylcholine molecules in meat animal species and meat cut locations.

Phosphatidylcholine (PC) is an essential component of the plasma membrane. Its profile varies with species and tissues. However, the PC profiles in meat have not been explored in depth. This study aimed to investigate the differences in PC profiles between various meat animal species and meat cut sites, along with the identification of characteristic PC molecules. The results demonstrated that the PC profiles of chicken meat differed from those of other species. Significant differences were also observed between the PC profiles of pork meat and the meat obtained from other species. The amount of PCs containing ether bonds was high in pork meat. PCs containing an odd number of carbon atoms were characteristic of beef and lamb meats. Furthermore, PC profiles differed based on the muscle location in chicken and pork. These results suggest that the PC profiles of skeletal muscles are indicators of animal species and muscle location.

[A case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis].

Pembrolizumab is an immunoglobulin G4 isotype antibody that targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used in the treatment of advanced non-small cell lung cancer (NSCLC). The safety and efficacy of immunotherapy for autoimmune disease are currently unknown;immune-related adverse events induced by immune checkpoint inhibitors (ICIs) have been reported. We report a case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis. A 72-year-old man with a 3-year history of ulcerative colitis maintained clinical remission with mesalazine. The recurrence of lung adenocarcinoma was diagnosed and treated with pembrolizumab as second-line treatment. Diarrhea and bloody stool recurred 5 months after the first administration of pembrolizumab. The colitis did not respond to corticosteroids and infliximab. Because of the recurrence of ulcerative colitis, treatment of the lung adenocarcinoma was discontinued, and the patient died 1 year after the first administration of pembrolizumab. Few cases of severe colitis induced by the administration of pembrolizumab in patients with ulcerative colitis have been reported. This case suggests that the clinical stratification of autoimmune disease and typical standards of effectiveness of treatment are needed for patients with autoimmune disease who are treated with ICIs.

Titania Nanofilms from Titanium Complex-Containing Polymer Langmuir-Blodgett Films.

This paper proposes a method of fabricating low-dimensional TiO2 nanofilms at room temperature under ambient pressure conditions. The titanium-containing polymer complex Ti-p(DDA/acac) was synthesized by reacting an amphiphilic copolymer (p(DDA/acac)) with a titanium complex. Its ultrathin films were prepared using the Langmuir-Blodgett (LB) technique. The monolayer was found to be free from hydrolysis and cross-linking side reactions, even at the air-water interface. The transferred LB films (nanosheets) were oxidized by ultraviolet irradiation at room temperature. The photo-oxidized material has an amorphous and porous structure with subnanometer-scale controllability (0.18 nm per layer). Photocatalytic performance was demonstrated by converting multilayered LB films of Ti-(DDA/acac) and the silicon-containing polymer p(DDA/SQ) into ultrathin hetero-multilayers of TiO2 and SiO2 under UV-O3 treatment. The scalability affords a uniform photopattern formation of photo-oxidized TiO2 films over several hundreds of micrometers.

Biomimetic Polyelectrolytes Based on Polymer Nanosheet Films and Their Proton Conduction Mechanism.

We report a biomimetic polyelectrolyte based on amphiphilic polymer nanosheet multilayer films. Copolymers of poly( N-dodecylacrylamide- co-vinylphosphonic acid) [p(DDA/VPA)] form a uniform monolayer at the air-water interface. By depositing such monolayers onto solid substrates using the Langmuir-Blodgett (LB) method, multilayer lamellae films with a structure similar to a bilayer membrane were fabricated. The proton conductivity at the hydrophilic interlayer of the lamellar multilayer films was studied by impedance spectroscopy under temperature- and humidity-controlled conditions. At 60 °C and 98% relative humidity (RH), the conductivity increased with increasing mole fraction of VPA ( n) up to 3.2 × 10-2 S cm-1 for n = 0.41. For a film with n = 0.45, the conductivity decreased to 2.2 × 10-2 S cm-1 despite the increase of proton sources. The reason for this decrease was evaluated by studying the effect of the distance between the VPAs ( lVPA) on the proton conductivity as well as their activation energy. We propose that for n = 0.41, lVPA is the optimal distance not only to form an efficient two-dimensional (2D) hydrogen bonding network but also to reorient water and VPA. For n = 0.45, on the other hand, the lVPA was too close for a reorientation. Therefore, we concluded that there should be an optimal distance to obtain high proton conductivity at the hydrophilic interlayer of such multilayer films.

Cellulose Nanofiber Nanosheet Multilayers by the Langmuir-Blodgett Technique.

We describe a systematic approach for producing cellulose nanofiber (CNF) nanosheets using the Langmuir-Blodgett (LB) technique. The CNFs were obtained from sulfuric acid hydrolysis of commercially available microfibrillated cellulose. Needle-like CNFs, negatively charged by grafted sulfate groups, were maintained at the air-water interface, assisted by amphiphilic polymer, poly( N-dodecyl acrylamide) (pDDA). The CNFs produced a stable monolayer. The surface pressure increased steadily with a high collapse pressure of 50 mN m-1 when spread with formic acid and pDDA. The composite monolayers were transferred onto solid substrates as Y-type LB films using a vertical dipping method. Upstroke and downstroke transfer ratios of the films were, respectively, unity and 0.88, indicating that full coverage was achieved by the monolayer even for more than 200 layers. Results obtained using atomic force microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy showed that CNF nanosheets possess well-defined layer structures with average monolayer thickness of 5.3 nm. The relative amount of CNFs in the nanosheets was calculated as 62.6 wt % using the quartz crystal microbalance technique. The as-prepared nanosheets are optically transparent to visible light and have high hydrophobicity. In fact, the nanosheet transparency was higher than 88% at 600 nm wavelength for 24 layers. A miniscule amount of pDDA enables demonstration of free-standing CNF nanosheets with 1 cm width and 45.6 nm thickness (23 layers).

Dibenzoarsepins: Planarization of 8π-Electron System in the Lowest Singlet Excited State.

Dibenzo[b,f]arsepins possessing severely distorted cores compared to those of other heteropins were synthesized. These derivatives exhibited dual photoluminescence in the green-to-red region (500-700 nm) and the near-ultraviolet region (<380 nm), which could be attributed to the planarization of the arsepin core in the lowest singlet excited (S1 ) state. The computational approach for the assessment of the aromatic indices revealed that the dibenzoarsepins studied show aromaticity (8π system) in the S1 states in line with Baird's rule. The lone pair electrons of the arsenic atoms play a crucial role in the aromaticity in the S1 states.

High-Density and Monolayer-Level Integration of π-Conjugated Units: Amphiphilic Carbazole Homopolymer Langmuir-Blodgett Films.

Precise integration of π-conjugated units is a key issue to achieve molecular (nano) electronic devices based on organic semiconductor materials. We specifically examine the Langmuir-Blodgett technique, which allows high-density integration of π-conjugated units. In this study, we designed a carbazole containing acrylamide-based homopolymer [poly(9-ethyl-3-carbazolyl acrylamide) (pCzAA)], in which the π-conjugated unit is connected with a hydrophilic amide unit directly as a side chain. Its Langmuir-Blodgett film formation properties were investigated. The pCzAA polymer took a stable monolayer formation in the presence of a small amount (ca. 10 mol %) of poly( N-dodecylacrylamide) (pDDA). Compared with amphiphilic carbazole-containing copolymers described in earlier reports, the direct connection of π-conjugated units through amide bonding enables the Cz content in monolayers to exceed that of the copolymer monolayers (ca. 30 mol %) dramatically. pCzAA:pDDA takes highly ordered layer structures toward the out-of-plane direction, although no structural order is formed in the in-plane direction. This method is a practical means to develop low-dimensional and high-density integration of π-conjugated units for molecular electronics.