Design and synthesis of proton-dopable organic semiconductors

This paper shows how protonated 3,4-ethylene dioxythiophene moieties can be used as an end group to make organic conductors. An organic semiconductor 2,5-bis(5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene is designed and synthesized. This molecule could be doped by protonic acid in both solution and solid-state, resulting in a broad absorption in the near-infrared range corresponding to polaron and bipolaron absorption. Electrical conductivity of ca. 0.1 S cm⁻¹ was obtained at 100 °C (to avoid the water uptake by the acid). The adducts with protons bound at the end-thiophene α-position were confirmed by ¹H Nuclear Magnetic Resonance spectra.

The use of protonated 3,4-ethylenedioxythiophene moieties as an end group could be a promising approach to prepare organic conductors.     

Paraneoplastic Opsoclonus-myoclonus Syndrome with Anti-Hu and Anti-SOX-1 Antibodies after Immune-checkpoint Inhibitor Treatment Combined with Chemotherapy in a Patient with Small-cell Lung Cancer

A 69-year-old man with advanced small-cell lung cancer achieved partial remission after 3 courses of immunochemotherapy that included atezolizumab. Ten days after the last treatment, he developed paraneoplastic opsoclonus-myoclonus syndrome and required mechanical ventilation. Serology testing detected anti-Hu and anti-SOX-1 antibodies. Despite steroid pulse therapy, various anticonvulsants, continuous intravenous sedation, and a fourth course of chemotherapy without atezolizumab, his condition failed to improve. Paraneoplastic opsoclonus-myoclonus syndrome with autoantibodies after immune-checkpoint inhibitor treatment has not been reported previously. Although a causal relationship between immune-checkpoint inhibitors and paraneoplastic syndromes has been suggested, the mechanism remains unknown.     

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor

Background:There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.Materials and methods:A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.Results:Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.Conclusions:Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.     

Unravelling the one-pot conversion of biomass-derived furfural and levulinic acid to 1,4-pentanediol catalysed by supported RANEY® Ni–Sn alloy catalysts

Bimetallic Ni–Sn alloys have been recognised as promising catalysts for the transformation of furanic compounds and their derivatives into valuable chemicals. Herein, we report the utilisation of a supported bimetallic RANEY® nickel–tin alloy supported on aluminium hydroxide (RNi–Sn(x)/AlOH; x is Ni/Sn molar ratio) catalysts for the one-pot conversion of biomass-derived furfural and levulinic acid to 1,4-pentanediol (1,4-PeD). The as prepared RNi–Sn(1.4)/AlOH catalyst exhibited the highest yield of 1,4-PeD (78%). The reduction of RNi–Sn(x)/AlOH with H₂ at 673–873 K for 1.5 h resulted in the formation of Ni–Sn alloy phases (e.g., Ni₃Sn and Ni₃Sn₂) and caused the transformation of aluminium hydroxide (AlOH) to amorphous alumina (AA). The RNi–Sn(1.4)/AA 673 K/H₂ catalyst contained a Ni₃Sn₂ alloy as the major phase, which exhibited the best yield of 1,4-PeD from furfural (87%) at 433 K, H₂ 3.0 MPa for 12 h and from levulinic acid (up to 90%) at 503 K, H₂ 4.0 MPa, for 12 h. Supported RANEY® Ni–Sn(1.5)/AC and three types of supported Ni–Sn(1.5) alloy (e.g., Ni–Sn(1.5)/AC, Ni–Sn(1.5)/c-AlOH, and Ni–Sn(1.5)/γ-Al₂O₃) catalysts afforded high yields of 1,4-PeD (65–87%) both from furfural and levulinic acid under the optimised reaction conditions.

The RANEY® Ni–Sn(x) alloy catalysed the one-pot conversion of biomass-derived furfural and levulinic acid to allow remarkable yield of 1,4-pentanediol (up to 90%) under the mild reaction conditions.     

Coordination-based vapochromic behavior of a luminescent Pt(ii) complex with potassium ions

Vapochromic Pt(ii) complexes that exhibit color and luminescence changes induced by the presence of vapor molecules have drawn considerable attention because of their potential use as vapor sensors. Generally, the vapochromic responsiveness of Pt(ii)-based complexes is difficult to envisage, because a typical molecular design facilitates the stabilization of a vapor-adsorbed form through weak intermolecular interactions. Herein, we investigate the vapochromic behavior of a Pt(ii) complex with potassium ions, which act as vapor coordination sites, by strongly stabilizing the vapor-adsorbed form. Upon exposure to N,N-dimethylacetamide and N,N-dimethylformamide vapors, the complex exhibits crystal structural transformation with luminescence spectral changes. Crystal structural analysis indicates that the vapor molecules are coordinated to the potassium ions after vapor exposure. This study suggests the possibility of inducing Pt(ii)-based vapochromic responsiveness through establishing potassium-ion-based vapor coordination sites.

A luminescent Pt(ii) complex with potassium ions was successfully synthesized and its coordination-based vapochromic behavior was investigated.     

Human breast milk exosomes attenuate intestinal damage

Pediatric Surgery International - Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given...     

Potential role of the PD-L1 expression and tumor-infiltrating lymphocytes on neuroblastoma

Pediatric Surgery International - The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway has garnered much attention for its roles in clinical oncology. The aim of this study was...     

Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single‐arm study

Cryoprobe is a novel transbronchial biopsy (TBB) tool that yields larger tissue samples than forceps. Pathological diagnosis and biomarker analysis, such as genetic alterations and programmed death‐ligand 1 (PD‐L1) expression, are paramount for precision medicine against lung cancer. We evaluated the safety and usefulness of cryoprobe TBB for lung cancer diagnosis and biomarker analysis. In this single‐center, prospective single‐arm study, patients suspected of having or diagnosed with primary lung cancer underwent cryoprobe TBB using flexible bronchoscopy after conventional forceps TBB from the same lesion. Cryoprobe TBB was performed in 121 patients. The incidence rate of severe bleeding and serious adverse events (4% [90% confidence interval: 2%‐9%]) was significantly lower than the expected rate (20% with 30% threshold, P < 0.01). Combining both central and peripheral lesions, the diagnostic yield rate of cryoprobe samples was 76% and that of forceps samples was 84%. Compared with forceps TBB samples, cryoprobe TBB samples were larger (cryoprobe 15 mm² vs forceps 2 mm²) and resulted in a larger proportion of definite histomorphological diagnosis (cryoprobe 86% vs forceps 74%, P < 0.01), larger amounts of DNA extracted from samples (median: cryoprobe, 1.60 µg vs forceps, 0.58 µg, P = 0.02) and RNA (median: cryoprobe, 0.62 µg vs forceps, 0.17 µg, P < 0.01) extracted from samples, and tended to yield greater rates of PD‐L1 expression >1% (51% vs 42%). In conclusion, cryoprobe is a safe and useful tool for obtaining lung cancer tissue samples of adequate size and quality, which allow morphological diagnosis and biomarker analysis for precision medicine against lung cancer.     

Spatial and temporal expansion of intrahepatic metastasis by molecularly‐defined clonality in multiple liver cancers

Multiple hepatocellular carcinoma (HCC) is divided into two categories: intrahepatic metastasis (IM), which is a true relapse of HCC, and multicentric origin (MO), which is a second primary tumor. Clinical diagnosis of multiple HCC is usually made based on tumor location and/or time to recurrence; however, it is often difficult to distinguish the two types of multiple HCC. Using 41 matched pairs of multiple HCC specimens, we confirmed the accuracy of clinical diagnoses using exome sequence data and investigated the importance of discriminating the type of multiple HCC. Genomic analysis revealed that 18 (43.9%) patients diagnosed as having genomic IM had common mutations in a pair of HCC tumors with the main tumor of these patients being more progressive compared to those with genomic MO. The accuracy of clinical diagnosis based on lobe (Definition 1) and segment (Definition 2) were 68.3% and 78.0%, respectively. Intriguingly, recurrence ≥2 years after initial surgery for 3 patients was IM. The survival of patients with clinical IM was significantly shorter than for those with clinical MO based on both Definition 1 (P = 0.045) and Definition 2 (P = 0.043). However, mean survival was not different between the patients with genomic IM and those with MO (P = 0.364). Taken together, genomic analysis elucidated that liver cancer may spread more extensively and more slowly than previously thought. In addition, distinguishing multiple HCC as IM or MC may have provided biological information but was not of clinical importance with respect to patient prognosis.