[Current state of genetic analysis in multiple myeloma and future perspectives].

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. Recent advances in next-generation sequencing technologies have facilitated in-depth genetic exploration of MM, unveiling a more comprehensive genomic landscape that extends beyond classical chromosomal alterations, such as IGH translocations and hyperdiploidy. These studies have elucidated recurrent mutations across various functional pathways including those involving MAPK, NF-κB, cell cycle regulation, and epigenetic modulation. With respect to clinical utility, studies have shown that the number of genetic alterations and biallelic events in TP53 are associated with worse prognosis, and CRBN mutations with resistance to immunomodulatory drugs. We recently analyzed the full landscape of genetic alterations in relapsed and refractory MM using circulating tumor DNA (ctDNA), revealing TP53 mutations as the most frequent driver mutation. Notably, more than half of TP53 mutations were present in only ctDNA, suggesting a subclonal origin. Mutations in six genes, including KRAS and TP53, were associated with poor progression-free survival. In addition, the number of ctDNA mutations was identified as a prognostic factor independent of IGH translocations and clinical factors. Here we summarize recent progress in genetic analysis of MM, focusing on clinical relevance.

[Synthesis of Modified Nucleosides Using 4'-Carbon Radicals].

Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving ß-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.

W18O49 Nanofibers Functionalized with Graphene as a Selective Sensing of NO2 Gas at Room Temperature.

Recent trends in two-dimensional (2D) graphene have demonstrated significant potential for gas-sensing applications with significantly enhanced sensitivity even at room temperature. Herein, this study presents fabrication of distinctive gas sensor based on one-dimensional (1D) W18O49 nanofibers decorated 2D graphene, specifically coated on copper (Cu)-based interdigitated electrodes formed by DC sputtering, which can selectively detect NO2 gas at room temperature. The sensor device fabricated using W18O49/Gr1.5% (i.e., W18O49 nanofibers hybrid nanocomposite with 1.5 wt % graphene) displays excellent overall sensing performance at 27 °C (room temperature) with high response (∼150-160 times) to NO2 gas. The W18O49/Gr1.5%-based sensor device reflects the highly selective detection toward NO2 gas among various gases with quick response time of 3 s and speedy recovery in 6 s. The limit of detection of ∼0.3 ppm with excellent reproducibility and stability for 3 months in all weather conditions (tested in humidity conditions 20-97%) are superior features of the device under test. However, W18O49/Gr3% displayed higher selectivity for NO2 but resulted with comparatively reduced sensitivity than W18O49/Gr1.5% sensor. The enhanced sensing performance could be attributed to the graphene content to decorate the nanofibers on it, oxygen vacancies/defects, and the contacts between the sensing material and Cu. This favorable synthesis and properties of self-assembled hybrid composite materials provide a potential utilization for detecting NO2 gas in environmental safety inspection.

Aromatic 2,2-Diphenylethylamine Ligand Exchange of FA0.9Cs0.1PbBr3 Perovskite Nanocrystals for High-Efficiency Pure Green Light-Emitting Diodes.

Perovskite nanocrystals (NCs) with long alkyl ligands cannot easily form high-quality composite films owing to their poor dispersibility in π-conjugated small molecules and polymer host materials. In this study, we demonstrated that the aromatic ligand exchange of mixed-cation FA0.9Cs0.1PbBr3 NCs using 2,2-diphenylethylamine (DPEA) can not only enable the fabrication of high-efficiency light-emitting diodes (LEDs) but also allows dispersibility in host materials. The DPEA-NC film exhibited a pure green wavelength of 530 nm and a full width at half-maximum of 20.9 nm with a photoluminescence quantum yield of 90.9%. A DPEA-NC LED achieved a luminance of 39,700 cd/m2 and an external quantum efficiency of 18.6% even in a thick NC film. Interestingly, the DPEA-NCs formed a composite film with small-molecule tris(4-carbazoyl-9-ylphenyl)amine. The operational stability of this composite LED was eight times higher than that of the DPEA-NC LED owing to enhanced hole-electron charge balance and the suppression of perovskite NC degradation. Therefore, the aromatic DPEA ligand exchange of perovskite NCs is an effective way to improve their electrical properties and operational device stabilities.

Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma.

Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. In this study, we performed a comprehensive genetic analysis of 178 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNA), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely, HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1. Among them, CD274 (24%) was the most frequently altered, followed by TP53 (20%), CDKN2A (19%), ARID1A (15%), HLA-A (15%), BCOR (14%), and MSN (14%). Chromosome X losses were the most common arm-level CNAs in females (∼40%), and alterations of four X-linked driver genes (MSN, BCOR, DDX3X, and KDM6A) were more frequent in males and females harboring chromosome X losses. Among X-linked drivers, MSN was the most recurrently altered, and its expression was lost in approximately one-third of cases using immunohistochemical analysis. Functional studies of human cell lines showed that MSN disruption promoted cell proliferation and NF-κB activation. Moreover, MSN inactivation increased sensitivity to NF-κB inhibition in vitro and in vivo. In addition, recurrent deletions were observed at the origin of replication in the EBV genome (6%). Finally, by integrating the 34 drivers and 19 significant arm-level CNAs, nonnegative matrix factorization and consensus clustering identified two molecular groups with different genetic features and prognoses irrespective of clinical prognostic factors. Together, these findings could help improve diagnostic and therapeutic strategies in ENKTCL. Significance: Integrative genetic analyses and functional studies in extranodal NK/T-cell lymphoma identify frequent disruptions of X-linked drivers, reveal prognostic molecular subgroups, and uncover recurrent MSN alterations that confer sensitivity to NF-κB inhibition.

Two Cases of a Portal Annular Pancreas in Patients Undergoing Pancreaticoduodenectomy.

Introduction: Portal annular pancreas (PAP) is a congenital anomaly resulting from aberrant fusion of the ventral and dorsal pancreatic buds around the portal vein (PV). PAP was classified into three types by Joseph et al., based on the location of the main pancreatic duct around the PV. The presence of PAP is important for the surgical procedure because it is associated with the postoperative pancreatic fistula. There are no standardized surgical procedures of resection and reconstruction for PAP. Case Presentation: We report 2 cases of subtotal stomach-preserving pancreatoduodenectomy in patients with PAP. One case of PAP was discovered coincidentally intraoperatively, and the other case was diagnosed before surgery. The first case was an 84-year-old male patient who underwent surgery for distal bile duct cancer. PAP was noticed intraoperatively when the uncinate process of the pancreas was detached from behind the PV. The second case was an 84-year-old female patient who also underwent surgery for distal bile duct cancer. We recognized PAP from preoperative computed tomography images. In both cases, the ductal anatomy was consistent with type IIIA PAP, and the dorsal pancreas was resected using a stapling device. During the postoperative period, there was no clinically relevant postoperative pancreatic fistula. Conclusion: PAP is rarely encountered intraoperatively; however, it is important to recognize it before surgery and take it into consideration when deciding upon the procedures for resection and reconstruction.

Synthesis of fluorescent 5-heteroarylpyrimidine-containing oligonucleotides via post-synthetic trifluoromethyl conversion.

Post-synthetic conversion of the trifluoromethyl group to a heteroaryl group at the C5 position of the pyrimidine base in DNA oligonucleotides was achieved. Specifically, the oligonucleotides containing 5-trifluoromethylpyrimidine bases were treated with o-phenylenediamines and o-aminothiophenols as nucleophiles to afford the corresponding 5-(benzimidazol-2-yl)- and 5-(benzothiazol-2-yl)-pyrimidine-modified bases. Furthermore, evaluation of the fluorescence properties of the obtained oligonucleotides revealed that among them the oligonucleotide containing 5-(5-methylbenzimidazol-2-yl)cytosine exhibited the highest fluorescence intensity. These results indicated that post-synthetic trifluoromethyl conversion, which is practical and operationally simple, is a powerful tool for exploring functional oligonucleotides.

ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone.

ABSTRACT: It remains elusive how driver mutations, including those detected in circulating tumor DNA (ctDNA), affect prognosis in relapsed/refractory multiple myeloma (RRMM). Here, we performed targeted-capture sequencing using bone marrow plasma cells (BMPCs) and ctDNA of 261 RRMM cases uniformly treated with ixazomib, lenalidomide, and dexamethasone in a multicenter, prospective, observational study. We detected 24 and 47 recurrently mutated genes in BMPC and ctDNA, respectively. In addition to clonal hematopoiesis-associated mutations, varying proportion of driver mutations, particularly TP53 mutations (59.2% of mutated cases), were present in only ctDNA, suggesting their subclonal origin. In univariable analyses, ctDNA mutations of KRAS, TP53, DIS3, BRAF, NRAS, and ATM were associated with worse progression-free survival (PFS). BMPC mutations of TP53 and KRAS were associated with inferior PFS, whereas KRAS mutations were prognostically relevant only when detected in both BMPC and ctDNA. A total number of ctDNA mutations in the 6 relevant genes was a strong prognostic predictor (2-year PFS rates: 57.3%, 22.7%, and 0% for 0, 1, and ≥2 mutations, respectively) and independent of clinical factors and plasma DNA concentration. Using the number of ctDNA mutations, plasma DNA concentration, and clinical factors, we developed a prognostic index, classifying patients into 3 categories with 2-year PFS rates of 57.9%, 28.6%, and 0%. Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM. This study is a part of the C16042 study, which is registered at www.clinicaltrials.gov as #NCT03433001.

Mogrol stimulates G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and insulin secretion from pancreatic ß-cells and alleviates hyperglycemia in mice.

Target identification is a crucial step in elucidating the mechanisms by which functional food components exert their functions. Here, we identified the G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) as a target of the triterpenoid mogrol, a class of aglycone mogroside derivative from Siraitia grosvenorii. Mogrol, but not mogrosides, activated cAMP-response element-mediated transcription in a TGR5-dependent manner. Additionally, mogrol selectively activated TGR5 but not the other bile acid-responsive receptors (i.e., farnesoid X receptor, vitamin D receptor, or muscarinic acetylcholine receptor M3). Several amino acids in TGR5 (L71A2.60, W75AECL1, Q77AECL1, R80AECL1, Y89A3.29, F161AECL2, L166A5.39, Y240A6.51, S247A6.58, Y251A6.62, L262A7.35, and L266A7.39) were found to be important for mogrol-induced activation. Mogrol activated insulin secretion under low-glucose conditions in INS-1 pancreatic ß-cells, which can be inhibited by a TGR5 inhibitor. Similar effects of mogrol on insulin secretion were observed in the isolated mouse islets. Mogrol administration partially but significantly alleviated hyperglycemia in KKAy diabetic mice by increasing the insulin levels without affecting the ß-cell mass or pancreatic insulin content. These results suggest that mogrol stimulates insulin secretion and alleviates hyperglycemia by acting as a TGR5 agonist.

Pan-Cancer Comparative and Integrative Analyses of Driver Alterations Using Japanese and International Genomic Databases.

Using 48,627 samples from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), we present a pan-cancer landscape of driver alterations and their clinical actionability in Japanese patients. Comparison with White patients in Genomics Evidence Neoplasia Information Exchange (GENIE) demonstrates high TP53 mutation frequencies in Asian patients across multiple cancer types. Integration of C-CAT, GENIE, and The Cancer Genome Atlas data reveals many cooccurring and mutually exclusive relationships between driver mutations. At pathway level, mutations in epigenetic regulators frequently cooccur with PI3K pathway molecules. Furthermore, we found significant cooccurring mutations within the epigenetic pathway. Accumulation of mutations in epigenetic regulators causes increased proliferation-related transcriptomic signatures. Loss-of-function of many epigenetic drivers inhibits cell proliferation in their wild-type cell lines, but this effect is attenuated in those harboring mutations of not only the same but also different epigenetic drivers. Our analyses dissect various genetic properties and provide valuable resources for precision medicine in cancer. SIGNIFICANCE: We present a genetic landscape of 26 principal cancer types/subtypes, including Asian-prevalent ones, in Japanese patients. Multicohort data integration unveils numerous cooccurring and exclusive relationships between driver mutations, identifying cooccurrence of multiple mutations in epigenetic regulators, which coordinately cause transcriptional and phenotypic changes. These findings provide insights into epigenetic regulator-driven oncogenesis. This article is featured in Selected Articles from This Issue, p. 695.

Anti-HTLV-1 immunity combined with proviral load as predictive biomarkers for adult T-cell leukemia-lymphoma.

Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.

The Clock-Drawing Test as a Useful Screening Assessment of Preoperative Cognitive Impairment with Readmission After Transcatheter Aortic Valve Implantation.

Background: Transcatheter aortic valve implantation (TAVI) has recently become more common as a treatment for severe, symptomatic aortic stenosis (AS). Cognitive impairment (CI) is strongly associated with the prognosis of TAVI patients. However, some cognitive assessments currently in use are difficult to perform routinely in the clinical setting. To easier CI evaluation, we investigated whether CI using the clock-drawing test (CDT), one part of the Mini-Cog, affects the postoperative prognosis of TAVI patients with AS. Methods: The present study enrolled 52 patients (median age, 85 years; 28.8% male) who underwent TAVI and were discharged between 2019 and 2021. The outcome was readmission for all causes within one year of discharge and patients were grouped according to whether they were readmitted or not. Cognitive function was assessed using the Mini-Cog which combines verbal playback and CDT. Results: Of the 52, 11 patients (21.2%) comprised readmission group, including 4 (36.4%) each for fracture and infection, and 1 (9.1%) each for heart failure, subdural hematoma, and pneumothorax. Median Mini-Cog score was lower in the readmission group than in the non-readmission group (4 vs. 5; P < 0.05). The frequency of Mini-Cog score < 3 (indicative of CI) and CDT failure were significantly higher in the readmission group than in the non-readmission group, respectively (46% vs. 7%, P < 0.01) (46% vs. 12%, P < 0.05). Both of Mini-Cog score < 3 and CDT failure were independently associated with readmission. The areas under the curve showed CDT was an indicator of readmission with similar accuracy to the Mini-Cog score < 3. Kaplan-Meier curves showed significant differences in readmission after 1 year between the 2 Mini-Cog groups with scores of < 3 or ≥ 3 points and CDT failure and success. Conclusion: The CDT may be a very easy and simple screening assessment of preoperative CI with readmission within one year after TAVI.

Inter- and intra-tumor heterogeneity of genetic and immune profiles in inherited renal cell carcinoma.

Patients with von Hippel-Lindau disease (vHL) are at risk of developing spatially and temporally multiple clear cell renal cell carcinomas (ccRCCs), which offers a valuable opportunity to analyze inter- and intra-tumor heterogeneity of genetic and immune profiles within the same patient. Here, we perform whole-exome and RNA sequencing, digital gene expression, and immunohistochemical analyses for 81 samples from 51 ccRCCs of 10 patients with vHL. Inherited ccRCCs are clonally independent and have less genomic alterations than sporadic ccRCCs. Hierarchical clustering of transcriptome profiles shows two clusters with distinct immune signatures: immune hot and cold clusters. Interestingly, not only samples from the same tumors but also different tumors from the same patients tend to show a similar immune signature, whereas samples from different patients frequently exhibit different signatures. Our findings reveal the genetic and immune landscape of inherited ccRCCs, demonstrating the relevance of host factors in shaping anti-tumor immunity.

Chemical Conversion of 5-Fluoromethyl- and 5-Difluoromethyl-Uracil Bases in Oligonucleotides Using Postsynthetic Modification Strategy.

This article describes the postsynthetic modification of oligonucleotides (ONs) containing 2'-deoxy-5-fluoromethyluridine (dUCH2F ) and 2'-deoxy-5-difluoromethyluridine (dUCHF2 ). Reactions of fully protected and controlled pore glass (CPG)-attached ONs containing dUCH2F and dUCHF2 in basic solutions result in deprotection of all protecting groups except for the 4,4'-dimethoxytrityl group, cleavage from CPG, and conversion of the fluoromethyl or difluoromethyl groups to afford the corresponding ONs containing 5-substituted 2'-deoxyuridines. Moreover, the difluoromethyl group can be converted to formyl, oxime, or hydrazone via the postsynthetic conversion of protection- and CPG-free ON containing dUCHF2 . © 2023 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of fully protected and CPG-attached oligonucleotides containing 2'-deoxy-5-fluoromethyluridine and 2'-deoxy-5-difluoromethyluridine Basic Protocol 2: Postsynthetic modification of fully protected and CPG-attached oligonucleotides containing 2'-deoxy-5-fluoromethyluridine Basic Protocol 3: Postsynthetic modification of fully protected and CPG-attached oligonucleotide containing 2'-deoxy-5-difluoromethyluridine Basic Protocol 4: Postsynthetic modification of protection- and CPG-free oligonucleotide containing 2'-deoxy-5-difluoromethyluridine Support Protocol: Synthesis of 2'-deoxy-5-fluoromethyluridine and 2'-deoxy-5-difluoromethyluridine phosphoramidites.

Synthesis of purine derivatives of Me-TaNA and properties of Me-TaNA-modified oligonucleotides.

We previously reported that pyrimidine derivatives of methylated 2'-O,4'-C-methyleneoxy-bridged nucleic acid (Me-TaNA), a unique consecutive three-acetal-containing nucleic acid, are promising building blocks for chemically modified oligonucleotides. Herein, purine derivatives of Me-TaNA (Me-TaNA-A and -G) were synthesized and introduced into oligonucleotides. During the synthesis, we found stereoselective introduction of a substituent on the 4' carbons by using 2',3'-carbonate compounds as substrates. When forming duplexes with single-stranded RNA, the modified oligonucleotides, including purine derivatives of Me-TaNA, showed higher duplex stability than the natural oligonucleotide. This study enabled the use of Me-TaNA for the chemical modification of various oligonucleotide sequences because synthesis of Me-TaNAs with all four nucleobases was achieved.

Sustained Lumen Area by Paclitaxel-Coated Balloon Following Rotational Atherectomy for Napkin-Ring Left Main Trunk Ostial Lesion.

Late lumen enlargement after percutaneous coronary intervention (PCI) with drug-coated balloon has contributed to good clinical results. However, late lumen enlargement with drug-coated balloon following rotational atherectomy has not been well reported. This report describes a case of calcified napkin-ring ostial lesion at the left main trunk that showed a sustained lumen area after PCI with drug-coated balloon following rotational atherectomy. An 85-year-old female patient was admitted to the hospital with dyspnea. Echocardiography showed hypokinesis in the anteroseptal and inferior walls. Electrocardiograph-gated cardiac computed tomography showed a calcified ostial lesion in the left main trunk. Invasive angiography of the coronary artery showed severe stenosis in the left main trunk ostium. Percutaneous coronary intervention was performed with a drug-coated balloon after rotational atherectomy. The minimal lumen area measured by intravascular ultrasound grew mildly from 4.09 to 4.17 mm2 immediately after PCI. Follow-up angiography and intravascular ultrasound performed after 6 months showed that the minimal lumen area in the left main trunk ostium was further enlarged from 4.17 to 4.69 mm2. The presence of sustained lumen area after PCI with drug-coated balloon following rotational atherectomy for a napkin-ring left main trunk ostial lesion was confirmed. This case demonstrates sustained lumen area after drug-coated balloon following rotational atherectomy in the left main trunk ostium, improving the patient's chest symptom. Hence, drug-coated balloon after rotational atherectomy may be an option for complex stent sites, such as the left main trunk ostium in geriatric patients and sites with highly calcified lesions.

Expansion of Phosphoramidite Chemistry in Solid-Phase Oligonucleotide Synthesis: Rapid 3'-Dephosphorylation and Strand Cleavage.

In solid-phase oligonucleotide synthesis, a solid support modified with a universal linker is frequently used to prepare oligonucleotides bearing non-natural- or non-nucleosides at the 3'-end. Generally, harsh basic conditions such as hot aqueous ammonia or methylamine are required to release oligonucleotides by 3'-dephosphorylation via the formation of cyclic phosphate with the universal linker. To achieve 3'-dephosphorylation under milder conditions, we used O-alkyl phosphoramidites instead of the commonly used O-cyanoethyl phosphoramidites at the 3'-end of oligonucleotides. Alkylated phosphotriesters are more alkali-tolerant than their cyanoethyl counterparts because the latter generates phosphodiesters via E2 elimination under basic conditions. Among the designed phosphoramidites, alkyl-extended analogs exhibited rapid and efficient 3'-dephosphorylation compared to conventional cyanoethyl and methyl analogs under mild basic conditions such as aqueous ammonia at room temperature for 2 h. Moreover, nucleoside phosphoramidites bearing 1,2-diols were synthesized and incorporated into oligonucleotides. 1,2,3,4-Tetrahydro-1,4-epoxynaphthalene-2,3-diol-bearing phosphoramidite behaved like a universal linker at the 3'-terminus, allowing dephosphorylation and strand cleavage of the oligonucleotide chain to occur efficiently. Our strategy using this new phosphoramidite chemistry is promising for the tandem solid-phase synthesis of diverse oligonucleotides.

Influence of Strong Ionic Interaction on the Kinetics of Graphite Intercalation Compound Formation.

Graphite intercalation compounds (GICs) of anions have attracted much attention as a positive electrode for use in dual-ion batteries. In this study, GICs of bis(trifluoromethanesulfonyl)amide (TFSA) anions were electrochemically synthesized in ionic liquids with lithium or magnesium salts to investigate the kinetics of GICs formation. By varying the concentrations of LiTFSA or Mg(TFSA)2 , the activation energy of interfacial anion transfer resistance was discovered to be correlated with the viscosity of the ionic liquid electrolytes. Such a change in activation energy is unique to ionic liquids and not seen in common molecular solvent electrolytes. In addition, ionic liquids with nearly identical viscosities exhibited similar resistances and activation energies. The relationship between the viscosity of ionic liquids and the kinetic parameters of interfacial anion transfer found in this study provides important insights for the construction of dual-ion batteries that aim for both high capacity and high rate capability.

Association between low body temperature on admission and in-hospital mortality according to body mass index categories of patients with sepsis.

Hypothermia has been shown to be associated with a high mortality rate among patients with sepsis. However, the relationship between hypothermia and body mass index (BMI) with respect to mortality remains to be elucidated. We conducted this study to assess the association between hypothermia and survival outcomes of patients with sepsis according to BMI categories. This secondary analysis of a prospective cohort study enrolled 1184 patients (aged ≥ 16 years) with sepsis hospitalized in 59 intensive care units in Japan. Patients were divided into 3 BMI categories (<18.5 [low], 18.5-24.9 [normal], >24.9 [high] kg/m2) and 2 body temperature (36 °C and ≥ 36 °C) groups. The primary outcome was in-hospital mortality rate. Associations between hypothermia and BMI categories with respect to in-hospital mortality were evaluated using multivariate logistic regression analysis. Of the 1089 patients, 223, 612, and 254 had low, normal, and high BMI values, respectively. Patients with body temperature < 36 °C (hypothermia) had a higher in-hospital mortality rate than that had by those without hypothermia in the normal BMI group (25/63, 39.7% vs. 107/549, 19.5%); however, this was not true for patients in the low or high BMI groups. A significant interaction was observed between hypothermia and normal BMI for in-hospital mortality (odds ratio, 1.56; 95% confidence interval, 1.00-3.41; P value for interaction = .04); however, such an interaction was not found between hypothermia and low or high BMIs. Patients with sepsis and hypothermia in the normal BMI subgroup may have a higher mortality risk than that of those in the low or high BMI subgroups and, therefore, require more attention.