The Effect of Nutrients on Subjective Accomplishment at Work: Results from a Health Survey and a Single-Arm Dietary Intervention Study.

In Japan, many workers are exposed to chronic stress, sleep deprivation, and nutritional imbalance. They tend still to go to work when ill, leading to decreased work performance and productivity, which has become a major social problem. We conducted a human entry study with the aim of finding a link between these two factors and proposing an optimized diet, believing that a review of diet may lead to an improvement in labor productivity. In this study, we used subjective accomplishment (SA) as a measure of productivity. First, we compared nutrient intake between groups with high and low SA using data from a health survey of 1564 healthy male and female adults. Significant differences were found in the intake of 13 nutrients in males and 15 nutrients in females, including potassium, vitamin A, insoluble fiber, and biotin. Recommended daily intake of these nutrients was determined from survey data. Next, we designed test meals containing sufficient amounts of 17 nutrients and conducted a single-arm intervention study (registration code UMIN000047054) in Kameyama City, Mie Prefecture, Japan. Healthy working adults (males and females aged 20-79 years) were recruited and supplied with test meals, which were eaten once a day 5 days a week for 8 weeks. SA was significantly higher and daytime sleepiness (DS) was significantly lower after lunch on workdays in younger participants (under 60 years) when they ate the test meals as breakfast or lunch. Our results suggest that SA and DS, which change daily, are strongly influenced by the meal eaten before work, and that taking the 17 nutrients may help prevent presenteeism and improve labor productivity.

Application of on-line sample preconcentration by large-volume dual preconcentration by isotachophoresis and stacking (LDIS) on straight-channel microchips.

In this study, large-volume dual preconcentration by isotachophoresis and stacking (LDIS) which is an on-line sample preconcentration technique coupling large-volume sample stacking with an electroosmotic flow pump (LVSEP) with transient isotachophoresis (tITP) was applied to microchip electrophoresis (MCE) for improving both detection sensitivities and peak shapes. To realize LDIS in MCE, we investigated experimental procedures for injecting a short plug of a leading electrolyte (LE) solution into a straight microchannel without any sophisticated injector apparatus. We found that a short LE plug could be injected into a sample-filled straight-channel only by making the liquid level of the LE solution in an outlet reservoir higher than that in an inlet one. By applying a reversed-polarity voltage to the microchip, anionic analytes injected throughout the microchannel were first enriched by LVSEP, followed by tITP. Through the second preconcentration effect by tITP in LDIS, sensitivity enhancement factor (SEF) and asymmetry factor for a standard dye were improved from 878 and 0.62 to 1330 and 1.14, respectively, relative to those in conventional LVSEP. It should be noted that more viscous running buffer containing sieving polymers could be employed to the LDIS analysis, which was effective for improving the SEF and the separation efficiencies, especially for bio-polymeric compounds. Finally, LDIS was applied to the oligosaccharide and protein analyses in MCE, resulting in the SEFs of 1410 and ca. 50 for maltotriose and bovine milk casein, respectively.

An integrated modeling approach for estimating monthly global rainfall erosivity.

Modeling monthly rainfall erosivity is vital to the optimization of measures to control soil erosion. Rain gauge data combined with satellite observations can aid in enhancing rainfall erosivity estimations. Here, we presented a framework which utilized Geographically Weighted Regression approach to model global monthly rainfall erosivity. The framework integrates long-term (2001-2020) mean annual rainfall erosivity estimates from IMERG (Global Precipitation Measurement (GPM) mission's Integrated Multi-satellitE Retrievals for GPM) with station data from GloREDa (Global Rainfall Erosivity Database, n = 3,286 stations). The merged mean annual rainfall erosivity was disaggregated into mean monthly values based on monthly rainfall erosivity fractions derived from the original IMERG data. Global mean monthly rainfall erosivity was distinctly seasonal; erosivity peaked at ~ 200 MJ mm ha-1 h-1 month-1 in June-August over the Northern Hemisphere and ~ 700 MJ mm ha-1 h-1 month-1 in December-February over the Southern Hemisphere, contributing to over 60% of the annual rainfall erosivity over large areas in each hemisphere. Rainfall erosivity was ~ 4 times higher during the most erosive months than the least erosive months (December-February and June-August in the Northern and Southern Hemisphere, respectively). The latitudinal distributions of monthly and seasonal rainfall erosivity were highly heterogeneous, with the tropics showing the greatest erosivity. The intra-annual variability of monthly rainfall erosivity was particularly high within 10-30° latitude in both hemispheres. The monthly rainfall erosivity maps can be used for improving spatiotemporal modeling of soil erosion and planning of soil conservation measures.

Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.

Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching.

BACKGROUND: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.

Gold nanoparticle-powered screening of membrane protein-specific lipids from complex lipid mixtures.

Membrane proteins (MPs) are affected by binding of specific lipids. We previously developed a methodology for systematically analyzing MP-lipid interactions leveraging surface plasmon resonance (SPR). In this method, the gold sensor chip surface was modified with a self-assembled monolayer (SAM), which allowed for a larger amount of MP-immobilization. However, the laborious lipid purification step remained a bottleneck. To address this issue, a new strategy has been developed utilizing gold nanoparticles (AuNPs) instead of the gold sensor chip. AuNPs were coated with SAM, on which MP was covalently anchored. The MP-immobilized AuNPs were mixed with a lipid mixture, and the recovered lipids were quantified by LC-MS. Bacteriorhodopsin (bR) was used as an MP to demonstrate this concept. We optimized immobilization conditions and confirmed the efficient immobilization of bR by dynamic light scattering and electron micrographs. Washing conditions for pulldown experiments were optimized to efficiently remove non-specific lipids. A new binding index was introduced to qualitatively reproduce the known affinity of lipids for bR. Consequently, the low-abundant and least-studied lipid S-TeGD was identified as a candidate for bR-specific lipids. This technique can skip the laborious lipid purification process, accelerating the screening of MP-specific lipids from complex lipid mixtures.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

An innovative detection technique for capillary electrophoresis: Localized terahertz emission-time domain spectroscopy.

Terahertz (THz) time-domain spectroscopy (TDS) is a recently emerging analysis method which can provide unique information on molecular vibration and rotation induced by inter/intra-molecular interactions. Although the application of THz-TDS to high-performance microscale separation methods like capillary electrophoresis (CE) has been anticipated, it has been hindered due to the diffraction limit of THz wave (typically, hundreds µm). In order to realize CE-THz-TDS, in this study, we placed a narrow open-tubular capillary on the surface of a GaAs semiconductor substrate as a "localized" THz-emitter. By focusing femtosecond pulsed laser beams at the surface of a gallium arsenide (GaAs) substrate closest to the capillary, THz waves were locally generated to pass through the capillary, so that THz absorbance spectra were obtained from the capillary which has narrower inner diameter than the diffraction limit. As a typical result from acetic acid analysis in the CE-THz-TDS platform, information on the refractive index and extinction coefficient was obtained, which showed non-linear and linear concentration dependence, respectively, similar to conventional THz-TDS using large liquid cells. Finally, CE-THz-TDS analysis of several carboxylic acids was demonstrated. Two acids were successfully separated and detected with THz-TDS, where their electrophoretic mobility values were estimated as close to those obtained with conventional contactless conductivity detection. Our proposed CE-THz-TDS showed the potential for the systematic analysis of inter/intra-molecular weak interactions like hydrogen bonds, which are unable to obtain with conventional detectors.

An integrated framework for improving watershed management planning.

Proper land use and management (LUM) planning is pivotal to curbing land degradation and ensuring sustainable use of limited watershed resources. Despite decades of research and development efforts, land degradation remains a serious environmental problem in many parts of the world. Issues regarding the sustainability of current LUM initiatives are due to poor linkages between the ecological and socio-economic dimensions of LUM decisions, and an integrated framework allowing LUM interventions to be properly planned and implemented is lacking. In this study, we developed an integrated framework to identify, evaluate, and propose LUM alternatives with ecological and socio-economic benefits. The framework comprises six components: (i) identification of land use problems and setting of objectives, (ii) identification of the best-performing land use-based integrated solutions, (iii) formulation of LUM alternatives and modeling of key indicators, (iv) cost-benefit analysis, (v) evaluation of the LUM alternatives with stakeholders engagement, and (vi) communication of the LUM alternatives to relevant stakeholders to obtain institutional and financial support for implementation. To demonstrate the use of this framework, we conducted a case study in the Aba Gerima watershed of the Upper Blue Nile basin in Ethiopia. This study used extensive plot- and watershed-scale observations (2015-2019) obtained under both conventional and improved sustainable land management practices. We analyzed changes in runoff, soil loss, soil organic carbon (SOC) stock, and land productivity of five LUM alternatives as compared to a baseline scenario (existing farming practices). The results showed that the LUM alternatives reduced runoff by 11-71% and soil loss by 66-95%, and SOC stock and watershed-scale land productivity were improved by 36-104% and 48-134%, respectively. Evaluation of LUM alternatives by stakeholders, including land users, policy makers, and researchers, produced divergent results. In particular, land users prioritized implementation of sustainable land management practices without altering existing land uses. The integrated framework developed in this study can serve as a valuable tool for identifying, evaluating, and proposing LUM alternatives and facilitating decision-making in planning and implementation of LUM practices in watersheds experiencing land degradation.

Ability of minimally invasive surgery to decrease incisional surgical site infection occurrence in patients with colorectal cancer and other gastroenterological malignancies.

Background: Surgical site infection (SSI) is one of the most important complications of surgery for gastroenterological malignancies because it leads to a prolonged postoperative hospital stay and increased inpatient costs. Furthermore, SSI can delay the initiation of postoperative treatments, including adjuvant chemotherapy, negatively affecting patient prognosis. Identifying the risk factors for SSI is important to improving intra- and postoperative wound management for at-risk patients. Methods: Patients with gastroenterological malignancies who underwent surgery at our institution were retrospectively reviewed and categorized according to the presence or absence of incisional SSI. Clinicopathological characteristics such as age, sex, body mass index, malignancy location, postoperative blood examination results, operation time, and blood loss volume were compared between groups. The same analysis was repeated of only patients with colorectal malignancies. Results: A total of 528 patients (330 men, 198 women; mean age, 68 ± 11 years at surgery) were enrolled. The number of patients with diseases of the esophagus, stomach, small intestine, colon and rectum, liver, gallbladder, and pancreas were 25, 150, seven, 255, 51, five, and 35, respectively. Open surgery was performed in 303 patients vs. laparoscopic surgery in 225 patients. An incisional SSI occurred in 46 patients (8.7%). Multivariate logistic regression analysis showed that postoperative hyperglycemia (serum glucose level ≥140 mg/dl within 24 h after surgery), colorectal malignancy, and open surgery were independent risk factors for incisional SSI. In a subgroup analysis of patients with colorectal malignancy, incisional SSI occurred in 27 (11%) patients. Open surgery was significantly correlated with the occurrence of incisional SSI (P = 0.024). Conclusions: Postoperative hyperglycemia and open surgery were significant risk factors for SSI in patients with gastroenterological malignancies. Minimally invasive surgery could reduce the occurrence of incisional SSI.

Quantitative analysis of drug distribution in heterogeneous tissues using dual-stacking capillary electrophoresis-mass spectrometry.

BACKGROUND AND PURPOSE: Intratumour heterogeneity frequently leads to drug resistance, which is a major issue in drug discovery. Drug distribution is one of the key factors for elucidating the resistance mechanism; however, quantitative and regional drug measurement is challenging. Here, we developed a novel ultra-sensitive analytical method and applied it to HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd), aiming to explore its payload (DXd) distribution within heterogeneous tissues. EXPERIMENTAL APPROACH: The developed analytical method is named LDMS-CE-MS, a capillary electrophoresis-mass spectrometry (CE-MS) coupled with a novel sample preconcentration/separation method called "large-volume dual-sample stacking by micelle collapse and sweeping (LDMS)". First, the analytical performance of LDMS-CE-MS for DXd detection was evaluated. Subsequently, we evaluated the bystander effect of HER3-DXd, where tumour tissues were excised from xenograft models and clinical specimens after administration of HER3-DXd. HER3-high expression, adjacent, and HER3-low expression regions were then sampled by laser microdissection to quantify the released DXd. KEY RESULTS: LDMS concentrated DXd by 1000-fold and separated it from the hydrophilic bio-matrix through continuous capture and release by the charged micelles, allowing quantification at sub-attomole-level. DXd concentrations decreased in the order of antigen-high expression > adjacent > antigen-low expression regions in the tumour xenograft model, whereas in clinical specimens, adjacent and antigen-high expression regions had approximately the same concentration. These distributions represent a bystander effect. CONCLUSIONS AND IMPLICATIONS: Our LDMS-CE-MS successfully visualized the attomole-level drug distributions in heterogeneous clinical specimens. This new platform opens a new era of quantitative pharmacokinetic analysis, facilitating drug discovery and development.

Clinical impact of lymphocyte/C-reactive protein ratio on postoperative outcomes in patients with rectal cancer who underwent curative resection.

Cancer-related systemic inflammation influences postoperative outcomes in cancer patients. Although the relationship between inflammation-related markers and postoperative outcomes have been investigated in many studies, their clinical significance remains to be elucidated in rectal cancer patients. We focused on the lymphocyte count/C-reactive protein ratio (LCR) and its usefulness in predicting short- and long-term outcomes after rectal cancer surgery. Patients with rectal cancer who underwent curative resection at our institution between 2010 and 2018 were enrolled in this study. We comprehensively compared the effectiveness of 11 inflammation-related markers, including LCR and other clinicopathological characteristics, in predicting postoperative complications and survival. Receiver operating characteristic curve analysis indicated that LCR had the highest area under the curve value for predicting the occurrence of postoperative complications. In the multivariate analysis, male sex (odds ratio [OR]: 2.21, 95% confidence interval [CI] 1.07-4.57, P = 0.031), low tumor location (OR: 2.44, 95% CI 1.23-4.88, P = 0.011), and low LCR (OR: 3.51, 95% CI 1.63-7.58, P = 0.001) were significantly and independently associated with the occurrence of postoperative complications. In addition, multivariate analysis using Cox's proportional hazard regression model for the prediction of survival showed that low LCR (≤ 12,600) was significantly associated with both poor overall survival (hazard ratio [HR]: 2.07, 95% CI 1.03-4.15, P = 0.041) and recurrence-free survival (HR: 2.21, 95% CI 1.22-4.01, P = 0.009). LCR is a useful marker for predicting both short- and long-term postoperative outcomes in rectal cancer patients who underwent curative surgery.

Impact of anatomical liver resection on patient survival in KRAS-wild-type colorectal liver metastasis: A multicenter retrospective study.

BACKGROUND: Liver resection is a standard therapy for colorectal liver metastasis. However, the impact of anatomical resection and nonanatomical resection on the survival in patients with Kirsten rat sarcoma-wild-type and Kirsten rat sarcoma-mutated colorectal liver metastasis remain unclear. We investigated whether anatomical resection versus nonanatomical resection improves survival in colorectal liver metastasis stratified by Kirsten rat sarcoma mutational status. METHODS: Among 639 consecutive patients with colorectal liver metastasis who underwent primary liver resection between January 2008 and December 2017, 349 patients were excluded due to their unknown Kirsten rat sarcoma mutational status, or due to receiving anatomical resection with concomitant non-anatomical resection, radiofrequency, or R2 resection. Accordingly, 290 patients with colorectal liver metastasis were retrospectively assessed. The relationships between resection types and survival were investigated in Kirsten rat sarcoma-wild-type and -mutated groups. RESULTS: Anatomical resection was performed in 77/186 (41%) and 44/104 (42%) patients with Kirsten rat sarcoma-wild-type and Kirsten rat sarcoma-mutated genetic statuses, respectively. For both, the clinical-pathologic factors were comparable, except a larger maximum tumor size and surgical margin were observed in anatomical resection cases. Anatomical resection patients had significantly longer recurrence-free survival and overall survival than nonanatomical resection cases in the Kirsten rat sarcoma-wild-type group (recurrence-free survival, P < .001; overall survival, P = .005). No significant recurrence-free survival or overall survival differences were observed between Kirsten rat sarcoma-mutated anatomical resection and non-anatomical resection (recurrence-free survival, P = .132; overall survival, P = .563). Although, intrahepatic recurrence in Kirsten rat sarcoma-wild-type and -mutated colorectal liver metastasis was comparable (P = .973), extrahepatic recurrence was increased in Kirsten rat sarcoma-mutated versus -wild-type colorectal liver metastasis (P < .001). CONCLUSION: In contrast to Kirsten rat sarcoma-mutated colorectal liver metastasis with higher extrahepatic recurrence after liver resection, local liver control via anatomical resection improved the postoperative survival in patients with Kirsten rat sarcoma-wild-type colorectal liver metastasis.

Tracking metabolites at single-cell resolution reveals metabolic dynamics during plant mitosis.

Analyzing only one cell allows the changes and characteristics of intracellular metabolites during the chromosome segregation process to be precisely captured and mitotic sub-phases to be dissected at the metabolite level.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching.

BACKGROUND: Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence. METHODS: Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described. RESULTS: During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P < .001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence. CONCLUSION: The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.

Recent advances in microscale separation techniques for lipidome analysis.

This review paper highlights the recent research on liquid-phase microscale separation techniques for lipidome analysis over the last 10 years, mainly focusing on capillary liquid chromatography (LC) and capillary electrophoresis (CE) coupled with mass spectrometry (MS). Lipids are one of the most important classes of biomolecules which are involved in the cell membrane, energy storage, signal transduction, and so on. Since lipids include a variety of hydrophobic compounds including numerous structural isomers, lipidomes are a challenging target in bioanalytical chemistry. MS is the key technology that comprehensively identifies lipids; however, separation techniques like LC and CE are necessary prior to MS detection in order to avoid ionization suppression and resolve structural isomers. Separation techniques using µm-scale columns, such as a fused silica capillary and microfluidic device, are effective at realizing high-resolution separation. Microscale separation usually employs a nL-scale flow, which is also compatible with nanoelectrospray ionization-MS that achieves high sensitivity. Owing to such analytical advantages, microscale separation techniques like capillary/microchip LC and CE have been employed for more than 100 lipidome studies. Such techniques are still being evolved and achieving further higher resolution and wider coverage of lipidomes. Therefore, microscale separation techniques are promising as the fundamental technology in next-generation lipidome analysis.

Increased biological antioxidant potential in the cerebrospinal fluid of transient global amnesia patients.

Oxidative stress may accompany the pathological process in transient global amnesia (TGA). We measured the biological antioxidant potential (BAP) in the cerebrospinal fluid (CSF) of TGA patients. We enrolled 13 TGA patients (7 men, 6 women; mean age 65.0 years [48-70 years]) and 24 control subjects (12 men, 12 women; mean age 38.2 years [17-65 years]; age did not correlate with csfBAP in this group). We performed brain MRI in all TGA patients, and CA1 lesions were noted by MRI in 5 subjects. We measured csfBAP, total antioxidant properties, in all TGA patients and controls. csfBAP levels were higher in TGA patients than in controls (p = 0.024, 0.028). csfBAP levels in TGA patients did not differ between MRI-positive and -negative subgroups. Elevated csfBAP levels were observed in TGA patients, suggesting that oxidative stress may have a role in the pathogenesis of TGA.

Quantitation of Cell Membrane Permeability of Cyclic Peptides by Single-Cell Cytoplasm Mass Spectrometry.

Cyclic peptides (CPs) have attracted attention as next-generation drugs because they possess both cell-permeable potential as small molecules and specific affinity similar to antibodies. As intracellular molecules are important targets of CPs, quantitation of the intracellular retention and transmembrane permeability of CPs is necessary for drug development. However, permeated CPs within cells cannot be directly assessed by conventional permeability assays using methods such as artificial membranes and cell monolayers. Here, we propose a new approach using single-cell cytoplasm mass spectrometry (SCC-MS). After cells were incubated with CPs, the cytoplasm was directly collected from a single cell using a microneedle followed by nanoelectrospray ionization mass spectrometry detection of the CPs. The height of the CP peak was plotted against time and fitted with a simple function, y = a(1 - e-bx), to calculate the apparent permeability coefficient (Papp) for both the influx and efflux directions. MCF-7 cells were selected as model cancer cells and cultured with cyclosporin A (CsA) and its demethylated analogs (dmCsA-1, -2, and -3) as model CPs. Papp values (10-6 cm/s) obtained from cells incubated with 50 µM CPs ranged from 0.017 to 0.121 for influx and 0.20 to 1.48 for efflux. The higher efflux ratio was possibly caused by efflux transporters such as P-glycoprotein, a well-known receptor of CsA. The equilibrated intracellular concentration of CPs was estimated to be as low as 4.1-6.8 µM, which showed good consistency with the high efflux ratio. SCC-MS is promising as a reliable permeability assay for next-generation CP-based pharmaceuticals.

Relationships between the response of the sweet taste receptor, salivation toward sweeteners, and sweetness intensity.

Sweeteners are widely used in food products, and their sweetness potency is usually evaluated by comparing it with that of sucrose. This, however, has led to confusion as some sweeteners are evaluated based on their maximum value of sweet taste response, while others are evaluated by their threshold value. Here, we aimed to develop a novel nonverbal sweetness evaluation system through the sweet taste signal transduction by comparing the responses of the sweet taste receptor, salivation, taste intensity, and preference among six sweeteners. The hT1r2/hT1r3 sweet taste receptor responses represented the input signal of the sweet taste signal transduction, while salivation, sweet taste intensity, and participants' preferences represented the output signals by the gustatory-salivary reflex, primary gustatory cortex area, and the secondary gustatory cortex, respectively. Our results showed that the sweet taste receptor, sweet intensity, and salivary secretion responses were concentration-dependent and expressed exponentially. Moreover, the results comparing coefficients showed 15-35 times more sensitivity between the response of hT1r2/hT1r3 and the salivation or the sweet taste intensity in non-nutrient sweeteners. The preference graph curve was not exponential, suggesting that the sweetener preference was not related to the sweet taste receptor, salivation, or sweet taste intensity. These results may suggest that the sweet taste signal of the non-nutritive sweeteners might be maintained by taste reception by hT1r2/hT1r3 to taste recognition in the primary gustatory area and that receptor responses and salivation could be used as indicators of sweetness intensity.