Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: "resolved" (regular HR behavior following HR rules), "semiresolved" (irregular HR behavior), and "formula-assigned" (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases, and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages, and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5063 MassBank MS/MS records and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http://prime.psc.riken.jp/ .

We compared liver volume and function kinetics after partial hepatectomy according to extent of resection and severity of coexisting liver disease in 57 adults with uneventful postoperative courses. Liver volume and massiveness of resection, or resection rate, were estimated on computed tomography. Patients were categorized into three groups on the basis of reaction rate: small (< 30%), medium (30%-50%) and large (> 50%). The regenerative patterns of normal livers in the medium and large groups consisted of three phases: a rapid increase during the first month, some decrease in the second month and a final, slower increase. This contrasted with the pattern of injured livers with chronic hepatitis or cirrhosis, which generally showed a phase of less rapid, gradual increase. The regeneration rate (volume gain, cm3/day) during the first month was found to be proportional to resection rate in the presence or absence of liver disease. Normal livers regenerated at least twice as rapidly as injured livers in patients with comparable resection rates. Normal livers reached plateau levels within 1 to 2 mo regardless of the massiveness of resection, whereas regeneration took 3 to 5 mo in injured livers. Liver function (albumin, bilirubin) recovered concomitantly with liver volume in the medium group, whereas in the large group they generally returned to their initial values behind volume restoration, particularly in cirrhotic patients. In conclusion, human liver regeneration is strongly influenced by the massiveness of the resection and presence of coexisting liver disease. However, we found that some cirrhotic livers can regenerate, albeit more slowly and less completely, as long as the extent of hepatectomy remains within safe functional limits.

(Groups II and IV) was 10 years younger than that of the HBsAg negative patients (Groups I and III). First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan. RESULTS.The male-to-female ratio was higher in HCVAb negative groups (II and III). The HCVAb positive groups (I and IV) had a significantly poorer hepatic reserve and smaller resections than the HCVAb negative groups. Because the tumors were more advanced (as determined by TNM staging) in Group II, the 3-year crude and disease free survival rates were lower in Group II than in Group I. However, HCVAb negative groups (II and III), when compared at 5 years with the limited subsets of patients who had tumors at earlier stages or a curative resection, had significantly better crude and disease free 5-year survival rates than the HCVAb positive group (I). CONCLUSIONS. Clinicopathologic features differ from one another in accordancewith the viral seromarkers in HCC patients. Significantly better crude and disease free survival after complete resection were promising results for patients with non-HCV-related HCC. By comparison, for patients with HCV-related HCC, the risk of intrahepatic recurrences never subsided even in later years after complete resection. Therefore, posthepatectomy follow-up management should be individualized depending on the viral serologic status of HCC patients. quency of carcinogenesis between HCV-related and hepatitis B virus (HBV) -related liver diseases. With regard to surgery, it is also im-

BackgroundLiquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) is used for comprehensive metabolome and lipidome analyses. Compound identification relies on similarity matching of the retention time (RT), precursor m/z, isotopic ratio, and MS/MS spectrum with reference compounds. For sphingolipids, however, little information on the RT and MS/MS references is available.ResultsNegative-ion ESI–MS/MS is a useful method for the structural characterization of sphingolipids. We created theoretical MS/MS spectra for 21 sphingolipid classes in human and mouse (109,448 molecules), with substructure-level annotation of unique fragment ions by MS-FINDER software. The existence of ceramides with β-hydroxy fatty acids was confirmed in mouse tissues based on cheminformatic- and quantum chemical evidences. The RT of sphingo- and glycerolipid species was also predicted for our LC condition. With this information, MS-DIAL software for untargeted metabolome profiling could identify 415 unique structures including 282 glycerolipids and 133 sphingolipids from human cells (HEK and HeLa) and mouse tissues (ear and liver). ConclusionsMS-DIAL and MS-FINDER software programs can identify 42 lipid classes (21 sphingo- and 21 glycerolipids) with the in silico RT and MS/MS library. The library is freely available as Microsoft Excel files at the software section of our RIKEN PRIMe website (http://prime.psc.riken.jp/).Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-017-0205-3) contains supplementary material, which is available to authorized users.

Background. The mode of tumor growth of intrahepatic cholangiocarcinoma (CC) varies considerably from patient to patient. This study describes the clinicopathologic variety of the extraductal mass‐forming type of CC. Methods. Patients with CC characterized by an extraductal mass (n = 26) who underwent hepatectomy from 1976 through 1992 were clinicopathologically classified into three types: Type I (n = 7), no biliary stricture; Type II (n = 13), biliary stricture without jaundice; and Type III (n = 6), biliary stricture with jaundice. Results. Type I included three patients with microductular‐trabecular arrangement and behavior reminiscent of hepatocellular carcinoma (high association with chronic liver disease, mild positivity for alpha‐fetoprotein [AFP], no lymph node metastasis, but frequent intrahepatic metastasis), in contrast to the other typical cholangiocarcinoma. Hepatolithiasis was associated only with Type II CC. The serum positivity for AFP and carcinoembryonic antigen was much higher in Type I CC, whereas positivity of CA 19‐9 was highest in Type III. Involvement of the portal vein, hepatic artery, or hepatic duct was most frequent in Type III CC, which necessitated resection of the extrahepatic bile duct and hepatectomy. Conclusion. The clinicopathologic behavior of intrahepatic CC differs considerably according to the presence or absence of stricture of the biliary tree. Thus, CC without biliary stricture behaves more like hepatocellular carcinoma, whereas CC with biliary stricture is more like hilar or extrahepatic bile duct carcinoma.