Novel subgroups of obesity and their association with outcomes: a data-driven cluster analysis.

BACKGROUND: Obesity is associated with various complications and decreased life expectancy, and substantial heterogeneity in complications and outcomes has been observed. However, the subgroups of obesity have not yet been clearly defined. This study aimed to identify the subgroups of obesity especially those for target of interventions by cluster analysis. METHODS: In this study, an unsupervised, data-driven cluster analysis of 9,494 individuals with obesity (body mass index ≥ 35 kg/m2) was performed using the data of ICD-10, drug, and medical procedure from the healthcare claims database. The prevalence and clinical characteristics of the complications such as diabetes in each cluster were evaluated using the prescription records. Additionally, renal and life prognoses were compared among the clusters. RESULTS: We identified seven clusters characterised by different combinations of complications and several complications were observed exclusively in each cluster. Notably, the poorest prognosis was observed in individuals who rarely visited a hospital after being diagnosed with obesity, followed by those with cardiovascular complications and diabetes. CONCLUSIONS: In this study, we identified seven subgroups of individuals with obesity using population-based data-driven cluster analysis. We clearly demonstrated important target subgroups for intervention as well as a metabolically healthy obesity group.

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. STUDY DESIGN: This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. RESULTS: In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). CONCLUSION: Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.

Orai2 channel regulates prostaglandin E2 production in TNFα/IL1α-stimulated astrocytes.

Astrocytes are glial cells that serve homeostatic functions in the central nervous system (CNS). Recent research, however, suggests that under pathological conditions, astrocytes are stimulated by various factors and actively participate in CNS inflammation. In the present study, we found that astrocytes upregulate various inflammatory factors including prostaglandin E2 (PGE2 ) by co-stimulation with tumor necrosis factor-alpha (TNFα) and interleukin-1alpha (IL1α). These TNFα/IL1α-stimulated astrocytes also showed increased Ca2+ release from the endoplasmic reticulum (ER) and increased expression of Orai2, a member of the store-operated calcium channel (SOCC) family. To reveal the role of Orai2, we used astrocytes in which Orai2 was knocked-down (KD) or knocked-out (KO). The expression of the prostaglandin E synthase Ptges and the production of PGE2 were higher in Orai2-KD astrocytes than in WT astrocytes when stimulated with TNFα and IL1α. Orai2-KO astrocytes also showed increased expression of Ptges and increased PGE2 production. The expression of Ptgs2, another PGE2 synthetic enzyme, was also upregulated in Orai2-KO astrocytes. Moreover, Orai2-KO astrocytes showed increased store-operated calcium entry (SOCE) and increased Orai1 expression. These results suggest that Orai2 is upregulated in TNFα/IL1α-stimulated astrocytes and reduces PGE2 production to some extent, modulating CNS inflammation. Our findings may aid in understanding how astrocytes are associated with inflammatory responses, and the identification of new targets that modulate astrocytic reactivity.

How Many Steps Per Day are Necessary to Prevent Postoperative Complications Following Hepato-Pancreato-Biliary Surgeries for Malignancy?

PURPOSE: The current study was designed to investigate the association between the average preoperative physical activity and postoperative outcomes in patients undergoing surgeries for hepato-pancreato-biliary (HPB) malignancy. METHODS: Patients who were scheduled to undergo open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were included. The average steps per day were recorded by a pedometer and calculated for each patient during the preoperative waiting period. Physical activity levels were classified according to the average number of daily steps as poor (< 5000 steps/day) and good (≥ 5000 steps/day). RESULTS: Of the 105 eligible patients, 78 met the inclusion criteria. The median number of steps per day was 6174. There were 48 patients (62%) with good physical activity and 30 patients (38%) with poor physical activity. Patients with poor physical activity revealed a significantly higher rate of major complications with Clavien grade ≥ 3 (63% vs. 35%, p = 0.016), a higher rate of infectious complications (53% vs. 23%, p = 0.006), and a longer postoperative hospital stay (median, 30 vs. 21 days, p < 0.001) compared with those with good physical activity. After a multivariate analysis, poor physical activity was identified as an independent risk factor for the development of major complications (odds ratio, 2.842, p = 0.042) and infectious complications (odds ratio, 3.844, p = 0.007). CONCLUSIONS: The current study demonstrated that preoperative physical activity levels are associated with the incidence of major postoperative complications following HPB surgery for malignancy.

Rapid automated diagnosis of primary hepatic tumour by mass spectrometry and artificial intelligence.

BACKGROUND AND AIMS: Complete surgical resection with negative margin is one of the pillars in treatment of liver tumours. However, current techniques for intra-operative assessment of tumour resection margins are time-consuming and empirical. Mass spectrometry (MS) combined with artificial intelligence (AI) is useful for classifying tissues and provides valuable prognostic information. The aim of this study was to develop a MS-based system for rapid and objective liver cancer identification and classification. METHODS: A large dataset derived from 222 patients with hepatocellular carcinoma (HCC, 117 tumours and 105 non-tumours) and 96 patients with mass-forming cholangiocarcinoma (MFCCC, 50 tumours and 46 non-tumours) were analysed by Probe Electrospray Ionization (PESI) MS. AI by means of support vector machine (SVM) and random forest (RF) algorithms was employed. For each classifier, sensitivity, specificity and accuracy were calculated. RESULTS: The overall diagnostic accuracy exceeded 94% in both the AI algorithms. For identification of HCC vs non-tumour tissue, RF was the best, with 98.2% accuracy, 97.4% sensitivity and 99% specificity. For MFCCC vs non-tumour tissue, both algorithms gave 99.0% accuracy, 98% sensitivity and 100% specificity. CONCLUSIONS: The herein reported MS-based system, combined with AI, permits liver cancer identification with high accuracy. Its bench-top size, minimal sample preparation and short working time are the main advantages. From diagnostics to therapeutics, it has the potential to influence the decision-making process in real-time with the ultimate aim of improving cancer patient cure.

Clinical Benefit of Preoperative Exercise and Nutritional Therapy for Patients Undergoing Hepato-Pancreato-Biliary Surgeries for Malignancy.

BACKGROUND: The impact of prehabilitation on physical fitness and postoperative course after hepato-pancreato-biliary (HPB) surgeries for malignancy is unknown. The current study aimed to investigate the effect of preoperative exercise and nutritional therapies on nutritional status, physical fitness, and postoperative outcomes of patients undergoing an invasive HPB surgery for malignancy. METHODS: Patients who underwent open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were subjected to prehabilitation. Patients before the introduction of prehabilitation were included as historical control subjects for 1:1 propensity score-matching (no-prehabilitation group). The preoperative nutritional status and postoperative course were compared between the two groups. RESULTS: The prehabilitation group consisted of 76 patients scheduled to undergo HPB surgeries for malignancy. An identical number of patients were selected as the no-prehabilitation group after propensity score-matching. During the waiting period, serum albumin levels were significantly deteriorated in the no-prehabilitation group, whereas this index did not deteriorate or even improved in the prehabilitation group. By performing prehabilitation, a 6-min walk distance and total muscle/fat ratio were significantly increased during the waiting period. Although the overall incidence of postoperative complications did not differ between the two groups, the postoperative hospital stay was shorter in the prehabilitation group than in the no-prehabilitation group (median, 23 vs 30 days; p = 0.045). CONCLUSION: The introduction of prehabilitation prevented nutritional deterioration, improved physical fitness before surgery, and shortened the postoperative hospital stay for the patients undergoing HPB surgeries for malignancy.

Range limitation in hip internal rotation and fifth metatarsal stress fractures (Jones fracture) in professional football players.

PURPOSE: To identify unknown risk factors associated with fifth metatarsal stress fracture (Jones fracture). METHODS: A case-controlled study was conducted among male Japanese professional football (soccer) players with (N = 20) and without (N = 40) a history of Jones fracture. Injury history and physical examination data were reviewed, and the two groups were compared. Univariate and multivariate logistic regression controlling for age, leg dominance and body mass index were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to describe the association between physical examination data and the presence or absence of Jones fractures. RESULTS: From 2000 to 2014, among 162 professional football club players, 22 (13.6%; 21 Asians and one Caucasian) had a history of Jones fracture. Thirteen out of 22 (60%) had a Jones fracture in their non-dominant leg. The mean range of hip internal rotation (HIR) was restricted in players with a history of Jones fracture [25.9° ± 7.5°, mean ± standard deviation (SD)] compared to those without (40.4° ± 11.1°, P < 0.0001). Logistic regression analyses demonstrated that HIR limitation increased the risk of a Jones fracture (OR = 3.03, 95% CI 1.45-6.33, P = 0.003). Subgroup analysis using data prior to Jones fracture revealed a causal relationship, such that players with a restriction of HIR were at high risk of developing a Jones fracture [Crude OR (95% CI) = 6.66 (1.90-23.29), P = 0.003, Adjusted OR = 9.91 (2.28-43.10), P = 0.002]. In addition, right HIR range limitation increased the risks of developing a Jones fracture in the ipsilateral and the contralateral feet [OR = 3.11 (1.35-7.16) and 2.24 (1.22-4.12), respectively]. Similarly, left HIR range limitation increased the risks in the ipsilateral or the contralateral feet [OR (95% CI) = 4.88 (1.56-15.28) and 2.77 (1.08-7.08), respectively]. CONCLUSION: The restriction of HIR was associated with an increased risk of developing a Jones fracture. Since the HIR range is a modifiable factor, monitoring and improving the HIR range can lead to prevent reducing the occurrence of this fracture. LEVEL OF EVIDENCE: III.

2-(Trimethylsilyl)phenyl Trimethylsilyl Ethers as Stable and Readily Accessible Benzyne Precursors.

Stable 2-(trimethylsilyl)phenyl trimethylsilyl ethers, readily obtained from the corresponding halogenated phenols in two steps, were identified as novel benzyne precursors. These species were converted to benzynes by a domino reaction of O-desilylation, O-nonaflylation, and ß-elimination under mild conditions using nonafluorobutanesulfonyl fluoride (NfF) and tetrabutylammonium triphenyldifluorosilicate (TBAT). The generated benzynes were trapped by various arynophiles to afford a wide variety of benzo-fused heterocycles.

Intact Endogenous Metabolite Analysis of Mice Liver by Probe Electrospray Ionization/Triple Quadrupole Tandem Mass Spectrometry and Its Preliminary Application to in Vivo Real-Time Analysis.

Probe electrospray ionization (PESI) is a recently developed ionization technique that enables the direct detection of endogenous compounds like metabolites without sample preparation. In this study, we have demonstrated the first combination use of PESI with triple quadrupole tandem mass spectrometry (MS/MS), which was then applied to intact endogenous metabolite analysis of mice liver, achieving detection of 26 metabolites including amino acids, organic acids, and sugars. To investigate its practicality, metabolic profiles of control and CCl4-induced acute hepatic injury mouse model were measured by the developed method. Results showed clear separation of the two groups in score plots of principal component analysis and identified taurine as the primary contributor to group separation. The results were further validated by the established gas chromatography/MS/MS method, demonstrating the present method's usefulness. In addition, we preliminarily applied the method to real-time analysis of an intact liver of a living mouse. We successfully achieved monitoring of the real-time changes of two tricarboxylic acid cycle intermediates, α-ketoglutaric acid and fumaric acid, in the liver immediately after pyruvic acid injection via a cannulated tube to the portal vein. The present method achieved an intact analysis of metabolites in liver without sample preparation, and it also demonstrates future possibility to establish in vivo real-time metabolome analysis of living animals by PESI/MS/MS.

A new species of the genus Trichopagurus de Saint Laurent, 1968 (Crustacea: Decapoda: Anomura: Paguridae) from a semi-submerged marine cave in Okinawa Island, southwestern Japan.

A new hermit crab species of Paguridae, Trichopagurus spinibrachium n. sp., is described on the basis of a single male specimen collected from the anchialine environment of a semi-submerged marine cave in Okinawa Island, Ryukyu Islands, southwestern Japan. It is morphologically similar to T. macrochela Komai & Osawa, 2005 and T. tenuidactylus Komai, 2013, but differs in the shape and armature of the ocular, antennular and antennal peduncles, chelipeds, and ambulatory legs. The new species may be distinguished from all known congeners by the stronger armature of the carpi and meri of both chelipeds. Trichopagurus spinibrachium n. sp. is the third species of the genus recorded from submarine caves, although it may also occur on nearby coral reefs as does T. macrochela and T. trichophthalmus (Forest, 1954).

The impact of goal-directed prehabilitation therapy on functional capacity in patients undergoing hepatobiliary and pancreatic surgery: A randomized clinical trial.

BACKGROUND: Emerging evidence has supported the idea that goal-directed prehabilitation is a promising approach to boost functional capacity in preoperative patients. However, its usefulness has not been tested in the hepatobiliary and pancreatic fields. The objective of this trial was to investigate the efficacy of goal-directed prehabilitation for improving functional capacity in patients who were planned to undergo major hepatobiliary and pancreatic operations. METHODS: This assessor-blinded, parallel-arm, randomized clinical trial recruited patients who were scheduled for major hepatobiliary and pancreatic surgeries for malignancy. Patients were randomly allocated into the step goal-directed prehabilitation group as the test group and into the conventional prehabilitation group as the control group. Patients in the goal-directed prehabilitation group participated in a walking prehabilitation program with an intergrading goal of the step count. Patients in the conventional prehabilitation group received standard physical and nutritional prehabilitation. The primary outcome was change in the 6-minute walking distance, which ranged from the time before starting prehabilitation (baseline) to the time after completing prehabilitation (immediately before surgery). RESULTS: Among 180 randomized patients, 144 patients were included in the primary analysis (73 patients in the conventional prehabilitation group and 71 patients in the goal-directed prehabilitation group). The mean change in the 6-minute walking distance was 27 meters in the conventional prehabilitation group and 31 meters in the goal-directed prehabilitation group (P = .633). CONCLUSION: In patients undergoing major hepatobiliary and pancreatic surgeries for malignancies, a goal-directed prehabilitation program did not result in a significantly greater increase in functional capacity than did conventional prehabilitation. REGISTRATION NUMBER: UMIN000038791 (https://www.umin.ac.jp/).

Morphological and phylogenetic study of Acanthosquilla Manning, 1963 (Stomatopoda: Nannosquillidae) mantis shrimps, with description of two new species from the Ryukyu Islands, Japan.

Three species of nannosquillid mantis shrimps, including two new species, Acanthosquilla ryukyuensis n. sp. and Acanthosquilla shoheii n. sp., are described based on specimens collected from the Ryukyu Islands, Japan. The two new species resemble A. derijardi Manning, 1970, but can be distinguished from A. derijardi by the following features: 1) rostral plate anterolateral corner forms almost a right angle; 2) the distal tip of the antennular somite dorsal process reaches or slightly falls short of proximal half of rostral plate; and 3) eighth thoracic somite (= TS8) posterior margin is black medially. Furthermore, A. ryukyuensis n. sp. and A. shoheii n. sp. are easy to identify by the bifurcated lateral tooth of the telson, and by the posterodorsal pattern of the telson, respectively. In this study, molecular analyses based on partial sequences of mitochondrial 12S and 16S ribosomal DNA, cytochrome oxidase subunit I (COI), and the partial nuclear gene of 28S ribosomal DNA recovers these three species of Acanthosquilla and A. multifasciata (Wood-Mason, 1895) (the type species of the genus) in a single clade. The resulting trees also suggest the polyphyly of Nannosquillidae but with low nodal support. Detailed examinations of the morphological and color features and DNA barcoding results allowed us to delineate intraspecific variations and interspecific differences. The number and shape of setae under the dorsal spine of raptorial claw carpus was found to be useful in distinguishing A. shoheii n. sp. from A. derijardi and A. ryukyuensis n. sp., while combinations of the coloration of the rostral plate, posterior margin of TS8 and posterodorsal surface of telson are useful to distinguish the three species.

Two new species of Parahesione (Annelida: Hesionidae) associated with ghost shrimps (Crustacea: Decapoda) and their phylogenetic relationships.

Two new species of Hesionidae, Parahesione pulvinata sp. nov. and Parahesione apiculata sp. nov. are described based on materials collected at tidal flats in Okinawa (Japan) from burrows of the ghost shrimps Neocallichirus jousseaumei and Glypturus armatus. The two new species are characterized by having eight enlarged cirri, dorsal cirrophores with dorsal foliose lobe and biramous parapodia, and by lacking median antenna. Parahesione apiculata sp. nov. has digitate lobes on the posterior margin of the dorsal foliose lobe (absent in P. pulvinata sp. nov.). The two new species were never found outside the ghost shrimp burrows, suggesting they are obligate symbionts. Phylogenetic analyses based on four concatenated genes suggest that the symbiotic lifestyle has evolved several times in Hesionidae.

Antithyroid drug-induced leukopenia and G-CSF administration: a long-term cohort study.

Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves' disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.

The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production.

Vascular cognitive impairment (VCI) refers to cognitive alterations caused by vascular disease, which is associated with various types of dementia. Because chronic cerebral hypoperfusion (CCH) induces VCI, we used bilateral common carotid artery stenosis (BCAS) mice as a CCH-induced VCI model. Transient receptor potential ankyrin 1 (TRPA1), the most redox-sensitive TRP channel, is functionally expressed in the brain. Here, we investigated the pathophysiological role of TRPA1 in CCH-induced VCI. During early-stage CCH, cognitive impairment and white matter injury were induced by BCAS in TRPA1-knockout but not wild-type mice. TRPA1 stimulation with cinnamaldehyde ameliorated BCAS-induced outcomes. RNA sequencing analysis revealed that BCAS increased leukemia inhibitory factor (LIF) in astrocytes. Moreover, hydrogen peroxide-treated TRPA1-stimulated primary astrocyte cultures expressed LIF, and culture medium derived from these cells promoted oligodendrocyte precursor cell myelination. Overall, TRPA1 in astrocytes prevents CCH-induced VCI through LIF production. Therefore, TRPA1 stimulation may be a promising therapeutic approach for VCI.

Combined Hypophysitis and Type 1 Diabetes Mellitus Related to Immune Checkpoint Inhibitors.

Context: The occurrence of multiple endocrinopathies due to immune checkpoint inhibitors (ICIs) is a relatively common adverse event. However, the occurrence of a combination of hypophysitis and type 1 diabetes mellitus (T1DM) is extremely rare, and its clinical features are unclear. Objective: We comparatively analyzed the clinical features of this combination and each individual ICI-induced endocrinopathy. Methods: We reported 3 cases that we encountered and reviewed previously reported cases of patients with combined hypophysitis and T1DM due to ICIs. Results: Anti-programmed cell death-1 (anti-PD-1) antibodies were prescribed to all 3 cases. The duration from ICI initiation to the onset of endocrine disease was 12 to 48 weeks. Several human leukocyte antigen (HLA) haplotypes that have disease susceptibility to hypophysitis were detected in all 3 patients. With the 17 previously reported cases, combined endocrinopathies were more common in men (85%). The onset age was in the 60s for both combined and single endocrinopathies. Anti-PD-1 antibodies were used in most of the cases (90%). The time from ICI initiation to the onset of endocrinopathies was 24 (8-76) weeks for hypophysitis and 32 (8-76) weeks for T1DM in patients with combined endocrinopathies, which was not significantly different from that for each single endocrinopathy. Conclusion: We presented 3 cases of patients with combined endocrinopathies of hypophysitis and T1DM that may have been caused by anti-PD-1 antibodies. There was no difference in the time from ICI initiation to the onset of endocrinopathies between combined and single endocrinopathies. Further case accumulation and pathogenic investigations are required.

Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis.

Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.

A new infaunal species of the genus Enosteoides Johnson, 1970 (Crustacea: Decapoda: Anomura: Porcellanidae) from Okinawa, southwestern Japan.

A new porcellanid species of the genus Enosteoides Johnson, 1970 is described on the basis of a single specimen collected from the burrow of an unidentified snapping shrimp of the genus Alpheus Fabricius, 1798, on the subtidal coarse sediment in Okinawa Island, Ryukyu Islands, southwestern Japan. Enosteoides lapis n. sp. is similar to E. melissa (Miyake, 1942) and E. philippinensis Dolorosa Werding, 2014 in the general morphology of the frontal region of the carapace, third thoracic sternite, and ambulatory legs, but is distinguished from both by the dorsal surface of the carapace being more strongly uneven, as well as by the absence of dense plumose setae on the lateral margins of the carapace, anterodorsal surfaces of the chelae, and anterior and posterior margins of the ambulatory meri.

Triple-negative breast cancer: histological subtypes and immunohistochemical and clinicopathological features.

To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.