dataesr/scientific-paragraphs-categorization huggingface dataset:
Raw data (see Additional file 2) were analyzed using both GenEX and RealTime StatMiner® software. Both integrate quality controls, selection of best endogenous controls, clustering, differential expression, and two-way ANOVA analysis. The samples included in miRNA profiling were A2, A3, A5, A6, A7, A9, A10, and A11 vs. C1, C4, C5, C6, C7, and C10. The miRNA profiling and analyses were performed as paid service by the IMA-GIF platform for high-throughput quantitative PCR, ICSN CNRS, Gif-sur-Yvette, France. Expression profiles of miR-146a, miR-221, miR-654-5p, and miR-656 were assessed using Taqman assays on Fluidigm 48. 48 array in technical triplicates; for fibroblast samples, two different miRNA extractions from consecutive passages were analyzed and six miRNAs were used as reference miRNAs (see Additional file 1: Figure  S2  and Additional file 2 for raw data); for peripheral blood mononuclear cells (PBMC), only one extraction was analyzed and seven miRNAs were used as reference miRNAs (see Additional file 1: Figure  S3  and Additional file 2 for raw data).
Acknowledgements We are grateful to the patients and their family members for their participation in our study. Written informed consent was obtained from the patient for publication of their individual details in this manuscript. The consent form is held by the authors' institution in the patients' clinical notes and is available for review by the Editor-in-Chief. We thank  Prishila Ponien  and  Eric Jacquet  for their We thank  Frédéric Tores  and  Xander Houbaert  for their advice on the statistical analyses. We acknowledge the use of the bioresources of the Necker Imagine DNA biobank ( BB-033-00065 ). This program received a state subsidy managed by the  National Research Agency  under the  "Investments for the Future" program  bearing the reference  ANR-10-IHU-01  and the " ANR-SAMENTA 2012" program.
We included patients at diagnosis of MM and patients at relapse with no previous renal involvement of MM. Patients were divided in two groups based on the availability of novel agents in France. More specifically because bortezomib became available as a first line therapy in 2007, we separated patients in two groups representing two periods of time: those admitted between '1999 and 2007' and between '2008 and 2014'. We defined the dialysis independence by the time the patient does not need chronic dialysis anymore. We collected the survival data defined by myeloma-related death and death from any cause. Complete renal recovery was defined as a decrease of serum creatinine below 177 μmol/l (2 mg/dl) after the beginning of myeloma treatment. Comparisons between groups for numerical variables were performed by the Mann-Whitney U test.
There are differences between this study and ours. This study included only 3-5% of patients necessitating dialysis at the time of diagnosis. Our study focused on even more severe presentations with almost 50% of patients necessitating dialysis at hospital admission. Moreover, in our study, the high number of patients on hematological relapse in the '2008-2014' period may have had an impact on survival analysis. Relapse is of poor prognosis in MM. 12  Maybe if the relapse rate in the two groups had been comparable, we could have found an improvement in survival in the most recent period as in the study by Dimolpoulos et al. 8  Our study has several limitations. First, our collected data does not allow us to affirm that renal involvement in all the patients is due to myeloma kidney. Cases of renal failure related to dehydration or drug toxicity could have been recorded and analyzed in our cohort.
Also, there are only few data available in our cohort on renal histology. Moreover, the type of dialysis modality was not recorded. Second, we analyzed concomitantly patients at diagnosis of MM and patients at relapse. Those two populations have different hematological and renal response rates. 13 Finally, plasma concentration and bioavailability of CT drugs could have been modified by dialysis itself. 12 tudies focusing on myeloma patients requiring dialysis are now needed to determine the best treatment options. On this topic, the results of two multicenter studies are awaited. 14, 15 n conclusion, our study shows that, in myeloma patients with severe renal involvement, active therapy leads to a better dialysis independence achievement. Whether this increase in dialysis-free survival leads to improvement in survival remains to be demonstrated in this subgroup of patients and in the myeloma patients requiring dialysis in the course of the disease.
5 KCl, 25 glucose, 25 NaHCO 3 , 1. 25 NaH 2 PO 4 , 2 CaCl 2 , 1 MgCl 2 , 10 mM pyruvic acid bubbled with 95% O 2 and 5% CO 2. Signals were amplified using with EPC9-2 and EPC10-4 amplifiers (HEKA Elektronik, Lambrecht, Germany). All recordings were performed at 34 °C, using a temperature control system (Bath-controller V, Luigs and Neumann, Ratingen, Germany) and slices were continuously superfused with extracellular solution, at a rate of 2 ml min À 1. Slices were visualized under an Olympus BX51WI microscope (Olympus, Rungis, France), with a 4 Â /0. 13 objective for the placement of the stimulating electrode and a 40 Â /0. 80 water-immersion objective for the localization of cells for wholecell recordings. Current-clamp recordings were filtered at 2. 5 kHz and sampled at 5 kHz and voltage-clamp recordings were filtered at 5 kHz and sampled at 10 kHz, with the Patchmaster v2 Â 32 program (HEKA Elektronik).
We therefore pooled the data for Dt STDP ¼ À 500 ms and Dt STDP ¼ þ 500 ms (Dt STDP ¼ ± 500 ms), which are presented as a single average on the figures. Recordings on neurons were made over a period of 10 min at baseline, and for at least 50 min after the SDTP protocols; long-term changes in synaptic efficacy were measured for the last 10 min. We individually measured and averaged 60 successive EPSCs, comparing the last 10 min of the recording with the 10-minute baseline recording. Whole-cell recordings were made in voltage-clamp mode during baseline and for the 60 min of recording after the STDP protocol, and in current-clamp mode during STDP protocol. Experiments were excluded if input resistance (Ri) varied by more than 20%. For the random Dt STDP patterns, we used the following algorithm (programmed in Igor Pro 6.
DHK was washed out at the STDP protocol offset. The full DHK washout took 15 min (the light gray area in the figures) and, during this period, a significant and transient decrease in EPSC magnitude (due to the DHK-induced inward shift in I holding and AMPAR desensitization  26  ) was observed. Accordingly, in all figures, synaptic efficacy changes are illustrated from 15 min after the removal of DHK. Synaptic efficacy changes were evaluated 50-60 min after the start of the DHK washout (at least 30 min after the full recovery of baseline I holding ). Electrophysiological data analysis. Off-line analysis was performed with Fitmaster (Heka Elektronik). Spontaneous post-synaptic currents (sPSCs) were identified using a semi-automated amplitude threshold based detection software (Mini Analysis 6.
0. 7 Program, Synaptosoft, Fort Lee, NJ, USA) and were visually confirmed. Analysis of NMDAR-EPSCs was performed using a custom-build analysis in Python. After removal of the stimulation artifacts, NMDAR-EPSCs decay was normalized and fitted to a bi-exponential curve. The fast and slow decay times of NMDAR-EPSCs (tau1 and tau2, respectively) were then quantified. Statistical analysis was performed with Prism 5. 02 software (San Diego, CA, USA). In all cases 'n' refers to an experiment on a single cell from a single slice. In average, 2 cells per animal were obtained. All results are expressed as mean±s. e. m. in the text and in the figures (except as mean ± s. d. in the figures for plasticity graphs: normalized EPSC versus time), and statistical significance was assessed in unpaired t-tests or in one-sample t-tests, as appropriate, using the indicated significance threshold (P), or one-way ANOVA with Bonferroni correction, where specified.
Acknowledgements We thank the members of the  LV laboratory, Hugues Berry ,  Ilya Prokin ,  Olivier Manzoni  and  Christian Giaume , for helpful suggestions and critical comments. We thank  Giuseppe Gangarossa  and  Sylvie Perez  for assistance with immunohistochemistry. S. V. is a Research Fellow of the MRT and the  LabEx MemoLife. This work was supported by grants from  INSERM, College de France ,  CNRS  and  Fondation de France.
For short waves, coth(NHK/f) tends to 1, and eq. (  1 ) becomes ω α θ = -. N sin ( ) (2) In this study, we derived N from three World Ocean Database (WOD) Conductivity Temperature Depth (CTD) profiles to be about 10 -3 s -1 near the bottom, and the local slope was about 0. 04. Because the topography is very complex, θ could not be accurately determined, but it fell in the range between 10 and 20 degrees. The estimated frequency from eq. (  2 ) was approximately 1. 10 × 10 -6 to 2. 18 × 10 -6 Hz, which corresponded to a period of about 5. 3-10. 5 days. When we considered the topography at a slightly larger scale to account for the influence of both Island 1 (I1) and Island 2 (I2) (Fig. 1b ), θ was a relatively small value of about 10°. Then, the inferred frequency was about 1. 10 × 10 -6 Hz, which was similar to the observed period of about 9-14 days.
The valid ADCP data were from a depth of 40 m to the position of the upper ADCP and from the position of the deep ADCP to 120 m below. Short gaps caused by flagged data or redeployment of the mooring were subsequently filled by linear interpolation. WOD CTD profiles. Three CTD profiles ~100 km north of M1 and M2 (S1-S3 in Fig. 1b ) were obtained from WOD09 to estimate the deep layers' stratification. Sea surface data from satellites. Daily absolutely dynamic topography and surface geostrophic velocities in February 2012 and February 2013 were obtained from AVISO gridded dataset to illustrate the dynamical background at the surface.
Acknowledgements This work was supported by the " Strategic Priority Research Program"   of the Chinese Academy of Sciences  (projects  XDB06020102 ,  XDA11010302 ,  XDA11010304 ), the  Recruitment Program of Global Experts , the  National Natural Science Foundation of China  (projects  41476012 ,  91228202 ,  41476013 ,  41276024 ,  41521005 ,  41476011  and  41476014 ), the  CAS/SAFEA International Partnership Program for Creative Research Teams , the  National Key Scientific Instrument and Equipment Development Project  ( 2012YQ12003910 ) and the  Infrastructure Construction Project of Xisha & Nansha Station  ( KZCX2-YW-Y202 ,  KZCX2-EW-Y040 ). This study benefited from the SLA data generated by DUACS and distributed by AVISO (ftp://ftp. aviso. oceanobs. com), WOD09 data from https://www.
Acknowledgments The authors thank  Gaël Guillou  for helping in the isotope ratio analysis of the samples and  Dr. Qiuying Han  for her helping in the identification of macroalgae species. This work was jointly funded by the  Natural Science Foundation of China  ( 41106101  and  41376121 ), the  Strategic Priority Research Program  of the  Chinese Academy of Sciences  ( XDA11020405 ) and the  Natural Science Foundation of Shandong Province  ( JQ201414 ).
Acknowledgments This work was financed by the statutory program of the  Institute of Oceanology, Polish Academy of Sciences (Temat II. 4,IO PAN), and the  Ministry of Science and Higher Education of Poland  (Decision No. 190/N-WŁOCHY/2008/0 ). We would like to thank  Prof. Grażyna Kowalewska  for valuable comments and support. We are grateful to  Dr. Jan Warzocha  of the  Sea Fisheries Institute in Gdynia  for collecting the samples in 2008.
Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.
005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10 -5 ) and higher grade (P for trend = 0. 005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10. 59; 95 % confidence interval (CI) 5. 15-21. 80] and progesterone receptor-positive (OR 5. 04;. With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10 -12 ). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.
In a study including 50 male BRCA1/2 mutation carriers, it was suggested that BRCA2 MBCs may represent a subgroup of tumours with a peculiar phenotype not identified in FBC and characterised by an aggressive biological behaviour  [16]. Furthermore, in a study including 28 male BRCA1/2 mutation carriers, a possible BRCA2 phenotype characterised by micropapillary histology was suggested  [17]. In other, smaller studies, BRCA2 MBCs were associated with younger age at diagnosis and positive lymph node status  [14, 15]. In this study, we report pathology data characteristics of 419 BRCA1/2 MBCs derived from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), who conducted the largest study of its kind to date. The main objective of our study was to characterise the pathologic features of BRCA1/2 MBCs and contrast those with the characteristics of BRCA1/2 FBCs, as well as with MBCs in the general population.
CIMBA study participants CIMBA collects data on male and female BRCA1 or BRCA2 pathogenic mutation carriers older than 18 years of age, with the majority recruited through cancer genetics clinics  [18]. CIMBA data were submitted by 55 study groups in 24 countries based in Europe, North America and Australia. Pathology data from MBC cases for the present analysis were collected by 35 study groups (Additional file 1). Key variables collected for all CIMBA patients include year of birth, age at cancer diagnosis (breast, ovarian or prostate cancers), age at last observation, family membership, race and/or ethnicity and information on applicable prophylactic surgeries. This work was restricted to male and female mutation carriers who had been diagnosed with breast cancer and were of self-reported European ancestry.
Tumour pathology data MBC pathology data were obtained from a range of sources, namely medical, pathology or tumour registry records and immunohistochemical staining and/or scoring of tissue microarrays (TMAs) (Additional file 3). The data included information on ER, PR and HER2 status; morphological subtype; lymph node involvement; TNM (tumour, node, metastasis) staging; and histologic grade. For ER, PR and HER2, status was classified as negative or positive. The vast majority of centres employed a cut-off of either ≥10 % or ≥1 % of tumour nuclei staining positive to define ER/PR receptor positivity, which was not centrally reclassified, owing to the low proportion of records with supporting staining data (Additional file 3). HER2 status was determined using immunohistochemistry (IHC) to detect strong complete membrane staining (with 3+ considered positive) with in situ hybridisation to detect HER2 gene amplification in equivocal cases.
Consistency checks were performed to validate receptor data against supplementary scoring information when provided. Central pathology review was not performed. Each carcinoma was assigned to a morphologic subgroup (ductal, lobular, medullary, other), which was confirmed using the World Health Organisation International Classification of Diseases 0 code for the classification of tumour type when present. Lymph node status, along with the number of nodes showing metastatic carcinoma, was provided when available. Staging data were based on the AJCC Cancer Staging Manual, Sixth Edition  [19] , with data provided on overall stage and its major attributes (primary tumour size, regional lymph node involvement and presence of distant metastasis). Histologic grade was determined by local pathologists using modifications of the Scarff-Bloom-Richardson histological grading system as grade 1, 2 or 3.
SEER data We obtained MBC pathology data from the SEER 18 Registries Database for cases diagnosed from 1973 to 2011  [20]. For this study, we selected only male Caucasian cases diagnosed with invasive breast cancer. For SEER cases, pathology characteristics included age at diagnosis; morphologic subgroup; tumour grade; lymph node status; adjusted stage based on the AJCC Cancer Staging Manual, Sixth Edition  [19] ; ER, PR and HER2 status. Tumour grade was classified as grade 1 (well differentiated), grade 2 (moderately differentiated) or grade 3 (poorly differentiated). SEER includes unselected MBCs, most of which are of unknown BRCA1/2 mutation status. On the basis of published data  [3, 21, 22] , about 10 % of MBC cases are expected to be due to BRCA1 or BRCA2 mutations.
Statistical methods Logistic regression was used to assess the association between pathologic characteristics and male BRCA1/2 mutation carrier status, as well as to compare pathologic characteristics with data from female BRCA1/2 mutation carriers and from male breast tumours arising in the general population using SEER data. In the logistic regression analysis, each pathologic characteristic was treated as the explanatory variable. The outcome variables were BRCA mutation status (BRCA1/BRCA2), sex (female/male) and carrier status (general population/BRCA1 mutation carrier and general population/BRCA2 mutation carrier), with the first term used as the reference group. For assessment of continuous or ordered variables, such as age at diagnosis, stage and grade, tests for trend were also performed.
Analyses within CIMBA data were adjusted for age at diagnosis and country of origin, whereas comparisons between CIMBA and SEER data were adjusted only for age at diagnosis. In addition, an adjustment for calendar year of diagnosis was included in all analyses, based on the following groupings: up to 1990, 1991-2000 and after 2000. A robust variance approach was used to allow for dependencies between related individuals. All analyses were carried out using Stata v13 software (StataCorp, College Station, TX, USA).
When we compared the pathologic characteristics of MBC in BRCA1 and BRCA2 mutation carriers, we observed no statistically significant differences. However, tumours in BRCA1 mutation carriers were more likely to present with more advanced stage (42. 9 % vs. 23. 5 %, P for trend = 0. 11) and were more frequently ER-(9. 7 % vs. 3. 3 %, P = 0. 17) and PR-(21. 4 % vs. 13. 2 %, P = 0. 27) than tumours in BRCA2 mutation carriers (Additional file 4). Characterisation of BRCA2 MBCs: comparison with BRCA2 FBC and with MBC in the general population We evaluated possible pathologic differences between invasive breast cancers arising in male and female BRCA2 mutation carriers by comparing available data from female mutation carriers with breast cancer in the CIMBA dataset. Data from 3750 country-matched female BRCA2 mutation carriers diagnosed with invasive breast cancer were included in this analysis (Table  1 ).
The results revealed that there were significantly fewer invasive lobular carcinomas among male BRCA2 mutation carriers than among female BRCA2 mutation carriers [odds ratio (OR) 0. 14, 95 % confidence interval (CI) 0. 05-0. 43]. In addition, We then compared pathologic features of MBC arising in BRCA2 mutation carriers with characteristics of MBC in the general U. S. population as represented by SEER. We extracted pathology data of 6351 men with invasive breast cancer from the SEER 18 database. There were no statistically significant differences in pathology characteristics between MBCs arising in BRCA2 mutation carriers and those arising in the general population, with the exception of grade and lymph node status (Table  2 ). The comparison between MBCs arising in BRCA1 mutation carriers with those of 6351 MBCs from the SEER database showed no significant differences in pathologic characteristics (Additional file 6).
Discussion To date, most of the available knowledge on MBC is based on MBC arising in the general population, whose BRCA1/2 mutation status is largely unknown. In this study, we sought to determine whether MBC arising in BRCA1 and BRCA2 mutation carriers displayed specific pathologic characteristics. We used data on 419 MBCs with BRCA1 and BRCA2 mutations from an international consortium (CIMBA). The CIMBA series represents the largest collection of MBCs arising in BRCA1 and BRCA2 mutation carriers to date. In our series, the majority of MBC cases (375 of 419, 89. 5 %) were BRCA2 mutation carriers, a finding which corroborates prior, smaller studies. In this study, we conducted the first comparison of the pathologic features of breast cancer arising in male and female BRCA1/2 mutation carriers, taking advantage of the previously collected pathology data from female BRCA1/2 mutation carriers assembled by CIMBA  [13].
However, it is worth noting that breast cancers in female BRCA2 mutation carriers frequently show a lobular morphology  [13] , thus suggesting differences in the pathogenic mechanisms of male and female BRCA2 breast cancer. The number of MBC cases with BRCA1 mutations in our datasets was much smaller than the number of BRCA2 mutation carriers, and our results in this subset of patients should therefore be interpreted with caution. We found that BRCA1 MBC cases were of significantly higher stage, and more frequently ER+ and PR+, than BRCA1 FBCs. Despite the small sample size, our results suggest that hormone receptor pathways also are a driving force in BRCA1 MBC. It is well known that most of the breast tumours arising in female BRCA1 mutation carriers tend to be ER-and PR-, with a small percentage being ER +  [13, 27, 28].
The importance of histologic grade as a prognostic factor in breast cancer has been ascertained in FBC  [30]. Recent data indicate that high-grade tumours are associated with shorter disease-free survival and overall survival rates in MBC patients  [25]. Thus, on the basis of our results, we can suggest that BRCA2 MBC may display an aggressive phenotype and possibly a more unfavourable prognosis. This is a question in need of additional survival data that we are planning to collect within CIMBA. In this study, tumour pathology data were collected through several mechanisms, including medical records, pathology reports and TMAs. Given the global distribution of CIMBA study sites, central pathology review was not feasible. Laboratory methods for tissue preparation, IHC, biochemical assays, scoring systems and data interpretation vary widely (Additional file 3), and misclassifications cannot be excluded.