dataesr/scientific-paragraphs-categorization huggingface dataset:
H2A. J Is a Marker of Luminal Breast and Prostate Cancer Cells H2AFJ was reported to be over-expressed in some cancers  [7] [8] [9] 11] , and interrogation of the Cancer Genome Atlas (TCGA) database showed that prostate and breast cancer expressed high levels of H2AFJ mRNA (Figure  4 , left panel). H2AFJ RNA was also highly expressed in many cancer cell lines derived from glandular tissues such as the breast, pancreas, lung, colorectum, thyroid, esophagus, stomach, and prostate according to the Broad Cancer Cell Line Encyclopedia (CCLE) (Figure  4 , right panel). Left panel: Log2 of H2AFJ RNA levels from transcriptomic data in the Cancer Genome Atlas (TCGA) for prostate adenocarcinoma (PRAD), adrenocorticol carcinoma (ACC), breast carcinoma (BRCA), uveal melanoma (UVM), bladder carcinoma (BLCA), kidney chromophobe carcinoma (KICH), liver hepatocellular carcinoma (LIHC), kidney renal papillary cell carcinoma (KIRP), colon/rectal adenocarcinoma (COAD), thymoma (THYM), skin cutaneous melanoma (SKCM), sarcoma (SARC), pancreatic adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), diffuse large B-cell lymphoma (DLBC), thyroid carcinoma (THCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), testicular germ cell tumors (TGCT), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian Left panel: Log2 of H2AFJ RNA levels from transcriptomic data in the Cancer Genome Atlas (TCGA) for prostate adenocarcinoma (PRAD), adrenocorticol carcinoma (ACC), breast carcinoma (BRCA), uveal melanoma (UVM), bladder carcinoma (BLCA), kidney chromophobe carcinoma (KICH), liver hepatocellular carcinoma (LIHC), kidney renal papillary cell carcinoma (KIRP), colon/rectal adenocarcinoma (COAD), thymoma (THYM), skin cutaneous melanoma (SKCM), sarcoma (SARC), pancreatic adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), diffuse large B-cell lymphoma (DLBC), thyroid carcinoma (THCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), testicular germ cell tumors (TGCT), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV), lung adenocarcinoma (LUAD), pheochromocytoma and paraganglioma (PCPG), uterine carcinosarcoma (UCS), glioblastoma (GBM), acute myeloid leukemia (LAML), brain lower grade glioma (LGG).
Right panel: Log2 of H2AFJ RNA levels from transcriptomic data of cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia (CCLE). Tissues and cell lines of breast origin are shown in blue. Interestingly, immunofluorescence experiments showed that H2A. J was expressed at much higher levels in breast and prostate cancer cell lines of luminal cell origin  [30, 31]  compared to basal or non-luminal cell origin  [30] [31] [32]  (Figure  5A-C ), and Western blotting confirmed this result for the breast cancer lines (Figure  5D ). Since we observed high expression of H2A. J in normal breast and prostate luminal epithelial cells compared to basal cells (Figures  1  and 2 ), this observation suggests that luminal cancer cells retain the high H2AFJ expression of their cell of origin and that H2A.
J expression might represent an additional marker of luminal epithelial cancer cells. serous cystadenocarcinoma (OV), lung adenocarcinoma (LUAD), pheochromocytoma and paraganglioma (PCPG), uterine carcinosarcoma (UCS), glioblastoma (GBM), acute myeloid leukemia (LAML), brain lower grade glioma (LGG). Right panel: Log2 of H2AFJ RNA levels from transcriptomic data of cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia (CCLE). Tissues and cell lines of breast origin are shown in blue. Interestingly, immunofluorescence experiments showed that H2A. J was expressed at much higher levels in breast and prostate cancer cell lines of luminal cell origin  [30, 31]  compared to basal or non-luminal cell origin  [30] [31] [32]  (Figure  5A-C ), and Western blotting confirmed this result for the breast cancer lines (Figure  5D ).
Since we observed high expression of H2A. J in normal breast and prostate luminal epithelial cells compared to basal cells (Figures  1  and 2 ), this observation suggests that luminal cancer cells retain the high H2AFJ expression of their cell of origin and that H2A. J expression might represent an additional marker of luminal epithelial cancer cells. Consistent with previous reports  [7] , breast cancer transcriptome databases  [33]  show that H2AFJ RNA expression was highest in luminal-B breast cancer cells, followed by luminal-A, HER2-E, Normal breast-like, and Basal-like (Figure  6 ). of the indicated cancer cell lines. ß-actin was used as a loading control. The numbers under the panels represent the intensity ratios for H2A. J/ß-actin signals normalized to the T47D ratio. Ub-H2AJ refers to a putative ubiquitinated form of H2A.
J. Consistent with previous reports  [7] , breast cancer transcriptome databases  [33]  show that H2AFJ RNA expression was highest in luminal-B breast cancer cells, followed by luminal-A, HER2-E, Normal breast-like, and Basal-like (Figure  6 ). We performed IHC staining of a tissue microarray composed of 76 malignant core tissue samples (58 ER-negative breast cancer samples and 18 ER-positive samples) (Figure  7  and Supplementary Figure  S5 ). Luminal breast cancers are typically ER-positive whereas basal breast cancers are typically ER-negative  [30]. Quantification of the H2A. J signal showed significantly higher levels of H2A. J staining for the ER-positive breast cancers that is consistent with the higher H2AFJ RNA levels for luminal versus basal breast cancers (Figure  6 ). This result suggests that H2A.
H2AFJ Expression in Relation to Breast Cancer Survival Breast cancers with a high expression of H2AFJ had a slightly higher survival rate compared to breast cancers that expressed low levels of H2AFJ (Figure  8 ). Since luminal breast cancer cells express H2AFJ at higher levels than basal breast cancer cells, this survival difference may reflect the more aggressive nature of basal versus luminal breast cancer  [35]. Separating the breast cancer survival data according to PAM50 intrinsic molecular subtypes, high H2AFJ expression was correlated with a slightly elevated survival for all subtypes except luminal A breast cancer for which it showed significant negative correlation with survival (Supplementary Figure  S7 ). The curves were calculated with bc-GenExMiner v4. 7  [27]  using the optimal splitting criterion on breast cancer cohorts from TCGA and the Swedish Cancerome Analysis Network-Breast (SCAN-B) Initiative (GSE96058 and GSE81538).
H2AFJ Expression in Relation to Survival for Other TCGA Cancer Types Prostate cancer patients with higher than median H2AFJ expression tended to show slightly better survival compared to patients with lower than median H2AFJ, but this difference did not reach statistical significance because there were only 10 death events in The curves were calculated with bc-GenExMiner v4. 7  [27]  using the optimal splitting criterion on breast cancer cohorts from TCGA and the Swedish Cancerome Analysis Network-Breast (SCAN-B) Initiative (GSE96058 and GSE81538).
H2AFJ Expression in Relation to Survival for Other TCGA Cancer Types Prostate cancer patients with higher than median H2AFJ expression tended to show slightly better survival compared to patients with lower than median H2AFJ, but this difference did not reach statistical significance because there were only 10 death events in this TCGA cohort of 498 primary prostate cancer patients (Supplementary Figure  S8 ). Interrogation of all TCGA cancers in the OncoLnc survival database [28] indicated that H2AFJ significantly affected the survival of 4/21 cancer types: high H2AFJ expression was associated with poorer survival for brain lower-grade glioma (LGG), kidney renalcell carcinoma (KIRC), and skin cutaneous melanoma (SKCM), but higher survival for bladder urothelial carcinoma (BLCA) (Supplementary Figure  S8 ).
We performed gene set enrichment analyses (GSEA) using the c2 gene signature and Hallmark collections from the Molecular Signatures Database (MSigDB)  [37]  to identify gene sets whose We first performed differential gene expression analysis for T47D cells treated with tamoxifen versus proliferating cells. 2462 genes showed differential expression (1279 upregulated and 1183 down-regulated genes with FDR < 0. 01) for tamoxifen-treated versus proliferating T47D cells (Figure  10A  and Supplementary Table  S2 ). Tamoxifen is thought to induce the proliferative arrest of mammary epithelial cells by modifying the expression of genes regulated by the estrogen receptor transcription factor ESR1  [36]. We performed gene set enrichment analyses (GSEA) using the c2 gene signature and Hallmark collections from the Molecular Signatures Database (MSigDB)  [37]  to identify gene sets whose expression is affected by tamoxifen treatment.
Furthermore, 27 of the genes that are differentially expressed in the H2A. J-KO cells are also putative direct targets of ESR1 (ADAMTS8, APBB2, CXCL12, FAM189A2, FHL2, FOS, GAS6, GRIK3, HES1, HSPB8, LRP4, MAPT, NDRG1, NEDD9, NEK10, OLFML3, PDZK1, RBBP8, ROBO2, SCGB2A1, SEL1L3, SLC7A5, STC1, SULF2, SULT1A2, TFF1, TNS1) according to ChIP-seq data obtained by the Encode consortium and the ChEA transcription factor database  [39, 40]. These results suggest that H2A. J function is linked to estrogen-regulated gene expression. We confirmed this RNA-seq differential expression analysis by reverse transcriptase coupled to quantitative PCR experiments to determine the RNA levels for five estrogenresponsive genes (PDKZ1, SPINK5, SPINK13, SULF2, and TFF1) in the T47D cells versus the two H2A. J-KO cells lines (Supplementary Figure  11A ).
The GTEx RNA expression databank for human tissues generally correlated with the protein expression in that testis, prostate, adipose, and breast tissue showed high H2AFJ RNA expression whereas brain and heart were low. However, our previous work showed significant accumulation of H2A. J protein in mouse liver and kidney  [5] , whereas the GTEx data indicate that H2AFJ RNA levels are low in human liver and kidney. H2AFJ might be expressed at higher levels in mouse liver and kidney compared to humans, or there might be post-transcriptional regulation that accounts for significant H2A. J protein accumulation in these organs despite relatively low RNA levels. We previously noted that H2A. J protein accumulates to higher levels in senescent compared to quiescent human fibroblasts, even though both types of fibroblasts express similar levels of H2AFJ RNA  [5].
al. (DOI: 10. 5281/zenodo. 4674274). The modified code is available in Zenodo (DOI: 10. 5281/zenodo. 5517186). Single-cell RNA-seq of normal human prostate cells [25] was analyzed with the Web site provided by the Strand Lab (https://strandlab. net/sc. data/hu. pd. deep/, accessed on 19 July 2021). Single-cell RNA-seq data of normal mouse prostate cells [26] was interrogated through the Broad Institute Single Cell Portal (https://singlecell. broadinstitute. org/single_cell/study/SCP859/, accessed on 20 July 2021).
Introduction: Metformin is among the most frequently prescribed drugs worldwide for a variety of indications. Although metformin has several important advantages, for example being easy to store and administer, it is associated with a high incidence of gastrointestinal side effects. Slower-release formulations of metformin may reduce the incidence of side effects while maintaining efficacy; however, there is a lack of systematic evidence available to guide head-to-head comparisons between different metformin formulations. Methods: PubMed, Web of Science, OVID EMBASE, MEDLINE, The Cochrane database and Clinicaltrials. gov were systematically searched (from inception to 25 January 2021). Trials that randomized adult participants to extendedrelease formulation of metformin (met-XR), delayed-release (met-DR) or immediate-release metformin (met-IR) were included.
METHODS This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines  [21]. The systematic review protocol was registered prospectively in PROSPERO (CRD42020167692; Supplementary Text S1) prior to data collection. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors and therefore ethical approval was not required.
Literature Searches, Search Strategies and Eligibility Criteria Systematic literature searches using pre-specified terms (Supplementary Text S2) were performed on PubMed, Ovid EMBASE, Ovid Medline, Cochrane library, Clinicaltrials. gov and Web of Science from database inception to 25 January 2021. No language or location restrictions were applied. Studies that randomised adults to any 'extended-release' formulation of metformin (encompassing slowrelease, extended-release, controlled-release and delayed-release preparations) versus immediaterelease metformin (met-IR) were included (Supplementary Table  S1 ). Studies were included if they randomised patients for any indication. All treatment indications were screened for and diagnosed according to local criteria in each study, and we did not apply exclusions with respect to this.
No restrictions were applied with respect to the length of follow-up period. Efficacy outcomes were change in fasting plasma glucose (FPG; mg/dl and mmol/l), change in glycated haemoglobin (HbA1c; %), body mass index (BMI; kg/m 2 ), mean body weight (kg), lipid profiles (including total, HDL, LDL cholesterol and triglycerides; mg/dl). Any side effects, including GI effects, reported by individual studies were recorded. Data reported only in meeting abstracts was included if the abstract contained sufficient information for assessment. One meeting abstract  [22]  contained sufficient information and therefore was included in the meta-analysis. Where insufficient information for complete assessment was available, authors were contacted for further information. A total of seven authors were contacted; however none responded.
Statistical Analysis The principal summary measures were unadjusted odds ratios (OR) (for dichotomous data) or mean difference (MD) (for continuous data). Meta-analysis and meta-regression were performed using Review Manager (RevMan Version 5. 3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014) and the metafor package in R version 3. 5. 1 (R Foundation for Statistical Computing, Vienna, Austria). Funnel plots were constructed to assess publication bias. Meta-analyses with five or more studies included were also subjected to Egger's test. Heterogeneity between studies was assessed using the I 2 statistic. We implemented randomeffects meta-analyses using restricted maximum-likelihood (REML) estimator. Meta-regression was performed with fasting plasma glucose as the dependent variable and metformin dose as the predictor variable.
ACKNOWLEDGEMENTS Funding. JLT-A and SEO are both funded by the  British Heart Foundation  ( RG/17/12/33167 ) and the  Medical Research Council (UK)  ( MC_UU_00014/4 ). A further  Medical Research Council  grant ( MR/T016701/1 ) also funded JLT-A. RMR acknowledges the support of the  British Heart Foundation  ( RE/18/5/34216 ). CEA is supported by an  Action Medical Research grant (UK)  ( GN2788 ) and by a  Medical Research.
Of note, participants who will not complete all the training sessions will still be included in the analysis. Sensibility analyses will be conducted to examine whether the number of completed sessions influence the effects of the intervention. To accelerate and facilitate knowledge dissemination, all articles will be preprinted, and data and code shared on public repositories. Patients adherence to the impact trial Patients adherence to the training programme (ie, if the planned training session is completed or not, and why in case of no completion) and to the other measures are documented in an electronic case report form (eCRF) powered by REDCap. 70 To promote patient retention and complete follow-up (ie, 1, 3, 6 and 12 months after the end of the intervention), participants will be contacted by phone by a research assistant 2 weeks before the follow-up measurement.
Stimuli: Stimuli representing PA and sedentary behaviours will be created using the Unity software. A set of 195 pictures including 14 avatars (50% women) in either active (walking and running) and inactive posture (sit on a cubicle) will be tested in a pilot study to identify the 48 pictures the most associated with 'movement and physically active behaviours' and the 48 pictures the most associated with 'rest and physically inactive behaviours' using two Visual Analogue Scale (VAS 1; 'please indicate how this image is, in your opinion, associated with a behaviour that requires: 0=no physical exertion at all, Open access 100=a lot of physical exertion'; VAS 2; 'please indicate how closely this image is associated with: 0=resting, sedentary behaviour, 100=movement, very active behaviour'). The credibility of the pictures will also be tested ('how realistic do you think this person's behavior is? Realistic meaning that the images may resemble to a real-life behavior'; on a VAS from 0=behaviour not at all realistic; 100=behaviour very realistic) and for agreeableness ('how pleasant/sympathetic do you find the person in this image? For example, would you like to talk to her/him'; from 0=very unpleasant/antipathetic, 100=very pleasant/ sympathetic).
Randomisation and blinding The research assistants and the participants will be blinded to the allocation of the groups. At the end of the trial, the success of the participant blinding will be examined by the participants to guess in what group there were, including a percentage of certainty. Moreover, the success of research assistants blinding will be examined by asking each research assistant if they were able to detect the group (comparator vs intervention) when they conducted the data collection. The randomisation will be generated on a computer and will be performed using permuted blocks (size=8). To ensure that the research team will be blinded to the randomisation, an independent coworker will carry out the randomisation. The patient's identification number will be used to determine the sequence of randomisation.
Primary outcome The primary outcome will be the sum of accelerometerbased time spent in light-intensity, moderate-intensity and vigorous-intensity PA over 1 week after the CBM intervention (in minutes per week). Following recommendations in patients,  73  a three-axis accelerometer (Actigraph GT3X+; Pensacola, USA) will be used to assess PA. Patients will be given the accelerometer and related indications during the first training session. They will be asked to wear the accelerometer for the full week and to return during the next appointment. They will be instructed on how to wear the device (ie, over the right hip, affixed to an elastic belt, preferably worn under their waistbands). Currently, the waist-mounted Actigraph is the most used device to objectively measure PA. 74  One-minute epochs will be used for data analyses and non-wear time will be defined as ≥59 consecutive minutes of zero counts.
Daily data will be included if the wear time is ≥10 waking hours per day. 75 Data will be included if ≥4 days met the aforementioned conditions. 76 The time spent in light, moderate and vigorous PA over the week will be determined through previously validated cut points,  77  in bouts lasting at least 10 min. Then, in the week following the rehabilitation period, participants will be asked to wear the accelerometer for 1 week. The sum of times spent in light-intensity, moderate-intensity and vigorous-intensity PA during this period (in minutes per week) will be used as the primary outcome. Of note, because the duration of the rehabilitation period may strongly vary between patients, it is possible that some patients will be still in the hospital after 3 weeks, while other will leave the service sooner (eg, at 2 weeks).
Secondary analyses The aforementioned models will be tested at 1, 3, 6 and 12 months after the intervention. Moreover, to examine the effect of the intervention during the rehabilitation period, mixed effects models will be used. These models account for the nested structure of the data (ie, multiple observations within a single participant), thereby providing accurate parameter estimates with acceptable type I error rates. 78 oreover, these models do not require an equal number of observations across participants, thereby allowing participants with missing observations to be included in the analyses without the need to impute those missing data. To formally examine the effect of the intervention on the evolution of PA within the rehabilitation period, models will include interaction terms between conditions (intervention group vs comparator group) and number of days within the rehabilitation programme (linear and quadratic).
Secondary outcomes Automatic precursors of PA Approach tendencies The Visual-Approach/Avoidance-by-the-Self Task. 71 computerised reaction-time task assessing automatic approach tendencies towards PA and sedentary behaviours. During the rehabilitation, 1 week after, as well as 1, Open access require data to fulfil their duties within the scope of the research project. On the online CRFs and other specific documents, participants are only identified by a unique participant number. The online CRF will be created using REDCap. Data recording: The dataset will be accompanied by a README file, which will describe the directory hierarchy and file naming convention. The directory will contain an INFO file describing the experimental protocol used in that experiment. This INFO file will also record any deviation from the protocol and other useful contextual information.
Data anonymisation: Individual participant information collected during the study is considered confidential and disclosure to third parties is prohibited. Subject confidentiality will be ensured by using subject identification code numbers to correspond to treatment data in the computer files. Only a minority of personnel (ie, the principal investigator and chief medical officer) will have access to the data in a non-coded form. Data storage: Participant data on a secure database in accordance with the General Data Protection Regulations (2018). Three copies of the data will be stored. First, original data will be stored on the principal investigator's computer, which will be backed up daily, and protected by a password. Additionally, data will be stored on a secure server hosted by the University of Geneva.
Finally, data will be stored on an external device at a different location and be protected by a password. The original notebook will be stored in the principal investigator's laboratory. Local version of the data for statistical analysis will remain on a university computer, and be password protected. Each person who collected the data will have the responsibility to annotate their data within the metadata. Nevertheless, the principal investigator will have the responsibility to weekly check that the data is properly processed, documented and stored. All study data will be archived for a minimum of 10 years beyond the end of the randomised controlled trial. Trial monitoring: The PI will organise a proper training of all involved study personnel to ensure that the study will be conducted according to the protocol.