--- tags: - sentence-transformers - sentence-similarity - feature-extraction - generated_from_trainer - dataset_size:919 - loss:MultipleNegativesRankingLoss base_model: intfloat/e5-base-v2 widget: - source_sentence: 'query: Bcp1 is a chaperone for Rpl23.' sentences: - "passage: Effects of exercise training on health status in patients with chronic\ \ heart failure: HF-ACTION randomized controlled trial. CONTEXT Findings from\ \ previous studies of the effects of exercise training on patient-reported health\ \ status have been inconsistent. \n OBJECTIVE To test the effects of exercise\ \ training on health status among patients with heart failure. \n DESIGN, SETTING,\ \ AND PATIENTS Multicenter, randomized controlled trial among 2331 medically stable\ \ outpatients with heart failure with left ventricular ejection fraction of 35%\ \ or less. Patients were randomized from April 2003 through February 2007. \n\ \ INTERVENTIONS Usual care plus aerobic exercise training (n = 1172), consisting\ \ of 36 supervised sessions followed by home-based training, vs usual care alone\ \ (n = 1159). Randomization was stratified by heart failure etiology, which was\ \ a covariate in all models. \n MAIN OUTCOME MEASURES Kansas City Cardiomyopathy\ \ Questionnaire (KCCQ) overall summary scale and key subscales at baseline, every\ \ 3 months for 12 months, and annually thereafter for up to 4 years. The KCCQ\ \ is scored from 0 to 100 with higher scores corresponding to better health status.\ \ Treatment group effects were estimated using linear mixed models according to\ \ the intention-to-treat principle. \n RESULTS Median follow-up was 2.5 years.\ \ At 3 months, usual care plus exercise training led to greater improvement in\ \ the KCCQ overall summary score (mean, 5.21; 95% confidence interval, 4.42 to\ \ 6.00) compared with usual care alone (3.28; 95% confidence interval, 2.48 to\ \ 4.09). The additional 1.93-point increase (95% confidence interval, 0.84 to\ \ 3.01) in the exercise training group was statistically significant (P < .001).\ \ After 3 months, there were no further significant changes in KCCQ score for\ \ either group (P = .85 for the difference between slopes), resulting in a sustained,\ \ greater improvement overall for the exercise group (P < .001). Results were\ \ similar on the KCCQ subscales, and no subgroup interactions were detected. \ \ \n CONCLUSIONS Exercise training conferred modest but statistically significant\ \ improvements in self-reported health status compared with usual care without\ \ training. Improvements occurred early and persisted over time. \n TRIAL REGISTRATION\ \ clinicaltrials.gov Identifier: NCT00047437." - 'passage: Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics-an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies-to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes-most with human orthologs-to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process.' - 'passage: ABC of burns. Introduction. Burns are one of the most devastating conditions encountered in medicine. The injury represents an assault on all aspects of the patient, from the physical to the psychological. It affects all ages, from babies to elderly people, and is a problem in both the developed and developing world. All of us have experienced the severe pain that even a small burn can bring. However the pain and distress caused by a large burn are not limited to the immediate event. The visible physical and the invisible psychological scars are long lasting and often lead to chronic disability. Burn injuries represent a diverse and varied challenge to medical and paramedical staff. Correct management requires a skilled multidisciplinary approach that addresses all the problems facing a burn patient. This series provides an overview of the most important aspects of burn injuries for hospital and non-hospital healthcare workers.​workers. Figure 1 Top: Child with 70% full thickness burns, which required resuscitation, intensive care support, and extensive debridement and skin grafting. Left: The same child one year later at a burns camp, having made a good recovery. A reasonable outcome is possible ...' - source_sentence: 'query: Mice without IFN-γ or its receptor are highly susceptible to EAM induced with α-MyHC/CFA.' sentences: - "passage: Human papillomavirus and Papanicolaou tests to screen for cervical cancer.\ \ BACKGROUND Screening for cervical cancer based on testing for human papillomavirus\ \ (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical\ \ intraepithelial neoplasia, but whether this gain represents overdiagnosis or\ \ protection against future high-grade cervical epithelial neoplasia or cervical\ \ cancer is unknown. \n METHODS In a population-based screening program in Sweden,\ \ 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to\ \ have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap\ \ test alone (control group). Women with a positive HPV test and a normal Pap\ \ test result were offered a second HPV test at least 1 year later, and those\ \ who were found to be persistently infected with the same high-risk type of HPV\ \ were then offered colposcopy with cervical biopsy. A similar number of double-blinded\ \ Pap smears and colposcopies with biopsy were performed in randomly selected\ \ women in the control group. Comprehensive registry data were used to follow\ \ the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical\ \ intraepithelial neoplasia or cancer detected at enrollment and at subsequent\ \ screening examinations were calculated. \n RESULTS At enrollment, the proportion\ \ of women in the intervention group who were found to have lesions of grade 2\ \ or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence\ \ interval [CI], 13 to 102) than the proportion of women in the control group\ \ who were found to have such lesions. At subsequent screening examinations, the\ \ proportion of women in the intervention group who were found to have grade 2\ \ or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with\ \ grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions\ \ of control women who were found to have such lesions. Women with persistent\ \ HPV infection remained at high risk for grade 2 or 3 lesions or cancer after\ \ referral for colposcopy. \n CONCLUSIONS The addition of an HPV test to the\ \ Pap test to screen women in their mid-30s for cervical cancer reduces the incidence\ \ of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent\ \ screening examinations. (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].)." - 'passage: Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.' - "passage: the Development of Autoimmune Myocarditis in Mice by an BACKGROUND Interleukin\ \ (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th)\ \ 1 responses. This effect is believed to be mediated primarily through the activation\ \ of STAT4 and subsequent production of interferon (IFN)-gamma. Methods and Results-\ \ We examined the role of IL-12 receptor (IL-12R) signaling in the development\ \ of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin\ \ immunization. Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were\ \ resistant to the induction of myocarditis. Treatment with exogenous IL-12 exacerbated\ \ disease. We questioned whether IFN-gamma is required for the disease-promoting\ \ activity of IL-12. On the contrary, we found that IFN-gamma suppresses EAM.\ \ Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency\ \ exacerbated myocarditis. Spleens from IFN-gamma-deficient mice immunized with\ \ cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+,\ \ CD8+, and IL-2-producing cells; and heightened ability to produce cytokines\ \ on stimulation in vitro. Treatment of mice with recombinant IFN-gamma suppressed\ \ the development of myocarditis. \n CONCLUSIONS IL-12/IL-12R/STAT4 signaling\ \ promotes the development of EAM. In contrast, IFN-gamma plays a protective role.\ \ The disease-limiting effects of IFN-gamma might be explained by its ability\ \ to control the expansion of activated T lymphocytes." - source_sentence: 'query: Oxidative phosphorylation is one of the primary glycometabolic pathways in cells.' sentences: - 'passage: Vesicular Glycolysis Provides On-Board Energy for Fast Axonal Transport Fast axonal transport (FAT) requires consistent energy over long distances to fuel the molecular motors that transport vesicles. We demonstrate that glycolysis provides ATP for the FAT of vesicles. Although inhibiting ATP production from mitochondria did not affect vesicles motility, pharmacological or genetic inhibition of the glycolytic enzyme GAPDH reduced transport in cultured neurons and in Drosophila larvae. GAPDH localizes on vesicles via a huntingtin-dependent mechanism and is transported on fast-moving vesicles within axons. Purified motile vesicles showed GAPDH enzymatic activity and produced ATP. Finally, we show that vesicular GAPDH is necessary and sufficient to provide on-board energy for fast vesicular transport. Although detaching GAPDH from vesicles reduced transport, targeting GAPDH to vesicles was sufficient to promote FAT in GAPDH deficient neurons. This specifically localized glycolytic machinery may supply constant energy, independent of mitochondria, for the processive movement of vesicles over long distances in axons.' - 'passage: NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.' - "passage: Anxiety OBJECTIVES To examine the effect of routinely administered psychiatric\ \ questionnaires on the recognition, management, and outcome of psychiatric disorders\ \ in non-psychiatric settings. \n DATA SOURCES Embase, Medline, PsycLIT, Cinahl,\ \ Cochrane Controlled Trials Register, and hand searches of key journals. \n\ \ METHODS A systematic review of randomised controlled trials of the administration\ \ and routine feedback of psychiatric screening and outcome questionnaires to\ \ clinicians in non-psychiatric settings. Narrative overview of key design features\ \ and end points, together with a random effects quantitative synthesis of comparable\ \ studies. \n MAIN OUTCOME MEASURES Recognition of psychiatric disorders after\ \ feedback of questionnaire results; interventions for psychiatric disorders;\ \ and outcome of psychiatric disorders. \n RESULTS Nine randomised studies were\ \ identified that examined the use of common psychiatric instruments in primary\ \ care and general hospital settings. Studies compared the effect of the administration\ \ of these instruments followed by the feedback of the results to clinicians,\ \ with administration with no feedback. Meta-analytic pooling was possible for\ \ four of these studies (2457 participants), which measured the effect of feedback\ \ on the recognition of depressive disorders. Routine administration and feedback\ \ of scores for all patients (irrespective of score) did not increase the overall\ \ rate of recognition of mental disorders such as anxiety and depression (relative\ \ risk of detection of depression by clinician after feedback 0.95, 95% confidence\ \ interval 0.83 to 1.09). Two studies showed that routine administration followed\ \ by selective feedback for only high scorers increased the rate of recognition\ \ of depression (relative risk of detection of depression after feedback 2.64,\ \ 1.62 to 4.31). This increased recognition, however, did not translate into an\ \ increased rate of intervention. Overall, studies of routine administration of\ \ psychiatric measures did not show an effect on patient outcome. \n CONCLUSIONS\ \ The routine measurement of outcome is a costly exercise. Little evidence shows\ \ that it is of benefit in improving psychosocial outcomes of those with psychiatric\ \ disorder managed in non-psychiatric settings." - source_sentence: 'query: Medications to treat obesity are highly effective.' sentences: - "passage: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.\ \ OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing\ \ weight and improving health status. \n DESIGN Updated meta-analysis of randomised\ \ trials. \n DATA SOURCES Medline, Embase, the Cochrane controlled trials register,\ \ the Current Science meta-register of controlled trials, and reference lists\ \ of identified articles. All data sources were searched from December 2002 (end\ \ date of last search) to December 2006. STUDIES REVIEWED Double blind randomised\ \ placebo controlled trials of approved anti-obesity drugs used in adults (age\ \ over 18) for one year or longer. \n RESULTS 30 trials of one to four years'\ \ duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10\ \ sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were\ \ new and 16 had previously been identified. Attrition rates averaged 30-40%.\ \ Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval\ \ 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant\ \ by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were\ \ significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat\ \ reduced the incidence of diabetes and improved concentrations of total cholesterol\ \ and low density lipoprotein cholesterol, blood pressure, and glycaemic control\ \ in patients with diabetes but increased rates of gastrointestinal side effects\ \ and slightly lowered concentrations of high density lipoprotein. Sibutramine\ \ improved [corrected] concentrations of high density lipoprotein cholesterol\ \ and triglycerides [corrected] Rimonabant improved concentrations of high density\ \ lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control\ \ in patients with diabetes but increased the risk of mood disorders. \n CONCLUSIONS\ \ Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing\ \ effects on cardiovascular risk profiles, and have specific adverse effects." - "passage: Cost-effectiveness of options for the diagnosis of high blood pressure\ \ in primary care: a modelling study. BACKGROUND The diagnosis of hypertension\ \ has traditionally been based on blood-pressure measurements in the clinic, but\ \ home and ambulatory measurements better correlate with cardiovascular outcome,\ \ and ambulatory monitoring is more accurate than both clinic and home monitoring\ \ in diagnosing hypertension. We aimed to compare the cost-effectiveness of different\ \ diagnostic strategies for hypertension. \n METHODS We did a Markov model-based\ \ probabilistic cost-effectiveness analysis. We used a hypothetical primary-care\ \ population aged 40 years or older with a screening blood-pressure measurement\ \ greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general\ \ population. We compared three diagnostic strategies-further blood pressure measurement\ \ in the clinic, at home, and with an ambulatory monitor-in terms of lifetime\ \ costs, quality-adjusted life years, and cost-effectiveness. \n FINDINGS Ambulatory\ \ monitoring was the most cost-effective strategy for the diagnosis of hypertension\ \ for men and women of all ages. It was cost-saving for all groups (from -£56\ \ [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged\ \ 40 years) and resulted in more quality-adjusted life years for men and women\ \ older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to\ \ 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when\ \ assessed with a wide range of deterministic sensitivity analyses around the\ \ base case, but was sensitive if home monitoring was judged to have equal test\ \ performance to ambulatory monitoring or if treatment was judged effective irrespective\ \ of whether an individual was hypertensive. \n INTERPRETATION Ambulatory monitoring\ \ as a diagnostic strategy for hypertension after an initial raised reading in\ \ the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory\ \ monitoring are counterbalanced by cost savings from better targeted treatment.\ \ Ambulatory monitoring is recommended for most patients before the start of antihypertensive\ \ drugs. \n FUNDING National Institute for Health Research and the National\ \ Institute for Health and Clinical Excellence." - 'passage: GSK-3-mediated phosphorylation enhances Maf-transforming activity. The Maf oncoproteins are b-Zip transcription factors of the AP-1 superfamily. They are involved in developmental, metabolic, and tumorigenic processes. Maf proteins are overexpressed in about 50% of human multiple myelomas. Here, we show that Maf-transforming activity is controlled by GSK-3-dependent phosphorylation and that phosphorylation by GSK-3 can increase the oncogenic activity of a protein. Using microarray analysis, we identify a gene-expression subprogram regulated by GSK-3-mediated Maf phosphorylation involved in extracellular matrix remodeling and relevant to cancer progression. We also demonstrate that GSK-3 triggers MafA sequential phosphorylation on residues S61, T57, T53, and S49, inducing its ubiquitination and degradation. Paradoxically, this phosphorylation increases MafA-transcriptional activity through the recruitment of the coactivator P/CAF. We further demonstrate that P/CAF protects MafA from ubiquitination and degradation, suggesting that, upon the release of the coactivator complex, MafA becomes polyubiquitinated and degraded to allow the response to terminate.' - source_sentence: 'query: Upregulation of dynein in Drosophila neurons increases the number of microtubule plus-ends growing toward the cell body of each neuron.' sentences: - 'passage: Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.' - 'passage: Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear. We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. Moreover, Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth. As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation.' - 'passage: Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial Importance Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection. Objectives To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes. Design, Setting, and Patients Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized. Randomization was stratified by metformin use. Interventions Once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Main Outcomes and Measures The primary end point was change in hemoglobing A1c (HbA1c) from baseline to week 26. Secondary end points included change from baseline in body weight and adverse events. Results Baseline characteristics were comparable across treatment groups. Of the 632 randomized patients (mean age, 57.1 years [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%); oral semaglutide reductions were significant vs placebo (dosage-dependent estimated treatment difference [ETD] range for oral semaglutide vs placebo, –0.4% to –1.6%; P = .01 for 2.5 mg, <.001 for all other dosages). Reductions in body weight were greater with oral semaglutide (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg), and significant for oral semaglutide dosages of 10 mg or more vs placebo (dosage-dependent ETD range, –0.9 to –5.7 kg; P < .001). Adverse events were reported by 63% to 86% (371 of 490 patients) in the oral semaglutide groups, 81% (56 of 69 patients) in the subcutaneous semaglutide group, and 68% (48 of 71 patients) in the placebo group; mild to moderate gastrointestinal events were most common. Conclusions and Relevance Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks. These findings support phase 3 studies to assess longer-term and clinical outcomes, as well as safety. Trial Registration clinicaltrials.gov Identifier: NCT01923181' pipeline_tag: sentence-similarity library_name: sentence-transformers --- # SentenceTransformer based on intfloat/e5-base-v2 This is a [sentence-transformers](https://www.SBERT.net) model finetuned from [intfloat/e5-base-v2](https://huggingface.co/intfloat/e5-base-v2). It maps sentences & paragraphs to a 768-dimensional dense vector space and can be used for semantic textual similarity, semantic search, paraphrase mining, text classification, clustering, and more. ## Model Details ### Model Description - **Model Type:** Sentence Transformer - **Base model:** [intfloat/e5-base-v2](https://huggingface.co/intfloat/e5-base-v2) - **Maximum Sequence Length:** 512 tokens - **Output Dimensionality:** 768 dimensions - **Similarity Function:** Cosine Similarity ### Model Sources - **Documentation:** [Sentence Transformers Documentation](https://sbert.net) - **Repository:** [Sentence Transformers on GitHub](https://github.com/UKPLab/sentence-transformers) - **Hugging Face:** [Sentence Transformers on Hugging Face](https://huggingface.co/models?library=sentence-transformers) ### Full Model Architecture ``` SentenceTransformer( (0): Transformer({'max_seq_length': 512, 'do_lower_case': False}) with Transformer model: BertModel (1): Pooling({'word_embedding_dimension': 768, 'pooling_mode_cls_token': False, 'pooling_mode_mean_tokens': True, 'pooling_mode_max_tokens': False, 'pooling_mode_mean_sqrt_len_tokens': False, 'pooling_mode_weightedmean_tokens': False, 'pooling_mode_lasttoken': False, 'include_prompt': True}) (2): Normalize() ) ``` ## Usage ### Direct Usage (Sentence Transformers) First install the Sentence Transformers library: ```bash pip install -U sentence-transformers ``` Then you can load this model and run inference. ```python from sentence_transformers import SentenceTransformer # Download from the 🤗 Hub model = SentenceTransformer("sentence_transformers_model_id") # Run inference sentences = [ 'query: Upregulation of dynein in Drosophila neurons increases the number of microtubule plus-ends growing toward the cell body of each neuron.', 'passage: Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.', 'passage: Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear. We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. Moreover, Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth. As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation.', ] embeddings = model.encode(sentences) print(embeddings.shape) # [3, 768] # Get the similarity scores for the embeddings similarities = model.similarity(embeddings, embeddings) print(similarities.shape) # [3, 3] ``` ## Training Details ### Training Dataset #### Unnamed Dataset * Size: 919 training samples * Columns: sentence_0 and sentence_1 * Approximate statistics based on the first 919 samples: | | sentence_0 | sentence_1 | |:--------|:----------------------------------------------------------------------------------|:-------------------------------------------------------------------------------------| | type | string | string | | details | | | * Samples: | sentence_0 | sentence_1 | |:----------------------------------------------------------------------------------------------------------------------------------------------|:---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | query: Cancer-associated fibroblasts (CAFs) have no known interaction with cancer cells in the formation and activation of CAFs. | passage: Microenvironmental regulation of tumor progression and metastasis Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal ce... | | query: Eilat virus (EILV) produced in mosquitos elicits rapid and long-lasting neutralizing antibodies in nonhuman primates. | passage: A chikungunya fever vaccine utilizing an insect-specific virus platform Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RN... | | query: Glial calcium waves influence seizures. | passage: An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic ac... | * Loss: [MultipleNegativesRankingLoss](https://sbert.net/docs/package_reference/sentence_transformer/losses.html#multiplenegativesrankingloss) with these parameters: ```json { "scale": 20.0, "similarity_fct": "cos_sim" } ``` ### Training Hyperparameters #### Non-Default Hyperparameters - `per_device_train_batch_size`: 32 - `per_device_eval_batch_size`: 32 - `multi_dataset_batch_sampler`: round_robin #### All Hyperparameters
Click to expand - `overwrite_output_dir`: False - `do_predict`: False - `eval_strategy`: no - `prediction_loss_only`: True - `per_device_train_batch_size`: 32 - `per_device_eval_batch_size`: 32 - `per_gpu_train_batch_size`: None - `per_gpu_eval_batch_size`: None - `gradient_accumulation_steps`: 1 - `eval_accumulation_steps`: None - `torch_empty_cache_steps`: None - `learning_rate`: 5e-05 - `weight_decay`: 0.0 - `adam_beta1`: 0.9 - `adam_beta2`: 0.999 - `adam_epsilon`: 1e-08 - `max_grad_norm`: 1 - `num_train_epochs`: 3 - `max_steps`: -1 - `lr_scheduler_type`: linear - `lr_scheduler_kwargs`: None - `warmup_ratio`: 0.0 - `warmup_steps`: 0 - `log_level`: passive - `log_level_replica`: warning - `log_on_each_node`: True - `logging_nan_inf_filter`: True - `save_safetensors`: True - `save_on_each_node`: False - `save_only_model`: False - `restore_callback_states_from_checkpoint`: False - `no_cuda`: False - `use_cpu`: False - `use_mps_device`: False - `seed`: 42 - `data_seed`: None - `jit_mode_eval`: False - `bf16`: False - `fp16`: False - `fp16_opt_level`: O1 - `half_precision_backend`: auto - `bf16_full_eval`: False - `fp16_full_eval`: False - `tf32`: None - `local_rank`: 0 - `ddp_backend`: None - `tpu_num_cores`: None - `tpu_metrics_debug`: False - `debug`: [] - `dataloader_drop_last`: False - `dataloader_num_workers`: 0 - `dataloader_prefetch_factor`: None - `past_index`: -1 - `disable_tqdm`: False - `remove_unused_columns`: True - `label_names`: None - `load_best_model_at_end`: False - `ignore_data_skip`: False - `fsdp`: [] - `fsdp_min_num_params`: 0 - `fsdp_config`: {'min_num_params': 0, 'xla': False, 'xla_fsdp_v2': False, 'xla_fsdp_grad_ckpt': False} - `fsdp_transformer_layer_cls_to_wrap`: None - `accelerator_config`: {'split_batches': False, 'dispatch_batches': None, 'even_batches': True, 'use_seedable_sampler': True, 'non_blocking': False, 'gradient_accumulation_kwargs': None} - `parallelism_config`: None - `deepspeed`: None - `label_smoothing_factor`: 0.0 - `optim`: adamw_torch_fused - `optim_args`: None - `adafactor`: False - `group_by_length`: False - `length_column_name`: length - `project`: huggingface - `trackio_space_id`: trackio - `ddp_find_unused_parameters`: None - `ddp_bucket_cap_mb`: None - `ddp_broadcast_buffers`: False - `dataloader_pin_memory`: True - `dataloader_persistent_workers`: False - `skip_memory_metrics`: True - `use_legacy_prediction_loop`: False - `push_to_hub`: False - `resume_from_checkpoint`: None - `hub_model_id`: None - `hub_strategy`: every_save - `hub_private_repo`: None - `hub_always_push`: False - `hub_revision`: None - `gradient_checkpointing`: False - `gradient_checkpointing_kwargs`: None - `include_inputs_for_metrics`: False - `include_for_metrics`: [] - `eval_do_concat_batches`: True - `fp16_backend`: auto - `push_to_hub_model_id`: None - `push_to_hub_organization`: None - `mp_parameters`: - `auto_find_batch_size`: False - `full_determinism`: False - `torchdynamo`: None - `ray_scope`: last - `ddp_timeout`: 1800 - `torch_compile`: False - `torch_compile_backend`: None - `torch_compile_mode`: None - `include_tokens_per_second`: False - `include_num_input_tokens_seen`: no - `neftune_noise_alpha`: None - `optim_target_modules`: None - `batch_eval_metrics`: False - `eval_on_start`: False - `use_liger_kernel`: False - `liger_kernel_config`: None - `eval_use_gather_object`: False - `average_tokens_across_devices`: True - `prompts`: None - `batch_sampler`: batch_sampler - `multi_dataset_batch_sampler`: round_robin
### Framework Versions - Python: 3.12.12 - Sentence Transformers: 3.4.1 - Transformers: 4.57.6 - PyTorch: 2.12.0+cu130 - Accelerate: 1.13.0 - Datasets: 2.21.0 - Tokenizers: 0.22.2 ## Citation ### BibTeX #### Sentence Transformers ```bibtex @inproceedings{reimers-2019-sentence-bert, title = "Sentence-BERT: Sentence Embeddings using Siamese BERT-Networks", author = "Reimers, Nils and Gurevych, Iryna", booktitle = "Proceedings of the 2019 Conference on Empirical Methods in Natural Language Processing", month = "11", year = "2019", publisher = "Association for Computational Linguistics", url = "https://arxiv.org/abs/1908.10084", } ``` #### MultipleNegativesRankingLoss ```bibtex @misc{henderson2017efficient, title={Efficient Natural Language Response Suggestion for Smart Reply}, author={Matthew Henderson and Rami Al-Rfou and Brian Strope and Yun-hsuan Sung and Laszlo Lukacs and Ruiqi Guo and Sanjiv Kumar and Balint Miklos and Ray Kurzweil}, year={2017}, eprint={1705.00652}, archivePrefix={arXiv}, primaryClass={cs.CL} } ```