tbuckley/cabot-search huggingface dataset:
Abstract P328: Current Status Of HIV-infected Men Who Have Sex With Men: A Real-world Cross-sectional Study In Underdeveloped Southwest China
Authors: Liyu Ran, Yi Huang, Xiaoqing He, Wei Huang
Journal: Circulation (2020)

Background: The prevalence of human immunodeficiency virus (HIV) among men who have sex with men (MSM) remains high and has shown an upward trend in China. However, the status of HIV-infected MSM in the underdeveloped southwest of China is unknown. The study aimed to evaluate the real-world status of HIV-infected MSM and to compare the characteristics between HIV-infected ‘men who have sex with men only’ (MSMO) and ‘men who have sex with men and women’ (MSMW). Method: The study was conducted with HIV-infected MSM patients in Chongqing in 2017. A questionnaire addressing socio-demographic characteristics, sexual behaviors, condom use, clinical signs and symptoms, and HIV detection and transmission routes was used. Results: A total of 865 HIV-infected MSM were enrolled. More than 70% of MSM had experienced their first sexual intercourse before 20 years old. More than 55.8% of the patients had a high income. Compared with MSMW, more MSMO went to college (60.2% vs. 48.7%), and more often (20.9% vs. 8.7%) use condom during anal sex. Weight loss was the most common sign (15.1%). The numbers of male partners and high-risk sexual behaviors among HIV-infected MSM remained high (30.6%), and few patients (4.6%) agreed to voluntary counseling and testing (VCT). Routine health examination was the most frequently (72.7%) used detection method . Homosexual behavior may be the most frequent transmission route (87.9%) among HIV-infected MSMO and MSMW. Conclusion: The findings indicate that the government should promote more prevention strategies against HIV transmission and detection among MSM.
Abstract MP70: Conventional and Novel Lipid Measures and Subsequent Risk of Lower-extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (aric) Study
Authors: Minghao Kou, Ning Ding, Shoshana Ballew, Maya Salameh, Seth S Martin, Elizabeth Selvin, Gerardo M HEISS, Christie M Ballantyne, Kunihiro Matsushita, Ron C Hoogeveen
Journal: Circulation (2020)

Introduction: The association of conventional lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]) with incident peripheral artery diseases (PAD) has been reported. Understanding novel lipids (remnant lipoprotein cholesterol [RLP-C], LDL-TG, small dense LDL-C [sdLDL-C], Apo-E containing HDL [ApoE-HDL]) in this regard could inform risk classification and preventive approaches for PAD. Hypothesis: Some novel lipids will be more evidently related to incident PAD than some conventional lipid measures. Methods: In 8808 ARIC participants (mean age 62.6 [SD 5.7] y) free of PAD at baseline (visit 4, 1996-98), we assessed the associations of each lipid measure (as quartiles and continuous variable) and incident PAD-related hospitalization through 2015 using multivariable Cox models. Since some lipids are closer biologically correlated than others, indicating collective effects among lipids, we used factor analysis to identify underlying factors and modeled them for PAD risk. Results: There were 262 incident PAD cases. After accounting for potential confounders, HDL-C, TG, RLP-C, LDL-TG, and ApoE-HDL were independently associated with incident PAD, with the largest hazard ratio between Q4 and Q1 for HDL-C (Table). LDL-C showed a J-shaped association, and Q4 and Q3 became significant when compared to Q2 (1.57 [1.09-2.25] and 1.46 [1.02-2.11], respectively). The associations of LDL-TG, and ApoE-HDL remained significant after adjusting for LDL-C. The factor analysis identified 3 factors (Factor 1: mainly loaded by TG, RLC, LDL-TG and sdLDL-C; Factor 2: by total cholesterol, LDL-C, and sdLDL-C; Factor 3: by HDL-C and ApoE-HDL), and only Factor 3 showed an independent association with incident PAD (0.78 [0.65-0.93]). Conclusions: These findings suggest the importance of HDL-related and TG-related lipids in the development of PAD, with potential therapeutic implications.
Abstract P3-11-25: Real-world treatment patterns and clinical outcomes among women with HR+/HER2- advanced or metastatic breast cancer treated in real-world settings in Italy and Germany
Authors: Michelino De Laurentiis, Nadia Harbeck, Ernest Law, Mayank Ajmera, Debanjali Mitra, Keith Davis, Sara Brucker, Sabino De Placido
Journal: Cancer Research (2020)

Abstract Background: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) that, when combined with an aromatase inhibitor (AI) or fulvestrant, has been shown in clinical trials to prolong progression-free survival (PFS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (ABC/MBC). This study sought to describe real-world treatment patterns and clinical outcomes among patients with HR+/HER2- ABC/MBC treated with palbociclib in clinical practice settings in Italy and Germany. Methods: MARIA is an ongoing non-interventional, prospective multi-center study that includes women in Italy and Germany initiating their first or second therapy in the HR+/HER2- ABC/mBC setting. Data from 67 sites were used to assess patient and treatment characteristics and progression-free survival (PFS) among patients receiving palbociclib in combination with AI or fulvestrant. Landmark PFS estimates at 6-, 12-, and 18-months were reported by line of therapy (first- and second-line). Results: Overall, 72 patients formed the interim analytic cohort. Among these, 63 (47%) and 9 (7%) received palbociclib + AI as first- and second-line therapy, respectively. Twenty-six (20%) and 37 (27%) of patients received palbociclib + fulvestrant as first- and second-line therapy, respectively. Approximately 96%, 78%, and 64% of patients receiving palbociclib + AI as first-line therapy were progression free at 6-, 12-, and 18-months, respectively. Among patients receiving palbociclib + fulvestrant as first-line therapy, 6-, 12-, and 18-month PFS was 91%, 64%, and 39%, respectively. For second-line therapy, 6-, 12-, and 18-month PFS was 75%, 38%, 38% among palbociclib + AI users and 71%, 54%, and 45% for palbociclib + fulvestrant. Conclusions: This interim analysis indicates that PFS among women with ABC/mBC HR+/HER2-negative breast cancer in Italy and Germany receiving palbociclib, in combination with letrozole or fulvestrant is comparable to published randomized clinical trial results and other real-world observational studies. Further follow-up is required for longitudinal analysis and to estimate overall survival. Funding: Pfizer Citation Format: Michelino De Laurentiis, Nadia Harbeck, Ernest Law, Mayank Ajmera, Debanjali Mitra, Keith Davis, Sara Brucker, Sabino De Placido. Real-world treatment patterns and clinical outcomes among women with HR+/HER2- advanced or metastatic breast cancer treated in real-world settings in Italy and Germany [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-25.
Abstract 17214: Pilot Study on the Utility of Biomarkers and the Updated ISHLT Primary Graft Dysfunction Scoring Guidelines in Lung Transplantation
Authors: Lourdes Chacon, Gabriel Loor, Daoud Daoud, Jonathan Mase, Hassan Virk, Natalie Debolske, Hyewon Choi, Peter Jindra, Matthew Cusick, Luiz Sampaio, Doris A Taylor
Journal: Circulation (2019)

Background: Previous studies have linked baseline pro-inflammatory molecules to primary graft dysfunction (PGD) after lung transplantation (LTx); yet transplant programs rarely utilize biomarker as...
Randomized trial to assess bone mineral density (BMD) effects of zoledronic acid (ZA) in postmenopausal women (PmW) with breast cancer
Authors: A. Tevaarwerk, J. A. Stewart, R. Love, N. C. Binkley, S. Black, J. Eickhoff, D. L. Mulkerin
Journal: Journal of Clinical Oncology (2007)

19558 Introduction: Osteoporotic fracture represents a major source of morbidity in PmW. Breast cancer patients can be at additional risk because of treatment related estrogen deprivation. The favorable effects of bisphosphonates in osteoporosis and potential reduction of metastases warrant evaluation of ZA in PmW at high risk for breast cancer relapse. We assessed whether ZA 4 mg IV every 12 weeks x 4 doses was associated with an increase in BMD. Secondary objectives included defining ZA’s toxicity profile in this setting, and assessing for differences in overall cancer relapse. Methods: PmW with node positive or stage III breast cancer diagnosed less than 5 years earlier were randomized to ZA or observation. BMD was assessed by dual energy xray absorptiometry (DXA) for all subjects at 0 and 12 months. A toxicity evaluation was performed pre- and post-treatment for patients receiving ZA. Study endpoint occurred when subjects completed the DXAs, had disease progression or declined further treatment. We calculated change in BMD between 0 and 12 months at the L1–4 spine and femur neck. Results: 66 women have enrolled since 2000; 49 women have completed DXAs at 0 and 12 months (observation 23, ZA 26). Median age was 52 (range 40–81 yr), median ECOG performance status was 0 (range 0–1), and most women received concurrent tamoxifen (observation 74%, ZA 61%). Over 12 months, L1–4 spine BMD decreased in the observation arm (-0.006 ± 0.034 g/cm 2 ) and increased in the ZA arm (p&lt;0.001; 0.050 ± 0.042 g/cm 2 ). No significant BMD change occurred at the femur neck. Only three grade 3 events occurred (2 arthralgia, 1 myalgia). Side effects were mild and transient, but as frequent as 87% following dose 1. The most common side effects were fatigue, myalgia and arthralgia. No clinically significant changes in creatinine or calcium occurred. Osteonecrosis of the jaw was not observed. Of the 66 women enrolled, 7 have relapsed (observation 4, ZA 3) but time since diagnosis is less than 10 years for most patients. Conclusions: ZA administered every 12 weeks for 4 doses leads to a statistically and clinically significant change in BMD at the lumbar spine. Toxicity was mild but common. There are as yet no significant differences in cancer relapse. No significant financial relationships to disclose.
The microbiome adds to the complexity of parathyroid hormone action on bone
Authors: Sundeep Khosla
Journal: Journal of Clinical Investigation (2020)

Parathyroid hormone (PTH) has complex effects on bone, including stimulating bone formation and regulating the hematopoietic stem cell (HSC) niche. In the current issue of the JCI, Li et al. demonstrated that the microbiome, through the production of short-chain fatty acids and in particular, butyrate, is necessary for the ability of PTH to increase osteoblast numbers and stimulate bone formation. In addition to implications for the treatment of osteoporosis with PTH analogs, this pathway may be part of a broader mechanism through which the microbiome serves its key function of modulating the immune system.
Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia
Authors: Ann-Kristin Schmaelter, Myriam Labopin, Gerard Socié, Maija Itälä-Remes, Didier Blaise, Ibrahim Yakoub-Agha, Edouard Forcade, Jan Cornelissen, Arnold Ganser, Dietrich Beelen, Hélène Labussière-Wallet, Jakob Passweg, Bipin N. Savani, Christoph Schmid, Arnon Nagler, Mohamad Mohty
Journal: Blood Cancer Journal (2020)

Abstract Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) ( n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p &lt; 10 −5 ), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p &lt; 10 −5 ) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p &lt; 10 −4 ) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p &lt; 10 −4 ) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p &lt; 10 −3 ). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.
Abstract MP55: Protein Intake is Associated With Lower Risk of Type 2 Diabetes in the Framingham Offspring Study
Authors: Richard T Pickering, Mengjie Yuan, Martha R Singer, Laura Lara Castor, Lynn L Moore
Journal: Circulation (2020)

Introduction: Diet and exercise are key prevention strategies for type 2 diabetes (T2DM). Few longitudinal studies have examined separate effects of animal and plant proteins on T2DM risk and results are conflicting. The goal of this study was to evaluate the association between usual intake of dietary protein (total, animal, and plant) and T2DM risk. Methods: Data from middle-aged men and women in the longitudinal Framingham Offspring Study (FOS) with approximately 20 years of follow-up were used. Diet was assessed using three-day diet records (exams 3 and 5); protein intake was adjusted for body weight using the residuals from a linear regression model. Glucose was measured after an overnight fast; impaired fasting glucose (IFG) was defined as a FG &gt;100; diabetes was diagnosed using a standardized and validated FOS protocol. To estimate the hazards ratios) (HR) for IFG or T2DM, Cox proportional hazards models were used to adjust for confounding by age, sex, education level, physical activity, cigarette smoking, height, energy intake, and weight-adjusted carbohydrate intake. Results: Subjects with the highest total protein intakes (≥100 g, men, ≥90 g women) had 34% reduced risks of IFG/T2DM (HR: 0.66; 95% CI: 0.51, 0.85). In this cohort, intakes of animal protein were more than double those of plant protein. The highest intakes of animal protein (≥65 g, men; ≥55 g, women) vs. lower intakes (&lt;55 g, men; &lt;40 g, women) were linked with 33% reduced risks of IFG/T2DM (95% CI: 0.55, 0.82) while intermediate levels of intake were linked with 29% lower risks. In contrast, moderate and higher intakes of plant protein (20-25 g and ≥25 g vs. &lt;20 g) led to non-statistically significant 6-12% risk reductions. Beneficial effects of total protein were stronger for women (HR: 0.53; 95% CI: 0.36, 0.80) than for men (HR: 0.80; 95% CI 0.57, 1.13). In secondary analyses, we evaluated effect modification by other dietary and lifestyle factors. In particular, both men and women with higher intakes of protein and higher levels of physical activity had statistically significant reductions in long-term risk of IFG/T2DM (31%, 39%, and 22% risk reductions among active adults with higher intakes of total, animal, and plant protein, respectively) compared with more sedentary adults who had lower intakes of protein. In contrast, higher physical activity levels alone (among those with lower protein intakes) were associated with non-statistically significant 13-14% lower risks of IFG/T2DM. Conclusions: This prospective study of middle-aged men and women provides important evidence to suggest that dietary protein when combined with an active lifestyle, may be a strategy for lowering long-term risk of diabetes. In this study, animal protein had stronger beneficial effects, but future studies are needed in population groups with higher intakes of plant protein to determine whether these effects would be comparable.
Treatment of metastatic colorectal cancer with aimpila, a glycoside/alpha-fetoprotein complex
Authors: V. Pak, O. Molchanov, M. Vincent
Journal: Journal of Clinical Oncology (2007)

3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetoprotein (PAFP) and a glycosidic apoptosis inducer (AI). PAFP is able to bind selectively to the AFP receptor-positive cancer cells and deliver the AI intracellularly due to AFP receptor-mediated endocytosis. The AI opens mitochondrial permeability transition pores, resulting in apoptosis. Preclinically, the complex is cytotoxic. We investigated the single agent activity of aimpila in patients (pts) with liver metastatic colorectal cancer (mCRC). Methods: Eligibility Criteria: Age &gt;18 yrs, mCRC, any prior treatment, having documented progressive metastatic liver disease. Treatment consisted of oral capsules at a fixed sub-maximal dose (0.3 mg of active substance in an oral capsule, twice a day for 8 weeks). 12 pts were accrued, 6 chemonaïve; median ECOG performance status was 0, median age 56 years (range 45–65), and median time from previous treatment failure was 9.0 months (range 1–20). CT scans were performed before and after. Results: Of the 12 patients, 9 are evaluable for response by RECIST. Two achieved a complete response (CR), 1 a partial response (PR); subsequent confirmatory CT scans are pending. Three achieved stabilization (SD), in 2 cases = 2 months; 3 experienced disease progression. Of 3 non-evaluable pts, 1 experienced clinical deterioration without a CT scan, 1 experienced stable disease &gt;2 months but with both lesions &lt;10 mm in diameter, and a third developed nausea and vomiting leading to interruption of treatment, the only recorded significant adverse event. CEA estimations before and after treatment are available from 2 pts; 1 pt (radiological CR) going from 816 ng/ml to 268 ng/ml; the other (radiological SD) going from 1,243 ng/ml to 638 ng/ml. In this latter patient, one of the liver lesions disappeared, radiologically. The PR pt and 1 of the SD pts had progressed after previous oxaliplatin-based chemotherapy. Median survival has not yet been reached, with a median follow-up of 4 months. Conclusion: Single agent aimpila was well-tolerated in this patient population and produced major objective responses in some patients with liver mCRC. Further study is warranted. [Table: see text]
Mammalian Alternative Translation Initiation Is Mostly Nonadaptive
Authors: Chuan Xu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2020)

Abstract Alternative translation initiation (ATLI) refers to the existence of multiple translation initiation sites per gene and is a widespread phenomenon in eukaryotes. ATLI is commonly assumed to be advantageous through creating proteome diversity or regulating protein synthesis. We here propose an alternative hypothesis that ATLI arises primarily from nonadaptive initiation errors presumably due to the limited ability of ribosomes to distinguish sequence motifs truly signaling translation initiation from similar sequences. Our hypothesis, but not the adaptive hypothesis, predicts a series of global patterns of ATLI, all of which are confirmed at the genomic scale by quantitative translation initiation sequencing in multiple human and mouse cell lines and tissues. Similarly, although many codons differing from AUG by one nucleotide can serve as start codons, our analysis suggests that using non-AUG start codons is mostly disadvantageous. These and other findings strongly suggest that ATLI predominantly results from molecular error, requiring a major revision of our understanding of the precision and regulation of translation initiation.
The MUC16 mucin gene upregulates gene transcripts associated with invasion
Authors: J. P. Diaz, S. Kehoe, D. Thapi, N. Rosales, X. Ma, X. J. Yan, D. R. Spriggs
Journal: Journal of Clinical Oncology (2007)

21057 Background: The MUC16 gene encodes the CA125 ovarian cancer antigen and may play a role in invasion. The aim of this study is to investigate the properties of MUC16 in vitro. Methods: PCR was used to create a DNA construct, MUC16–1R-GFP, containing all of the MUC 16 sequence proximal to the second cysteine loop repeat and a GFP-vector construct. SKOv-3 and T-80 cell lines were selected because they are negative for immunologically active CA125. Transfections were performed utilizing the phrGFP II C vector system. Stable transfectants were sorted for GFP by FACS and were grown as populations. The growth rate of the transfected populations were compared to vector only. Periodically the stable transfectants were analyzed by FACS for GFP and OC125 mAb. The in vitro invasive potential was examined, using a Matrigel® invasion assay. RT PCR was used to examine the effect of MUC16 constructs for a panel of invasion focused genes. Immunoblotting was performed on the 1R protein and probed for all genes that were significantly changed on RT PCR. Results: The SKOv-3 1R transfected cell lines produce measurable CA125 into the cell culture medium (4–10 U/mL) while T-80 1R cell lines did not. Analysis of the in vitro growth rate did not demonstrate any difference between the transfectant and vector only cell lines. The 1R-GFP transfected lines showed MUC16 cell surface expression by FACS analysis. Invasion assay of the MUC16 transfectants demonstrated substantially more invasive potential than vector only (SKOV-3: 36% vs. 15% invasion; T-80: 35% vs. 23% invasion). Several transcripts associated with invasion and metastasis were up-regulated 3–9 fold including CDH1, FN1, IL1B, MMP7 and MMP9. Transcripts for the tyrosine kinases SYK and HTATIP2 were down-regulated 16–20 fold respectively. Western immunoblotting confirmed the RT PCR findings. Conclusions: The1R-GFP construct did not alter the growth rate of transfectants in vitro; however; the SKOV-3 1R and T-80 1R cell line did have substantially more invasive potential than vector only. Five transcripts associated with invasion were up-regulated, and 2 transcripts for kinases were down-regulated in the transfected cell lines. These data supports an association between MUC 16 and invasive potential. No significant financial relationships to disclose.
Voicing the Need for Amyotrophic Lateral Sclerosis Environmental Research
Authors: Stephen A. Goutman, Eva L. Feldman
Journal: JAMA Neurology (2020)

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ニューロピリン1は胸腺由来のナチュラル調節性T細胞上では発現するが,粘膜産生の誘導性Foxp3 + の制御性T細胞では発現しない
Authors: M Weiss Jonathan, M Bilate Angelina, Gobert Michael, Ding Yi, DE Lafaille Maria A. Curotto, N Parkhurst Christopher, Xiong Huizhong, Dolpady Jayashree, B Frey Alan, Ruocco Maria Grazia, Yang Yi, Floess Stefan, Huehn Jochen, OH Soyoung, O Li Ming, E Niec Rachel, Y Rudensky Alexander, L Dustin Michael, R Littman Dan, J Lafaille Juan
Journal: The Journal of Experimental Medicine (2012)