tbuckley/cabot-search huggingface dataset:
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Authors: Cutler T. Lewandowski, Megan S. Laham, Gregory R.J. Thatcher
Journal: Acta Pharmaceutica Sinica B (2022)

The function of ATP binding cassette protein A1 (ABCA1) is central to cholesterol mobilization. Reduced ABCA1 expression or activity is implicated in Alzheimer's disease (AD) and other disorders. Therapeutic approaches to boost ABCA1 activity have yet to be translated successfully to the clinic. The risk factors for AD development and progression, including comorbid disorders such as type 2 diabetes and cardiovascular disease, highlight the intersection of cholesterol transport and inflammation. Upregulation of ABCA1 can positively impact APOE lipidation, insulin sensitivity, peripheral vascular and blood–brain barrier integrity, and anti-inflammatory signaling. Various strategies towards ABCA1-boosting compounds have been described, with a bias toward nuclear hormone receptor (NHR) agonists. These agonists display beneficial preclinical effects; however, important side effects have limited development. In particular, ligands that bind liver X receptor (LXR), the primary NHR that controls ABCA1 expression, have shown positive effects in AD mouse models; however, lipogenesis and unwanted increases in triglyceride production are often observed. The longstanding approach, focusing on LXRβ vs. LXRα selectivity, is over-simplistic and has failed. Novel approaches such as phenotypic screening may lead to small molecule NHR modulators that elevate ABCA1 function without inducing lipogenesis and are clinically translatable.
Population sizes, HIV prevalence, and HIV prevention among men who paid for sex in sub-Saharan Africa (2000–2020): A meta-analysis of 87 population-based surveys
Authors: Caroline Hodgins, James Stannah, Salome Kuchukhidze, Lycias Zembe, Jeffrey W. Eaton, Marie-Claude Boily, Mathieu Maheu-Giroux
Journal: PLoS Medicine (2022)

Background Key populations, including sex workers, are at high risk of HIV acquisition and transmission. Men who pay for sex can contribute to HIV transmission through sexual relationships with both sex workers and their other partners. To characterize the population of men who pay for sex in sub-Saharan Africa (SSA), we analyzed population size, HIV prevalence, and use of HIV prevention and treatment. Methods and findings We performed random-effects meta-analyses of population-based surveys conducted in SSA from 2000 to 2020 with information on paid sex by men. We extracted population size, lifetime number of sexual partners, condom use, HIV prevalence, HIV testing, antiretroviral (ARV) use, and viral load suppression (VLS) among sexually active men. We pooled by regions and time periods, and assessed time trends using meta-regressions. We included 87 surveys, totaling over 368,000 male respondents (15–54 years old), from 35 countries representing 95% of men in SSA. Eight percent (95% CI 6%–10%; number of surveys [ N s ] = 87) of sexually active men reported ever paying for sex. Condom use at last paid sex increased over time and was 68% (95% CI 64%–71%; N s = 61) in surveys conducted from 2010 onwards. Men who paid for sex had higher HIV prevalence (prevalence ratio [PR] = 1.50; 95% CI 1.31–1.72; N s = 52) and were more likely to have ever tested for HIV (PR = 1.14; 95% CI 1.06–1.24; N s = 81) than men who had not paid for sex. Men living with HIV who paid for sex had similar levels of lifetime HIV testing (PR = 0.96; 95% CI 0.88–1.05; N s = 18), ARV use (PR = 1.01; 95% CI 0.86–1.18; N s = 8), and VLS (PR = 1.00; 95% CI 0.86–1.17; N s = 9) as those living with HIV who did not pay for sex. Study limitations include a reliance on self-report of sensitive behaviors and the small number of surveys with information on ARV use and VLS. Conclusions Paying for sex is prevalent, and men who ever paid for sex were 50% more likely to be living with HIV compared to other men in these 35 countries. Further prevention efforts are needed for this vulnerable population, including improved access to HIV testing and condom use initiatives. Men who pay for sex should be recognized as a priority population for HIV prevention.
Predicting early biochemical progression in prostate cancer patients staged with PSMA PET and multiparametric magnetic resonance imaging
Authors: D. Meijer, P.J. Van Leeuwen, M.L. Donswijk, T.N. Boellaard, I.G. Schoots, H.G. Van Der Poel, N.H. Hendrikse, D.E. Oprea-Lager, A.N. Vis
Journal: European Urology (2021)
Unclear Diagnostic Testing Standard
Authors: Zhen Wang, Juliana Vanderpluym, Mohammad Murad
Journal: JAMA (2021)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Douglas K. Owens, MD, MS; Lori Pbert, PhD; Michael Silverstein, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
A Phase I/IIa Study of the CD38 Antibody MOR202 Alone and in Combination with Pomalidomide or Lenalidomide in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Marc S. Raab, Manik Chatterjee, Hartmut Goldschmidt, Hermine Agis, Igor Blau, Hermann Einsele, Monika Engelhardt, Barbara Ferstl, Martin Gramatzki, Christoph Röllig, Katja Weisel, Tiantom Jarutat, Dominika Weinelt, Jan Endell, Rainer Boxhammer, Christian Peschel
Journal: Blood (2016)
The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases
Authors: Vasanti S. Malik, Frank B. Hu
Journal: Nature Reviews Endocrinology (2022)

Sugar-sweetened beverages (SSBs) are a major source of added sugars in the diet. A robust body of evidence has linked habitual intake of SSBs with weight gain and a higher risk (compared with infrequent SSB consumption) of type 2 diabetes mellitus, cardiovascular diseases and some cancers, which makes these beverages a clear target for policy and regulatory actions. This Review provides an update on the evidence linking SSBs to obesity, cardiometabolic outcomes and related cancers, as well as methods to grade the strength of nutritional research. We discuss potential biological mechanisms by which constituent sugars can contribute to these outcomes. We also consider global trends in intake, alternative beverages (including artificially-sweetened beverages) and policy strategies targeting SSBs that have been implemented in different settings. Strong evidence from cohort studies on clinical outcomes and clinical trials assessing cardiometabolic risk factors supports an aetiological role of SSBs in relation to weight gain and cardiometabolic diseases. Many populations show high levels of SSB consumption and in low-income and middle-income countries, increased consumption patterns are associated with urbanization and economic growth. As such, more intensified policy efforts are needed to reduce intake of SSBs and the global burden of obesity and chronic diseases. Evidence from cohort studies and clinical trials supports an aetiological role of sugar-sweetened beverage (SSB) intake in the development of obesity and related chronic diseases. This Review provides an up-to-date view, considering the evidence, potential mechanisms and policy actions to reduce the global intake of SSBs.
Trends in Medicare Reimbursement for Common Vitreoretinal Procedures: 2011 to 2020
Authors: Nicolaas P. DeRuyter, Shriji Patel, Qingxia Chen, Henry Leder, Ella Leung, Rahul Reddy, Jill Blim, Carl C. Awh, Paul Hahn
Journal: Ophthalmology (2022)
Prostatic Artery Embolisation (PAE) versus Transurethral Resection of the Prostate (TURP) for benign prostatic hyperplasia: Two-year outcomes of a randomised, open-label, single-centre trial
Authors: D. Abt, G. Müllhaupt, L. Hechelhammer, S. Markart, S. Güsewell, H-P. Schmid, D.S. Engeler
Journal: European Urology (2021)
Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England
Authors: Nick Andrews, Julia Stowe, Freja Kirsebom, Samuel Toffa, Ruchira Sachdeva, Charlotte Gower, Mary Ramsay, Jamie Lopez Bernal
Journal: Nature Medicine (2022)

Booster vaccination with messenger RNA (mRNA) vaccines has been offered to adults in England starting on 14 September 2021. We used a test-negative case-control design to estimate the relative effectiveness of a booster dose of BNT162b2 (Pfizer-BioNTech) compared to only a two-dose primary course (at least 175 days after the second dose) or unvaccinated individuals from 13 September 2021 to 5 December 2021, when Delta variant was dominant in circulation. Outcomes were symptomatic coronavirus disease 2019 (COVID-19) and hospitalization. The relative effectiveness against symptomatic disease 14-34 days after a BNT162b2 or mRNA-1273 (Moderna) booster after a ChAdOx1-S (AstraZeneca) and BNT162b2 as a primary course ranged from around 85% to 95%. Absolute vaccine effectiveness ranged from 94% to 97% and was similar in all age groups. Limited waning was seen 10 or more weeks after the booster. Against hospitalization or death, absolute effectiveness of a BNT162b2 booster ranged from around 97% to 99% in all age groups irrespective of the primary course, with no evidence of waning up to 10 weeks. This study provides real-world evidence of substantially increased protection from the booster vaccine dose against mild and severe disease irrespective of the primary course.
Reply
Authors: Takahiro Kodama, Tetsuo Takehara
Journal: Hepatology (2022)

With interest, we read the letter by Lee et al. and their study evaluating the value of serum thrombospondin‐2 (TSP‐2) as a predictive biomarker of advanced liver fibrosis (F ≥ 3) (ALF) in diabetic patients with NAFLD.[1] This large‐scale cohort study demonstrates that serum TSP‐2 level is capable of identifying those with ALF at high accuracy (area under the receiver operating characteristic curve [AUROC]: 0.80). They also show that serum TSP‐2 level is independently associated with the presence of ALF. These findings are consistent with our study,[2] further strengthening the high reliability of TSP‐2 as a noninvasive biomarker of ALF in patients with NAFLD. Meanwhile, as Lee et al. showed, there is a difference in the performance of TSP‐2 in the diagnosis of ALF, which is comparable to Fibrosisi‐4 index (FIB‐4) and NAFLD fibrosis score (NFS) in our study, but significantly better than them in Lee et al.’s study. This may be attributed to the different clinical backgrounds of the patients in the two studies (diabetes mellitus complication rate was about 30% in our study and 100% in Lee et al.’s study), but it should be noted here that diagnostic accuracy of FIB‐4 and NFS greatly differs between the two studies. Our data show relatively high accuracy of these tests (FIB‐4 AUROC: 0.78; NFS AUROC: 0.81), which is consistent with the result of a recent meta‐analysis of noninvasive tests for histologically defined ALF (F ≥ 3) in patients with NAFLD (FIB‐4 AUROC: 0.76 [n = 5393]; NFS AUROC: 0.73 [n = 3248]).[3] In sharp contrast, their accuracy in Lee et al.’s study is surprisingly poor (FIB‐4 AUROC: 0.60; NFS AUROC: 0.58).[1] This result raises a concern of the accuracy of ALF diagnosis in Lee et al.’s study, which was done solely based on vibration controlled transient elastography value without histological evidence. Taken together, it is unclear whether discrepancy of diagnostic accuracy of FIB‐4 and NFS for ALF between two studies is due to the suboptimal performance of these noninvasive tests in diabetic patients or to the difference of methodology used for ALF diagnosis. Therefore, it is desired for further careful comparison of the performance of TSP‐2 and other noninvasive tests as a biomarker of ALF in diabetic patients with biopsy‐proven NAFLD. Nevertheless, these two studies complementary support the usefulness of serum TSP‐2 in patients with NAFLD as a diagnostic biomarker of ALF and NASH as well as a predictive biomarker of future disease progression including fibrosis progression, shown by Lee et al., and occurrence of hepatic complications (liver cancer and decompensative events) shown by us.
RETRACTED ARTICLE: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway
Authors: Chun-Hua Wei, Gang Wu, Qian Cai, Xi-Can Gao, Fan Tong, Rui Zhou, Rui-Guang Zhang, Ji-Hua Dong, Yu Hu, Xiao-Rong Dong
Journal: Journal of Hematology & Oncology (2017)

Abstract Background Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. Methods Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). Results miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. Conclusions miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.
Implications of guideline-based, risk-stratified restaging transurethral resection of HG Ta urothelial carcinoma on BCG therapy outcomes
Authors: P.J. Hensley, K. Bree, N. Brooks, J. Matulay, R. Li, G. Nogueras González, S. Nagaraju, N. Navai, H. Grossman, C. Dinney, A. Kamat
Journal: European Urology (2021)
Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients
Authors: Navchetan Kaur, Boris Oskotsky, Atul J. Butte, Zicheng Hu
Journal: Genome biology (2022)

Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression.
EAU BCR risk classification as decision tool for salvage radiotherapy? A multicenter study
Authors: F. Preisser, R.S. Abrams-Pompe, P.J. Stelwagen, D. Böhmer, F. Zattoni, A. Magli, J. Gómez Rivas, R. Vives Dilme, M. Sepulcri, A. Eguibar, I. Heidegger, C. Arnold, C.D. Fankhauser, F.K.H. Chun, H. Van Der Poel, G. Gandaglia, T. Wiegel, R.C.N. Van Den Bergh, D. Tilki
Journal: European Urology (2021)
Rheumatoid Factor and Anti–Modified Protein Antibody Reactivities Converge on IgG Epitopes
Authors: Aisha M. Mergaert, Zihao Zheng, Michael F. Denny, Maya F. Amjadi, S. Janna Bashar, Michael A. Newton, Vivianne Malmström, Caroline Grönwall, Sara S. McCoy, Miriam A. Shelef
Journal: Arthritis & Rheumatology (2022)

Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA.Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc.The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.
Precision Medicine in Low- and Middle-Income Countries
Authors: Jerald P. Radich, Edward Briercheck, Daniel T. Chiu, Manoj P. Menon, Olga Sala Torra, Cecilia C.S. Yeung, Edus H. Warren
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine, whereby targeted therapy is directed at cancers based on the specific genetic lesions in the cancer. Can such precision approaches be delivered in LMICs? We offer some examples of novel partnerships and creative solutions that suggest that precision medicine may be possible in LMICs given heavy doses of will, creativity, and persistence and a little luck.
Quantitative Proteomics Using Isobaric Labeling: A Practical Guide
Authors: Xiulan Chen, Yaping Sun, Tingting Zhang, Lian Shu, Peter Roepstorff, Fuquan Yang
Journal: Genomics Proteomics & Bioinformatics (2021)

In the past decade, relative proteomic quantification using isobaric labeling technology has developed into a key tool for comparing the expression of proteins in biological samples. Although its multiplexing capacity and flexibility make this a valuable technology for addressing various biological questions, its quantitative accuracy and precision still pose significant challenges to the reliability of its quantification results. Here, we give a detailed overview of the different kinds of isobaric mass tags and the advantages and disadvantages of the isobaric labeling method. We also discuss which precautions should be taken at each step of the isobaric labeling workflow, to obtain reliable quantification results in large-scale quantitative proteomics experiments. In the last section, we discuss the broad applications of the isobaric labeling technology in biological and clinical studies, with an emphasis on thermal proteome profiling and proteogenomics.
Head-to-head comparison between high-resolution microultrasound imaging and multiparametric MRI in detecting and local staging of bladder cancer: The bus-miss protocol
Authors: P. Diana, A. Uleri, N. Frego, R. Contieri, D. Maffei, P.P. Avolio, L. Balzarini, F. D’Orazio, P. Colombo, G. Lughezzani, N. Buffi, A.R. Saita, P. Casale, M. Lazzeri, R. Hurle
Journal: European Urology (2021)
Can we predict of the response of high risk non muscle invasive bladder cancer patients to intravesical bacillus calmette-guerin? The role of immunological markers
Authors: A. Elbatta, A. Elsawy, H. Abol-Enein, A-A. Zeidan, M. Zahran, M. Shehata, A. Shokeir, A. Awadalla
Journal: European Urology (2021)
Efficacy and Safety of Zanubrutinib in Patients with Treatment-Naive Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with Del(17p): Initial Results from Arm C of the Sequoia (BGB-3111-304) Trial
Authors: Constantine S. Tam, Tadeusz Robak, Paolo Ghia, Brad S. Kahl, Patricia Walker, Wojciech Janowski, David Simpson, Mazyar Shadman, Peter S. Ganly, Luca Laurenti, Stephen Opat, Monica Tani, Hanna Ciepluch, Emma Verner, Martin Simkovic, Anders Österborg, Marek Trněný, Alessandra Tedeschi, Jason Paik, Carol Marimpietri, Shibao Feng, Jane Huang, Peter Hillmen, Jennifer R. Brown
Journal: Blood (2019)
Triglyceride-Glucose index (TyG) is associated with sperm parameters and sperm DNA fragmentation in primary infertile men: a cross-sectional study
Authors: L. Boeri, P. Capogrosso, E. Pozzi, L. Candela, F. Belladelli, W. Cazzaniga, G. Fallara, N. Schifano, E. Ventimiglia, D. Cignoli, G. Colandrea, M. Alfano, C. Abbate, F. Montorsi, A. Salonia
Journal: European Urology (2021)
Overall Adverse events of drugs for metastatic renal cell carcinoma: Real world reporting patterns from eudra vigilance database
Authors: C. De Nunzio, R. Lombardo, G. Tema, O.A. Voglino, F. Cancrini, V. Baldassarri, A. Nacchia, C. Plaza Alonso, A. Zarraonandia Andraca, M. Ruibal Mondes, A. Tubaro
Journal: European Urology (2021)
Preliminary results of in vivo focal transperineal laser ablation treatment of the prostate: Correlation of mpMRI and CEUS imaging to histology in radical prostatectomy specimen
Authors: L.A.M.J.G. Van Riel, R.A.A. Van Kollenburg, T.M. De Reijke, D. Savci-Heijink, M.R.W. Engelbrecht, H.P. Beerlage, T.G. Van Leeuwen, J.R. Oddens, D.M. De Bruin
Journal: European Urology (2021)