tbuckley/cabot-search huggingface dataset:
Frailty, aging, and periodontal disease: Basic biologic considerations
Authors: Daniel Clark, Eftychia Kotronia, Sheena E. Ramsay
Journal: Periodontology 2000 (2021)

Aging is associated with the development of disease. Periodontal disease is one of the many diseases and conditions that increase in prevalence with age. In addition to the traditional focus on individual age-related conditions, there is now a greater recognition that multisystem conditions such as frailty play an important role in the health of older populations. Frailty is a clinical condition in older adults that increases the risk of adverse health outcomes. Both frailty and periodontal disease are common chronic conditions in older populations and share several risk factors. There is likely a bidirectional relationship between periodontal disease and frailty. Comorbid systemic diseases, poor physical functioning, and limited ability to self-care in frail older people have been implicated as underlying the association between frailty and periodontal disease. In addition, both frailty and periodontal disease also have strong associations with inflammatory dysregulation and other age-related pathophysiologic changes that may similarly underlie their development and progression. Investigating age-related changes in immune cells that regulate inflammation may lead to a better understanding of age-related disease and could lead to therapeutic targets for the improved management of frailty and periodontal disease.
Increasing Representation of Women as Editors in Medical Journals
Authors: Elizabeth A. Jacobs, Ishani Ganguli, Sharon K. Inouye
Journal: JAMA Network Open (2021)

Ana-Catarina Pinho-Gomes, DPhil; Amy Vassallo, PhD; Kelly Thompson, PhD; Kate Womersley, MBBS; Robyn Norton, PhD; Mark Woodward, PhD
Priming of NLRP3 inflammasome activation by Msn kinase MINK1 in macrophages
Authors: Kaixiang Zhu, Xuexiao Jin, Zhexu Chi, Sheng Chen, Songquan Wu, Richard D. Sloan, Xuai Lin, Dante Neculai, Di Wang, Hu Hu, Linrong Lu
Journal: Cellular and Molecular Immunology (2021)
TET3 promotes AML growth and epigenetically regulates glucose metabolism and leukemic stem cell associated pathways
Authors: Alex Jose Pulikkottil, Shiva Bamezai, Tobias Ammer, Fabian Mohr, Kristin Feder, Naidu M. Vegi, Tamoghna Mandal, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Amit Sinha, Christian Buske, Vijay P. S. Rawat
Journal: Leukemia (2021)
DNA Logic Circuits for Multiple Tumor Cells Identification Using Intracellular MicroRNA Molecular Bispecific Recognition
Authors: Qiqi Yang, Fan Yang, Wenhao Dai, Xiangdan Meng, Wei Wei, Yaru Cheng, Jinhong Dong, Huiting Lu, Haifeng Dong
Journal: Advanced Healthcare Materials (2021)

Abstract The aberrant expression level of intracellular microRNAs (miRNAs) holds great promise for differentiating cell types at the molecular level. However, cell subtype discrimination based on a single miRNA molecular level is not sufficient and reliable. Herein, multiple identifiable and reporting modules are integrated into a single DNA circuit for multiple cancer cell subtypes identification based on miRNAs bispecific recognition. The DNA three‐dimensional (3D) logic gate nano‐hexahedron framework extends three recognition modules and three reporting modules to form three “AND” logic gates. Each Boolean operator “AND” returns an “ON” signal in the presence of bispecific miRNAs, simultaneously enabling three types of cell subtype identification. It not only enables the discrimination of cancer cells A549 and MCF‐7 from normal cells NHDF but also successfully distinguishes different types of cancer cells. The bispecific intracellular miRNA controllable DNA circuit, with low signal‐to‐noise ratio, easily extends to various cell type discrimination by adjusting the miRNA species, provides huge opportunities for accurately differentiating multiple cell types at the molecular level.
Development and Validation of Machine Learning–based Model for the Prediction of Malignancy in Multiple Pulmonary Nodules: Analysis from Multicentric Cohorts
Authors: Kezhong Chen, Yuntao Nie, Samina Park, Kai Zhang, Yangming Zhang, Yuan Liu, Bengang Hui, Lixin Zhou, Xun Wang, Qingyi Qi, Hao Li, Guannan Kang, Yuqing Huang, Yingtai Chen, Jiabao Liu, Jian Cui, Mingru Li, In Kyu Park, Chang Hyun Kang, Haifeng Shen, Yingshun Yang, Tian Guan, Yaxiao Zhang, Fan Yang, Young Tae Kim, Jun Wang
Journal: Clinical Cancer Research (2021)

Nodule evaluation is challenging and critical to diagnose multiple pulmonary nodules (MPNs). We aimed to develop and validate a machine learning-based model to estimate the malignant probability of MPNs to guide decision-making.A boosted ensemble algorithm (XGBoost) was used to predict malignancy using the clinicoradiologic variables of 1,739 nodules from 520 patients with MPNs at a Chinese center. The model (PKU-M model) was trained using 10-fold cross-validation in which hyperparameters were selected and fine-tuned. The model was validated and compared with solitary pulmonary nodule (SPN) models, clinicians, and a computer-aided diagnosis (CADx) system in an independent transnational cohort and a prospective multicentric cohort.The PKU-M model showed excellent discrimination [area under the curve; AUC (95% confidence interval (95% CI)), 0.909 (0.854-0.946)] and calibration (Brier score, 0.122) in the development cohort. External validation (583 nodules) revealed that the AUC of the PKU-M model was 0.890 (0.859-0.916), higher than those of the Brock model [0.806 (0.771-0.838)], PKU model [0.780 (0.743-0.817)], Mayo model [0.739 (0.697-0.776)], and VA model [0.682 (0.640-0.722)]. Prospective comparison (200 nodules) showed that the AUC of the PKU-M model [0.871 (0.815-0.915)] was higher than that of surgeons [0.790 (0.711-0.852), 0.741 (0.662-0.804), and 0.727 (0.650-0.788)], radiologist [0.748 (0.671-0.814)], and the CADx system [0.757 (0.682-0.818)]. Furthermore, the model outperformed the clinicians with an increase of 14.3% in sensitivity and 7.8% in specificity.After its development using machine learning algorithms, validation using transnational multicentric cohorts, and prospective comparison with clinicians and the CADx system, this novel prediction model for MPNs presented solid performance as a convenient reference to help decision-making.
Targeting of promising transmembrane proteins for diagnosis and treatment of pancreatic ductal adenocarcinoma
Authors: Vida Mashayekhi, Orsola Mocellin, Marcel H.A.M. Fens, Gerard C. Krijger, Lodewijk A.A. Brosens, Sabrina Oliveira
Journal: Theranostics (2021)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer due to the relatively late diagnosis and the limited therapeutic options. Current treatment regimens mainly comprise the cytotoxic agents gemcitabine and FOLFIRINOX. These compounds have shown limited efficacy and severe side effects, highlighting the necessity for earlier detection and the development of more effective, and better-tolerated treatments. Although targeted therapies are promising for the treatment of several types of cancer, identification of suitable targets for early diagnosis and targeted therapy of PDAC is challenging. Interestingly, several transmembrane proteins are overexpressed in PDAC cells that show low expression in healthy pancreas and may therefore serve as potential targets for treatment and/or diagnostic purposes. In this review we describe the 11 most promising transmembrane proteins, carefully selected after a thorough literature search. Favorable features and potential applications of each target, as well as the results of the preclinical and clinical studies conducted in the past ten years, are discussed in detail.
L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.
Authors: Qing-lei Gao, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, John Low, Beihua Kong, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Rongyu Zang, Ding Ma
Journal: Journal of Clinical Oncology (2021)

e17526 Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib, significantly improves progression-free survival (PFS) versus placebo. This is the first study to evaluate the efficacy and tolerability of the olaparib (Lynparza), an oral PARPi, in patients with platinum-sensitive relapsed (PSR) ovarian cancer, carried out exclusively in Asia. Methods: In this open-label, single arm trial, patients with PSR high grade epithelial ovarian cancer who had received ≥2 previous lines of platinum-based chemotherapy with a response, were enrolled from 28 centres in China and Malaysia. All patients received oral olaparib (300 mg) tablet twice daily until disease progression or unacceptable toxicity. The primary endpoint was PFS assessed by investigator according to RECIST 1.1 criteria. Secondary endpoints included time to TFST, PFS2, TSST, OS, and safety endpoints included adverse events (AEs). Subgroup analysis of PFS was examined by BRCA status. Data were summarized by descriptive statistics; time-to-event endpoints were analyzed using Kaplan-Meier method. Primary analysis was performed when 60% of PFS events had been achieved. Results: Between 2018 and 2020, the 224 patients recruited into this study received oral olaparib (full analysis set). 224 patients (91.5% from China and 8.5% from Malaysia) provided BRCA mutation status by blood and tissue testing. 47.3% patients were BRCAm, 41.1% patients were gBRCAm,52.2% patients were BRCAwt and 0.4% patients were BRCA unknown. 35.7% patients had received ＞2 lines of chemotherapy. At data cut-off (Dec 25 th , 2020), 139 patients had disease progression; median PFS (mPFS) was 16.1 (95% CI 13.3-18.3) m in all patients. The mPFS was 21.2m, 21.4m and 11.0m in BRCAm, gBRCA and BRCAwt subgroups, respectively. The overall incidence of any AE and SAE was 99.1% and 25.4%, respectively. There were 9.4% patients who discontinued therapy due to the treatment related AE. The most common AEs were anemia, nausea and vomiting. Conclusions: The L-MOCA study demonstrates olaparib maintenance treatment is effective and well tolerated in Asian PSR ovarian cancer patients regardless of BRCA status. Clinical trial information: NCT03534453. [Table: see text]
Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription
Authors: Qinjunjie Chen, Haibo Wang, Zheng Li, Fengwei Li, Leilei Liang, Yiran Zou, Hao Shen, Jun Li, Yong Xia, Zhangjun Cheng, Tian Yang, Kui Wang, Feng Shen
Journal: Journal of Hepatology (2021)

Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer with high aggressiveness and extremely poor prognosis. The role of circular RNAs (circRNAs) in ICC carcinogenesis and progression remains to be determined.CircRNA microarray was performed to screen significantly upregulated circRNAs in paired ICC and non-tumor tissues. Colony formation, transwell, and xenograft models were used to examine the role of circRNAs in ICC proliferation and metastasis. RNA pulldown, mass spectrometry, chromatin immunoprecipitation, RNA-binding protein immunoprecipitation, chromatin isolation by RNA purification, electrophoretic mobility shift assay, and luciferase reporter assays were used to explore the molecular sponge role of the circRNA (via miRNA binding), and the interaction between circRNA and RNA-binding proteins.Hsa_circ_0050898, which originated from exon 1 to exon 20 of the ACTN4 gene (named circACTN4), was significantly upregulated in ICC. High circACTN4 expression was associated with enhanced tumor proliferation and metastasis in vitro and in vivo, as well as a worse prognosis following ICC resection. In addition, circACTN4 upregulated Yes-associated protein 1 (YAP1) expression by sponging miR-424-5p. More importantly, circACTN4 also recruited Y-box binding protein 1 (YBX1) to stimulate Frizzled-7 (FZD7) transcription. Furthermore, circACTN4 overexpression in ICC cells enhanced the interaction between YAP1 and β-catenin, which are the core components of the Hippo and Wnt signaling pathways, respectively.CircACTN4 was upregulated in ICC and promoted ICC proliferation and metastasis by acting as a molecular sponge of miR-424-5p, as well as by interacting with YBX1 to transcriptionally activate FZD7. These results suggest that circACTN4 is a potential prognostic marker and therapeutic target for ICC.Intrahepatic cholangiocarcinoma is a primary liver cancer associated with aggressiveness and extremely poor prognosis. It is essential for therapeutic development that we uncover relevant pathogenic pathways. Herein, we showed that a circular RNA (circACTN4) was highly expressed in intrahepatic cholangiocarcinoma and was positively associated with tumor growth and metastasis through key developmental signaling pathways. Thus, circACTN4 could be a prognostic biomarker and therapeutic target for intrahepatic cholangiocarcinoma.
Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
Authors: Gaëtan Poulen, Emilie Aloy, Claire M. Bringuier, Nadine Mestre-Francés, Emaëlle V.F. Artus, Maïda Cardoso, Jean-Christophe Perez, Christophe Goze-Bac, Hassan Boukhaddaoui, Nicolas Lonjon, Yannick N. Gerber, Florence E. Perrin
Journal: Theranostics (2021)

No curative treatment is available for any deficits induced by spinal cord injury (SCI).Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates.Methods: The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia.We orally administrated GW2580, a CSF1R inhibitor that inhibits microglia proliferation.In mice and nonhuman primates, we then analyzed treatment outcomes on locomotor function and spinal cord pathology.Finally, we used cell-specific transcriptomic analysis to uncover GW2580-induced molecular changes in microglia.Results: First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissue preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves motor function recovery, and promotes tissue protection.Finally, GW2580-treatment in mice induced down-regulation of proliferation-associated transcripts and inflammatory associated genes in microglia that may account for reduced neuroinflammation and improved functional recovery following SCI.Conclusion: Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.
Authors’ response: Sequencing bias for residue 28 of the neuraminidase of the recent highly pathogenic avian influenza virus A(H5N8)
Authors: Ivan M Susloparov, Natalia P Kolosova, Aleksey V Danilenko, Aleksandr B Ryzhikov
Journal: Eurosurveillance (2021)

Preview this article: Authors’ response: Sequencing bias for residue 28 of the neuraminidase of the recent highly pathogenic avian influenza virus A(H5N8), Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/26/36/eurosurv-26-36-5-1.gif
Effect of a Telecare Case Management Program for Older Adults Who Are Homebound During the COVID-19 Pandemic
Authors: Arkers Kwan Ching Wong, Frances Kam Yuet Wong, Karen Kit Sum Chow, Siu Man Wong, Paul Hong Lee
Journal: JAMA Network Open (2021)

Older adults who are homebound can be difficult to reach owing to their functional limitations and social distancing during the COVID-19 pandemic, leaving their health needs unrecognized at an earlier stage.To determine the effectiveness of a telecare case management program for older adults who are homebound during the COVID-19 pandemic.This randomized clinical trial was conducted among 68 older adults in Hong Kong from May 21 to July 20, 2020, with a last follow-up date of October 20, 2020. Inclusion criteria were being 60 years or older, owning a smartphone, and going outside less than once a week in the previous 6 months.Participants in the telecare group received weekly case management from a nurse supported by a social service team via telephone call and weekly video messages covering self-care topics delivered via smartphone for 3 months. Participants in the control group received monthly social telephone calls.The primary outcome was the change in general self-efficacy from before the intervention to after the intervention at 3 months. Self-efficacy was measured by the Chinese version of the 10-item, 4-point General Self-efficacy Scale, with higher scores representing higher self-efficacy levels. Analysis was performed on an intention-to-treat basis.A total of 68 participants who fulfilled the criteria were enrolled (34 in the control group and 34 in the intervention group; 56 [82.4%] were women; and mean [SD] age, 71.8 [6.1] years). At 3 months, there was no statistical difference in self-efficacy between the telecare group and the control group. Scores for self-efficacy improved in both groups (β = 1.68; 95% CI, -0.68 to 4.03; P = .16). No significant differences were found in basic and instrumental activities of daily living, depression, and use of health care services. However, the telecare group showed statistically significant interactions of group and time effects on medication adherence (β = -8.30; 95% CI, -13.14 to -3.47; P = .001) and quality of life (physical component score: β = 4.99; 95% CI, 0.29-9.69; P = .04).In this randomized clinical trial, participants who received the telecare program were statistically no different from the control group with respect to changes in self-efficacy, although scores in both groups improved. After the intervention, the telecare group had better medication adherence and quality of life than the control group, although the small sample size may limit generalizability. A large-scale study is needed to confirm these results.ClinicalTrials.gov Identifier: NCT04304989.
Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer
Authors: Alain R. Thierry, Brice Pastor, Ekaterina Pisareva, Francois Ghiringhelli, Olivier Bouché, Christelle De La Fouchardière, Julie Vanbockstael, Denis Smith, Eric François, Mélanie Dos Santos, Damien Botsen, Stephen Ellis, Marianne Fonck, Thierry André, Emmanuel Guardiola, Faiza Khemissa, Benjamin Linot, J. Martin-Babau, Yves Rinaldi, Eric Assenat, Lea Clavel, Sophie Dominguez, Celine Gavoille, David Sefrioui, Veronica Pezzella, Caroline Mollevi, Marc Ychou, Thibault Mazard
Journal: JAMA Network Open (2021)

The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management.
A genome-wide association meta-analysis identifies new eosinophilic esophagitis loci
Authors: Xiao Chang, Michael March, Frank Mentch, Kenny Nguyen, Joseph Glessner, Huiqi Qu, Yichuan Liu, Glen Furuta, Seema Aceves, Nirmala Gonsalves, Kari Nadeau, Antonella Cianferoni, Jonathan Spergel, Patrick Sleiman, Hakon Hakonarson
Journal: Journal of Allergy and Clinical Immunology (2021)
A Tale of 2 Epidemics
Authors: Melissa Sutton
Journal: JAMA Internal Medicine (2021)

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Abstract 2745: Diagnostic Algorithm Using Office and Home Blood Pressures to Exclude White Coat Hypertension
Authors: Sujith Kuruvilla, Kiran Nallella, Anne Mani, Geetha Pinto, Daichi Shimbo, Joseph Schwartz, William Gerin, Thomas Pickering
Journal: Circulation (2007)

Background: It has been suggested that the diagnosis of sustained hypertension (SHTN), defined as clinic blood pressure (CBP) ≥140 or ≥90 mmHg plus a daytime ambulatory BP (ABP) ≥135 or ≥85 mmHg can be optimized by taking home BP (HBP) in those with high CBP, and obtaining ABP only if HBP is normal (&lt;135/85). This study tested whether a higher cutoff value for CBP using Receiver Operator Curves (ROC) based on systolic and diastolic CBP for the diagnosis of SHT (95% specificity) would improve the efficiency of the algorithm for diagnosing SHT and reduce the number of subjects requiring HBP and ABP to establish the diagnosis. Methods and Results: We assessed CBP, ABP and HBP in 229 normotensive and untreated hypertensive subjects. CBP was high in 84 subjects. Of these, 74 (88%) had SHTN, and 10 (12%) white coat HTN (WCH- high CBP but normal ABP). With HBP, 69 (82%) had high HBP, and of these 63 (91%) had SHT. Based on traditional algorithm, 15 subjects require ABP monitoring to diagnose SHT, which would be confirmed in 11. Using the ROC algorithm, 55 of 84 subjects (50 SHT; 5 WCH) would be classified as ``hypertensive” (at or above the CBP cut-off); 29 subjects would fall below the cut-off and require HBP (with 24 having SHT); 5 subjects would require ABP. The sensitivity and specificity for diagnosing SHT were 100% and 40% for the traditional algorithm, and 100% and 20% for the ROC algorithm. Conclusions: The ROC algorithm is as effective as the traditional algorithm for diagnosing SHT, and requires fewer HBPs (29 vs. 84) and ABPs (5 vs. 15). Therefore, this algorithm may have widespread indications for the screening of ambulatory hypertension.
心拍出量に対するインピーダンス・カルジオグラフィ 手首-足首電極配置の信頼性
Authors: Paredes Oscar Luis, Shite Junya, Shinke Toshiro, Watanabe Satoshi, Otake Hiromasa, Matsumoto Daisuke, Imuro Yusuke, Ogasawara Daisuke, Sawada Takahiro, Yokoyama Mitsuhiro
Journal: Circulation (2006)
AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update
Authors: Sidney C. Smith, Jerilyn Allen, Steven N. Blair, Robert O. Bonow, Lawrence M. Brass, Gregg C. Fonarow, Scott M. Grundy, Loren Hiratzka, Daniel Jones, Harlan M. Krumholz, Lori Mosca, Richard C. Pasternak, Thomas Pearson, Marc A. Pfeffer, Kathryn A. Taubert
Journal: Journal of the American College of Cardiology (2006)