tbuckley/cabot-search huggingface dataset:
Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer
Authors: Jiaqi Liu, Hengqiang Zhao, Yukuan Huang, Shouping Xu, Yan Zhou, Wei Zhang, Jiaqi Li, Yue Ming, Xinyu Wang, Sen Zhao, Kai Li, Xiying Dong, Yunlong Ma, Tianyi Qian, Xinyi Chen, Zeyu Xing, Yan Zhang, Hongyan Chen, Zhihua Liu, Da Pang, Meng Zhou, Zhihong Wu, Xiaowo Wang, Xiang Wang, Nan Wu, Jianzhong Su
Journal: Molecular Cancer (2021)

Abstract Early detection is crucial to improve breast cancer (BC) patients’ outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78–0.79 to 0.93–0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.
A standard calculation methodology for human doubly labeled water studies
Authors: John R. Speakman, Yosuke Yamada, Hiroyuki Sagayama, Elena S.F. Berman, Philip N. Ainslie, Lene F. Andersen, Liam J. Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E. Blaak, Stephane Blanc, Alberto G. Bonomi, Carlijn V.C. Bouten, Pascal Bovet, Maciej S. Buchowski, Nancy F. Butte, Stefan G.J.A. Camps, Graeme L. Close, Jamie A. Cooper, Seth A. Creasy, Sai Krupa Das, Richard Cooper, Lara R. Dugas, Cara B. Ebbeling, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W. Fudge, Annelies H. Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B. Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M. Joosen, Peter Katzmarzyk, Kitty P. Kempen, Misaka Kimura, William E. Kraus, Robert F. Kushner, Estelle V. Lambert, William R. Leonard, Nader Lessan, David S. Ludwig, Corby K. Martin, Anine C. Medin, Erwin P. Meijer, James C. Morehen, James P. Morton, Marian L. Neuhouser, Theresa A. Nicklas, Robert M. Ojiambo, Kirsi H. Pietiläinen, Yannis P. Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L. Prentice, Roberto A. Rabinovich, Susan B. Racette, David A. Raichlen, Eric Ravussin, Rebecca M. Reynolds, Susan B. Roberts, Albertine J. Schuit, Anders M. Sjödin, Eric Stice, Samuel S. Urlacher, Giulio Valenti, Ludo M. Van Etten, Edgar A. Van Mil, Jonathan C.K. Wells, George Wilson, Brian M. Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J. Murphy-Alford, Cornelia U. Loechl, Edward L. Melanson, Amy H. Luke, Herman Pontzer, Jennifer Rood, Dale A. Schoeller, Klaas R. Westerterp, William W. Wong
Journal: Cell Reports Medicine (2021)

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.
SEPNZ warm UP BJSM tendinopathy, back pain and OA: sorting the evidence
Authors: Blair Jarratt
Journal: British Journal of Sports Medicine (2021)

While the waves of the global pandemic continue to pound the borders of New Zealand—we are one of the luckiest countries in the world to live a relatively ‘normal life’ with community eradication of the virus leaving this small drop in the Pacific Ocean the envy of many of countries. Our children know of only minimal ‘lockdown’ periods, so it is with the greatest sympathy that I write in this international journal to others that are still severely restricted. New Zealand has been able to come out of the lockdown with an explosion of sports, and we watch and wait for our international friends to have similar freedom and the dream of Olympic games again. The front cover of this BJSM was from the recent Redbull ignite rugby union sevens tournament played in the beachside town on Mount Maunganui. Eighth men and eight women’s teams united together to find hidden sevens talent from New Zealand in a weekend competition which was a feast of athleticism, energy and colour.

Spectators strolled freely …
Adaptive Therapy and the Cost of Drug-Resistant Mutants
Authors: Dominik Wodarz
Journal: Cancer Research (2021)

The concept of adaptive cancer therapy proposes that the use of drugs at less than maximum tolerated dose can provide clinical benefits by allowing persisting drug-sensitive cells to competitively suppress drug-resistant cells; this can delay the outgrowth of these cell clones. The adaptive therapy concept has been developed with mathematical models and has subsequently been explored in clinical trials with promising results. In studies performed so far, a fitness cost of drug-resistant cells has been invoked for this treatment approach to be beneficial. In new work, it is shown that a clinical benefit can be achieved even in the absence of a fitness cost for resistant cells, which broadens the applicability of adaptive therapy.See related article by Strobl et al., p. 1135.
Recommendations for shaping the future of low back pain prevention research
Authors: Giovanni Ferreira, Mark Hancock
Journal: British Journal of Sports Medicine (2021)

Prevention is a fundamental tenet of medicine but has been largely ignored in low back pain (LBP), where clinical care and research have focused on the treatment of those currently experiencing an episode of LBP. For example, while a recent review of LBP prevention included 40 trials,1 there are several thousand trials evaluating treatments for LBP. Clinical practice guidelines are largely silent on the issue of prevention of LBP, providing little guidance to clinicians.

It is now recognised that LBP is typically an episodic condition, with many people having a symptom trajectory that includes periods of recovery interspersed with frequent recurrences or ongoing low levels of pain with flare-ups.2 Much of the LBP burden, therefore, results from recurrences and flare-ups. Given this, we believe that the rationale and evidence for a greater focus on secondary or tertiary prevention are overwhelming. In this editorial, we outline recommendations for shaping future LBP prevention research to ensure the best use of research resources.

Preventing a first-ever LBP episode (primary …
Abstract PS3-30: Peri-operative diagnostic accuracy of magnetic resonance imaging and ultrasonography in breast cancer: A meta-analysis
Authors: Jason A Mouabbi, Zeyad Sako, Ahmed Abdalla, Tarik Hadid, Mothaffar F Rimawi
Journal: Cancer Research (2021)

Abstract Background: Accurate determination of the extent of tumor is essential when a breast-conserving therapy (BCT) is considered. Due to its high sensitivity, breast magnetic resonance imaging (MRI) is increasingly used for the accurate diagnosis and surgical planning of breast cancers. However, a recent meta-analysis showed that peri-operative evaluation with MRI leads to higher mastectomy rates in patients that could have potentially underwent BCT. Objective: The aim of this study is to compare the pre-operative diagnostic accuracy of MRI to ultrasonography (US) in breast cancer. Methods: We identified eligible studies that examined peri-operative tumor size using MRI and US and compared it to its pathological counterpart. Databases of PubMed, Embase and Google Scholar were reviewed. To keep the study homogenous, only studies evaluating invasive ductal carcinoma were included and studies evaluating ductal carcinoma in-situ and lobular ductal carcinoma were excluded. An accurate tumor estimation by MRI or US was defined as within 10 mm from the pathological tumor size. An overestimation was defined as imaging tumor size more than 10 mm larger than its pathological counterpart. Odds ratios (ORs) were calculated using a random-effects model with 2-sided p-value of 0.05 set as the significance level. Results: Twenty-five studies with 3,562 patients were included in the final analysis. MRI was 1.6-fold more accurate than US in preoperative diagnostic evaluation of breast cancer (OR 1.65; 95% confidence interval (CI) 1.24-2.18, p-value &amp;lt;0.00001). However, MRI was 20 folds more likely to overestimate the tumor size compared to US (OR 20.25; 95% CI 9.46-43.33; p-value &amp;lt;0.0001). Conclusion: MRI remains the most accurate modality for the diagnosis of breast cancer. However, it is highly likely to overestimate tumor size and can result in unnecessary mastectomies. US is a reasonable diagnostic option for most patients with breast cancer. Citation Format: Jason A Mouabbi, Zeyad Sako, Ahmed Abdalla, Tarik Hadid, Mothaffar F Rimawi. Peri-operative diagnostic accuracy of magnetic resonance imaging and ultrasonography in breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-30.
Bending the Curve in Cardiovascular Disease Mortality
Authors: David Calvin Goff, Sadiya Sana Khan, Donald Lloyd-Jones, Donna K. Arnett, Mercedes R. Carnethon, Darwin R. Labarthe, Matthew Shane Loop, Russell V. Luepker, Michael V. McConnell, George A. Mensah, Mahasin S. Mujahid, Martin Enrique O’Flaherty, Dorairaj Prabhakaran, Véronique Roger, Wayne D. Rosamond, Stephen Sidney, Gina S. Wei, Janet S. Wright
Journal: Circulation (2021)

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the “Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40” symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.
Abstract PS17-55: Reactive oxygen species scavengers in triple negative breast cancer
Authors: Francois P Duhoux, Tânia Capelôa, Pierre Sonveaux, Francoise Derouane
Journal: Cancer Research (2021)

Abstract Reactive oxygen species (ROS) are well known to play important roles in cancer. In particular, ROS of mitochondrial origin (mtROS) promote DNA mutations and cell death when produced at high levels, but rather stimulate autophagy and metastatic spread when produced at subcytotoxic levels [1]. Multiple metabolic pathways and oncogenic regulators linked to ROS have been studied in cancer cells, including MAPK/ERK, PI3K/AKT, PTEN, PKD, BREF2, HIF-1, NF-κB and p53 [2]. Abnormalities in these pathways can contribute to tumor development.By producing mtROS, mitochondria control and could even trigger metastatic spread, meaning that the use of specific mitochondria-targeted superoxide inhibitors/scavengers, such as mitoquinol mesylate (MitoQ), could reduce and/or prevent metastatic dissemination. This has been studied and reported with the use of MitoTempo, which prevents metastasis of naturally metastatic MDA-MB-231 human breast cancer cells implanted in mice [1]. Here, we show that MitoQ impairs MDA-MB-231 and SkBr3 human breast cancer cell migration and invasion in vitro, and MDA-MB-231 metastasis to the lungs in mice in vivo. In metastatic take assays, tail vein-injected MDA-MB-231 cells pretreated with MitoQ formed significantly less metastases after 4 weeks compared to vehicle. In spontaneous metastatic assays, mice bearing orthotopic MDA-MB-231 tumors were treated with ± 20 mg/kg MitoQ (per os) for 6 weeks. Primary tumors were surgically removed to allow metastatic outgrowth. In this model, MitoQ decreased primary tumor recurrence as well as the number of lung micro-metastases. Additionally, RNAseq studies in two human breast cancer cell lines identified that MitoQ significantly modulated a common set of metabolic genes in vitro and in vivo. They can be used as biomarkers of response. These results, together with a successful Phase I clinical trial and the fact that MitoQ does not interfere with the cytotoxic effects of chemotherapy, confirm that MitoQ is a potential candidate to be clinically tested in triple negative breast cancer patients. References: 1.Porporato PE et al. A mitochondrial switch promotes tumor metastasis. Cell Rep. 2014;8(3):754-66.2.Payen VL, et al. Pro- and antitumor effects of mitochondrial reactive oxygen species. Cancer Metastasis Rev. 2019;38(1-2):189-203. Citation Format: Francois P Duhoux, Tânia Capelôa, Pierre Sonveaux, Francoise Derouane. Reactive oxygen species scavengers in triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-55.
Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time
Authors: Elaine Ku, Charles E. McCulloch, Deborah B. Adey, Libo Li, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Under current US national policy, determining a patient’s eligibility for kidney transplantation waitlist registration requires the patient’s GFR to be ≤20 ml/min. Because disease progression is faster for Black versus White patients, this policy may contribute to racial disparities in accruable time on the waitlist before dialysis initiation. The authors used models to determine the association between race and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m 2 , finding this time was shorter for Black versus White patients. They then estimated that allowing registration of Black patients on the transplant waitlist at higher levels of kidney function (as early as an eGFR of 24–25 ml/min per 1.73 m 2 ) had the potential to reduce the observed disparities in accruable wait time. Background Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. Methods We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFR cr ), cystatin C (eGFR cys ), or both (eGFR cr-cys ). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m 2 . We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. Results By eGFR cr , 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m 2 and ESKD was 32% shorter for Blacks versus Whites. By eGFR cys , 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFR cr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24–25 ml/min per 1.73 m 2 might improve racial equity in accruable wait time before ESKD onset. Conclusions Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.
Response to Concomitant Enzalutamide and 177Lu-PSMA-617 Radioligand Therapy in ATM-Mutated Metastatic Castration Resistant Prostate Cancer
Authors: Swayamjeet Satapathy, Chandan Krushna Das, Ashwin Singh Parihar, Ashwani Sood, Bhagwant R. Mittal
Journal: Clinical Nuclear Medicine (2021)

Radioligand therapy with 177Lu-PSMA-617 has emerged as a promising treatment modality for patients with mCRPC (metastatic castration resistant prostate cancer). However, genomic defects in DNA damage repair mechanisms have been proposed to affect the radiosensitivity of prostate cancers. Patients harboring such deleterious mutations are, thus, unlikely to respond to 177Lu-PSMA-617 alone and would need a more tailored therapeutic approach. We report the case of a 68-year-old man with ATM mutation-positive mCRPC who showed exceptional response to concomitant administration of enzalutamide with 177Lu-PSMA-617.
Body ownership as a proxy for individual and social separation and connection
Authors: Marina Scattolin, Maria Serena Panasiti, Salvatore Maria Aglioti
Journal: Behavioral and Brain Sciences (2021)

Abstract Lee and Schwartz procedures of separation offer a much needed interpretation of the literature on moral cleansing. However, body ownership as a grounded mechanism of separation and connection has been neglected. We argue that embodiment may be employed to connect the self to desirable aspects of cognitive and emotional interactions and disembodiment to disconnect from undesirable elements.
Incidence of non-B subtypes of HIV-1 in Galicia, Spain: high frequency and diversity of HIV-1 among men who have sex with men
Authors: M T Cuevas, A Fernández-García, A Sánchez-García, M González-Galeano, M Pinilla, M Sánchez-Martínez, V García, L Pérez-Álvarez, Collective Study group of HIV-  newly diagnose
Journal: Eurosurveillance (2009)

An increase in HIV transmission among men who have sex with men (MSM) has been reported in eight regions of Spain from 2003 to 2007. In order to study the incidence of HIV-1 genetic forms in Galicia, northwest of Spain, in particular the spread of HIV-1 variants among MSM, 93 newly diagnosed HIV-1 patients, including those with acute and recently acquired infections, were studied for a year from August 2008 to August 2009. Thirty eight (41%) were MSM. Of them, nine (24%) were infected by non-B viruses, including seven different genetic forms. The analysis of transmission clusters showed that 23 (60%) MSM grouped in different clusters and mostly in large clusters. Resistance mutations were detected in six (16%) MSM.
Risk of Spinal Hematoma After Lumbar Puncture—Reply
Authors: Jacob Bodilsen, Henrik Nielsen
Journal: JAMA (2021)

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