tbuckley/cabot-search huggingface dataset:
Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients.
Authors: Tenna V Henriksen, Noelia Tarazona, Thomas Reinert, Juan Antonio Carbonell-Asins, Derrick Renner, Shruti Sharma, Desamparados Roda, Marisol Huerta, Susana Roselló, Lene H. Iversen, Kåre Andersson Gotschalck, Anders Husted Madsen, Per Vadgaard Andersen, Ole Thorlacius-Ussing, Uffe S. Løve, Himanshu Sethi, Alexey Aleshin, Andres Cervantes, Claus Lindbjerg Andersen
Journal: Journal of Clinical Oncology (2021)

11 Background: Timely detection of recurrence, as well as identification of patients at high risk of recurrence after surgery and after completion of adjuvant therapy, are major challenges in the treatment of colorectal cancer (CRC). Postsurgical circulating tumor DNA (ctDNA) analysis is a promising tool for the identification of patients with minimal residual disease (MRD) and a high risk of recurrence. The objective of this prospective, multicenter study was to determine whether serial postsurgical ctDNA analysis could identify the patients at high risk of recurrence, provide an assessment of adjuvant therapy efficacy and detect relapse earlier than standard-of-care radiological imaging. Methods: The cohort comprises 265 stage I-III CRC patients, the to-date largest cohort assessed for ctDNA. All patients had the tumor resected and a subset of 62.6% (166 /265) was additionally treated with ACT. Plasma samples (n = 1503) were collected at various time points for a median follow-up of 28.4 months (range: 1.2-51.0 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic single nucleotide variants (SNVs) were identified. Personalized multiplex PCR assays were designed to track tumor-specific SNVs (Signatera, bespoke mPCR NGS assay) in each patient’s plasma sample. Results: Postoperative ctDNA status prior to ACT was assessed in 218 patients, of which 9.17% (20/218) were identified to be MRD-positive and 75% (15/20) eventually relapsed. The remaining 25% (5/20) of MRD-positive patients that did not relapse, received ACT. In contrast, only 13.6% (27/198) of MRD-negative cases relapsed (HR: 11: 95% CI: 5.7-20; p &lt; 0.001). Longitudinal ctDNA-positive status, post-definitive therapy (n = 202) was associated with a HR of 36 (95% CI: 16-81; p &lt; 0.001). For a subset of 155 patients postoperative CEA and ctDNA measurements were compared, wherein, ctDNA-positive status was found to be significantly associated with RFS (HR, 7.1; 95% CI, 3.4-15; P &lt; 0.001) compared to CEA (HR, 1.2; 95% CI, 0.46-3.1; P = 0.73). Serial ctDNA analysis detected MRD up to a median of 8 months (0.56 - 21.6 months) ahead of radiologic relapse. Conclusion: Postoperative ctDNA positive status was associated with markedly reduced RFS compared to CEA. The study also shows that effective therapy can be curative in a portion of MRD-positive patients. In a longitudinal setting, ctDNA analysis predicted the risk of recurrence and is a more reliable biomarker for treatment response monitoring.
Climate Change in the Supreme Court
Authors: Lisa Heinzerling
Journal: New England Journal of Medicine (2022)

In Massachusetts v. Environmental Protection Agency, the Supreme Court confronted the issue of climate change for the first time. The Court held that the Clean Air Act gives the Environmental Protection Agency the authority to regulate greenhouse gases and that the agency may not decline to exercise this authority based either on factors not present in the statute or inconclusive gestures toward uncertainty in the science of climate change. I had the privilege of serving as the lead author of the winning briefs in this case. This Article provides an insider's perspective on the choices that went into bringing and briefing the case. This Article is an edited version of the 20th Annual Natural Resources Law Institute Distinguished Lecture, delivered in the fall of 2007 at Lewis & Clark Law School.
Increase in suicide following an initial decline during the COVID-19 pandemic in Japan
Authors: Takanao Tanaka, Shohei Okamoto
Journal: Nature Human Behaviour (2021)

There is increasing concern that the coronavirus disease 2019 (COVID-19) pandemic could harm psychological health and exacerbate suicide risk. Here, based on month-level records of suicides covering the entire Japanese population in 1,848 administrative units, we assessed whether suicide mortality changed during the pandemic. Using difference-in-difference estimation, we found that monthly suicide rates declined by 14% during the first 5 months of the pandemic (February to June 2020). This could be due to a number of complex reasons, including the government's generous subsidies, reduced working hours and school closure. By contrast, monthly suicide rates increased by 16% during the second wave (July to October 2020), with a larger increase among females (37%) and children and adolescents (49%). Although adverse impacts of the COVID-19 pandemic may remain in the long term, its modifiers (such as government subsidies) may not be sustained. Thus, effective suicide prevention-particularly among vulnerable populations-should be an important public health consideration.
Behavior is multiply determined, and perception has multiple components: The case of moral perception
Authors: Ana P Gantman, Jay J Van Bavel
Journal: Behavioral and Brain Sciences (2016)

We introduce two propositions for understanding top-down effects on perception. First, perception is not a unitary construct but is composed of multiple components. Second, behavior is multiply determined by cognitive processes. We call for a process-oriented research approach to perception and use our own research on moral perception as a "case study of case studies" to examine these issues.
BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology
Authors: Camille Bigenwald, Jessica Le Berichel, C. Matthias Wilk, Rikhia Chakraborty, Steven T. Chen, Alexandra Tabachnikova, Rebecca Mancusi, Harshal Abhyankar, Maria Casanova-Acebes, Ilaria Laface, Guray Akturk, Jenielle Jobson, Zoi Karoulia, Jerome C. Martin, John Grout, Anahita Rafiei, Howard Lin, Markus G. Manz, Alessia Baccarini, Poulikos I. Poulikakos, Brian D. Brown, Sacha Gnjatic, Amaia Lujambio, Kenneth L. McClain, Jennifer Picarsic, Carl E. Allen, Miriam Merad
Journal: Nature Medicine (2021)
Covid-19: Reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected Elisabeth MahaseConcerns have been raised over how much protection a single dose of the Pfizer BioNTech covid-19 vaccine provides, following reports from Israel that it is much lower than expected.4
Trends in Oncology Clinical Trials Launched Before and During the COVID-19 Pandemic
Authors: Elizabeth B. Lamont, Sheila S. Diamond, Ron G. Katriel, Lisa L. Ensign, Jingshu Liu, Emelly Rusli, G. Caleb Alexander
Journal: JAMA Network Open (2021)

This cohort study evaluates the association of the coronavirus disease 2019 (COVID-19) pandemic with clinical research and development for cancer by studying the initiation of oncology clinical trials over time.
Cultural competence in vaccine rollout: migrants would face difficulties accessing covid-19 vaccines
Authors: Lauren Z Waterman
Journal: BMJ (2021)

Hanif and colleagues highlight the importance of cultural competence in covid-19 vaccine rollout so that ethnic minority communities are not left out.1 Particular attention should be paid to asylum seekers and undocumented migrants. These populations have been disproportionately affected by the pandemic, with potentially significant barriers to accessing vaccines.

A rapid evidence review relating to the negative social and psychological impacts of the pandemic, …
Abstract 18014: Did Patients With Peripheral Artery Disease Benefit From the Survival Improvement After Myocardial Infarction? Insights From the FAST-MI Program, 1995-2010
Authors: Victor Aboyans, Etienne Puymirat, Francois Schiele, Meyer Elbaz, Simon Cattan, Didier Blanchard, Parick Henry, Jean Ferrières, Tabassome Simon, Nicolas Danchin
Journal: Circulation (2015)

Introduction: Patients with peripheral artery disease (PAD) are at risk for acute myocardial infarction (AMI). The prognosis of patients after AMI has substantially improved over the last 20 years. Whether survival has similarly improved in patients with or without PAD is unknown. Methods: We compared the management and mortality after AMI according to clinical PAD status in 4 French nationwide registries conducted with similar methodology in 1995, 2000, 2005 and 2010. Each included during one month all patients admitted to cardiology departments in general, academic or private hospitals for AMI with symptoms onset ≤ 48 hours. Results: Among the 10,610 patients, 962 (9.1%) had PAD. PAD remained constant in NSTEMI patients (12%), while it decreased from 9.7% to 4.8% among STEMI patients. Median age increased in PAD patients (1995 vs 2010: 73 vs 75 years, P&lt;0.05) but decreased in no-PAD patients (65 to 63 years, P&lt;0.04). Women’s rates remained stable (PAD: 26 to 22%, no-PAD 29 to 27%). High cholesterol, obesity, diabetes, and hypertension rates increased significantly, irrespective of PAD status. Smoking rates decreased in PAD patients (29% to 23%, P=0.02), but increased in no-PAD patients (31 to 35%, P=0.02). The rates of early PCI (&lt;72 hours) increased (PAD: 10% to 48%; no-PAD: 15 to 72%); so did the early use of antiplatelet drugs (PAD: 84% to 98 %; no-PAD: 92 to 98%), ACE-I or ARBs (PAD: 45 to 56%; no-PAD: 46 to 64%), beta-blockers (PAD: 48 to 71%; no-PAD: 66 to 80%) and statins (PAD: 10% to 85%; no-PAD: 10 to 88%). In PAD patients, 30-day mortality decreased from 23.5% to 5.3% (HR 2010 vs 1995, adjusted for baseline characteristics: 0.23, 0.12-0.43). Their 1-year mortality decreased from 33 to 23% (HR 0.60, 0.41-0.88), but among 30-day survivors, no favorable trend was found for 1-year mortality (adjusted HR 2010 vs 1995: 1.54, 0.87-2.71). In no-PAD patients, adjusted HR for 30-day death (2010 vs 1995) was 0.33, (0.26-0.43), and 1-year survival also improved among 30-day survivors (adjusted HR 0.65, 0.50-0.85). Conclusion: After AMI, early survival has considerably increased in PAD patients as for no-PAD patients. However, no further survival improvement has been found in PAD patients beyond the 30 days, emphasizing the need for stronger secondary prevention.
Factors associated with long-term survival in patients with early-onset and standard-onset colorectal cancer.
Authors: Riya Jayesh Patel, Michael Lyudmer, Adel Chergui, Seda Serra Tolu, Devika Rao, Andreas Kaubisch, Jennifer W. Chuy, Tarek N. Elrafei, Ana Acuna-Villaorduna, Sanjay Goel
Journal: Journal of Clinical Oncology (2021)

141 Background: Differences in incidence, clinical features, and survival between early-onset (EO) and standard-onset (SO) colorectal cancer (CRC) are well-established. Factors associated with longer survival have not been reported. We aim to determine clinical and treatment factors associated with longer survival in patients (pts) with metastatic EO and SO CRC. Methods: Pts with metastatic CRC diagnosed between 2010-2019 at two NYC hospitals were identified by tumor registry and classified as EO (diagnosis at &lt; 50 years) or SO (diagnosis at ≥ 50 years). Median overall survival (OS) was calculated for each group using Kaplan Meier curves. Long-term survival was defined as OS &gt; 2 years (EO-CTC median OS). Data was collected by chart review and compared between short vs long-term survivors in EO and SO CRC pts independently. Stata v15 was used for statistical analysis. Results: Of 646 pts, 144 (22.3%) had EO and 502 (77.7%) had SO. High grade tumors were more likely in EO (33.3% vs 24%, OR: 1.59, p = 0.04) than SO; whereas no differences were seen in gender, sidedness, KRAS mutation or chemotherapy. Biologics were used more frequently in EO than SO (OR = 1.7; p = 0.008]. Median OS was 2.1 and 1.9 years in EO and SO. There were 53 (36.8%) and 175 (35.1%) long-term survivors in EO and SO groups. In pts with SO, metastasectomy, irinotecan-based chemotherapy and use of biologics were significantly associated with long-term survival, whereas metastasectomy was the only associated factor in pts with EO. Conclusions: Metastatectomy was the only factor associated with longer survival in both EO and SO groups. Other clinical/pathological and treatment-related factors associated with long-term survival among SO-CRC were not associated with long-term survival among EO-CRC patients. [Table: see text]
Relationship of HER2 alteration and MSI status in colorectal adenocarcinoma.
Authors: Miao-zhen Qiu, Cai-Yun He, Rui-hua Xu
Journal: Journal of Clinical Oncology (2021)

121 Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with MSI-H is an open question. Methods: From February 2017 to February 2020, CRC patients who received tumor specimens next-generation sequencing and detail record of clinic-pathologic information were enrolled. HER2 alteration and its relationship with MSI-H were analyzed. Results: There were totally 55 patients (7.5%) with HER2 alteration including 29 (4.0%) HER2 somatic mutations, 24 (3.3%) HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. For HER2 mutated cases, 48.3% were MSI-H, while none of HER2 amplification cases were MSI-H. MSI-H was found in 5.2% in our cohort and 36.8% MSI-H patients were HER2 mutated. MSI-H had less frequency of lung metastasis. The mPFS for first line chemotherapy was significantly higher in MSS cases than in MSI-H cases, 11.5 months vs 3.5 months, P = 0.032. MSI-H patients with HER2 mutation had significantly worse mPFS for PD-1 antibody than those without HER2 alteration, P = 0.036. Conclusions: High MSI-H rate is found in HER2 mutated cases but no MSI-H in HER2 amplification cases. MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without.
SAT0219 Infectious osteitis pubis. a report of 20 cases
Authors: D Wendling, A Lohse, E Toussirot
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteitis pubis covers several different entities and may lead to nosologic confusion. Infectious osteitis pubis (IOP) should be used when underlying infection is found. <h3>Objectives</h3> To analyse the main characteristics of IOP in a monocenter series. <h3>Methods</h3> Retrospective study about IOP with analysis of clinical, biological, imaging, bacteriological and pathological features. Inclusion criteria: osteitis pubis with favourable outcome under antibiotics. <h3>Results</h3> Twenty cases were analysed; 13 men,7 women; aged 16–77 years. IOP followed surgical procedure of the pelvis or urinary tract (8/20), was post-traumatic (2/20), regional infection related (3/20), or of unknown origin (7/20). Two cases of diabetes and one chronic steroid treatment were present. Pain was constant, with a delay in diagnosis of over 1 month. Elevated ESR(15/20), hyperleukocytosis (6/20), positive cultures of blood (3) or urine (4) were found. X-rays modifications were constant. Cultures of suppurative scars were positive in 4 cases, whereas cultures of pubis biopsies were positive in 1 out of 9 cases. Mononuclear subacute osteomyelitis was found histologically in 5/9 biopsies, without suppurative or necrotic changes. Outcome was favourable in all cases under antibiotics in a period of 1 to 12 months. Spine or sacro-iliac extension occured in 3 cases. <h3>Conclusion</h3> IOP should be considered as a septic arthritis to reduce the delay in diagnosis and in instauration of targeted antibiotherapy.
Shared Health Governance
Authors: Jennifer Prah Ruger
Journal: The American Journal of Bioethics (2011)

Health and Social Justice (Ruger 2009a ) developed the "health capability paradigm," a conception of justice and health in domestic societies. This idea undergirds an alternative framework of social cooperation called "shared health governance" (SHG). SHG puts forth a set of moral responsibilities, motivational aspirations, and institutional arrangements, and apportions roles for implementation in striving for health justice. This article develops further the SHG framework and explains its importance and implications for governing health domestically.
THU0645-HPR ULTRASOUND EDUCATION FOR RHEUMATOLOGIST IN RUSSIA: REALITIES AND WHAT IS NEEDED TO IMPROVE.
Authors: N. Dudnikova, A. Mikhailova, O. Alekseeva, A. Demina, A. Volkov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Musculoskeletal ultrasonography (MSUS) is a valuable imaging modality for the practicing rheumatologist. In everyday practice, physical examination is limited by its sensitivity and subjectivity of assessment. MSUS is inexpensive, available, and allows repeat examination as soon as necessary. Thus, MSUS has become the “third eye” of the rheumatologist, in that it allows more detailed examination of muscles, bones, and joints, just as the stethoscope provides further details about the respiratory and cardiovascular systems. Most ultrasound examinations in Russia, including abdominal and vascular sonography, echocardiography, are conducted by trained physician - radiologist, called “ultrasonography specialists”. Nevertheless, it is very difficult to perform MSUS, mainly because standardized ultrasound protocols fore same region are different for various diseases and often do not provide physicians with the information they need, and also may been mistake. The conduct of MSUS by rheumatologists themselves is limited to the need for 4-month radiology (ultrasound) certification. However, the number of rheumatologists conducting MSUS themselves is increasing. Training week small group courses are provided by VA Nasonova Research Institute of Rheumatology for the practicing rheumatologist and other physicians. Objectives: We analyzed the training and awareness of the rheumatologists and radiologists in MSUS, as well as their commitment for participation in our courses. Methods: We studied a one and a half-year period, from June 2018 to December 2019. During this time, 57 applications were submitted to participate in the courses. All participants who arrived were tested before starting the course. Test included 40 general questions about MSUS. Test results as well as commitment to training were analyzed in two groups: rheumatologists and radiologists. Nonparametric statistics were used for data processing. Results: Among 57 applications submitted for the courses, 26 were from rheumatologists and 31 from radiologists, but the courses were attended by 13 rheumatologists and 26 radiologists (68%). Thus, commitment was reliably higher in radiologists (84%) than in rheumatologists (50%). Fisher’s methods show high statistically significance (Χ 2 = 7,51, p = 0,006). Although the test focused on ultrasound, it was surprise for us that the median percentage of correct answers was higher in rheumatologists - 64 (54; 80)%, than radiologists (“ultrasonography specialists”) 48 (40; 62)%. Difference also were significantly (p = 0,04). Conclusion: Thus, despite better preparedness of rheumatologist, motivation to study MSUS prevails among radiologists. It is necessary to actively introduce MSUS into general rheumatologic educational programs in order to motivate rheumatologists to study MSUS. Changes in professional standard will also encourage wide use of MSUS by rheumatologists. Disclosure of Interests: None declared
Sixty seconds on . . . covid influencers
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Pardon?Get with the programme, Grandad.Influencers are very . . .influential these days.And they don't just encourage people on social media to buy things they don't need. Really? What else do they do?Help spearhead public health campaigns, it seems.The fact checking organisation Full Fact 1 did some digging and found that the government paid £63 000 (€71 000; $85 000) to 42 social media influencers to promote the national NHS test and trace service last year.This equates to roughly £1500 per influencer on average.
Query theory: Knowing what we want by arguing with ourselves
Authors: Elke U. Weber, Eric J. Johnson
Journal: Behavioral and Brain Sciences (2011)

Abstract Mercier and Sperber (M&amp;S) argue that reasoning is social and argumentative, and that this explains many apparently irrational judgment phenomena. We look at the relationship between interpersonal and intrapersonal argumentation and discuss parallels and differences from the perspective of query theory , a memory-based model of constructive preferences. We suggest an important goal is to integrate models across inference and preference.
Patients' reliance on non-nephrologists for chronic kidney disease treatment and advice
Authors: Tyler Barrett, PL Ephraim, JA Greene, S Peskoe, JF Pendergast, C Hauer, TS Strigo, F Hills-Briggs, T Browne, G Jackson, RC Greer, CJ Diamantidis, LE Boulware
Journal: Journal of the American Society of Nephrology (2019)
GTB-PPI: Predict Protein–Protein Interactions Based on L1-Regularized Logistic Regression and Gradient Tree Boosting
Authors: Bin Yu, Cheng Chen, Hongyan Zhou, Bingqiang Liu, Qin Ma
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Protein–protein interactions (PPIs) are of great importance to understand genetic mechanisms, delineate disease pathogenesis, and guide drug design. With the increase of PPI data and development of machine learning technologies, prediction and identification of PPIs have become a research hotspot in proteomics. In this study, we propose a new prediction pipeline for PPIs based on gradient tree boosting (GTB). First, the initial feature vector is extracted by fusing pseudo amino acid composition (PseAAC), pseudo position-specific scoring matrix (PsePSSM), reduced sequence and index-vectors (RSIV), and autocorrelation descriptor (AD). Second, to remove redundancy and noise, we employ L1-regularized logistic regression (L1-RLR) to select an optimal feature subset. Finally, GTB-PPI model is constructed. Five-fold cross-validation showed that GTB-PPI achieved the accuracies of 95.15% and 90.47% on Saccharomyces cerevisiae and Helicobacter pylori datasets, respectively. In addition, GTB-PPI could be applied to predict the independent test datasets for Caenorhabditis elegans, Escherichia coli, Homo sapiens, and Mus musculus, the one-core PPI network for CD9, and the crossover PPI network for the Wnt-related signaling pathways. The results show that GTB-PPI can significantly improve accuracy of PPI prediction. The code and datasets of GTB-PPI can be downloaded from https://github.com/QUST-AIBBDRC/GTB-PPI/.