tbuckley/cabot-search huggingface dataset:
From washing hands to washing consciences and polishing reputations
Authors: Matthieu Légeret, Ulrich Hoffrage
Journal: Behavioral and Brain Sciences (2021)

Abstract While Lee and Schwarz propose grounded procedures of separation as an explanation for physical cleansing in various domains (e.g., washing one's hands), we suggest that separation can also account for behavioral cleansing aimed at washing consciences and polishing reputations. We discuss this extension in terms of degrees of behavioral cleansing, motivations, and intentions behind cleansing, and social settings.
Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome
Authors: Sarah Raevens, Maxine Boret, Michel De Pauw, Michael B. Fallon, Hans Van Vlierberghe
Journal: Hepatology (2021)

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post‐LT outcome. Pre‐LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end‐stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post‐LT and are considered “pulmonary indications” for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1‐antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post‐LT survival, as well as the reciprocal impact of LT on the evolution of lung function.
IMGN779, a Next Generation CD33-Targeting ADC, Combines Effectively with Cytarabine in Acute Myeloid Leukemia (AML) Preclinical Models, Resulting in Increased DNA Damage Response, Cell Cycle Arrest and Apoptosis In Vitro and Prolonged Survival In Vivo
Authors: Sharlene Adams, Meghan Kelly, Rebecca McCarthy, Alan Wilhelm, Krystal Watkins, Leanne Lanieri, Callum M. Sloss, Angela Romanelli
Journal: Blood (2017)
NHS reorganisation: We don’t need a big bang
Authors: Fiona Godlee
Journal: BMJ (2021)

What do you call a government that embarks on the biggest upheaval of the NHS in its 63 year history, at breakneck speed, while simultaneously trying to make unprecedented financial savings?The politically correct answer has got to be: mad."So began The BMJ's response to Andrew Lansley's proposed reforms in January 2011. 1 Should we say the same about the government's plans to reverse the Lansley reforms, coming as they do in the teeth of a pandemic, with hospitals at full stretch and a mass vaccination programme under way? 2 7
Abstract 17092: Coronary Artery Aneurysms Are More Common in Post-COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C) Than Pre-Pandemic Kawasaki Disease
Authors: Justin M Pick, Shuo Wang, Sharon Wagner-Lees, Sarah Badran, Jacqueline R Szmuszkovicz, Pierre Wong, Jodie Votava-Smith
Journal: Circulation (2020)

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is thought to be a delayed reaction to SARS-CoV-2 exposure. Coronary artery aneurysms (CAA) have been described in the MIS-C diagnostic criteria, with many symptoms mimicking Kawasaki disease (KD). Our institution has seen a significant rise in KD-like illness during the current COVID-19 pandemic. Objectives: We sought to describe the variation in coronary artery (CA) involvement between traditional KD and post-COVID-19 pandemic KD/MIS-C cases. Methods: We identified children admitted to our center with KD from April to June 2016 - 2017 and those with MIS-C/KD from April 1 - June 6, 2020, with review of clinical and echocardiogram data. Presence of CAA (any CA z-score ≥ +2.5), z-scores of the left main (LMCA), left anterior descending (LAD), and right coronary artery (RCA), and presence of cardiac and valvar dysfunction were evaluated. Nonparametric Wilcoxon rank sum test was used to compare the groups. Results: There were 26 patients in the 2016-17 KD group and 24 in the 2020 KD/MIS-C group; results are shown in Table 1. The groups had similar median age, and 2016-17 KD patients were more likely to be male. 2020 KD/MIS-C patients were more likely to have CAA than 2016-17 KD patients (54% vs 26%, p=0.05). The LAD had larger median z-score in 2020 KD/MIS-C than KD (p=0.017). RCA and LMCA z-scores of 2020 KD/MIS-C patients tended to be larger than 2016-17 KD but did not reach statistical significance (p=0.097, p=0.07 respectively). More 2020 KD/MIS-C patients had cardiac dysfunction, not statistically significant (13% vs 0%, p=NS), with no differences in valve function or effusion. Conclusions: Our spring 2020 cohort of MIS-C/KD patients had higher incidence of CAA, particularly larger LAD z-scores than those with KD pre-COVID-19 pandemic. Coronary arteries should be thoroughly assessed in patients presenting with MIS-C symptoms. Future studies are needed to determine long term outcomes in this cohort.
ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders
Authors: Jia Li, Maureen Fredericks, Marishka Cannell, Kathryn Wang, Dianne Sako, Michelle C. Maguire, Rosa Grenha, Katia Liharska, Lavanya Krishnan, Troy Bloom, Elitza P. Belcheva, Pedro A. Martinez, Roselyne Castonguay, Sarah Keates, Mark J. Alexander, Hyunwoo Choi, Asya V. Grinberg, R. Scott Pearsall, Paul Oh, Ravindra Kumar, Rajasekhar N.V.S. Suragani
Journal: Journal of Clinical Investigation (2021)

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-β superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9). ActRIIB:ALK4-Fc and ActRIIB-Fc administered to mice exerted differential effects — concordant with SPR results — on vessel outgrowth in a retinal explant assay. ActRIIB:ALK4-Fc induced a systemic increase in muscle mass and function in wild-type mice and in murine models of Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and disuse atrophy. Importantly, ActRIIB:ALK4-Fc improved neuromuscular junction abnormalities in murine models of DMD and presymptomatic ALS and alleviated acute muscle fibrosis in a DMD model. Furthermore, in combination therapy ActRIIB:ALK4-Fc increased the efficacy of antisense oligonucleotide M12-PMO on dystrophin expression and skeletal muscle endurance in an aged DMD model. ActRIIB:ALK4-Fc shows promise as a therapeutic agent, alone or in combination with dystrophin rescue therapy, to alleviate muscle weakness and comorbidities of neuromuscular disorders.
Primary Malignant Melanoma of the Oropharynx Presented on 18F-FDG PET/CT
Authors: JingXing Xiao, Min Su, Dong Wang
Journal: Clinical Nuclear Medicine (2021)

Primary malignant melanoma in the oropharynx is extremely rare. A 49-year-old man presented with a 3-month history of progressive dysphagia. An outside CT scan of the head and neck showed a space-occupying lesion in the oropharynx. Staging with FDG PET/CT demonstrated a hypermetabolic mass in the right wall of the oropharynx. A biopsy revealed malignant melanoma. The patient underwent total resection of the tumor, with no recurrence after 6-month follow-up.
Cost effectiveness analysis of strategies to combat HIV/AIDS in developing countries
Authors: Daniel R Hogan, Rob Baltussen, Chika Hayashi, Jeremy A Lauer, Joshua A Salomon
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To assess the costs and health effects of a range of interventions for preventing the spread of HIV and for treating people with HIV/AIDS in the context of the millennium development goal for combating HIV/AIDS. <b>Design</b> Cost effectiveness analysis based on an epidemiological model. <b>Setting</b> Analyses undertaken for two regions classified using the WHO epidemiological grouping–Afr-E, countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, countries in South East Asia with high adult and high child mortality. <b>Data sources</b> Biological and behavioural parameters from clinical and observational studies and population based surveys. Intervention effects and resource inputs based on published reports, expert opinion, and the WHO-CHOICE database. <b>Main outcome measures</b> Costs per disability adjusted life year (DALY) averted in 2000 international dollars ($Int). <b>Results</b> In both regions interventions focused on mass media, education and treatment of sexually transmitted infections for female sex workers, and treatment of sexually transmitted infections in the general population cost &lt; $Int150 per DALY averted. Voluntary counselling and testing costs &lt; $Int350 per DALY averted in both regions, while prevention of mother to child transmission costs &lt; $Int50 per DALY averted in Afr-E but around $Int850 per DALY in Sear-D. School based education strategies and various antiretroviral treatment strategies cost between $Int500 and $Int5000 per DALY averted. <b>Conclusions</b> Reducing HIV transmission could be done most efficiently through mass media campaigns, interventions for sex workers and treatment of sexually transmitted infections where resources are most scarce. However, prevention of mother to child transmission, voluntary counselling and testing, and school based education would yield further health gains at higher budget levels and would be regarded as cost effective or highly cost effective based on standard international benchmarks. Antiretroviral therapy is at least as cost effective in improving population health as some of these interventions. This article is part of a series examining the cost effectiveness of strategies to achieve the millennium development goals for health
Specificity of mRNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures
Authors: Gongwang Yu, Hanbing Zhu, Xiaoshu Chen, Jian-Rong Yang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The secondary structure is a fundamental feature of both non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs). However, our understanding of the secondary structures of mRNAs, especially those of the coding regions, remains elusive, likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs. Indeed, mRNAs have recently been found to adopt diverse alternative structures, but the overall functional significance remains untested. We hereby approach this problem by estimating the folding specificity, i.e., the probability that a fragment of an mRNA folds back to the same partner once refolded. We show that the folding specificity of mRNAs is lower than that of ncRNAs and exhibits moderate evolutionary conservation. Notably, we find that specific rather than alternative folding is likely evolutionarily adaptive since specific folding is frequently associated with functionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding. Our findings reveal a novel facet of the RNA structurome with important functional and evolutionary implications and indicate a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.
Efficacy Results of a Phase 2 Trial Evaluating Idelalisib Plus Ofatumumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia
Authors: Benjamin L. Lampson, Haesook T Kim, Matthew S. Davids, Jeremy S. Abramson, Arnold S. Freedman, Caron A. Jacobson, Philippe Armand, Robin M. Joyce, Jon E. Arnason, Laura Z. Rassenti, Thomas J. Kipps, Samantha Huang, Joshua Fein, John Hanna, Stacey Marie Fernandes, David C. Fisher, Jennifer R. Brown
Journal: Blood (2017)
Disease monitoring with quantitative serum IgA levels provides a more reliable response assessment in multiple myeloma patients
Authors: Alissa Visram, Iuliana Vaxman, Abdullah S. Al Saleh, Harsh Parmar, Angela Dispenzieri, Prashant Kapoor, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Rahma Warsame, Taxiarchis Kourelis, Mustaqeem Siddiqui, Wilson Gonsalves, Eli Muchtar, John A. Lust, Nelson Leung, Robert A. Kyle, David Murray, S. Vincent Rajkumar, Shaji Kumar
Journal: Leukemia (2021)

Unlike IgG monoclonal proteins (MCPs), IgA MCP quantification is unreliable due to beta-migration of IgA MCPs on serum protein electrophoresis (SPEP). The utility of nephelometric quantitative IgA (qIgA) to monitor IgA multiple myeloma (MM) is unclear. We retrospectively studied disease response kinetics using qIgA versus MCPs by SPEP, and developed and validated novel qIgA disease assessment criteria in 491 IgA MM patients. The SPEP MCP nadir occurred a median of 41 (IQR 0-102) days before the qIgA. The median time to achieve a partial response (PR) was shorter using standard IMWG versus qIgA response criteria (32 vs 58 days, p < 0.001). Stratification by qIgA criteria, unlike IMWG criteria, led to clear separation of the progression-free survival curves of patients achieving a PR or very good PR. There was a consistent trend toward earlier detection of disease progression using qIgA versus IMWG progression criteria. In conclusion, monitoring IgA MM using MCP-based IMWG criteria may be falsely reassuring, given that MCP levels on SPEP decrease faster than qIgA levels. The qIgA response criteria more accurately stratify patients based on the progression risk and may detect disease progression earlier, which may lead to more consistent measurement of trial endpoints and improved patient outcomes.
Covid-19: Ethnicity vaccination gap narrows in England, but concerns remain
Authors: Shaun Griffin
Journal: BMJ (2021)

The gap between the number of black people and white people vaccinated against covid-19 in England has slightly narrowed in the past few weeks, although it is still a concern and requires attention, say experts.

As of 13 January, data from the OpenSAFELY platform showed that twice as many white people aged over 80 (43%) had been vaccinated as black people (21%).1 By 11 February, when 91% of this age group had been vaccinated, 91% of white people had been vaccinated, compared with only 58% of black people and 72% of people from South Asian backgrounds.2

The latest dataset also looked at vaccine coverage among 70-79 year olds and showed that 85% of this age group (1.76 million) had been vaccinated by 11 …
Behavioral and Genomic Sensory Adaptations Underlying the Pest Activity of<i>Drosophila suzukii</i>
Authors: Sylvia M Durkin, Mahul Chakraborty, Antoine Abrieux, Kyle M Lewald, Alice Gadau, Nicolas Svetec, Junhui Peng, Miriam Kopyto, Christopher B Langer, Joanna C Chiu, J J Emerson, Li Zhao
Journal: Molecular Biology and Evolution (2021)

Abstract Studying how novel phenotypes originate and evolve is fundamental to the field of evolutionary biology as it allows us to understand how organismal diversity is generated and maintained. However, determining the basis of novel phenotypes is challenging as it involves orchestrated changes at multiple biological levels. Here, we aim to overcome this challenge by using a comparative species framework combining behavioral, gene expression, and genomic analyses to understand the evolutionary novel egg-laying substrate-choice behavior of the invasive pest species Drosophila suzukii. First, we used egg-laying behavioral assays to understand the evolution of ripe fruit oviposition preference in D. suzukii compared with closely related species D. subpulchrella and D. biarmipes as well as D. melanogaster. We show that D. subpulchrella and D. biarmipes lay eggs on both ripe and rotten fruits, suggesting that the transition to ripe fruit preference was gradual. Second, using two-choice oviposition assays, we studied how D. suzukii, D. subpulchrella, D. biarmipes, and D. melanogaster differentially process key sensory cues distinguishing ripe from rotten fruit during egg-laying. We found that D. suzukii’s preference for ripe fruit is in part mediated through a species-specific preference for stiff substrates. Last, we sequenced and annotated a high-quality genome for D. subpulchrella. Using comparative genomic approaches, we identified candidate genes involved in D. suzukii’s ability to seek out and target ripe fruits. Our results provide detail to the stepwise evolution of pest activity in D. suzukii, indicating important cues used by this species when finding a host, and the molecular mechanisms potentially underlying their adaptation to a new ecological niche.
Abstract PS1-31: Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy
Authors: Xin Wang, Wenyan Wang, Jiaxiang Liu, Xiangzhi Meng, Jiaqi Liu, Changyuan Guo, Ying Song, Ningyi Cui, Qiao Li, Zeyu Xing, Jie Wang, Menglu Zhang, Kexin Feng, Pilin Wang, Xiang Wang
Journal: Cancer Research (2021)

Abstract Background: Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). ALN status is an important prognostic factor for choosing the type of axillary lymph node surgery. Many patients with axillary pCR could replace axillary lymph node dissection (ALND) with sentinel lymph node biopsy (SLNB). Our goal is to develop a new predictive clinical model to detect axillary pCR after NAC and provide clinical clues for avoiding ALND. Methods: A retrospective series of 547 patients who had biopsy-proven positive ALNs at diagnosis from 2007 to 2014 in National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences were involved. We analyzed the clinicopathologic features and developed a nomogram to predict the probability of ALN pCR. Univariate assessment was performed using chi-square test. A multivariate logistic regression stepwise model was used to generate a nomogram to predict ALN pCR in node positive patients. The receiver operating characteristic (ROC) curve was established and the area under the curve (AUC) was calculated to evaluate the accuracy of the model. Internal validation was estimated using 50-50 hold out validation method. Nomogram was validated externally with the prospective cohorts of 167 patients from 2016 to 2018 of Cancer Hospital of Chinese Academy of Medical Sciences and 75 patients from 2018 to 2019 of Beijing Tiantan hospital.Results: In the retrospective study, 172 (31.4%) patients achieved axillary pCR after NAC. Multivariate analysis indicated that clinical nodal (N) stage, hormone receptor (HR) status and clinical response of primary tumor after NAC were significant independent predictors for axillary pCR (P&amp;lt;0.05). The AUCs of the internal validation for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.862 and 0.766, respectively.Conclusion: We developed a nomogram to predict axillary pCR in node positive breast cancer patients after NAC. The predictive model performed well in prospective external validation. This practical tool could provide information to surgeons about whether to avoid ALND after NAC. Citation Format: Xin Wang, Wenyan Wang, Jiaxiang Liu, Xiangzhi Meng, Jiaqi Liu, Changyuan Guo, Ying Song, Ningyi Cui, Qiao Li, Zeyu Xing, Jie Wang, Menglu Zhang, Kexin Feng, Pilin Wang, Xiang Wang. Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy [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 PS1-31.
Covid-19 deaths in Africa: prospective systematic postmortem surveillance study
Authors: Lawrence Mwananyanda, Christopher J Gill, William MacLeod, Geoffrey Kwenda, Rachel Pieciak, Zachariah Mupila, Rotem Lapidot, Francis Mupeta, Leah Forman, Luunga Ziko, Lauren Etter, Donald Thea
Journal: BMJ (2021)

To directly measure the fatal impact of coronavirus disease 2019 (covid-19) in an urban African population.Prospective systematic postmortem surveillance study.Zambia's largest tertiary care referral hospital.Deceased people of all ages at the University Teaching Hospital morgue in Lusaka, Zambia, enrolled within 48 hours of death.Postmortem nasopharyngeal swabs were tested via reverse transcriptase quantitative polymerase chain reaction (PCR) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deaths were stratified by covis-19 status, location, age, sex, and underlying risk factors.372 participants were enrolled between June and September 2020; PCR results were available for 364 (97.8%). SARS-CoV-2 was detected in 58/364 (15.9%) according to the recommended cycle threshold value of <40 and in 70/364 (19.2%) when expanded to any level of PCR detection. The median age at death among people with a positive test for SARS-CoV-2 was 48 (interquartile range 36-72) years, and 69% (n=48) were male. Most deaths in people with covid-19 (51/70; 73%) occurred in the community; none had been tested for SARS-CoV-2 before death. Among the 19/70 people who died in hospital, six were tested before death. Among the 52/70 people with data on symptoms, 44/52 had typical symptoms of covid-19 (cough, fever, shortness of breath), of whom only five were tested before death. Covid-19 was identified in seven children, only one of whom had been tested before death. The proportion of deaths with covid-19 increased with age, but 76% (n=53) of people who died were aged under 60 years. The five most common comorbidities among people who died with covid-19 were tuberculosis (22; 31%), hypertension (19; 27%), HIV/AIDS (16; 23%), alcohol misuse (12; 17%), and diabetes (9; 13%).Contrary to expectations, deaths with covid-19 were common in Lusaka. Most occurred in the community, where testing capacity is lacking. However, few people who died at facilities were tested, despite presenting with typical symptoms of covid-19. Therefore, cases of covid-19 were under-reported because testing was rarely done not because covid-19 was rare. If these data are generalizable, the impact of covid-19 in Africa has been vastly underestimated.