tbuckley/cabot-search huggingface dataset:
Ecological Specialization and Evolutionary Reticulation in Extant Hyaenidae
Authors: Michael V Westbury, Diana Le Duc, David A Duchêne, Arunkumar Krishnan, Stefan Prost, Sereina Rutschmann, Jose H Grau, Love Dalén, Alexandra Weyrich, Karin Norén, Lars Werdelin, Fredrik Dalerum, Torsten Schöneberg, Michael Hofreiter
Journal: Molecular Biology and Evolution (2021)

During the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four species: the bone-cracking spotted, striped, and brown hyenas, and the specialized insectivorous aardwolf. Previous studies investigated the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. Here, we generated an aardwolf genome and analyzed it together with the remaining three species to reveal their evolutionary relationships, genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection, suggesting putative key adaptations to carrion and termite feeding, respectively. A family-wide expansion in olfactory receptor genes suggests that an acute sense of smell was a key early adaptation. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, putatively linked to their similarly slow decline in effective population size over the last ∼2 million years. High levels of genetic diversity and more stable population sizes through time are seen in the spotted hyena and aardwolf. Taken together, our findings highlight how ecological specialization can impact the evolutionary history, demographics, and adaptive genetic changes of an evolutionary lineage.
A Proinflammatory Cytokine Network Profile in Th1/Type 1 Effector B Cells Delineates a Common Group of Patients in Four Systemic Autoimmune Diseases
Authors: Quentin Simon, Alexis Grasseau, Marina Boudigou, Laëtitia Le Pottier, Eléonore Bettachioli, Divi Cornec, Bénédicte Rouvière, Christophe Jamin, Lucas Le Lann, Maria Orietta Borghi, Rocio Aguilar‐Quesada, Yves Renaudineau, Marta E. Alarcón‐Riquelme, Jacques‐Olivier Pers, Sophie Hillion
Journal: Arthritis & Rheumatology (2021)

The effector T cell and B cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases, but the association of these cytokine networks with the heterogeneity of clinical manifestations and immune profiles has not been carefully examined. This study was undertaken to examine whether cytokine profiles can delineate distinct groups of patients in 4 systemic autoimmune diseases (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and systemic sclerosis).A total of 179 patients and 48 healthy volunteers were enrolled in the multicenter cross-sectional PRECISE Systemic Autoimmune Diseases (PRECISESADS) study. Multi-low-dimensional omics data (cytokines, autoantibodies, circulating immune cells) were examined. Coculture experiments were performed to test the impact of the cytokine microenvironment on T cell/B cell cross-talk.A proinflammatory cytokine profile defined by high levels of CXCL10, interleukin-6 (IL-6), IL-2, and tumor necrosis factor characterized a distinct group of patients in the 4 systemic autoimmune diseases. In each disease, this proinflammatory cluster was associated with a specific circulating immune cell signature, more severe disease, and higher levels of autoantibodies, suggesting an uncontrolled proinflammatory Th1 immune response. We observed in vitro that B cells reinforce Th1 differentiation and naive T cell proliferation, leading to the induction of type 1 effector B cells and IgG production. This process was associated with an increase in CXCL10, IL-6, IL-2, and interferon-γ production.This composite analysis brings new insights into human B cell functional heterogeneity based on T cell/B cell cross-talk, and proposes a better stratification of patients with systemic autoimmune diseases, suggesting that combined biomarkers would be of great value for the design of personalized treatments.
“Consensus on Placebo and Nocebo Effects Connects Science with Practice:” Reply to “Questioning the Consensus on Placebo and Nocebo Effects”
Authors: Andrea W.M. Evers, Luana Colloca, Charlotte Blease, Jens Gaab, Karin B. Jensen, Lauren Y. Atlas, Chris J. Beedie, Fabrizio Benedetti, Ulrike Bingel, Christian Büchel, Jet Bussemaker, Ben Colagiuri, Alia J. Crum, Damien G. Finniss, Andrew L. Geers, Jeremy Howick, Regine Klinger, Stefanie Helena Meeuwis, Karin Meissner, Vitaly Napadow, Keith J. Petrie, Winfried Rief, Ionica Smeets, Tor D. Wager, Vishvarani Wanigasekera, Lene Vase, John M. Kelley, Irving Kirsch
Journal: Psychotherapy and Psychosomatics (2021)
Saliva for molecular detection of SARS-CoV-2 in school-age children
Authors: Hanan Al Suwaidi, Abiola Senok, Rupa Varghese, Zulfa Deesi, Hamda Khansaheb, Sabeel Pokasirakath, Bino Chacko, Ibrahim Abufara, Tom Loney, Alawi Alsheikh-Ali
Journal: Clinical Microbiology and Infection (2021)
Abstract 9895: Does Race Influence Decision-making for Advanced Heart Failure Therapies?
Authors: Khadijah Breathett, Erika Yee, Natalie Pool, Megan Hebdon, Janice Crist, Shannon Knapp, Ashley Larsen, Sade Solola, Luis Luy, Kathryn Herrera-Theut, Leanne Zabala, Jeff Stone, Marylyn McEwen, Elizabeth Calhoun, Nancy Sweitzer
Journal: Circulation (2019)

Background: Race influences medical decision-making, but its impact on the allocation of advanced heart failure (HF) therapies is unknown. We hypothesized that race would influence allocation of ad...
Global Landscape of Native Protein Complexes in <i>Synechocystis</i> sp. PCC 6803
Authors: Chen Xu, Bing Wang, Lin Yang, Lucas Zhongming Hu, Lanxing Yi, Yaxuan Wang, Shenglan Chen, Andrew Emili, Cuihong Wan
Journal: Genomics Proteomics & Bioinformatics (2021)

Synechocystis sp. PCC 6803 (hereafter: Synechocystis) is a model organism for studying photosynthesis, energy metabolism, and environmental stress. Although known as the first fully sequenced phototrophic organism, Synechocystis still has almost half of its proteome without functional annotations. In this study, by using co-fractionation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS), we define 291 multi-protein complexes, encompassing 24,092 protein-protein interactions (PPIs) among 2062 distinct gene products. This information not only reveals the roles of photosynthesis in metabolism, cell motility, DNA repair, cell division, and other physiological processes, but also shows how protein functions vary from bacteria to higher plants due to changes in interaction partners. It also allows us to uncover the functions of hypothetical proteins, such as Sll0445, Sll0446, and Sll0447 involved in photosynthesis and cell motility, and Sll1334 involved in regulation of fatty acid biogenesis. Here we present the most extensive PPI data for Synechocystis so far, which provide critical insights into fundamental molecular mechanisms in cyanobacteria.
Abstract PS13-13: The value of shear-wave elastography for prediction of treatment response to neoadjuvant chemotherapy in patients with breast cancer
Authors: Soong June Bae, Min Ji Kim, Yoon Jin Cha, Na Lae Eun, Dooreh Kim, Janghee Lee, Sung Gwe Ahn, Eon Ju Son, Joon Jeong
Journal: Cancer Research (2021)

Abstract Introduction Recently, Shear-wave elastography (SWE) has been known to be useful for the diagnosis of breast cancer and lymph node metastasis. However, little is known about whether SWE can predict the response to neoadjuvant chemotherapy in patients with breast cancer. This study aimed to investigate the relationship between treatment response and elasticity values. Method Pre-treatment shear-wave elastography was performed in 394 patients who underwent neoadjuvant chemotherapy followed by surgery at Gangnam Severance Hospital from January 2012 to May 2020. We evaluated the pathologic complete response (pCR, defined as ypTis/T0, No) according to elasticity values such as ‘Mean stiffness’, ‘Minimum stiffness’, ‘Maximum stiffness’, and ‘Ratio’. Results A total of 394 patients, 147 (37.3%) achieved pCR. All elasticity values were significantly lower in patients with pCR after neoadjuvant chemotherapy than those with the residual invasive tumor. In the multivariable analysis, the mean stiffness (OR 0.995; 95% CIs, 0.989-1.000; P=0.039) and the maximum stiffness (OR 0.995; 95% CIs, 0.990-0.999; P=0.024) were independent predictive factors for pCR after adjusting clinic-pathologic factors. Besides, the tumor-infiltrating lymphocytes (TILs) evaluated in biopsy samples were inversely correlated with pre-treatment mean stiffness (CC -0.053, P=0.044), and elasticity ratio (CC-0.288, P=0.033). Conclusion In this study, pre-treatment elasticity values measured by SWE were significantly associated with pCR in breast cancer. Our results suggest that SWE can be a useful diagnostic tool for predicting treatment response in patients with breast cancer who will receive neoadjuvant chemotherapy. Citation Format: Soong June Bae, Min Ji Kim, Yoon Jin Cha, Na Lae Eun, Dooreh Kim, Janghee Lee, Sung Gwe Ahn, Eon Ju Son, Joon Jeong. The value of shear-wave elastography for prediction of treatment response to neoadjuvant chemotherapy in patients with 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 PS13-13.
Abstract PS19-28: Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo
Authors: Islam Yahiya, Heba Helmy, Ahmed Sultan
Journal: Cancer Research (2021)

Abstract Epidemiological studies and experimental analysis indicate that dietary factors influence thedevelopment of breast cancer, suggesting the role of natural products as modifying factors againstbreast cancer. Thymoquinone (TQ) (a dietary phytochemical compound) the main active ingredientof the volatile oil of black seed (Nigella sativa) has been used to be safe when administered to awide variety of normal cells. In addition, Tamoxifen (TAM), a nonsteroidal triphenylethylene derivateand selective ER modulator, has been used as a single agent in the treatment of ER positive breastcancer.In the present study, we report the possible chemo-sensitizing effect of TQ as a promisingconventional chemotherapeutic agent, using a panel of human breast cancer cell lines, MCF-7, ZR-75-1, T-47D and BT-20 respectively in vitro and in vivo.Our data revealed that TQ, TAM or combined treatments significantly inhibited cell viability of MCF-7, T-47D, ZR-75-1 but slightly of BT-20 cell lines consistently with down-regulation of signaltransducer and activator of transcription 3 (STAT 3), mTOR, cyclin D1, oncogenic β-catenin,signaling a specific transcription factor and PPAR-gamma in a dose dependent manner. Mostimportantly, combined treatment enhanced inhibition of cell viability, DNA fragmentation andapoptosis induction through Caspase-3 activation and Bcl-2 down regulation in all tested cell linesbut this effect was limited in BT-20 cells compared to controls. Moreover, our data was supported bymicroscopic examination using electron scanning microscopy that revealed many apoptoticalterations after combined treatment compared to each TQ or TAM. Furthermore, confocalfluorescence microscopy examination revealed that only combined treatment showed a significantinhibition of filopodia formation as a sign of invasion inhibition in both BT-20 and MCF-7 humanbreast cancer cell lines. In vivo, tumor xenotransplants of human ZR-75-1 cells revealed that onlycombined treatment showed a significant regression in tumor size by 53% after 72h and enhancedE-cadherin expression as analyzed by immunohistochemistry and confocal fluorescencemicroscopy.Taken together, our findings provide strong in vitro and in vivo molecular evidences in support ofour hypothesis that Thymoquinone synchronized as chemo-preventive agent with Tamoxifen to inhibithuman breast cancer cell lines proliferation, invasion and induce apoptosis that might have a potentialimplication in breast cancer prevention and treatment. Citation Format: Islam Yahiya, Heba Helmy, Ahmed Sultan. Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo [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 PS19-28.
Abstract SP147: Aging
Authors: M Stratton
Journal: Cancer Research (2021)

Abstract As for most human cancer types we now have substantial understanding of the landscape of somatic mutations in breast cancer. However, there is relatively little knowledge of the somatic mutations present in normal breast epithelium. This may potentially be instructive in identifying the earliest stages of breast neoplasia and in understanding why the risk of breast cancer is high compared to other tissues of the body. By sequencing laser capture microdissected elements of normal breast epithelium from healthy women, women with breast cancer and women with breast cancer predisposition we are able to provide the first comprehensive insights into somatic mutagenesis in normal breast and compare these with other normal human tissues. Citation Format: M Stratton. Aging [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 SP147.
Differentiation syndrome with lower‐intensity treatments for acute myeloid leukemia
Authors: Amir T. Fathi, Eytan M. Stein, Courtney D. DiNardo, Mark J. Levis, Pau Montesinos, Stéphane de Botton
Journal: American Journal of Hematology (2021)

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.
Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease
Authors: Johan Boender, Ferdows Atiq, Marjon H. Cnossen, Johanna G. van der Bom, Karin Fijnvandraat, Joke de Meris, Moniek P. M. de Maat, Karin P. M. van Galen, Britta A. P. Laros-van Gorkom, Karina Meijer, Jeroen Eikenboom, Frank W. G. Leebeek
Journal: HemaSphere (2021)

Von Willebrand factor (VWF) multimer analysis is important in the classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is time consuming and inaccurate in detecting subtle changes in multimer patterns. Although VWF multimer densitometric analysis may be useful, the accuracy needs further investigation before it can be widely applied. In this study we aimed to validate VWF multimer densitometric analysis in a large cohort of VWD patients and to identify patient characteristics associated with densitometric outcomes. Patients were included from the Willebrand in the Netherlands (WiN) study, in which a bleeding score (BS) was obtained, and blood was drawn. For multimer analysis, citrated blood was separated on an agarose gel and visualized by Western blotting. IMAGEJ was used to generate densitometric images and medium-large VWF multimer index was calculated. We included 560 VWD patients: 328 type 1, 211 type 2, and 21 type 3 patients. Medium-large VWF multimer index performed excellent in distinguishing visually classified normal VWF multimers from reduced high-molecular-weight (HMW) multimers (area under the curve [AUC]: 0.96 [0.94-0.98], P &lt; 0.001), normal multimers from absence of HMW multimers (AUC 1.00 [1.00-1.00], P &lt; 0.001), and type 2A and 2B from type 2M and 2N (AUC: 0.96 [0.94-0.99], P &lt; 0.001). Additionally, higher medium-large VWF multimer index was associated with lower BS in type 1 VWD: β = -7.6 (-13.0 to -2.1), P = 0.007, adjusted for confounders. Densitometric analysis of VWF multimers had an excellent accuracy compared with visual multimer analysis and may contribute to a better understanding of the clinical features such as the bleeding phenotype of VWD patients.
Long-Term Association of Air Pollution and Hospital Admissions Among Medicare Participants Using a Doubly Robust Additive Model
Authors: Mahdieh Danesh Yazdi, Yan Wang, Qian Di, Yaguang Wei, Weeberb J. Requia, Liuhua Shi, Matthew Benjamin Sabath, Francesca Dominici, Brent A. Coull, John S. Evans, Petros Koutrakis, Joel D. Schwartz
Journal: Circulation (2021)

Studies examining the nonfatal health outcomes of exposure to air pollution have been limited by the number of pollutants studied and focus on short-term exposures.We examined the relationship between long-term exposure to fine particulate matter with an aerodynamic diameter <2.5 micrometers (PM2.5), NO2, and tropospheric ozone and hospital admissions for 4 cardiovascular and respiratory outcomes (myocardial infarction, ischemic stroke, atrial fibrillation and flutter, and pneumonia) among the Medicare population of the United States. We used a doubly robust method for our statistical analysis, which relies on both inverse probability weighting and adjustment in the outcome model to account for confounding. The results from this regression are on an additive scale. We further looked at this relationship at lower pollutant concentrations, which are consistent with typical exposure levels in the United States, and among potentially susceptible subgroups.Long-term exposure to fine PM2.5 was associated with an increased risk of all outcomes with the highest effect seen for stroke with a 0.0091% (95% CI, 0.0086-0.0097) increase in the risk of stroke for each 1-µg/m3 increase in annual levels. This translated to 2536 (95% CI, 2383-2691) cases of hospital admissions with ischemic stroke per year, which can be attributed to each 1-unit increase in fine particulate matter levels among the study population. NO2 was associated with an increase in the risk of admission with stroke by 0.00059% (95% CI, 0.00039-0.00075) and atrial fibrillation by 0.00129% (95% CI, 0.00114-0.00148) per ppb and tropospheric ozone was associated with an increase in the risk of admission with pneumonia by 0.00413% (95% CI, 0.00376-0.00447) per parts per billion. At lower concentrations, all pollutants were consistently associated with an increased risk for all our studied outcomes.Long-term exposure to air pollutants poses a significant risk to cardiovascular and respiratory health among the elderly population in the United States, with the greatest increase in the association per unit of exposure occurring at lower concentrations.
Improving the identification of frail elderly newly diagnosed multiple myeloma patients
Authors: Claudia A. M. Stege, Kazem Nasserinejad, Saskia K. Klein, Gert-Jan Timmers, Mels Hoogendoorn, Paula F. Ypma, Inger S. Nijhof, Gerjo A. Velders, Leonie Strobbe, Nazik Durdu-Rayman, Matthijs Westerman, Marjan A. Davidis-van Schoonhoven, Roel J. W. van Kampen, Aart Beeker, Ad Koster, Amanda C. Dijk, Niels W. C. J. van de Donk, Ellen van der Spek, Rineke B. L. Leys, Matthijs H. Silbermann, Kaz Groen, Nicole C. H. P. van der Burg-de Graauw, Harm A. M. Sinnige, Klaas G. van der Hem, Henriette Levenga, Yavuz M. Bilgin, Pieter Sonneveld, Mark-David Levin, Sonja Zweegman
Journal: Leukemia (2021)
Association of Recreational Cannabis Legalization With Maternal Cannabis Use in the Preconception, Prenatal, and Postpartum Periods
Authors: Kara R. Skelton, Amelie A. Hecht, Sara E. Benjamin-Neelon
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Recent studies have revealed increases in population-level cannabis use after legalization of recreational cannabis. However, the association of cannabis legalization with maternal cannabis use during important life stages remains unknown. <h3>Objective</h3> To investigate the association of legalization of recreational cannabis with maternal cannabis use during the preconception, prenatal, and postpartum periods. <h3>Design, Setting, and Participants</h3> This repeated cross-sectional study used state-level data on women who delivered live-born infants in the US from the Pregnancy Risk Assessment Monitoring System from January 2004 to December 2018. Data from 2 states that had legalized recreational cannabis (Alaska and Maine) and 2 states that had not legalized recreational cannabis (New Hampshire and Vermont) were used. Women completed surveys 2 to 6 months after delivery, reporting preconception, prenatal, and postpartum cannabis use. <h3>Exposure</h3> State recreational cannabis legalization. <h3>Main Outcomes and Measures</h3> The 3 primary outcomes were self-reported cannabis use during the 12 months before pregnancy (preconception), during pregnancy (prenatal), and the 2 to 6 months after pregnancy (postpartum). A difference-in-differences analysis was used to compare changes in the prevalence of maternal cannabis use during each period before and after state legalization of recreational cannabis, controlling for maternal characteristics (age, race/ethnicity, educational level, income, cigarette smoking, and breastfeeding) and state fixed effects. State-specific survey weights were used. <h3>Results</h3> The analytic sample included 23 082 women in the preconception period, 23 859 in the prenatal period, and 26 610 in the postpartum period. In each analysis, most women were married (range among all groups, 63.9%-64.8%), aged 25 to 34 years (preconception, 55.4%; prenatal, 55.9%; postpartum, 56.1%), and had an annual household income less than $50 000 (preconception, 55.7%; prenatal, 56.3%; postpartum, 55.5%). In adjusted analyses, preconception and postpartum cannabis use increased significantly in states that had legalized recreational cannabis compared with states that had not legalized it (preconception risk difference, 0.0457 [95% CI, 0.0013-0.0900];<i>P</i> = .04; postpartum risk difference, 0.0539 [95% CI, 0.0259-0.0818];<i>P</i> &lt; .001). The risk difference for prenatal cannabis use was not significant (0.0070; 95% CI, −0.0120 to 0.0260;<i>P</i> = .47). <h3>Conclusions and Relevance</h3> In this repeated cross-sectional study, recreational cannabis legalization was associated with changes in maternal cannabis use before and after pregnancy. The findings suggest that future studies should undertake an interdisciplinary approach to maximize benefit and application of findings to future public health, health care, and policy sectors.