tbuckley/cabot-search huggingface dataset:
In hypertension, a quadpill containing quarter doses of 4 BP drugs reduced BP at 12 wk vs. standard-dose monotherapy
Authors: Krysta Brown, Anthony A. Donato MD
Journal: Annals of Internal Medicine (2022)

Source Citation Chow CK, Atkins ER, Hillis GS, et al. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. Lancet. 2021;398:1043-52. 34469767
Inoperable Early-Stage Non–Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy
Authors: Megan E. Daly
Journal: Journal of Clinical Oncology (2022)

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable, early-stage non-small-cell lung cancer. SABR results in high rates of in-field tumor control, but among larger and more biologically aggressive tumors, regional and distant failures are problematic. Cytotoxic chemotherapy is rarely used in this patient population and the benefit is unclear. Alternative systemic therapy options with a milder side-effect profile are of considerable interest, and several randomized phase III trials are currently testing immune checkpoint inhibitors in this setting. We review the rationale, data, and ongoing studies evaluating systemic therapy in medically inoperable, early-stage non-small-cell lung cancer treated with SABR.
36P Indirect comparison of mobocertinib trial data vs real-world data in patients with EGFR exon 20 insertion (ex20ins)+ non-small cell lung cancer (NSCLC)
Authors: P. Christopoulos, T. Prawitz, J-L. Hong, H.M. Lin, L. Hernandez, S. Jin, M. Tan, I. Proskorovsky, J. Lin, P. Zhang, J. Patel, S-H.I. Ou, M. Thomas, A. Stenzinger
Journal: Annals of Oncology (2022)
Correction to: Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model
Authors: Kevin Clayton, Jean Christophe Delpech, Shawn Herron, Naotoshi Iwahara, Maria Ericsson, Takashi Saito, Takaomi C. Saido, Seiko Ikezu, Tsuneya Ikezu
Journal: Molecular Neurodegeneration (2021)

An amendment to this paper has been published and can be accessed via the original article.
A Direct Measure of Tuberculosis Incidence — Effect of Community Screening
Authors: Guy B. Marks, Jennifer Ho, Phuong Thi Bich Nguyen, Thu Anh Nguyen, Khanh Luu Boi, Khoa Hien Tran, Son Van Nguyen, Nhung Viet Nguyen, Hoa Binh Nguyen, Linh Nhat Nguyen, Frances L. Garden, Greg J. Fox
Journal: New England Journal of Medicine (2022)
IMPACT OF PERCUTANEOUS CORONARY INTERVENTION OF CHRONIC TOTAL OCCLUSIONS ON ABSOLUTE PERFUSION IN REMOTE MYOCARDIUM
Authors: Ruben Willem De Winter, Stefan Schumacher, Pepijn Van Diemen, Ruurt Jukema, Yvemarie Somsen, Wynand Stuijfzand, Roel Driessen, Michiel Bom, Henk Everaars, Albert van Rossum, Peter van de Ven, Maksymilian Opolski, Niels Verouden, Ibrahim Danad, Pieter Raijmakers, Alexander Nap, Paul Knaapen
Journal: Journal of the American College of Cardiology (2022)
Abstract P102: Comparison Of Existing Cardiovascular Risk Prediction Models In Haiti: Implications For Primary Prevention In Lower-income Countries
Authors: Lily D Yan, Jean Lookens Pierre, Vanessa Rouzier, Michel Théard, Alexandra Apollon, Stephano St-Preux, Justin Kingery, Kenneth A Jamerson, Marie Deschamps, Jean W Pape, Monika M Safford, Margaret Mcnairy
Journal: Circulation (2022)

Introduction: Cardiovascular diseases (CVD) are rapidly increasing in low-middle income countries. Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention. Available CVD risk prediction models are built on predominantly Caucasian, high-income country populations, and have not been evaluated in lower-income countries. We aimed to compare six existing models for predicted 10-year risk of CVD and identify high-risk groups for targeted prevention in Haiti. Methods: We used cross-sectional data within the Haiti CVD Cohort Study, including 653 adults ≥ 40 years without known history of CVD. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility. Results: Seventy percent (460/653) were female, 65.5% (428/653) lived on a daily income of ≤1 USD, 57.0% (372/653) had hypertension, 14.5% (95/653) had hypercholesterolemia, 9.3% (61/653) had diabetes mellitus, and 5.5% (36/653) were current smokers. Predicted 10-year CVD risk ranged from 3.9% in adjusted PCE (IQR 1.7-8.4) to 9.8% in Framingham-BMI (IQR 5.0-17.8), and Spearman correlation coefficients ranged from 0.87 to 0.98. The percent of the cohort categorized as high risk using the uniform threshold of 10-year CVD risk ≥ 7.5% ranged from 28.8% in the adjusted PCE model to 62.0% in the Framingham-BMI model (χ 2 = 331, p value &lt; 0.001). Statin eligibility also varied widely. Conclusions: In the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on model choice. There is a need to design and validate CVD risk prediction tools for low-middle income countries.
Abstract 073: A Mediterranean Diet Pattern Is Associated With Lower Risk Of Adverse Pregnancy Outcomes In US Women: Results From The NuMoM2b Cohort
Authors: Nour Makarem, Kristi Chau, Eliza C Miller, Cynthia Gyamfi-Bannerman, Isabella Tous, Whitney A Booker, Janet M Catov, David Haas, William GROBMAN, Lisa Levine, Rebecca McNeil, Noel N Merz, Uma Reddy, Ron Wapner, Melissa Wong, Natalie A Bello
Journal: Circulation (2022)

Introduction: Adverse pregnancy outcomes (APOs) are associated with an increased risk of developing cardiovascular disease (CVD). While the Mediterranean diet pattern has been inversely related to CVD outcomes, its association with APOs in US women has not been previously evaluated. Hypothesis: Adherence to a Mediterranean diet pattern during the periconception period is associated with lower risk of APOs. Methods: Racially and ethnically diverse women (n=8075, mean age: 27±6y) from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort were enrolled across 8 US medical centers from 2010-13. An Alternate Mediterranean Diet (aMed) score was computed from data on habitual diet in the 3 months around conception, assessed using a semi-quantitative food frequency questionnaire in the first trimester. APOs were prospectively ascertained and defined as developing 1 or more of the following: gestational hypertension, preeclampsia/eclampsia, gestational diabetes, preterm delivery, small for gestational age, or stillbirth. Multivariable logistic regression was used to examine associations of the aMed score and its components with any APO and individual APOs. Results: Women in the highest vs. lowest quintile of the aMed score had 21% lower odds of developing any APO, and 36% and 52% lower odds of preeclampsia/eclampsia and gestational diabetes, respectively; a linear trend across aMed score categories was detected (p-trend&lt;0.05) ( Figure ). When aMed score components were examined separately, higher intakes of vegetables, fruits, legumes, and fish and lower intakes of red meat were related to up to 26% lower odds of APOs. Conclusions: Greater adherence to a Mediterranean diet pattern is related to lower risk of APOs, with evidence of a dose-response relationship, highlighting the potential of this diet pattern in CVD primordial prevention efforts in US women. Long-term studies are needed to assess whether dietary modification in the periconception period can reduce risk of APOs and future CVD.
PARP Inhibitors – Trapped in a Toxic Love Affair
Authors: Dragomir B. Krastev, Andrew J. Wicks, Christopher J. Lord
Journal: Cancer Research (2021)

Abstract It is often the case that when an investigational cancer drug first enters clinical development, its precise mechanism of action is unclear. This was the case for PARP inhibitors (PARPi) used to treat homologous recombination–defective cancers. In 2012, nearly a decade after the first PARPi entered clinical development, work from Murai and colleagues demonstrated that clinical PARPi not only inhibit the catalytic activity of PARP1, PARylation, but also “trap” PARP1 on DNA; this latter effect being responsible for much of the tumor cell cytotoxicity caused by these drugs. We discuss how this work not only changed our understanding about how PARPi work, but also stimulated subsequent dissection of how PARP1 carries out its normal function in the absence of inhibitor. See related article by Murai and colleagues, Cancer Res 2012;72:5588–5599.
Distinct Pathogenesis of Clonal Hematopoiesis Revealed By Single Cell RNA Sequencing Integrated with Highly Sensitive Genotyping Method
Authors: Masahiro Marshall Nakagawa, Ryosaku Inagaki, Yutaka Kuroda, Yasuhito Nannya, Lanying Zhao, Yotaro Ochi, June Takeda, Qi Xingxing, Akinori Yoda, Ayana Kon, Nobuyuki Kakiuchi, Hideki Makishima, Shuichi Matsuda, Seishi Ogawa
Journal: Blood (2021)
Within-job gender pay inequality in 15 countries
Authors: Andrew M. Penner, Trond Petersen, Are Skeie Hermansen, Anthony Rainey, István Boza, Marta M. Elvira, Olivier Godechot, Martin Hällsten, Lasse Folke Henriksen, Feng Hou, Aleksandra Kanjuo Mrčela, Joe King, Naomi Kodama, Tali Kristal, Alena Křížková, Zoltán Lippényi, Silvia Maja Melzer, Eunmi Mun, Paula Apascaritei, Dustin Avent-Holt, Nina Bandelj, Gergely Hajdu, Jiwook Jung, Andreja Poje, Halil Sabanci, Mirna Safi, Matthew Soener, Donald Tomaskovic-Devey, Zaibu Tufail
Journal: Nature Human Behaviour (2022)

Extant research on the gender pay gap suggests that men and women who do the same work for the same employer receive similar pay, so that processes sorting people into jobs are thought to account for the vast majority of the pay gap. Data that can identify women and men who do the same work for the same employer are rare, and research informing this crucial aspect of gender differences in pay is several decades old and from a limited number of countries. Here, using recent linked employer-employee data from 15 countries, we show that the processes sorting people into different jobs account for substantially less of the gender pay differences than was previously believed and that within-job pay differences remain consequential.
Machine learning in vascular surgery: a systematic review and critical appraisal
Authors: Ben Li, Tiam Feridooni, Cesar Cuen-Ojeda, Teruko Kishibe, Charles de Mestral, Muhammad Mamdani, Mohammed Al-Omran
Journal: npj Digital Medicine (2022)

Abstract Machine learning (ML) is a rapidly advancing field with increasing utility in health care. We conducted a systematic review and critical appraisal of ML applications in vascular surgery. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to March 1, 2021. Study screening, data extraction, and quality assessment were performed by two independent reviewers, with a third author resolving discrepancies. All original studies reporting ML applications in vascular surgery were included. Publication trends, disease conditions, methodologies, and outcomes were summarized. Critical appraisal was conducted using the PROBAST risk-of-bias and TRIPOD reporting adherence tools. We included 212 studies from a pool of 2235 unique articles. ML techniques were used for diagnosis, prognosis, and image segmentation in carotid stenosis, aortic aneurysm/dissection, peripheral artery disease, diabetic foot ulcer, venous disease, and renal artery stenosis. The number of publications on ML in vascular surgery increased from 1 (1991–1996) to 118 (2016–2021). Most studies were retrospective and single center, with no randomized controlled trials. The median area under the receiver operating characteristic curve (AUROC) was 0.88 (range 0.61–1.00), with 79.5% [62/78] studies reporting AUROC ≥ 0.80. Out of 22 studies comparing ML techniques to existing prediction tools, clinicians, or traditional regression models, 20 performed better and 2 performed similarly. Overall, 94.8% (201/212) studies had high risk-of-bias and adherence to reporting standards was poor with a rate of 41.4%. Despite improvements over time, study quality and reporting remain inadequate. Future studies should consider standardized tools such as PROBAST and TRIPOD to improve study quality and clinical applicability.
Transplanted human cones incorporate into the retina and function in a murine cone degeneration model
Authors: Sylvia J. Gasparini, Karen Tessmer, Miriam Reh, Stephanie Wieneke, Madalena Carido, Manuela Völkner, Oliver Borsch, Anka Swiersy, Marta Zuzic, Olivier Goureau, Thomas Kurth, Volker Busskamp, Günther Zeck, Mike O. Karl, Marius Ader
Journal: Journal of Clinical Investigation (2022)

Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function.
Abstract P035: Seasonal Variations In Blood Pressure Control Among U.S. Adults With Hypertension, 2011-2018
Authors: Andrew Y Hwang, Steven M Smith
Journal: Circulation (2022)

Introduction: Blood pressure (BP) varies seasonally, typically manifesting as increased BP during the winter and reduced BP during the summer, that may contribute to difficulty in maintaining BP control among individuals with hypertension. We investigated seasonal differences in population-level BP control among U.S. adults with hypertension and whether such associations were modified by demographic and socioeconomic characteristics. Methods: We used cross-sectional 2011-2018 National Health and Nutrition Examination Survey (NHANES) data to identify participants aged ≥20 years with hypertension (defined as self-report, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or antihypertensive medication use). Participants were categorized into two seasonal periods - winter-spring (November to April) and summer-fall (May to October) - based on their NHANES examination month. Survey-weighted logistic regression modeling was performed to analyze the association of BP control (&lt;140/90 mmHg) with six-month seasonal period, adjusted for age, sex, race and ethnicity, income level, education level, and insurance status. Subgroup analyses were also performed, stratifying by demographic and socioeconomic characteristics. Results: Across all panel years, 4,350 participants had examinations in the winter-spring and 4,521 in the summer-fall season. Mean (SEM) systolic BP was significantly higher in the winter-spring season compared to the summer-fall season (136.2 [0.48] mmHg vs 134.7 [0.61] mmHg; p=0.02). A significantly lower proportion of participants had controlled BP during the winter-spring season compared to participants during the summer-fall season (50.7% vs 55.2%; unadjusted odds ratio [OR]: 0.84 [95% CI: 0.72—0.98]), though the association was modestly attenuated after adjusting for covariates (adjusted OR [aOR]: 0.88 [95% CI: 0.75—1.05]). Similar observations were seen among those taking antihypertensive medication (62.5% vs 67.7%; aOR: 0.83 [95% CI: 0.69—0.99]). Subgroup analyses in the overall hypertensive population did not reveal evidence of heterogeneity of effect across age, sex, race and ethnicity, income level, education level, or insurance status. Conclusions: Seasonal variations in population-level BP control were observed among U.S. adults with hypertension, with a lower prevalence of BP control seen among those on antihypertensive treatment during the winter-spring season than the summer-fall season. No demographic or socioeconomic characteristics appeared to be more susceptible to these seasonal variations.
Detection of F1 Hybrids from Single-genome Data Reveals Frequent Hybridization in Hymenoptera and Particularly Ants
Authors: Arthur Weyna, Lucille Bourouina, Nicolas Galtier, Jonathan Romiguier
Journal: Molecular Biology and Evolution (2022)

Hybridization occupies a central role in many fundamental evolutionary processes, such as speciation or adaptation. Yet, despite its pivotal importance in evolution, little is known about the actual prevalence and distribution of current hybridization across the tree of life. Here we develop and implement a new statistical method enabling the detection of F1 hybrids from single-individual genome sequencing data. Using simulations and sequencing data from known hybrid systems, we first demonstrate the specificity of the method, and identify its statistical limits. Next, we showcase the method by applying it to available sequencing data from more than 1,500 species of Arthropods, including Hymenoptera, Hemiptera, Coleoptera, Diptera, and Archnida. Among these taxa, we find Hymenoptera, and especially ants, to display the highest number of candidate F1 hybrids, suggesting higher rates of recent hybridization between previously isolated gene pools in these groups. The prevalence of F1 hybrids was heterogeneously distributed across ants, with taxa including many candidates tending to harbor specific ecological and life-history traits. This work shows how large-scale genomic comparative studies of recent hybridization can be implemented, uncovering the determinants of first-generation hybridization across whole taxa.
Specific Activation of the CD271 Intracellular Domain in Combination with Chemotherapy or Targeted Therapy Inhibits Melanoma Progression
Authors: Annalisa Saltari, Andreas Dzung, Marika Quadri, Natascia Tiso, Nicola Facchinello, Alberto Hernández-Barranco, Susana Garcia-Silva, Laura Nogués, Corinne Isabelle Stoffel, Phil F. Cheng, Patrick Turko, Ossia M. Eichhoff, Francesca Truzzi, Alessandra Marconi, Carlo Pincelli, Héctor Peinado, Reinhard Dummer, Mitchell P. Levesque
Journal: Cancer Research (2021)

Abstract CD271 (NGFR) is a neurotrophin receptor that belongs to the tumor necrosis receptor (TNFR) family. Upon ligand binding, CD271 can mediate either survival or cell death. Although the role of CD271 as a marker of tumor-initiating cells is still a matter of debate, its role in melanoma progression has been well documented. Moreover, CD271 has been shown to be upregulated after exposure to both chemotherapy and targeted therapy. In this study, we demonstrate that activation of CD271 by a short β-amyloid–derived peptide (Aβ(25–35)) in combination with either chemotherapy or MAPK inhibitors induces apoptosis in 2D and 3D cultures of eight melanoma cell lines. This combinatorial treatment significantly reduced metastasis in a zebrafish xenograft model and led to significantly decreased tumor volume in mice. Administration of Aβ(25–35) in ex vivo tumors from immunotherapy- and targeted therapy–resistant patients significantly reduced proliferation of melanoma cells, showing that activation of CD271 can overcome drug resistance. Aβ(25–35) was specific to CD271-expressing cells and induced CD271 cleavage and phosphorylation of JNK (pJNK). The direct protein–protein interaction of pJNK with CD271 led to PARP1 cleavage, p53 and caspase activation, and pJNK-dependent cell death. Aβ(25–35) also mediated mitochondrial reactive oxygen species (mROS) accumulation, which induced CD271 overexpression. Finally, CD271 upregulation inhibited mROS production, revealing the presence of a negative feedback loop in mROS regulation. These results indicate that targeting CD271 can activate cell death pathways to inhibit melanoma progression and potentially overcome resistance to targeted therapy. Significance: The discovery of a means to specifically activate the CD271 death domain reveals unknown pathways mediated by the receptor and highlights new treatment possibilities for melanoma.
Abstract P168: The Association Between Bariatric Surgery And Cardiometabolic Risk Factors: The National Health And Nutrition Examination Survey
Authors: Rebecca Molinsky, Sayeed Ikramuddin, Fayez Siddiqui, Ryan Demmer
Journal: Circulation (2022)

Introduction: Bariatric surgery leads to significant weight loss and improvements in cardiometabolic risk factors. To date, limited data exist investigating the relationship between bariatric surgery and markers of impaired glucose regulation. We hypothesize that participants who underwent bariatric surgery will have lower levels of HOMA-IR, fasting glucose and A1c after multivariable adjustment. Methods: A total of 9134 participants (52% female, mean age 48 +/- 17.7) in the National Health and Nutrition Examination Survey (NHANES) who were older then 20 years of age, not pregnant and not taking any diabetic medication were assessed. Participants were classified as having bariatric surgery and not having bariatric surgery. Survey design adjusted linear models regressed cardiometabolic outcomes on bariatric surgery status. LSMEANS +/- standard error and p-values are presented summarizing the association between bariatric surgery status and cardiometabolic outcomes including HOMA-IR, glycohemoglobin, mean systolic and diastolic blood pressure, fasting glucose, triglycerides LDL and HDL. Results: Among the 9134 participants , 89 underwent bariatric surgery. Those with vs. without a history of bariatric surgery were 3 years older (51 +/- 12 vs 48 +/- 18 yrs, p &lt; 0.05), more likely to be female (80% vs. 52%, p &lt; 0.05) and more likely to report a history of depression (20.3% vs. 7.8%, p &lt; 0.05). After adjusting for demographic variables, behavioral risk factors and measures of adiposity, bariatric surgery was associated with lower HOMA-IR and triglycerides but higher HDL levels (Table). Conclusion: Bariatric Surgery was associated with HOMA-IR, triglycerides, and HDL in a nationally representative sample of U.S. adults.