tbuckley/cabot-search huggingface dataset:
Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: A nationally representative cohort study
Authors: Laith J. Abu-Raddad, Hiam Chemaitelly, Houssein H. Ayoub, Peter Coyle, Joel A. Malek, Ayeda A. Ahmed, Yasmin A. Mohamoud, Shameem Younuskunju, Patrick Tang, Zaina Al Kanaani, Einas Al Kuwari, Adeel A. Butt, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F. Abdul Rahim, Gheyath K. Nasrallah, Hadi M. Yassine, Mohamed Ghaith Al Kuwari, Hamad Eid Al Romaihi, Mohamed H. Al-Thani, Abdullatif Al Khal, Roberto Bertollini
Journal: PLoS Medicine (2021)

Background The epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study’s objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant. Methods and findings Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 individuals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic’s second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented. Conclusions In this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants.
Reverse Chemical Ecology Suggests Putative Primate Pheromones
Authors: Valeriia Zaremska, Isabella Maria Fischer, Giovanni Renzone, Simona Arena, Andrea Scaloni, Wolfgang Knoll, Paolo Pelosi
Journal: Molecular Biology and Evolution (2021)

Pheromonal communication is widespread among living organisms, but in apes and particularly in humans there is currently no strong evidence for such phenomenon. Among primates, lemurs use pheromones to communicate within members of the same species, whereas in some monkeys such capabilities seem to be lost. Chemical communication in humans appears to be impaired by the lack or malfunctioning of biochemical tools and anatomical structures mediating detection of pheromones. Here, we report on a pheromone-carrier protein (SAL) adopting a "reverse chemical ecology" approach to get insights on the structures of potential pheromones in a representative species of lemurs (Microcebus murinus) known to use pheromones, Old-World monkeys (Cercocebus atys) for which chemical communication has been observed, and humans (Homo sapiens), where pheromones and chemical communication are still questioned. We have expressed the SAL orthologous proteins of these primate species, after reconstructing the gene encoding the human SAL, which is disrupted due to a single base mutation preventing its translation into RNA. Ligand-binding experiments with the recombinant SALs revealed macrocyclic ketones and lactones as the best ligands for all three proteins, suggesting cyclopentadecanone, pentadecanolide, and closely related compounds as the best candidates for potential pheromones. Such hypothesis agrees with the presence of a chemical very similar to hexadecanolide in the gland secretions of Mandrillus sphinx, a species closely related to C. atys. Our results indicate that the function of this carrier protein has not changed much during evolution from lemurs to humans, although its physiological role has been certainly impaired in humans.
Prognostic value of global deep white matter DTI metrics for 1-year outcome prediction in ICU traumatic brain injury patients: an MRI-COMA and CENTER-TBI combined study
Authors: Louis Puybasset, Vincent Perlbarg, Jean Unrug, Didier Cassereau, Damien Galanaud, Grégory Torkomian, Valentine Battisti, Muriel Lefort, Lionel Velly, Vincent Degos, Guiseppe Citerio, Éléonore Bayen, Mélanie Pelegrini-Issac
Journal: Intensive Care Medicine (2021)
Isometric exercise versus high-intensity interval training for the management of blood pressure: a systematic review and meta-analysis
Authors: Jamie Edwards, Anthony De Caux, James Donaldson, Jonathan Wiles, Jamie O'Driscoll
Journal: British Journal of Sports Medicine (2021)

Objective We aimed to compare the efficacy of isometric exercise training (IET) versus high-intensity interval training (HIIT) in the management of resting blood pressure (BP). Design Systematic review and meta-analysis. Data sources PubMed (MEDLINE), the Cochrane library and SPORTDiscus were systematically searched. Eligibility criteria Randomised controlled trials published between 1 January 2000 and 1 September 2020. Research trials reporting the effects of IET or HIIT on resting BP following a short-term intervention (2–12 weeks). Results 38 studies were analysed (18 IET and 20 HIIT), including 1583 (672 IET and 911 HIIT) participants, of which 612 (268 IET and 344 HIIT) were controls. IET produced significantly greater reductions in resting BP compared with HIIT with systolic, diastolic and mean BP effect sizes of 8.50 mm Hg vs 2.86 mm Hg (Q=17.10, p&lt;0.001), 4.07 mm Hg vs 2.48 mm Hg (Q=4.71, p=0.03) and 6.46 mm Hg vs 3.15 mm Hg (Q=4.21, p=0.04) respectively. However, HIIT reduced resting heart rate significantly more than IET (3.17bpm vs 1.34bpm, Q=7.63, p=0.006). Conclusion While both modes are efficacious, IET appears to be the superior mode of exercise in the management of resting BP. However, HIIT may achieve wider physiological benefits, with greater reductions in resting heart rate.
Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life
Authors: Dominik Lewandowski, Christopher L. Sander, Aleksander Tworak, Fangyuan Gao, Qianlan Xu, Dorota Skowronska-Krawczyk
Journal: Progress in Retinal and Eye Research (2021)

The retinal pigment epithelium-photoreceptor interphase is renewed each day in a stunning display of cellular interdependence. While photoreceptors use photosensitive pigments to convert light into electrical signals, the RPE supports photoreceptors in their function by phagocytizing shed photoreceptor tips, regulating the blood retina barrier, and modulating inflammatory responses, as well as regenerating the 11-cis-retinal chromophore via the classical visual cycle. These processes involve multiple protein complexes, tightly regulated ligand-receptors interactions, and a plethora of lipids and protein-lipids interactions. The role of lipids in maintaining a healthy interplay between the RPE and photoreceptors has not been fully delineated. In recent years, novel technologies have resulted in major advancements in understanding several facets of this interplay, including the involvement of lipids in phagocytosis and phagolysosome function, nutrient recycling, and the metabolic dependence between the two cell types. In this review, we aim to integrate the complex role of lipids in photoreceptor and RPE function, emphasizing the dynamic exchange between the cells as well as discuss how these processes are affected in aging and retinal diseases.
Limited Introgression between Rock-Wallabies with Extensive Chromosomal Rearrangements
Authors: Sally Potter, Jason G Bragg, Rustamzhon Turakulov, Mark D B Eldridge, Janine Deakin, Mark Kirkpatrick, Richard J Edwards, Craig Moritz
Journal: Molecular Biology and Evolution (2021)

Chromosome rearrangements can result in the rapid evolution of hybrid incompatibilities. Robertsonian fusions, particularly those with monobrachial homology, can drive reproductive isolation amongst recently diverged taxa. The recent radiation of rock-wallabies (genus Petrogale) is an important model to explore the role of Robertsonian fusions in speciation. Here, we pursue that goal using an extensive sampling of populations and genomes of Petrogale from north-eastern Australia. In contrast to previous assessments using mitochondrial DNA or nuclear microsatellite loci, genomic data are able to separate the most closely related species and to resolve their divergence histories. Both phylogenetic and population genetic analyses indicate introgression between two species that differ by a single Robertsonian fusion. Based on the available data, there is also evidence for introgression between two species which share complex chromosomal rearrangements. However, the remaining results show no consistent signature of introgression amongst species pairs and where evident, indicate generally low introgression overall. X-linked loci have elevated divergence compared with autosomal loci indicating a potential role for genic evolution to produce reproductive isolation in concert with chromosome change. Our results highlight the value of genome scale data in evaluating the role of Robertsonian fusions and structural variation in divergence, speciation, and patterns of molecular evolution.
Community-Based Testing Sites for SARS-CoV-2 — United States, March 2020–November 2021
Authors: Mark F. Miller, Min Shi, Alison Motsinger-Reif, Clarice R. Weinberg, Joseph D. Miller, Erin Nichols
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Immediately following the March 13, 2020 declaration of COVID-19 as a national emergency (1), the U.S. government began implementing national testing programs for epidemiologic surveillance, monitoring of frontline workers and populations at higher risk for acquiring COVID-19, and identifying and allocating limited testing resources. Effective testing supports identification of COVID-19 cases; facilitates isolation, quarantine, and timely treatment measures that limit the spread of SARS-CoV-2 (the virus that causes COVID-19); and guides public health officials about the incidence of COVID-19 in a community. A White House Joint Task Force, co-led by the Department of Health and Human Services (HHS) and the Federal Emergency Management Agency (FEMA), created the Community-Based Testing Sites (CBTS) program working with state and local partners (2). This report describes the timeline, services delivered, and scope of the CBTS program. During March 19, 2020-April 11, 2021, the CBTS program conducted 11,661,923 SARS-CoV-2 tests at 8,319 locations across the United States and its territories, including 402,223 (3.5%) administered through Drive-Through Testing, 10,129,142 (86.9%) through Pharmacies+ Testing, and 1,130,558 (9.7%) through Surge Testing programs. Tests administered through the CBTS program yielded 1,176,959 (10.1%) positive results for SARS-CoV-2. Among tested persons with available race data,* positive test results were highest among American Indian or Alaska Native (14.1%) and Black persons (10.4%) and lowest among White persons (9.9%), Asian persons (7.3%), and Native Hawaiian or Other Pacific Islanders (6.4%). Among persons with reported ethnicity, 25.3% were Hispanic, 15.9% of whom received a positive test result. Overall, 82.0% of test results were returned within 2 days, but the percentage of test results returned within 2 days was as low as 40.7% in July 2020 and 59.3% in December 2020 during peak testing periods. Strong partnerships enabled a rapid coordinated response to establish the federally supported CBTS program to improve access to no-charge diagnostic testing, including for frontline workers, symptomatic persons and close contacts, and persons living in high-prevalence areas. In April 2021, the CBTS Pharmacies+ Testing and Surge Testing programs were expanded into the Increasing Community Access to Testing (ICATT) program. As of November 12, 2021, the CBTS and ICATT programs conducted approximately 26.6 million tests with approximately 10,000 active testing sites. Although the CBTS program represented a relatively small portion of overall U.S. SARS-CoV-2 testing, with its successful partnerships and adaptability, the CBTS program serves as a model to guide current community-based screening, surveillance, and disease control programs, and responses to future public health emergencies.
Expert Panel Consensus on Management of Advanced Cancer–Related Pain in Individuals With Opioid Use Disorder
Authors: Jessica S. Merlin, Dmitry Khodyakov, Robert Arnold, Hailey W. Bulls, Emily Dao, Jennifer Kapo, Caroline King, Diane Meier, Judith Paice, Christine Ritchie, Jane M. Liebschutz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Opioid use disorder (OUD) is an important comorbidity in individuals with advanced cancer, in whom pain is common. Full-agonist opioid medications are the cornerstone of cancer pain management, but the existing literature does not address how to manage cancer pain in patients with OUD. <h3>Objective</h3> To conduct an expert panel to develop consensus on the appropriateness of management of cancer pain in individuals with co-occurring advanced cancer and OUD. <h3>Evidence Review</h3> A 3-round modified Delphi process was completed from August to October 2020 with 2 cases: patient with advanced cancer, pain, and OUD treated with buprenorphine-naloxone or methadone. Participants rated management strategies in round 1, discussed results in round 2, and provided final responses in round 3. ExpertLens, an online approach to conducting modified Delphi panels, was used. Participants were experts in palliative care, addiction, or both, recruited by email from palliative care and addiction-focused professional groups, lists from prior studies, and snowball sampling. Data analysis was performed from November 2020 to July 2021. <h3>Findings</h3> Of 120 experts (median age, 40-49 years), most were White (78 participants [94%]), female (74 participants [62%]), and held MD or DO degrees (115 participants [96%]); 84 (70%) participated in all rounds. For a patient with OUD taking buprenorphine-naloxone, it was deemed appropriate to continue buprenorphine-naloxone with thrice-daily dosing. Continuing buprenorphine-naloxone and adding a full-agonist opioid was deemed to be appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for patients with a prognosis of months to years. For a patient with OUD taking methadone dispensed at a methadone clinic, it was deemed appropriate to take over prescribing and dose twice or thrice daily. Continuing methadone daily while adding another full-agonist opioid was deemed appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for those with a prognosis of months to years. <h3>Conclusions and Relevance</h3> The findings of this qualitative study provide urgently needed, consensus-based guidance for clinicians and highlight critical research and policy gaps needed to facilitate implementation.
160P Pembrolizumab re-challenge in patients with relapsed non-small cell lung cancer (NSCLC): A preliminary report of the REPLAY phase II trial - cohort I
Authors: S. Ponce Aix, E. Carcereny Costa, J. Bosch-Barrera, E. Felip Font, M. Guirado, J. Coves Sarto, M. Majem Tarruella, O.J. Juan Vidal, E. Dalmau Portulas, P. Diz, A.L.O. Ortega Granados, M. Domine Gomez, A. Blasco Cordellat, J. Mosquera Martinez, M.A. Sala Gonzalez, M. Dorta, V. Calvo de Juan, J. Zugazagoitia, A.B. Enguita, L. Paz-Ares
Journal: Annals of Oncology (2021)
Co-Targeting of MDM2 and CDK4/6 with Siremadlin and Ribociclib for the Treatment of Patients with Well-Differentiated or Dedifferentiated Liposarcoma: Results from a Proof-of-Concept, Phase Ib Study
Authors: Albiruni R. Abdul Razak, Sebastian Bauer, Cristina Suarez, Chia-Chi Lin, Richard Quek, Marie Luise Hütter-Krönke, Ricardo Cubedo, Stephane Ferretti, Nelson Guerreiro, Astrid Jullion, Elena J. Orlando, Giorgia Clementi, Janna Sand Dejmek, Ensar Halilovic, Claire Fabre, Jean-Yves Blay, Antoine Italiano
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are characterized by co-amplification of the murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) oncogenes. Siremadlin, a p53–MDM2 inhibitor, was combined with ribociclib, a CDK4/6 inhibitor, in patients with locally advanced/metastatic WDLPS or DDLPS who had radiologically progressed on, or despite, prior systemic therapy. Patients and Methods: In this proof-of-concept, phase Ib, dose-escalation study, patients received siremadlin and ribociclib across different regimens until unacceptable toxicity, disease progression, and/or treatment discontinuation: Regimen A [4-week cycle: siremadlin once daily (QD) and ribociclib QD (2 weeks on, 2 weeks off)], Regimen B [3-week cycle: siremadlin once every 3 weeks; ribociclib QD (2 weeks on, 1 week off)], and Regimen C [4-week cycle: siremadlin once every 4 weeks; ribociclib QD (2 weeks on, 2 weeks off)]. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of siremadlin plus ribociclib in one or more regimens. Results: As of October 16, 2019 (last patient last visit), 74 patients had enrolled. Median duration of exposure was 13 (range, 1–174) weeks. Dose-limiting toxicities occurred in 10 patients, most of which were Grade 3/4 hematologic events. The RDE was siremadlin 120 mg every 3 weeks plus ribociclib 200 mg QD (Regimen B). Three patients achieved a partial response, and 38 achieved stable disease. One patient (Regimen C) died as a result of treatment-related hematotoxicity. Conclusions: Siremadlin plus ribociclib demonstrated manageable toxicity and early signs of antitumor activity in patients with advanced WDLPS or DDLPS.
Ultrarapid Method for Coating Electrochemical Sensors with Antifouling Conductive Nanomaterials Enables Highly Sensitive Multiplexed Detection in Whole Blood
Authors: Sanjay S. Timilsina, Nolan Durr, Mohamed Yafia, Hani Sallum, Pawan Jolly, Donald E. Ingber
Journal: Advanced Healthcare Materials (2021)

The commercialization of electrochemical (EC)-sensors for medical diagnostics is currently limited by their rapid fouling in biological fluids, and use of potential antifouling coatings is hindered by the complexity and cost of application methods. Here, a simple ultrafast (< 1 min) method is described for coating EC-sensors with cross-linked bovine serum albumin infused with conductive, pentaamine-functionalized, graphene particles that can be stored at room temperature for at least 20-weeks, which provides unprecedented sensitivity and selectivity for diagnostic applications. The antifouling coating is applied directly on-chip using rapid heating via simple dip-coating, which provides unprecedented high levels of electrode conductivity for up to 9-weeks in unprocessed biological samples. This method is leveraged to develop a multiplexed platform for detecting clinically relevant biomarkers including myocardial infarction and traumatic brain injury using only 15 µL of blood. Single-digit pg mL-1 sensitivity is obtained within minutes in unprocessed human plasma and whole blood, which is faster and at least 50 times more sensitive than traditional enzyme-linked immunosorbent assays, and the signal generated is stable enough to be measured after 1 week of storage. The multiplexed EC-sensor platform is validated by analyzing 22 patient samples and demonstrating excellent correlation with reported clinical values.
Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse
Authors: Wenyu Zhang, Diethard Tautz
Journal: Molecular Biology and Evolution (2021)

Abstract Although the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.