tbuckley/cabot-search huggingface dataset:
Phylogenetic Signal, Congruence, and Uncertainty across Bacteria and Archaea
Authors: Carolina A Martinez-Gutierrez, Frank O Aylward
Journal: Molecular Biology and Evolution (2021)

Abstract Reconstruction of the Tree of Life is a central goal in biology. Although numerous novel phyla of bacteria and archaea have recently been discovered, inconsistent phylogenetic relationships are routinely reported, and many inter-phylum and inter-domain evolutionary relationships remain unclear. Here, we benchmark different marker genes often used in constructing multidomain phylogenetic trees of bacteria and archaea and present a set of marker genes that perform best for multidomain trees constructed from concatenated alignments. We use recently-developed Tree Certainty metrics to assess the confidence of our results and to obviate the complications of traditional bootstrap-based metrics. Given the vastly disparate number of genomes available for different phyla of bacteria and archaea, we also assessed the impact of taxon sampling on multidomain tree construction. Our results demonstrate that biases between the representation of different taxonomic groups can dramatically impact the topology of resulting trees. Inspection of our highest-quality tree supports the division of most bacteria into Terrabacteria and Gracilicutes, with Thermatogota and Synergistota branching earlier from these superphyla. This tree also supports the inclusion of the Patescibacteria within the Terrabacteria as a sister group to the Chloroflexota instead of as a basal-branching lineage. For the Archaea, our tree supports three monophyletic lineages (DPANN, Euryarchaeota, and TACK/Asgard), although we note the basal placement of the DPANN may still represent an artifact caused by biased sequence composition. Our findings provide a robust and standardized framework for multidomain phylogenetic reconstruction that can be used to evaluate inter-phylum relationships and assess uncertainty in conflicting topologies of the Tree of Life.
Sex-Specific Association of the X Chromosome With Cognitive Change and Tau Pathology in Aging and Alzheimer Disease
Authors: Emily J. Davis, Caroline W. Solsberg, Charles C. White, Elena Miñones-Moyano, Marina Sirota, Lori Chibnik, David A. Bennett, Philip L. De Jager, Jennifer S. Yokoyama, Dena B. Dubal
Journal: JAMA Neurology (2021)

The X chromosome represents 5% of the human genome in women and men, and its influence on cognitive aging and Alzheimer disease (AD) is largely unknown.
Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data
Authors: Olfa Harki, Quentin Boete, Jean-Louis Pépin, Claire Arnaud, Elise Belaidi, Gilles Faury, Charles Khouri, Anne Briançon-Marjollet
Journal: European Respiratory Journal (2021)

Background Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs. Methods We searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE −/− ) mice. We used the standardised mean difference (SMD) to compare results between studies. Results IH significantly increased mean arterial pressure (+13.90 (95% CI 11.88–15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima–media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58–1.62); absolute values +5.23 (2.81–7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE −/− mice (SMD 1.08 (95% CI 0.80–1.37)). Conclusions Our meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.
Screening and Risk Stratification Strategy Reduced Decompression Sickness Occurrence in Divers With Patent Foramen Ovale
Authors: Jakub Honěk, Martin Šrámek, Tomáš Honěk, Aleš Tomek, Luděk Šefc, Jaroslav Januška, Jiří Fiedler, Martin Horváth, Štěpán Novotný, Marek Brabec, Josef Veselka
Journal: JACC. Cardiovascular imaging (2021)
Safety and Efficacy of Telehealth Medication Abortions in the US During the COVID-19 Pandemic
Authors: Ushma D. Upadhyay, Leah R. Koenig, Karen R. Meckstroth
Journal: JAMA Network Open (2021)

This cohort study examines the safety and efficacy of fully remote, asynchronous medication abortion care during the COVID-19 pandemic.
Recent Advances in Aggregation‐Induced Emission Materials and Their Biomedical and Healthcare Applications
Authors: Wei He, Tianfu Zhang, Haotian Bai, Ryan T. K. Kwok, Jacky W. Y. Lam, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2021)

The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques.
Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases
Authors: Keith D. Lindor, Christopher L. Bowlus, James Boyer, Cynthia Levy, Marlyn Mayo
Journal: Hepatology (2021)

Guidance Statements 9 and 10 that were published in the 2018 Practice Guidance on primary biliary cholangitis (PBC) have been revised.[1] This American Association for the Study of Liver Diseases 2021 practice guidance on PBC is a focused update of the PBC guidance published in 2018. The major changes from the last guidance to this guidance include information about obeticholic acid (OCA). In May 2021, the Food and Drug Administration issued a new warning restricting the use of OCA in patients with advanced cirrhosis.[2] This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Two guidance statements that were published in the 2018 practice guidance on PBC have been revised as follows: 9. Fibrates can be considered as off-label alternatives for patients with PBC and inadequate response to ursodeoxycholic acid, although fibrates are discouraged in patients with decompensated liver disease. 10. OCA is contraindicated in patients with advanced cirrhosis. This is defined as cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia). Furthermore, we would recommend careful monitoring of any patient with cirrhosis, even if not advanced, receiving OCA. The authors are grateful for the valuable contributions of the American Association for the Study of Liver Diseases Practice Guideline Committee. Members of the committee include George Ioannou (chair); Rabab Ali, Scott W. Biggins, Roniel Cabrera, Henry Chang, Michael F. Chang, Albert Do, David S. Goldberg, R. W. Ray Kim (board liaison), Lindsay Y. King, Cynthia Levy, Jeff McIntyre, Jessica L. Mellinger, Anthony J. Michaels, Mindie H. Nguyen, Nadia Ovchinsky, Anjana A. Pillai, Daniel S. Pratt, Hugo R. Rosen, Christopher J. Sonnenday, Matthew J. Stotts, Lisa B. VanWagner, and Elizabeth C. Verna. Dr. Mayo consults for and received grants from Cymabay. She received grants from Intercept. Dr. Levy consults for, advises, and received grants from Intercept, Cymabay, Genfit, GSK, Pliant, Mirum, and Cara Therapeutics. She consults for and advises Escient, Teva, and Calliditas. She received grants from Gilead, Novartis, High Tide, Zydus, and Target PharmaSolutions. She receives royalities from Up-to-date.
DS14: Experience of using a scar‐assessment tool to evaluate scars after Mohs surgery via virtual consultation during the COVID‐19 pandemic
Authors: A Alani, T Oliphant
Journal: British Journal of Dermatology (2021)

Composite grafts have a well-established role in nasal reconstruction; however, there are few data on long-term outcomes.The patient's perspective of their facial scar after skin cancer surgery influences their perception of care and quality of life.In our practice, composite grafts are harvested from the crus of the helix.The secondary defect is repaired by simple linear closure, while the graft is secured to the defect with interrupted absorbable sutures.Typically, the graft is immobilized with a bolster dressing or basting suture and covered with a nonadherent dressing, which is removed after 7 days.Our objective was to determine patient satisfaction with composite grafts using the FACE-Q Skin Cancer questionnaire, which measures appearance satisfaction, quality of life and patient experience.We distributed a postal questionnaire (FACE-Q) to all 66 patients who had a composite graft performed in our centre over the last 5 years.This questionnaire also encouraged participants to provide comments about their experience and overall outcome.In total, we had a response rate of 41% (n = 27).Mean age was 71 years (range 48-93) and mean length of follow-up was 29 months (range 6-61).Twenty-three patients (85%) were very satisfied with their facial appearance, three (11%) were somewhat satisfied and one (4%) was dissatisfied.Twenty-five (92%) respondents were 'not at all bothered' by their scar, while one (4%) was 'moderately bothered' and one (4%) was 'a little bothered'.Nine (33%) respondents 'strongly disagreed' and 11 (41%) respondents 'disagreed' about having experienced worry related to their skin cancer.Four (15%) and three (11%) respondents 'agreed' and 'strongly agreed' to have worried about skin cancer, respectively.Twenty-four (89%) 'strongly disagreed' to experiencing any psychosocial distress related to their appearance after surgery, while two (7%) respondents 'somewhat disagreed' and one (4%) 'somewhat agreed'.Freetext comments from respondents were, overall, positive.Appearance satisfaction after surgery is an important, but often overlooked, treatment outcome.The FACE-Q Skin Cancer questionnaire provides the dermatological surgeon with a comprehensive set of meaningful scales for the facial skin cancer population.The limitations of this study are the small sample size and low response rate.However, the study has shown that composite graft repair offers good patient satisfaction.
Association of Vaccine Type and Prior SARS-CoV-2 Infection With Symptoms and Antibody Measurements Following Vaccination Among Health Care Workers
Authors: Amanda K. Debes, Shaoming Xiao, Elizabeth Colantuoni, Emily R. Egbert, Patrizio Caturegli, Avinash Gadala, Aaron M. Milstone
Journal: JAMA Internal Medicine (2021)

Discussion | In the United States in 2020, we found that the proportion of community-dwelling homebound adults aged 70 years or older substantially increased, particularly among Black non-Hispanic and Hispanic/Latino individuals.Although our study could not establish the reasons for this first major increase in the homebound population in a decade, a likely explanation is compliance with social distancing and other public health recommendations to minimize the risk of infection with SARS-CoV-2.Our study also found notable racial and ethnic differences.For example, White non-Hispanic individuals were more likely to reside alone, which may have left them without caregiving assistance.In contrast, Black non-Hispanic and Hispanic/Latino individuals were more likely to live in multiperson households, which may have increased their risk of being exposed to SARS-CoV-2.Although the reason for higher rates of being homebound among Black non-Hispanic and Hispanic/Latino populations is unknown, it may be due to greater regional incidence of SARS-CoV-2 or reduced resources to safely navigate leaving home (eg, private transportation and safe grocery shopping options).The respondents, particularly Black non-Hispanic and Hispanic/Latino individuals, infrequently used digital technologies, a finding that is consistent with results of a prior study and has implications for equity regarding expanded telemedicine use. 6 Other limitations of our study include that homebound rates may have fluctuated during the pandemic and by region, which we did not capture.The extent to which the increased prevalence of homebound older adults that we observed in 2020 will continue in 2021 as the COVID-19 pandemic abates, as well as the likely social, psychological, and physical effects, remains to be seen.
Protective Role of HO-1 Expressing CD16+ Patrolling Monocytes Against Hemolysis-Induced Endothelial Damage and Vaso-Occlusive Crisis in Sickle Cell Disease
Authors: Yunfeng Liu, Fangmiao Jing, Woelsung Yi, Avital Mendelson, Patricia Shi, Ronald Walsh, David F. Friedman, Caterina Minniti, Deepa Manwani, Stella T Chou, Karina Yazdanbakhsh
Journal: Blood (2017)
Effect of Cisplatin and Gemcitabine With or Without Berzosertib in Patients With Advanced Urothelial Carcinoma
Authors: Sumanta K. Pal, Paul H. Frankel, Amir Mortazavi, Matthew Milowsky, Ulka Vaishampayan, Mamta Parikh, Yung Lyou, Peng Weng, Rahul Parikh, Benjamin Teply, Robert Dreicer, Hamid Emamekhoo, Dror Michaelson, Christopher Hoimes, Tian Zhang, Sandy Srinivas, William Y. Kim, Yujie Cui, Edward Newman, Primo N. Lara
Journal: JAMA Oncology (2021)

Preclinical studies suggest that inhibition of single-stranded DNA repair by ataxia telangiectasia and Rad3 (ATR) may enhance the cytotoxicity of cisplatin, gemcitabine, and other chemotherapeutic agents. Cisplatin with gemcitabine remains the standard up-front therapy for treatment in patients with metastatic urothelial cancer.
Phase 1 clinical trial of the PI3Kδ inhibitor YY-20394 in patients with B-cell hematological malignancies
Authors: Bo Jiang, Junyuan Qi, Yuqin Song, Zengjun Li, Meifeng Tu, Lingyan Ping, Zongliang Liu, Hanying Bao, Zusheng Xu, Lugui Qiu
Journal: Journal of Hematology & Oncology (2021)

Abstract YY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20–200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted. Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&amp;draw=2&amp;rank=1 .
Continuation of Antipsychotic Treatment in Pregnancy—Do Not Panic
Authors: Amanda Yeaton-Massey, Elizabeth Fitelson, Patricia Robertson
Journal: JAMA Internal Medicine (2021)

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Lorlatinib in a Child with <i>ALK</i>-Fusion–Positive High-Grade Glioma
Authors: Aditi Bagchi, Brent A Orr, Olivia Campagne, Sandeep Dhanda, Sreenath Nair, Quynh Tran, Anthony M Christensen, Amar Gajjar, Larissa V Furtado, Aksana Vasilyeva, Frederick Boop, Clinton Stewart, Giles W Robinson
Journal: New England Journal of Medicine (2021)

Lorlatinib Response in ALK-Fusion–Positive Glioma A child near death with an ALK-fusion–positive high-grade glioma refractory to standard treatment had a dramatic response when treatment with lorla...
Covid-19: FDA set to grant full approval to Pfizer vaccine without public discussion of data
Authors: Gareth Iacobucci
Journal: BMJ (2021)

<h3>Background</h3> The use of potentially inappropriate medications (PIMs) is an important issue in older patients who are at risk of adverse drug events. <h3>Aim</h3> To determine the prevalence of PIM use, according to Beers criteria, among an older population (aged ≥65 years) in a large family medicine setting, and to identify the associated risks. <h3>Design &amp; setting</h3> A prospective cross-sectional study of patients aged ≥65 years was conducted from June 2017 to June 2018 at the Family and Community Medicine (FCM) clinics of King Saud Medical City (KSMC) in Riyadh, Saudi Arabia. <h3>Method</h3> This cross-sectional study included patients aged ≥65 years who were seen at new appointments or followed-up at the FCM clinics of KSMC in Riyadh, Saudi Arabia. Data were collected by extensive face-to-face interviews and from the patients’ medical records. <h3>Results</h3> A total of 270 older patients aged 72.41 ±6.23 years (mean ±standard deviation [SD]) were included in the present study. The prevalence of PIMs was 60.7% (<i>n</i> = 164). Multivariate analyses identified three independent variables associated with PIMs: incremental age per 5 years (odds ratio [OR] 1.47, 95% confidence intervals [CI] = 1.15 to 1.88; <i>P</i> = 0.002), female sex (OR 1.95, 95% CI = 1.10 to 3.42; <i>P</i> = 0.021), and polypharmacy (OR 8.21, 95% CI = 4.58 to 14.7; <i>P</i>&lt;0.001). The most common PIMs used were 39.4% related to proton pump inhibitors (PPI), 25.2% to diuretics (other than spironolactone), 10.6% to non-steroidal anti-inflammatory drugs (NSAIDs), and 8.7% to aspirin use. <h3>Conclusion</h3> This study showed high prevalence of PIMs. Increasing age, female sex, and polypharmacy were found to be significant risk factors for PIM use. The frequency of morbidities was not significantly different among patients with PIMs compared to those without PIMs, except for hypertension and osteoarthritis, which were more common in the PIMs group. The present study reinforces the importance of comprehensive medication management and reviews.
Phase II, Randomized Study of Spartalizumab (PDR001), an Anti–PD-1 Antibody, versus Chemotherapy in Patients with Recurrent/Metastatic Nasopharyngeal Cancer
Authors: Caroline Even, Hung-Ming Wang, Shau-Hsuan Li, Roger K-C Ngan, Arunee Dechaphunkul, Li Zhang, Chia-Jui Yen, Po Chung Chan, Somvilai Chakrabandhu, Brigette B.Y. Ma, Suebpong Tanasanvimon, Victor H.F. Lee, Pei-Jen Lou, Zujun Li, Alexander I. Spira, Ammar Sukari, Joël Guigay, Steven McCune, Juan Gonzalez-Maffe, Sebastian Szpakowski, Yao Yao, Hongzi Liang, Jennifer Mataraza, Romain Séchaud, Luigi Manenti, Darren W-T. Lim
Journal: Clinical Cancer Research (2021)

Abstract Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression. Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.