tbuckley/cabot-search huggingface dataset:
Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution
Authors: Ilias Georgakopoulos-Soares, Ofer Yizhar-Barnea, Ioannis Mouratidis, Martin Hemberg, Nadav Ahituv
Journal: Genome biology (2021)

Abstract Nullomers and nullpeptides are short DNA or amino acid sequences that are absent from a genome or proteome, respectively. One potential cause for their absence could be their having a detrimental impact on an organism. Results Here, we identify all possible nullomers and nullpeptides in the genomes and proteomes of thirty eukaryotes and demonstrate that a significant proportion of these sequences are under negative selection. We also identify nullomers that are unique to specific functional categories: coding sequences, exons, introns, 5′UTR, 3′UTR, promoters, and show that coding sequence and promoter nullomers are most likely to be selected against. By analyzing all protein sequences across the tree of life, we further identify 36,081 peptides up to six amino acids in length that do not exist in any known organism, termed primes. We next characterize all possible single base pair mutations that can lead to the appearance of a nullomer in the human genome, observing a significantly higher number of mutations than expected by chance for specific nullomer sequences in transposable elements, likely due to their suppression. We also annotate nullomers that appear due to naturally occurring variants and show that a subset of them can be used to distinguish between different human populations. Analysis of nullomers and nullpeptides across vertebrate evolution shows they can also be used as phylogenetic classifiers. Conclusions We provide a catalog of nullomers and nullpeptides in distinct functional categories, develop methods to systematically study them, and highlight the use of variability in these sequences in other analyses
Abstract 19445: Copolymer Treatment Preserves Function of Isolated Cardiac Mitochondria Only When Given Immediately Upon Reperfusion
Authors: Kareem S William, Michele M Salzman, Hunter F Douglas, Claudius Balzer, Kadambari C Shekar, Matthias L Riess
Journal: Circulation (2017)

Introduction: Poloxamer 188 (P188, MW 8350 D) is a triblock copolymer with a central hydrophobic chain and two hydrophilic tails that enable it to function as a patch when cellular membrane integri...
Association Between Human Papillomavirus Vaccination and Primary Ovarian Insufficiency in a Nationwide Cohort
Authors: Anders Hviid, Emilia Myrup Thiesson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Anecdotal case reports have suggested an association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency, but observational studies of HPV and primary ovarian insufficiency are rare, and their findings do not support an association. However, available studies have been limited by statistical power, and concerns about infertility after vaccination are associated with lower levels of uptake of the cancer-preventing vaccine in many countries. <h3>Objective</h3> To evaluate the risk of primary ovarian insufficiency after quadrivalent human papillomavirus (4HPV) vaccination. <h3>Design, Setting, and Participants</h3> This retrospective cohort study with follow-up from 2007 to 2016 used nationwide data for 996 300 Danish-born girls and women aged 11 to 34 years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of primary ovarian insufficiency diagnoses by 4HPV vaccination status with adjustment for age, calendar period, and a propensity score summarizing health care use. Data were analyzed from October 2020 to January 2021. <h3>Exposures</h3> Receiving 4HPV vaccination compared with receiving no vaccination. <h3>Main Outcomes and Measures</h3> The main outcome was hospital contacts for primary ovarian insufficiency, and the main outcome measures were HRs comparing rates of primary ovarian insufficiency among vaccinated and unvaccinated individuals. <h3>Results</h3> During 6 781 166 person-years of follow-up among 996 300 girls and women aged 11 to 34 years (505 829 vaccinated individuals [50.8%] and 490 471 unvaccinated individuals [49.2%]), 144 individuals were diagnosed with primary ovarian insufficiency, including 54 individuals diagnosed after 4HPV vaccination. The median (interquartile range) age of primary ovarian insufficiency diagnosis was 26.94 (12.68) years. The adjusted HR of primary ovarian insufficiency comparing 4HPV vaccination to no vaccination was 0.96 (95% CI, 0.55-1.68). <h3>Conclusions and Relevance</h3> This study found no association between HPV vaccination and primary ovarian insufficiency. However, given the rarity of the outcome in this study, the presence of a clinically relevant increase in rate of diagnosis cannot be excluded.
Clinical Phage Microbiology: a suggested framework and recommendations for the in-vitro matching steps of phage therapy
Authors: Daniel Gelman, Ortal Yerushalmy, Sivan Alkalay-Oren, Chani Rakov, Shira Ben-Porat, Leron Khalifa, Karen Adler, Mohanad Abdalrhman, Shunit Coppenhagen-Glazer, Saima Aslam, Robert T Schooley, Ran Nir-Paz, Ronen Hazan
Journal: The Lancet Microbe (2021)

Phage therapy is a promising solution for bacterial infections that are not eradicated by conventional antibiotics. A crucial element of this approach is appropriate matching of bacteriophages and antibiotics to the bacterial target according to the clinical setting. However, there is currently little consistency in the protocols used for the laboratory evaluation of bacteriophages intended for antibacterial treatment. In this Personal View, we suggest a framework aimed to match appropriate bacteriophage-based treatments in clinical microbiology laboratories. This framework, which we have termed Clinical Phage Microbiology, is based on the current research on phage treatments. In addition, we discuss special cases that might require additional relevant evaluation, including bacteriophage interactions with the host immune response, biofilm-associated infections, and polymicrobial infections. The Clinical Phage Microbiology pipeline could serve as the basis for future standardisation of laboratory protocols for personalised phage therapy.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer
Authors: T. Yoshino, G. Argilés, E. Oki, E. Martinelli, H. Taniguchi, D. Arnold, S. Mishima, Y. Li, B.K. Smruti, J.B. Ahn, I. Faud, C.E. Chee, K.-H. Yeh, P.-C. Lin, C. Chua, H.H. Hasbullah, M.A. Lee, A. Sharma, Y. Sun, G. Curigliano, H. Bando, F. Lordick, T. Yamanaka, J. Tabernero, E. Baba, A. Cervantes, A. Ohtsu, S. Peters, C. Ishioka, G. Pentheroudakis
Journal: Annals of Oncology (2021)
Molecular Landscape of Therapy-related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers
Authors: Sabine Khalife-Hachem, Khalil Saleh, Florence Pasquier, Christophe Willekens, Anthony Tarabay, Leony Antoun, Thomas Grinda, Cristina Castilla-Llorente, Matthieu Duchmann, Cyril Quivoron, Nathalie Auger, Veronique Saada, Suzette Delaloge, Alexandra Leary, Aline Renneville, Ileana Antony-Debre, Filippo Rosselli, Stéphane De Botton, Flore Salviat, Christophe Marzac, Jean-Baptiste Micol
Journal: HemaSphere (2021)

Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes. We investigated the impact of clonal hematopoiesis of indeterminate potential-associated mutations (CHIP-AMs defined as presence at TRMN stage of mutations described in CHIP with a frequency &gt;1%) on overall survival (OS) and the clinical relevance of a modified genetic ontogeny-based classifier that categorized patients in 3 subgroups. The most frequently mutated genes were TP53 (31%), DNMT3A (19%), IDH1/2 (13%), NRAS (13%), TET2 (12%), NPM1 (10%), PPM1D (9%), and PTPN11 (9%). CHIP-AMs were detected in 66% of TRMN patients, with no impact on OS. Yet, patients with CHIP-AM were older and had a longer time interval between solid tumor diagnosis and TRMN. According to our modified ontogeny-based classifier, we observed that the patients with TP53 or PPM1D mutations had more treatment lines and complex karyotypes, the “MDS-like” patients were older with more gene mutations, while patients with “De novo/pan-AML” mutations were younger with more balanced chromosomal translocations. Median OS within each subgroup was 7.5, 14.5, and 25.2 months, respectively, with statistically significant difference in multivariate analysis. These results support the integration of cytogenetic and molecular markers into the future TRMN classification to reflect the biological diversity of TRMN and its impact on outcomes.
Biofunctionalized composite scaffold to potentiate osteoconduction, angiogenesis, and favorable metabolic microenvironment for osteonecrosis therapy
Authors: Tongtong Zhu, Mengyang Jiang, Mingran Zhang, Liguo Cui, Xiaoyu Yang, Xukai Wang, Guangyao Liu, Jianxun Ding, Xuesi Chen
Journal: Bioactive Materials (2021)

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if no appropriate treatment is performed in time. Core decompression is a general treatment modality for early osteonecrosis. However, effective bone regeneration in the necrotic area is still a significant challenge. This study developed a biofunctionalized composite scaffold (PLGA/nHA30VEGF) for osteonecrosis therapy through potentiation of osteoconduction, angiogenesis, and a favorable metabolic microenvironment. The composite scaffold had a porosity of 87.7% and compressive strength of 8.9 MPa. PLGA/nHA30VEGF had an average pore size of 227.6 μm and a water contact angle of 56.5° with a sustained release profile of vascular endothelial growth factor (VEGF). After the implantation of PLGA/nHA30VEGF, various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment. Additionally, the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis. The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.
Abstract 12233: Ethnic Trends of Acute Ischemic Stroke Incidence and Risk Factors in a Multiethnic Population in Southeast Asia: A 12-year Study Using a Nationwide Stroke Registry
Authors: Dawn Cheah, Benjamin Y Tan, Pin Pin Pek, Zheng Huili, Deidre A De Silva, Aftab Ahmad, Bernard P Chan, Chang Hui Meng, Kong Keng, Sherry Young, Kok Foo Tang, Leonard L Yeo, Narayanaswamy Venketasubramanian, Andrew Ho, Marcus E Ong
Journal: Circulation (2019)

Introduction: Ethnicity has been shown to affect acute ischemic stroke (AIS) incidence, risk factors, treatment effectiveness, complications and functional outcomes. This study aims to describe the...
Smart Responsive Microarray Patches for Transdermal Drug Delivery and Biological Monitoring
Authors: Li Zhao, Chunyang Zhang, Juhaina M. Abu‐Ershaid, Mingshan Li, Yaocun Li, Yara Naser, Xianbing Dai, Marco T. A. Abbate, Ryan F. Donnelly
Journal: Advanced Healthcare Materials (2021)

Abstract Traditional drug delivery routes possess various disadvantages which make them unsuitable for certain population groups, or indeed unsuitable for drugs with certain physicochemical properties. As a result, a variety of alternative drug delivery routes have been explored in recent decades, including transdermal drug delivery. One of the most promising novel transdermal drug delivery technologies is a microarray patch (MAP), which can bypass the outermost skin barrier and deliver drugs directly into the viable epidermis and dermis. Unlike traditional MAPs which release loaded cargo simultaneously upon insertion into the skin, stimuli responsive MAPs based on biological stimuli are able to precisely release the drug in response to the need for additional doses. Thus, smart MAPs that are only responsive to certain external stimuli are highly desirable, as they provide safer and more efficient drug delivery. In addition to drug delivery, they can also be used for biological monitoring, which further expands their applications.
Measurement of the passage of mycophenolic acid into breast milk in a patient with lupus nephritis
Authors: Ana Huerta, Antonio F. Caballero Bermejo, Luis F. de Villa, Rosa Sedano, Belén Ruiz-Antorán, Cristina Avendaño-Solá, José Portoles Pérez, Aranzazu Sancho-López
Journal: Kidney International (2021)
Abstract 8815: Role of Regulatory T Cells in Atheroprotective Effects of Granulocyte Colony-Stimulating Factor
Authors: Hiroshi Hasegawa, Hiroyuki Takano, Raita Uchiyama, Kazutaka Ueda, Yoshihito kameda, Yoshio Kobayashi, Issei Komuro
Journal: Circulation (2011)

Background We and others have previously reported that granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling and dysfunction after myocardial infarction in animal models and human. We have also reported that G-CSF inhibits the progression of atherosclerosis in animal models, but its precise mechanism is still elusive. Because G-CSF was recently reported to enhance the cell number and function of regulatory T cells (Tregs), we investigated whether Tregs are critical for the protective effects of G-CSF on atherosclerosis. Methods We examined the effects of G-CSF (200 rg/kg) or saline on the atherosclerosis using apolipoprotein E-deficient (ApoE -/- ) mice. Twelve-week-old male ApoE -/- mice were subcutaneously administrated with 200 μg/kg of G-CSF or same volume of saline once a day for 5 consecutive days per a week for 4 weeks. After 28 days of G-CSF or saline treatment, mice were sacrificed and analyzed the atherosclerotic area of the aortic root. To deplete the function of Tregs, we injected intraperitoneally anti-mouse CD25 antibody (PC61). Furthermore, to determine the effect of Tregs, we examined the effects of G-CSF on atherosclerosis using ApoE -/- /CD28 -/- double knockout mice that lack Tregs. Results Atherosclerotic lesion of aortic sinus was significantly reduced in the G-CSF-treated mice compared with the saline-treated mice (35% reduction, Pμ0.05). G-CSF reduced the expression level of interferon-γ by 31% and increased the expression level of interleukin-10 by 20% in atherosclerotic lesions of aortic sinus. G-CSF increased the number of CD4 + CD25 + Tregs in lymph nodes and spleen, and enhanced the suppressive function of Tregs in vitro. G-CSF markedly increased the number of Foxp3-positive Tregs in atherosclerotic lesions of aortic sinus. Blood lipid concentrations were not significantly different between the G-CSF-treated mice and the saline-treated mice. Administration of anti-CD25 antibody (PC61) that depletes Tregs abrogated these atheroprotective effects of G-CSF. Moreover, in ApoE -/- /CD28 -/- mice, the protective effects of G-CSF on atherosclerosis were not recognized. Conclusions These findings suggest that Tregs play an important role in the atheroprotective effects of G-CSF.
A cluster randomised trial of the impact of a policy of daily testing for contacts of COVID-19 cases on attendance and COVID-19 transmission in English secondary schools and colleges
Authors: Bernadette C Young, David W Eyre, Saroj Kendrick, Chris White, Sylvester Smith, George Beveridge, Toby Nonnenmacher, Fegor Ichofu, Joseph Hillier, Ian Diamond, Emma Rourke, Fiona Dawe, Ieuan Day, Lisa Davies, Paul Staite, Andrea Lacey, James McCrae, Ffion Jones, Joseph Kelly, Urszula Bankiewicz, Sarah Tunkel, Richard Ovens, David Chapman, Peter Marks, Nick Hicks, Tom Fowler, Susan Hopkins, Lucy Yardley, Tim Ea Peto
Journal: The Lancet (2021)
As far as the AI can see
Authors: Cadman L. Leggett, David A. Katzka
Journal: Endoscopy (2021)

Staging of early esophageal adenocarcinoma (EAC) involves a complex process associated with profound clinical implications. Central to this process is the histologic evaluation of depth of invasion. Cancer infiltration limited to the mucosa (T1a) is associated with a lower risk of lymph node metastasis and overall improved survival compared with infiltration that extends into the submucosa (T1b) [1]. Consequently, endoscopic therapy can be considered curative in a subset of patients with T1a EAC but plays a limited role in patients with T1b EAC for which esophagectomy is associated with improved overall survival [2]. Ideally, staging of T1 EAC would be performed without the need for resection, avoiding an unnecessary intervention in patients with T1b EAC and thus preventing associated complications of esophageal perforation, bleeding, and stricture formation [3] [4] [5]. Unfortunately, imaging modalities, including endoscopic ultrasound, have demonstrated suboptimal performance in differentiating T1a from T1b EAC [6]. As a result, the endoscopist performing the staging procedure plays a fundamental role in determining whether an early-stage cancer can be safely resected and the appropriate technique to do so. In this process, the morphology, size, and adequate lift of the lesion away from the muscularis propria are taken into consideration. These factors are of critical importance not only to ensure adequate resection of the cancer but to mitigate the risk of complications. Most often, however, the only way to truly know if a lesion can be resected is to attempt its resection.
25603 Improvement in scalp psoriasis and quality of life with apremilast in patients with moderate to severe scalp psoriasis regardless of prior systemic treatment: Results from the phase 3, randomized STYLE study
Authors: Yao Wang, Linda Stein Gold, Mark Lebwohl, Bruce Strober, Zuoshun Zhang, Abby Van Voorhees
Journal: Journal of the American Academy of Dermatology (2021)
Childhood cancer medicines: understanding barriers to access
Authors: Prashant Yadav
Journal: The Lancet Global Health (2021)

The absence of timely diagnosis and equitable access to affordable and effective medicines lead to poor health outcomes for paediatric cancer in low-income and middle-income countries (LMICs). Access to medicines is a complex issue with multiple inter-related dimensions: availability, accessibility, affordability, and acceptability.1 Identification of priority actions for improved access to medicines, both globally and for specific countries, requires disentangling the many barriers to access. Multiple studies have outlined the current state of access to cancer medicines in LMICs by focusing on specific aspects of access or focusing on particular countries or territories.
Preliminary safety and antiviral activity of VIR-2218, an X-targeting HBV RNAi therapeutic, in chronic hepatitis B patients
Authors: Edward Gane, Young-Suk Lim, Pisit Tangkijvanich, James O’Beirne, Tien Huey Lim, Anna Bakardjiev, Xiao Ding, Lynn Connolly, Stephen Huang, Jae Kim, Phil Pang, Man-Fung Yuen
Journal: Journal of Hepatology (2020)
Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1
Authors: Itzchak Levy, Anat Wieder-Finesod, Vladyslav Litchevsky, Asaf Biber, Victoria Indenbaum, Liraz Olmer, Amit Huppert, Orna Mor, May Goldstein, Einav Gal Levin, Tammy Hod, Carmit Cohen, Yaniv Lustig, Galia Rahav
Journal: Clinical Microbiology and Infection (2021)

The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH.In this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored.At a median of 18 days (interquartile range 14-21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24-27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/μL (95% CI 648-757 cells/μL) to 633.8 cells/μL (95% CI 588-683 cells/μL) (p < 0.01).BNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.
Alan Richards Lyall
Authors: Hermione Lyall
Journal: BMJ (2021)

When my father, Alan Richards Lyall, aged 30, joined his colleague to become the second member of the general practice for the town of Laurencekirk and surrounding countryside in 1959, this was as a one-in-two on-call, with a half day on Fridays. He remained in that post for the following 30 years.

The A92, the main road from Dundee to Aberdeen, passed straight through the long high street, and many’s the night, my father went out with “Fred,” the ambulance driver, to attend her casualties. Laurencekirk High Street was a roll-call of agricultural life at that time, supporting a proud and productive farming community: three banks (all printing their own bank notes—Clydesdale, Royal …
Risks to surgeons and patients from HIV and hepatitis: Guidelines on precautions and management of exposure to blood or body fluids
Authors: D. C. Shanson, E. W. Taylor, Owen Gill, S. P.F. Hughes, D. C.E. Speller, G. D. Chisholm, A. M. Emmerson, G. A.J. Ayliffe, M. Casewell, E. M. Cooke, B. Cookson, B. Gazzard, P. Guillou, R. J. Heald, D. Jeffries, F. D. Johnstone, A. L.G. Peel, A. Percival, N. Soni
Journal: BMJ (1992)
Implementation of a national waterborne disease outbreak surveillance system: overview and preliminary results, France, 2010 to 2019
Authors: Jerome Pouey, Catherine Galey, Julie Chesneau, Gabrielle Jones, Nathalie Franques, Pascal Beaudeau, Damien Mouly
Journal: Eurosurveillance (2021)

Background Waterborne disease outbreaks (WBDO) associated with tap water consumption are probably underestimated in France. Aim In order to improve their detection, Santé publique France launched a surveillance system in 2019, based on the periodical analysis of health insurance data for medicalised acute gastroenteritis (mAGE). Methods Spatio-temporal cluster detection methods were applied to mAGE cases to prioritise clusters for further investigation. These investigations determined the plausibility that infection is of waterborne origin and the strength of association. Results Between January 2010 and December 2019, 3,323 priority clusters were detected (53,878 excess mAGE cases). They involved 3,717 drinking water supply zones (WSZ), 15.4% of all French WSZ. One third of these WSZ (33.4%; n = 1,242 WSZ) were linked to repeated clusters. Moreover, our system detected 79% of WBDO voluntarily notified to health authorities. Conclusion Environmental investigations of detected clusters are necessary to determine the plausibility that infection is of waterborne origin. Consequently, they contribute to identifying which WSZ are linked to clusters and for which specific actions are needed to avoid future outbreaks. The surveillance system incorporates three priority elements: linking environmental investigations with water safety plan management, promoting the systematic use of rainfall data to assess waterborne origin, and focusing on repeat clusters. In the absence of an alternative clear hypothesis, the occurrence of a mAGE cluster in a territory completely matching a distribution zone indicates a high plausibility of water origin.