tbuckley/cabot-search huggingface dataset:
Abstract 127: Vinculin Mediated Increase in Cardiac Function Confers Systemic Metabolic Efficiency and Increases in Healthspan and Lifespan
Authors: Ayla Sessions, Peter Min, Thekla Cordes, Christian Metallo, Adam Engler
Journal: Circulation Research (2017)

Despite limited regenerative capacity, compensatory mechanisms in cardiomyocytes may help maintain their function as we age, e.g. vinculin expression and localization to intercalated discs and costameres in aged organisms. This molecular mechanism, which is conserved from flies to non-human primates, helps sustain the sarcomere lattice structure and maintains cardiomyocyte function. In Drosophila melanogaster cardiac-restricted vinculin overexpression can extend lifespan up to 150%, but connections between cytoskeletal structure and metabolism are not apparent. We found that by prolonging heart function, the local and systemic energy requirements are dramatically altered; increased contractility resulted in sustained O 2 consumption with age but without localized metabolic changes in cardiomyocytes. However, systemic changes resulting from vinculin-mediated increases in cardiac function improved physical activity levels in Drosophila and energy metabolism. This work is the first to identify systemic metabolic improvements from a cytoskeletal perturbation in cardiomyocytes that result in extended organismal lifespan.
Erratum: The nuclear receptor interacting factor-3 transcriptional coregulator mediates rapid apoptosis in breast cancer cells through direct and bystander-mediated events (Cancer Research (2007) 67, (1775-1782))
Authors: S. Das, J. C. Nwachukwu, D. Li, A. J. Vulin, S. Martinez-Caballero, K. W. Kinnally, H. H. Samuels
Journal: Cancer Research (2007)
Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From <i>Escherichia coli</i> Are Linked to Flares in Systemic Lupus Erythematosus
Authors: Ryan J. Pachucki, Chelsea Corradetti, Lynne Kohler, Jay Ghadiali, Paul M. Gallo, Lauren Nicastro, Sarah A. Tursi, Stefania Gallucci, Çagla Tükel, Roberto Caricchio
Journal: Arthritis & Rheumatology (2020)

Objective Infections contribute to morbidity and mortality in systemic lupus erythematosus (SLE). Uropathogenic Escherichia coli (UPEC) are known to trigger urinary tract infections (UTIs) and form biofilms, which are multicellular communities of bacteria that are strengthened by amyloids such as curli. We previously reported that curli naturally form complexes with bacterial extracellular DNA (eDNA), and these curli/eDNA complexes induce hallmark features of lupus in mouse models. The present study was undertaken to investigate whether anti–curli/eDNA complex antibodies play a role in the pathogenesis of SLE or development of flares in SLE. Methods In total, 96 SLE patients who met at least 4 Systemic Lupus International Collaborating Clinics disease criteria were investigated. Anti–curli/eDNA complex antibodies in the plasma were tested for both IgG and IgA subclasses. Results were compared to that in 54 age‐, sex‐, and race/ethnicity‐matched healthy controls. Correlations of the levels of anti‐curli/eDNA antibodies with clinical parameters, lupus disease status, and frequency of bacteriuria were assessed. Results Anti‐curli/eDNA antibodies were detected in the plasma of SLE patients and healthy controls, and their levels correlated with the presence of asymptomatic persistent bacteriuria and occurrence of disease flares in lupus patients. Persistent bacteriuria contained curli‐producing UPEC, and this was associated with an inflammatory phenotype. Finally, curli/eDNA complexes cross‐reacted with lupus autoantigens, such as double‐stranded DNA, in binding autoantibodies. Conclusion These results suggest that UTIs and persistent bacteriuria are environmental triggers of lupus and its flares. Antibodies against curli/eDNA could serve as a sign of systemic exposure to bacterial products in SLE.
Analysis of the Metabolic State of Residual Multiple Myeloma Plasma Cells Reveals a Proliferative Subset with Glycolytic Gene Expression
Authors: Whitney Tevebaugh, James Douglas, Brian A Walker, Carolina D. Schinke, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Faith E. Davies, Joshua Epstein, Shmuel Yaccoby, Gareth J. Morgan, Sarah K Johnson
Journal: Blood (2017)
The challenge of fistula closure in Crohn's disease: an endoscopic technique for closure of a fistula
Authors: Satohiro Matsumoto, Hirosato Mashima
Journal: Endoscopy (2020)

Crohn's disease is associated with many intestinal complications, such as stenosis and fistula, and many cases require intestinal resection during the course of the disease. Although anti-tumor necrosis factor α (TNFα) agents are effective in inducing remission of active Crohnʼs disease, they are ineffective for certain intestinal complications, such as fistulas [1]. We attempted endoscopic closure for a patient in whom anti-TNFα agents were not effective in treating the fistula.
Re: Hanbing Song, Bobak Seddighzadeh, Matthew R. Cooperberg, Franklin W. Huang. Expression of ACE2 and TMPRSS2, the SARS-CoV-2 Receptor and Co-Receptor, in Prostate Epithelial Cells. Eur Urol. In press DOI: 10.1016/j.eururo.2020.04.065
Authors: Alessandro Rizzo, Veronica Mollica, Francesco Massari
Journal: European Urology (2020)
Delayed Expansion of Murine BCR-ABL1+ Leukemia By Genetic and Pharmacological Inhibition of NOX2
Authors: Hanna Grauers Wiktorin, Malin Nilsson, Tina Nilsson, Johan Gustafsson, Ebru Aydin, Anders Ståhlberg, Fredrik B Thoren, Kristoffer Hellstrand, Lars Palmqvist, Anna Martner
Journal: Blood (2017)
Cardiac segmentation on late gadolinium enhancement MRI: A benchmark study from multi-sequence cardiac MR segmentation challenge
Authors: Xiahai Zhuang, Jiahang Xu, Xinzhe Luo, Chen Chen, Cheng Ouyang, Daniel Rueckert, Victor M. Campello, Karim Lekadir, Sulaiman Vesal, Nishant RaviKumar, Yashu Liu, Gongning Luo, Jingkun Chen, Hongwei Li, Buntheng Ly, Maxime Sermesant, Holger Roth, Wentao Zhu, Jiexiang Wang, Xinghao Ding, Xinyue Wang, Sen Yang, Lei Li
Journal: Medical Image Analysis (2022)
<i>MEF2D</i> Fusions Drive Oncogenic Pre-BCR Signaling in B-ALL
Authors: Teresa Sadras, Markus Müschen
Journal: Blood Cancer Discovery (2020)

Abstract Summary: Chimeric fusion proteins involving transcriptional regulators are a common feature in pre-B acute lymphoblastic leukemia (B-ALL). However, systematic dissection of the core regulatory circuits by which these fusions exert their oncogenic effects is still required. Using chromatin immunoprecipitation sequencing and robust functional assays, Tsuzuki and colleagues identify the core transcription factor network directed by MEF2D fusions in B-ALL. The new findings demonstrate how activation of MEF2D fusions ultimately converge on pre-BCR signaling and lipid metabolism to drive malignant B-cell transformation. See related article by Tsuzuki et al., p. 82.
Biological and bioinspired materials: Structure leading to functional and mechanical performance
Authors: Yayun Wang, Steven E. Naleway, Bin Wang
Journal: Bioactive Materials (2020)

Nature has achieved materials with properties and mechanisms that go far beyond the current know-how of the engineering-materials industry. The remarkable efficiency of biological materials, such as their exceptional properties that rely on weak constituents, high performance per unit mass, and diverse functionalities in addition to mechanical properties, has been mostly attributed to their hierarchical structure. Key strategies for bioinspired materials include formulating the fundamental understanding of biological materials that act as inspiration, correlating this fundamental understanding to engineering needs/problems, and fabricating hierarchically structured materials with enhanced properties accordingly. The vast, existing literature on biological and bioinspired materials can be discussed in terms of functional and mechanical aspects. Through essential representative properties and materials, the development of bioinspired materials utilizes the design strategies from biological systems to innovatively augment material performance for various practical applications, such as marine, aerospace, medical, and civil engineering. Despite the current challenges, bioinspired materials have become an important part in promoting innovations and breakthroughs in the modern materials industry.
Assessment of primary ciliary dyskinesia predictive tools
Authors: Kaitlyn Palmas, Shivanthan Shanthikumar, Philip Robinson
Journal: European Respiratory Journal (2020)

<b>A novel real-world validation of two tools (PICADAR and NA-CDCF) that use routinely collected clinical data and help triage the need for primary ciliary dyskinesia diagnostic testing is performed, showing both tools perform well with equivalent performance</b>https://bit.ly/2YgzxlY
Africa's COVID-19 health technologies' watershed moment
Authors: Paul Adepoju
Journal: The Lancet Digital Health (2020)

The COVID-19 pandemic has spread across Africa, with every country on the continent confirming cases of the disease. In addition to efforts aimed at flattening the disease curve, improving diagnosis, and ensuring case finding and management align with global benchmarks, health systems in African countries are also facing several local challenges that foreign solutions may not effectively help with. These challenges are presenting opportunities for the health technologies sector in Africa, which is now seeing more activity than was anticipated at the outset of 2020.
The role of peripheral blood eosinophil counts in COVID‐19 patients
Authors: Guogang Xie, Fengming Ding, Lei Han, Dongning Yin, Hongzhou Lu, Min Zhang
Journal: Allergy (2020)

Coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread globally outside China. We aimed to investigate the role of peripheral blood eosinophil (EOS) as a marker in the course of the virus infection to improve the efficiency of diagnosis and evaluation of COVID-19 patients.
Professional self respect
Authors: S K Goolamali, J M Gumpel
Journal: BMJ (1999)

Guideline for primary care management of dementia Such guidelines should consider all relevant effective treatmentsEditor-Evidence based guidelines have a responsibility to consider all the relevant effective treatments and not to concentrate only on those with which clinicians are familiar.I was surprised by a serious omission from the North of England evidence based guidelines for the primary care management of dementia 1 -of category I evidence for the effectiveness of Ginkgo biloba extract in dementia, from a large randomised controlled trial. 2 The number needed to treat for a 4 point improvement in the cognitive subscale of the Alzheimer's disease assessment scale at one year of follow up has been calculated as 7.9 (95% confidence interval 4.2 to 67); for a significant improvement in the geriatric assessment by relative's rating instrument (a daily living and social behaviour score assessed by family members) it was 7.0 (3.3 to 97).The dose of G biloba extract was 120 mg a day. 3 G biloba extract is available over the counter, and the cost of a year's treatment (from one major supermarket) is £85.A year's treatment with donepezil, by contrast, costs £891 for 5 mg and £1248 for 10 mg.
Sexual violence in sport: American Medical Society for Sports Medicine Position Statement
Authors: Jennifer Scott Koontz, Margo Mountjoy, Kristin E Abbott, Cindy Miller Aron, Kathleen C Basile, Chad T Carlson, Cindy J Chang, Alex B Diamond, Sheila A Dugan, Brian Hainline, Stanley A Herring, B Elliot Hopkins, Elizabeth A Joy, Janet P Judge, Michele LaBotz, Jason Matuszak, Cody J McDavis, Rebecca A Myers, Aurelia Nattiv, Jeffrey L Tanji, Jessica Wagner, William O Roberts
Journal: British Journal of Sports Medicine (2020)

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a Position Statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the Task Force used an iterative process and expert consensus to finalise the Position Statement. The objective of this Position Statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.
Rapid roll out of SARS-CoV-2 antibody testing—a concern
Authors: Monique Andersson, Nicola Low, Neil French, Trisha Greenhalgh, Katie Jeffery, Andrew Brent, Jonathan Ball, Allyson Pollock, David McCoy, Miren Iturriza-Gomara, Iain Buchan, Helen Salisbury, Deenan Pillay, Will Irving
Journal: BMJ (2020)

We are writing to express concerns over aspects of the establishment of SARS-CoV-2 antibody testing in England. NHS England and NHS Improvement wrote to NHS trusts and pathology networks on 25 May 2020, asking them to offer antibody testing at short notice and ramp up capacity to thousands of samples a day.12

We have three concerns about the request. Firstly, there is no specific clinical indication for the test on an individual basis. Secondly, the performance of these assays has not yet been assessed to the standard typically required of a novel test. And thirdly, the resource implications are not considered.

We support the rapid provision of diagnostic tests for individual and public health and recognise the need to deliver at pace. It is essential, however, that quality systems, which have evolved over many years and are the foundation for delivering the right result of the right test to the right person at the right time, are not circumvented.

In usual clinical practice, antibody testing fulfils several purposes. In acute illness, an IgM antibody response can be used to diagnose an infectious …
High-throughput microfluidics for evaluating microbubble enhanced delivery of cancer therapeutics in spheroid cultures
Authors: Matthew D. Bourn, Damien V.B. Batchelor, Nicola Ingram, James R. McLaughlan, P. Louise Coletta, Stephen D. Evans, Sally A. Peyman
Journal: Journal of Controlled Release (2020)

Drug penetration into solid tumours remains a major challenge in the effective treatment of cancer. Microbubble (MB) mediated sonoporation offers a potential solution to this by enhancing the uptake of drugs into cells. Additionally, in using an ultrasound (US) trigger, drug delivery can be localised to the tumour, thus reducing the off-site toxicity associated with systemic delivery. The majority of in vitro studies involving the observation of MB-enhanced drug efficacy have been conducted on 2D monolayer cell cultures, which are known to be poor models for in vivo tumours. 3D spheroid cultures allow for the production of multicellular cultures complete with extracellular matrix (ECM) components. These cultures effectively recreate many of the physiological features of the tumour microenvironment and have been shown to be far superior to previous 2D monolayer models. However, spheroids are typically handled in well-plates in which the fluid environment is static, limiting the physiological relevance of the model. The combination of 3D cultures and microfluidics would allow for the production of a dynamic system in which spheroids are subjected to in vivo like fluid flow and shear stresses. This study presents a microfluidic device containing an array of spheroid traps, into which multiple pre-grown colorectal cancer (CRC) spheroids were loaded. Reservoirs interfaced with the chip use hydrostatic pressure to passively drive flow through the system and subject spheroids to capillary like flow velocities. The use of reservoirs also enabled multiple chips to be run in parallel, allowing for the screening of multiple therapeutic treatments (n = 690 total spheroids analysed). This microfluidic platform was used to investigate MB enhanced drug delivery and showed that co-delivery of 3 μM doxorubicin (DOX) + MB + US reduced spheroid viability to 48 ± 2%, compared to 75 ± 5% observed with 3 μM DOX alone. Delivery of drug loaded MBs (DLMBs), in which DOX-loaded liposomes (DOX-LS) were conjugated to MBs, reduced spheroid viability to 62 ± 3%, a decrease compared to the 75 ± 3% viability observed with DOX-LS in the absence of MBs + US.
Bactericidal coating to prevent early and delayed implant-related infections
Authors: F. Jahanmard, M. Croes, M. Castilho, A. Majed, M.J. Steenbergen, K. Lietaert, H.C. Vogely, B.C.H. van der Wal, D.A.C. Stapels, J. Malda, T. Vermonden, S. Amin Yavari
Journal: Journal of Controlled Release (2020)

The occurrence of an implant-associated infection (IAI) with the formation of a persisting bacterial biofilm remains a major risk following orthopedic biomaterial implantation. Yet, progress in the fabrication of tunable and durable implant coatings with sufficient bactericidal activity to prevent IAI has been limited. Here, an electrospun composite coating was optimized for the combinatorial and sustained delivery of antibiotics. Antibiotics-laden poly(ε-caprolactone) (PCL) and poly`1q`(lactic-co glycolic acid) (PLGA) nanofibers were electrospun onto lattice structured titanium (Ti) implants. In order to achieve tunable and independent delivery of vancomycin (Van) and rifampicin (Rif), we investigated the influence of the specific drug-polymer interaction and the nanofiber coating composition on the drug release profile and durability of the polymer-Ti interface. We found that a bi-layered nanofiber structure, produced by electrospinning of an inner layer of [PCL/Van] and an outer layer of [PLGA/Rif], yielded the optimal combinatorial drug release profile. This resulted in markedly enhanced bactericidal activity against planktonic and adherent Staphylococcus aureus for 6 weeks as compared to single drug delivery. Moreover, after 6 weeks, synergistic bacterial killing was observed as a result of sustained Van and Rif release. The application of a nanofiber-filled lattice structure successfully prevented the delamination of the multi-layer coating after press-fit cadaveric bone implantation. This new lattice design, in conjunction with the multi-layer nanofiber structure, can be applied to develop tunable and durable coatings for various metallic implantable devices. This is particularly appealing to tune the release of multiple antimicrobial agents over a period of weeks to prevent early and delayed onset IAI.
Consequences of Stability-Induced Epistasis for Substitution Rates
Authors: Noor Youssef, Edward Susko, Joseph P Bielawski
Journal: Molecular Biology and Evolution (2020)

Abstract Do interactions between residues in a protein (i.e., epistasis) significantly alter evolutionary dynamics? If so, what consequences might they have on inference from traditional codon substitution models which assume site-independence for the sake of computational tractability? To investigate the effects of epistasis on substitution rates, we employed a mechanistic mutation-selection model in conjunction with a fitness framework derived from protein stability. We refer to this as the stability-informed site-dependent (S-SD) model and developed a new stability-informed site-independent (S-SI) model that captures the average effect of stability constraints on individual sites of a protein. Comparison of S-SI and S-SD offers a novel and direct method for investigating the consequences of stability-induced epistasis on protein evolution. We developed S-SI and S-SD models for three natural proteins and showed that they generate sequences consistent with real alignments. Our analyses revealed that epistasis tends to increase substitution rates compared with the rates under site-independent evolution. We then assessed the epistatic sensitivity of individual site and discovered a counterintuitive effect: Highly connected sites were less influenced by epistasis relative to exposed sites. Lastly, we show that, despite the unrealistic assumptions, traditional models perform comparably well in the presence and absence of epistasis and provide reasonable summaries of average selection intensities. We conclude that epistatic models are critical to understanding protein evolutionary dynamics, but epistasis might not be required for reasonable inference of selection pressure when averaging over time and sites.
Day 100 Levels of Blood Immune Cells Are Prognostic Biomarkers for Allogeneic Hematopoietic Stem Cell Transplant Outcomes: Results from BMT CTN 0201
Authors: Shanelle M. Fernando, Brent R. Logan, Mingwei Fei, Stephanie J. Lee, Dennis Confer, Alan Howard, Shanmuganathan Chandrakasan, Cynthia R. Giver, Claudio Anasetti, Edmund K. Waller
Journal: Blood (2017)
Burden of disease in Gabon caused by loiasis: a cross-sectional survey
Authors: Luzia Veletzky, Jennifer Hergeth, Daniel R Stelzl, Johannes Mischlinger, Rella Zoleko Manego, Ghyslain Mombo-Ngoma, Matthew B B McCall, Ayôla A Adegnika, Selidji T Agnandji, Wolfram G Metzger, Pierre B Matsiegui, Heimo Lagler, Benjamin Mordmüller, Christine Budke, Michael Ramharter
Journal: The Lancet Infectious Diseases (2020)
Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry
Authors: Wojciech Francuzik, Franziska Ruëff, Andrea Bauer, Maria Beatrice Bilò, Victoria Cardona, George Christoff, Sabine Dölle-Bierke, Luis Ensina, Montserrat Fernández Rivas, Thomas Hawranek, Jonathan O'B Hourihane, Thilo Jakob, Nicos G. Papadopoulos, Claudia Pföhler, Iwona Poziomkowska-Gęsicka, Xavier Van der Brempt, Kathrin Scherer Hofmeier, Regina Treudler, Nicola Wagner, Bettina Wedi, Margitta Worm
Journal: Journal of Allergy and Clinical Immunology (2020)
レニン-アンギオテンシン(RA)系の阻害剤を投与した高血圧自然発症ラット(SHR)におけるプロアンギオテンシン12の血漿及び組織濃度
Authors: Nagata Sayaka, Kato Johji, Kuwasako Kenji, Kitamura Kazuo
Journal: Circulation (2009)
Nuclear Periphery Takes Center Stage: The Role of Nuclear Pore Complexes in Cell Identity and Aging
Authors: Ukrae H. Cho, Martin W. Hetzer
Journal: Neuron (2020)

In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging. In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging.