tbuckley/cabot-search huggingface dataset:
Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders
Authors: Jeroen L.M. van Doorn, Francesca Pennati, Hendrik H.G. Hansen, Baziel G.M. van Engelen, Andrea Aliverti, Jonne Doorduin
Journal: European Respiratory Journal (2021)

Respiratory muscle weakness is common in neuromuscular disorders (NMDs) and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in NMDs is crucial. In the last decade, ultrasound and magnetic resonance imaging (MRI) have emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as a tool in clinical respiratory management and as an outcome parameter in upcoming drug trials for NMDs, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by ultrasound and MRI, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as an outcome measure in daily practice and clinical trials.
Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo‐Controlled Trial
Authors: Yuanyuan Wang, Graeme Jones, Catherine Hill, Anita E. Wluka, Andrew B. Forbes, Andrew Tonkin, Sultana Monira Hussain, Changhai Ding, Flavia M. Cicuttini
Journal: Arthritis & Rheumatology (2021)

To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double-blind, placebo-controlled trial.Participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores.A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change -1.66% versus -2.17%, between-group difference 0.50% [95% confidence interval (95% CI) -0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score -36.0 versus -29.5, adjusted difference -2.7 [95% CI -27.1, 21.7]; mean change in stiffness score -14.2 versus -11.8, adjusted difference -0.2 [95% CI -12.2, 11.8]; mean change in function score -89.4 versus -87.5, adjusted difference 0.3 [95% CI -83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs).Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA.
Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study
Authors: Shinji Kuroda, Satoru Kikuchi, Yoshihiko Kakiuchi, Megumi Watanabe, Kazuya Kuwada, Tomoko Tsumura, Masahiko Nishizaki, Shunsuke Kagawa, Shiro Hinotsu, Toshiyoshi Fujiwara
Journal: International Journal of Surgery (2021)
Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient
Authors: A Spencer, RM Szydlo, PA Brookes, E Kaminski, S Rule, F van Rhee, KN Ward, G Hale, H Waldmann, JM Hows
Journal: Blood (1995)
Abstract 11556: Association of Chronic Kidney Disease With the Risk of Incident Heart Failure Subtypes and Effect Modification by Sickle Cell Trait in African-American Women
Authors: Juliet A Yirerong, Ahmed S Mohamed, Mary Roberts, Nora Franceschini, Charles B Eaton
Journal: Circulation (2018)

Introduction: Chronic Kidney Disease (CKD), Sickle Cell Trait (SCT) and Heart Failure (HF) are more common in African American (AA) women compared to White women. The association of CKD with incide...
Trends in Drug Overdose Mortality in Ohio During the First 7 Months of the COVID-19 Pandemic
Authors: Janet M. Currie, Molly K. Schnell, Hannes Schwandt, Jonathan Zhang
Journal: JAMA Network Open (2021)

This cross-sectional study uses data from the Ohio Department of Health to evaluate trends in drug overdose mortality in that state by type of drug and user age during the first 7 months of the COVID-19 epidemic.
Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts
Authors: Jodi M. Gilman, William A. Schmitt, Grace Wheeler, Randi M. Schuster, Jost Klawitter, Cristina Sempio, A. Eden Evins
Journal: JAMA Network Open (2021)

Among adults using medical cannabis frequently and recently, THC and CBD metabolite concentrations in urine often differed from expected exposure. Approximately one-third of samples from people reporting using CBD-dominant products contained no measurable CBD metabolite. Nearly 1 in 5 samples from those using vaped cannabis contained no detectable cannabinoids....
Perianal Crohn’s Disease Is Associated With Poor Disease Outcome: A Nationwide Study From the epiIIRN Cohort
Authors: Ohad Atia, Noa Asayag, Gili Focht, Rona Lujan, Oren Ledder, Shira Greenfeld, Revital Kariv, Iris Dotan, Hagit Gabay, Ran Balicer, Ziona Haklai, Daniel Nevo, Dan Turner
Journal: Clinical Gastroenterology and Hepatology (2021)
G-quadruplexes are transcription factor binding hubs in human chromatin
Authors: Jochen Spiegel, Sergio Martínez Cuesta, Santosh Adhikari, Robert Hänsel-Hertsch, David Tannahill, Shankar Balasubramanian
Journal: Genome biology (2021)

Abstract Background The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. Results Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes. Conclusions Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.
BNT162b2 vaccination effectively prevents the rapid rise of SARS-CoV-2 variant B.1.1.7 in high-risk populations in Israel
Authors: Ariel Munitz, Matan Yechezkel, Yoav Dickstein, Dan Yamin, Motti Gerlic
Journal: Cell Reports Medicine (2021)

Since the emergence of the SARS-CoV-2 pandemic, various genetic variants have been described. The B.1.1.7 variant, which emerged in England during December 2020, is associated with increased infectivity. Therefore, its pattern of spread is of great importance. The Israeli government established three national programs: massive RT-PCR testing, focused surveillance in nursing homes, and robust prioritized vaccination with BNT162b2. To define the impact of the aforementioned programs, we analyze data from ∼300,000 RT-PCR samples collected from December 6, 2020, to February 10, 2021. We reveal that the B.1.1.7 is 45% (95% confidence interval [CI]: 20%-60%) more transmissible than the wild-type strain and has become the dominant strain in Israel within 3.5 weeks. Despite the rapid increase in viral spread, focused RT-PCR testing and prioritized vaccination programs are capable of preventing the spread of the B.1.1.7 variant in the elderly. Therefore, proactive surveillance programs, combined with prioritized vaccination, are achievable and can reduce severe illness and subsequent death.
Biomaterials‐Based Delivery of Therapeutic Antibodies for Cancer Therapy
Authors: Qian‐Ni Ye, Yue Wang, Song Shen, Cong‐Fei Xu, Jun Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Considerable breakthroughs in the treatment of malignant tumors using antibody drugs, especially immunomodulating monoclonal antibodies (mAbs), have been made in the past decade. Despite technological advancements in antibody design and manufacture, multiple challenges face antibody‐mediated cancer therapy, such as instability in vivo, poor tumor penetration, limited response rate, and undesirable off‐target cytotoxicity. In recent years, an increasing number of biomaterials‐based delivery systems have been reported to enhance the antitumor efficacy of antibody drugs. This review summarizes the advances and breakthroughs in integrating biomaterials with therapeutic antibodies for enhanced cancer therapy. A brief introduction to the principal mechanism of antibody‐based cancer therapy is first established, and then various antibody immobilization strategies are provided. Finally, the current state‐of‐the‐art in biomaterials‐based antibody delivery systems and their applications in cancer treatment are summarized, highlighting how the delivery systems augment the therapeutic efficacy of antibody drugs. The outlook and perspective on biomaterials‐based delivery of antitumor antibodies are also discussed.
Abstract 14921: The Product of E/A and Log BNP is a Novel Parameter to Predict Left Ventricular Filling Pressure
Authors: Masayoshi Oikawa, Atsushi Kobayashi, Kento Wada, Takamasa Sato, Satoshi Suzuki, Akiomi Yoshihisa, Kazuhiko Nakazato, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2016)

Background: Increased mitral inflow early diastolic (E) velocity to tissue Doppler E’ ratio (E/E’) and elevated mitral E to late diastolic pattern ratio (E/A) are implicated as elevated left ventri...
Evolving changes in mortality of 13,301 critically ill adult patients with COVID-19 over 8 months
Authors: Pedro Kurtz, Leonardo S. L. Bastos, Leila F. Dantas, Fernando G. Zampieri, Marcio Soares, Silvio Hamacher, Jorge I. F. Salluh, Fernando A. Bozza
Journal: Intensive Care Medicine (2021)

Clinical characteristics and management of COVID-19 patients have evolved during the pandemic, potentially changing their outcomes. We analyzed the associations of changes in mortality rates with clinical profiles and respiratory support strategies in COVID-19 critically ill patients. A multicenter cohort of RT-PCR-confirmed COVID-19 patients admitted at 126 Brazilian intensive care units between February 27th and October 28th, 2020. Assessing temporal changes in deaths, we identified distinct time periods. We evaluated the association of characteristics and respiratory support strategies with 60-day in-hospital mortality using random-effects multivariable Cox regression with inverse probability weighting. Among the 13,301 confirmed-COVID-19 patients, 60-day in-hospital mortality was 13%. Across four time periods identified, younger patients were progressively more common, non-invasive respiratory support was increasingly used, and the 60-day in-hospital mortality decreased in the last two periods. 4188 patients received advanced respiratory support (non-invasive or invasive), from which 42% underwent only invasive mechanical ventilation, 37% only non-invasive respiratory support and 21% failed non-invasive support and were intubated. After adjusting for organ dysfunction scores and premorbid conditions, we found that younger age, absence of frailty and the use of non-invasive respiratory support (NIRS) as first support strategy were independently associated with improved survival (hazard ratio for NIRS first [95% confidence interval], 0.59 [0.54–0.65], p < 0.001). Age and mortality rates have declined over the first 8 months of the pandemic. The use of NIRS as the first respiratory support measure was associated with survival, but causal inference is limited by the observational nature of our data.
LKB1 Down-Modulation by miR-17 Identifies Patients With NSCLC Having Worse Prognosis Eligible for Energy-Stress–Based Treatments
Authors: Cristina Borzi, Monica Ganzinelli, Elisa Caiola, Marika Colombo, Giovanni Centonze, Mattia Boeri, Diego Signorelli, Laura Caleca, Eliana Rulli, Adele Busico, Iolanda Capone, Ugo Pastorino, Mirko Marabese, Massimo Milione, Massimo Broggini, Marina Chiara Garassino, Gabriella Sozzi, Massimo Moro
Journal: Journal of Thoracic Oncology (2021)

IntroductionPreclinical models recently unveiled the vulnerability of LKB1/KRAS comutated NSCLC to metabolic stress-based treatments. Because miR-17 is a potential epigenetic regulator of LKB1, we hypothesized that wild-type LKB1 (LKB1WT) NSCLC with high miR-17 expression may be sensitive to an energetic stress condition, and eligible for metabolic frailties-based therapeutic intervention.MethodsWe took advantage of NSCLC cell lines with different combinations of KRAS mutation and LKB1 deletion and of patient-derived xenografts (PDXs) with high (LKB1WT/miR-17 high) or low (LKB1WT/miR-17 low) miR-17 expression. We evaluated LKB1 pathway impairment and apoptotic response to metformin. We retrospectively evaluated LKB1 and miR-17 expression levels in tissue specimens of patients with NSCLC and PDXs. In addition, a lung cancer series from The Cancer Genome Atlas data set was analyzed for miR-17 expression and potential correlation with clinical features.ResultsWe identified miR-17 as an epigenetic regulator of LKB1 in NSCLC and confirmed targeting of miR-17 to LKB1 3′ untranslated region by luciferase reporter assay. We found that miR-17 overexpression functionally impairs the LKB1/AMPK pathway. Metformin treatment prompted apoptosis on miR-17 overexpression only in LKB1WT cell lines, and in LKB1WT/miR-17 high PDXs. A retrospective analysis in patients with NSCLC revealed an inverse correlation between miR-17 and LKB1 expression and highlighted a prognostic role of miR-17 expression in LKB1WT patients, which was further confirmed by The Cancer Genome Atlas data analysis.ConclusionsWe identified miR-17 as a mediator of LKB1 expression in NSCLC tumors. This study proposes a miR-17 expression score potentially exploitable to discriminate LKB1WT patients with NSCLC with impaired LKB1 expression and poor outcome, eligible for energy-stress-based treatments.
Addressing power asymmetries in global health: Imperatives in the wake of the COVID-19 pandemic
Authors: Seye Abimbola, Sumegha Asthana, Cristian Montenegro, Renzo R. Guinto, Desmond Tanko Jumbam, Lance Louskieter, Kenneth Munge Kabubei, Shehnaz Munshi, Kui Muraya, Fredros Okumu, Senjuti Saha, Deepika Saluja, Madhukar Pai
Journal: PLoS Medicine (2021)

The Coronavirus Disease 2019 (COVID-19AU : PleasenotethatCOVID À 19hasbeendefinedasCoro ) pandemic, the Black Lives Matter and Women in Global Health movements, and ongoing calls to decolonise global health have all created space for uncomfortable but important conversations that reveal serious asymmetries of power and privilege that permeate all aspects of global health.• In this article, we, a diverse, gender-balanced group of public (global) health researchers and practitioners (most currently living in the so-called global South), outline what we see as imperatives for change in a post-pandemic world.• At the individual level (including and especially ourselves), we emphasise the need to emancipate and decolonise our own minds (from the colonial conditionings of our education), straddle and use our privilege responsibly (to empower others and avoid elite capture), and build "Southern" networks (to affirm our ownership of global health).• At the organisational level, we call for global health organisations to practice real diversity and inclusion (in ways that go beyond the cosmetic), to localise their funding decisions (with people on the ground in the driving seat), and to progressively selfdecentralise (and so, divest themselves of financial, epistemic, and political power).• And at both the individual and organisational level, we emphasise the need to hold ourselves, our governments, and global health organisations accountable to these goals, and especially for governance structures and processes that reflect a commitment to real change.• By putting a spotlight on coloniality and existing inequalities, the COVID-19 pandemic inspires calls for a more equitable world and for a decolonised and decentralised approach to global health research and practice, one that moves beyond tokenistic box ticking about diversity and inclusion into real and accountable commitments to transformative change.AU
Abstract PO-012: Ultra-high dose rate (FLASH) irradiation does not alter microhomology mediated recombination under varying oxygen tension when compared to standard clinical dose rates
Authors: Paul Barghouth, Jonathan Ollivier, Pierre Montay-Gruel, Billy W. Loo, Marie-Catherine Vozenin, Charles Limoli, Richard Frock
Journal: Clinical Cancer Research (2021)

Abstract The mechanism(s) driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV) ionizing radiation (IR) dose-rate are not known. However, attenuated DNA damage and transient oxygen depletion are among a number of proposed models. In this study, we employ high-throughput genome-wide translocation sequencing (LAM-HTGTS), a highly-sensitive assay used to identify “prey” DNA double strand breaks (DSBs) via their translocation to a single CRISPR-Cas9 “bait” DSB break, to investigate the potential differences in DSBs and repair generated by 10 Gy delivered at CONV (0.13 Gy/s) or FLASH (5.106 Gy/s) dose rates with the eRT6 (PMB-Alcen, CHUV). Investigations were conducted under different oxygen tensions. IR exposure in HEK293T cells at normoxic (21% O2) conditions increased both the proportion and total number of translocations from the junctions recovered, as expected, but were indistinguishable between CONV-RT and FLASH-RT dose-rates. Although, increased proportions of translocations were observed as cells were acutely transitioned to either physioxic (4%) or hypoxic (&amp;lt;2%) conditions alone, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal overt differences in the level of increased translocations nor in junction structures, which were predominantly increased in microhomology utilization. We discuss these findings with other related LAM-HTGTS studies. Citation Format: Paul Barghouth, Jonathan Ollivier, Pierre Montay-Gruel, Billy W. Loo Jr., Marie-Catherine Vozenin, Charles Limoli, Richard Frock. Ultra-high dose rate (FLASH) irradiation does not alter microhomology mediated recombination under varying oxygen tension when compared to standard clinical dose rates [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-012.
Plant–Soil Feedbacks and Temporal Dynamics of Plant Diversity–Productivity Relationships
Authors: Madhav P. Thakur, Wim H. van der Putten, Rutger A. Wilschut, G.F. (Ciska) Veen, Paul Kardol, Jasper van Ruijven, Eric Allan, Christiane Roscher, Mark van Kleunen, T. Martijn Bezemer
Journal: Trends in Ecology & Evolution (2021)
The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer
Authors: Jiang Liu, Liyan Lao, Jianing Chen, Jiang Li, Wenfeng Zeng, Xiaofeng Zhu, Jiaqian Li, Xueman Chen, Linbin Yang, Yue Xing, Fei Chen, Di Huang, Xiaoqian Zhang, Wei Wei, Chang Gong, Shuya Huang, Zhigang Yu, Zhihua Li, Linhan Yang, Jinping Liu, Xiaozhen Liu, Qinghui Zheng, Xuli Meng, Jing Liang, Luyang Sun, Musheng Zeng, Mengfeng Li, Qiang Liu, Shicheng Su, Erwei Song
Journal: Nature Cancer (2021)
The Cortical Motor Areas and the Emergence of Motor Skills: A Neuroanatomical Perspective
Authors: Peter L. Strick, Richard P. Dum, Jean-Alban Rathelot
Journal: Annual Review of Neuroscience (2021)

What changes in neural architecture account for the emergence and expansion of dexterity in primates? Dexterity, or skill in performing motor tasks, depends on the ability to generate highly fractionated patterns of muscle activity. It also involves the spatiotemporal coordination of activity in proximal and distal muscles across multiple joints. Many motor skills require the generation of complex movement sequences that are only acquired and refined through extensive practice. Improvements in dexterity have enabled primates to manufacture and use tools and humans to engage in skilled motor behaviors such as typing, dance, musical performance, and sports. Our analysis leads to the following synthesis: The neural substrate that endows primates with their enhanced motor capabilities is due, in part, to (a) major organizational changes in the primary motor cortex and (b) the proliferation of output pathways from other areas of the cerebral cortex, especially from the motor areas on the medial wall of the hemisphere.
Case 12-2021: A 78-Year-Old Man with a Rash on the Scalp and Face
Authors: Michael K. Yoon, Hillary R. Kelly, Suzanne K. Freitag, Alexander G. Marneros, Miriam B. Barshak, Diane G. Brackett
Journal: New England Journal of Medicine (2021)

A 78-year-old man was admitted with a forehead and scalp rash and eyelid edema on the left side. The rash spread to the right side, with lesions appearing as punched-out erosions with hemorrhagic crust. The patient was unable to open his eyes; he began to have visual hallucinations and seemed confused. A diagnostic test was performed.
Exploring the Complexity of Death-Censored Kidney Allograft Failure
Authors: Manuel Mayrdorfer, Lutz Liefeldt, Kaiyin Wu, Birgit Rudolph, Qiang Zhang, Frank Friedersdorff, Nils Lachmann, Danilo Schmidt, Bilgin Osmanodja, Marcel G. Naik, Wiebke Duettmann, Fabian Halleck, Marina Merkel, Eva Schrezenmeier, Johannes Waiser, Michael Duerr, Klemens Budde
Journal: Journal of the American Society of Nephrology (2021)

Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL.In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time.GL is often multifactorial and more complex than previously thought.