tbuckley/cabot-search huggingface dataset:
Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment
Authors: Li Liang, Yi Shen, Zhifeng Dong, Xin Gu
Journal: Bioactive Materials (2021)

Stem cell-derived exosomes (SC-EXO) was an emerging therapeutic agent in regenerative medicine. Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction (ED) treatment. However, high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection. In this study, a Polydopamine nanoparticles (PDNPs) incorporated poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PDNPs-PELA) thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes (EXO). The hydrogels exhibited sol-gel transition at body temperature. Moreover, the in-situ polymerization of PDNPs using poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PELA) block copolymer as a template was found to be more stable dispersion in the gel system. After being encapsulated into the hydrogel, EXO shows sustained release behavior within two weeks. In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons, increase of the cavity's pressure, thereby restoring the erectile function. In particular, since the PDNPs in thermosensitive gels have excellent photoacoustic performance, the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging. These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.
26681 Noninvasive evaluation of density and diameter of dermal papillae in psoriatic and healthy skin: An intrapatient controlled study
Authors: Francesco Lacarrubba, Anna Elisa Verzì, Davide Francesco Puglisi, Beatrice Nardone, Maria Letizia Musumeci, Giuseppe Micali
Journal: Journal of the American Academy of Dermatology (2021)
Ivory Coast rolls out Ebola vaccine after first confirmed case since 1994
Authors: Luke Taylor
Journal: BMJ (2021)

Health officials in the Ivory Coast are scrambling to vaccinate healthcare workers and trace all social contacts of the first case of the Ebola virus reported there in 25 years.

An 18 year old woman in the city of Abidjan tested positive for Ebola on 14 August after she was admitted to hospital with a fever.1

Guinea, which experienced its own recent outbreak of Ebola, has sent the Ivory Coast 5000 vaccine doses, five vaccination experts, and monoclonal antibody treatments. The …
28325 Artificial intelligence (AI) in dermatology: An application in sub-Saharan Africa
Authors: Christophe Hsu, Philippe Gottfrois, Yi Xiao, Daudi Mavura, Hafidh Hassan, Fahafantsoa Rapelanoro Rabenja, Herizo Andriambololoniaina, Zhao Shuang, Chen Xiang, Alexander Navarini
Journal: Journal of the American Academy of Dermatology (2021)
Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation
Authors: Nicholas J. Thomas, Nathaniel J. Myall, Fangdi Sun, Tejas Patil, Rao Mushtaq, Chandler Yu, Sumi Sinha, Erqi L. Pollom, Seema Nagpal, D. Ross Camidge, Chad G. Rusthoven, Steve E. Braunstein, Heather A. Wakelee, Caroline E. McCoach
Journal: Journal of Thoracic Oncology (2021)

Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases.Data were retrospectively collected from three academic institutions. Two treatment groups (CNS-penetrant TKI alone versus TKI + CNS radiation therapy) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy.A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial progression (14.8 versus 20.5 mo, p = 0.51 [EGFR] and 18.1 versus 21.8 mo, p = 0.65 [ALK]), or time to treatment failure (13.8 versus 8.6 mo, p = 0.26 [EGFR] and 13.5 versus 23.2 mo, p = 0.95 [ALK]).These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively affecting progression.
Bedshift: perturbation of genomic interval sets
Authors: Aaron Gu, Hyun Jae Cho, Nathan C. Sheffield
Journal: Genome biology (2021)

Functional genomics experiments, like ChIP-Seq or ATAC-Seq, produce results that are summarized as a region set. There is no way to objectively evaluate the effectiveness of region set similarity metrics. We present Bedshift, a tool for perturbing BED files by randomly shifting, adding, and dropping regions from a reference file. The perturbed files can be used to benchmark similarity metrics, as well as for other applications. We highlight differences in behavior between metrics, such as that the Jaccard score is most sensitive to added or dropped regions, while coverage score is most sensitive to shifted regions.
VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury
Authors: Masahiro Yamashita, Miyuki Niisato, Yasushi Kawasaki, Sinem Karaman, Marius R. Robciuc, Yuji Shibata, Yoji Ishida, Ryosuke Nishio, Tomoyuki Masuda, Tamotsu Sugai, Masao Ono, Rubin M. Tuder, Kari Alitalo, Kohei Yamauchi
Journal: European Respiratory Journal (2021)

Background Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury. Methods LPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells. Results The early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosis via upregulation of integrin α v in the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages. Conclusions VEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.
Inactivation of CDKN2A in Childhood Acute Lymphoblastic Leukemia (ALL) Occurs Principally by Deletion and Is Strongly Correlated with Cytogenetic Subgroups.
Authors: Anthony V. Moorman, Sarina Sulong, Julie A.E. Irving, Jonathan C. Strefford, Marian C. Case, Lynne Minto, Christine J. Harrison, Andrew G. Hall
Journal: Blood (2007)
Characterization of Nonphysician Health Care Workers’ Burnout and Subsequent Changes in Work Effort
Authors: Liselotte N. Dyrbye, Brittny Major-Elechi, Prabin Thapa, J. Taylor Hays, Cathryn H. Fraser, Steven J. Buskirk, Colin P. West
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Burnout is a pervasive, unrelenting problem among health care workers (HCWs), with detrimental impact to patients. Data on the impact of burnout on workforce staffing are limited and could help build a financial case for action to address system-level contributors to burnout. <h3>Objective</h3> To explore the association of burnout and professional satisfaction with changes in work effort over 24 months in a large cohort of nonphysician HCWs. <h3>Design, Setting, and Participants</h3> This longitudinal cohort study was conducted in Rochester, Minnesota; Scottsdale and Phoenix, Arizona; Jacksonville, Florida; and community-based hospitals and health care facilities in the Midwest among nonphysician HCWs who responded to 2 surveys from 2015 to 2017. Analysis was completed November 25, 2020. <h3>Exposures</h3> Burnout, as measured by 2 items from the Maslach Burnout Inventory, and professional satisfaction. <h3>Main Outcomes and Measures</h3> The main outcome was work effort, as measured in full-time equivalent (FTE) units, recorded in payroll records. <h3>Results</h3> Data from 26 280 responders (7293 individuals aged 45-54 years [27.8%]; 20 263 [77.1%] women) were analyzed. A total of 8115 individuals (30.9%) had worked for the organization more than 15 years, and 6595 individuals (25.1%) were nurses. After controlling for sex, age, duration of employment, job category, baseline FTE, and baseline burnout, overall burnout (odds ratio [OR], 1.53; 95% CI, 1.38-1.70;<i>P</i> &lt; .001), high emotional exhaustion at baseline (OR, 1.54; 95% CI, 1.39-1.71;<i>P</i> &lt; .001), and high depersonalization at baseline (OR, 1.40; 95% CI, 1.21-1.62;<i>P</i> &lt; .001) were associated with an HCW reducing their FTE over the following 24 months. Conversely, satisfaction with the organization at baseline was associated with lower likelihood of reduced FTE (OR, 0.73; 95% CI, 0.65-0.83;<i>P</i> &lt; .001). Findings were similar when emotional exhaustion (OR per 1-point increase, 1.12; 95% CI, 1.10-1.16;<i>P</i> &lt; .001), depersonalization (OR per 1-point increase, 1.10; 95% CI, 1.06-1.14;<i>P</i> &lt; .001) and satisfaction with the organization (OR per 1-point increase, 0.83; 95% CI, 0.79-0.88;<i>P</i> &lt; .001) were modeled as continuous measures. Nurses represented the largest group (1026 of 1997 nurses [51.4%]) reducing their FTE over the 24 months. <h3>Conclusions and Relevance</h3> This cohort study found that burnout and professional satisfaction of HCWs were associated with subsequent changes in work effort over the following 24 months. These findings highlight the importance of addressing factors contributing to high stress among all HCWs as a workforce retention and cost reduction strategy.
Blood tube shortage: Healthcare staff should not be asked to delay tests, says BMA
Authors: Abi Rimmer
Journal: BMJ (2021)

Doctors have raised concerns about the effects that a shortage of blood tubes in England will have on patient care and the NHS, which already faces backlogs.

On 10 August NHS England issued guidance for healthcare workers, including medical directors and GPs, in the light of global shortages of blood tube products.1

It recommended that vitamin D testing, except …
Activation of the mTOR/HIF‐1α/VEGF axis promotes M1 macrophage polarization in non‐eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Bing Zhong, Jintao Du, Feng Liu, Yafeng Liu, Shixi Liu, Lifeng Xie, De yun Wang, Luo Ba
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression
Authors: Eric A. Osborn, Giovanni J. Ughi, Johan W. Verjans, Zhonglie Piao, Edouard Gerbaud, Mazen Albaghdadi, Haitham Khraishah, Mohamad B. Kassab, Richard A.P. Takx, Jie Cui, Adam Mauskapf, Changyu Shen, Robert W. Yeh, Michael T. Klimas, Ahmed Tawakol, Guillermo J. Tearney, Farouc A. Jaffer
Journal: JACC. Cardiovascular imaging (2021)
Megabase-scale presence-absence variation with Tripsacum origin was under selection during maize domestication and adaptation
Authors: Yumin Huang, Wei Huang, Zhuang Meng, Guilherme Tomaz Braz, Yunfei Li, Kai Wang, Hai Wang, Jinsheng Lai, Jiming Jiang, Zhaobin Dong, Weiwei Jin
Journal: Genome biology (2021)

Abstract Background Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (&lt; kilobase-scale) in higher eukaryotes, large-size SVs rarely exist in the genome, but they function as one of the key evolutionary forces for speciation and adaptation. Results In this study, we discover and characterize several megabase-scale presence-absence variations (PAVs) in the maize genome. Surprisingly, we identify a 3.2 Mb PAV fragment that shows high integrity and is present as complete presence or absence in the natural diversity panel. This PAV is embedded within the nucleolus organizer region (NOR), where the suppressed recombination is found to maintain the PAV against the evolutionary variation. Interestingly, by analyzing the sequence of this PAV, we not only reveal the domestication trace from teosinte to modern maize, but also the footprints of its origin from Tripsacum , shedding light on a previously unknown contribution from Tripsacum to the speciation of Zea species. The functional consequence of the Tripsacum segment migration is also investigated, and environmental fitness conferred by the PAV may explain the whole segment as a selection target during maize domestication and improvement. Conclusions These findings provide a novel perspective that Tripsacum contributes to Zea speciation, and also instantiate a strategy for evolutionary and functional analysis of the “fossil” structure variations during genome evolution and speciation.
Inborn errors of immunity manifesting as atopic disorders
Authors: Maryam Vaseghi-Shanjani, Kelsey L. Smith, Rahnuma J. Sara, Bhavi P. Modi, Anna Branch, Mehul Sharma, Henry Y. Lu, Elliot L. James, Kyla J. Hildebrand, Catherine M. Biggs, Stuart E. Turvey
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 15582: Hospitalized COVID-19 Patients With Elevated Cardiac Troponin I Have Increased Overall Mortality and Ventilation Requirements
Authors: George Hanna, Andre Johnson, Ayutyanont Napatkamon, Scott Kubomoto, Mimi S Biswas
Journal: Circulation (2020)

Introduction: Coronavirus disease 2019 (COVID-19) causes increased mortality and morbidity in patients with underlying cardiovascular disease. Elevated cardiac troponin I (cTnI) can suggest either a co-concurrent myocarditis or acute primary or secondary myocardial injury. Understanding how laboratory values predict disease severity is important for clinicians to guide therapy and triage patients. Hypothesis: cTnI may help identify the subsets of COVID-19 patients that progress to worse clinical outcomes. Methods: A cross sectional study was performed utilizing the 184 hospital United States database of HCA. Patients were selected based on inpatient visits to HCA facilities from February 2020 to May 2020 with a COVID-19 diagnosis and at least one cTnI lab test. Patients were divided according to an elevated or normal cTnI value based on the 99th percentile reference range of the test. Outcomes, such as mortality and need for mechanical ventilation, were compared. Results: 3968 patients hospitalized with COVID-19 were identified. Of those, 3158 patients had at least one cTnI test during their hospitalization. 829 (26%) had at least one positive cTnI during their hospitalization. 328 patients with at least one positive cTnI during their hospitalization died and 174 patients without a positive cTnI died (OR: 14.4 CI: 11.39 -18.30 p&lt;0.0001). 333 patients with positive cTnI required mechanical ventilation, but only 314 with negative cTnI required mechanical ventilation (p&lt;0.001). Conclusions: Patients with at least one positive cTnI during their hospitalization had increased mortality. Using a large nationwide database we confirmed previously published findings in smaller patient populations associating cardiovascular disease with COVID-19 severity. Patients with elevated cTnI were also more likely to require mechanical ventilation, suggesting the COVID-19 acute respiratory distress syndrome has a more complicated relationship to troponin levels. These findings suggest that patients with an increased cTnI should be triaged to receive aggressive management. Future steps would be to evaluate effects of aging and other risk factors on the outcome.
Dissemination of Transcatheter Aortic Valve Replacement in the United States
Authors: Javier A. Valle, Zhuokai Li, Andrzej S. Kosinski, Adam J. Nelson, Sreekanth Vemulapalli, Joseph Cleveland, David Fullerton, John C. Messenger, Jessica Y. Rove, Rory S. Bricker, Steven M. Bradley, Frederick A. Masoudi, Robert W. Yeh, Ehrin J. Armstrong, Stephen W. Waldo, John D. Carroll
Journal: Journal of the American College of Cardiology (2021)
Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups
Authors: Elio Mazzone, Giorgio Gandaglia, Guillame Ploussard, Giancarlo Marra, Massimo Valerio, Riccardo Campi, Andrea Mari, Andrea Minervini, Sergio Serni, Marco Moschini, Alessandro Marquis, Jean Baptiste Beauval, Roderick van den Bergh, Razvan-George Rahota, Timo Soeterik, Mathieu Roumiguiè, Luca Afferi, Junlong Zhuang, Hongqian Guo, Agostino Mattei, Paolo Gontero, Vito Cucchiara, Armando Stabile, Nicola Fossati, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2021)
Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases
Authors: Na Cai, Aurora Gomez-Duran, Ekaterina Yonova-Doing, Kousik Kundu, Annette I. Burgess, Zoe J. Golder, Claudia Calabrese, Marc J. Bonder, Marta Camacho, Rachael A. Lawson, Lixin Li, Caroline H. Williams-Gray, Emanuele Di Angelantonio, David J. Roberts, Nick A. Watkins, Willem H. Ouwehand, Adam S. Butterworth, Isobel D. Stewart, Maik Pietzner, Nick J. Wareham, Claudia Langenberg, John Danesh, Klaudia Walter, Peter M. Rothwell, Joanna M. M. Howson, Oliver Stegle, Patrick F. Chinnery, Nicole Soranzo
Journal: Nature Medicine (2021)
Multicancer Early Detection: Learning From the Past to Meet the Future
Authors: Ruth Etzioni, Roman Gulati, Noel S Weiss
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Multicancer early detection (MCED) tests may soon be available to screen for many cancers using a single blood test, yet little is known about these tests beyond their diagnostic performance. Taking lessons from the history of cancer early detection, we highlight 3 factors that influence how performance of early detection tests translates into benefit and benefit-harm trade-offs: the ability to readily confirm a cancer signal, the population testing strategy, and the natural histories of the targeted cancers. We explain why critical gaps in our current knowledge about each factor prevent reliably projecting the expected clinical impact of MCED testing at this point in time. Our goal is to communicate how much uncertainty there is about the possible effects of MCED tests on population health so that patients, providers, regulatory agencies, and the public are well informed about what is reasonable to expect from this potentially important technological advance. We also urge the community to invest in a coordinated effort to collect data on MCED test dissemination and outcomes so that these can be tracked and studied while the tests are rigorously evaluated for benefit, harm, and cost.
27603 Rapid itch relief with abrocitinib predicts later skin clearance: A post hoc analysis vs dupilumab and placebo in JADE COMPARE
Authors: Sonja Ständer, Gil Yosipovitch, Eric L. Simpson, Shawn G. Kwatra, Jacob P. Thyssen, Hernan Valdez, Ricardo Rojo, Marco DiBonaventura, Fan Zhang, Michael Cameron, Claire Feeney
Journal: Journal of the American Academy of Dermatology (2021)
National Trends in Out-of-Pocket Costs Among U.S. Adults With Diabetes Aged 18–64 Years: 2001–2017
Authors: Yu Wang, Joohyun Park, Rui Li, Elizabeth Luman, Ping Zhang
Journal: Diabetes Care (2021)

OBJECTIVE To assess national trends in out-of-pocket (OOP) costs among adults aged 18–64 years with diabetes in the U.S. RESEARCH DESIGN AND METHODS Using data from the 2001–2017 Medical Expenditure Panel Survey, we estimated total per person annual OOP costs (insurance premiums, prescription drug costs, inpatient and outpatient deductibles, copays, and other payments not covered by insurance) and high OOP cost rate, defined as the percentage of people with OOP spending &amp;gt;10% of their family’s pretax income. We examined trends overall, by subgroup (insurance type, income level, insulin use, size of patient’s employer, and whether the patient was enrolled in a high deductible health plan), and by type of service. Changes in trends were identified using joinpoint analysis; costs were adjusted to 2017 U.S. dollars. RESULTS From 2001 to 2017, OOP costs decreased 4.3%, from $4,328 to $4,139, and the high OOP cost rate fell 32%, from 28 to 19% (P &amp;lt; 0.001). Changes in the high OOP cost rate varied by subgroup, declining among those with public or no insurance and those with an income &amp;lt;200% of the federal poverty level (P &amp;lt; 0.001) but remaining stable among those with private insurance and higher income. Drug prescription OOP costs decreased among all subgroups (P &amp;lt; 0.001). Decreases in total (−$58 vs. −$37, P &amp;lt; 0.001) and prescription (−$79 vs. −$68, P &amp;lt; 0.001) OOP costs were higher among insulin users than noninsulin users. CONCLUSIONS OOP costs among U.S. nonelderly adults with diabetes declined, especially among those least able to afford them. Future studies may explore factors contributing to the decline in OOP costs and the impact on the quality of diabetes care and complication rates.
27660 Parasite infection in a patient with a CD30 clonal T-cell lymphocytic variant of hypereosinophilic syndrome: Cause or coincidence
Authors: Daniel Ramos-Rodriguez, Joan Garcias-Ladaria, María Nuñez Sanchez, María Peñaranda, Antonio Gutierrez, Juan Escalas Taberner
Journal: Journal of the American Academy of Dermatology (2021)