tbuckley/cabot-search huggingface dataset:
Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation
Authors: Yijun He, Wenhao Wang, Shaozhang Lin, Yixi Yang, Lizhi Song, Yihan Jing, Lihao Chen, Zaopeng He, Wei Li, Ao Xiong, Kelvin W.K. Yeung, Qi Zhao, Yuan Jiang, Zijie Li, Guoxian Pei, Zhi-Yong Zhang
Journal: Bioactive Materials (2021)

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) - osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.
Leptin brain entry via a tanycytic LepR–EGFR shuttle controls lipid metabolism and pancreas function
Authors: Manon Duquenne, Cintia Folgueira, Cyril Bourouh, Marion Millet, Anisia Silva, Jérôme Clasadonte, Monica Imbernon, Daniela Fernandois, Ines Martinez-Corral, Soumya Kusumakshi, Emilie Caron, S. Rasika, Eleonora Deliglia, Nathalie Jouy, Asturo Oishi, Massimiliano Mazzone, Eric Trinquet, Jan Tavernier, Young-Bum Kim, Stéphane Ory, Ralf Jockers, Markus Schwaninger, Ulrich Boehm, Ruben Nogueiras, Jean-Sébastien Annicotte, Stéphane Gasman, Julie Dam, Vincent Prévot
Journal: Nature Metabolism (2021)
Promoting Long‐Term Cultivation of Motor Neurons for 3D Neuromuscular Junction Formation of 3D In Vitro Using Central‐Nervous‐Tissue‐Derived Bioink
Authors: Jeong Sik Kong, Xuan Huang, Yeong‐Jin Choi, Hee‐Gyeong Yi, Junsu Kang, Sejin Kim, Jongmin Kim, Hyungseok Lee, Yeri Alice Rim, Ji Hyeon Ju, Wan Kyun Chung, Clifford J. Woolf, Jinah Jang, Dong‐Woo Cho
Journal: Advanced Healthcare Materials (2021)

Abstract 3D cell printing technology is in the spotlight for producing 3D tissue or organ constructs useful for various medical applications. In printing of neuromuscular tissue, a bioink satisfying all the requirements is a challenging issue. Gel integrity and motor neuron activity are two major characters because a harmonious combination of extracellular materials essential to motor neuron activity consists of disadvantages in mechanical properties. Here, a method for fabrication of 3D neuromuscular tissue is presented using a porcine central nervous system tissue decellularized extracellular matrix (CNSdECM) bioink. CNSdECM retains CNS tissue‐specific extracellular molecules, provides rheological properties crucial for extrusion‐based 3D cell printing, and reveals positive effects on the growth and maturity of axons of motor neurons compared with Matrigel. It also allows long‐term cultivation of human‐induced‐pluripotent‐stem‐cell‐derived lower motor neurons and sufficiently supports their cellular behavior to carry motor signals to muscle fibers. CNSdECM bioink holds great promise for producing a tissue‐engineered motor system using 3D cell printing.
Correction to Lancet Psychiatry 2021; published online July 16, 2020. https://doi.org/10.1016/S2215-0366(20)30307-2
Journal: The Lancet Psychiatry (2021)

Reports an error in How mental health care should change as a consequence of the COVID-19  by Carmen Moreno, Til Wykes, Silvana Galderisi, Merete Nordentoft, Nicolas Crossley, Nev Jones, Mary Cannon, Christoph U. Correll, Louise Byrne, Sarah Carr, Eric Y. H. Chen, Philip Gorwood, Sonia Johnson, Hilkka Karkkainen, John H. Krystal, Jimmy Lee, Jeffrey Lieberman, Carlos Lopez-Jaramillo, Miia Mannikko, Michael R. Phillips, Hiroyuki Uchida, Eduard Vieta, Antonio Vita and Celso Arango (The Lancet Psychiatry, 2020[Sep], Vol 7[9], 813-824). In the original article, the word Scandinavia has been corrected to Switzerland in relation to service users becoming more common in guiding mental health services. This correction has been made to the online version. (The following abstract of the original article appeared in record 2020-64057-025). The unpredictability and uncertainty of the COVID-19 pandemic;the associated lockdowns, physical distancing, and other containment strategies;and the resulting economic breakdown could increase the risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Advances in adjunct therapy against tuberculosis: Deciphering the emerging role of phytochemicals
Authors: Samreen Fatima, Anjna Kumari, Ved Prakash Dwivedi
Journal: MedComm (2021)

Abstract Eastern countries are a major source of medicinal plants, which set up a rich source of ethnopharmacologically known medicines used in the treatment of various diseases. These traditional medicines have been known as complementary, alternative, or nonconventional therapy across globe for ages. Tuberculosis (TB) poses a huge global burden and leads to maximum number of deaths due to an infectious agent. Treatment of TB using Directly Observed Treatment Short‐course (DOTS) therapy comprises multiple antibiotics is quite lengthy and causes serious side‐effects in different organs. The length of the TB treatment leads to withdrawal from the patients, which paves the way for the emergence of drug resistance in the bacterial population. These concerns related to therapy need serious and immediate interventions. Traditional medicines using phytochemicals has shown to provide tremendous potential in TB treatment, mainly in the eradication of Mycobacterium tuberculosis ( M.tb ), increasing natural immunity, and managing the side effects of anti‐TB drugs. This review describes the antituberculosis potential of selected ethnopharmacologically important phytochemicals as potential immune‐modulator and as an adjunct‐therapy in TB. This review will be a useful reference for researchers working on ethnopharmacology and will open the door for the discovery of novel agents as an adjunct‐therapy to tuberculosis.
P-185 A prospective, randomized, controlled, multicenter phase III clinical trial of apatinib combined with neoadjuvant chemoradiotherapy for patients with locally advanced, HER2-negative, Siewert’s type II-III adenocarcinoma of esophagogastric junction
Authors: Q. Zhao, J. Wang, H. Gou, Y. Li, Y. Cheng, Z. Zhang, D. Wang, X. Zhao, Y. Liu, S. Jing, P. Yang, Y. Tian, Y. Liu
Journal: Annals of Oncology (2021)
Abstract #4600: Chk1 inhibitors override the DNA damage checkpoint and enhance anti-tumor activity of irinotecan in p53-deficient tumor xenografts in mice
Authors: Joe Davide, Ron Diehl, Vicki South, Rob Lobell, Rob Garbaccio, Vadim Dudkin, Mark Fraley, Laura Sepp-Lorenzino, Weikang Tao
Journal: Cancer Research (2009)

DNA damage can activate both Chk1- and p53-mediated checkpoints which function independently to prevent cells from entering mitosis and subsequent mitotic catastrophe by enforcing cell cycle arrest. In p53-deficient cells, the control of the progression into mitosis in response to DNA damage relies solely on the Chk1-mediated checkpoint and thus the inhibition of Chk1 could selectively sensitize p53-deficient cancer cells to mitotic catastrophe. Chk1 inhibitors have been developed as p53-dependent chemosensitizers. We have evaluated the checkpoint-abrogating and anti-tumor activities of several potent and specific Chk1 inhibitors in a mouse tumor xenograft model. When administered in combination with irinotecan, Chk1 inhibitors promoted mitotic entry in p53-deficient tumors but not in p53-competent tumors as measured by the quantification of phospho-histone H3 using an immunohistochemistry assay. In addition, while Chk1 inhibitors alone lack anti-tumor activity, they can synergize with irinotecan to suppress tumor growth. The enhancement of anti-tumor effect by Chk1 inhibitors is affected by the dose of irinotecan as well as the dosing schedule. Furthermore, we determined the minimum duration of Chk1 inhibition and the optimal dosing schedule required for promoting mitotic entry and augmenting the suppression of tumor growth using the osmotic minipump to dose Chk1 inhibitors. We found that ~ 6-hour inhibition of Chk1 was needed to abrogate the checkpoint function and enhance anti-tumor efficacy and that administration of Chk1 inhibitors subsequent to irinotecan displayed stronger synergistic effect than co-administration of two agents. These results provide guidance to the clinical development of Chk1 inhibitors.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4600.
Improving Tumor Penetration of Antibodies and Antibody–Drug Conjugates: Taking Away the Barriers for Trojan Horses
Authors: Guus A.M.S. van Dongen
Journal: Cancer Research (2021)

Abstract The high affinity of an antibody can result in restricted tumor penetration and heterogenous tumor distribution, with preferential binding of the antibody to tumor cells localized around tumor vasculature. This so-called “binding site barrier” effect limits the efficacy of antibody-based therapies like antibody–drug conjugates (ADC). In this issue, Bordeau and colleagues introduce an original approach to overcome this barrier through transient competitive inhibition of antibody–antigen binding. By coadministration of an anti-idiotypic anti-trastuzumab domain antibody as a competitive inhibitor, increased tumor penetration of trastuzumab as well as enhanced efficacy of the ADC ado-trastuzumab emtansine were observed in tumor-bearing mice See related article by Bordeau et al., p. 4145
Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas
Authors: Gi-Ming Wang, Gino Cioffi, Nirav Patil, Kristin A Waite, Robert Lanese, Quinn T Ostrom, Carol Kruchko, Michael E Berens, James R Connor, Justin D Lathia, Joshua B Rubin, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2021)

Abstract Background Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States. Methods Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC’s NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models were performed by age group, generating hazard ratios to assess male-to-female survival differences. Results Overall, glioma incidence was higher in males. Male-to-female incidence was lowest in ages 0-9 years (IRR: 1.04, 95% CI: 1.01-1.07, P = .003), increasing with age, peaking at 50-59 years (IRR: 1.56, 95% CI: 1.53-1.59, P &amp;lt; .001). Females had worse survival for ages 0-9 (HR: 0.93, 95% CI: 0.87-0.99), though male survival was worse for all other age groups, with the difference highest in those 20-29 years (HR: 1.36, 95% CI: 1.28-1.44). Incidence and survival differences by age and sex also varied by histological subtype of glioma. Conclusions To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. The current work shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival.
Efficacy and safety of discontinuing antibiotic treatment for uncomplicated respiratory tract infections when deemed unnecessary. A multicentre, randomized clinical trial in primary care
Authors: Carl Llor, Ana Moragas, Carolina Bayona, Josep M. Cots, Silvia Hernández, Olga Calviño, Migdalia Rodríguez, Marc Miravitlles
Journal: Clinical Microbiology and Infection (2021)

To determine the benefits and harms of discontinuing unnecessary antibiotic therapy for uncomplicated respiratory tract infections (RTI) when antibiotics are considered no longer necessary.Multicentre, open-label, randomized controlled clinical trial in primary care centres from 2017 to 2020 (ClinicalTrials.gov, NCT02900820). Adults with RTIs-acute rhinosinusitis, sore throat, influenza or acute bronchitis-who had previously taken any dose of antibiotic for less than 3 days, which physicians no longer deemed necessary were recruited. The patients were randomly assigned in a 1:1 ratio to discontinuing antibiotic therapy or the usual strategy of continuing antibiotic treatment. The primary outcome was the duration of severe symptoms (number of days scoring 5 or 6 on a six-item Likert scale). Secondary outcomes included days with symptoms, moderate symptoms (scores of 3 or 4), antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.A total of 467 patients were randomized, out of which 409 were considered valid for the analysis. The mean (SD) duration of severe symptoms was 3.0 (1.5) days for the patients assigned to discontinuation and 2.8 (1.3) days for those allocated to the control group (mean difference 0.2 days; 95% CI -0.1 to 0.4 days). Patients randomized to the discontinuation group used fewer antibiotics after the baseline visit (52/207 (25.1%) versus 182/202 (90.1%); p 0.001). Patients assigned to antibiotic continuation presented a relative risk of adverse events of 1.47 (95% CI 0.80-2.71), but the need for further health-care contact in the following 3 months was slightly lower (RR 0.61; 95% CI 0.28-1.37).Discontinuing antibiotic treatment for uncomplicated RTIs when clinicians consider it unnecessary is safe and notably reduces antibiotic consumption.
COVID-19 hospitalisation, mortality, vaccination, and postvaccination trends among people with schizophrenia in Israel: a longitudinal cohort study
Authors: Dana Tzur Bitan, Khalaf Kridin, Arnon Dov Cohen, Orly Weinstein
Journal: The Lancet Psychiatry (2021)

Individuals with schizophrenia have an increased risk of severe COVID-19 outcomes, nonetheless, no previous study has provided a year-long account of this risk, or assessed postvaccination trends in this population. This study assessed temporal trends in COVID-19 hospitalisation and mortality among people with schizophrenia during the first year of the pandemic, the predictors for COVID-19 vaccination, postvaccination infection, admission to hospital, and mortality.In this longitudinal cohort study, people with schizophrenia (n=25 539) and controls (n=25 539) were assessed for COVID-19 outcomes before and after vaccination, up to April 30, 2021. Cox proportional hazard regression models and Kaplan-Meier analyses were done to assess longitudinal trends. The study used the databases of Clalit Health Services, the largest health-care organisation in Israel.The sample included 51 078 participants, of which 31 141 (61·0%) male and 19 937 (39·0%) female participants, with a mean age of 51·94 years (SD 15·62). Most of the sample was from the general Jewish population (75·9%), followed by the Arab (19·1%) and Jewish Ultraorthodox population (5·1%). Overall of 51 078 individuals, 356 (0·7%) people had been hospitalised, 133 (0·3%) had died, and a total of 27 400 (53·6%) had been vaccinated. People with schizophrenia showed a higher risk for COVID-19 hospitalisation (HR 4·81, 95% CI 3·57-6·48, p<0·0001) and mortality (HR 2·52, 95% CI 1·64-3·85, p<0·0001), and showed a sharper decline in survival as time progressed. The control group showed a sharper incline in probability to vaccinate (log-rank=309·88, p<0·0001). Medical comorbidity of diabetes, hypertension, obesity, or ischaemic heart disease played a significant role in predicting vaccination rates in the schizophrenia group (all p<0·0001), but not in the control group. Hospitalisation and mortality disparities remained higher among people with schizophrenia who had not been vaccinated in comparison to controls (incidence rate difference of 6·2 and 3·2, respectively) but substantially declined in fully vaccinated groups (incidence rate difference of 1·1 and -0·9, respectively).People with schizophrenia have higher hospitalisation and mortality risk, yet have lower rates of vaccination than in the general population. Disparities in COVID-19 severe outcomes can be substantially reduced by national vaccination plans aimed at actively reaching out to people with schizophrenia.No funding.
Association of Inpatient Continuity of Care With Complications and Length of Stay Among Hospitalized Medicare Enrollees
Authors: James S. Goodwin, Shuang Li, Erin Hommel, Ann B. Nattinger, Yong-Fang Kuo, Mukaila Raji
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Continuity in primary care is associated with improved outcomes, but less information is available on the association of continuity of care in the hospital with hospital complications. <h3>Objective</h3> To assess whether the number of hospitalists providing care is associated with subsequent hospital complications and length of stay. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used multilevel logistic regression models to analyze Medicare claims for medical admissions from 2016 to 2018 with a length of stay longer than 4 days. Admissions with multiple charges on the same day from a hospitalist or an intensive care unit (ICU) stay during hospital days 1 to 3 were excluded. The data were accessed and analyzed from November 1, 2020, to April 30, 2021. <h3>Exposures</h3> The number of different hospitalists who submitted charges during hospital days 1 to 3. <h3>Main Outcomes and Measures</h3> Overall length of stay and transfer to ICU or a new diagnosis of drug toxic effects on hospital day 4 or later. <h3>Results</h3> Among the 617 680 admissions, 362 376 (58.7%) were women, with a mean (SD) age of 80.2 (8.4) years. In 306 037 admissions (49.6%), the same hospitalist provided care on days 1 to 3, while 2 hospitalists provided care in 274 658 admissions (44.5%), and 3 hospitalists provided care in 36 985 admissions (6.0%). There was no significant association between the number of different hospitalists on days 1 to 3 and either length of stay or subsequent ICU transfers. Admissions seeing 2 or 3 hospitalists had a slightly greater adjusted odds of subsequent new diagnoses of drug toxic effects (2 hospitalists: odds ratio [OR], 1.04; 95% CI, 1.02-1.07; 3 hospitalists: OR, 1.07; 95% CI, 1.03-1.12). <h3>Conclusions and Relevance</h3> There was little evidence that receiving care from multiple hospitalists was associated with worse outcomes for patients receiving all their general medical care from hospitalists.
Abstract 14794: Stratification of Cardiovascular Risk Using an Unbiased Proteomic Approach
Authors: Peter Ganz, Alex A Stewart, Ramin Farzaneh-Far, Robert E Mehler, Stephen A Williams, Trudi M Foreman, Richard M Lawn, Mary A Whooley
Journal: Circulation (2012)

Individuals with stable coronary heart disease (CHD) have widely divergent risk for cardiovascular (CV) events. Current methods for CV risk stratification are imprecise, and may lead to both over-t...
Do Steroids Matter? A Retrospective Review of Premedication for Taxane Chemotherapy and Hypersensitivity Reactions
Authors: Olivia M. Lansinger, Savanna Biedermann, Zihuai He, A. Dimitrios Colevas
Journal: Journal of Clinical Oncology (2021)

Despite the widespread use of the taxanes paclitaxel and docetaxel for a variety of cancers and their well-known association with hypersensitivity reactions (HSRs), there is still significant variation in the prescribing practices of steroids for premedication. Premedication almost always includes dexamethasone, which can be associated with multiple adverse effects if taken for extended periods of time. This study reviews the pattern of steroid premedication in patients who received paclitaxel or docetaxel at Stanford Cancer Institute between January 2010 and June 2020.We used an electronic query of the electronic medical record followed up with a manual review of patient charts to ask whether we could find a correlation between steroid premedication dosing and the incidence or severity of HSRs with the first taxane dose. Variables considered included steroid dose and route, dose and type of taxane, clinical cancer group, sex, and race.Five thousand two hundred seventeen patients were identified as having received paclitaxel or docetaxel, and 3,181 met criteria for our analysis. There were 264 (8.3%) HSRs. In adjusted multivariate analysis, we found no correlation of HSR rate or severity among any of the variables evaluated except gynecology oncology clinic patients, who had an increased risk (hazard ratio [HR] 1.34) of HSRs overall and high-grade HSRs (HR 2.34), and female patients, who had a higher rate of HSRs overall (HR 1.26), but not high-grade HSRs.Neither dexamethasone dose nor route correlated with subsequent HSRs. Given the potential for adverse events from repeated high-dose steroids, our findings suggest that routine use of lower doses, such as a single 10 mg dose of dexamethasone, as premedication for taxanes to prevent HSRs is preferable to the current prescribing guidelines.