tbuckley/cabot-search huggingface dataset:
Aerogels in drug delivery: From design to application
Authors: Carlos A. García-González, Alejandro Sosnik, József Kalmár, Iolanda De Marco, Can Erkey, Angel Concheiro, Carmen Alvarez-Lorenzo
Journal: Journal of Controlled Release (2021)

Aerogels are the lightest processed solid materials on Earth and with the largest empty volume fraction in their structure. Composition versatility, modularity, and feasibility of industrial scale manufacturing are behind the fast emergence of aerogels in the drug delivery field. Compared to other 3D materials, the high porosity (interconnected mesopores) and high specific surface area of aerogels may allow faster loading of small-molecule drugs, less constrained access to inner regions of the matrix, and more efficient interactions of the biological milieu with the polymer matrix. Processing in supercritical CO2 medium for both aerogel production (drying) and drug loading (impregnation) has remarkable advantages such as absence of an oxidizing environment, clean manufacture, and easiness for the scale-up under good manufacturing practices. The aerogel solid skeleton dictates the chemical affinity to the different drugs, which in turn determines the loading efficiency and the release pattern. Aerogels can be used to increase the solubility of BCS Class II and IV drugs because the drug can be deposited in amorphous state onto the large surface area of the skeleton, which facilitates a rapid contact with the body fluids, dissolution, and release. Conversely, tuning the aerogel structure by functionalization with drug-binding moieties or stimuli-responsive components, application of coatings and incorporation of drug-loaded aerogels into other matrices may enable site-specific, stimuli-responsive, or prolonged drug release. The present review deals with last decade advances in aerogels for drug delivery. An special focus is paid first on the loading efficiency of active ingredients and release kinetics under biorelevant conditions. Subsequent sections deal with aerogels intended to address specific therapeutic demands. In addition to oral delivery, the physical properties of the aerogels appear to be very advantageous for mucosal administration routes, such as pulmonary, nasal, or transdermal. A specific section devoted to recent achievements in gene therapy and theranostics is also included. In the last section, scale up strategies and life cycle assessment are comprehensively addressed.
Abstract PS9-44: Breaking the silent struggles: Development of a cancer caregiver support program
Authors: Joyce Marie Koerber, Magdolna Solti
Journal: Cancer Research (2021)

Abstract Background/Purpose: 4.6 million Americans serve as unpaid caregivers for someone with cancer. The burden of caregiving poses challenges to one’s physical, psychological, financial and spiritual health. Our project aimed to explore caregiver needs and provide comprehensive information and practical guidance to enhance coping during and after treatment. Methods: We conducted targeted interviews with 50 caregivers of patients with high risk cancers (brain, head and neck, lung, gastrointestinal, gynecologic, breast and hematologic cancers) to prioritize and discuss their most pressing concerns. Caregiver quality of life and well-being was assessed using validated tools that were measured at baseline and 6 months later. A Caregiver Resource Manual was developed with a list of tangible resources and provided to all families. Supportive interventions included counseling, palliative care, referral to nutrition and support groups. Results: The interviewed caregivers included spouses, children, friends and parents. At baseline, 55% of patients had stage IV disease. Within 6-months, 38% of patients expired or progressed, 59% stayed in remission or remained stable on treatment. At baseline, 65% of caregivers reported moderate/high distress, 39% scored moderately/high in feeling their life was imposed upon, and 58% scored moderately/high in difficulty meeting their own medical needs. After intervention, moderate/high scores improved by 25% in distress, 18% in feeling life was imposed upon and 12% in attending to medical needs. The well-being survey found an 8% increase in all aspects assessed.Conclusion: Our project recognized patients and caregivers as one unit of care with information and support needed for both. The interventions improved caregiver stress and overall well-being. We found a gap in adequately preparing families for progressive nature of disease highlighting the need for proactive palliative care in the future. Citation Format: Joyce Marie Koerber, Magdolna Solti. Breaking the silent struggles: Development of a cancer caregiver support program [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-44.
Engineering the MSC Secretome: A Hydrogel Focused Approach
Authors: Marissa E. Wechsler, Varsha V. Rao, Alexandra N. Borelli, Kristi S. Anseth
Journal: Advanced Healthcare Materials (2021)

The therapeutic benefits of exogenously delivered mesenchymal stromal/stem cells (MSCs) have been largely attributed to their secretory properties. However, clinical translation of MSC-based therapies is hindered due to loss of MSC regenerative properties during large-scale expansion and low survival/retention post-delivery. These limitations might be overcome by designing hydrogel culture platforms to modulate the MSC microenvironment. Hydrogel systems could be engineered to i) promote MSC proliferation and maintain regenerative properties (i.e., stemness and secretion) during ex vivo expansion, ii) improve MSC survival, retention, and engraftment in vivo, and/or iii) direct the MSC secretory profile using tailored biochemical and biophysical cues. Herein, it is reviewed how hydrogel material properties (i.e., matrix modulus, viscoelasticity, dimensionality, cell adhesion, and porosity) influence MSC secretion, mediated through cell-matrix and cell-cell interactions. In addition, it is highlighted how biochemical cues (i.e., small molecules, peptides, and proteins) can improve and direct the MSC secretory profile. Last, the authors' perspective is provided on future work toward the understanding of how microenvironmental cues influence the MSC secretome, and designing the next generation of biomaterials, with optimized biophysical and biochemical cues, to direct the MSC secretory profile for improved clinical translation outcomes.
Reassessing the Net Benefit of Cancer Drugs With Evolution of Evidence Using the ASCO Value Framework
Authors: Seanthel Delos Santos, Noah Witzke, Bishal Gyawali, Vanessa Sarah Arciero, Amanda Putri Rahmadian, Louis Everest, Matthew C. Cheung, Kelvin K. Chan
Journal: Journal of the National Comprehensive Cancer Network (2021)

Regulatory approval of oncology drugs is often based on interim data or surrogate endpoints. However, clinically relevant data, such as long-term overall survival and quality of life (QoL), are often reported in subsequent publications. This study evaluated the ASCO-Value Framework (ASCO-VF) net health benefit (NHB) at the time of approval and over time as further evidence arose.FDA-approved oncology drug indications from January 2006 to December 2016 were reviewed to identify clinical trials scorable using the ASCO-VF. Subsequent publications of clinical trials relevant for scoring were identified (until December 2019). Using ASCO-defined thresholds (≤40 for low and ≥45 for substantial benefit), we assessed changes in classification of benefit at 3 years postapproval.Fifty-five eligible indications were included. At FDA approval, 40.0% were substantial, 10.9% were intermediate, and 49.1% were low benefit. We then identified 90 subsequent publications relevant to scoring, including primary (28.9%) and secondary endpoint updates (47.8%), safety updates (31.1%), and QoL reporting (47.8%). There was a change from initial classification of benefit in 27.3% of trials (10.9% became substantial, 9.1% became low, and 7.3% became intermediate). These changes were mainly due to updated hazard ratios (36.4%), toxicities (56.4%), new tail-of-the-curve bonus (9.1%), palliation bonus (14.5%), or QoL bonus (18.2%). Overall, at 3 years postapproval, 40.0% were substantial, 9.1% were intermediate, and 50.9% were low benefit.Because there were changes in classification for more than one-quarter of indications, in either direction, reassessing the ASCO-VF NHB as more evidence becomes available may be beneficial to inform clinical shared decision-making. On average, there was no overall improvement in the ASCO-VF NHB with longer follow-up and evolution of evidence.
Why are weight loss outcomes unequal despite similar reductions in gastric volume?
Authors: Vivek Kumbhari
Journal: Endoscopy (2021)

Although considered by many as unjustified, the perception of bariatric surgery by patients and healthcare providers remains poor [1]. Therefore, the development of non-surgical minimally invasive strategies that alter the gastrointestinal tract to induce the physical and physiologic effects of bariatric surgery is required. An endoscopic technique that exclusively emulates the physical elements of surgery (restriction/volume reduction) will not fully reproduce the weight loss and metabolic benefits observed by patients undergoing the most commonly performed bariatric surgery, namely laparoscopic sleeve gastrectomy (LSG) [2]. However, until the precise pathologic mechanisms causing the profound physiologic alterations are discovered, the next best alternative is to offer an appealing, safe, well-tolerated, and effective technique that at least imitates the physical appearances of bariatric surgery, such as endoscopic sleeve gastroplasty (ESG) [3].
Explicit motor learning interventions are still relevant for ACL injury rehabilitation: do not put all your eggs in the implicit basket!
Authors: Elmar Kal, Toby Ellmers, Jed Diekfuss, Marinus Winters, John van der Kamp
Journal: British Journal of Sports Medicine (2021)

ACL ruptures are rapidly increasing.1 ACL injuries can have a profound impact on an athlete’s physical and psychological functioning, and sporting career. Current standard of care following ACL injury is neuromuscular rehabilitation to help athletes regain motor skills. Optimising how rehabilitation is delivered has the potential to further enhance motor relearning and reduce the risk of secondary knee injuries.2

ACL injury rehabilitation programmes aiming to reduce secondary injury risk often involve explicit learning strategies to improve biomechanics and increase neuromuscular control.3 Athletes are mostly instructed to consciously control movements using internally focused, verbal cues that prescribe desired movement patterns (eg, ‘do not bring your knees over your toes’ during squatting). Only with sustained practice does explicit learning result in consistent, fluent, and automatic, motor performance.

Recently, practitioners have been encouraged to minimise explicit learning during ACL injury rehabilitation, and use implicit learning interventions such as external focus cues.2 We contend that implicit interventions are not a panacea, and that explicit interventions remain important in ACL injury rehabilitation. We discuss key individual characteristics and contextual constraints that warrant the use of explicit interventions.

### Why would implicit learning be beneficial to ACL rehabilitation?

The theoretical advantage of implicit learning interventions is that athletes reach automaticity earlier in the learning process. Accordingly, implicit …
Respiratory workforce is in a state of constant crisis, doctors warn
Authors: Abi Rimmer
Journal: BMJ (2021)

The respiratory workforce has been left in a state of constant crisis by years of underinvestment, doctors have warned.

The British Thoracic Society said that UK respiratory services are so understaffed and under-resourced that they are unable both to deliver routine services and specialist clinics as well as treat patients with acute covid-19 and run …
Downregulated miR-451a as a feature of the plasma cfRNA landscape reveals regulatory networks of IL-6/IL-6R-associated cytokine storms in COVID-19 patients
Authors: Penghui Yang, Yingze Zhao, Jie Li, Chuanyu Liu, Linnan Zhu, Jie Zhang, Yeya Yu, Wen-Jing Wang, Guanglin Lei, Jin Yan, Fang Sun, Chengrong Bian, Fanping Meng, Zhe Xu, Changqing Bai, Beiwei Ye, Yuanyuan Guo, Liumei Shu, Xiaoju Yuan, Ning Zhang, Yuhai Bi, Yi Shi, Guizhen Wu, Shaogeng Zhang, George F. Gao, Longqi Liu, William J. Liu, Hai-Xi Sun
Journal: Cellular and Molecular Immunology (2021)
Protein Quality Control in Heart Disease: Using Established Drugs to Target Novel Mechanisms⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Francisco Villarreal, Wilbur Y.W. Lew
Journal: Journal of the American College of Cardiology (2010)
Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M
Authors: M. Elizabeth Deerhake, Keiko Danzaki, Makoto Inoue, Emre D. Cardakli, Toshiaki Nonaka, Nupur Aggarwal, William E. Barclay, Ru-Rong Ji, Mari L. Shinohara
Journal: Immunity (2021)
Esophageal adenocarcinoma on esophageal varices – endoscopic resection after transjugular intrahepatic portosystemic shunt
Authors: Andreas Probst, Christian Scheurig-Münkler, Stefan Gölder, Bei Huang, Helmut Messmann, Georg Braun
Journal: Endoscopy (2021)

Endoscopic resection is the first-choice therapy for T1a esophageal adenocarcinoma (EAC) [1]. In patients with liver cirrhosis, endoscopic resection might be difficult due to portal hypertension, esophageal varices, and coagulation disorders. Few case reports describe endoscopic resection in this setting and the optimal treatment strategy is not defined [2] [3] [4] [5].
Telangiectases in Systemic Sclerosis
Authors: Rebecca Jacobson, Ritesh Agnihothri, Anna Haemel
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests
Authors: Netta Barak, Roni Ben-Ami, Tal Sido, Amir Perri, Aviad Shtoyer, Mila Rivkin, Tamar Licht, Ayelet Peretz, Judith Magenheim, Irit Fogel, Ayalah Livneh, Yutti Daitch, Esther Oiknine-Djian, Gil Benedek, Yuval Dor, Dana G. Wolf, Moran Yassour, A. Klochendler, A. Eden, A. Klar, A. Geldman, A. Arbel, B. Shalom, B. L. Ochana, D. Avrahami-Tzfati, D. Neiman, D. Steinberg, D. Ben Zvi, E. Shpigel, G. Atlan, H. Klein, H. Chekroun, H. Shani, I. Hazan, I. Ansari, I. Magenheim, J. Moss, L. Peretz, L. Feigin, M. Saraby, M. Sherman, M. Bentata, M. Avital, M. Kott, M. Peyser, M. Weitz, M. Shacham, M. Grunewald, N. Sasson, N. Wallis, N. Azazmeh, N. Tzarum, O. Fridlich, R. Sher, R Condiotti, R. Refaeli, R. Zaken-Gallili, R. Helman, S. Ofek, S. Tzaban, S. Piyanzin, S. Anzi, S. Dagan, S. Lilenthal, T. Friehmann, Y. Kaufman, A. Saada, A. Dekel, A. Yeffet, A. Shaag, A. Michael-Gayego, E. Shay, E. Arbib, H. Onallah, K. Ben-Meir, L. Levinzon, L. Cohen-Daniel, L. Natan, M. Hamdan, M. Shwieki, O. Vorontsov, R. Barsuk, R. Abramovitch, R. Gutorov, S. Sirhan, S. Abdeen, Y. Yachnin, H. Golan-Berman, E. Amir, T. Fridman, E. Chabube Kripper, T. Miriam Rohrlich, G. Batshon, L. Mendelovitz
Journal: Science Translational Medicine (2021)

Pooling multiple swab samples before RNA extraction and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis has been proposed as a strategy to reduce costs and increase throughput of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. However, reports on practical large-scale group testing for SARS-CoV-2 have been scant. Key open questions concern reduced sensitivity due to sample dilution, the rate of false positives, the actual efficiency (number of tests saved by pooling), and the impact of infection rate in the population on assay performance. Here, we report an analysis of 133,816 samples collected between April and September 2020 and tested by Dorfman pooling for the presence of SARS-CoV-2. We spared 76% of RNA extraction and RT-PCR tests, despite the frequently changing prevalence (0.5 to 6%). We observed pooling efficiency and sensitivity that exceeded theoretical predictions, which resulted from the nonrandom distribution of positive samples in pools. Overall, our findings support the use of pooling for efficient large-scale SARS-CoV-2 testing.
Racial and Ethnic Differences in Echocardiographic Abnormalities and Myocardial Injury in Patients With Covid-19: The CIRC-19 Registry
Authors: M. S. Miller, G. Giustino, A. Kini, G. Stefanini, R. Bragato, E. Rashed, M. Vicenzi, T. Danilov, N. Kukar, N. Shaban, F. Fazzari, I. Rota, C. P. Oates, A. Camaj, S. Bienstock, S. K. Sharma, J. Silbiger, S. Lerakis, M. E. Goldman, L. B. Croft
Journal: Circulation (2020)
First Identified Cases of SARS-CoV-2 Variant B.1.1.7 in Minnesota — December 2020–January 2021
Authors: Melanie J. Firestone, Alexandra J. Lorentz, Xiong Wang, Kathryn Como-Sabetti, Sara Vetter, Kirk Smith, Stacy Holzbauer, Stephanie Meyer, Kristin Ehresmann, Richard Danila, Ruth Lynfield
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

the Minnesota Department of Health (MDH) announced the identification of the SARS-CoV-2 variant of concern (VOC) B.1.1.7,also referred to as 20I/501Y.V1 and VOC 202012/01, in specimens from five persons; on January 25, MDH announced the identification of this variant in specimens from three additional persons.The B.1.1.7 variant, which is reported to be more transmissible than certain other SARS-CoV-2 lineages* , † (1), was first reported in the United Kingdom in December 2020 (1).As of February 14, 2021, a total of 1,173 COVID-19 cases of the B.1.1.7 variant had been identified in 39 U.S. states and the District of Columbia (2).Modeling data suggest that B.1.1.7 could become the predominant variant in the United States in March 2021 (3).The B.1.1.7 variant has a mutation in the spike protein that causes S-gene target failure (SGTF) in the Thermo Fisher Scientific TaqPath COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) assay.The overall RT-PCR result is positive but is negative for the S-gene target and positive for the other two assay targets; SGTF has served as a proxy for identifying the B.1.1.7 variant (1).The MDH Public Health Laboratory (MDH-PHL) requested SARS-CoV-2 RT-PCR-positive specimens with SGTFs collected during November 1, 2020-January 12, 2021, from clinical laboratories that used the TaqPath assay, and 30 specimens were received.An additional specimen that had been collected from a household contact of a person with an SGTF specimen was requested and obtained from a clinical laboratory using another COVID-19 assay that does not detect SGTFs.MDH-PHL conducted whole genome sequencing to analyze the 31 specimens.§ The SARS-CoV-2 variant B.1.1.7 was identified in eight specimens from Minnesota residents, including six (19%) of the 31 specimens sequenced by MDH-PHL and two specimens sequenced through CDC's national * https://www.medrxiv.org/content/10.1101/2020.12.30.20249034v1.full.
Abstract 12653: The Therapy-related Clonal Hematopoiesis Driver Gene <i>Ppm1d</i> Promotes Inflammation and Non-ischemic Heart Failure in a Murine Model
Authors: Yoshimitsu Yura, Emiri Miura-Yura, Kenneth Walsh
Journal: Circulation (2020)

Background: Therapy-related clonal hematopoiesis in cancer patients is typically associated with somatic mutations in hematopoietic cell genes that encode regulators of the DNA-damage response (DDR) pathway. The Protein Phosphatase Mg2+/Mn2+ Dependent 1D ( PPM1D ) gene is the most frequently mutated DDR gene associated with therapy-related clonal hematopoiesis. While epidemiological evidence suggests an association between therapy-related clonal hematopoiesis and cardiovascular disease in cancer patients, causal and mechanistic relationships have never been evaluated in an experimental system. Methods: To test whether hematopoietic cell mutations in PPM1D can increase the susceptibility to cardiac stress, we evaluated cardiac dysfunction in response to angiotensin II infusion in a mouse model where clonal-hematopoiesis-associated mutations in Ppm1d were produced by CRISPR-Cas9 technology. Results: Mice transplanted with hematopoietic stem cells containing clinically relevant mutations in exon 6 of Ppm1d exhibited augmented cardiac remodeling following the continuous infusion of angiotensin II. Ppm1d -mutated macrophages showed impairments in the DDR pathway and had an augmented proinflammatory profile. Mice transplanted with Ppm1d mutated cells exhibited elevated IL-1β in the stressed myocardium, and bone marrow derived macrophages produced more IL-1β in response to LPS stimulation. The administration of an NLRP3 inflammasome inhibitor to mice reversed the cardiac phenotype induced by the Ppm1d -mutated hematopoietic stem cells under conditions of Angiotensin II-induced stress. Conclusions: A mouse model of Ppm1d -mediated clonal hematopoiesis was more susceptible to cardiac stress following of angiotensin II infusion. Mechanistically, disruption of the DDR pathway led to elevations in inflammatory cytokine production, and the NLRP3 inflammasome was shown to be essential for this augmented cardiac stress response. These data indicate that therapy-related clonal hematopoiesis involving mutations in PPM1D could contribute to the cardiac dysfunction observed in cancer survivors.
Multicenter evaluation of the Panbio™ COVID-19 rapid antigen-detection test for the diagnosis of SARS-CoV-2 infection
Authors: Paloma Merino, Jesús Guinea, Irene Muñoz-Gallego, Patricia González-Donapetry, Juan Carlos Galán, Nerea Antona, Gustavo Cilla, Silvia Hernáez-Crespo, José Luis Díaz-de Tuesta, Ana Gual-de Torrella, Fernando González-Romo, Pilar Escribano, Miguel Ángel Sánchez-Castellano, Mercedes Sota-Busselo, Alberto Delgado-Iribarren, Julio García, Rafael Cantón, Patricia Muñoz, María Dolores Folgueira, Manuel Cuenca-Estrella, Jesús Oteo-Iglesias, Sara Medrano, Alba Pérez, Alicia Galar, Oscar Martínez-Expósito, Izaskun Alejo-Cancho, M. Carmen Martín-Higuera, Marta Rolo, M. Jesús Estévez, Tania Bravo, Diego Vicente, Mila Montes
Journal: Clinical Microbiology and Infection (2021)