tbuckley/cabot-search huggingface dataset:
Cell-adaptable dynamic hydrogel reinforced with stem cells improves the functional repair of spinal cord injury by alleviating neuroinflammation
Authors: Xin Yuan, Weihao Yuan, Lu Ding, Ming Shi, Liang Luo, Yong Wan, Jiwon Oh, Yanfang Zhou, Liming Bian, David Y.B. Deng
Journal: Biomaterials (2021)

Spinal cord injury (SCI) is one of the most challenging clinical issues. It is characterized by the disruption of neural circuitry and connectivity, resulting in neurological disability. Adipose-derived stem cells (ADSCs) serve as a promising source of therapeutic cells for SCI treatment. However, the therapeutic outcomes of direct ADSCs transplantation are limited in the presence of an inflammatory microenvironment. Herein, a cell-adaptable neurogenic (CaNeu) hydrogel was developed as a delivery vehicle for ADSCs to promote neuronal regeneration after SCI. The dynamic network of CaNeu hydrogel loaded with ADSCs provides a cell-infiltratable matrix that enhances axonal growth and eventually leads to improved motor evoked potential, hindlimb strength, and coordination of complete spinal cord transection in rats. Furthermore, the CaNeu hydrogel also establishes an anti-inflammatory microenvironment by inducing a shift in the polarization of the recruited macrophages toward the pro-regeneration (M2) phenotype. Our study showed that the CaNeu-hydrogel‒mediated ADSCs delivery resulted in significantly suppressed neuroinflammation and apoptosis, and that this phenomenon involved the PI3K/Akt signaling pathway. Our findings indicate that the CaNeu hydrogel is a valuable delivery vehicle to assist stem cell therapy for SCI, providing a promising strategy for central nervous system diseases.
The Relevance of Urinalysis in the Hospitalization of Patients with COVID-19 and Nephrology Early Intervention
Authors: Lilia M. Rizo Topete, Giovanna Y. Arteaga Muller, Elisa M. Guerrero Gonzalez, Adrian Camacho-Ortiz, Luis C. Mata, Luis F. Rangel, Gabriela E. Aguilar Díaz
Journal: Journal of the American Society of Nephrology (2021)

Background: Multidisciplinary management of the COVID's patients is essential for their evolution, and the early detection ok AKI is a important role to avoid morbimortality. In March 2020, the pandemic by COVID-19 appeared in Mexico, and it led all the health system to change the intrahospital management. Methods: In a retrospective, observational analysis of all the patients >18 Y that were hospitalized at the Hospital Universitario de Monterrey, in the COVID area, from March to August 2020, we notice how the urinary sedimentation evaluation from the beginning could detect patients who could develop AKI or the need of RRT. All data were analyzed using SPSS statistical software (version 25;IBM Corporation, Armonk, New York). Results: A total of 344 patients hospitalized from March to August 2020. 220 patients with EGO since the beginning (obtained when our nephrology team take place on the presential participation on AEMA) 102 did not have proteinuria, and, on the other hand, the rest (61 or 37%) reported it. 95 patients (41.7%) had hematuria. Hematuria were more likely to be treated with KRT. Patients with hematuria demonstrated an increased tendency to require RRT: 38.2% of patients with hematuria versus 11.6% without hematuria, the greater chance that needs RRT (P<.001). Conclusions: The presence of active sedimentary urinary on COVID patients is frequent. The patients who present the combination of hematuria and proteinuria develop severe AKI (KDIGO 3 without RRT) or the need for RRT. Factors in patients such as to be on their upper edge of 40 years old, the presence of hyperkalemia, metabolic acidosis, also the hematuria and proteinuria, suggest the AKI risk that required RRT.
Association Between COVID-19 Diagnosis and In-Hospital Mortality in Patients Hospitalized With ST-Segment Elevation Myocardial Infarction
Authors: Marwan Saad, Kevin F. Kennedy, Hafiz Imran, David W. Louis, Ernie Shippey, Athena Poppas, Kenneth E. Wood, J. Dawn Abbott, Herbert D. Aronow
Journal: JAMA (2021)

<h3>Importance</h3> There has been limited research on patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19. <h3>Objective</h3> To compare characteristics, treatment, and outcomes of patients with STEMI with vs without COVID-19 infection. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of consecutive adult patients admitted between January 2019 and December 2020 (end of follow-up in January 2021) with out-of-hospital or in-hospital STEMI at 509 US centers in the Vizient Clinical Database (N = 80 449). <h3>Exposures</h3> Active COVID-19 infection present during the same encounter. <h3>Main Outcomes and Measures</h3> The primary outcome was in-hospital mortality. Patients were propensity matched on the likelihood of COVID-19 diagnosis. In the main analysis, patients with COVID-19 were compared with those without COVID-19 during the previous calendar year. <h3>Results</h3> The out-of-hospital STEMI group included 76 434 patients (551 with COVID-19 vs 2755 without COVID-19 after matching) from 370 centers (64.1% aged 51-74 years; 70.3% men). The in-hospital STEMI group included 4015 patients (252 with COVID-19 vs 756 without COVID-19 after matching) from 353 centers (58.3% aged 51-74 years; 60.7% men). In patients with out-of-hospital STEMI, there was no significant difference in the likelihood of undergoing primary percutaneous coronary intervention by COVID-19 status; patients with in-hospital STEMI and COVID-19 were significantly less likely to undergo invasive diagnostic or therapeutic coronary procedures than those without COVID-19. Among patients with out-of-hospital STEMI and COVID-19 vs out-of-hospital STEMI without COVID-19, the rates of in-hospital mortality were 15.2% vs 11.2% (absolute difference, 4.1% [95% CI, 1.1%-7.0%];<i>P</i> = .007). Among patients with in-hospital STEMI and COVID-19 vs in-hospital STEMI without COVID-19, the rates of in-hospital mortality were 78.5% vs 46.1% (absolute difference, 32.4% [95% CI, 29.0%-35.9%];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among patients with out-of-hospital or in-hospital STEMI, a concomitant diagnosis of COVID-19 was significantly associated with higher rates of in-hospital mortality compared with patients without a diagnosis of COVID-19 from the past year. Further research is required to understand the potential mechanisms underlying this association.
An ISN-DOPPS Survey of the Global Impact of COVID-19 Pandemic on Home Peritoneal Dialysis Services
Authors: Rehab B. Albakr, Brian Bieber, Ryan E. Aylward, Fergus Caskey, Gavin Dreyer, Rhys D. Evans, Murilo H. Guedes, Vivekanand Jha, Valerie A. Luyckx, Roberto Pecoits-Filho, Chimota T. Phiri, Ronald L. Pisoni, Bruce M. Robinson, Dibya Singh Shah, Elliot K. Tannor, Adrian Liew, Jeffrey Perl
Journal: Journal of the American Society of Nephrology (2021)

Background: Home dialysis may be able to minimize SARS-CoV2 exposure risks. The pandemic may have introduced unique challenges related to supply disruption and care delivery changes. We sought to assess the global burden of COVID-19 on peritoneal dialysis units (PD) and understand PD unit practice changes during this time. Methods: The Peritoneal Dialysis/Dialysis Outcomes and Practice Patterns Study (PDOPPS/DOPPS) and International Society of Nephrology (ISN) administered a webbased survey (1) to dialysis units selected based on a random sample stratified by region (November 2020 -March 2021), and (2) to an open invitation via ISN's membership list and social media (March 2021). Responses were compared across 10 ISN regions. Results: Returned surveys included 167 PD facilities across 52 countries. Changes in several care domains including clinic communication and frequency, labwork frequency, method of communication, masking policies, changes in handling of PD effluent among infected individuals, PD supply disruption, access to methods of PD catheter insertion and frequency of new patient training are highlighted (table). Conclusions: Variability exists in routine PD care, and the availability and use of PPE, disruption in PD supplies among the different regions reflecting the availability of the resources and infrastructure differences. LMIC tended to be more severely impacted-this gap needs to be addressed in anticipation of future pandemics for treatment continuity. Although remote technology use among PD patients to communicate with their physicians has increased during the pandemic, optimal communication frequency, methods and schedule of routine bloodwork needs to be better elucidated.
Corrections to “REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours”
Authors: C. Lévy, D. Allouache, J. Lacroix, A.E. Dugué, S. Supiot, M. Campone, M. Mahe, S. Kichou, M. Leheurteur, C. Hanzen, V. Dieras, Y. Kirova, F. Campana, E. Le Rhun, L. Gras, T. Bachelot, M.-P. Sunyach, I. Hrab, J. Geffrelot, K. Gunzer, J.-M. Constans, J.-M. Grellard, B. Clarisse, X. Paoletti
Journal: Annals of Oncology (2015)
NIMG-12. MR SUSCEPTIBILITY IMAGING FOR DETECTION OF TUMOR-ASSOCIATED MACROPHAGES IN GLIOBLASTOMA
Authors: Amir Nazem, Samantha Guiry, Mehrdad Pourfathi, Jeffrey B Ware, Hannah Anderson, Srikant Kamesh Iyer, Brianna F Moon, Yi Fan, Walter R Witschey, Rahim Rizi, Stephen J Bagley, Arati Desai, Donald M O’Rourke, Steven Brem, MacLean Nasrallah, S Ali Nabavizadeh
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) tumor microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, here we investigated non-invasive quantitative susceptibility mapping (QSM) and T2* MRI relaxometry to quantify iron as imaging biomarkers for TAMs in adult patients with GBM. METHODS In this prospective study, 21 adult patients with GBM were enrolled between 2016 to 2019. Patients underwent a 3D single echo gradient echo sequence in addition to standard anatomical sequences on a 3 Tesla MRI. QSM images were reconstructed using the morphology-enabled dipole inversion (MEDI) algorithm. In 3 subjects, ex vivo imaging of surgical specimens was performed on a Bruker 9.4 Tesla 8.9 cm vertical bore MR using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated by a pixel-wise monoexponential fitting. Each specimen was stained with hematoxylin and eosin, as well as with CD68, CD86, CD206, and L-Ferritin. RESULTS Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). Moreover, the mean susceptibility significantly correlated with positivity percent for CD68 (ρ=0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ=0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). High mean susceptibility in the necrotic core was associated with inferior PFS (hazard ratio,4.5, p=0.016). CONCLUSION MR Susceptibility Imaging can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.
JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma
Authors: Yosuke Miyamoto, Toshiyuki Kozuki, Keisuke Aoe, Sae Wada, Daijiro Harada, Michihiro Yoshida, Jun Sakurai, Katsuyuki Hotta, Nobukazu Fujimoto
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background JME-001 is a phase II trial assessing the efficacy and safety of cisplatin, pemetrexed, and nivolumab as first-line therapy in malignant pleural mesothelioma (MPM). Patients and methods Patients with untreated, unresectable MPM with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were included. The primary endpoint is the centrally reviewed objective response rate. The secondary endpoints include (1) response rate assessed by investigators, (2) disease control rate, (3) overall survival, (4) progression-free survival, (5) duration of response, and (6) time to response. Safety and adverse events will also be evaluated. Cisplatin (75 mg/m 2 ), pemetrexed (500 mg/m 2 ), and nivolumab (360 mg/body) were administered intravenously every 3 weeks with a total of 4–6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression or unacceptable toxicity. Tissue samples were required and collected for programmed death ligand 1 analysis. Results Eighteen patients (mean age 69.2 years, 15 men) were enrolled between January 2018 and May 2019. The ECOG PS was 0 in 3 patients and 1 in 15 patients. Fourteen (77.8%; 95% CI 52.4% to 93.6%) patients had an objective response. The disease control rate was 94.4% (95% CI 72.7% to 99.9%). Fourteen (77.8%) patients had partial response (PR), three had stable disease, and one was not evaluable. Tumor shrinkage was observed in 10/14 (71.4%) patients with epithelioid, and 2/2 (100%) patients with sarcomatoid or biphasic histological subtype had PR. Ten (55.6%) patients experienced grade 3 or worse adverse events, including disorder of metabolism or nutrition (33.3%), loss of appetite (27.8%), anemia (16.7%), and hyponatremia (11.1%). No treatment-related deaths occurred. Conclusions The safety and efficacy of this study strongly support a definitive trial of this combination. Trial registration number UMIN000030892.
TCT-359 Treatment Effect of Primary Percutaneous Coronary Intervention on In-Hospital Outcomes of Active Cancer Patients Presenting With ST-Elevation Myocardial Infarction
Authors: Mohamed Mohamed, Harriette Van Spall, Mohamad Alkhouli, Safi Khan, Ana Barac, Ahmad Shoaib, Islam Elgendy, Deepak Bhatt, Mamas Mamas
Journal: Journal of the American College of Cardiology (2021)
AAV5 delivery of CRISPR-Cas9 supports effective genome editing in mouse lung airway
Authors: Shun-Qing Liang, Christopher J. Walkey, Alexa E. Martinez, Qin Su, Mary E. Dickinson, Dan Wang, William R. Lagor, Jason D. Heaney, Guangping Gao, Wen Xue
Journal: Molecular Therapy (2021)

Genome editing in the lung has the potential to provide long-term expression of therapeutic protein to treat lung genetic diseases. Yet efficient delivery of CRISPR to the lung remains a challenge. The NIH Somatic Cell Genome Editing (SCGE) Consortium is developing safe and effective methods for genome editing in disease tissues. Methods developed by consortium members are independently validated by the SCGE small animal testing center to establish rigor and reproducibility. We have developed and validated a dual adeno-associated virus (AAV) CRISPR platform that supports effective editing of a lox-stop-lox-Tomato reporter in mouse lung airway. After intratracheal injection of the AAV serotype 5 (AAV5)-packaged S. pyogenes Cas9 (SpCas9) and single guide RNAs (sgRNAs), we observed ∼19%-26% Tomato-positive cells in both large and small airways, including club and ciliated epithelial cell types. This highly effective AAV delivery platform will facilitate the study of therapeutic genome editing in the lung and other tissue types.
SARS-CoV-2–specific B- and T-cell immunity in a population-based study of young Swedish adults
Authors: Sophia Björkander, Likun Du, Fanglei Zuo, Sandra Ekström, Yating Wang, Hui Wan, Natalia Sherina, Lisanne Schoutens, Juni Andréll, Niklas Andersson, Antonios Georgelis, Anna Bergström, Harold Marcotte, Inger Kull, Lennart Hammarström, Erik Melén, Qiang Pan-Hammarström, Catarina Almqvist, Niklas Andersson, Natalia Ballardini, Anna Bergström, Sophia Björkander, Petter Brodin, Anna Castel, Sandra Ekström, Antonios Georgelis, Lennart Hammarström, Qiang Pan-Hammarström, Jenny Hallberg, Christer Jansson, Maura Kere, Inger Kull, André Lauber, Alexandra Lövquist, Erik Melén, Jenny Mjösberg, Ida Mogensen, Lena Palmberg, Göran Pershagen, Niclas Roxhed, Jochen Schwenk
Journal: Journal of Allergy and Clinical Immunology (2021)

Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot.A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.
TCT-400 Rapid Pacing Is an Independent Predictor of Higher Implantation Depth Using Self-Expandable Devices in TAVR
Authors: Verena Veulemans, Oliver Maier, Kerstin Piayda, Stephan Binneboessel, Shazia Afzal, Amin Polzin, Patrick Horn, Christian Jung, Ralf Westenfeld, Tobias Zeus
Journal: Journal of the American College of Cardiology (2021)
Spatiotemporal depletion of tumor-associated immune checkpoint PD-L1 with near-infrared photoimmunotherapy promotes antitumor immunity
Authors: Shunichi Taki, Kohei Matsuoka, Yuko Nishinaga, Kazuomi Takahashi, Hirotoshi Yasui, Chiaki Koike, Misae Shimizu, Mitsuo Sato, Kazuhide Sato
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Near-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells. Methods We used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models. Results Although PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the ‘photoimmuno’ effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors. Conclusions Local PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics.
Wound healing: potential therapeutic options
Authors: D.C. Bosanquet, K.G. Harding
Journal: British Journal of Dermatology (2021)

This review highlights the range of therapeutic options available to clinicians treating difficult-to-heal wounds. While certain treatments are established in daily clinical practice, most therapeutic interventions lack robust and rigorous data regarding their efficacy, which would help to determine when, and for whom, they should be used. The purpose of this review is to give a broad overview of the available interventions, with a brief summary of the evidence base for each intervention.
U.S. FDA Drug Approvals for Gynecological Malignancies: A Decade in Review
Authors: Shaily Arora, Preeti Narayan, Gwynn Ison, Tara Berman, Daniel L. Suzman, Suparna Wedam, Tatiana M. Prowell, Soma Ghosh, Reena Philip, Christy L. Osgood, Jennifer J. Gao, Mirat Shah, Danielle Krol, Sakar Wahby, Melanie Royce, Christina Brus, Erik W. Bloomquist, Mallorie H. Fiero, Shenghui Tang, Richard Pazdur, Amna Ibrahim, Laleh Amiri-Kordestani, Julia A. Beaver
Journal: Clinical Cancer Research (2021)

Over the last decade, there has been tremendous progress in the treatment of patients with gynecologic cancers with a changing therapy landscape. This summary provides an overview of U.S. Food and Drug Administration (FDA) approvals for gynecologic cancers from 2010 to 2020, totaling 17 new indications. For each of the approved indications, endpoints, trial design, results, and regulatory considerations are outlined. Among these 17 indications, six received accelerated approval (AA) and 11 received regular approval (RA). As of September 2021, of the six AA, three have subsequently demonstrated clinical benefit resulting in conversion to RA and the remaining three have ongoing clinical trials that have not yet reported results. Approval decisions for these 17 indications were supported by primary efficacy endpoints of progression-free survival (n = 10), objective response rate (n = 6), and overall survival (n = 1) and showed a favorable benefit-risk profile. Among the 17 indications, 15 received priority review and three applications participated in one or more novel Oncology Center of Excellence initiatives, including Real Time Oncology Review, Assessment Aid, and Project Orbis. Current FDA thinking on drug development opportunities and regulatory initiatives currently under way will be discussed.
Fasting-mimicking diet blocks triple-negative breast cancer and cancer stem cell escape
Authors: Giulia Salvadori, Federica Zanardi, Fabio Iannelli, Riccardo Lobefaro, Claudio Vernieri, Valter D. Longo
Journal: Cell Metabolism (2021)

Metastatic tumors remain lethal due to primary/acquired resistance to therapy or cancer stem cell (CSC)-mediated repopulation. We show that a fasting-mimicking diet (FMD) activates starvation escape pathways in triple-negative breast cancer (TNBC) cells, which can be identified and targeted by drugs. In CSCs, FMD lowers glucose-dependent protein kinase A signaling and stemness markers to reduce cell number and increase mouse survival. Accordingly, metastatic TNBC patients with lower glycemia survive longer than those with higher baseline glycemia. By contrast, in differentiated cancer cells, FMD activates PI3K-AKT, mTOR, and CDK4/6 as survival/growth pathways, which can be targeted by drugs to promote tumor regression. FMD cycles also prevent hyperglycemia and other toxicities caused by these drugs. These data indicate that FMD has wide and differential effects on normal, cancer, and CSCs, allowing the rapid identification and targeting of starvation escape pathways and providing a method potentially applicable to many malignancies.