tbuckley/cabot-search huggingface dataset:
COVID-19-Associated Nephropathy (COVAN): An Emerging Entity of Severe Viral Podocyte Injury and Collapsing Glomerulopathy in Kidney Biopsies
Authors: Surya V. Seshan, Steven Salvatore, Billie S. Fyfe-Kirschner, Ronald Miick, Aqeel A. Siddiqui, Mohamed Kahila, Ramya Ramakrishnan, Richard E. Freundlich, Anthony D. Nicastri
Journal: Journal of the American Society of Nephrology (2020)

Background: COVID19 caused by novel Coronavirus SARS-COV-2 initially presenting primarily as a respiratory illness, is now known to affect several organ systems as part of multiorgan failure including acute kidny injury (AKI), some cases also manifesting nephrotic range proteinuria or syndrome  Methods: 10 renal biopsies from 6 institutions (1 transplant) performed in April-May 2020 were processed for light microscopy, immunostaining (IS) and electron microscopy (EM) for clinco-pathologic analysis  Results: The 10 patients ranged from 25-73 years (Mean 43), male:female 5:5, 8 African American, 1 Hispanic, 1 Asian Indian, having pre-existing co-morbidities of hypertension (7), Diabetes mellitus (5), obesity (9), presenting with AKI (10), nephrotic syndrome (9), proteinuria ranging from 1 5-25g/24hrs, lung symptoms or pneumonia (7), fever (5)  SARS-COV-2 RT-PCR positive (7), IgG antibody positive (2), both negative (1)  All kidney biopsies showed widespread acute tubular injury with focal necrosis, 9 with typical features of segmental/global collapsing glomerulopathy in 10-53% of glomeruli, global glomerulosclerosis (0-35%), focal tubular microcystic changes (8), patchy (7) or diffuse (2) active tubulointerstitial inflammation and scarring (10-40%), focal & diffuse peritubular capillary inflammation, moderate vascular sclerosis anddiabetic kidney disease in 2  No immune deposits were localized by IS  By EM, varied glomerular capillary wall wrinkling and collapse with segmental or global loss of patency (7), total foot process effacement (7), with hyperplastic and vacuolated epithelial cells having protein droplets are noted  The endothelial cells are variably swollen, with tubuloreticular inclusions in 2  Viral particles are identified within cells of glomeruli and tubulointerstitium, scattered or in clustesr in the cytoplasm and endoplasmic reticulum vesicles, confirmed by IS  Conclusions: The constellation of typical glomerular collapsing features with tubulointerstitial findings and localization of virus by EM, suggests a distinct viral associated nephropathy, reminicent of HIV associated nephropathy  A role for viral cytopathic effect, cytokines and underlying APOL1 gene variants could be considered
Targeted nanomedicines for the treatment of bone disease and regeneration
Authors: Farideh Ordikhani, Nooshin Zandi, Mozhdeh Mazaheri, Gaurav A. Luther, Mahsa Ghovvati, Abolfazl Akbarzadeh, Nasim Annabi
Journal: Medicinal Research Reviews (2020)

Targeted delivery by either passive or active targeting of therapeutics to the bone is an attractive treatment for various bone related diseases such as osteoporosis, osteosarcoma, multiple myeloma, and metastatic bone tumors. Engineering novel drug delivery carriers can increase therapeutic efficacy and minimize the risk of side effects. Developmnet of nanocarrier delivery systems is an interesting field of ongoing studies with opportunities to provide more effective therapies. In addition, preclinical nanomedicine research can open new opportunities for preclinical bone-targeted drug delivery; nevertheless, further research is needed to progress these therapies towards clinical applications. In the present review, the latest advancements in targeting moieties and nanocarrier drug delivery systems for the treatment of bone diseases are summarized. We also review the regeneration capability and effective delivery of nanomedicines for orthopedic applications.
Abstract 16361: Clinical and Genetic Determinants of Heart Failure: Optimized by Machine Learning and Mendelian Randomization
Authors: Xiaodong Zhuang, Lizhen Liao, Xinxue Liao
Journal: Circulation (2019)

Introduction: Identifying unrecognized, potentially modifiable risk factors is essential for heart failure (HF) management. Hypothesis: Atherosclerosis Risk in Communities (ARIC) study is used for ...
Experiences of Bereaved Family Members Receiving Commemorative Paintings
Authors: Marisa A. Azad, Marilyn Swinton, France J. Clarke, Alyson Takaoka, Meredith Vanstone, Anne Woods, Anne Boyle, Neala Hoad, Feli Toledo, Joshua Piticaru, Deborah J. Cook
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Although family members of patients who die in the intensive care unit commonly experience long-term psychological distress, end-of-life bereavement support programs for such relatives are uncommon. Whether art influences the grief experience of families is largely unexplored. <h3>Objective</h3> To explore the influence of personalized paintings created to honor deceased critically ill patients on family members' bereavement experience. <h3>Design, Setting, and Participants</h3> A qualitative descriptive analysis was conducted of semistructured interviews of grieving relatives who received a painting after the death of their loved one. The deceased patients were from a 21-bed medical-surgical intensive care unit. Eleven families were invited to receive a painting, of whom 1 family declined. A total of 22 family members of 10 patients who died in the intensive care unit were interviewed in the study between July 11, 2017, and May 19, 2019. <h3>Interventions</h3> Patients were enrolled in an end-of-life care program that elicits and implements wishes of patients and their families to bring peace during the dying process. Selected families of 10 decedents were invited to receive a painting to honor their loved one 1 to 10 months after the patient's death. Using details about the patient's life story, the artist created individualized paintings to commemorate each patient. <h3>Main Outcomes and Measures</h3> The experiences of family members receiving a personalized painting and its reported influence on their grieving experience. <h3>Results</h3> The family members of 10 decedents (mean [SD] age, 60 [14] years; 5 women [50%]; 8 White patients [80%]) were interviewed. The central theme of art to facilitate healing was illustrated through the following domains: the cocreation process, painting narratives, postmortem connections, and legacy. The process of cocreating the paintings with the artist and family members involved reminiscing, storytelling, and creativity. Family members emphasized the role of art to facilitate healing, exemplified through connections with images portrayed that deeply resonated with memories of their loved one. Participants indicated that the paintings validated that the patient was remembered, helped families feel less alone during a time of grief, honored the loved one's life, and enhanced connections between family members and clinicians. <h3>Conclusions and Relevance</h3> This qualitative study's findings suggest that the creation of personalized paintings commemorating the lives of patients may help foster legacy and postmortem connections with clinicians and may help family members in their healing process.
A Blood-based Assay for Assessment of Tumor Mutational Burden in First-line Metastatic NSCLC Treatment: Results from the MYSTIC Study
Authors: Han Si, Michael Kuziora, Katie J. Quinn, Elena Helman, Jiabu Ye, Feng Liu, Urban Scheuring, Solange Peters, Naiyer A. Rizvi, Philip Z. Brohawn, Koustubh Ranade, Brandon W. Higgs, Kimberly C. Banks, Vikram K. Chand, Rajiv Raja
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Tumor mutational burden (TMB) has been shown to be predictive of survival benefit in patients with non–small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors. Measuring TMB in the blood (bTMB) using circulating cell-free tumor DNA (ctDNA) offers practical advantages compared with TMB measurement in tissue (tTMB); however, there is a need for validated assays and identification of optimal cutoffs. We describe the analytic validation of a new bTMB algorithm and its clinical utility using data from the phase III MYSTIC trial. Patients and Methods: The dataset used for the clinical validation was from MYSTIC, which evaluated first-line durvalumab (anti–PD-L1 antibody) ± tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 antibody) or chemotherapy for metastatic NSCLC. bTMB and tTMB were evaluated using the GuardantOMNI and FoundationOne CDx assays, respectively. A Cox proportional hazards model and minimal P value cross-validation approach were used to identify the optimal bTMB cutoff. Results: In MYSTIC, somatic mutations could be detected in ctDNA extracted from plasma samples in a majority of patients, allowing subsequent calculation of bTMB. The success rate for obtaining valid TMB scores was higher for bTMB (809/1,001; 81%) than for tTMB (460/735; 63%). Minimal P value cross-validation analysis confirmed the selection of bTMB ≥20 mutations per megabase (mut/Mb) as the optimal cutoff for clinical benefit with durvalumab + tremelimumab. Conclusions: Our study demonstrates the feasibility, accuracy, and reproducibility of the GuardantOMNI ctDNA platform for quantifying bTMB from plasma samples. Using the new bTMB algorithm and an optimal bTMB cutoff of ≥20 mut/Mb, high bTMB was predictive of clinical benefit with durvalumab + tremelimumab versus chemotherapy.
The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells
Authors: Ashraf S. Yousif, Larance Ronsard, Pankaj Shah, Tatsushi Omatsu, Maya Sangesland, Thalia Bracamonte Moreno, Evan C. Lam, Vladimir D. Vrbanac, Alejandro B. Balazs, Hans-Christian Reinecker, Daniel Lingwood
Journal: Immunity (2020)
Ретроспективний аналіз ефективності лікування хворих на пептичну виразку дванадцятипалої кишки
Authors: A.L. Demydova
Journal: GASTROENTEROLOGY (2020)

У роботі проведено ретроспективний аналіз ефективності лікування хворих на пептичну виразку дванадцятипалої кишки (ПВДПК) за 10 років, з моменту початку впровадження у клінічну практику положень Маастрихтських консенсусів. Виявлено, що частота звернень пацієнтів з приводу ПВДПК не зменшилась. Відмічено вірогідне збільшення частоти повторних звернень через невдалу ерадикацію з приводу даної патології (20,7 % в 1996 році проти 38,8 % у 2006 році, р &lt; 0,01) і зростання відсотка реінфікованих пацієнтів з 5,8 % в 1996 році до 24,7 % у 2006 році. Не зафіксовано різниці в гендерному складі серед реінфікованих хворих та тих, які звернулися повторно. Серед найбільш працездатної частини населення віком від 20 до 50 років Львівського регіону кожен третій пацієнт з ПВДПК звертався для повторного лікування протягом року.
Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS
Authors: Christof Kugler, Christian Thielscher, Bertrand A. Tambe, Martin K. Schwarz, Annett Halle, Frank Bradke, Gabor C. Petzold
Journal: Cell Reports Medicine (2020)

Stroke leads to the degeneration of short-range and long-range axonal connections emanating from peri-infarct tissue, but it also induces novel axonal projections. However, this regeneration is hampered by growth-inhibitory properties of peri-infarct tissue and fibrotic scarring. Here, we tested the effects of epothilone B and epothilone D, FDA-approved microtubule-stabilizing drugs that are powerful modulators of axonal growth and scar formation, on neuroplasticity and motor outcomes in a photothrombotic mouse model of cortical stroke. We find that both drugs, when administered systemically 1 and 15 days after stroke, augment novel peri-infarct projections connecting the peri-infarct motor cortex with neighboring areas. Both drugs also increase the magnitude of long-range motor projections into the brainstem and reduce peri-infarct fibrotic scarring. Finally, epothilone treatment induces an improvement in skilled forelimb motor function. Thus, pharmacological microtubule stabilization represents a promising target for therapeutic intervention with a wide time window to ameliorate structural and functional sequelae after stroke.
Against Bioethics
Authors: Samia A. Hurst
Journal: Annals of Internal Medicine (2007)

Medical Writings: Book Notes3 April 2007Against BioethicsSamia A. Hurst, MDSamia A. Hurst, MD From Geneva University Medical School, Geneva , Switzerland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-7-200704030-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Baron J. 248 pages. Cumberland, RI: The MIT Press; 2006. $29.00. ISBN 0262025965. Order at mitpress.mit.edu.Field of medicine: Medical ethics.Format: Softcover book.Audience: Medical ethicists, members of ethics committees and institutional review boards, physicians, and biomedical researchers.Purpose: To show how issues that engage bioethics can be illuminated by applied utilitarianism and decision analysis.Content: The author's main proposals are that influential principles of bioethics can be understood in strictly utilitarian terms, and that doing so makes one both more lucid and more apt to base decisions on robust grounds. He brings together utilitarian moral theory, elements of ... Author, Article, and Disclosure InformationAffiliations: From Geneva University Medical School, Geneva , Switzerland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 April 2007Volume 146, Issue 7Page: 543KeywordsBioethicsConflicts of interestDecision analysisDecision makingEcologyMedical ethicsPsychologyResearch ethicsSoftware tools ePublished: 3 April 2007 Issue Published: 3 April 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Retinal Vascular Diseases
Authors: Arnall Patz
Journal: New England Journal of Medicine (1978)

RETINAL vascular diseases are important to the internist, for they frequently represent manifestations of systemic disorders, and to the ophthalmologist because they are major causes of visual impairment. For example, diabetic retinopathy is the leading cause of new blindness in the United States in patients under 60 years of age, and retinopathy developing in sickle-cell anemia is an important cause of visual impairment in black Americans.Observations on the retinal vessels frequently provide the internist with important clues to the status of the vasculature in other organs that cannot be readily studied. The eye is unique, owing to the transparency . . .
Early Combined Immunosuppression Reduces Complications in Long-standing Crohn's Disease: A Post Hoc Analysis of REACT
Authors: Jurij Hanzel, Christopher Ma, Guangyong Zou, Siddharth Singh, Parambir S. Dulai, Brian G. Feagan, Geert R. D’Haens, William J. Sandborn, Vipul Jairath
Journal: Clinical Gastroenterology and Hepatology (2020)
Chondrolaryngoplasty in transgender women: Prospective analysis of voice and aesthetic satisfaction
Authors: Mateus Morais Aires, Daniela de Vasconcelos, Bruno Teixeira de Moraes
Journal: International Journal of Transgender Health (2020)

Introduction: Chondrolaryngoplasty or "tracheal shaving" is cosmetic surgery to reduce the laryngeal prominence in transgender women. Complications may include damage to the vocal folds and epiglottic destabilization or aesthetic dissatisfaction. Objective: To assess and compare acoustic and perceptual voice outcomes and aesthetic satisfaction of transgender women submitted to chondrolaryngoplasty. Methods: Prospective interventional cohort of transgender women submitted to chondrolaryngoplasty between March 2018 and October 2019. Voice analysis included simple-blind application of the GRBAS Hirano scale by speech therapist and measurement of the fundamental frequency, in the preoperative and 1-month postoperative periods. The visual analog scale was used to analyze the aesthetic satisfaction, before and 6-months after chondrolaryngoplasty. Results: Fifteen patients participated, with a mean age of 31.7 ± 8.3 years (range 22-51 years). The mean postoperative follow-up period was 15.3 ± 6.1 months (range 6-25 months). There was a significant improvement in the visual analog scale for aesthetic satisfaction, with a preoperative mean = 0.7 ± 1.0 and a postoperative mean = 9.3 ± 1.1 (95% CI for difference = 7.3 to 9.6; p < 0.001). All patients presented a positive variation. The preoperative mean fundamental frequency was 171.3 ± 41.2 Hz and the postoperative, 177.1 ± 39.5 Hz, with no statistical significance (95% CI for difference = -30.1 to 41.7; p = 0.74). There was no statistically significant difference in the pre- and postoperative comparison of each component of the GRBAS scale. One (7%) patient presented a hyperpigmented scar and 2 (13%) reported hoarseness during the first postoperative week. There were no major complications such as disinsertion of the epiglottis or vocal folds. Conclusion: Chondrolaryngoplasty led to significant aesthetic satisfaction in transgender women. The surgery caused no noticeable vocal change in pitch or perception.
急性リンパ芽球性白血病小児の予後因子消失における性差:東京小児がん研究グループ(TCCSG)による研究
Authors: Tsuchida M, Ikuta K, Hanada R, Manabe A, Saito T, Koike K, Toyoda Y, Kinoshita A, Kaneko T, Okimoto Y, Kajiwara M, Hayashi Y, Kumagai M, Maeda M, Isoyama K, Fujita H, Sotomatsu M, Sugita K, Yabe H, Takayama J, Kikuchi A, Ohara A, Hoshi Y, Hosoya R, Bessho F, Nakazawa S
Journal: Blood (2001)
Novichok nerve agent poisoning
Authors: David Steindl, Wolfgang Boehmerle, Roland Körner, Damaris Praeger, Marcel Haug, Jens Nee, Adrian Schreiber, Franziska Scheibe, Katharina Demin, Philipp Jacoby, Rudolf Tauber, Sven Hartwig, Matthias Endres, Kai-Uwe Eckardt
Journal: The Lancet (2020)
Abstract 13470: Mitochondrial Translocation of Dynamin-Reated Protein 1 Promotes Lethal Ischemia-Reperfusion Injury
Authors: Yi Dong, Vishnu V Undyala, Rita Kumar, Karin Przyklenk
Journal: Circulation (2012)

Background: Mitochondrial fission is the dynamic process by which mitochondria are cleaved and fragmented. Recent reports suggest that pharmacologic inhibition of fission attenuates lethal ischemia...
TCT-201 Predictors of acute kidney injury in patients undergoing transcatheter aortic valve replacement
Authors: Sang Yong Om, Yong-Hoon Yoon, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Osung Kwon, Ungjeong Do, Kyusup Lee, Do-yoon Kang, Cheol Hyun Lee, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)
Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load
Authors: Sabelo Hadebe, Jermaine Khumalo, Sandisiwe Mangali, Nontobeko Mthembu, Hlumani Ndlovu, Martyna Scibiorek, Amkele Ngomti, Frank Kirstein, Frank Brombacher
Journal: Journal of Allergy and Clinical Immunology (2020)

B cells play an important role in allergies through secretion of IgE. IL-4 receptor α (IL-4Rα) is key in allergic asthma and regulates type 2 cytokine production, IgE secretion, and airway hyperresponsiveness. IL-4 activation of B cells is essential for class switching and contributes to the induction of B effector 2 (Be2) cells. The role of Be2 cells and signaling via IL-4Rα in B cells is not clearly defined.We sought to find out whether IL-4Rα-responsive B cells or Be2 function was essential in experimental allergic asthma.Mice lacking IL-4Rα on B cells (mb1creIL-4Rα-/lox) or littermate controls (IL-4Rα-/lox) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitized and challenged with high-dose house dust mite (>10 μg) or with low-dose house dust mite (<3 μg). We also adoptively transferred naive IL-4Rα-/lox or IL-4Rα-/- B cells into μMT-/- mice a day before sensitization or a day before challenge. We analyzed lung inflammation, cellular infiltrate, and airway hyperresponsiveness.We found that IL-4Rα signaling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4Rα signaling on B cells was essential for germinal centers and in the effector phase of allergic responses. Be2 cells were essential in airway hyperresponsiveness, but not in other parameters.IL-4Rα signaling on B cells is deleterious in allergic asthma because it is required for optimal TH2 responses, Be2 function, germinal center formation, and T follicular helper cells, especially when the load of the antigen is limiting.
Freeze‐Thawing Chitosan/Ions Hydrogel Coated Gauzes Releasing Multiple Metal Ions on Demand for Improved Infected Wound Healing
Authors: Jian Xiao, Yajiao Zhou, Mengqi Ye, Ying An, Kangning Wang, Qiuji Wu, Liwan Song, Junwen Zhang, Huacheng He, Qianwen Zhang, Jiang Wu
Journal: Advanced Healthcare Materials (2020)

Abstract Imbalance of metal ions in the wound microenvironment is a key factor that leads to delayed wound healing. However, single metal administration to enhance wound repair is usually not enough due to the overlapping nature of the wound healing phases. Herein, a facile freeze‐thawing strategy is developed to incorporate chitosan/ions hydrogel into medical gauzes to realize on‐demand release of multiple ions to accelerate wound healing. In vitro study reveals that the gauzes can temporally release multiple metal ions on demand, and the released metal ions show effectiveness in killing bacteria and expediting cell migration. In vivo studies demonstrate that the metal ions loaded gauzes can efficiently enhance infected wound healing. Further histological analysis find that these metal ion‐loaded gauzes accelerate wound healing by promoting granulation formation, collagen deposition and maturation, re‐epithelization, angiogenesis, and inhibiting inflammation via regulating the expression of inflammatory factors (e.g., tumor necrosis factor‐ α ) and polarization of macrophages. Thus, this novel metal ions delivery system has great potential in infected tissue repair and antibacterial applications.
Coiled coil-based therapeutics and drug delivery systems
Authors: Johanna Utterström, Sajjad Naeimipour, Robert Selegård, Daniel Aili
Journal: Advanced Drug Delivery Reviews (2020)

Coiled coils are characterized by an arrangement of two or more α-helices into a superhelix and one of few protein motifs where the sequence-to-structure relationship to a large extent have been decoded and understood. The abundance of both natural and de novo designed coil coils provides a rich molecular toolbox for self-assembly of elaborate bespoke molecular architectures, nanostructures, and materials. Leveraging on the numerous possibilities to tune both affinities and preferences for polypeptide oligomerization, coiled coils offer unique possibilities to design modular and dynamic assemblies that can respond in a predictable manner to biomolecular interactions and subtle physicochemical cues. In this review, strategies to use coiled coils in design of novel therapeutics and advanced drug delivery systems are discussed. The applications of coiled coils for generating drug carriers and vaccines, and various aspects of using coiled coils for controlling and triggering drug release, and for improving drug targeting and drug uptake are described. The plethora of innovative coiled coil-based molecular systems provide new knowledge and techniques for improving efficacy of existing drugs and can facilitate development of novel therapeutic strategies.
Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation
Authors: Louisa Goumidi, Florian Thibord, Kerri L. Wiggins, Ruifang Li-Gao, Mickael R. Brown, Astrid van Hylckama Vlieg, Joan-Carles Souto, José-Manuel Soria, Manal Ibrahim-Kosta, Noémie Saut, Delphine Daian, Robert Olaso, Philippe Amouyel, Stéphanie Debette, Anne Boland, Pascal Bailly, Alanna C. Morrison, Denis O. Mook-Kanamori, Jean-François Deleuze, Andrew Johnson, Paul S. de Vries, Maria Sabater-Lleal, Jacques Chiaroni, Nicholas L. Smith, Frits R. Rosendaal, Daniel I. Chasman, David-Alexandre Trégouët, Pierre-Emmanuel Morange
Journal: Blood (2020)