tbuckley/cabot-search huggingface dataset:
Association of Initiation of Dialysis With Hospital Length of Stay and Intensity of Care in Older Adults With Kidney Failure
Authors: Helen Tam-Tham, Pietro Ravani, Jianguo Zhang, Robert G. Weaver, Robert R. Quinn, Matthew T. James, Ping Liu, Braden J. Manns, Marcello Tonelli, Paul E. Ronksley, Tyrone G. Harrison, Chandra Thomas, Sara Davison, Brenda R. Hemmelgarn
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Comparative outcome data examining the association of dialysis initiation with hospital length of stay and intensity of care in older adults with kidney failure are scarce, and prior studies are limited to patients treated by nephrology teams. <h3>Objective</h3> To compare in-hospital days and intensity of care among older adults with kidney failure who were treated vs not treated with maintenance dialysis. <h3>Design, Setting, and Participants</h3> This population-based, retrospective cohort study included adults in Alberta, Canada, 65 years or older with kidney failure, defined by at least 2 consecutive outpatient estimated glomerular filtration rate values of less than 10 mL/min/1.73 m<sup>2</sup>spanning a period of at least 90 days from May 15, 2002, to March 31, 2014. Data were analyzed from August 1, 2017, to August 29, 2019. <h3>Exposures</h3> Time-varying exposure to maintenance dialysis for treatment of kidney failure. <h3>Main Outcomes and Measures</h3> The primary outcome was rate of in-hospital days. Secondary outcomes included rates of hospital admissions, intensive care unit admissions, cardiopulmonary resuscitations, inpatient palliative care, and emergency department visits; risk of in-hospital death; and time to admission to long-term care. <h3>Results</h3> A total of 968 patients (median age, 78.5 [interquartile range, 72.4-84.7] years; 489 men [50.5%]; median follow-up, 2.0 [interquartile range, 0.8-3.9] years) were included in the analysis. Patients who underwent dialysis spent more adjusted in-hospital days per person-year (36.25 [95% CI, 30.72-41.77] vs 14.65 [95% CI, 12.28-17.02]; incidence rate ratio [IRR], 2.47 [95% CI, 1.99-3.08]). However, the dialysis group did not have a higher rate of hospital admissions (1.18 [95% CI 1.07-1.29] vs 1.32 [95% CI 1.17-1.48] per year; IRR, 0.89 [95% CI, 0.77-1.03]). Patients in the dialysis group had a higher rate of intensive care unit admissions per 1000 hospitalizations (98.37 [95% CI, 81.09-115.65] vs 54.51 [95% CI, 37.76-71.26]; IRR, 1.80 [95% CI, 1.28-2.54]) and lower rates of inpatient palliative care per 1000 in-hospital days (3.92 [95% CI, 3.13-4.72] vs 8.60 [95% CI, 6.3-11.0]; IRR, 0.45 [95% CI, 0.32-0.64]). <h3>Conclusions and Relevance</h3> In this cohort study, compared with nondialysis care, patients who received maintenance dialysis spent more time in the hospital and were more likely to be admitted to intensive care units. This finding suggests trade-offs between longer survival and higher intensity of use of health care services as a function of dialysis initiation. Maintenance dialysis may be a proxy for the type of philosophy of care driving increased in-hospital time and intensive care and less use of palliative care.
Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial
Authors: Arka De, Sunita Kumari, Akash Singh, Amritjyot Kaur, Rattiram Sharma, Ashish Bhalla, Navneet Sharma, Naveen Kalra, Virendra Singh
Journal: Clinical Gastroenterology and Hepatology (2020)
131P Association of Hla Class I and Class Ii Alleles with Breast Cancer in Eastern Indian Population
Authors: S. Dasgupta, S. Mukhopadhyay, J. Basak, A. Chakraborty, D. Bhattacharya Majumder, S. Gangopadhyay, A. Mukhopadhyay
Journal: Annals of Oncology (2012)
Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma
Authors: Tatjana Bilich, Annika Nelde, Jens Bauer, Simon Walz, Malte Roerden, Helmut R. Salih, Katja Weisel, Britta Besemer, Ana Marcu, Maren Lübke, Juliane Schuhmacher, Marian C. Neidert, Hans-Georg Rammensee, Stefan Stevanović, Juliane S. Walz
Journal: Blood Cancer Journal (2020)

Abstract The B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18-restricted ligand P(BCMA) B*18 . Additionally, P(BCMA) B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA) B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8 + T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA) B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA) B*18 -specific CD8 + T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA) B*18 using patient-derived P(BCMA) B*18 -specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.
Layer-by-Layer Biomaterials for Drug Delivery
Authors: Dahlia Alkekhia, Paula T. Hammond, Anita Shukla
Journal: Annual Review of Biomedical Engineering (2020)

Controlled drug delivery formulations have revolutionized treatments for a range of health conditions. Over decades of innovation, layer-by-layer (LbL) self-assembly has emerged as one of the most versatile fabrication methods used to develop multifunctional controlled drug release coatings. The numerous advantages of LbL include its ability to incorporate and preserve biological activity of therapeutic agents; coat multiple substrates of all scales (e.g., nanoparticles to implants); and exhibit tuned, targeted, and/or responsive drug release behavior. The functional behavior of LbL films can be related to their physicochemical properties. In this review, we highlight recent advances in the development of LbL-engineered biomaterials for drug delivery, demonstrating their potential in the fields of cancer therapy, microbial infection prevention and treatment, and directing cellular responses. We discuss the various advantages of LbL biomaterial design for a given application as demonstrated through in vitro and in vivo studies.
Impact of a deep learning assistant on the histopathologic classification of liver cancer
Authors: Amirhossein Kiani, Bora Uyumazturk, Pranav Rajpurkar, Alex Wang, Rebecca Gao, Erik Jones, Yifan Yu, Curtis P. Langlotz, Robyn L. Ball, Thomas J. Montine, Brock A. Martin, Gerald J. Berry, Michael G. Ozawa, Florette K. Hazard, Ryanne A. Brown, Simon B. Chen, Mona Wood, Libby S. Allard, Lourdes Ylagan, Andrew Y. Ng, Jeanne Shen
Journal: npj Digital Medicine (2020)

Artificial intelligence (AI) algorithms continue to rival human performance on a variety of clinical tasks, while their actual impact on human diagnosticians, when incorporated into clinical workflows, remains relatively unexplored. In this study, we developed a deep learning-based assistant to help pathologists differentiate between two subtypes of primary liver cancer, hepatocellular carcinoma and cholangiocarcinoma, on hematoxylin and eosin-stained whole-slide images (WSI), and evaluated its effect on the diagnostic performance of 11 pathologists with varying levels of expertise. Our model achieved accuracies of 0.885 on a validation set of 26 WSI, and 0.842 on an independent test set of 80 WSI. Although use of the assistant did not change the mean accuracy of the 11 pathologists (
A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans
Authors: Sarah C. Edwards, Caroline E. Sutton, Kristin Ladell, Emma J. Grant, James E. McLaren, Fiona Roche, Pradyot Dash, Nopporn Apiwattanakul, Walid Awad, Kelly L. Miners, Stephen J. Lalor, Julie C. Ribot, Song Baik, Barry Moran, Aoife McGinley, Valerie Pivorunas, Lori Dowding, Michael Macoritto, Jesus Paez-Cortez, Anthony Slavin, Graham Anderson, Bruno Silva-Santos, Karsten Hokamp, David A. Price, Paul G. Thomas, Rachel M. McLoughlin, Kingston H.G. Mills
Journal: The Journal of Experimental Medicine (2020)

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.
Ocular Point-of-Care Ultrasonography to Diagnose Posterior Chamber Abnormalities
Authors: Steven L. Propst, Jonathan M. Kirschner, Christian C. Strachan, Steven K. Roumpf, Laura M. Menard, Elisa J. Sarmiento, Benton R. Hunter
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Diagnosing posterior chamber ocular abnormalities typically requires specialist assessment. Point-of-care ultrasonography (POCUS) performed by nonspecialists, if accurate, could negate the need for urgent ophthalmologist evaluation. <h3>Objective</h3> This meta-analysis sought to define the diagnostic test characteristics of emergency practitioner–performed ocular POCUS to diagnose multiple posterior chamber abnormalities in adults. <h3>Data Sources</h3> PubMed (OVID), MEDLINE, EMBASE, Cochrane, CINAHL, and SCOPUS were searched from inception through June 2019 without restrictions. Conference abstracts and trial registries were also searched. Bibliographies of included studies and relevant reviews were manually searched, and experts in the field were queried. <h3>Study Selection</h3> Included studies compared ocular POCUS performed by emergency practitioners with a reference standard of ophthalmologist evaluation. Pediatric studies were excluded. All 116 studies identified during abstract screening as potentially relevant underwent full-text review by multiple authors, and 9 studies were included. <h3>Data Extraction and Synthesis</h3> In accordance with PRISMA guidelines, multiple authors extracted data from included studies. Results were meta-analyzed for each diagnosis using a bivariate random-effects model. Data analysis was performed in July 2019. <h3>Main Outcomes and Measures</h3> The outcomes of interest were diagnostic test characteristics of ocular POCUS for the following diagnoses: retinal detachment, vitreous hemorrhage, vitreous detachment, intraocular foreign body, globe rupture, and lens dislocation. <h3>Results</h3> Nine studies (1189 eyes) were included. All studies evaluated retinal detachment, but up to 5 studies assessed each of the other diagnoses of interest. For retinal detachment, sensitivity was 0.94 (95% CI, 0.88-0.97) and specificity was 0.94 (95% CI, 0.85-0.98). Sensitivity and specificity were 0.90 (95% CI, 0.65-0.98) and 0.92 (95% CI, 0.75-0.98), respectively, for vitreous hemorrhage and were 0.67 (95% CI, 0.51-0.81) and 0.89 (95% CI, 0.53-0.98), respectively, for vitreous detachment. Sensitivity and specificity were high for lens dislocation (0.97 [95% CI, 0.83-0.99] and 0.99 [95% CI, 0.97-1.00]), intraocular foreign body (1.00 [95% CI, 0.81-1.00] and 0.99 [95% CI, 0.99-1.00]), and globe rupture (1.00 [95% CI, 0.63-1.00] and 0.99 [95% CI, 0.99-1.00]). Results were generally unchanged in sensitivity analyses of studies with low risk of bias. <h3>Conclusions and Relevance</h3> This study suggests that emergency practitioner–performed ocular POCUS is an accurate test to assess for retinal detachment in adults. Its utility in diagnosing other posterior chamber abnormalities is promising but needs further study.
Art in Endoscopy: “Disrupted Coral at the Great ‘Barrett’ Reef”
Authors: Jeroen de Groof, Jacques Bergman
Journal: Endoscopy (2020)

A neoplastic area in a Barrett’s esophagus is seen in the upper right quadrant of this image, in obvious contrast to the normal surrounding mucosa. The neoplastic lesion is clearly demarcated here by blue light imaging in magnification mode, which allows better visualization of mucosal and vascular patterns. The optical chromoscopy technique is provided by the Fujifilm ELUXEO 7000 endoscopy system.
Phase III study of pembrolizumab (pembro) plus olaparib versus enzalutamide (enza) or abiraterone acetate (abi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who progressed on chemotherapy: KEYLYNK-010.
Authors: Evan Y. Yu, Se Hoon Park, Yi-Hsiu Huang, Mostefa Bennamoun, Lu Xu, Jeri Kim, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2020)

TPS256 Background: Pembro, a PD-1 inhibitor, and olaparib, a PARP inhibitor, have some single-agent antitumor activity in mCRPC. The phase 1b/2 KEYNOTE-365 study (NCT02861573) showed promising activity with pembro and olaparib in pts with mCRPC unselected for homologous recombination deficiency, warranting further investigation. Methods: KEYLYNK-010 (NCT03834519) is a phase 3 trial to evaluate efficacy and safety of pembro + olaparib in molecularly unselected enza- or abi-pretreated pts with mCRPC who progressed with taxane chemotherapy. An estimated 780 pts will be randomly assigned 2:1 to receive pembro 200 mg IV every 3 wk plus olaparib 300 mg orally twice daily or abi 1000 mg orally once daily + prednisone/prednisolone 5 mg orally twice daily (enza-pretreated pts) or enza 160 mg/day orally (abi-pretreated pts). Stratification will be by prior treatment (abi/enza) and measurable disease (yes/no). Adults (≥18 y) with histologically confirmed mCRPC who progressed on androgen deprivation therapy ≤6 mo of screening, and an ECOG PS of 0 or 1 are eligible. Pts previously received either abi or enza (but not both) as well as 1 docetaxel-based regimen. Pts are required to provide tumor tissue for biomarker analysis. Responses will be assessed by CT/MRI and radionuclide bone imaging per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by blinded independent central review (BICR) every 9 wk during the first year and every 12 wk thereafter. Treatment will continue with up to 2 y of pembro (35 cycles) and olaparib or abi/enza until disease progression, unacceptable toxicity, or consent withdrawal. Primary end points are OS and rPFS. Secondary end points are time to initiation of subsequent anticancer therapy; ORR, and DOR per PCWG3-modified RECIST v1.1 by BICR; time to PSA progression; time to first symptomatic skeletal event; time to radiographic soft tissue progression; time to pain progression; and safety. Exploratory end points are identification of molecular (genomic, metabolic, or proteomic) biomarkers indicative of response. Accrual began May 2, 2019. Clinical trial information: NCT03834519.
Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren’s syndrome
Authors: Jin-lei Sun, Hao-ze Zhang, Su-ying Liu, Chao-feng Lian, Zhi-lei Chen, Ti-hong Shao, Shuo Zhang, Li-ling Zhao, Cheng-mei He, Mu Wang, Wen Zhang, Hua Chen, Feng-chun Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. Methods We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. Results We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. Conclusion Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.
Alcohol-Induced Deaths Among American Indian and Alaska Native Individuals—“Drinking Was What I and Others Just Did”
Authors: Spero M. Manson
Journal: JAMA Network Open (2020)

Susan Spillane, PhD; Meredith S. Shiels, PhD; Ana F. Best, PhD; Emily A. Haozous, PhD; Diana R. Withrow, PhD; Yingxi Chen, PhD; Amy Berrington de González, DPhil; Neal D. Freedman, PhD
Efficacy of immune checkpoint inhibitors (ICIs) in rare histological variants of bladder cancer.
Authors: Errol James Philip, Francis Wright, Daniel Myung Kim, Daniel Kwon, Hansen Ho, Son Ho, Edna Cheung, Emily Chan, Sima P. Porten, Anthony C. Wong, Hala Borno, Arpita Desai, Jonathan Chou, David Yoonsuk Oh, Rahul Raj Aggarwal, Lawrence Fong, Eric Jay Small, Terence W. Friedlander, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2020)

502 Background: ICIs are effective agents in metastatic urothelial carcinoma in both platinum-refractory and frontline settings. Responses in patients (pts) with non-urothelial histological variants are not well defined. Methods: We undertook a retrospective analysis of pts with metastatic bladder cancer treated with ICI monotherapy. Pts were identified as having a variant histology if any non-urothelial component was present. Fisher’s exact test was used to assess differences in ORR by histology. Results: Between 12/2014 and 10/2019, 102 pts received ICI monotherapy, of whom 93 were evaluable for response and 33 had variant histology. Median age was 70 yrs, 66% were male, 50% received prior platinum-based chemotherapy. Most received pembrolizumab (66%) or atezolizumab (33%). ORR in the overall cohort was 26% (15% PR, 11% CR), with 12% having SD. Histology breakdown and responses are shown in Table. Although twice as many responses were seen in urothelial pts as in pts with variant histologies (ORR 31% vs 15%), this difference was non-significant (p = 0.14). Conclusions: In this large single-institution cohort, ORR in a heterogeneous population of bladder cancer pts was consistent with data previously reported in clinical trials. Pts with variant histologies had numerically lower responses relative to pure urothelial histology, but this difference was not statistically significant. Clinical benefit to ICIs was seen across multiple variant histologies suggesting potential efficacy in this patient population that should be confirmed prospectively.[Table: see text]
Long Noncoding RNA MRPL23-AS1 Promotes Adenoid Cystic Carcinoma Lung Metastasis
Authors: Chu-Wen Chen, Min Fu, Zhi-Hao Du, Fei Zhao, Wen-Wen Yang, Li-Hua Xu, Sheng-Lin Li, Xi-Yuan Ge
Journal: Cancer Research (2020)

Abstract Lung metastasis is a major factor affecting long-term survival in patients with adenoid cystic carcinoma. Here, we showed that the long noncoding RNA (lncRNA) MRPL23 antisense RNA 1 (MRPL23-AS1) was highly expressed and correlated with lung metastasis and overall survival in patients with salivary adenoid cystic carcinoma (SACC). MRPL23-AS1 positively regulated epithelial–mesenchymal transition by forming an RNA–protein complex with enhancer of zeste homolog 2 (EZH2). MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of patients with SACC, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an “exosomecrine” manner. MRPL23-AS1–enriched exosomes increased microvascular permeability and facilitated the metastasis of SACC in vivo. Collectively, these findings highlight a molecular mechanism of lung metastasis in SACC. MRPL23-AS1 may represent a biomarker and target for clinical intervention to control this intractable disease. Significance: This study identifies a novel metastasis-promoting lncRNA MRPL23-AS1, which mediates the transcriptional silencing of E-cadherin through forming an RNA–protein complex with EZH2.
A study of gene mutations and how they relate to the different types of ichthyosis
Authors: J.K. Simpson, M. Martinez‐Queipo, A. Onoufriadis, S. Tso, E. Glass, L. Liu, T. Higashino, W. Scott, C. Tierney, M.A. Simpson, R. Desomchoke, L. Youssefian, A.H. SaeIdian, H. Vahidnezhad, A. Bisquera, J. Ravenscroft, C. Moss, E.A. O'Toole, N. Burrows, S. Leech, E.A. Jones, D. Lim, A. Ilchyshyn, N. Goldstraw, M.J. Cork, S. Darne, J. Uitto, A.E. Martinez, J.E. Mellerio, J.A. McGrath
Journal: British Journal of Dermatology (2020)

Ichthyosis is a disorder in which the skin is very thick and scaly. It is usually caused by a genetic mistake (mutation). “Autosomal recessive” ichthyosis occurs when parents who are healthy carriers both pass on a mutant gene to their child, so the child inherits a double dose of the mutation and cannot make normal skin. Scientists have already discovered mutations in 13 genes that cause ichthyosis. This study looks at whether the type of mutation (genotype) tells us anything about the type of ichthyosis (phenotype). The doctors examined 146 ichthyosis patients, average age 17 years, from 124 families, recruited from 13 English hospitals. They extracted DNA from blood or saliva. They found mutations in 83% of patients; the other 17% presumably have mutations not detectable by current techniques or in different genes. There were mutations in 10 different ichthyosis genes, mostly a gene called TGM1. To some extent different genotypes corresponded to different phenotypes. TGM1 ichthyosis usually has large, brown scales while ALOX12B mutations cause fine white scaling. ABCA12 mutations cause more severe ichthyosis, including the very serious harlequin type with distorted fingers; by contrast patients with milder ichthyosis usually had TGM1 or ALOX12B mutations. Nearly half of the babies with ALOX12B mutations were born with the top of their ear folded over. Some TGM1 patients had abnormally red skin while others with exactly the same mutation did not. In conclusion, this large study provides a lot of new information about ichthyosis, but genotype only partly predicts phenotype. This is a summary of the study: Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis