tbuckley/cabot-search huggingface dataset:
Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma
Authors: Benjamin M. Ellingson, John Sampson, Achal Singh Achrol, Manish K. Aghi, Krystof Bankiewicz, Chencai Wang, Martin Bexon, Steven Brem, Andrew Brenner, Sajeel Chowdhary, John R. Floyd, Seunggu Han, Santosh Kesari, Dina Randazzo, Michael A. Vogelbaum, Frank Vrionis, Miroslaw Zabek, Nicholas Butowski, Melissa Coello, Nina Merchant, Fahar Merchant
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). Patients and Methods: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. Results: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P &amp;lt; 0.0001; HR = 0.3) and mRANO (P &amp;lt; 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P &amp;lt; 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007). Conclusions: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.
Endogenous Leptin Signaling in the Caudal Nucleus Tractus Solitarius and Area Postrema Is Required for Energy Balance Regulation
Authors: Matthew R. Hayes, Karolina P. Skibicka, Theresa M. Leichner, Douglas J. Guarnieri, Ralph J. DiLeone, Kendra K. Bence, Harvey J. Grill
Journal: Cell Metabolism (2016)
Association Between Donor-Recipient Biological Relationship and Allograft Outcomes After Living Donor Kidney Transplant
Authors: S. Ali Husain, Kristen L. King, Navin Sanichar, R. John Crew, Jesse D. Schold, Sumit Mohan
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US. <h3>Objective</h3> To examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020. <h3>Exposures</h3> Donor-recipient biological relationship. <h3>Main Outcomes and Measures</h3> The primary outcome was death-censored allograft failure. Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non–African American donors. <h3>Results</h3> Among the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall (median [IQR], 3 [2-3] vs 5 [4-5]). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10;<i>P</i> = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors. <h3>Conclusions and Relevance</h3> In this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.
The genomic basis of geographic differentiation and fiber improvement in cultivated cotton
Authors: Shoupu He, Gaofei Sun, Xiaoli Geng, Wenfang Gong, Panhong Dai, Yinhua Jia, Weijun Shi, Zhaoe Pan, Junduo Wang, Liyuan Wang, Songhua Xiao, Baojun Chen, Shufang Cui, Chunyuan You, Zongming Xie, Feng Wang, Jie Sun, Guoyong Fu, Zhen Peng, Daowu Hu, Liru Wang, Baoyin Pang, Xiongming Du
Journal: Nature Genetics (2021)
COVID-19 and Cardiovascular Disease
Authors: Mina K. Chung, David A. Zidar, Michael R. Bristow, Scott J. Cameron, Timothy Chan, Clifford V. Harding, Deborah H. Kwon, Tamanna Singh, John C. Tilton, Emily J. Tsai, Nathan R. Tucker, John Barnard, Joseph Loscalzo
Journal: Circulation Research (2021)

A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.
Low numbers of disabled doctors mean potential loss of insightful care for everyone
Authors: Hannah Kuper, Tom Shakespeare, Carmen Soto, Sara Booth
Journal: BMJ (2021)

The BMA report Disability in the medical profession: survey findings 2020 highlights the fact that disabled doctors are not getting the workplace adjustments they need.1 It also uncovers broader exclusion and discrimination in the medical profession in the UK.

The report states that “disabled doctors and medical students are a valuable part of our profession, bringing unique perspectives and insight …
A Case of Gene Fragmentation in Plant Mitochondria Fixed by the Selection of a Compensatory Restorer of Fertility-Like PPR Gene
Authors: Tan-Trung Nguyen, Noelya Planchard, Jennifer Dahan, Nadège Arnal, Sandrine Balzergue, Abdelilah Benamar, Pierre Bertin, Véronique Brunaud, Céline Dargel-Graffin, David Macherel, Marie-Laure Martin-Magniette, Martine Quadrado, Olivier Namy, Hakim Mireau
Journal: Molecular Biology and Evolution (2021)

The high mutational load of mitochondrial genomes combined with their uniparental inheritance and high polyploidy favors the maintenance of deleterious mutations within populations. How cells compose and adapt to the accumulation of disadvantageous mitochondrial alleles remains unclear. Most harmful changes are likely corrected by purifying selection, however, the intimate collaboration between mitochondria- and nuclear-encoded gene products offers theoretical potential for compensatory adaptive changes. In plants, cytoplasmic male sterilities are known examples of nucleo-mitochondrial coadaptation situations in which nuclear-encoded restorer of fertility (Rf) genes evolve to counteract the effect of mitochondria-encoded cytoplasmic male sterility (CMS) genes and restore fertility. Most cloned Rfs belong to a small monophyletic group, comprising 26 pentatricopeptide repeat genes in Arabidopsis, called Rf-like (RFL). In this analysis, we explored the functional diversity of RFL genes in Arabidopsis and found that the RFL8 gene is not related to CMS suppression but essential for plant embryo development. In vitro-rescued rfl8 plantlets are deficient in the production of the mitochondrial heme-lyase complex. A complete ensemble of molecular and genetic analyses allowed us to demonstrate that the RFL8 gene has been selected to permit the translation of the mitochondrial ccmFN2 gene encoding a heme-lyase complex subunit which derives from the split of the ccmFN gene, specifically in Brassicaceae plants. This study represents thus a clear case of nuclear compensation to a lineage-specific mitochondrial genomic rearrangement in plants and demonstrates that RFL genes can be selected in response to other mitochondrial deviancies than CMS suppression.
Sleep disturbance in adult dermatologic patients: A cross-sectional study on prevalence, burden, and associated factors
Authors: Max Spindler, Katarzyna Przybyłowicz, Marlena Hawro, Karsten Weller, Ulrich Reidel, Martin Metz, Marcus Maurer, Tomasz Hawro
Journal: Journal of the American Academy of Dermatology (2021)
Charcot–Leyden Crystals in Rapidly Progressing Plastic Bronchitis
Authors: Kota Ikari, Junichiro Tezuka, Tsubasa Matsumoto, Moeri Tsuji, Masaru Kawamura, Takuya Oda, Shigeharu Ueki
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Charcot–Leyden Crystals in Rapidly Progressing Plastic Bronchitis." American Journal of Respiratory and Critical Care Medicine, 204(4), pp. e54–e55
Budesonide and a retinoid X receptor-selective ligand bexarotene prevent the development of ultraviolet B-induced skin cancer in SKH-1 hairless mice
Authors: Xiuwei Tang, Arianna L. Kim, Huaijie Zhu, Levy Kopelovich, David R. Bickers, Mohammad Athar
Journal: Cancer Research (2005)

4304  Solar ultraviolet (UV) B is a ubiquitous environmental carcinogen and a known risk factor for human nonmelanoma skin cancers (NMSC), including Squamous Cell Carcinomas (SCCs). The development of SCC directly correlates with cumulative exposure to UV radiation. Mutations in the p53 gene, as well as elevated cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) activity, are associated with the pathogenesis of SCC, and they may play a pivotal role in the development of SCCs in susceptible mice and human cohorts, as well as in the general population. Budesonide, one of the newest topical corticosteroids designed to maximize anti-inflammatory effects, is known to have chemopreventive as well as therapeutic efficacy in animal models of various cancers, particularly lung cancer. Bexarotene is a receptor-selective vitamin A derivative, and the classic retinoids are known to be effective for the treatment of pre-cancerous lesions, such as leukoplakia, actinic keratosis, and cervical dysplasia. This study assessed the chemopreventive effects of topically applied budesonide and bexarotene in UVB-induced SCC development in SKH-1 hairless mice. The SKH-1 mice, 25 mice in each group, were irradiated with 180 mJ/cm2 UVB twice a week for a total of 35 weeks. The mice in Group 1 received only UVB irradiation, whereas those in Group 2 received a vehicle, followed by UVB. The dorsal skin of the mice in groups 3 to 5 received budesonide (16 mg/kg body weight) or bexarotene (34 mg/kg body weight) or a combination of the two, 30 minutes prior to UVB irradiation. At week 35, an average of 11 or 12 tumors per mouse were detected in the UVB-irradiated or the UVB/vehicle-treated groups, respectively. Budesonide or bexarotene, when applied alone, showed on average a two-fold decrease in the number and size of the tumors. A combination treatment of budesonide and bexarotene showed a dramatic reduction in tumor multiplicity and growth. Mice treated with both budesonide and bexarotene showed overall decreases of 90% in both tumor number and size. Moreover, the budesonide/bexarotene treatment reduced the tumor incidence to 38%. Only 5 out of 13 mice developed visible tumors, with the remaining 8 mice tumor-free at week 35 following treatment. The budesonide/bexarotene treatment also reduced UVB-induced overexpression of cell cycle proteins, such as cyclins B1 and D1, which derive proliferation, and also inhibited the expression of COX-2 and ODC. In summary, our data indicate that budesonide and bexarotene are potent inhibitors of UVB-induced skin cancers in SKH-1 mice and that the combinational treatment could be a useful chemopreventive strategy for skin cancer.
Myocardial Fibrosis and Inflammation by CMR Predict Cardiovascular Outcome in People Living With HIV
Authors: Philipp de Leuw, Christophe T. Arendt, Annette E. Haberl, Daniel Froadinadl, Gerrit Kann, Timo Wolf, Christoph Stephan, Gundolf Schuettfort, Moises Vasquez, Luca Arcari, Hui Zhou, Hafisyatul Zainal, Monika Gawor, Eleftherios Vidalakis, Michael Kolentinis, Moritz H. Albrecht, Felicitas Escher, Thomas J. Vogl, Andreas M. Zeiher, Eike Nagel, Valentina O. Puntmann
Journal: JACC. Cardiovascular imaging (2021)

The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART). PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood. This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization). A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events. Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).
Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose
Authors: Hubert Blain, Edouard Tuaillon, Lucie Gamon, Amandine Pisoni, Stephanie Miot, Marie-Christine Picot, Jean Bousquet
Journal: JAMA (2021)

Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2
Erratum: A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities
Authors: Y Kochi, R Yamada, A Suzuki, J B Harley, S Shirasawa, T Sawada, S-C Bae, S Tokuhiro, X Chang, A Sekine, A Takahashi, T Tsunoda, Y Ohnishi, K M Kaufman, C P Kang, C Kang, S Otsubo, W Yumura, A Mimori, T Koike, Y Nakamura, T Sasazuki, K Yamamoto
Journal: Nature Genetics (2005)
Pernio after COVID‐19 vaccination
Authors: S. Lopez, P. Vakharia, T. Vandergriff, E.E. Freeman, R. Vasquez
Journal: British Journal of Dermatology (2021)

However, this limitation was reduced by using validated algorithms. 5,6 Secondly, reverse causation and possible confounders may limit the establishment of firm causal inferences even in well-designed observational studies.The strengths of our study are the large sample, the use of validated algorithms, and the proper matching of cases and controls.In conclusion, our study utilized a population-wide database and indicates that patients with SSDs do not appear to have a higher risk of developing psoriasis and PsA.Further well-designed studies are warranted.
Abstract PO-062: Why drug and radiation combination synergism or antagonism can be quantitatively determined with the mass-action law based pharmacodynamics equation, algorithm and computer simulation
Authors: Ting-Chao Chou
Journal: Clinical Cancer Research (2021)

Abstract Biological system-analysis by the mass-action law with biophysical, biochemical and mathematical induction-and-deduction leads to the derivation of &amp;gt;300 reaction rate equations. These derived equations led to general biodynamics/pharmacodynamics and bioinformatics (MAL-BD/PD/BI) general paradigms for “Dose” and “Effect”. 1. Median-Effect Eq. (MEE) for single drug or entity, regardless, in vitro, in animals or in human, where Dm and m values signify the median-effect dose “potency” and “shape” (dynamic order), respectively. 2. Combination Index Eq. (CIE), where CI&amp;lt;1, =1, and &amp;gt;1 indicates synergism, additive effect and antagonism, respectively, in combinations. Since all terms in MEE and CIE are relativity ratios, they are dimensionless quantities. Therefore, MEE and CIE are fundamental MAL-BD/PD/BI/CI principle independent to entity’s physical nature (chemicals, biologicals, natural products, radiation, liquid, or gas); independent to unit (ug, nM, mg/ml. mg/kg, IU, rad or multiples of infection); and independent to mode or mechanism of actions (competitive, noncompetitive, uncompetitive, sequential, ordered, ping-pong or random). Comprehensive details are available in Chou TC, Pharmacol. Rev. 58: 621-681, 2006 (specifically on p.655 and p.660), It also discussed in Chou, Integrative Biol. 3: 548-559, 2011, and many more recent papers on chemotherapy and radiation therapy combinations, as indicated in Google scholars. The above 2006 Chou article, as of January 12, 2021, has 3,835 citations in 1,054 biomedical journals internationally, encompassing nearly all disciplines in biomedical sciences. Citation Format: Ting-Chao Chou. Why drug and radiation combination synergism or antagonism can be quantitatively determined with the mass-action law based pharmacodynamics equation, algorithm and computer simulation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-062.
Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m<sup>6</sup>A signaling
Authors: Kaiju Sun, Yangyang Du, Yuzhu Hou, Mingyue Zhao, Jiajia Li, Yazhe Du, Lingxiao Zhang, Changbao Chen, Hongmei Yang, Fei Yan, Rui Su
Journal: Theranostics (2021)

The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N
ICBP90 Regulates <i>MIF</i> Expression, Glucocorticoid Sensitivity, and Apoptosis at the <i>MIF</i> Immune Susceptibility Locus
Authors: Jie Yao, Lin Leng, Weiling Fu, Jia Li, Christian Bronner, Richard Bucala
Journal: Arthritis & Rheumatology (2021)

Macrophage migration inhibitory factor (MIF) is an inflammatory and neurorendocrine mediator that counterregulates glucocorticoid immunosuppression. MIF polymorphisms, which comprise a variant promoter microsatellite (-794 CATT5-8 ), are linked genetically to autoimmune disease severity and to glucocorticoid resistance. While invasive stimuli increase MIF expression, MIF also is up-regulated by glucocorticoids, which serve as a physiologic regulator of inflammatory responses. This study was undertaken to define interactions between the MIF promoter, the glucocorticoid receptor (GR), and the transcription factor inverted CCAAT box binding protein 90 kd (ICBP90) (also referred to as UHRF1), which binds to the promoter in a -794 CATT5-8 length-dependent manner, to regulate MIF transcription.Interactions of ICBP90, GR, and activator protein 1 (AP-1) with MIF -794 CATT5-8 promoter constructs were assessed by coimmunoprecipitation, Western blotting, and genetic knockdown. Nuclear colocalization studies were performed using anti-transcription factor antibodies and confocal microscopy of glucocorticoid-treated cells. MIF transcription was studied in CEM-C7 T cells, and the impact of the MIF -794 CATT5-8 microsatellite variation confirmed in peripheral blood T cells and in rheumatoid synovial fibroblasts of defined MIF genotype. Functional interactions were quantified by apoptosis and apoptotic signaling in high- and low-genotypic MIF-expressing human cells.We defined functional interactions between the transcription factors ICBP90, the GR, and AP-1 that up-regulated MIF transcription in a -794 CATT5-8 length-dependent manner. Experimental reduction of ICBP90, GR, or AP-1 decreased MIF expression and increased glucocorticoid sensitivity, leading to enhanced apoptosis in T lymphocytes and in rheumatoid synovial fibroblasts.These findings suggest a mechanism for genetic variation of glucocorticoid-regulated MIF transcription, with implications for autoimmune disease severity and glucocorticoid responsiveness.