tbuckley/cabot-search huggingface dataset:
Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China
Authors: Jin-jin Zhang, Xiang Dong, Yi-yuan Cao, Ya-dong Yuan, Yi-bin Yang, You-qin Yan, Cezmi A. Akdis, Ya-dong Gao
Journal: Allergy (2020)

Abstract Background Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS‐CoV‐2. Methods Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID‐19 patients, with confirmed result of SARS‐CoV‐2 viral infection, were extracted and analyzed. Results An approximately 1:1 ratio of male (50.7%) and female COVID‐19 patients was found, with an overall median age of 57.0 years. All patients were community‐acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self‐reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground‐glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe ( r = .486, P &lt; .001) and nonsevere ( r = .469, P &lt; .001) patients after hospital admission. Significantly higher levels of D‐dimer, C‐reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P &lt; .001). Conclusion Detailed clinical investigation of 140 hospitalized COVID‐19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS‐CoV‐2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.
Characteristics and Health Status of Informal Unpaid Caregivers — 44 States, District of Columbia, and Puerto Rico, 2015–2017
Authors: Valerie J. Edwards, Erin D. Bouldin, Christopher A. Taylor, Benjamin S. Olivari, Lisa C. McGuire
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2015, an estimated 17.7 million U.S. persons were informal caregivers who provided substantial services through in-home, unpaid assistance to their family members and friends (1). Caregiving can have many benefits, such as enhancing the bond between caregiver and recipient, but it can also place an emotional and physical strain on caregivers, leading to higher rates of depression, lower quality of life, and poorer overall health (2). As the U.S. population continues to age (3), the need for informal caregivers will likely increase. However, little nationally representative information on prevalence of caregivers is available. This study examined demographic characteristics and health status of informal caregivers from 44 states,* the District of Columbia (DC), and Puerto Rico, based on data from the Behavioral Risk Factor Surveillance System (BRFSS) collected during 2015-2017. Overall, approximately one in five adults reported that they had provided care to a family member or friend in the preceding 30 days. Fifty-eight percent of caregivers were women, and a majority were non-Hispanic white, with at least some college education, and married or living with a partner. Across all states, 19.2% of caregivers reported being in fair or poor health, although significant state-to-state variation occurred. Caregivers provide important support to family members, friends, and the health care system and might compromise their own health to provide this support (1,2). Better understanding of caregivers and the challenges they face could inform implementation of improvements in support systems that could enhance not only the health of the caregiver, but that of the care recipient as well. For example, additional data regarding demographics at the state level might aid in more effective planning and support of caregivers with evidence-based programs and assistance (https://www.cdc.gov/aging/publications/features/caring-for-yourself.html).
Angiotensin II and pro-inflammatory cytokines synergistically increased COX-2 mRNA and protein expression in lung fibroblasts.
Authors: Takaya Matsuzuka, Kathryn Miller, Lara Pickel, Chiyo Doi, Masaaki Tamura
Journal: Cancer Research (2007)

583  Angiotensin II (Ang II) is the key effecter of the renin-angiotensin system. Although Ang II receptor blockers and angiotensin-converting enzyme inhibitors are potential candidates for cancer chemoprevention, the precise mechanism(s) by which Ang II induces tumorigenesis are not yet clear. Since our previous study revealed that Ang II stimulates Cyclooxygenase-2 (COX-2) in cardiovascular tissues and intestinal epithelial cells and COX-2 expression is shown to be associated with carcinogenesis, we further investigated a mechanism by which Ang II stimulates COX-2 expression. Although an increased COX-2 expression has been observed in a variety of cancer cells including colon, prostate and lung, high levels of COX-2 expression were also detected in tumor stroma. Since tumor stroma play important roles in tumorigenesis and tumor development, the aim of this study was to investigate whether synergistic induction of COX-2 occurs by Ang II and pro-inflammatory cytokines in primary cultured lung fibroblasts. Ang II induced COX-2 expression in lung fibroblasts with a dose-dependent manner (10 -9 to 10-7M). This stimulation was completely blocked by 1 µM Ang II subtype 1 (AT1) receptor antagonist losartan but not by AT2 receptor antagonist PD123319 implying that Ang II stimulates COX-2 induction through the AT1 receptor. Ang II synergistically enhanced induction of COX-2 by pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The increase in the pro-inflammatory cytokine-induced COX-2 expression with Ang II was over 2-fold as compared to the expression induced by cytokine alone. In addition, the duration of COX-2 expression by IL-1β or TNF-α was significantly prolonged by co-stimulation of Ang II. The Ang II-induced COX-2 expression was markedly attenuated by p38 mitogen-activated protein kinase (MAPK) inhibitor, whereas pro-inflammatory cytokine- induced COX-2 expression was attenuated by both p38 MAPK and p44/42 MAPK inhibitors. In contrast, A549, human lung adenocarcinoma cell line or BEAS-2B, human bronchial epithelial cell did not show the induction of COX-2 by Ang II despite that these cell lines express the AT1 receptor. These results clearly suggest that Ang II has pro-tumorigenic effects by stimulating COX-2 expression in lung stromal fibroblasts synergistically with pro-inflammatory cytokines. These results indicate that the AT1 receptor in fibroblasts is a potentially important target for lung cancer chemoprevention. This work was supported by KSU Terry C. Johnson Center for Basic Cancer Research, KSU Provost’s fund, KSU CVM Dean’s fund.
Perivascular spaces in the brain: anatomy, physiology and pathology
Authors: Joanna M. Wardlaw, Helene Benveniste, Maiken Nedergaard, Berislav V. Zlokovic, Humberto Mestre, Hedok Lee, Fergus N. Doubal, Rosalind Brown, Joel Ramirez, Bradley J. MacIntosh, Allen Tannenbaum, Lucia Ballerini, Ravi L. Rungta, Davide Boido, Melanie Sweeney, Axel Montagne, Serge Charpak, Anne Joutel, Kenneth J. Smith, Sandra E. Black
Journal: Nature Reviews Neurology (2020)
Readmission and Mortality After Hospitalization for Myocardial Infarction and Heart Failure
Authors: Dennis T. Ko, Rohan Khera, Geoffrey Lau, Feng Qiu, Yongfei Wang, Peter C. Austin, Maria Koh, Zhenqiu Lin, Douglas S. Lee, Harindra C. Wijeysundera, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2020)
Pervasive Suicidal Integrases in Deep-Sea Archaea
Authors: Catherine Badel, Violette Da Cunha, Patrick Forterre, Jacques Oberto
Journal: Molecular Biology and Evolution (2020)

Mobile genetic elements (MGEs) often encode integrases which catalyze the site-specific insertion of their genetic information into the host genome and the reverse reaction of excision. Hyperthermophilic archaea harbor integrases belonging to the SSV-family which carry the MGE recombination site within their open reading frame. Upon integration into the host genome, SSV integrases disrupt their own gene into two inactive pseudogenes and are termed suicidal for this reason. The evolutionary maintenance of suicidal integrases, concurring with the high prevalence and multiples recruitments of these recombinases by archaeal MGEs, is highly paradoxical. To elucidate this phenomenon, we analyzed the wide phylogenomic distribution of a prominent class of suicidal integrases which revealed a highly variable integration site specificity. Our results highlighted the remarkable hybrid nature of these enzymes encoded from the assembly of inactive pseudogenes of different origins. The characterization of the biological properties of one of these integrases, IntpT26-2 showed that this enzyme was active over a wide range of temperatures up to 99 °C and displayed a less-stringent site specificity requirement than comparable integrases. These observations concurred in explaining the pervasiveness of these suicidal integrases in the most hyperthermophilic organisms. The biochemical and phylogenomic data presented here revealed a target site switching system operating on highly thermostable integrases and suggested a new model for split gene reconstitution. By generating fast-evolving pseudogenes at high frequency, suicidal integrases constitute a powerful model to approach the molecular mechanisms involved in the generation of active genes variants by the recombination of proto-genes.
Uptake, engagement, and adherence to pre-exposure prophylaxis offered after population HIV testing in rural Kenya and Uganda: 72-week interim analysis of observational data from the SEARCH study
Authors: Catherine A Koss, Edwin D Charlebois, James Ayieko, Dalsone Kwarisiima, Jane Kabami, Laura B Balzer, Mucunguzi Atukunda, Florence Mwangwa, James Peng, Yusuf Mwinike, Asiphas Owaraganise, Gabriel Chamie, Vivek Jain, Norton Sang, Winter Olilo, Lillian B Brown, Carina Marquez, Kevin Zhang, Theodore D Ruel, Carol S Camlin, James F Rooney, Douglas Black, Tamara D Clark, Monica Gandhi, Craig R Cohen, Elizabeth A Bukusi, Maya L Petersen, Moses R Kamya, Diane V Havlir
Journal: The Lancet HIV (2020)

Optimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda.
Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations
Authors: Longbo Zhang, Tianxiang Huang, Shannon Teaw, Lena H. Nguyen, Lawrence S. Hsieh, Xuan Gong, Lindsay H. Burns, Angélique Bordey
Journal: Science Translational Medicine (2020)

Inhibiting filamin A has therapeutic effects in a model of tuberous sclerosis complex and a subset of focal cortical dysplasia.
Ian Calder: forensic pathologist who investigated unexplained deaths
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Credit: James Calder

Ian Calder investigated some of the most headline grabbing, mysterious, and unexplained deaths of the past 50 years, including those of the bankrupt newspaper tycoon Robert Maxwell; the “body in the bag,” M16 agent Gareth Williams; and Stuart Lubbock, who was found dead in the entertainer Michael Barrymore’s pool in 2001.

Born in Norwich, the only child of an engineer of Scottish descent, Calder was educated at Norwich School, where he enjoyed science and sport. As a state scholar he studied medicine at the University of St Andrews in Fife, where he continued his enjoyment of playing rugby. After qualifying in 1962, he trained in pathology at Addenbrooke’s Hospital in Cambridge and later in forensic medicine at the Westminster, Royal Marsden, and St George’s hospitals in London before being appointed senior lecturer at the London Hospital. He was awarded doctorates in both medicine and science. He had a natural talent for teaching and sought out those students with the worst results and transferred them into his tutorial group, claiming that they were often the bright but wayward rugby players who required a little direction to get them back on course. With his somewhat unorthodox approach of conducting tutorials in the pub, he had a 100% attendance rate and never had a student fail the pathology examination.

In 1964, Calder married Dorothy Hubbard, a nurse at the Norfolk and Norwich Hospital, whom he had met when she was 16 years old. They settled in Cambridge, and he became a fellow of St Edmund’s College Cambridge and the Wellcome Institute of Comparative Neurology. The couple had a long and happy marriage and had two children—James, …
The Patatin‐Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability
Authors: Xiuyun Wang, Min Guo, Qian Wang, Qingjie Wang, Shasha Zuo, Xu Zhang, Hui Tong, Jizheng Chen, Huimin Wang, Xiaowei Chen, Junyuan Guo, Xiong Su, Hui Liang, Hongwen Zhou, John Zhong Li
Journal: Hepatology (2020)

Background and Aims The regulation of hepatic very‐low‐density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin‐like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown. Approach and Results Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal‐mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL‐TAG metabolism in PNPLA7‐knockdown primary hepatocytes. Conclusion PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE.
Consistent Reduction in HAE Attack Rate with Lanadelumab Regardless Of Baseline Attack Frequency: Interim Findings From the Phase 3 HELP Study Open Label Extension (OLE)
Authors: Aleena Banerji, Marc Riedl, Raffi Tachdjian, Christina Nurse, Kim Paes, Huamin Li, Sorena Kiani-Alikhan
Journal: Journal of Allergy and Clinical Immunology (2020)
Oncolytic Adenovirus Armed with BiTE, Cytokine, and Checkpoint Inhibitor Enables CAR T Cells to Control the Growth of Heterogeneous Tumors
Authors: Caroline E. Porter, Amanda Rosewell Shaw, Youngrock Jung, Tiffany Yip, Patricia D. Castro, Vlad C. Sandulache, Andrew Sikora, Stephen Gottschalk, Michael M. Ittman, Malcolm K. Brenner, Masataka Suzuki
Journal: Molecular Therapy (2020)

No single cancer immunotherapy will likely defeat all evasion mechanisms of solid tumors, including plasticity of tumor antigen expression and active immune suppression by the tumor environment. In this study, we increase the breadth, potency, and duration of anti-tumor activity of chimeric antigen receptor (CAR) T cells using an oncolytic virus (OV) that produces cytokine, checkpoint blockade, and a bispecific tumor-targeted T cell engager (BiTE) molecule. First, we constructed a BiTE molecule specific for CD44 variant 6 (CD44v6), since CD44v6 is widely expressed on tumor but not normal tissue, and a CD44v6 antibody has been safely administered to cancer patients. We then incorporated this BiTE sequence into an oncolytic-helper binary adenovirus (CAdDuo) encoding an immunostimulatory cytokine (interleukin [IL]-12) and an immune checkpoint blocker (PD-L1Ab) to form CAdTrio. CD44v6 BiTE from CAdTrio enabled HER2-specific CAR T cells to kill multiple CD44v6+ cancer cell lines and to produce more rapid and sustained disease control of orthotopic HER2+ and HER2-/- CD44v6+ tumors than any component alone. Thus, the combination of CAdTrio with HER2.CAR T cells ensures dual targeting of two tumor antigens by engagement of distinct classes of receptor (CAR and native T cell receptor [TCR]), and significantly improves tumor control and survival.
Associations between Upper Respiratory Symptom Scores of Puerto Rican Residents, Pro-Inflammatory Potential of Indoor Settled Dust, and Level of Water Damage to Homes during Hurricane Maria
Authors: Sukeina Nasser, Hayat Srour, Benjamin Bolanos, Filipa Godoy-Vitorino, Kerry Kinney, Juan Maestre, Humberto Cavallin
Journal: Journal of Allergy and Clinical Immunology (2020)
Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer.
Authors: Shintaro Narita, Kyoko Nomura, Shingo Hatakeyama, Masahiro Takahashi, Toshihiko Sakurai, Sadafumi Kawamura, Senji Hoshi, Masanori Ishida, Toshiaki Kawaguchi, Shigeto Ishidoya, Jiro Shimoda, Hiromi Sato, Koji Mitsuzuka, Tatsuo Tochigi, Norihiko Tsuchiya, Chikara Ohyama, Yoichi Arai, Kengo Nagashima, Tomonori Habuchi
Journal: Journal of Clinical Oncology (2020)

247 Background: The treatment strategy for patients with newly diagnosed metastatic hormone naïve prostate cancer (mHNPC) has changed in recent years. Thus, an accurate assessment of prognosis is critical. Conditional net survival provides the more appropriate method of estimating survival from cancer. The purpose of this study was to identify predictive factors associated with conditional net survival in patients with mHNPC initially treated with androgen deprivation therapy (ADT). Methods: The medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to five years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results: During follow-up (median, 2.95 years), 208 patients died, 169 from progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. The overall conditional 5-yearnet OS rate at baseline was 0.582, and the overall conditional 5-year net OS rates for patients who survived for1, 2, 3, 4, and 5 years were 0.566 (−0.16), 0.615 (+3.3), 0.550 (−0.32), 0.702 (+1.2), and 0.811 (+2.29), respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions: The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient’s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors.
Multidrug-Resistant <i>Candida auris</i> Concern Stems From New York Cases
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Although multidrug-resistant Candida auris infections are rare, New York health officials advise close monitoring of cases after 3 patients in the state were found to have C auris that was resistant to all 3 classes of commonly prescribed antifungal drugs (pan resistance).
Association between serum sodium levels and fever in children: An indirect clinical effect of pyrogenic cytokines on sodium levels
Authors: Jose Rojas Camayo, Patricio Gallardo, Yeh Ling Yiin Dillon, Kenny Castro Ochoa, Mariella Cabrera Quijada, Malliany Camejo Leonor, Maria Fermin, Davami Rosario Garcia, George Vermenton, David Lindsay
Journal: Journal of Allergy and Clinical Immunology (2020)
Inflammatory markers to predict prognosis in renal cell carcinoma (RCC) patients treated with immune checkpoint inhibitors (ICIs).
Authors: Lucia Carril, Alfonso Gomez De Liano Lista, Javier Pozas, Teresa Alonso Gordoa, Alejandra Bernardini, Alberto Carretero-González, Maria Cruz Martin Soberón, Juan Manuel Manuel Sepulveda Sanchez, Jesus Paramio, Daniel Castellano, Guillermo De Velasco
Journal: Journal of Clinical Oncology (2020)

757 Background: Immune checkpoint inhibitors have increased survival in mRCC across all risk groups. In this new treatment paradigm, inflammatory markers could add prognostic information to the International metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients treated with ICI. Methods: We conducted a multicenter retrospective analysis of mRCC patients treated with ICI from 2013 to 2019. Clinical, pathological and laboratory data including blood cell counts were collected. Multivariate Cox-regression models were performed to evaluate the independent prognostic significance of the IMDC score, the derived neutrophil to lymphocyte ratio (dNLR) and LDH at baseline, as well as the inflammatory prognostic index (IPI). Results: A total of 104 patients were included. Of these, 19% were treatment-naïve, 34% had received one previous line of treatment and 47% had received two or more previous lines of treatment. Distribution of IMDC model for favorable, intermediate and poor risk was 23%,57% and 20%. Median OS was 15 months and the disease control rate (DCR) was 51%. The multivariate analysis identified the IMDC risk score, the dNLR and the IPI as independent predictors of OS. In addition, both inflammatory markers, the IPI and the dNLR, were able to improve the prognostic value of the IMDC risk score (p = 0.01 and p = 0.006, respectively). Specifically, in patients with 0 or 1 IMDC risk factors, both the IPI and the dNLR were able to subclassify additional prognostic subgroups (i.e. dNLR &gt; 3 vs ≤3 HR = 3,16; 95% CI; 1.71-5.76). Conclusions: Adding IPI and/or dNLR may add further information about the benefit of ICIs in mRCC patients with 0 or 1 IMDC risk factors. Inflammatory systemic markers may improve the prognostic performance of the IMDC model.[Table: see text]
Real-World Evidence of Reductions in Health Resource Utilization (HRU) and Improved Efficacy Outcomes Associated with Reslizumab Treatment in Adults with Severe Eosinophilic Asthma (SEA) in the United States
Authors: Michael Wechsler, Stephen Peters, Bradley Chipps, Tanisha Hill, Rinat Ariely, Michael Depietro, Emi Terasawa, Darren Thomason, Reynold Panettieri
Journal: Journal of Allergy and Clinical Immunology (2020)