tbuckley/cabot-search huggingface dataset:
Abstract 15514: Ace Inhibitors, Angiotensin Receptor Blockers, and Outcomes in Hospitalized Patients With Severe Covid-19 Pneumonia
Authors: Prabhjot Grewal, Jeanwoo Yoo, Aikaterini Papamanoli, Azad Mojahedi, Simrat Dhaliwal, Jacquelyn Nakamura, Joshua Abata, Jacob Robin, Jenny Fung, Jessica Hotelling, Sahil Rawal, Nikitha Karkala, Stella T Tsui, Alexandra Coritsidis, Luis Marcos, Michelle E Bloom, Hal Skopicki, Andreas P Kalogeropoulos
Journal: Circulation (2020)

Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.
Ultra‐Wide Range Pressure Sensor Based on a Microstructured Conductive Nanocomposite for Wearable Workout Monitoring
Authors: Yongrok Jeong, Jimin Gu, Jaiyeul Byun, Junseong Ahn, Jaebum Byun, Kyuyoung Kim, Jaeho Park, Jiwoo Ko, Jun‐ho Jeong, Morteza Amjadi, Inkyu Park
Journal: Advanced Healthcare Materials (2021)

Conventional flexible pressure sensors are not suitable for high-pressure applications due to their low saturation pressure. In this study, an ultra-wide range pressure sensor is designed based on the optimized microstructure of the polyimide/carbon nanotubes (PI/CNT) nanocomposite film. The sensing range of the pressure sensor is expanded by adopting polyimide (PI) with a high elastic modulus as a matrix material and its sensitivity is improved through functional sensing film with tip-flattened microdome arrays. As a result, the pressure sensor can measure a wide pressure range (≈ 0-3000 kPa) and possesses the sensitivity of ≈ 5.66 × 10-3 -0.23 × 10-3 kPa-1 with high reliability and durability up to 1000 cycles. The proposed sensor is integrated into the hand and foot pressure monitoring systems for workout monitoring. The representative values of the pressure distribution in the hands and feet during the powerlifting are acquired and analyzed through Pearson's correlation coefficient (PCC). The analyzed results suggest that the pressure sensor can provide useful real-time information for healthcare and sports performance monitoring.
Covid-19, trust, and Wellcome: how charity’s pharma investments overlap with its research efforts
Authors: Tim Schwab
Journal: BMJ (2021)

pharma investments overlap with its research effortsThe major funder of health research stands to gain financially from the pandemic, raising questions about transparency and accountability Tim Schwab independent journalistAn increasingly clear feature of the covid-19 pandemic is that the public health response is being driven not only by governments and multilateral institutions, such as the World Health Organisation, but also by a welter of public-private partnerships involving drug companies and private foundations.
4P Immunohybridoma cell-based vaccine for the treatment of patients with castration-resistant prostate cancer
Authors: S. Hawlina, H.H. Chowdhury, M. Gabrijel, S. Trkov Bobnar, M. Kreft, G. Lenart, M. Cukjati, A.N. Kopitar, A. Ihan, L. Ležaić, M. Gamek, A. Kmetec, M. Jeras, R. Zorec
Journal: Annals of Oncology (2021)
A fast and facile platform for fabricating phase-change materials-based drug carriers powered by chemical Marangoni effect
Authors: Meng-Hsuan Hsieh, Hao-Ji Wei, Kuan-Hung Chen, Hung-Chen Wang, Chia-Hsiang Yu, Ting-Hsuan Lu, Yen Chang, Hsing-Wen Sung
Journal: Biomaterials (2021)
Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats
Authors: Audrey Franceschi Biagioni, Giada Cellot, Elisa Pati, Neus Lozano, Belén Ballesteros, Raffaele Casani, Norberto Cysne Coimbra, Kostas Kostarelos, Laura Ballerini
Journal: Biomaterials (2021)

Engineered small graphene oxide (s-GO) sheets were previously shown to reversibly down-regulate glutamatergic synapses in the hippocampus of juvenile rats, disclosing an unexpected translational potential of these nanomaterials to target selective synapses in vivo. Synapses are anatomical specializations acting in the Central Nervous System (CNS) as functional interfaces among neurons. Dynamic changes in synaptic function, named synaptic plasticity, are crucial to learning and memory. More recently, pathological mechanisms involving dysfunctional synaptic plasticity were implicated in several brain diseases, from dementia to anxiety disorders. Hyper-excitability of glutamatergic neurons in the lateral nucleus of the amygdala complex (LA) is substantially involved in the storage of aversive memory induced by stressful events enabling post-traumatic stress disorder (PTSD). Here we translated in PTSD animal model the ability of s-GO, when stereotaxically administered to hamper LA glutamatergic transmission and to prevent the behavioral response featured in long-term aversive memory. We propose that s-GO, by interference with glutamatergic plasticity, impair LA-dependent memory retrieval related to PTSD.
Persistence of Δ-9-Tetrahydrocannabinol in Human Breast Milk
Authors: Erica M. Wymore, Claire Palmer, George S. Wang, Torri D. Metz, David W. A. Bourne, Cristina Sempio, Maya Bunik
Journal: JAMA Pediatrics (2021)

the toxic effects of calcineurin inhibitors, alternative interventions or low-dose approaches are needed for long-term treatments.The anti-CD20 monoclonal antibody rituximab emerged as a promising steroid-sparing drug in patients with SDNS. 1,2n the present study, single-dose rituximab, withdrawing steroids, resulted in effective control of SDNS.Given the limited adverse effects, rituximab should be considered as the main steroid-sparing drug in patients with SDNS.Previous reports indicate that MMF can maintain steroidfree remission in children with SDNS. 2 However, existing small and uncontrolled studies on MMF generated conflicting data 2,3 : the minimum dose of MMF sufficient to maintain remission of SDNS is unknown, and variable doses (ranging from 700 mg/ m 2 -1200 mg/m 2 daily) are reported. 4his study aimed to address the efficacy of low-dose MMF, and the inefficacy provides useful evidence for designing future trials.The adherence to MMF, monitored with monthly reports, was complete in all patients.The strategy of monitoring may represent a weakness and better strategies to estimate MMF exposure are to be defined.Conclusions | Rituximab was effective in maintaining longterm remission of SDNS; MMF given at low dose (350 mg/m 2 twice daily) was, instead, inadequate.The effect of higher doses (1200 mg/m 2 ) deserve testing in randomized clinical trials.
Frequency, management, and resource use of adverse events (AEs) in nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients receiving apalutamide or enzalutamide: A real-world study.
Authors: Shan Jiang, Della Varghese, Sreevalsa Appukkuttan, Shelby Corman, Nehemiah Kebede, Kajan Gnanasakthy, Cynthia Macahilig, A. Reginald Waldeck, Arif Hussain
Journal: Journal of Clinical Oncology (2021)

217 Background: Second generation androgen receptor inhibitors (SGARIs), apalutamide (APA) and enzalutamide (ENZ) and darolutamide, are approved in the United States (US) for the treatment of nmCRPC. The objectives of this study were to describe the frequency of AEs and actions taken to manage AEs among nmCRPC patients treated with APA or ENZ and their downstream resource implications. Methods: This is a further descriptive analysis of a retrospective chart review study conducted in 43 US nmCRPC-treating sites. In our sample, the 43 physicians identified 699 nmCRPC patients initiating treatment with APA (N = 368) or ENZ (N = 333) with 2 patients receiving both, between February 1, 2018 and December 31, 2018 and AEs were collected as reported in regular clinical practice. A representative subset of patients, experiencing at least 1 AE for either APA (N = 125) or ENZ (N = 125), were selected randomly from the initial cohort, and their detailed chart data were extracted to understand the actions taken to manage AEs. Results: Of the initial cohort of nmCRPC patients, 72.0% and 78.7% of men receiving APA (N = 368) and ENZ (N = 333) experienced ≥1 AE, respectively. The three most common AEs reported were fatigue/asthenia (APA, 30.2%; ENZ, 38.7%), hot flush (APA, 14.1%; ENZ, 13.5%), and arthralgia (APA, 14.4%; ENZ, 12.9%). Cognitive and mental changes were observed in 5.4% (APA) and 7.8% (ENZA) men. The subset analysis of randomly selected patients experiencing ≥1 AE (APA, 125; ENZ, 125) were mostly Caucasian (APA, 72.8%; ENZ, 71.2%), ECOG score 0-1 (APA, 84%; ENZ, 88%), median prostate specific antigen (PSA) value 13 ng/ml and 11 ng/ml (APA, ENZ; respectively). Actions to address AEs included treatment of AE, SGARI discontinuation, dose reduction and hospitalization (Table). Specifically, treatment discontinuation due to AE was observed in 8.0% (APA) and 12.8 (%) of men. AEs were often not resolved (APA, 43.6%; ENZ, 39.4%), and the median duration of days to resolve AEs were 60.0 for APA and 56.0 for ENZ. Conclusions: This real-world study highlights the clinical and resource use burden of AEs among nmCRPC patients treated with APA and ENZ. The results demonstrate the importance of safety and tolerability as key considerations in shared clinician-patient decision-making regarding SGARI therapy in nmCRPC. [Table: see text]
Bringing Together Behavioral Science, Community Engagement, and Cultural Adaptations to Increase Alcohol Abstinence Among American Indian and Alaska Native People Using Contingency Management Therapy
Authors: Stephanie S. O’Malley, Maria C. Crouch, Stephen T. Higgins
Journal: JAMA Psychiatry (2021)

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Abstract 15378: Impact of Delirium on Mortality in Patients Hospitalized for Heart Failure: A National Inpatient Sample Study
Authors: Charlotte Ritchie, Ryan Walters, Sriram Ramaswamy, Venkata M Alla
Journal: Circulation (2020)

Introduction: Heart Failure (HF) is one of the leading causes of hospitalization in USA accounting for ≈ 800,000 hospital discharges and $11 billion annually. Delirium is a common problem in the elderly hospitalized patients and can occur in 30-80%. Hypothesis: Given the increasing age of the HF population, we hypothesized that rate of delirium in HF hospitalizations is increasing and that delirium is associated adverse outcomes in HF hospitalizations. Methods: We queried the 2001-2014 Nationwide Inpatient Sample to identify hospitalizations that included a primary discharge diagnosis of HF (ICD-9-CM: 428.xx) stratified by presence or absence of delirium (ICD-9-CM: 239.0, 290.41, 293.0, 293.1, 348.31). The delirium trend was evaluated using orthogonal polynomial contrasts, whereas differences between delirium and non-delirium for in-hospital mortality, length of stay (LOS), and hospital costs were evaluated using propensity-score matched cohorts; match robustness was evaluated via propensity distributions and standardized mean differences. Results: Of the 12.8 million hospitalizations with HF, 89,489 (0.7%) had a diagnosis of delirium. The rate of delirium increased slightly from 0.3% in 2001 to 0.4% in 2007 and increased significantly to 1.6% by 2014 (quadratic p trend &lt; .001). Major predictors of delirium included advanced age, Caucasian race, underlying dementia or psychiatric diagnoses, higher Elixhauser Comorbidity Index, renal failure, cardiogenic shock, and coronary artery bypass surgery. In the propensity-score matched analysis of 76,411 hospitalization with delirium compared to 76,612 without delirium, in-hospital mortality (odds ratio: 1.67, 95% CI: 1.51-1.77), LOS (rate ratio [RR]: 1.47, 95% CI: 1.45-1.51), and hospital costs (RR: 1.44, 95% CI: 1.41-1.48) were all statistically higher in the presence of delirium (all p &lt; 0.001). Conclusions: In patients hospitalized with HF, delirium is an independent predictor of increased in-hospital mortality, longer LOS, and excess hospital costs despite adjustment for baseline characteristics. Whether interventions targeting prevention, early recognition, and treatment of delirium will mitigate this excess risk requires evaluation in future studies.
SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription
Authors: Abdulaziz Almuqrin, Andrew D. Davidson, Maia Kavanagh Williamson, Philip A. Lewis, Kate J. Heesom, Susan Morris, Sarah C. Gilbert, David A. Matthews
Journal: Genome Medicine (2021)

Abstract Background ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to the cell nucleus alongside the SARS-CoV-2 S glycoprotein gene. Methods We used direct RNA sequencing to analyse transcript expression from the ChAdOx1 nCoV-19 genome in human MRC-5 and A549 cell lines that are non-permissive for vector replication alongside the replication permissive cell line, HEK293. In addition, we used quantitative proteomics to study over time the proteome and phosphoproteome of A549 and MRC5 cells infected with the ChAdOx1 nCoV-19 vaccine. Results The expected SARS-CoV-2 S coding transcript dominated in all cell lines. We also detected rare S transcripts with aberrant splice patterns or polyadenylation site usage. Adenovirus vector transcripts were almost absent in MRC-5 cells, but in A549 cells, there was a broader repertoire of adenoviral gene expression at very low levels. Proteomically, in addition to S glycoprotein, we detected multiple adenovirus proteins in A549 cells compared to just one in MRC5 cells. Conclusions Overall, the ChAdOx1 nCoV-19 vaccine’s transcriptomic and proteomic repertoire in cell culture is as expected. The combined transcriptomic and proteomics approaches provide a detailed insight into the behaviour of this important class of vaccine using state-of-the-art techniques and illustrate the potential of this technique to inform future viral vaccine vector design.
Physician, Heal Thy Double Stigma — Doctors with Mental Illness and Structural Barriers to Disclosure
Authors: Omar S. Haque, Michael A. Stein, Amelia Marvit
Journal: New England Journal of Medicine (2021)

Throughout the medical school admissions process, training, and licensure activities, students and physicians with histories of mental illness face structural barriers that result in discrimination and discourage disclosure and care seeking.
Prevalence of Keratoconus in Persons With Down Syndrome in a National Registry in Norway
Authors: Olav Kristianslund, Liv Drolsum
Journal: JAMA Network Open (2021)

research has suggested that Down syndrome is associated with greater frequency of eye rubbing and possibly with more atopy. 2,4,6 Other researchers have speculated about whether keratoconus is linked to chromosome 21. 6 Few previous studies of keratoconus in persons with Down syndrome have been carried out in Northern Europe.A case-control study by Haugen et al 2 revealed a thinner cornea, higher keratometry values, and a greater incidence of keratoconus in a group of participants with Down syndrome; 5 of 47 individuals with Down syndrome (10.6%) had keratoconus compared with 1 of 51 control participants (2.0%).In studies from various regions, proportions lower than those that we found have been reported in young patients, whereas higher proportions have often been reported in selected hospital populations.To our knowledge, no previous study has reported a national prevalence of keratoconus in persons with Down syndrome.The present study used data from a nationwide patient registry in Norway, thereby avoiding the risk of selection bias.Nevertheless, no routine screening is performed for this condition, and it is reasonable to suspect that a substantial number of cases are undiagnosed, which represents a limitation of the present study in addition to some uncertainty regarding diagnosis registration.
Osteocytes regulate neutrophil development through IL-19: a potent cytokine for neutropenia treatment
Authors: Min Xiao, Wuju Zhang, Wen Liu, Linlin Mao, Jincheng Yang, Le Hu, Sheng Zhang, Yaling Zheng, Anling Liu, Qiancheng Song, Yuhua Li, Guozhi Xiao, Zhipeng Zou, Xiaochun Bai
Journal: Blood (2021)
Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models
Authors: Ming Chen, Yunan Chen, Qingwei Huo, Lei Wang, Shuyi Tan, Afzal Misrani, Jinxiang Jiang, Jian Chen, Shiyuan Chen, Jiawei Zhang, Sidra Tabassum, Jichen Wang, Xi Chen, Cheng Long, Li Yang
Journal: Molecular Neurodegeneration (2021)

Abstract Background Before the deposition of amyloid-beta plaques and the onset of learning memory deficits, patients with Alzheimer’s disease (AD) experience olfactory dysfunction, typified by a reduced ability to detect, discriminate, and identify odors. Rodent models of AD, such as the Tg2576 and APP/PS1 mice, also display impaired olfaction, accompanied by aberrant in vivo or in vitro gamma rhythms in the olfactory pathway. However, the mechanistic relationships between the electrophysiological, biochemical and behavioral phenomena remain unclear. Methods To address the above issues in AD models, we conducted in vivo measurement of local field potential (LFP) with a combination of in vitro electro-olfactogram (EOG), whole-cell patch and field recordings to evaluate oscillatory and synaptic function and pharmacological regulation in the olfactory pathway, particularly in the olfactory bulb (OB). Levels of protein involved in excitation and inhibition of the OB were investigated by western blotting and fluorescence staining, while behavioral studies assessed olfaction and memory function. Results LFP measurements demonstrated an increase in gamma oscillations in the OB accompanied by altered olfactory behavior in both APP/PS1 and 3xTg mice at 3–5 months old, i.e. an age before the onset of plaque formation. Fewer olfactory sensory neurons (OSNs) and a reduced EOG contributed to a decrease in the excitatory responses of M/T cells, suggesting a decreased ability of M/T cells to trigger interneuron GABA release indicated by altered paired-pulse ratio (PPR), a presynaptic parameter. Postsynaptically, there was a compensatory increase in levels of GABA A R α1 and β3 subunits and subsequent higher amplitude of inhibitory responses. Strikingly, the GABA uptake inhibitor tiagabine (TGB) ameliorated abnormal gamma oscillations and levels of GABA A R subunits, suggesting a potential therapeutic strategy for early AD symptoms. These findings reveal increased gamma oscillations in the OB as a core indicator prior to onset of AD and uncover mechanisms underlying aberrant gamma activity in the OB. Conclusions This study suggests that the concomitant dysfunction of both olfactory behavior and gamma oscillations have important implications for early AD diagnosis: in particular, awareness of aberrant GABAergic signaling mechanisms might both aid diagnosis and suggest therapeutic strategies for olfactory damage in AD.
Genomic characterization and molecular taxonomy of sarcomatoid variant prostate cancer.
Authors: Mary Duong, Alex Barrett, Jeff Schaeffer, Tim Taxter, Mitchell E. Gross
Journal: Journal of Clinical Oncology (2021)

168 Background: Sarcomatoid carcinoma is a rare and aggressive histologic variant pattern of prostate cancer with morphologic features associated with both mesenchymal and epithelial tissue elements. While sarcomatoid cancer can be found concurrently with adenocarcinoma in untreated specimens, it is most often encountered in post-treatment biopsies. Limited data is available to categorize genomic alterations in sarcomatoid prostate cancer or to genetically define any potential relationship between sarcomtaoid and adenocarcinoma patterns from the same patient. Methods: Clinical characteristics, histology, and genomic alterations for 5 cases of sarcomatoid prostate cancer and 2193 cases with adenocarcinoma are presented. All cases were analyzed for genomic alterations against a custom panel via Tempus xT tissue biopsy assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth and whole transcriptome RNA sequencing) for germline and/or somatic mutations. The xT assay detects single nucleotide variants, specific insertion/deletions, amplifications and gene fusions, as well as TMB and MSI status. Results: Patterns of genomic alterations in sarcomatoid cancer are tabulated and compared with adenocarcinoma. Of note, BRCA2 alterations were found in 2 of 5 sarcomatoid cases including 1 example of BRCA2 loss and 1 variant of undetermined significance (p.K2316R). Sequential analysis of samples from the subject with BRCA2 loss demonstrates genomic alterations that are shared across multiple samples despite different histologic patterns and following 14 months of treatment with GnRH antagonist and abiraterone (Table). Conclusions: Sarcomatoid prostate cancer shares many genomic alterations with that found in adenocarcinoma. Genomic characterization of this variant form of prostate cancer may reveal clinically actionable genetic changes. [Table: see text]