tbuckley/cabot-search huggingface dataset:
Emergence of hostility during alprazolam treatment
Authors: J F Rosenbaum, S W Woods, J E Groves, G L Klerman
Journal: American Journal of Psychiatry (1984)

Of 80 patients given alprazolam, eight became hostile early in treatment. The authors suggest that alprazolam-induced hostility may be more likely in patients with well-suppressed chronic anger and resentment and cite reports of hostility associated with other benzodiazepines.
The assessment of short- and long-term changes in lung function in cystic fibrosis using <sup>129</sup>Xe MRI
Authors: Laurie J. Smith, Alex Horsley, Jody Bray, Paul J.C. Hughes, Alberto Biancardi, Graham Norquay, Martin Wildman, Noreen West, Helen Marshall, Jim M. Wild
Journal: European Respiratory Journal (2020)

Introduction Xenon-129 ( 129 Xe) ventilation magnetic resonance imaging (MRI) is sensitive to detect early cystic fibrosis (CF) lung disease and response to treatment. 129 Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change. Methods 29 children and adults with CF and a range of disease severity were assessed twice, a median (interquartile range (IQR)) of 16.0 (14.4–19.5) months apart. Patients underwent 129 Xe-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. 11 patients repeated 129 Xe-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from 129 Xe-MRI. Results At baseline, mean± sd age was 23.0±11.1 years and forced expiratory volume in 1 s (FEV 1 ) z-score was −2.2±2.0. Median (IQR) VDP was 9.5 (3.4–31.6)% and LCI was 9.0 (7.7–13.7). Within- and inter-visit repeatability of VDP was high. At 16 months there was no single trend of 129 Xe-MRI disease progression. Visible 129 Xe-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is &gt;±1.6%. For longer-term follow-up, changes in VDP of up to ±7.7% can be expected, or ±4.1% for patients with normal FEV 1 . No patient had a significant change in FEV 1 ; however, 59% had change in VDP &gt;±1.6%. In patients with normal FEV 1 , there were significant changes in ventilation and in VDP. Conclusions 129 Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and end-point for clinical trials.
The Research Agenda for Stop the Bleed
Authors: Stephen W. Lu, David A. Spain
Journal: JAMA Network Open (2020)

Eric Goralnick, MD, MS; Chibuike Ezeibe, MD; Muhammad Ali Chaudhary, MD; Justin McCarty, DO, MPH; Juan P. Herrera-Escobar, MD, MPH; Tomas Andriotti, MD, MPH; Elzerie de Jager, MBBS(Hons); Daniel Ospina-Delgado, MD; Craig Goolsby, MD, MEd; Richard Hunt, MD; Joel S. Weissman, PhD; Adil Haider, MD, MPH; Lenworth Jacobs, MD, MPH; and the Stop the Bleed National Research Agenda Consensus Conference Working Group; Erin Andrade, MD, MPH; Jeremy Brown, MD; Eileen M. Bulger, MD; Frank K. Butler, MD; David Callaway, MD, MPA; Edward J. Caterson, MD, PhD; Niteesh K. Choudhry, MD, PhD; Michael R. Davis, MD; Alex Eastman, MD, MPH; Brian J. Eastridge, MD; Jonathan L. Epstein, MEMS, NRP; Conor L. Evans, PhD; Marianne Gausche-Hill, MD; Mark L. Gestring, MD; Scott A. Goldberg, MD, MPH; Dan Hanfling, MD; John Bradley Holcomb, MD; Carl-Oscar Jonson, PhD; David R. King, MD; Sean Kivlehan, MD, MPH; Russ S. Kotwal, MD, MPH; Jon R. Krohmer, MD; Nomi Levy-Carrick, MD, MPhil; Matthew Levy, DO, MSc, NRP; Joan José Meléndez Lugo, MD; David P. Mooney, MD, MPH; Matthew D Neal, MD; Robert Niskanen, MSEE; Patrick O’Neill, BS; Habeeba Park, MD; Peter T. Pons, MD; Erik Prytz, PhD; Todd E. Rasmussen, MD; Michael A. Remley, ATP; Robert Riviello, MD; Ali Salim, MD; Stacy Shackelfold, MD; E. Reed Smith, MD; Ronald M. Stewart, MD; Mamta Swaroop, MD; Kevin Ward, MD; Tarsicio Uribe-Leitz, MD, MPH; Molly P. Jarman, PhD, MPH; Gezzer Ortega, MD, MPH
Predicting response to immunotherapy in advanced non-small-cell lung cancer using tumor mutational burden radiomic biomarker
Authors: Bingxi He, Di Dong, Yunlang She, Caicun Zhou, Mengjie Fang, Yongbei Zhu, Henghui Zhang, Zhipei Huang, Tao Jiang, Jie Tian, Chang Chen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Tumor mutational burden (TMB) is a significant predictor of immune checkpoint inhibitors (ICIs) efficacy. This study investigated the correlation between deep learning radiomic biomarker and TMB, including its predictive value for ICIs treatment response in patients with advanced non-small-cell lung cancer (NSCLC). Methods CT images from 327 patients with TMB data (TMB median=6.067 mutations per megabase (range: 0 to 42.151)) were retrospectively collected and randomly divided into a training (n=236), validation (n=26), and test cohort (n=65). We used 3D-densenet to estimate the target tumor area, which used 1020 deep learning features to distinguish High-TMB from Low-TMB patients and establish the TMB radiomic biomarker (TMBRB). The TMBRB was developed in the training cohort combined with validation cohort and evaluated in the test cohort. The predictive value of TMBRB was assessed in a cohort of 123 NSCLC patients who had received ICIs (survival median=462 days (range: 16 to 1128)). Results TMBRB discriminated between High-TMB and Low-TMB patients in the training cohort (area under the curve (AUC): 0.85, 95% CI: 0.84 to 0.87))and test cohort (AUC: 0.81, 95% CI: 0.77 to 0.85). In this study, the predictive value of TMBRB was better than that of a histological subtype (AUC of training cohort: 0.75, 95% CI: 0.72 to 0.77; AUC of test cohort: 0.71, 95% CI: 0.66 to 0.76) or Radiomic model (AUC of training cohort: 0.75, 95% CI: 0.72 to 0.77; AUC of test cohort: 0.74, 95% CI: 0.69 to 0.79). When predicting immunotherapy efficacy, TMBRB divided patients into a high- and low-risk group with distinctly different overall survival (OS; HR: 0.54, 95% CI: 0.31 to 0.95; p=0.030) and progression-free survival (PFS; HR: 1.78, 95% CI: 1.07 to 2.95; p=0.023). Moreover, TMBRB had a better predictive ability when combined with the Eastern Cooperative Oncology Group performance status (OS: p=0.007; PFS: p=0.003). Visual analysis revealed that tumor microenvironment was important for predicting TMB. Conclusion By combining deep learning technology and CT images, we developed an individual non-invasive biomarker that could distinguish High-TMB from Low-TMB, which might inform decisions on the use of ICIs in patients with advanced NSCLC.
Is There Any Role for 18F-Fluciclovine PET/CT in the Presence of Undetectable PSA in Prostate Cancer Patients After Definitive Treatment?
Authors: Ajalaya Teyateeti, Achiraya Teyateeti, Homer A. Macapinlac, Yang Lu
Journal: Clinical Nuclear Medicine (2020)

Purpose The aim of this study was to investigate the role of 18 F-fluciclovine PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment in the presence of undetectable prostate-specific antigen (PSA). Patients and Methods This retrospective study was conducted in PC patients who had undetectable PSA level and underwent fluciclovine PET/CT within a 2-week interval of PSA examination and without interval treatment or other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on fluciclovine PET/CT were collected. Comparisons between groups of positive and negative fluciclovine PET/CT were done by using descriptive statistics. Results A total of 34 fluciclovine PET/CTs from 34 patients met the inclusion criteria. There were 4 positive (11.8%) and 30 negative fluciclovine PET/CTs (88.2%). All of the patients with positive results had an initial Gleason score of 7 or higher and locally advanced tumor (T3–T4). More common features at the time of diagnosis among positive study patients as compared with negative ones were atypical histologic variants (25% vs 0%) and very high-risk PC (50% vs 30%). Most of the patients with positive study received second-line hormonal therapy (HT) (50%), whereas patients with negative results received first-line HT (53.3%). Chemotherapy naivety was less common among positive patients (75% vs 96.7%). Sites of involvement on positive fluciclovine PET/CTs were pelvic lymph nodes (2/4, 50%), lung and mediastinal lymph node (1/4, 25%), and prostatectomy bed (1/4, 25%). Conclusions In the presence of undetectable PSA in PC patients after definitive treatment, fluciclovine PET/CT would benefit most to patients with Gleason score of 7 or higher, high disease burden (T3–T4), and atypical histologic variants at the time of diagnosis, and the ones who have history of second-line HT and/or chemotherapy.
Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities — Wyoming, 2020
Authors: Anna W. Callaghan, Anna N. Chard, Patricia Arnold, Cody Loveland, Noah Hull, Mona Saraiya, Sharon Saydah, Wendy Dumont, Laura G. Frakes, Daniel Johnson, ReaAnna Peltier, Clayton Van Houten, A. Angelica Trujillo, Jazmyn Moore, Dale A. Rose, Margaret A. Honein, David Carrington, Alexia Harrist, Susan L. Hills
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.
Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy
Authors: Qi Zhan, Kaikai Yi, Hongzhao Qi, Sidi Li, Xueping Li, Qixue Wang, Yunfei Wang, Chaoyong Liu, Mingzhe Qiu, Xubo Yuan, Jin Zhao, Xin Hou, Chunsheng Kang
Journal: Theranostics (2020)

Rationale: Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. Methods: Herein, by manipulating the exosome membrane, blood exosomes with high abundance and safety are engineered as a versatile combinatorial delivery system, where the doxorubicin (Dox) and cholesterol-modified miRNA21 inhibitor (miR-21i) are co-embedded into the lipid bilayer of exosomes, and the magnetic molecules and endosomolytic peptides L17E are bind to the exosome membrane through ligand-receptor coupling and electrostatic interactions, respectively. Results: It is proved that such engineering strategy not only preserves their intrinsic features, but also readily integrates multiple properties of tumor targeting, efficient transfection and gene/chemo combination therapy into blood exosomes. The lipid bilayer structure of exosomes allows them to co-load Dox and miR-21i with high-payloads. Moreover, profiting from the integration of magnetic molecules and L17E peptides, the engineered exosomes exhibit an enhanced tumor accumulation and an improved endosome escape ability, thereby specifically and efficiently delivering encapsulated cargos to tumor cells. As a result, a remarkable inhibition of tumor growth is observed in the tumor-bearing mice, and without noticeable side effects. Conclusions: This study demonstrates the potential of engineered blood exosomes as feasible co-delivery nanosystem for tumor-targeted and efficient combination therapy. Further development by replacing the drugs combined regimens can potentially make this engineered exosome become a general platform for the design of safe and effective combination therapy modality.
Abstract PR12: Genetic aberrations dictate distinct tumor immune landscape and chemosensitivity in HGSOC
Authors: Shuang Zhang, Sonia Iyer, Hao Ran, Wei Wei, Robert A. Weinberg, Benjamin G. Neel
Journal: Clinical Cancer Research (2020)

Abstract High-grade serous ovarian cancer (HGSOC) is the most common and deadly subtype of ovarian epithelial cancer and is known for its aggressiveness, high recurrence rate, metastasis to other sites, development of resistance to conventional chemotherapy, and general lack of response to immune checkpoint inhibitors. The absence of genomically relevant, immune-competent HGSOC models represents a major barrier to developing new therapies. Taking advantage of a mouse fallopian tube organoid system that we developed, along with lentiviral gene transduction and/or CRISPR/Cas9 technology, we generated multiple new HGSOC models containing combinations of mutations seen in human HGSOC, including homologous recombination (HR)-proficient (Tp53-/-;Ccne1amp;Akt2ampand Tp53-/-;Ccne1amp;Krasamp) and -deficient (Tp53-/-;Brca1-/-;Pten-/-and Tp53-/-;Brca1-/-;Mycamp), and poorly characterized (Tp53-/-;Pten-/-;Nf1-/-) models. These models differ in proliferation, differentiation, and polarity/organoid structure in vitro, as well as tumorigenic capacity and behavior upon orthotopic injection into syngeneic mice. Organoids bearing different mutational spectra show differential sensitivity to conventional HGSOC chemotherapies, signal transduction inhibitors and DDR inhibitors, and evoke distinctly different immune microenvironment in vivo. In particular, the immune microenvironment induced by HR-deficient tumors shows more T-cell infiltration/Treg cells, whereas HR-proficient lines show lower T-cell infiltration but higher levels of myeloid-derived suppressor cells and macrophages. The results of these studies suggest novel, genotype-informed combination therapies for this devastating disease. This abstract is also being presented as Poster B19. Citation Format: Shuang Zhang, Sonia Iyer, Hao Ran, Wei Wei, Robert A. Weinberg, Benjamin G. Neel. Genetic aberrations dictate distinct tumor immune landscape and chemosensitivity in HGSOC [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr PR12.
Targeting p16<sup>INK4a</sup> Promotes Lipofibroblasts and Alveolar Regeneration after Early-Life Injury
Authors: Maéva Zysman, Bruno Ribeiro Baptista, Laure-Aléa Essari, Sara Taghizadeh, Charlotte Thibault de Ménonville, Clément Giffard, Amelle Issa, Marie-Laure Franco-Montoya, Marielle Breau, Rachid Souktani, Abdel Aissat, Laurence Caeymaex, Muriel Lizé, Jeanne Tran Van Nhieu, Camille Jung, Robert Rottier, Marcio Do Cruzeiro, Serge Adnot, Ralph Epaud, François Chabot, Sophie Lanone, Jorge Boczkowski, Laurent Boyer
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Promoting endogenous pulmonary regeneration is crucial after damage to restore normal lungs and prevent the onset of chronic adult lung diseases.Objectives: To investigate whether the cell-cycle inhibitor p16INK4a limits lung regeneration after newborn bronchopulmonary dysplasia (BPD), a condition characterized by the arrest of alveolar development, leading to adult sequelae.Methods: We exposed p16INK4a-/- and p16INK4aATTAC (apoptosis through targeted activation of caspase 8) transgenic mice to postnatal hyperoxia, followed by pneumonectomy of the p16INK4a-/- mice. We measured p16INK4a in blood mononuclear cells of preterm newborns, 7- to 15-year-old survivors of BPD, and the lungs of patients with BPD.Measurements and Main Results: p16INK4a concentrations increased in lung fibroblasts after hyperoxia-induced BPD in mice and persisted into adulthood. p16INK4a deficiency did not protect against hyperoxic lesions in newborn pups but promoted restoration of the lung architecture by adulthood. Curative clearance of p16INK4a-positive cells once hyperoxic lung lesions were established restored normal lungs by adulthood. p16INK4a deficiency increased neutral lipid synthesis and promoted lipofibroblast and alveolar type 2 (AT2) cell development within the stem-cell niche. Besides, lipofibroblasts support self-renewal of AT2 cells into alveolospheres. Induction with a PPARγ (peroxisome proliferator-activated receptor γ) agonist after hyperoxia also increased lipofibroblast and AT2 cell numbers and restored alveolar architecture in hyperoxia-exposed mice. After pneumonectomy, p16INK4a deficiency again led to an increase in lipofibroblast and AT2 cell numbers in the contralateral lung. Finally, we observed p16INK4a mRNA overexpression in the blood and lungs of preterm newborns, which persisted in the blood of older survivors of BPD.Conclusions: These data demonstrate the potential of targeting p16INK4a and promoting lipofibroblast development to stimulate alveolar regeneration from childhood to adulthood.
Clinical Features of Patients Infected With Coronavirus Disease 2019 With Elevated Liver Biochemistries: A Multicenter, Retrospective Study
Authors: Yu Fu, Rui Zhu, Tao Bai, Ping Han, Qin He, Mengjia Jing, Xiaofeng Xiong, Xi Zhao, Runze Quan, Chaoyue Chen, Ying Zhang, Meihui Tao, Jianhua Yi, Dean Tian, Wei Yan
Journal: Hepatology (2020)

Background and Aims In December 2019, an outbreak of coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China. Although it has been reported that some patients with COVID‐19 showed elevated liver biochemistries, there are few studies regarding the clinical features and prognosis of these patients. Approach and Results In this multicenter, retrospective study, we collected data on laboratory‐confirmed patients with COVID‐19 from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. Data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase, aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. Multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C‐reactive protein level (OR, 1.007; P = 0.008), elevated white blood count (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in patients with COVID‐19. Conclusions Elevated liver biochemistries were common in patients with COVID‐19. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.
Biomaterial 3D collagen I gel culture model: A novel approach to investigate tumorigenesis and dormancy of bladder cancer cells induced by tumor microenvironment
Authors: Yaqi Qiu, Shi Qiu, Linghui Deng, Ling Nie, Lina Gong, Xinyang Liao, Xiaonan Zheng, Kun Jin, Jiakun Li, Xiang Tu, Liangren Liu, Zhenhua Liu, Yige Bao, Jianzhong Ai, Tianhai Lin, Lu Yang, Qiang Wei
Journal: Biomaterials (2020)
Assessing small airway function for early detection of lung function impairment
Authors: S. Hasan Arshad, Ramesh Kurukulaaratchy, Hongmei Zhang, Claire Hodgekiss, Wilfried Karmaus, John W. Holloway, Graham Roberts
Journal: European Respiratory Journal (2020)

<b>Both impulse oscillometry and spirometry provide comparable information for small to mid-airway function. However, spirometry is more sensitive in detecting bronchodilator reversibility.</b>https://bit.ly/2XyQ0Sa
Impact of disconnected pancreatic duct syndrome on endoscopic ultrasound-guided drainage of pancreatic fluid collections
Authors: Lillian Wang, Sherif Elhanafi, Andrew C. Storm, Mark D. Topazian, Shounak Majumder, Barham K. Abu Dayyeh, Michael J. Levy, Bret T. Petersen, John A. Martin, Suresh T. Chari, Santhi S. Vege, Vinay Chandrasekhara
Journal: Endoscopy (2020)

Endoscopic intervention for pancreatic fluid collections (PFCs) with disconnected pancreatic duct syndrome (DPDS) has been associated with failures and increased need for additional endoscopic and non-endoscopic interventions. The primary aim of this study was to determine the outcomes of endoscopic ultrasound (EUS)-guided transmural drainage of PFCs in patients with DPDS.In patients undergoing EUS-guided drainage of PFCs from January 2013 to January 2018, demographic profiles, procedural indications and details, adverse events, outcomes, and subsequent interventions were retrospectively collected. Overall treatment success was determined by PFC resolution on follow-up imaging or stent removal without recurrence.EUS-guided drainage of PFCs was performed in 141 patients. DPDS was present in 57 of them (40 %) and walled-off necrosis was the most frequent type of PFC (55 %). DPDS was not associated with lower clinical success, increased number of repeat interventions, or increased time to PFC resolution. Patients with DPDS were more likely to be treated with permanent transmural plastic double-pigtail stents (odds ratio [OR] 6.4; 95 % confidence interval [CI] 2.5 - 16.5; P < 0.001). However, when stents were removed, DPDS was associated with increased PFC recurrence after stent removal (OR 8.0; 95 %CI 1.2 - 381.8; P = 0.04).DPDS frequently occurs in patients with PFCs but does not negatively impact successful resolution. DPDS is associated with increased PFC recurrence after stent removal.