tbuckley/cabot-search huggingface dataset:
Trajectories of Posttraumatic Stress in Youths After Natural Disasters
Authors: Betty S. Lai, Annette M. La Greca, Ahnalee Brincks, Courtney A. Colgan, Michelle P. D’Amico, Sarah Lowe, Mary Lou Kelley
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Disaster exposure is associated with the development of posttraumatic stress (PTS) symptoms in youths. However, little is known about how to predict which youths will develop chronic PTS symptoms after disaster exposure. <h3>Objective</h3> To evaluate PTS symptom trajectories among youths after 4 major US hurricanes and assess factors associated with those trajectories. <h3>Design, Setting, and Participants</h3> This cohort study used integrative data analysis to combine data from 4 studies of youths’ responses to natural disasters (hurricanes Andrew [1992], Charley [2004], Ike [2005], and Katrina [2008]) at time points ranging from 3 to 26 months after the disasters. Those studies recruited and surveyed youths aged 6 to 16 years at schools via convenience sampling of schools near the path of destruction for each hurricane. This study was conducted from August 2017 to August 2020, and pooled data were analyzed from February 2019 to October 2020. <h3>Exposure</h3> Experience of a natural disaster during the ages of 6 to 16 years. <h3>Main Outcomes and Measures</h3> Posttraumatic stress symptoms were assessed using the University of California, Los Angeles, Posttraumatic Stress Disorder Reaction Index (UCLA PTSD-RI) and the UCLA PTSD-RI-Revised. Latent class growth analyses were used to evaluate the youths’ PTS symptom trajectories and associated factors. <h3>Results</h3> Among 1707 youths included in the study, the mean (SD) age was 9.61 (1.60) years, 922 (54%) were female, and 785 (46%) self-identified as White non-Hispanic. Four PTS symptom trajectories were identified: chronic (171 participants [10%]), recovery (393 [23%]), moderate-stable (563 [33%]), and low-decreasing (580 [34%]). Older youths were less likely to be in the chronic group; compared with the chronic group, each 1-year increase in age was associated with increased odds of being in the other groups (recovery: odds ratio [OR], 1.78 [95% CI, 1.29-2.48]; moderate-stable: OR, 1.94 [95% CI, 1.43-2.62]; and low-decreasing: OR, 2.71 [95% CI, 1.99-3.71]). Compared with males, females had higher odds of being in the chronic group than in any other group (recovery group: OR, 0.48 [95% CI, 0.26-0.91]; moderate-stable group: OR, 0.37 [95% CI, 0.21-0.64]; and low-decreasing group: OR, 0.25 [95% CI, 0.14-0.44]). <h3>Conclusions and Relevance</h3> In this cohort study, few youths reported chronic distress, and trajectories among most youths reflected recovery or low-decreasing PTS symptoms. Older age and identification as male were factors associated with decreased odds of a chronic trajectory. Youths with chronic or moderate-stable trajectories may benefit from intervention.
Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai
Authors: Indraneel Mittra, Gauravi A Mishra, Rajesh P Dikshit, Subhadra Gupta, Vasundhara Y Kulkarni, Heena Kauser A Shaikh, Surendra S Shastri, Rohini Hawaldar, Sudeep Gupta, C S Pramesh, Rajendra A Badwe
Journal: BMJ (2021)

To test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening. Prospective, cluster randomised controlled trial. 20 geographically distinct clusters located in Mumbai, India, randomly allocated to 10 screening and 10 control clusters; total trial duration was 20 years (recruitment began in May 1998; database locked in March 2019 for analysis). 151 538 women aged 35-64 with no history of breast cancer. Women in the screening arm (n=75 360) received four screening rounds of clinical breast examination (conducted by trained female primary health workers) and cancer awareness every two years, followed by five rounds of active surveillance every two years. Women in the control arm (n=76 178) received one round of cancer awareness followed by eight rounds of active surveillance every two years. Downstaging of breast cancer at diagnosis and reduction in mortality from breast cancer. Breast cancer was detected at an earlier age in the screening group than in the control group (age 55.18 (standard deviation 9.10) v 56.50 (9.10); P=0.01), with a significant reduction in the proportion of women with stage III or IV disease (37% (n=220) v 47% (n=271), P=0.001). A non-significant 15% reduction in breast cancer mortality was observed in the screening arm versus control arm in the overall study population (age 35-64; 20.82 deaths per 100 000 person years (95% confidence interval 18.25 to 23.97) v 24.62 (21.71 to 28.04); rate ratio 0.85 (95% confidence interval 0.71 to 1.01); P=0.07). However, a post hoc subset analysis showed nearly 30% relative reduction in breast cancer mortality in women aged 50 and older (24.62 (20.62 to 29.76) v 34.68 (27.54 to 44.37); 0.71 (0.54 to 0.94); P=0.02), but no significant reduction in women younger than 50 (19.53 (17.24 to 22.29) v 21.03 (18.97 to 23.44); 0.93 (0.79 to 1.09); P=0.37). A 5% reduction in all cause mortality was seen in the screening arm versus the control arm, but it was not statistically significant (rate ratio 0.95 (95% confidence interval 0.81 to 1.10); P=0.49). These results indicate that clinical breast examination conducted every two years by primary health workers significantly downstaged breast cancer at diagnosis and led to a non-significant 15% reduction in breast cancer mortality overall (but a significant reduction of nearly 30%in mortality in women aged ≥50). No significant reduction in mortality was seen in women younger than 50 years. Clinical breast examination should be considered for breast cancer screening in low and middle income countries. Clinical Trials Registry of India CTRI/2010/091/001205; ClinicalTrials.gov NCT00632047.
Genome‐Wide Reduction in Chromatin Accessibility and Unique Transcription Factor Footprints in Endothelial Cells and Fibroblasts in Scleroderma Skin
Authors: Pei‐Suen Tsou, Pamela J. Palisoc, Mustafa Ali, Dinesh Khanna, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2021)

Systemic sclerosis (SSc) is characterized by widespread fibrosis and vascular complications. This study was undertaken to examine the chromatin landscape and transcription factor footprints in SSc, using an assay for genome-wide chromatin accessibility.Dermal endothelial cells (ECs) and fibroblasts were isolated from healthy controls and patients with diffuse cutaneous SSc (dcSSc). Assay for transposase-accessible chromatin with sequencing (ATAC-seq) was performed to assess genome-wide chromatin accessibility at a read depth of ~150 million reads per sample. Transcription factor footprinting and motif binding analysis were performed, followed by functional experiments.Chromatin accessibility was significantly reduced in dcSSc patients compared to healthy controls. Differentially accessible chromatin loci were enriched in pathways and gene ontologies involved in the nervous system, cell membrane projections and cilia motility, nuclear and steroid receptors, and nitric oxide. In addition, chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. We found significant down-regulation of the neuronal gene NRXN1 and up-regulation of SNAI2 and ETV2 in dcSSc ECs. In dcSSc fibroblasts, down-regulation of the neuronal gene ENTPD1 and up-regulation of RUNX2 were confirmed. Further functional analysis revealed that ETV2 and NRXN1 dysregulation affected angiogenesis in ECs, while ENTPD1 enhanced profibrotic properties in dcSSc fibroblasts.Our data identify the chromatin blueprint of dcSSc, and suggest that neuronal-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting the key pathways and transcription factors identified might present novel therapeutic approaches in SSc.
Patients Hospitalized for De Novo Versus Worsening Chronic Heart Failure in the United States
Authors: Stephen J. Greene, Taylor S. Triana, Raluca Ionescu-Ittu, Sherry Shi, Annie Guérin, Mary M. DeSouza, Paul D. Kessler, Aylin Tugcu, Maria Borentain, G. Michael Felker
Journal: Journal of the American College of Cardiology (2021)
Diagnosis and Treatment of Multiple Sclerosis
Authors: Marisa P. McGinley, Carolyn H. Goldschmidt, Alexander D. Rae-Grant
Journal: JAMA (2021)

<h3>Importance</h3> Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. <h3>Observations</h3> MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid–specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. <h3>Conclusions and Relevance</h3> MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.
Wireless skin sensors for physiological monitoring of infants in low-income and middle-income countries
Authors: Shuai Xu, Alina Y Rwei, Bellington Vwalika, Maureen P Chisembele, Jeffrey S A Stringer, Amy Sarah Ginsburg, John A Rogers
Journal: The Lancet Digital Health (2021)

Globally, neonatal mortality remains unacceptability high. Physiological monitoring is foundational to the care of these vulnerable patients to assess neonatal cardiopulmonary status, guide medical intervention, and determine readiness for safe discharge. However, most existing physiological monitoring systems require multiple electrodes and sensors, which are linked to wires tethered to wall-mounted display units, to adhere to the skin. For neonates, these systems can cause skin injury, prevent kangaroo mother care, and complicate basic clinical care. Novel, wireless, and biointegrated sensors provide opportunities to enhance monitoring capabilities, reduce iatrogenic injuries, and promote family-centric care. Early validation data have shown performance equivalent to (and sometimes exceeding) standard-of-care monitoring systems in premature neonates cared for in high-income countries. The reusable nature of these sensors and compatibility with low-cost mobile phones have the future potential to enable substantially lower monitoring costs compared with existing systems. Deployment at scale, in low-income countries, holds the promise of substantial improvements in neonatal outcomes.
CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images
Authors: Tahereh Javaheri, Morteza Homayounfar, Zohreh Amoozgar, Reza Reiazi, Fatemeh Homayounieh, Engy Abbas, Azadeh Laali, Amir Reza Radmard, Mohammad Hadi Gharib, Seyed Ali Javad Mousavi, Omid Ghaemi, Rosa Babaei, Hadi Karimi Mobin, Mehdi Hosseinzadeh, Rana Jahanban-Esfahlan, Khaled Seidi, Mannudeep K. Kalra, Guanglan Zhang, L. T. Chitkushev, Benjamin Haibe-Kains, Reza Malekzadeh, Reza Rawassizadeh
Journal: npj Digital Medicine (2021)

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95% compared to radiologists (70%). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership.
Abstract PS17-31: Investigating the estrogen receptor Y537S mutation in transgenic models of luminal B breast cancer
Authors: Gabriella Johnson, Joshua Roccamo, Cynthia Lavoie, Dongmei Zuo, Virginie Sanguin-Gendreau, Adrian Lee, Zheqi Li, Steffi Oesterreich, William Muller
Journal: Cancer Research (2021)

Abstract Breast cancer is the most prevalent cancer in women and over two-thirds of cases express the estrogen receptor (ER). Significantly, metastatic ER positive breast cancer is the leading cause of breast cancer mortality. Despite the success of endocrine therapy to treat ER-positive breast cancers, resistance to treatment is a major problem and relapse commonly occurs though patients initially respond well to treatment. The ER Y537S mutant represents one of the most common gain-of-function mutations detected in the metastatic biopsies of patients with ER-positive breast cancer. Previous in-vitro analyses have shown that the ER Y537S mutant exhibits enhanced ER transcriptional activity by adopting a ligand-independent agonist confirmation. In our study, we seek to provide a deeper understanding of the role of this mutant by modeling the human ER Y537S mutant (ER Y541S in mice). Our lab has generated a Cre-inducible knock-in mouse model expressing the activating point mutation driven by the endogenous ER promoter, and it has been shown that when expressed ubiquitously the mutated ER leads to dramatic developmental effects. In order to further our observations in the context of endocrine resistant metastatic breast cancer, we characterize mamary tumour growth of the ER Y541S mutant in combination with luminal B models of mammary tumourigenesis. Consistent with the notion that these ER mutations occur seldom in primary tumours, preliminary data shows that tumour onset and tumour outgrowth is unaffected by the activating point mutation. When analysing tumours from both ER mutant and wildtype ER control animals, it was found that tumours with mutant ER display more basal-like cytokeratins at the RNA level via RNA sequencing and at the protein level via immunohistochemistry. This expression pattern is often associated with poorer prognosis in the clinic. Through ongoing analyses, we also seek to better understand our model through tumour regression studies (doxycycline withdrawal), treatment with tamoxifen and blocking the main source of estrogens via ovariotomies. By studying the ER Y537S mutation in models of luminal B breast cancer, we hope to investigate the factors leading to tumour recurrence and provide a deeper understanding of potential escape pathways to therapy. Citation Format: Gabriella Johnson, Joshua Roccamo, Cynthia Lavoie, Dongmei Zuo, Virginie Sanguin-Gendreau, Adrian Lee, Zheqi Li, Steffi Oesterreich, William Muller. Investigating the estrogen receptor Y537S mutation in transgenic models of luminal B breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-31.
Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study
Authors: W Wolfgang Fleischhacker, Jana Podhorna, Martina Gröschl, Sanjay Hake, Yihua Zhao, Songqiao Huang, Richard S E Keefe, Michael Desch, Ronald Brenner, David P Walling, Emilio Mantero-Atienza, Kazuyuki Nakagome, Stephane Pollentier
Journal: The Lancet Psychiatry (2021)
Lysophospholipid acylation modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle
Authors: Patrick J. Ferrara, Xin Rong, J. Alan Maschek, Anthony R.P. Verkerke, Piyarat Siripoksup, Haowei Song, Thomas D. Green, Karthickeyan C. Krishnan, Jordan M. Johnson, John Turk, Joseph A. Houmard, Aldons J. Lusis, Micah J. Drummond, Joseph M. McClung, James E. Cox, Saame Raza Shaikh, Peter Tontonoz, William L. Holland, Katsuhiko Funai
Journal: Journal of Clinical Investigation (2021)

Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analysis of primary myocytes from individuals who were insulin-sensitive and lean (LN) or insulin-resistant with obesity (OB) revealed several species of lysophospholipids (lyso-PLs) that were differentially abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle–specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lysophosphatidylcholine/phosphatidylcholine, concomitant with improved skeletal muscle insulin sensitivity. Conversely, skeletal muscle–specific overexpression of LPCAT3 (LPCAT3-MKI) promoted glucose intolerance. The absence of LPCAT3 reduced phospholipid packing of cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.
Small extracellular vesicles‐based cell‐free strategies for therapy
Authors: Yeye Guo, Huaishan Wang, Lili Huang, Lingling Ou, Jinjin Zhu, Shujing Liu, Xiaowei Xu
Journal: MedComm (2021)

Small extracellular vesicles (sEVs) are extracellular nanovesicles that contain bioactive proteins, lipids, RNA, and DNA. A variety of biological process is regulated with sEVs. sEVs are an intercellular messenger regulating recipient cell function and play a role in disease initiation and progression. sEVs derived from certain cells, such as mesenchymal stem cells and immune cells, have the potential for clinical therapy as they possess the characteristics of their parental cells. With better understanding of sEVs biogenesis, their transportation properties, extended circulatory capability, and exceptional biocompatibility, sEVs emerge as a potential therapeutic tool in the clinic. Here, we summarize applications of sEVs-based therapies in different diseases and current knowledge about the strategies in bioengineered sEVs, as well as the challenges for their use in clinical settings.
SVR12 Rate of 98.6% in 992 HCV Genotype 1b-Infected Patients Treated with ABT-450/r/Ombitasvir and Dasabuvir With or Without Ribavirin
Authors: Massimo Colombo, Ola Weiland, Daniel E. Cohen, Jean-Francois J. DuFour, Hendrik Reynaert, Moises Diago, Erica Villa, Adrian Streinu-Cercel, Wangang Xie, Tolga Baykal, Jeffrey Enejosa, Eoin Coakley, Roger Trinh, Thomas Podsadecki
Journal: Hepatology (2014)
Corrigendum to ‘Long acting anti-infection constructs on titanium [Journal of Controlled Release 326 (2020) 91–105]’
Authors: Stefano Perni, Hadil Faris Alotaibi, Abdulla A. Yergeshov, Trinh Dang, Timur I. Abdullin, Polina Prokopovich
Journal: Journal of Controlled Release (2021)
Abstract PS14-25: Outcomes of metastatic male breast cancer
Authors: Izzet Dogan, Nijat Khanmammadov, Adnan Aydıner, Pınar Saip
Journal: Cancer Research (2021)

Abstract Background: Breast cancer is rare in men. The prognosis of male breast cancer (MBC) is poor than female breast cancer. The study aims to evaluate the clinical features and prognosis in metastatic male breast cancer (mMBC). Method: The data of 28 patients were retrospectively reviewed. The clinical and histopathological features of the patients were recorded. Overall survival (OS) and prognostic factors evaluated with Kaplan-Meier analysis and Cox-regression analysis. Results: The median follow-up period was 55.1 months (range, 6.6-205.6). The median age at diagnosis was 57 years (range, 26-86). Seven (27%) of the patients were de-novo metastatic. Invasive ductal carcinoma (92.6%) was the most common pathological subtype. The ratio of HER2 positivity in patients was 21.6%, and estrogen and progesterone receptor's positivity were 96.4% and 71.4%, respectively. The most common metastatic locations of disease were bone-75%, lung-39.3%, brain-21.4%, and surrenal-10.7%. Six of the patients received trastuzumab-based chemotherapy. A total of 14 (50%) patients deceased during the study period. The median OS was 42.6±10.7 months (range, 21.6-63.7) for all patients. One-, three- and five-years overall survival ratios were 95.7%, 54.2%, and 36.6%, respectively. In univariate analysis, Brain metastasis (p=0.033), the number of metastatic sites (p=0.045), and the history of regular alcohol consumption (p=0.008) were a statistically significant factor on OS. However, the results were not confirmed in multivariate analysis. Also, we found that trastuzumab-based treatment and de-novo metastasis were not affecting on OS in mMBC. Conclusions: Due to the rarity, the data of mMBC is limited. In this study, we observed that the prognosis of mMBC was poor. Despite the low number of patients, we detected that having brain metastasis, the number of metastatic sites, and history of alcohol consumption may be a prognostic factor in univariate analysis. Citation Format: Izzet Dogan, Nijat Khanmammadov, Adnan Aydıner, Pınar Saip. Outcomes of metastatic male breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-25.