tbuckley/cabot-search huggingface dataset:
Amniotic fluid biomarkers predict the severity of congenital cytomegalovirus infection
Authors: Olesya Vorontsov, Lorinne Levitt, Daniele Lilleri, Gilad W. Vainer, Orit Kaplan, Licita Schreiber, Alessia Arossa, Arseno Spinillo, Milena Furione, Or Alfi, Esther Oiknine-Djian, Meital Kupervaser, Yuval Nevo, Sharona Elgavish, Moran Yassour, Maurizio Zavattoni, Tali Bdolah-Abram, Fausto Baldanti, Miriam Geal-Dor, Zichria Zakay-Rones, Nili Yanay, Simcha Yagel, Amos Panet, Dana G. Wolf
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDCytomegalovirus (CMV) is the most common intrauterine infection, leading to infant brain damage. Prognostic assessment of CMV-infected fetuses has remained an ongoing challenge in prenatal care, in the absence of established prenatal biomarkers of congenital CMV (cCMV) infection severity. We aimed to identify prognostic biomarkers of cCMV-related fetal brain injury.METHODSWe performed global proteome analysis of mid-gestation amniotic fluid samples, comparing amniotic fluid of fetuses with severe cCMV with that of asymptomatic CMV-infected fetuses. The levels of selected differentially excreted proteins were further determined by specific immunoassays.RESULTSUsing unbiased proteome analysis in a discovery cohort, we identified amniotic fluid proteins related to inflammation and neurological disease pathways, which demonstrated distinct abundance in fetuses with severe cCMV. Amniotic fluid levels of 2 of these proteins - the immunomodulatory proteins retinoic acid receptor responder 2 (chemerin) and galectin-3-binding protein (Gal-3BP) - were highly predictive of the severity of cCMV in an independent validation cohort, differentiating between fetuses with severe (n = 17) and asymptomatic (n = 26) cCMV, with 100%-93.8% positive predictive value, and 92.9%-92.6% negative predictive value (for chemerin and Gal-3BP, respectively). CONCLUSIONAnalysis of chemerin and Gal-3BP levels in mid-gestation amniotic fluids could be used in the clinical setting to profoundly improve the prognostic assessment of CMV-infected fetuses.FUNDINGIsrael Science Foundation (530/18 and IPMP 3432/19); Research Fund - Hadassah Medical Organization.
First Extensive Analysis of <sup>18</sup>F-Labeled Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in a Large Cohort of Patients With HIV-Associated Hodgkin Lymphoma: Baseline Total Metabolic Tumor Volume Affects Prognosis
Authors: Nicolas Louarn, Lionel Galicier, Rémi Bertinchamp, David Lussato, Françoise Montravers, Éric Oksenhendler, Pascal Merlet, Laurence Gérard, Laetitia Vercellino
Journal: Journal of Clinical Oncology (2022)

18F-labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) data in HIV-associated Hodgkin lymphoma (HIV-HL) are scarcely reported. In addition to the description of the characteristics of both baseline and interim 18F-FDG PET-CT examinations (PET1 and iPET, respectively), the aim of this study was to assess the prognostic value of PET1 and previously identified clinical parameters in this population.PET1 of 109 patients with HIV-HL, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy regimen since 2007, and 104 iPET were centrally reviewed. All the patients were enrolled in an ongoing prospective single-center cohort of HIV-associated lymphoma.Most patients had a disseminated disease according to the Ann Arbor classification (30% stage III and 43% stage IV), with especially bone marrow and liver as extranodal localizations. After a median follow-up of 6.7 years, 12 patients relapsed (11%) and 13 died (12%). Five-year progression-free survival (PFS) was 75.1%, and 5-year overall survival was 86.1%. Median total metabolic tumor volume (TMTV) was 121.4 cm3. The optimal TMTV cutoff identified for prognostic analysis was 527 cm3, with a 2-year PFS of 71% in the 20 patients with TMTV > 527 cm3, compared with 91% in the 89 patients with TMTV ≤ 527 cm3 (P = .004). On multivariate analysis, a high TMTV was the only parameter independently associated with PFS.In this large series of HIV-HL patients with a homogeneous management, high TMTV on PET1 examination was associated with a poor prognosis.
Abstract P214: Plant-based Diets And Risk Of Hospitalization With Respiratory Infection: Results From The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Karla Kendrick, Hyunju Kim, Rebholz Casey, Elizabeth Selvin, Lyn Steffen, Stephen P Juraschek
Journal: Circulation (2022)

Introduction: The benefits of plant-based diets may depend on the type of plant; unhealthy plant foods, such as sugar and refined grains, have detrimental health consequences. Micronutrients in plants decrease inflammation and are essential for proper immune function. Deficiencies in these nutrients can contribute to a pro-inflammatory state and may increase risk of infection. Methods: We conducted a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) Study. Participants completed food frequency questionnaires in 1993-1996 (visit 3). We used reported intakes to calculate a plant-based diet index (PDI), healthy plant-based diet index (hPDI), and an unhealthy plant-based diet (uPDI). Active surveillance is conducted for all hospitalizations. We used Cox models to examine the associations of three plant-based diet indices (in quintiles) with risk of pneumonia and influenza, and other infection-related hospitalizations identified by ICD codes. Results: In our sample of 11,956 adults there were 2522 hospitalizations with respiratory infections and 4308 hospitalizations with any infection during a median follow-up of ~22 years. The incidence of hospitalization with respiratory infections and any infection was lower among those adults consuming more plant-based foods (Table) . Higher hPDI was associated with a lower risk of hospitalization with any infection or respiratory infection. Higher PDI was associated with a lower risk of hospitalization with any infection. Significant associations were not observed with the uPDI. Conclusions: Adults who adhere to diets high in any plant foods, as well as healthy plant foods, have a lower risk of hospitalization with infections. Adherence to diets high in healthy plant foods specifically is associated with lower risk of hospitalizations with respiratory infections.
All-Trans Retinoic Acid Plus Low-Dose Rituximab Vs Low-Dose Rituximab in Corticosteroid-Resistant or Relapsed ITP
Authors: Ye-Jun Wu, Hui Liu, Qiao-Zhu Zeng, Yi Liu, Jing-Wen Wang, Wen-Sheng Wang, Jia Feng, He-Bing Zhou, Qiu-Sha Huang, Hai-Xia Fu, Xiao-Lu Zhu, Yun He, Hao Jiang, Ying-Jun Chang, Lan-Ping Xu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2021)
Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis
Authors: Wilian Correa-Macedo, Vinicius M. Fava, Marianna Orlova, Pauline Cassart, Ron Olivenstein, Joaquín Sanz, Yong Zhong Xu, Anne Dumaine, Renata H.M. Sindeaux, Vania Yotova, Alain Pacis, Josée Girouard, Barbara Kalsdorf, Christoph Lange, Jean-Pierre Routy, Luis B. Barreiro, Erwin Schurr
Journal: Journal of Clinical Investigation (2021)

Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (M. tuberculosis) followed by rapid progression to disease. Alveolar macrophages (AMs) are the first cells of the innate immune system that engage M. tuberculosis, but how HIV and antiretroviral therapy (ART) affect the anti-mycobacterial response of AMs is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AMs to M. tuberculosis, we obtained AMs by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as preexposure prophylaxis (PrEP) to prevent HIV infection. Following in vitro challenge with M. tuberculosis, AMs from each group displayed overlapping but distinct profiles of significantly up- and downregulated genes in response to M. tuberculosis. Comparatively, AMs isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AMs from HC subjects challenged with M. tuberculosis responded with pronounced chromatin accessibility changes while AMs obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AMs.
Cardiomyocytic FoxP3 is involved in Parkin-mediated mitophagy during cardiac remodeling and the regulatory role of triptolide
Authors: Xi-Chun Pan, Ya-Lan Xiong, Jia-Hui Hong, Ya Liu, Yan-Yan Cen, Tao Liu, Qun-Fang Yang, Hui Tao, Yu-Nong Li, Hai-Gang Zhang
Journal: Theranostics (2022)

Rationale: Forkhead/winged helix transcriptional factor P3 (FoxP3) is a well-studied transcription factor that maintains the activity of T cells, but whether cardiomyocytic FoxP3 participates in cardiac remodeling (CR) remains unclear.The present study was to investigate the role of cardiomyocytic FoxP3 in CR from the perspective of mitophagy.Methods: CR was induced by angiotensin II (AngII) in vitro, or by isoproterenol (Iso) in vivo using male C57 mice or FoxP3 DTR mice.Histological changes were observed by hematoxylin-eosin and Masson staining.Molecular changes were detected by immunohistochemistry, immunofluorescence, immunoblotting, and real-time PCR.Mitophagy was shaped by transmission electron microscopy and co-localization.The mRNA expression was operated by siRNA or adeno associated virus (AAV).Molecular interactions were detected by co-localization, immunoprecipitation (IP), and chromatin IP.Results: The expression and nuclear translocation of cardiomyocytic FoxP3 were downregulated in CR, while they were upregulated after triptolide (TP) treatment.In left ventricle (LV) remodeling in mice, autophagy was activated continuously in the myocardium, and TP significantly attenuated it.AngII induced massive mitophagy characterized by the activation of autophagy regulatory protein 5 (Atg5)-dependent autophagic flux.Critically, Parkin was identified as the main adaptor mediated myocardial mitophagy and was responsible for the effect of TP.Moreover, FoxP3 was responsible for the downregulation of Parkin and inhibited AngII-induced cardiac mitophagy.We found that mitophagy increased significantly and the inhibition of TP treatment reversed completely in FoxP3-deficient LVs.Mechanistically, FoxP3 interacted with a motif located downstream of the activating transcription 4 (ATF4)-binding motif involved in the promoter of Parkin and hijacked free nuclear ATF4 to decrease Parkin mRNA expression in CR.Conclusion: Cardiomyocytic FoxP3 could negatively regulate Parkin-mediated mitophagy in CR, and restoring cardiomyocytic FoxP3 activity provided a cardioprotective strategy by inhibiting excessive cardiac mitophagy.
Abstract P230: Chronically Uncertain: How Families Of Children With Hypoplastic Left Heart Syndrome Manage The Condition
Authors: Michael D Green
Journal: Circulation (2022)

Introduction: 41 years ago, comfort care was the only choice for families to care for children with Hypoplastic Left Heart Syndrome (HLHS), meaning that all children born with this condition would die. Recent developments in biomedical care provides families other options. This condition is extremely rare, and research is primarily quantitative and focused on interventions to prolong the life of individuals effected. There is a research gap on barriers and facilitators to care for these families. Objective: Qualitatively describe everyday experience and illuminate social determinants of health for families who have a child with Hypoplastic Left Heart Syndrome. Methods: 5 families currently seeking care for their child at Dartmouth-Hitchcock Health were interviewed using a semi-structured interview guide. These families were recruited through physician referral, and this study was deemed exempt by the Dartmouth-Hitchcock Health Institutional Review Board. The interview transcripts were coded and subsequently examined for overarching themes utilizing deductive analysis. Additionally, the 2 physicians who provided referrals were interviewed separately from the families to illuminate their perspective, and compare them to the families'. Results: The families interviewed in this study are in a chronic state of uncertainty involving their child’s condition. Clinicians provide medical advice and guidance on what physically happens with these children’s bodies. Still, these physical observations have large implications on life outside of the clinic. Surgical interventions for HLHS were unsuccessful for a long period but are now improving clinical outcomes, the families interviewed are hopeful about other biomedical innovations that could help them. Conclusion: These families still do not know what their future holds because when they were first informed of their child’s diagnosis, they were told they were going into a rapidly developing research landscape. Their outcome in this landscape was one where their children were all able to live through the first three intensive procedures that reconstructed their child’s heart. Despite the chronic uncertainty they face, they also are chronically hopeful for biomedical innovation to enhance their lifestyle.
Abstract P031: Does The Place Of Residence Influence Your Risk Of Being Hypertensive? A Case Study From Nepal
Authors: Ishor Sharma, Karen Campbell, Jason M Were, Juan Camilo Vargas-Gonzalez, Saverio Stranges
Journal: Circulation (2022)

Introduction: Area level factors could be an independent risk factor for disease and negative health outcomes. Despite the multiple studies on risk factors for hypertension, area-level influence is poorly investigated especially in low- and middle-income countries. Hypothesis: This study aims to test the hypothesis that area-level deprivation (AD) is significantly associated with the risk of hypertension independent of individual risk factors in the context of Nepal. Methods: The study is based on the latest Nepal Demographic Health Survey conducted in 2016. The area-level deprivation index was constructed and validated based on the material (household assets, household structure), social and geospatial features. The index ranged from 52 to 146 with higher scores representing higher levels of deprivation. Individuals aged 15 and above were identified as hypertensive if they met any of the following criteria: i) systolic blood pressure ≥140 mmHg; ii) diastolic blood pressure ≥90 mmHg; iii) taking antihypertensive medication irrespective of their blood pressure readings during the survey; iv) history of earlier diagnosis of hypertension by any health care provider. Associations between the quartiles of AD and hypertension were investigated using two-level logistic regression. Further, potential cross-level interaction and mediated pathways between AD and hypertension were explored. Results: The overall prevalence of hypertension was approximately 23% of which nearly 50% were unaware of their high blood pressure status at the time of the survey. Individuals from the least deprived areas seemed to have higher odds of hypertension compared to highly deprived areas (Odds Ratio=1.54 (95% CI 1.26, 1.89); p-trend=&lt;0.001). Literate individuals from deprived areas were likely to have a higher risk of hypertension compared to those without formal education. However, the association was not significant in the least deprived areas (p-interaction &lt;0.001). Overweight/obesity seems to explain a significant magnitude of the indirect pathway (67%) between AD and hypertension in the context of Nepal. Conclusion: Residing in the least deprived or more affluent areas might increase an individual’s risk of being hypertensive. Association between individual risk factors and hypertension is likely to vary across the areas with varying levels of deprivation. These results seem paradoxical and are inconsistent with epidemiological data from high-income countries. Over-nutrition and changing lifestyle, driven by affluence and higher disposable income, could explain this counterintuitive association in the context of a country like Nepal which is undergoing a rapid socio-demographic and epidemiological transition.
Social Functioning in Individuals Affected by Childhood Maltreatment: Establishing a Research Agenda to Inform Interventions
Authors: Monique C. Pfaltz, Sarah L. Halligan, Shilat Haim-Nachum, Marie R. Sopp, Fredrik Åhs, Rahel Bachem, Eleonora Bartoli, Habte Belete, Tilahun Belete, Azi Berzengi, Daniel Dukes, Aziz Essadek, Naved Iqbal, Laura Jobson, Rachel Langevin, Einat Levy-Gigi, Antonia M. Lüönd, Chantal Martin-Soelch, Tanja Michael, Misari Oe, Miranda Olff, Deniz Ceylan, Vijaya Raghavan, Muniarajan Ramakrishnan, Vedat Sar, Georgina Spies, Dany Laure Wadji, Rachel Wamser-Nanney, Natalia E. Fares-Otero, Ulrich Schnyder, Soraya Seedat
Journal: Psychotherapy and Psychosomatics (2022)

Childhood maltreatment (CM) is linked to impairments in various domains of social functioning. Here, we argue that it is critical to identify factors that underlie impaired social functioning as well as processes that mediate the beneficial health effects of positive relationships in individuals exposed to CM. Key research recommendations are presented, focusing on: (1) identifying attachment-related alterations in specific inter- and intrapersonal processes (e.g., regulation of closeness and distance) that underlie problems in broader domains of social functioning (e.g., lack of perceived social support) in individuals affected by CM; (2) identifying internal (e.g., current emotional state) and external situational factors (e.g., cultural factors, presence of close others) that modulate alterations in specific social processes; and (3) identifying mechanisms that explain the positive health effects of intact social functioning. Methodological recommendations include: (1) assessing social processes through interactive and (close to) real-life assessments inside and outside the laboratory; (2) adopting an interdisciplinary, lifespan perspective to assess social processes, using multi-method assessments; (3) establishing global research collaborations to account for cultural influences on social processes and enable replications across laboratories and countries. The proposed line of research will contribute to globally develop and refine interventions that prevent CM and further positive relationships, which - likely through buffering the effects of chronic stress and corresponding allostatic load - foster resilience and improve mental and physical health, thereby reducing personal suffering and the societal and economic costs of CM and its consequences. Interventions targeting euthymia and psychological well-being are promising therapeutic concepts in this context.
Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants
Authors: Hung Fu Tseng, Bradley K. Ackerson, Yi Luo, Lina S. Sy, Carla A. Talarico, Yun Tian, Katia J. Bruxvoort, Julia E. Tubert, Ana Florea, Jennifer H. Ku, Gina S. Lee, Soon Kyu Choi, Harpreet S. Takhar, Michael Aragones, Lei Qian
Journal: Nature Medicine (2022)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case–control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron or Delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variants determined by S gene target failure status (16% Delta and 84% Omicron). The two-dose VE against Omicron infection at 14–90 days was 44.0% (95% confidence interval, 35.1–51.6%) but declined quickly. The three-dose VE was 93.7% (92.2–94.9%) and 86.0% (78.1–91.1%) against Delta infection and 71.6% (69.7–73.4%) and 47.4% (40.5–53.5%) against Omicron infection at 14–60 days and &gt;60 days, respectively. The three-dose VE was 29.4% (0.3–50.0%) against Omicron infection in immunocompromised individuals. The three-dose VE against hospitalization with Delta or Omicron was &gt;99% across the entire study population. Our findings demonstrate high, durable three-dose VE against Delta infection but lower effectiveness against Omicron infection, particularly among immunocompromised people. However, three-dose VE of mRNA-1273 was high against hospitalization with Delta and Omicron variants.
New Insights into the Comparative Effectiveness of Fentanyl and Morphine Infusions in ICU Patients
Authors: Paul J. Young, Audrey De Jong
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire
68Ga-DOTA-FAPI-04 PET/CT Imaging in a Case of Cardiac Angiosarcoma
Authors: Tingting Xu, Haoyuan Ding, Hongjian Ban, Yan Zhu, Yue Chen
Journal: Clinical Nuclear Medicine (2022)

Abstract A 30-year-old woman presented with sudden syncope. Further examination revealed a mass in the right atrium. 18 F-FDG showed increased tracer uptake in the mass. 68 Ga-DOTA-FAPI-04 showed increased tracer uptake of thickened pericardium around the mass, but no obviously increased tracer uptake in the mass. The mass that invaded the adjacent pericardium was found during the operation. Postoperative pathology confirmed the diagnosis of right atrium angiosarcoma. Our case demonstrated that 68 Ga-DOTA-FAPI-04 is not superior to 18 F-FDG in the imaging of cardiac angiosarcoma, but it is still possible to produce beneficial value in the evaluation of the involvement of the lesion.
Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in <i>EGFR</i>-Mutant Lung Cancer
Authors: Anup Kumar Biswas, Seoyoung Han, Yifan Tai, Wanchao Ma, Courtney Coker, S. Aidan Quinn, Ahmad Rushdi Shakri, Timothy James Zhong, Hanna Scholze, Galina G. Lagos, Angeliki Mela, Katia Manova-Todorova, Elisa de Stanchina, Adolfo A. Ferrando, Cathy Mendelsohn, Peter Canoll, Helena A. Yu, Paul K. Paik, Anjali Saqi, Catherine A. Shu, Mark G. Kris, Joan Massague, Swarnali Acharyya
Journal: Cancer Discovery (2022)

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using metastatic models of EGFR-mutant lung cancer, we show that cancer cells expressing high intracellular S100A9 escape osimertinib and initiate brain relapses. Mechanistically, S100A9 upregulates ALDH1A1 expression and activates the retinoic acid (RA) signaling pathway in osimertinib-refractory cancer cells. We demonstrate that the genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. Importantly, S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients. Our study, therefore, identifies a novel, therapeutically targetable S100A9-ALDH1A1-RA axis that drives brain relapse. Treatment with the EGFR TKI osimertinib prolongs the survival of patients with EGFR-mutant lung cancer; however, patients develop metastatic relapses, often to the brain. We identified a novel intracellular S100A9-ALDH1A1-RA signaling pathway that drives lethal brain relapse and can be targeted by pan-RAR antagonists to prevent cancer progression and prolong patient survival. This article is highlighted in the In This Issue feature, p. 873.