tbuckley/cabot-search huggingface dataset:
Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis
Authors: Cristina Mesa-Vieira, Andreas D Haas, Diana Buitrago-Garcia, Zayne M Roa-Diaz, Beatrice Minder, Magda Gamba, Dante Salvador, Daniel Gomez, Meghann Lewis, Wendy C Gonzalez-Jaramillo, Aurélie Pahud de Mortanges, Chepkoech Buttia, Taulant Muka, Natalia Trujillo, Oscar H Franco
Journal: The Lancet Public Health (2022)

BackgroundExposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict.MethodsIn this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251.FindingsOf the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23–40); prevalence of current major depressive disorder of 25% (17–34); and prevalence of generalised anxiety disorder of 14% (5–35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90–0·99]), lifetime post-traumatic stress disorder (0·88 [0·83–0·92]), and current generalised anxiety disorder (0·87 [0·78–0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81–0·95]) and major depressive disorder (0·81 [0·77–0·86]). Migrating to a middle-income (8·09 [3·06–21·40]) or low-income (39·29 [11·96–129·70]) country was associated with increased prevalence of generalised anxiety disorder.InterpretationMigrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults.FundingMarie Skłodowska-Curie Actions (Horizon 2020—COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.
Nomenclature Dilemma of Metabolic Associated Fatty Liver Disease (MAFLD): Considerable Proportions of MAFLD Are Metabolic Healthy
Authors: Huiyul Park, Eileen L. Yoon, Mimi Kim, Seon Cho, Eun-Hee Nah, Dae Won Jun
Journal: Clinical Gastroenterology and Hepatology (2022)
Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease
Authors: Kristen J. Brennand
Journal: American Journal of Psychiatry (2022)

There is an urgent and unmet need to advance our ability to translate genetic studies of psychiatric disorders into clinically actionable information, which could transform diagnostics and even one day lead to novel (and potentially presymptomatic) therapeutic interventions. Today, although there are hundreds of significant loci associated with psychiatric disorders, resolving the target gene(s) and pathway(s) impacted by each is a major challenge. Integrating human induced pluripotent stem cell-based approaches with CRISPR-mediated genomic engineering strategies makes it possible to study the impact of patient-specific variants within the cell types of the brain. As the scale and scope of functional genomic studies expands, so does our ability to resolve the complex interplay of the many risk variants linked to psychiatric disorders. In this review, the author discusses some of the technological advances that make it possible to ask exciting questions that are fundamental to our understanding of psychiatric disorders. How do distinct risk variants converge and interact with each other (and the environment) across the diverse cell types that comprise the human brain? Can clinical trajectories and/or therapeutic response be predicted from genetic profiles? Just as critically, by spreading the message that genetic risk for psychiatric disorders is biological and fundamentally no different than for other human conditions, we can dispel the stigma associated with mental illness.
Extracellular magnetic labeling of biomimetic hydrogel-induced human mesenchymal stem cell spheroids with ferumoxytol for MRI tracking
Authors: Sen Yan, Ke Hu, Miao Zhang, Jingyi Sheng, Xueqin Xu, Shijia Tang, Yan Li, Sheng Yang, Guangxiang Si, Yu Mao, Yi Zhang, Feimin Zhang, Ning Gu
Journal: Bioactive Materials (2022)

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.
Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial
Authors: Rolando Pajon, Yamuna D. Paila, Bethany Girard, Groves Dixon, Katherine Kacena, Lindsey R. Baden, Hana M. El Sahly, Brandon Essink, Kathleen M. Mullane, Ian Frank, Douglas Denhan, Edward Kerwin, Xiaoping Zhao, Baoyu Ding, Weiping Deng, Joanne E. Tomassini, Honghong Zhou, Brett Leav, Florian Schödel
Journal: Nature Medicine (2022)

Abstract The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial. While mRNA-1273 demonstrated high efficacy in prevention of COVID-19, including severe disease, its effect on the viral dynamics of SARS-CoV-2 infections is not understood. Here, in exploratory analyses, we assessed the impact of mRNA-1273 vaccination in the ongoing COVE trial (number NCT04470427) on SARS-CoV-2 copy number and shedding, burden of disease and infection, and viral variants. Viral variants were sequenced in all COVID-19 and adjudicated COVID-19 cases ( n = 832), from July 2020 in the blinded part A of the study to May 2021 of the open-label part B of the study, in which participants in the placebo arm started to receive the mRNA-1273 vaccine after US Food and Drug Administration emergency use authorization of mRNA-1273 in December 2020. mRNA-1273 vaccination significantly reduced SARS-CoV-2 viral copy number (95% confidence interval) by 100-fold on the day of diagnosis compared with placebo (4.1 (3.4–4.8) versus 6.2 (6.0–6.4) log 10 copies per ml). Median times to undetectable viral copies were 4 days for mRNA-1273 and 7 days for placebo. Vaccination also substantially reduced the burden of disease and infection scores. Vaccine efficacies (95% confidence interval) against SARS-CoV-2 variants circulating in the United States during the trial assessed in this post hoc analysis were 82.4% (40.4–94.8%) for variants Epsilon and Gamma and 81.2% (36.1–94.5%) for Epsilon. The detection of other, non-SARS-CoV-2, respiratory viruses during the trial was similar between groups. While additional study is needed, these data show that in SARS-CoV-2-infected individuals, vaccination reduced both the viral copy number and duration of detectable viral RNA, which may be markers for the risk of virus transmission.
SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis Patients
Authors: Sushma Shankar, Joseph Beckett, Tom Tipton, Ane Ogbe, Mwila Kasanyinga, Christina Dold, Sheila Lumley, Fungai Dengu, Gianluca Rompianesi, Faysal Elgilani, Stephanie Longet, Alexandra Deeks, Rebecca P. Payne, Christopher J.A. Duncan, Alex Richter, Thushan I. de Silva, Lance Turtle, Katherine Bull, Martin Barnardo, Peter J. Friend, Susanna J. Dunachie, Joanna Hester, Fadi Issa, Eleanor Barnes, Miles W. Carroll, Paul Klenerman
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Patients on hemodialysis (HD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mount poor neutralizing antibody responses after two-dose vaccination. Although serological responses have been associated with reduced rates of reinfection, the relationship between cellular immunogenicity and protection has not been established. We report, for the first time, high incidence of reinfection in patients on HD who are vaccine naive (25%), which identifies that T cell responses do not predict protection against reinfection. Instead, patients on HD who went on to become reinfected had mounted highly variable and sometimes robust proliferative T cell responses to a broad array of SARS-CoV-2 peptide pools during the primary infection. The understanding that SARS-CoV-2–specific T cell responses are not predictive of protection against future infection will be a critical issue when measuring clinical efficacy of vaccination in these vulnerable cohorts, particularly when facing rapidly emerging variants of concern.
Discovery of Biomarkers of Resistance to Immune Checkpoint Blockade in NSCLC Using High-Plex Digital Spatial Profiling
Authors: Myrto Moutafi, Sandra Martinez-Morilla, Prajan Divakar, Ioannis Vathiotis, Niki Gavrielatou, Thazin Nwe Aung, Vesal Yaghoobi, Aileen I Fernandez, Jon Zugazagoitia, Roy S Herbst, Kurt A Schalper, David L Rimm
Journal: Journal of Thoracic Oncology (2022)
Lack of Representation in Psychiatric Research: A Data-Driven Example From Scientific Articles Published in 2019 and 2020 in the <i>American Journal of Psychiatry</i>
Authors: Sarah L. Pedersen, Rachel Lindstrom, Paula M. Powe, Kelly Louie, César Escobar-Viera
Journal: American Journal of Psychiatry (2022)

The authors examined representation and accuracy of descriptions of sociodemographic identities in psychiatric research through quantifying data contained in recently published articles from a high-impact psychiatry journal.Sociodemographic data were aggregated from articles (i.e., studies that provide information on individual samples) published in the American Journal of Psychiatry in 2019 and 2020 (N=125). Articles were coded by two raters for sociodemographic data, acknowledgment of lack of representation as a limitation, and focus on health disparities or inequities.While 90% of studies provided the age of participants and 84% provided information about the sex/gender of participants, only 43% presented information about the racial or ethnicity identities of participants. One study reported the sexual identity of participants. Lack of representation relative to 2019 U.S. Census data was found for multiple racial groups, Latino/Hispanic individuals, and women (genetic studies only). Only 25% of studies acknowledged lack of representation as a limitation, and two studies focused on health disparities or inequities.These findings highlight a need to increase representation in psychiatric research and improve accuracy of language when describing the sociodemographic characteristics of participants.
Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating Factor
Authors: Yuan Min Wang, Karli Shaw, Geoff Yu Zhang, Edmund Y.M. Chung, Min Hu, Qi Cao, Yiping Wang, Guoping Zheng, Huiling Wu, Steven J. Chadban, Hugh J. McCarthy, David C.H. Harris, Fabienne Mackay, Shane T. Grey, Stephen I. Alexander
Journal: Journal of the American Society of Nephrology (2022)

The cytokine IL-33 is an activator of innate lymphoid cells 2 (ILC2s) in innate immunity and allergic inflammation. B cell activating factor (BAFF) plays a central role in B cell proliferation and differentiation, and high levels of this protein cause excess antibody production, including IgA. BAFF-transgenic mice overexpress BAFF and spontaneously develop glomerulonephritis that resembles human IgA nephropathy.We administered IL-33 or PBS to wild-type and BAFF-transgenic mice. After treating Rag1-deficient mice with IL-33, with or without anti-CD90.2 to preferentially deplete ILC2s, we isolated splenocytes, which were adoptively transferred into BAFF-transgenic mice.BAFF-transgenic mice treated with IL-33 developed more severe kidney dysfunction and proteinuria, glomerular sclerosis, tubulointerstitial damage, and glomerular deposition of IgA and C3. Compared with wild-type mice, BAFF-transgenic mice exhibited increases of CD19+ B cells in spleen and kidney and ILC2s in kidney and intestine, which were further increased by administration of IL-33. Administering IL-33 to wild-type mice had no effect on kidney function or histology, nor did it alter the number of ILC2s in spleen, kidney, or intestine. To understand the role of ILC2s, splenocytes were transferred from IL-33-treated Rag1-deficient mice into BAFF-transgenic mice. Glomerulonephritis and IgA deposition were exacerbated by transfer of IL-33-stimulated Rag1-deficient splenocytes, but not by ILC2 (anti-CD90.2)-depleted splenocytes. Wild-type mice infused with IL-33-treated Rag1-deficient splenocytes showed no change in kidney function or ILC2 numbers or distribution.IL-33-expanded ILC2s exacerbated IgA glomerulonephritis in a mouse model. These findings indicate that IL-33 and ILC2s warrant evaluation as possible mediators of human IgA nephropathy.
Mobile Robotic Platform for Contactless Vital Sign Monitoring
Authors: Hen-Wei Huang, Jack Chen, Peter R. Chai, Claas Ehmke, Philipp Rupp, Farah Z. Dadabhoy, Annie Feng, Canchen Li, Akhil J. Thomas, Marco da Silva, Edward W. Boyer, Giovanni Traverso
Journal: Cyborg and Bionic Systems (2022)

The COVID-19 pandemic has accelerated methods to facilitate contactless evaluation of patients in hospital settings. By minimizing in-person contact with individuals who may have COVID-19, healthcare workers can prevent disease transmission and conserve personal protective equipment. Obtaining vital signs is a ubiquitous task that is commonly done in person by healthcare workers. To eliminate the need for in-person contact for vital sign measurement in the hospital setting, we developed Dr. Spot, a mobile quadruped robotic system. The system includes IR and RGB cameras for vital sign monitoring and a tablet computer for face-to-face medical interviewing. Dr. Spot is teleoperated by trained clinical staff to simultaneously measure the skin temperature, respiratory rate, and heart rate while maintaining social distancing from patients and without removing their mask. To enable accurate, contactless measurements on a mobile system without a static black body as reference, we propose novel methods for skin temperature compensation and respiratory rate measurement at various distances between the subject and the cameras, up to 5 m. Without compensation, the skin temperature MAE is 1.3°C. Using the proposed compensation method, the skin temperature MAE is reduced to 0.3°C. The respiratory rate method can provide continuous monitoring with a MAE of 1.6 BPM in 30 s or rapid screening with a MAE of 2.1 BPM in 10 s. For the heart rate estimation, our system is able to achieve a MAE less than 8 BPM in 10 s measured in arbitrary indoor light conditions at any distance below 2 m.
Engineered <i>Escherichia coli</i> Nissle 1917 with urate oxidase and an oxygen-recycling system for hyperuricemia treatment
Authors: Rui Zhao, Zimai Li, Yuqing Sun, Wei Ge, Mingyu Wang, Huaiwei Liu, Luying Xun, Yongzhen Xia
Journal: Gut Microbes (2022)

Hyperuricemia is the second most prevalent metabolic disease to human health after diabetes. Only a few clinical drugs are available, and most of them have serious side effects. The human body does not have urate oxidase, and uric acid is secreted via the kidney or the intestine. Reduction through kidney secretion is often the cause of hyperuricemia. We hypothesized that the intestine secretion could be enhanced when a recombinant urate-degrading bacterium was introduced into the gut. We engineered an Escherichia coli Nissle 1917 strain with a plasmid containing a gene cassette that encoded two proteins PucL and PucM for urate metabolism from Bacillus subtilis, the urate importer YgfU and catalase KatG from E. coli, and the bacterial hemoglobin Vhb from Vitreoscilla sp. The recombinant E. coli strain effectively degraded uric acid under hypoxic conditions. A new method to induce hyperuricemia in mice was developed by intravenously injecting uric acid. The engineered Escherichia coli strain significantly lowered the serum uric acid when introduced into the gut or directly injected into the blood vessel. The results support the use of urate-degrading bacteria in the gut to treat hyperuricemia. Direct injecting bacteria into blood vessels to treat metabolic diseases is proof of concept, and it has been tried to treat solid tumors.
Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
Authors: Federico Rodriguez-Porcel, Kathryn A Wyman-Chick, Carla Abdelnour Ruiz, Jon B Toledo, Daniel Ferreira, Prabitha Urwyler, Rimona S Weil, Joseph Kane, Andrea Pilotto, Arvid Rongve, Bradley Boeve, John-Paul Taylor, Ian McKeith, Dag Aarsland, Simon J G Lewis
Journal: Translational Neurodegeneration (2022)

Abstract The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.
Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML
Authors: Musa Yilmaz, Hagop Kantarjian, Nicholas J. Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney DiNardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A. Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver
Journal: Blood Cancer Journal (2022)

Abstract In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [ N = 27]) and doublet (LIC + FLT3 inhibitor, [ N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% ( N = 65) and 25% ( N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P &lt; 0.01), and flow-cytometry negativity (83% versus 38%, P &lt; 0.01) than doublets. At the end of the first cycle, the median time to ANC &gt; 0.5 (40 versus 21 days, P = 0.15) and platelet &gt; 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P &lt; 0.01). LIC combined with FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3 mutated AML that should be further validated prospectively.
What can work and how? An overview of evidence-based interventions and delivery strategies to support health and human development from before conception to 20 years
Authors: Tyler Vaivada, Zohra S Lassi, Omar Irfan, Rehana A Salam, Jai K Das, Christina Oh, Bianca Carducci, Reena P Jain, Daina Als, Naeha Sharma, Emily C Keats, George C Patton, Margaret E Kruk, Robert E Black, Zulfiqar A Bhutta
Journal: The Lancet (2022)
Neuroendocrine and Rare Tumor Advances: A New and Promising TRAIL Emerges
Authors: Dwight H. Owen, Nikolaos A. Trikalinos
Journal: Clinical Cancer Research (2022)

ONC201 is an oral selective antagonist of the dopamine D2 receptor and direct activator of caseinolytic protease P. In a phase II study, ONC021 was shown to be well tolerated with notable efficacy in patients with the rare neuroendocrine neoplasms pheochromocytomas-paragangliomas, although biomarkers for activity remain to be elucidated. See related article by Anderson et al., p. 1773.