653 results match your criteria: "at Harvard University[Affiliation]"

Throughout the COVID-19 pandemic, researchers have studied how Americans' attitudes toward health experts influence their health behaviors and policy opinions. Fewer, however, consider the potential gap between individual and expert opinion about COVID-19, and how that might shape health attitudes and behavior. This omission is notable, as discrepancies between individual and expert opinion could help explain why some Americans fail to take action to protect themselves and others from the virus.

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The field of mechanobiology, which focuses on the key role that physical forces play in control of biological systems, has grown enormously over the past few decades. Here, I provide a brief personal perspective on the development of the tensegrity theory that contributed to the emergence of the mechanobiology field, the key role that crossing disciplines has played in its development, and how it has matured over time. I also describe how pursuing questions relating to mechanochemical transduction and mechanoregulation can lead to the creation of novel technologies and open paths for development of new therapeutic strategies for a broad range of diseases and disorders.

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CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility.

Mol Psychiatry

June 2024

F. M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive.

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Design of an Ultralow Molecular Weight Heparin That Resists Heparanase Biodegradation.

J Med Chem

February 2023

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, CLS-11090, Boston, Massachusetts 02215, United States.

Heparanase, an endo-β-d-glucuronidase produced by a variety of cells and tissues, cleaves the glycosidic linkage between glucuronic acid (GlcA) and a 3-O- or 6-O-sulfated glucosamine, typified by the disaccharide -[GlcA-GlcNS3S6S]-, which is found within the antithrombin-binding domain of heparan sulfate or heparin. As such, all current forms of heparin are susceptible to degradation by heparanase with neutralization of anticoagulant properties. Here, we have designed a heparanase-resistant, ultralow molecular weight heparin as the structural analogue of fondaparinux that does not contain an internal GlcA residue but otherwise displays potent anticoagulant activity.

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Strategies for Naming and Addressing Structural Racism in Immigrant Mental Health.

Am J Public Health

January 2023

Ivo H. Cerda is with Harvard Medical School, Boston, MA. Anjeli R. Macaranas is a student at Harvard University, Cambridge, MA. Cindy H. Liu is with the Departments of Pediatric Newborn Medicine and Psychiatry, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. Justin A. Chen is with the Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston.

Immigrants account for 13.7% of the US population, and the great majority of these individuals originate from Latin America or Asia. Immigrant communities experience striking inequities in mental health care, particularly lower rates of mental health service use despite significant stressors.

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Ribonucleic acid (RNA) therapeutics are being actively researched as a therapeutic modality in preclinical and clinical studies. They have become one of the most ubiquitously known and discussed therapeutics in recent years in part due to the ongoing coronavirus pandemic. Since the first approval in 1998, research on RNA therapeutics has progressed to discovering new therapeutic targets and delivery strategies to enhance their safety and efficacy.

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Loose bodies (LBs) from patients with osteochondritis dissecans (OCD) are usually removed and discarded during surgical treatment of the defect. In this study, we address the question of whether these LBs contain sufficient viable and functional chondrocytes that could serve as a source for autologous chondrocyte implantation (ACI) and how the required prolonged in vitro expansion affects their phenotype. Chondrocytes were isolated from LBs of 18 patients and compared with control chondrocyte from non-weight-bearing joint regions ( = 7) and bone marrow mesenchymal stromal cells (BMSCs, = 6) obtained during primary arthroplasty.

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Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics.

Adv Sci (Weinh)

March 2023

John A. Paulson School of Engineering and Applied Sciences, Harvard University, 150 Western Ave, Allston, MA, 02134, USA.

Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections.

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Objective: To examine the relationships between age, healthspan and chronic illness among former professional American-style football (ASF) players.

Methods: We compared age-specific race-standardised and body mass index-standardised prevalence ratios of arthritis, dementia/Alzheimer's disease, hypertension and diabetes among early adult and middle-aged (range 25-59 years) male former professional ASF players (n=2864) with a comparator cohort from the National Health and Nutrition Examination Survey and National Health Interview Survey, two representative samples of the US general population. Age was stratified into 25-29, 30-39, 40-49 and 50-59 years.

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Cytokine conjugation to enhance T cell therapy.

Proc Natl Acad Sci U S A

January 2023

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Adoptive T cell transfer (ACT) therapies suffer from a number of limitations (e.g., poor control of solid tumors), and while combining ACT with cytokine therapy can enhance effectiveness, this also results in significant side effects.

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DNA plasmids are an essential tool for delivery and expression of RNAs and proteins in cell culture experiments. The preparation of plasmids typically involves a laborious process of bacterial cloning, validation, and purification. While the expression plasmids can be designed and ordered from the contract manufacturers, the cost may be prohibitive when a large number of plasmids is required.

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Chemotherapy Dose Shapes the Expression of Immune-Interacting Markers on Cancer Cells.

Cell Mol Bioeng

December 2022

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 USA.

Introduction: Tumor and immune cells interact through a variety of cell-surface proteins that can either restrain or promote tumor progression. The impacts of cytotoxic chemotherapy dose and delivery route on this interaction profile remain incompletely understood, and could support the development of more effective combination therapies for cancer treatment.

Methods And Results: Here, we found that exposure to the anthracycline doxorubicin altered the expression of numerous immune-interacting markers (MHC-I, PD-L1, PD-L2, CD47, Fas, and calreticulin) on live melanoma, breast cancer, and leukemia cells in a dose-dependent manner .

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Background: A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.

Results: Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen.

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The future of engineered immune cell therapies.

Science

November 2022

Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.

Immune cells are being engineered to recognize and respond to disease states, acting as a "living drug" when transferred into patients. Therapies based on engineered immune cells are now a clinical reality, with multiple engineered T cell therapies approved for treatment of hematologic malignancies. Ongoing preclinical and clinical studies are testing diverse strategies to modify the fate and function of immune cells for applications in cancer, infectious disease, and beyond.

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The COVID-19 public health crisis has spotlighted the need to improve global hygiene and sanitization. In addition to causing staggering rates of transmission and fatality, COVID-19 has severely impacted the quality of life and mental health of global citizens. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) encourage hand hygiene as the first defense against the spread of infection, yet frequent handwashing is often impractical.

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Article Synopsis
  • In drop-based microfluidics, a new device called the PIPE chip can create droplets for up to 96 conditions simultaneously, enhancing high-throughput screening in time-sensitive studies.
  • The PIPE chip generates two types of optically barcoded droplet libraries using different fluorescent particles, which allows for rapid measurement and identification of distinct populations through fluorescence detection and advanced data clustering methods.
  • This technology improves efficiency in multiplexed assays by streamlining the encapsulation process and minimizing sample preparation time for downstream analysis.
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The experiences of care of people with lived experience of homelessness are rarely embraced to change care delivery. We conducted qualitative group and one-on-one interviews utilizing experience group methodology with 27 people with lived experience of homelessness currently housed in one permanent housing community in central Texas. We analyzed data using an inductive thematic approach to identify shared obstacles and barriers to receiving health care.

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Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia.

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Diverse processes in cancer are mediated by enzymes, which most proximally exert their function through their activity. High-fidelity methods to profile enzyme activity are therefore critical to understanding and targeting the pathological roles of enzymes in cancer. Here, we present an integrated set of methods for measuring specific protease activities across scales, and deploy these methods to study treatment response in an autochthonous model of Alk-mutant lung cancer.

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What clinicians of status owe health workers earning low wages has been changed by the events of the past 2 years of the COVID-19 pandemic, national racial reckoning, and increasing national income and wealth inequality. Reasons why clinicians of status should actively promote the interests of health workers earning low wages are numerous and urgent.

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Background: Maternal depression is a major determinant of offspring mental health. Yet, little is understood about how the duration and timing of maternal depression shapes youth risk for depressive symptoms, which if understood could inform when best to intervene. This study aimed to determine how the timing and duration of maternal depression was related to offspring depression in emerging adulthood, and if these associations varied by sex.

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The standard view of embryogenesis is one of cooperation driven by the cells' shared genetics and evolutionary interests. However, numerous examples from developmental biology and agriculture reveal a surprising amount of competition among body cells, tissues, and organs for both metabolic and informational resources. To explain the existence of such competition we had hypothesized that evolution uses limiting "reservoirs" of resource molecules as a communication medium - a global scratchpad, to enable tissues across the body to coordinate growth.

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