tbuckley/cabot-search huggingface dataset:
Laboratory confirmed vaccine-induced immune thrombotic thrombocytopenia: Retrospective analysis of reported cases after vaccination with ChAdOx-1 nCoV-19 in Germany
Authors: Thomas Thiele, Karin Weisser, Linda Schönborn, Markus B. Funk, Gabriele Weber, Andreas Greinacher, Brigitte Keller-Stanislawski
Journal: The Lancet Regional Health - Europe (2021)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse event of SARS-CoV-2 vaccination. We describe the characteristics of patients reported in Germany based on the Brighton Collaboration (BC) case definition criteria for Thrombosis and Thrombocytopenia Syndrome (TTS) and focus on patients with complete anti-platelet factor 4 (PF4)-antibody laboratory work up.The adverse drug reaction database of the Paul-Ehrlich Institute was queried for TTS cases following ChAdOx1 nCoV-19 vaccination from February 1, until May 21, 2021. Cases with reports from the Greifswald laboratory were analysed in detail.PF4 antibody tests were available for 69 suspected TTS cases reported to the Paul-Ehrlich Institute, of whom 52 patients fulfilled the BC case definition; 37 (71%) women, 15 (29%) men, median age 46·0 years (interquartile range 31·0-60·3 years). Cerebral venous sinus thrombosis was confirmed in 37 (71%), (additional) multiple thromboses in 19 (37%) patients. Twelve patients died. Non-survivors showed lower platelet counts compared to survivors (median nadir 15,000/µL vs 49,000/µL; p<0·0001). Combined anti-PF4/heparin IgG ELISA and PF4-dependent platelet activation testing yielded sensitivity of 96% (95% confidence interval 87-100%) and specificity of 77% (50-93%) for TTS. Four patients with thrombocytopenia but without thrombosis presented with severe headache or cerebral bleeding, explaining the lower specificity.VITT has high mortality and can present with isolated thrombocytopenia, severe headache, and bleeding. Demonstration of platelet activating anti-PF4 IgG has high sensitivity for TTS and captures a wider spectrum of clinically relevant VITT than the current BC case definition.Deutsche Forschungsgemeinschaft: 374031971-TRR240; Domagk-Programm Universitätsmedizin Greifswald.
Antigen presentation and interferon signatures in B cells driven by localized ablative cancer immunotherapy correlate with extended survival
Authors: Kaili Liu, Ashley R. Hoover, Jason R. Krawic, Christa I. DeVette, Xiao-Hong Sun, William H. Hildebrand, Mark L. Lang, Robert C. Axtell, Wei R. Chen
Journal: Theranostics (2021)

Rationale: B cells have emerged as key regulators in protective cancer immunity.However, the activation pathways induced in B cells during effective immunotherapy are not well understood.Methods: We used a novel localized ablative immunotherapy (LAIT), combining photothermal therapy (PTT) with intra-tumor delivery of the immunostimulant N-dihydrogalactochitosan (GC), to treat mice bearing mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT).We used single-cell RNA sequencing to compare the transcriptional changes induced by PTT, GC and PTT+GC in B cells within the tumor microenvironment (TME).Results: LAIT significantly increased survival in the tumor-bearing mice, compared to the treatment by PTT and GC alone.We found that PTT, GC and PTT+GC increased the proportion of tumor-infiltrating B cells and induced gene expression signatures associated with B cell activation.Both GC and PTT+GC elevated gene expression associated with antigen presentation, whereas GC elevated transcripts that regulate B cell activation and GTPase function and PTT+GC induced interferon response genes.Trajectory analysis, where B cells were organized according to pseudotime progression, revealed that both GC and PTT+GC induced the differentiation of B cells from a resting state towards an effector phenotype.The analyses confirmed upregulated interferon signatures in the differentiated tumor-infiltrating B cells following treatment by PTT+GC but not by GC.We also observed that breast cancer patients had significantly longer survival time if they had elevated expression of genes in B cells that were induced by PTT+GC therapy in the mouse tumors.Conclusion: Our findings show that the combination of local ablation and local application of immunostimulant initiates the activation of interferon signatures and antigen-presentation in B cells which is associated with positive clinical outcomes for breast cancer.These findings broaden our understanding of LAIT's regulatory roles in remodeling TME and shed light on the potentials of B cell activation in clinical applications.
Humoral and cellular correlates of a novel immune-related adverse event and its treatment
Authors: Amrit S Gonugunta, Mitchell S von Itzstein, Hong Mu-Mosley, Farjana Fattah, J David Farrar, Angela Mobely, Sawsan Rashdan, Sunny Lai, Salman F Bhai, Bonnie L Bermas, David Karp, Quan-Zhen Li, Edward K Wakeland, David E Gerber
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of longitudinal biospecimens, we analyzed serial autoantibodies, cytokines, and cellular populations. Months after ICI initiation and preceding clinical toxicity, the patient developed broad increases in cytokines (most notably interleukin-6 (IL-6), interferon-γ (IFNγ), C-X-C motif chemokine ligand 2 (CXCL2), and C–C motif chemokine ligand 17 (CCL17)), autoantibodies (including anti-angiotensin receptor, α-actin, and amyloid), CD8 T cells, and plasmablasts. Such changes were not observed in healthy controls and ICI-treated patients without irAE. Administration of corticosteroids resulted in immediate and profound decreases in cytokines, autoantibodies, and inflammatory cells. This case highlights the potential for late-onset changes in humoral and cellular immunity in patients receiving ICI. It also demonstrates the biologic effects of corticosteroids on these parameters. Application of humoral and cellular immune biomarkers across ICI populations may inform toxicity monitoring and management.
The impact of achieving and maintaining near-complete or complete skin clearance on patient quality of life in moderate-to-severe psoriasis
Authors: Caitriona Ryan, Luis Puig, Carla Zema, Elizabeth H.Z. Thompson, Min Yang, Eric Wu, Arielle Bensimon, Xin Huang, Avani D. Joshi, Boni Elewski
Journal: Journal of the American Academy of Dermatology (2021)
Immune and Genome Engineering as the Future of Transplantable Tissue
Authors: Jennifer Elisseeff, Stephen F. Badylak, Jef D. Boeke
Journal: New England Journal of Medicine (2021)

Dramatic advancements in the use of synthetic and mechanical devices to replace tissues have been made, but restoring tissue and organ structure and function remains challenging. This review discusses the origins, innovations, and future of regenerative medicine and transplantation, which are closely intertwined.
Thoracic Endometriosis
Authors: Mei-Ling Chen, Chia-Ying Li
Journal: New England Journal of Medicine (2021)

A 26-year-old woman presented with intermittent small-volume hemoptysis coinciding with her menses. CT of the chest showed a cavitary nodule that was then resected. Histopathological analysis of the lesion revealed endometrial glands, consistent with a diagnosis of thoracic endometriosis.
Letter to the editor: Reactivation of HBV triggered by SARS‐CoV‐2 in a patient with cirrhosis
Authors: Marta Librero Jiménez, María Ángeles López Garrido, María Carmen Fernández Cano
Journal: Hepatology (2021)

HBV reactivation can occur spontaneously, but it is more frequently triggered by immunosuppressors, immunologic diseases, or transplantation. It can also be caused by coinfection with HCV or HDV, or even by elimination of HCV in patients treated with direct-acting antivirals. In patients receiving antivirals for the treatment of chronic hepatitis, reactivation can also be caused by low levels of the drug (due to lack of therapeutic adherence or interaction with other treatments) or new mutations of the virus.[1] Reactivation is characterized by a sudden rise of HBV DNA, which can be followed by an elevation of alanine transaminase (ALT) levels (with or without bilirubin) several weeks after.[2] It should be treated with a nucleoside/nucleotide analogue (tenofovir or entecavir) as early as possible, regardless of ALT levels. Despite antiviral treatment, up to 25%–50% of patients may still develop severe hepatitis, hepatic failure, or even death.[3] A 37-year-old male was admitted with asthenia, hyperoxia, and jaundice for the last 4 days. The patient had a cirrhosis caused by HBV chronic infection; he had never developed previous decompensations and was taking tenofovir-disoproxil-fumarate (TDF). Initial laboratory tests were made (Figure 1), and acute-on-chronic liver failure was diagnosed. He was taking TDF properly and denied consuming alcohol, drug abuse, or unprotected sexual intercourses. A complete study for acute liver injury was made (including viral and autoimmunity tests), and all results were normal. On admission, the patient was tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting positive. He assumed a risk contact 10 days before, but no breathing symptoms since then. DNA HBV was tested, and 4 million copies were detected (previously undetectable); treatment with entecavir was started. The virus was also tested for mutations but none of them were identified. Unfortunately, liver function worsened progressively as shown in Figure 1, leading finally to death 3 weeks later. In our case, other more common causes were initially excluded: Medication adherence was appropriate, serology tests were negative, no new immunosuppressive therapies were initiated, and viral mutations were excluded. For this reason, and judging by the temporary coincidence with infection by SARS-CoV2, we propose the coinfection with this virus as the cause of HBV reactivation. The underlying pathogenesis of transient reactivation of HBV in COVID-19 remains unclear, although it could be similar to HCV or HDV, causing reactivation of HBV replication. In summary, we would like to highlight the singularity of our case report, as it is the first patient with cirrhosis with chronic infection of HBV who presumably developed a reactivation of HBV triggered by SARS-CoV-2.
Engineered Cell‐Derived Vesicles Displaying Targeting Peptide and Functionalized with Nanocarriers for Therapeutic microRNA Delivery to Triple‐Negative Breast Cancer in Mice
Authors: Rajendran JC Bose, Uday Sukumar Kumar, Fernando Garcia‐Marques, Yitian Zeng, Frezghi Habte, Jason R McCarthy, Sharon Pitteri, Tarik F Massoud, Ramasamy Paulmurugan
Journal: Advanced Healthcare Materials (2021)

Polymeric nanocarriers (PNCs) can be used to deliver therapeutic microRNAs (miRNAs) to solid cancers. However, the ability of these nanocarriers to specifically target tumors remains a challenge. Alternatively, extracellular vesicles (EVs) derived from tumor cells show homotypic affinity to parent cells, but loading sufficient amounts of miRNAs into EVs is difficult. Here, it is investigated whether uPAR-targeted delivery of nanococktails containing PNCs loaded with therapeutic antimiRNAs, and coated with uPA engineered extracellular vesicles (uPA-eEVs) can elicit synergistic antitumor responses. The uPA-eEVs coating on PNCs increases natural tumor targeting affinities, thereby enhancing the antitumor activity of antimiRNA nanococktails. The systemic administration of uPA-eEV-PNCs nanococktail shows a robust tumor tropism, which significantly enhances the combinational antitumor effects of antimiRNA-21 and antimiRNA-10b, and leads to significant tumor regression and extension of progression free survival for syngeneic 4T1 tumor-bearing mice. In addition, the uPA-eEV-PNCs-antimiRNAs nanococktail plus low dose doxorubicin results in a synergistic antitumor effect as evidenced by inhibition of tumor growth, reduction of lung metastases, and extension of survival of 4T1 tumor-bearing mice. The targeted combinational nanococktail strategy could be readily translated to the clinical setting by using autologous cancer cells that have flexibility for ex vivo expansion and genetic engineering.
3D-printed oxygen-releasing scaffolds improve bone regeneration in mice
Authors: Ashley L. Farris, Dennis Lambrechts, Yuxiao Zhou, Nicholas Y. Zhang, Naboneeta Sarkar, Megan C. Moorer, Alexandra N. Rindone, Ethan L. Nyberg, Alexander Perdomo-Pantoja, S.J. Burris, Kendall Free, Timothy F. Witham, Ryan C. Riddle, Warren L. Grayson
Journal: Biomaterials (2021)

Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (μtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable μtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-μtank scaffolds. PCL-μtank scaffolds were loaded with pure O2 at 300-500 psi. When placed at atmospheric pressures, the scaffolds released O2 over a period of up to 8 h. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that μtank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O2-loaded, hASC-seeded, PCL-μtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-μtank scaffolds may enhance hASC-mediated bone tissue regeneration.
6. Glycemic Targets: <i>Standards of Medical Care in Diabetes—2022</i>
Journal: Diabetes Care (2021)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
A Case of Microsatellite Instability–High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis
Authors: Steven M. Blum, William R. Jeck, Lindsay Kipnis, Ronald Bleday, Jonathan A. Nowak, Matthew B. Yurgelun
Journal: Journal of the National Comprehensive Cancer Network (2021)

Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease &gt;10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.
Mortality Risk from PM2.5: A Comparison of Modeling Approaches to Identify Disparities across Racial/Ethnic Groups in Policy Outcomes
Authors: Elisheba Spiller, Jeremy Proville, Ananya Roy, Nicholas Z. Muller
Journal: Environmental Health Perspectives (2021)

Regulatory analyses of air pollution policies require the use of concentration-response functions and underlying health data to estimate the mortality and morbidity effects, as well as the resulting benefits, associated with policy-related changes in fine particulate matter ≤2.5μm (PM2.5)]. Common practice by U.S. federal agencies involves using underlying health data and concentration-response functions that are not differentiated by racial/ethnic group.We aim to explore the policy implications of using race/ethnicity-specific concentration-response functions and mortality data in comparison to standard approaches when estimating the impact of air pollution on non-White racial/ethnic subgroups.Using new estimates from the epidemiological literature on race/ethnicity-specific concentration-response functions paired with race/ethnicity-specific mortality rates, we estimated the mortality impacts of air pollution from all sources from a uniform increase in concentrations and from the regulations imposed by the Mercury Air Toxics Standards.Use of race/ethnicity-specific information increased PM2.5-related premature mortality estimates in older populations by 9% and among older Black Americans by 150% for all-source pollution exposure. Under a uniform degradation of air quality and race/ethnicity-specific information, older Black Americans were found to have approximately 3 times higher mortality relative to White Americans, which is obscured under a non-race/ethnicity-specific modeling approach. Standard approaches of using non-racial/ethnic specific information underestimate the benefits of the Mercury Air Toxics Standards to older Black Americans by almost 60% and overestimate the benefits to older White Americans by 14% relative to using a race/ethnicity-specific modeling approach.Policy analyses incorporating race/ethnicity-specific concentration-response functions and mortality data relative to nondifferentiated inputs underestimate the overall magnitude of PM2.5 mortality burden and the disparity in impacts on older Black American populations. Based on our results, we recommend that the best available race/ethnicity-specific inputs are used in regulatory assessments to understand and reduce environmental injustices. https://doi.org/10.1289/EHP9001.
151P CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with doublet chemotherapy (Nab-PTX &amp; S-1) and apatinib (anti-angiogenic TKI) for the first-line treatment of stage IV gastric cancer (GC)
Authors: Q. Xue, B. Wang, X. Wang, X. Ding, Y. Liu, X. Wang, N. Liu, H. Zhan, B. Ke, B. Li, M. Cai, J. Deng, L. Wu, W. Huang, H. Liu, Y. Sun, H. Liang
Journal: Annals of Oncology (2021)
Tailoring noble metal nanoparticle designs to enable sensitive lateral flow immunoassay
Authors: Xirui Chen, Lu Ding, Xiaolin Huang, Yonghua Xiong
Journal: Theranostics (2021)

Lateral flow immunoassay (LFIA) with gold nanoparticles (AuNPs) as signal reporters is a popular point-of-care diagnostic technique. However, given the weak absorbance of traditional 20-40 nm spherical AuNPs, their sensitivity is low, which greatly limits the wide application of AuNP-based LFIA. With the rapid advances in materials science and nanotechnology, the synthesis of noble metal nanoparticles (NMNPs) has enhanced physicochemical properties such as optical, plasmonic, catalytic, and multifunctional activity by simply engineering their physical parameters, including the size, shape, composition, and external structure. Using these engineered NMNPs as an alternative to traditional AuNPs, the sensitivity of LFIA has been significantly improved, thereby greatly expanding the working range and application scenarios of LFIA, particularly in trace analysis. Therefore, in this review, we will focus on the design of engineered NMNPs and their demonstration in improving LFIA. We highlight the strategies available for tailoring NMNP designs, the effect of NMNP engineering on their performance, and the working principle of each engineering design for enhancing LFIA. Finally, current challenges and future improvements in this field are briefly discussed.
Abstract 13226: Epinephrine versus Norepinephrine in Cardiac Arrest Patients With Postresuscitation Shock
Authors: Wulfran Bougouin, Kaci Slimani, Marie Renaudier, Yannick Binois, Marine Paul, Florence Dumas, Lionel Lamhaut, Thomas Loeb, Sofia Ortuno, Nicolas Deye, Sebastian Voicu, Frankie BEGANTON, daniel jost, Armand Mekontso-Dessap, Eloi Marijon, Xavier JOUVEN, Nadia Aissaoui, Alain Cariou
Journal: Circulation (2021)

Backgound: Whether epinephrine or norepinephrine is preferable as the continuous intravenous vasopressor used to treat postresuscitation shock is unclear. Objectives: To compare outcomes of patients with postresuscitation shock after out-of-hospital cardiac arrest according to whether the continuous intravenous vasopressor used was epinephrine or norepinephrine. Methods: We conducted an observational multicenter study of consecutive patients managed in 2011-2018 for postresuscitation shock. The primary outcome was all-cause hospital mortality, and secondary outcomes were cardiovascular hospital mortality and unfavorable neurological outcome (Cerebral Performance Category 3 to 5). A multivariate regression analysis and a propensity score analysis were performed, as well as several sensitivity analyses. Results: Of the 766 patients included in five hospitals, 285 (37%) received epinephrine and 481 (63%) norepinephrine. All-cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95%CI, 1.4-4.7; P =0.002). Cardiovascular hospital mortality was also higher with epinephrine (aOR 5.5; 95%CI 3.0-10.3; P &lt;0.001), as was the proportion of patients with CPC of 3 to 5 at hospital discharge. Sensitivity analyses produced consistent results. The analysis involving adjustment on a propensity score to control for confounders showed similar findings (aOR 2.1; 95%CI 1.1-4.0; P =0.02). Conclusions: Among patients with postresuscitation shock after out-of-hospital cardiac arrest, use of epinephrine was associated with higher all-cause and cardiovascular-specific mortality, compared with norepinephrine infusion. A randomized controlled trial comparing the two vasopressors in this population is warranted.
Gender trends in research output among matched dermatology residency applicants
Authors: David X. Zheng, Mehak K. Kalra, Jatin Narang, Anna Eversman, Frederick C. Morgan, Elizabeth E. Obi, Wilhemina Osei-Koomson, Emma R. Russell, Angela H. Wei, Melissa A. Levoska, Jeffrey F. Scott, Christina Wong
Journal: Journal of the American Academy of Dermatology (2021)