tbuckley/cabot-search huggingface dataset:
This Month in JAAD Case Reports: March 2021
Authors: Brett Sloan
Journal: Journal of the American Academy of Dermatology (2021)

Coronavirus disease 19 (COVID-19) has rarely been associated with immune thrombocytopenic purpura (ITP). Of the few cases reported, >90% had at least 1 symptom of COVID-19.1Bhattacharjee S. Banerjee M. Immune thrombocytopenia secondary to COVID-19: a systematic review.SN Compr Clin Med. 2020; 2: 2048-2058Crossref Google Scholar In the November edition of JAAD Case Reports, Lobos et al2Lobos P. Lobos C. Aravena P. Immune thrombocytopenic purpura associated with coronavirus disease 2019 infection in an asymptomatic young healthy patient.JAAD Case Rep. 2020; 6: 1129-1131Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar reported a 22 year old healthy active male who presented via a tele-dermatology consultation with an asymptomatic petechial eruption on his lower extremities after vigorous exercise. His review of symptoms was negative for COVID-19 symptoms yet he had reported gingival bleeding and a buccal hematoma after a dental procedure 1 day prior. A full laboratory workup revealed a platelet count of 1000/μL and an oropharyngeal swab positive for SARS-Cov-2. Fortunately, he remained asymptomatic of COVID-19 symptoms and his platelet count and petechial eruption improved after receiving intravenous immunoglobulin and eltrombopag. Numerous cutaneous eruptions have been associated with COVID-19. Given the well-known association of viruses with ITP, it is not surprising that SARS-Cov-2 is added to this list. The case presented by Lobos et al2Lobos P. Lobos C. Aravena P. Immune thrombocytopenic purpura associated with coronavirus disease 2019 infection in an asymptomatic young healthy patient.JAAD Case Rep. 2020; 6: 1129-1131Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar is a great example of the utility of tele-dermatology during this pandemic and a stark reminder to have a low threshold on thoroughly investigating any petechial eruption regardless of symptomology. None to report.
Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes
Authors: Shulan Han, Wenjie Wang, Shengfang Wang, Tingyuan Yang, Guifeng Zhang, Di Wang, Ruijun Ju, Yu Lu, Huimei Wang, Lianyan Wang
Journal: Theranostics (2021)

Background: Among the many immunosuppressive cells in the tumor microenvironment, tumor-associated-macrophages (TAMs) are well known to contribute to tumor development. TAMs can be conditioned (polarized) to transition between classical M1-like macrophages, or alternatively to M2-like macrophages. Both are regulated by signaling molecules in the microenvironment. M1-like TAMs can secrete classic inflammatory cytokines that kill tumors by promoting tumor cell necrosis and immune cell infiltration into the tumor microenvironment. In contrast, M2-like TAMs exhibit powerful tumor-promoting functions, including degradation of tumor extracellular matrix, destruction of basement membrane, promotion of angiogenesis, and recruitment of immunosuppressor cells, all of which further promote tumor progression and distal metastasis. Therefore, remodeling the tumor microenvironment by reversing the TAM phenotype will be favorable for tumor therapy, especially immunotherapy. Methods: PLGA nanoparticles encapsulating baicalin and melanoma antigen Hgp peptide fragment 25-33 were fabricated using the ultrasonic double-emulsion technique. The nanoparticles were further loaded with CpG fragments and used conjugated M2pep and α-pep peptides on their surfaces to produce novel nano-complexes. The capability to target M2-like TAMs and anti-tumor immunotherapy effects of nano-complexes were evaluated by flow cytometry and confocal microscopy in vitro. We also investigated the survival and histopathology of murine melanoma models administrated with different nanocomplexes. Improvements in the tumor microenvironment for immune attack of melanoma-bearing mice were also assessed. Results: The nano-complexes were effectively ingested by M2-like TAMs in vitro and in vivo, and the acidic lysosomal environment triggered the disintegration of polydopamine from the nanoparticle surface, which resulted in the release of the payloads. The released CpG played an important role in transforming the M2-like TAMs into the M1-like phenotype that further secreted inflammatory cytokines. The reversal of TAM released cytokines and gradually suppressed tumor angiogenesis, permitting the remodeling of the tumor microenvironment. Moreover, the activated TAMs also presented antigen to T cells, which further stimulated the antitumor immune response that inhibited tumor metastasis. Activated T cells released cytokines, which stimulated NK cell infiltration and directly resulted in killing tumor cells. The baicalin released by M1-like TAMs also killed tumor cells. Conclusion: The nano-complexes facilitated baicalin, antigen, and immunostimulant delivery to M2-like TAMs, which polarized and reversed the M2-like TAM phenotype and remodeled the tumor microenvironment to allow killing of tumor cells.
Association of Race, Socioeconomic Factors, and Treatment Characteristics With Overall Survival in Patients With Limited-Stage Small Cell Lung Cancer
Authors: Kexun Zhou, Huashan Shi, Ruqin Chen, Jordan J. Cochuyt, David O. Hodge, Rami Manochakian, Yujie Zhao, Sikander Ailawadhi, Yanyan Lou
Journal: JAMA Network Open (2021)

<h3>Importance</h3> It has been established that disparities in race and socioeconomic status are associated with outcomes of non–small cell lung cancer. However, it remains unknown whether this extends to stage I, II, or III small cell lung cancer (SCLC), or limited-stage SCLC (L-SCLC). <h3>Objective</h3> To investigate the associations of race, socioeconomic factors, and treatment characteristics with survival among patients with L-SCLC. <h3>Design, Setting, and Participants</h3> Demographic information for patients with L-SCLC diagnosed between 2004 and 2014 was obtained from the National Cancer Database. The follow-up end point is death or last follow-up (date of last contact). Patients were divided into 5 mutually exclusive cohorts by race. Data analysis was performed in October 2019. <h3>Main Outcomes and Measures</h3> Cox proportional hazards models were used to calculate univariable and multivariable models. Multivariable analyses were conducted to assess the associations of race and socioeconomic factors with risk-adjusted outcomes. Overall survival between groups was depicted by Kaplan-Meier curves. <h3>Results</h3> Of 72 409 patients analyzed (median [range] age, 67.0 [23.0-90.0] years), 40 289 (55.6%) were women. The distribution of disease stage was 10 619 patients (14.7%) with stage I disease, 7689 patients (10.6%) with stage II disease, and 54 101 patients (74.7%) with stage III disease. The median (range) duration of follow-up was 8.2 (2.4-15.8) months. Compared with White patients, the hazard of death decreased to 0.92 (95% CI, 0.89-0.95;<i>P</i> &lt; .001) for African American patients and 0.83 (95% CI, 0.77-0.91;<i>P</i> &lt; .001) for Asian patients. The difference in median survival among different racial groups was significant only among those with stage III SCLC. Other factors associated with better survival were female sex, high income, high education, private insurance, diagnostic confirmation by positive cytological analysis, increase in number of sampled regional lymph nodes, and earlier stage at diagnosis. <h3>Conclusions and Relevance</h3> This analysis highlights disparities in race and socioeconomic factors associated with outcomes of L-SCLC. Racial minorities, including African American and Asian patients, have better survival than White patients for L-SCLC after adjustment for sociodemographic factors.
Abstract 14215: Trends in Palliative Care Use in Patients With Adult Congenital Heart Disease at the End-Of-Life
Authors: Vidang Nguyen, Jill Steiner, Eric Krieger, Yonatan Buber, Karen Stout
Journal: Circulation (2019)

Introduction: At the end of life, patients with adult congenital heart disease (ACHD) have high in-hospital mortality and resource utilization. Palliative care consultations (PCC) may facilitate ad...
Privacy protections to encourage use of health-relevant digital data in a learning health system
Authors: Deven McGraw, Kenneth D. Mandl
Journal: npj Digital Medicine (2021)

The National Academy of Medicine has long advocated for a "learning healthcare system" that produces constantly updated reference data during the care process. Moving toward a rapid learning system to solve intractable problems in health demands a balance between protecting patients and making data available to improve health and health care. Public concerns in the U.S. about privacy and the potential for unethical or harmful uses of this data, if not proactively addressed, could upset this balance. New federal laws prioritize sharing health data, including with patient digital tools. U.S. health privacy laws do not cover data collected by many consumer digital technologies and have not been updated to address concerns about the entry of large technology companies into health care. Further, there is increasing recognition that many classes of data not traditionally considered to be healthcare-related, for example consumer credit histories, are indeed predictive of health status and outcomes. We propose a multi-pronged approach to protecting health-relevant data while promoting and supporting beneficial uses and disclosures to improve health and health care for individuals and populations. Such protections should apply to entities collecting health-relevant data regardless of whether they are covered by federal health privacy laws. We focus largely on privacy but also address protections against harms as a critical component of a comprehensive approach to governing health-relevant data. U.S. policymakers and regulators should consider these recommendations in crafting privacy bills and rules. However, our recommendations also can inform best practices even in the absence of new federal requirements.
Therapy of lymphoma by immune checkpoint inhibitors: the role of T cells, NK cells and cytokine-induced tumor senescence
Authors: Fatima Ahmetlic, Josia Fauser, Tanja Riedel, Vera Bauer, Carolin Flessner, Nadine Hömberg, Roman Hennel, Ellen Brenner, Kirsten Lauber, Martin Röcken, Ralph Mocikat
Journal: Journal for ImmunoTherapy of Cancer (2021)

Although antibodies blocking immune checkpoints have already been approved for clinical cancer treatment, the mechanisms involved are not yet completely elucidated. Here we used a λ-MYC transgenic model of endogenously growing B-cell lymphoma to analyze the requirements for effective therapy with immune checkpoint inhibitors. Growth of spontaneous lymphoma was monitored in mice that received antibodies targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein-4, and the role of different immune cell compartments and cytokines was studied by in vivo depletion experiments. Activation of T and natural killer cells and the induction of tumor senescence were analyzed by flow cytometry. On immune checkpoint blockade, visible lymphomas developed at later time points than in untreated controls, indicating an enhanced tumor control. Importantly, 20% to 30% of mice were even long-term protected and did never develop clinical signs of tumor growth. The therapeutic effect was dependent on cytokine-induced senescence in malignant B cells. The proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor (TNF) were necessary for the survival benefit as well as for senescence induction in the λ-MYC model. Antibody therapy improved T-cell functions such as cytokine production, and long-time survivors were only observed in the presence of T cells. Yet, NK cells also had a pronounced effect on therapy-induced delay of tumor growth. Antibody treatment enhanced numbers, proliferation and IFN-γ expression of NK cells in developing tumors. The therapeutic effect was fully abrogated only after depletion of both, T cells and NK cells, or after ablation of either IFN-γ or TNF. Tumor cell senescence may explain why patients responding to immune checkpoint blockade frequently show stable growth arrest of tumors rather than complete tumor regression. In the lymphoma model studied, successful therapy required both, tumor-directed T-cell responses and NK cells, which control, at least partly, tumor development through cytokine-induced tumor senescence.
Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago
Authors: Masatoshi Matsunami, Kae Koganebuchi, Minako Imamura, Hajime Ishida, Ryosuke Kimura, Shiro Maeda
Journal: Molecular Biology and Evolution (2021)

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 - 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.
Prussian blue nanozyme-mediated nanoscavenger ameliorates acute pancreatitis via inhibiting TLRs/NF-κB signaling pathway
Authors: Xue Xie, Jiulong Zhao, Wei Gao, Jie Chen, Bing Hu, Xiaojun Cai, Yuanyi Zheng
Journal: Theranostics (2021)

Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism.
Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments
Authors: Xiaoxu Wei, Yunhua Chen, Xianjie Jiang, Miao Peng, Yiduo Liu, Yongzhen Mo, Daixi Ren, Yuze Hua, Boyao Yu, Yujuan Zhou, Qianjin Liao, Hui Wang, Bo Xiang, Ming Zhou, Xiaoling Li, Guiyuan Li, Yong Li, Wei Xiong, Zhaoyang Zeng
Journal: Molecular Cancer (2021)

Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM.In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis.Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.
Black US doctor is fired after complaint about talk on racism in medicine
Authors: Jeanne Lenzer
Journal: BMJ (2021)

A doctor has been fired from her “dream job” as a small group facilitator at a medical school in California after she shared personal and historical incidents of racism during a talk with students.

Aysha Khoury, a 42 year old internist, was hired in July 2019 by Kaiser Permanente School of Medicine in Pasadena, which opened in 2020, does not charge fees, and encourages applications from students from diverse backgrounds. She was particularly excited about the school’s focus on “achieving equity,” the “elimination of health disparities,” and the promotion of “inclusiveness and diversity,” she said.

Khoury was asked to facilitate a discussion about “legacies of power structures and institutionalised racism that result in gender bias and race bias in medicine today” for a class held in August 2020. She has said that she “decided to show up fully as a Black woman and physician,” wearing “a T shirt with the words …
Author Correction: Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
Authors: Sheng Chih Jin, Sara A. Lewis, Somayeh Bakhtiari, Xue Zeng, Michael C. Sierant, Sheetal Shetty, Sandra M. Nordlie, Aureliane Elie, Mark A. Corbett, Bethany Y. Norton, Clare L. van Eyk, Shozeb Haider, Brandon S. Guida, Helen Magee, James Liu, Stephen Pastore, John B. Vincent, Janice Brunstrom-Hernandez, Antigone Papavasileiou, Michael C. Fahey, Jesia G. Berry, Kelly Harper, Chongchen Zhou, Junhui Zhang, Boyang Li, Hongyu Zhao, Jennifer Heim, Dani L. Webber, Mahalia S. B. Frank, Lei Xia, Yiran Xu, Dengna Zhu, Bohao Zhang, Amar H. Sheth, James R. Knight, Christopher Castaldi, Irina R. Tikhonova, Francesc López-Giráldez, Boris Keren, Sandra Whalen, Julien Buratti, Diane Doummar, Megan Cho, Kyle Retterer, Francisca Millan, Yangong Wang, Jeff L. Waugh, Lance Rodan, Julie S. Cohen, Ali Fatemi, Angela E. Lin, John P. Phillips, Timothy Feyma, Suzanna C. MacLennan, Spencer Vaughan, Kylie E. Crompton, Susan M. Reid, Dinah S. Reddihough, Qing Shang, Chao Gao, Iona Novak, Nadia Badawi, Yana A. Wilson, Sarah J. McIntyre, Shrikant M. Mane, Xiaoyang Wang, David J. Amor, Daniela C. Zarnescu, Qiongshi Lu, Qinghe Xing, Changlian Zhu, Kaya Bilguvar, Sergio Padilla-Lopez, Richard P. Lifton, Jozef Gecz, Alastair H. MacLennan, Michael C. Kruer
Journal: Nature Genetics (2021)
Similar distribution of peripheral blood eosinophil counts in European and East Asian populations from investigations of large-scale general population studies: the Nagahama Study
Authors: Hironobu Sunadome, Susumu Sato, Hisako Matsumoto, Kimihiko Murase, Takahisa Kawaguchi, Yasuharu Tabara, Kazuo Chin, Fumihiko Matsuda, Toyohiro Hirai
Journal: European Respiratory Journal (2021)

<b>There is ambiguity in the interpretation of peripheral blood total eosinophil count, and several proposed cut-off values or thresholds of 300 cells per μL have been used to identify the patients who are most likely to benefit from inhaled corticosteroids</b>https://bit.ly/3ktCxof
Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination
Authors: Jiali Yu, Michael D. Green, Shasha Li, Yilun Sun, Sara N. Journey, Jae Eun Choi, Syed Monem Rizvi, Angel Qin, Jessica J. Waninger, Xueting Lang, Zoey Chopra, Issam El Naqa, Jiajia Zhou, Yingjie Bian, Long Jiang, Alangoya Tezel, Jeremy Skvarce, Rohan K. Achar, Merna Sitto, Benjamin S. Rosen, Fengyun Su, Sathiya P. Narayanan, Xuhong Cao, Shuang Wei, Wojciech Szeliga, Linda Vatan, Charles Mayo, Meredith A. Morgan, Caitlin A. Schonewolf, Kyle Cuneo, Ilona Kryczek, Vincent T. Ma, Christopher D. Lao, Theodore S. Lawrence, Nithya Ramnath, Fei Wen, Arul M. Chinnaiyan, Marcin Cieslik, Ajjai Alva, Weiping Zou
Journal: Nature Medicine (2021)
A Bispecific Single-Domain Antibody Boosts Autologous Vγ9Vδ2-T Cell Responses Toward CD1d in Chronic Lymphocytic Leukemia
Authors: Iris de Weerdt, Roeland Lameris, Jurjen M. Ruben, Renate de Boer, Jan Kloosterman, Lisa A. King, Mark-David Levin, Paul W.H.I. Parren, Tanja D. de Gruijl, Arnon P. Kater, Hans J. van der Vliet
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Although considerable progress has been made with autologous T cell–based therapy in B-cell malignancies, application in chronic lymphocytic leukemia (CLL) lags behind due to disappointing response rates as well as substantial toxicity that is of particular concern in the elderly CLL population. Vγ9Vδ2-T cells form a conserved T-cell subset with strong intrinsic immunotherapeutic potential, largely because of their capacity to be triggered by phosphoantigens that can be overproduced by CLL and other malignant cells. Specific activation of Vγ9Vδ2-T cells by a bispecific antibody may improve the efficacy and toxicity of autologous T-cell–based therapy in CLL. Experimental Design: We evaluated CD1d expression in a cohort of 78 untreated patients with CLL and generated and functionally characterized a CD1d-specific Vγ9Vδ2-T cell engager based on single-domain antibodies (VHH). Results: CD1d was expressed by CLL in the majority of patients, particularly in patients with advanced disease. The CD1d-specific Vγ9Vδ2-T cell engager induced robust activation and degranulation of Vγ9Vδ2-T cells, enabling Vγ9Vδ2-T cells from patients with CLL to lyse autologous leukemic cells at low effector-to-target ratios. Expression of CD1d on CLL cells is upregulated by all-trans retinoic acid, and sensitizes the malignant cells to bispecific VHH-induced lysis. Furthermore, we provide evidence that the Vγ9Vδ2-T cell receptor retains responsiveness to phosphoantigens when the bispecific VHH is bound, and aminobisphosphonates can therefore enhance bispecific Vγ9Vδ2-T cell engager–mediated tumor-specific killing. Conclusions: Collectively, our data demonstrate the immunotherapeutic potential of this novel CD1d-specific Vγ9Vδ2-T cell engager in CLL.