tbuckley/cabot-search huggingface dataset:
Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases
Authors: Marcia A Friedman, Jeffrey R Curtis, Kevin L Winthrop
Journal: Annals of the Rheumatic Diseases (2021)

Patients with rheumatic diseases are at increased risk of infectious complications; vaccinations are a critical component of their care. Disease-modifying antirheumatic drugs may reduce the immunogenicity of common vaccines. We will review here available data regarding the effect of these medications on influenza, pneumococcal, herpes zoster, SARS-CoV-2, hepatitis B, human papilloma virus and yellow fever vaccines. Rituximab has the most substantial impact on vaccine immunogenicity, which is most profound when vaccinations are given at shorter intervals after rituximab dosing. Methotrexate has less substantial effect but appears to adversely impact most vaccine immunogenicity. Abatacept likely decrease vaccine immunogenicity, although these studies are limited by the lack of adequate control groups. Janus kinase and tumour necrosis factor inhibitors decrease absolute antibody titres for many vaccines, but do not seem to significantly impact the proportions of patients achieving seroprotection. Other biologics (interleukin-6R (IL-6R), IL-12/IL-23 and IL-17 inhibitors) have little observed impact on vaccine immunogenicity. Data regarding the effect of these medications on the SARS-CoV-2 vaccine immunogenicity are just now emerging, and early glimpses appear similar to our experience with other vaccines. In this review, we summarise the most recent data regarding vaccine response and efficacy in this setting, particularly in light of current vaccination recommendations for immunocompromised patients.
Reducing Obstetric Morbidity in In Vitro Fertilization Pregnancies
Authors: Daniela Diego, Heather S. Hipp
Journal: JAMA Network Open (2021)

Yuanyuan Wang, PhD; Huifeng Shi, PhD; Lian Chen, MD; Danni Zheng, PhD; Xiaoyu Long, MD; Yunjun Zhang, PhD; Haibo Wang, PhD; Ying Shi, MPH; Yangyu Zhao, MD; Yuan Wei, MD; Jie Qiao, MD, PhD
MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration
Authors: Ting Pan, Wenjing Song, Hongbao Xin, Haiyue Yu, He Wang, Dandan Ma, Xiaodong Cao, Yingjun Wang
Journal: Bioactive Materials (2021)

Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors - scaffold degradation behavior and miRNA release profile - on osteogenesis and bone formation is still poorly understood. Herein, we construct a series of miRNA-activated hydrogel scaffolds (MAHSs) generated by 3D printing with different crosslinking degree to screened the interplay between scaffold degradation and miRNA release in the osteoinduction activity both
From the Community to the Bench and Back Again: The Value of Patient and Community Engagement in Cancer Research
Authors: Amy E. Leader, Andrew E. Aplin
Journal: Cancer Discovery (2021)

Abstract Summary: Currently, patients and community members have more frequent interaction with clinical and population scientists than basic scientists, leading to gaps in their engagement across the cancer research continuum. Engaging patients and community members in all types of cancer research can bring personal experiences and societal factors to the forefront, informing scientists about these concerns and leading to research that is more responsive to patient and community needs. Engaging patients with cancer and community members as partners in research helps ensure that the scientific evidence generated is useful to patients and—more importantly—trusted by patients. This bidirectional engagement between patients/community members and research investigators fosters a collaborative and ethical foundation for scientific discovery. Although community-engaged research has been in existence for decades, more recent attention by national organizations to embed patients with cancer and community members into the research process has accelerated the importance of these efforts. Here, we describe the importance of patient and community engagement (PCE) in cancer research. We outline key principles in undertaking PCE in cancer research, provide a framework for PCE throughout the cancer research continuum, review metrics for evaluating the effectiveness of PCE in cancer research, and share opportunities for PCE in cancer research going forward.
Do Not Dismiss That Wenckebach
Authors: Seri Hanayneh, Ramil Goel
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The global incidence of bullous pemphigoid: a systematic review and meta‐analysis
Authors: M.S.M. Persson, N. Begum, M.J. Grainge, K.E. Harman, D. Grindlay, S. Gran
Journal: British Journal of Dermatology (2021)

Background Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. Objectives The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. Methods Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. Results Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8–13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2–60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8–18·2) and 5·6 (95% CI 3·5–9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0–29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. Conclusions The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.
Aberrant activation of the CD45-Wnt signaling axis promotes stemness and therapy resistance in colorectal cancer cells
Authors: So-Yeon Park, Ji-Young Kim, Gyu-Beom Jang, Jang-Hyun Choi, Jee-Heun Kim, Choong-Jae Lee, Sunjae Lee, Jeong-Heum Baek, Kwan-Kyu Park, Jin-Man Kim, Hee Jin Chang, Nam-Chul Cho, Jeong-Seok Nam
Journal: Theranostics (2021)

Rationale: Chemoradiation (CRT) is commonly used as an adjuvant or neoadjuvant treatment for colorectal cancer (CRC) patients. However, resistant cells manage to survive and propagate after CRT, increasing the risk of recurrence. Thus, better understanding the mechanism of resistant cancer cells is required to achieve better clinical outcomes. Methods: Here, we explored gene expression profiling of CRC patient tumors to identify therapy resistance genes and discovered that protein tyrosine phosphatase receptor type C (PTPRC), which encodes CD45, was increased in remnant tumor tissues after CRT and correlated with metastasis. Through multiple validations using patient tumors and CRC cell lines, we found for the first time the increase of CD45 expression in CRC (EpCAM+) epithelial cells surviving after CRT. Thus, we investigated the biological role and downstream events of CD45 were explored in human CRC cells and CRC mouse models. Results: Increased CD45 expression in cancer cells in pretreated primary tumors accounts for poor regression and recurrence-free survival in CRT-treated patients. High CD45 expression promotes CRC cell survival upon 5-fluorouracil or radiation treatment, while CD45 depletion sensitizes CRC cells to CRT. Intriguingly, CD45 is preferentially expressed in cancer stem-like cells (CSCs), as determined by spheroid culture and the expression of CSC markers, and is required for the distinct functions of CSCs, such as cancer initiation, repopulation, and metastasis. Mechanistically, CD45 phosphatase activity promotes Wnt transcriptional activity by stabilizing the β-catenin protein, which collectively enhances stemness and the therapy-resistant phenotype. Conclusions: Our results highlight a novel function of CD45 as a mediator of CRT resistance and provide a potential therapy strategy for CRC therapy.
Dosing extracellular vesicles
Authors: Dhanu Gupta, Antje Maria Zickler, Samir El Andaloussi
Journal: Advanced Drug Delivery Reviews (2021)

Extracellular vesicles (EVs) are natural nanoparticles containing biologically active molecules. They are important mediators of intercellular communication and can be exploited therapeutically by various bioengineering approaches. To accurately determine the therapeutic potential of EVs in pre-clinical and clinical settings, dependable dosing strategies are of utmost importance. However, the field suffers from inconsistencies comprising all areas of EV production and characterisation. Therefore, a standardised and well-defined process in EV quantification, key to reliable therapeutic EV dosing, remains to be established. Here, we examined 64 pre-clinical studies for EV-based therapeutics with respect to their applied EV dosing strategies. We identified variations in effective dosing strategies irrespective of the applied EV purification method and cell source. Moreover, we found dose discrepancies depending on the disease model, where EV doses were selected without accounting for published EV pharmacokinetics or biodistribution patterns. We therefore propose to focus on qualitative aspects when dosing EV-based therapeutics, such as the potency of the therapeutic cargo entity. This will ensure batch-to-batch reliability and enhance reproducibility between applications. Furthermore, it will allow for the successful benchmarking of EV-based therapeutics compared to other nanoparticle drug delivery systems, such as viral vector-based or lipid-based nanoparticle approaches.
A Closer Look at Racial Differences in Diabetes Outcomes Among a Community Sample: Diabetes Distress, Self-care, and HbA1c
Authors: Vicki S. Helgeson, Jeanean B. Naqvi, Mary T. Korytkowski, Tiffany L. Gary-Webb
Journal: Diabetes Care (2021)

OBJECTIVE Approximately 34 million people in the U.S. have diabetes. With this illness come substantial changes to psychological and physical health. However, type 2 diabetes disproportionately affects non-Hispanic Black compared with non-Hispanic White populations. The purpose of this study was to examine racial differences in psychological, behavioral, and physical health over time among individuals recently diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Data were collected from a community sample of 193 adults recently diagnosed with type 2 diabetes (44% female; 45% Black). Measures of distress, self-care behaviors, and HbA1c were taken at an initial interview (time 1) and 6 months later (time 2). Individuals wore an Actical accelerometer to assess physical activity and participated in three 24-h dietary recall interviews to assess dietary intake within 2 weeks of the initial interview. RESULTS From time 1 to time 2, Black women showed the highest increase in depressive symptoms. There was a greater increase in regimen and physician distress among White compared with Black participants. White men and Black women reported a decline in medication adherence over time. There were no racial differences in changes in physical activity across 6 months. However, Black individuals had higher overall calorie consumption with greater protein, saturated fat, and cholesterol intake than White individuals. There were no race or sex differences in changes in glycemic stability. CONCLUSIONS Initial adjustment to a diagnosis of type 2 diabetes differentially influences Black and White men and women in terms of depressive symptoms, diabetes distress, and self-care.
Identifying the best predictive diagnostic criteria for psoriasis in children (&lt; 18 years): a UK multicentre case–control diagnostic accuracy study (DIPSOC study)*
Authors: E. Burden‐Teh, R. Murphy, S. Gran, T. Nijsten, C. Hughes, A. Abdul‐Wahab, A. Bewley, N. Burrows, S. Darne, J.E. Gach, R. Katugampola, C.S. Jury, K. Kuet, J. Llewellyn, T. McPherson, J.C. Ravenscroft, S. Taibjee, C. Wilkinson, K.S. Thomas
Journal: British Journal of Dermatology (2021)

Background In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. Objectives To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. Methods A case–control diagnostic accuracy study in 12 UK dermatology departments (2017–2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. Results The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. Conclusions This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.
Bacterial Genotoxin Accelerates Transient Infection–Driven Murine Colon Tumorigenesis
Authors: Yue Liu, Kai Fu, Eric M. Wier, Yifan Lei, Andrea Hodgson, Dongqing Xu, Xue Xia, Dandan Zheng, Hua Ding, Cynthia L. Sears, Jian Yang, Fengyi Wan
Journal: Cancer Discovery (2021)

Abstract Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which include the human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine–aspartic acid dyad. Injected via the type III secretion system (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection–accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependent genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection–accelerated colon tumorigenesis in mice. Significance: We identified UshA, a novel T3SS-dependent genotoxin in A/E pathogens that possesses direct DNA digestion activity and confers bacterially accelerated colon tumorigenesis in mice. Our results demonstrate that acute and noninvasive infection with A/E pathogens harbors a far-reaching impact on the development of colon cancer. This article is highlighted in the In This Issue feature, p. 1
Dietary spinach reshapes the gut microbiome in an Apc-mutant genetic background: mechanistic insights from integrated multi-omics
Authors: Ying-Shiuan Chen, Jia Li, Rani Menon, Arul Jayaraman, Kyongbum Lee, Yun Huang, Wan Mohaiza Dashwood, Ke Zhang, Deqiang Sun, Roderick H. Dashwood
Journal: Gut Microbes (2021)

Complex interrelationships govern the dynamic interactions between gut microbes, the host, and exogenous drivers of disease outcome. A multi-omics approach to cancer prevention by spinach (SPI) was pursued for the first time in the polyposis in rat colon (Pirc) model. SPI fed for 26 weeks (10% w/w, freeze-dried in the diet) exhibited significant antitumor efficacy and, in the Apc-mutant genetic background, β-catenin remained highly overexpressed in adenomatous polyps. However, in both wild type and Apc-mutant rats, increased gut microbiome diversity after SPI consumption coincided with reversal of taxonomic composition. Metagenomic prediction implicated linoleate and butanoate metabolism, tricarboxylic acid cycle, and pathways in cancer, which was supported by transcriptomic and metabolomic analyses. Thus, tumor suppression by SPI involved marked reshaping of the gut microbiome along with changes in host RNA-miRNA networks. When colon polyps were compared with matched normal-looking tissues via metabolomics, anticancer outcomes were linked to SPI-derived linoleate bioactives with known anti-inflammatory/ proapoptotic mechanisms, as well as N-aceto-2-hydroxybutanoate, consistent with altered butanoate metabolism stemming from increased α-diversity of the gut microbiome. In colon tumors from SPI-fed rats, L-glutamate and N-acetylneuraminate also were reduced, implicating altered mitochondrial energetics and cell surface glycans involved in oncogenic signaling networks and immune evasion. In conclusion, a multi-omics approach to cancer prevention by SPI provided mechanistic support for linoleate and butanoate metabolism, as well as tumor-associated changes in L-glutamate and N-acetylneuraminate. Additional factors, such as the fiber content, also warrant further investigation with a view to delaying colectomy and drug intervention in at-risk patients.
Resurgence of SARS-CoV-2 Infection in a Highly Vaccinated Health System Workforce
Authors: Jocelyn Keehner, Lucy E Horton, Nancy J Binkin, Louise C Laurent, David Pride, Christopher A Longhurst, Shira R Abeles, Francesca J Torriani
Journal: New England Journal of Medicine (2021)

Resurgence of Covid-19 in Vaccinated Health Workers From March through July 2021, a total of 227 health care workers at UCSD, 57% of whom were fully vaccinated, tested positive for SARS-CoV-2; the ...
A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza
Authors: Julie C.F. Rappe, Katja Finsterbusch, Stefania Crotta, Matthias Mack, Simon L. Priestnall, Andreas Wack
Journal: The Journal of Experimental Medicine (2021)

Cytokine-mediated immune-cell recruitment and inflammation contribute to protection in respiratory virus infection. However, uncontrolled inflammation and the “cytokine storm” are hallmarks of immunopathology in severe infection. Cytokine storm is a broad term for a phenomenon with diverse characteristics and drivers, depending on host genetics, age, and other factors. Taking advantage of the differential use of virus-sensing systems by different cell types, we test the hypothesis that specifically blocking TLR7-dependent, immune cell–produced cytokines reduces influenza-related immunopathology. In a mouse model of severe influenza characterized by a type I interferon (IFN-I)–driven cytokine storm, TLR7 antagonist treatment leaves epithelial antiviral responses unaltered but acts through pDCs and monocytes to reduce IFN-I and other cytokines in the lung, thus ameliorating inflammation and severity. Moreover, even in the absence of IFN-I signaling, TLR7 antagonism reduces inflammation and mortality driven by monocyte-produced chemoattractants and neutrophil recruitment into the infected lung. Hence, TLR7 antagonism reduces diverse types of cytokine storm in severe influenza.