tbuckley/cabot-search huggingface dataset:
Characterizing Demographic, Racial, and Geographic Diversity in Dementia Research
Authors: Sanne S. Mooldijk, Silvan Licher, Frank J. Wolters
Journal: JAMA Neurology (2021)

For informed decision making on diagnosis and treatment of dementia, physicians and their patients rely on the generalizability of evidence from published studies to clinical practice. However, it is uncertain whether everyday care of elderly patients with dementia is sufficiently captured in contemporary research.To systematically review contemporary dementia research in terms of study and patient characteristics in order to assess generalizability of research findings.PubMed was searched for dementia studies published in the top 100 journals in the fields of neurology and neuroscience, geriatrics, psychiatry, and general medicine between September 1, 2018, and August 31, 2019. Two reviewers extracted study characteristics, including setting, number of participants, age at diagnosis, and use of biomarkers.Among 513 identified studies, 211 (41%) included fewer than 50 individuals with dementia and were excluded. The remaining 302 studies included a median (interquartile range) of 214 patients (98-628) with a mean (SD) age at diagnosis of 74.1 years (8.0). Age at diagnosis differed with study setting. Patients in the 180 clinic-based studies had a mean (SD) age of 71.8 (6.4) years at time of diagnosis compared with 80.6 (4.7) years among patients in the 79 population-based studies (mean difference, 8.8 years; 95% CI, 7.3-10.2). Use of magnetic resonance imaging, positron emission tomography imaging, and cerebrospinal fluid imaging was mostly done in clinic-based studies (80% to 96%) and consequently in relatively young patients (mean [SD] age, 71.6 [5.1] years). A longitudinal design was more common in population-based studies than in clinic-based studies (82 % vs 40%). Most studies originated from North America and Europe (89%), including almost exclusively White participants (among 74 studies [22%] reporting on ethnicity: median [interquartile range], 89% [78-97]). The 3 most studied cohorts represented 21% of all included study populations.Contemporary dementia research is limited in terms of racial and geographic diversity and draws largely from clinic-based populations with relatively young patients. Greater inclusivity and deeper phenotyping in unselected cohorts could improve generalizability as well as diagnosis and development of effective treatments for all patients with dementia.
Association Between Cervical Artery Dissection and Aortic Dissection
Authors: Jens Witsch, Saad A. Mir, Neal S. Parikh, Santosh B. Murthy, Hooman Kamel, Babak B. Navi, Alan Z. Segal, Matthew E. Fink, Stephanie B. Rutrick, Monika M. Safford, Nupoor Narula, Parag Goyal, Mario Gaudino, Leonard N. Girardi, Richard B. Devereux, Mary J. Roman, Cenai Zhang, Alexander E. Merkler
Journal: Circulation (2021)
Energy Harvesting Untethered Soft Electronic Devices (Adv. Healthcare Mater. 17/2021)
Authors: Kyun Kyu Kim, Joonhwa Choi, Seung Hwan Ko
Journal: Advanced Healthcare Materials (2021)

Human–Machine Interfaces In article number 2002286, Seung Hwan Ko and co-workers review the cutting edge of wearable devices. Recent development of untethered devices consists of a range of cutting-edge technologies such as electromagnetic, triboelectric, and thermoelectric energy harvesting. Recent advances in bio-fuel-based electronics show numerous solutions to the remaining practical issues of continuous measurement without an external power source. Key advancements in untethered devices in various power sources are introduced with their principles and working mechanisms.
A multifunctional nano-therapeutic platform based on octahedral yolk-shell Au NR@CuS: Photothermal/photodynamic and targeted drug delivery tri-combined therapy for rheumatoid arthritis
Authors: Ruqi Huang, Caiyi Zhang, Yeyang Bu, Zheng Li, Xin Zheng, Shang Qiu, Jeremiah Ong'achwa Machuki, Lijie Zhang, Yun Yang, Kaijin Guo, Fenglei Gao
Journal: Biomaterials (2021)
Converging 2D Nanomaterials and 3D Bioprinting Technology: State‐of‐the‐Art, Challenges, and Potential Outlook in Biomedical Applications
Authors: Hadi Rastin, Negar Mansouri, Tran Thanh Tung, Kamrul Hassan, Arash Mazinani, Mahnaz Ramezanpour, Pei Lay Yap, Le Yu, Sarah Vreugde, Dusan Losic
Journal: Advanced Healthcare Materials (2021)

Abstract The development of next‐generation of bioinks aims to fabricate anatomical size 3D scaffold with high printability and biocompatibility. Along with the progress in 3D bioprinting, 2D nanomaterials (2D NMs) prove to be emerging frontiers in the development of advanced materials owing to their extraordinary properties. Harnessing the properties of 2D NMs in 3D bioprinting technologies can revolutionize the development of bioinks by endowing new functionalities to the current bioinks. First the main contributions of 2D NMS in 3D bioprinting technologies are categorized here into six main classes: 1) reinforcement effect, 2) delivery of bioactive molecules, 3) improved electrical conductivity, 4) enhanced tissue formation, 5) photothermal effect, 6) and stronger antibacterial properties. Next, the recent advances in the use of each certain 2D NMs (1) graphene, 2) nanosilicate, 3) black phosphorus, 4) MXene, 5) transition metal dichalcogenides, 6) hexagonal boron nitride, and 7) metal–organic frameworks) in 3D bioprinting technology are critically summarized and evaluated thoroughly. Third, the role of physicochemical properties of 2D NMSs on their cytotoxicity is uncovered, with several representative examples of each studied 2D NMs. Finally, current challenges, opportunities, and outlook for the development of nanocomposite bioinks are discussed thoroughly.
Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension
Authors: Kel Vin Woo, Isabel Y. Shen, Carla J. Weinheimer, Attila Kovacs, Jessica Nigro, Chieh-Yu Lin, Murali Chakinala, Derek E. Byers, David M. Ornitz
Journal: Journal of Clinical Investigation (2021)

Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH. Mice lacking endothelial FGFR1/2, mice with activated endothelial FGFR signaling, and human pulmonary artery endothelial cells (HPAECs) were challenged with hypoxia. We assessed the effect of FGFR activation and inhibition on right ventricular pressure, vascular remodeling, and endothelial-mesenchymal transition (EndMT), a known pathologic change seen in patients with PH. Hypoxia-exposed mice lacking endothelial FGFRs developed increased PH, while mice overexpressing a constitutively active FGFR in endothelial cells did not develop PH. Mechanistically, lack of endothelial FGFRs or inhibition of FGFRs in HPAECs led to increased TGF-β signaling and increased EndMT in response to hypoxia. These phenotypes were reversed in mice with activated endothelial FGFR signaling, suggesting that FGFR signaling inhibits TGF-β pathway–mediated EndMT during chronic hypoxia. Consistent with these observations, lung tissue from patients with PH showed activation of FGFR and TGF-β signaling. Collectively, these data suggest that activation of endothelial FGFR signaling could be therapeutic for hypoxia-induced PH.
Full-length dystrophin restoration via targeted exon integration by AAV-CRISPR in a humanized mouse model of Duchenne muscular dystrophy
Authors: Adrian Pickar-Oliver, Veronica Gough, Joel D. Bohning, Siyan Liu, Jacqueline N. Robinson-Hamm, Heather Daniels, William H. Majoros, Garth Devlin, Aravind Asokan, Charles A. Gersbach
Journal: Molecular Therapy (2021)

Targeted gene-editing strategies have emerged as promising therapeutic approaches for the permanent treatment of inherited genetic diseases. However, precise gene correction and insertion approaches using homology-directed repair are still limited by low efficiencies. Consequently, many gene-editing strategies have focused on removal or disruption, rather than repair, of genomic DNA. In contrast, homology-independent targeted integration (HITI) has been reported to effectively insert DNA sequences at targeted genomic loci. This approach could be particularly useful for restoring full-length sequences of genes affected by a spectrum of mutations that are also too large to deliver by conventional adeno-associated virus (AAV) vectors. Here, we utilize an AAV-based, HITI-mediated approach for correction of full-length dystrophin expression in a humanized mouse model of Duchenne muscular dystrophy (DMD). We co-deliver CRISPR-Cas9 and a donor DNA sequence to insert the missing human exon 52 into its corresponding position within the DMD gene and achieve full-length dystrophin correction in skeletal and cardiac muscle. Additionally, as a proof-of-concept strategy to correct genetic mutations characterized by diverse patient mutations, we deliver a superexon donor encoding the last 28 exons of the DMD gene as a therapeutic strategy to restore full-length dystrophin in >20% of the DMD patient population. This work highlights the potential of HITI-mediated gene correction for diverse DMD mutations and advances genome editing toward realizing the promise of full-length gene restoration to treat genetic disease.
Association of Population Screening for Breast Cancer Risk With Use of Mammography Among Women in Medically Underserved Racial and Ethnic Minority Groups
Authors: Candice Schwartz, Ifeanyi Beverly Chukwudozie, Silvia Tejeda, Ganga Vijayasiri, Ivy Abraham, Mylene Remo, Hiral A. Shah, Maria Rojas, Alicia Carillo, Loraine Moreno, Richard B. Warnecke, Kent F. Hoskins
Journal: JAMA Network Open (2021)

Black women bear a disproportionate burden of breast cancer mortality in the US, in part due to inequities in the use of mammography. Population screening for breast cancer risk in primary care is a promising strategy for mitigating breast cancer disparities, but it is unknown whether this strategy would be associated with increased mammography rates in underserved women of racial and ethnic minority groups.To examine whether providing individualized breast cancer risk estimates is associated with an increase in the rate of screening mammography.A cohort study was conducted in women receiving individualized risk estimates as part of routine primary health care at federally qualified health centers in medically underserved communities in Chicago, Illinois. The study was conducted from November 5, 2013, to December 19, 2014, with data acquisition completed on March 5, 2017; data analysis was performed from December 30, 2020, to February 2, 2021. A total of 347 women aged 25 to 69 years without a personal history of breast cancer presenting for an annual visit with their primary care clinician were enrolled.Breast cancer risk estimates were obtained with validated risk assessment tools as a standard component of the clinic check-in process. One of 4 women at average risk and all women at high risk were invited to participate in the study.The primary outcome was the mammography rate during 18 months of usual care compared with the rate during 18 months after implementation of risk assessment.Of the 347 women enrolled, 188 were age-eligible for mammography and were included in the analysis (mean [SD] age, 50.8 [7.04] years); 70 women (37.2%) were Hispanic, 114 (60.6%) were non-Hispanic African American, and 4 (2.1%) were from other racial and ethnic groups (4 non-Hispanic White women). Ninety-eight women (52.1%) had an average risk of developing breast cancer and 90 (47.9%) were at high risk. Overall, there was a nonsignificant increase in the mammography rate, from 38.8% during usual care to 48.9% following implementation of risk assessment (odds ratio, 1.37; 95% CI, 0.92-2.03). In preplanned subgroup analysis, the mammography rate among women at high risk was significantly higher after vs before risk assessment (51.1% vs 36.6%; odds ratio, 1.88; 95% CI, 1.10-3.23).In this study, providing individualized breast cancer risk estimates as a component of primary health care in federally qualified health centers was associated with increased use of mammography among women of racial and ethnic minority groups who were at high risk. Implementation of this approach in underserved communities could promote equity in the use of mammography and reduce racial disparities in breast cancer mortality. This strategy warrants further investigation.
Staphylococcal Infections in Hospitals
Authors: André J. Nahmias, Theodore C. Eickhoff
Journal: New England Journal of Medicine (1961)

The Susceptible HostIt has been observed from earliest reports on staphylococcal disease that in certain groups staphylococcal infections are particularly likely not only to develop but also to have a fatal outcome.4, 136 With the use of clinical or epidemiologic observations several factors have been correlated grossly with susceptibility to staphylococcal infections: general factors, such as age, sex, race and nutritional or metabolic status; and predisposing diseases, such as diabetes, cystic fibrosis, agammaglobulinemia, agranulocytosis, neoplasms, chronic lung disease, influenza and other viral infections. Other related factors are trauma, operative wounds, foreign bodies, burns, eczema and other dermatitides, urinary catheterization, intravenous . . .
Factors Predicting Long Term Survival after Reduced Intensity Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia.
Authors: Charles F. Craddock, Sudhir Tauro, Joanne E. Gregory, Laura Buckley, Janice Ward, Panos Kottaridis, Eleni Thelouli, Kirsty Thomson, Donald Milligan, Emma Das-Gupta, Effie Liakpopoulou, John Snowden, John Yin, Andrew Peniket, Mark Cook, Stephen MacKinnon, Nigel H. Russell
Journal: Blood (2007)
Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis
Authors: Feng Wang, Ming-Ming He, Yi-Chen Yao, Xia Zhao, Zhi-Qiang Wang, Ying Jin, Hui-Yan Luo, Ji-Bin Li, Feng-Hua Wang, Miao-Zhen Qiu, Zhi-Da Lv, De-Shen Wang, Yu-Hong Li, Dong-Sheng Zhang, Rui-Hua Xu
Journal: Cell Reports Medicine (2021)

This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).
Correction to: LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis
Authors: Yun-ping Hu, Yun-peng Jin, Xiang-song Wu, Yang Yang, Yong-sheng Li, Huai-feng Li, Shan-shan Xiang, Xiao-ling Song, Lin Jiang, Yi-jian Zhang, Wen Huang, Shi-li Chen, Fa-tao Liu, Chen Chen, Qin Zhu, Hong-zhuan Chen, Rong Shao, Ying-bin Liu
Journal: Molecular Cancer (2021)
It’s more vital than ever that we have data to support the debate on assisted dying
Authors: Jacky Davis
Journal: BMJ (2021)

In May 2021, Matt Hancock, the then secretary of state for health, commissioned the Office for National Statistics (ONS) to inject fresh evidence into the assisted dying debate.1 The ONS has been asked to investigate how many dying people in the UK take their own lives and how many travel abroad to access assisted dying. This will help us to understand what effect, if any, the UK ban on assisted dying has on these cases. This is an encouraging development that should be welcomed by all. The debate about possible UK legislation for assisted dying has never gone away and is about to pick up again. Not only are jurisdictions considering changing their laws, but Jersey will debate whether assisted dying should be legalised after a citizens' jury said it was in favour of changing the law. The matter is also currently being debated in the House of Lords in the form of a private member’s bill put forward by Baroness Meacher. The subject is emotive and the debate often polarised, with more heat than light …
Abstract 9638: Multimodal Mechanisms for Rapid Conversion of Atrial Fibrillation by Pulmonary Delivery of a Novel Flecainide Formulation
Authors: Fernanda Tessarolo Silva, Giovanna C. Pedreira, Sofia A. Medeiros, Alexandre Bortolotto, Bruna Araujo Silva, Alexandre Marum, Bruce Nearing, Michael Hurrey, Prashanti Madhavapeddi, Carlos Schuler, Luiz Belardinelli, Richard L Verrier
Journal: Circulation (2019)

Introduction: Flecainide administered with a handheld nebulizer causes signature increases in PR interval and QRS complex duration with potential to terminate atrial fibrillation (AF) by optimizing...
A Transatlantic Comparison of Patient-Reported Access to and Use of Aspirin in Contemporary Preventive Cardiology
Authors: Alan P. Jacobsen, Zi Lun Lim, Blair Chang, Kaleb D. Lambeth, Thomas M. Das, Colin Gorry, Michael McCague, William Wijns, Patrick W.J.C. Serruys, Roger S. Blumenthal, Seth S. Martin, John W. McEvoy
Journal: Journal of the American College of Cardiology (2021)
Belumosudil: First Approval
Authors: Hannah A. Blair
Journal: Drugs (2021)

Belumosudil (REZUROCK™) is a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor that has been developed by Kadmon Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD) and systemic sclerosis. In July 2021, belumosudil received its first approval in the USA for the treatment of adult and paediatric patients aged ≥ 12 years with cGVHD after failure of at least two prior lines of systemic therapy. Belumosudil is under regulatory review in Australia, Canada, the UK and Switzerland for cGVHD. Clinical development for systemic sclerosis is ongoing in the USA. This article summarizes the milestones in the development of belumosudil leading to this first approval for the treatment of cGVHD.
Utilization of a Colorectal Cancer Screening Test Among Individuals With Average Risk
Authors: Deborah A. Fisher, Nicole Princic, Lesley-Ann Miller-Wilson, Kathleen Wilson, A. Mark Fendrick, Paul Limburg
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Colorectal cancer (CRC) screening reduces CRC incidence and mortality. It is important to examine screening patterns over time, including after the introduction of new screening modalities. <h3>Objective</h3> To compare use of CRC screening tests before and after the availability of the multitarget stool DNA (mt-sDNA) test, given that endorsed options have changed. <h3>Design, Setting, and Participants</h3> This longitudinal cohort study used administrative claims data to examine CRC screening use in 2 discrete periods: before (August 1, 2011, to July 31, 2014) and after (August 1, 2016, to July 31, 2019) the mt-sDNA test became available. The MarketScan Commercial and Medicare Supplemental databases were queried for individuals aged 45 to 75 years between August 1, 2011, and July 31, 2019, with average risk of CRC and with continuous enrollment in the databases from August 1, 2001, to July 31, 2019. <h3>Main Outcomes and Measures</h3> The proportion of individuals up to date or not due for CRC screening during each measurement year and the type of screening test used among individuals due for screening. Data were reported overall and among individuals aged 45 to 49 or 50 years and older on August 1, 2011. <h3>Results</h3> A total of 97 776 individuals with average risk were identified. Individuals had a mean (SD) age of 50.8 (3.5) years, and 54 227 (55.5%) were women. The proportion of individuals with average risk aged 50 to 75 years with commercial or Medicare supplemental insurance who were up to date with CRC screening increased from 50.4% in 2011 (30 605 of 60 770) to 69.7% in 2019 (42 367 of 60 770). Among individuals due for screening and screened, the use of high-sensitivity fecal occult blood test (FOBT) decreased between 2011 (1088 of 6241 eligible individuals [17.7%]) and 2019 (195 of 2943 eligible individuals [6.6%]), and the use of mt-sDNA increased between 2016 (58 of 3014 eligible individuals [1.9%]) and 2019 (418 of 2943 eligible individuals [14.2%]). No consistent trends were observed with fecal immunochemical test (FIT) or screening colonoscopy. Computed tomography colonography, double-contrast barium enema, and flexible sigmoidoscopy were rarely performed. <h3>Conclusions and Relevance</h3> In this cohort study, the proportion of individuals with average risk who were up to date with CRC screening increased between 2011 and 2019 but remained suboptimal. There were no substantial changes in the use of the colonoscopy or FIT; however, there was an increase in the adoption of mt-sDNA and a decrease in the use of FOBT during the study period.
Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation
Authors: Yael Goldfarb, Tal Givony, Noam Kadouri, Jan Dobeš, Cristina Peligero-Cruz, Itay Zalayat, Golda Damari, Bareket Dassa, Shifra Ben-Dor, Yael Gruper, Bergithe E. Oftedal, Eirik Bratland, Martina M. Erichsen, Amund Berger, Ayelet Avin, Shir Nevo, Uku Haljasorg, Yael Kuperman, Adi Ulman, Rebecca Haffner-Krausz, Ziv Porat, Ulus Atasoy, Dena Leshkowitz, Eystein S. Husebye, Jakub Abramson
Journal: The Journal of Experimental Medicine (2021)

The autoimmune regulator (AIRE) is essential for the establishment of central tolerance and prevention of autoimmunity. Interestingly, different AIRE mutations cause autoimmunity in either recessive or dominant-negative manners. Using engineered mouse models, we establish that some monoallelic mutants, including C311Y and C446G, cause breakdown of central tolerance. By using RNAseq, ATACseq, ChIPseq, and protein analyses, we dissect the underlying mechanisms for their dominancy. Specifically, we show that recessive mutations result in a lack of AIRE protein expression, while the dominant mutations in both PHD domains augment the expression of dysfunctional AIRE with altered capacity to bind chromatin and induce gene expression. Finally, we demonstrate that enhanced AIRE expression is partially due to increased chromatin accessibility of the AIRE proximal enhancer, which serves as a docking site for AIRE binding. Therefore, our data not only elucidate why some AIRE mutations are recessive while others dominant, but also identify an autoregulatory mechanism by which AIRE negatively modulates its own expression.
Molecular predictors of response to pembrolizumab in thymic carcinoma
Authors: Yongfeng He, Archana Ramesh, Yuriy Gusev, Krithika Bhuvaneshwar, Giuseppe Giaccone
Journal: Cell Reports Medicine (2021)

Thymic carcinoma is rare and has a poorer prognosis than thymomas. The treatment options are limited after failure of platinum-based chemotherapy. We previously performed a single-center phase II study of pembrolizumab in patients with advanced thymic carcinoma, showing a 22.5% response rate. Here, we characterize the genomic and transcriptomic profile of thymic carcinoma samples from 10 patients (5 non-responders versus 5 responders) in this cohort, with the main aim of identifying potential predictors of response to immunotherapy. We find that expression of PDL1 and alterations in genes or pathways that correlated with PD-L1 expression (CYLD and BAP1) could be potential predictors for response or resistance to immunotherapy in patients with advanced thymic carcinoma. Our study provides insights into potential predictive markers/pathways to select patients with thymic carcinoma for anti-PD-1 immunotherapy.