tbuckley/cabot-search huggingface dataset:
OS13.3.A Establishment of a novel system to specifically trace and ablate quiescent/slow cycling cells in high-grade glioma
Authors: F Antonica, L Santomaso, G Aiello, D Pernici, E Miele, L Tiberi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND High-grade gliomas are the most common malignant brain tumors, with poor prognosis due to recurrence and tumor infiltration after surgical removal and chemotherapy. Quiescent/slow cycling stem cells have been proposed to be one of the main players of tumor relapse but their involvement in in the infiltration remain unclear. Despite they have been described in mouse models or after transcriptional profiling of human tumor samples, their direct visualization, targeting and ablation remains a challenge. MATERIAL AND METHODS Tumors were induced over-expressing oncogenic forms of MET and p53 in the subventricular zone (SVZ) of P2 mouse brain as well as human forebrain organoids. The co-expression with specific cell cycle sensors as well as lineage specific CreERT2 under control of stem cells promoters allowed to visualize and target glioma stem cells. RESULTS Here, we used a fluorescent cell cycle sensor to visualize quiescent tumor cells in mouse brain cancer and human cancer organoids. In particular, we characterized them within the tumor revealing the invasiveness capacity of slow cycling tumor cells. Furthermore, we generated a new system to specifically trace and ablate such cells. Indeed, lineage tracing experiments allowed to trace quiescent Prom1 progeny in the tumors after temozolomide treatment. In addition, the selective ablation of qProm1 in mouse brain cancer reduced tumor infiltration. Finally, time-lapse experiments showed that slow cycling cells are also able to infiltrate co-cultured human brain cancer organoids. CONCLUSION Overall, our data show that quiescent/slow cycling cells are key driver of tumor invasiveness, the major malignant feature of high-grade brain cancer.
Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy
Authors: Roni Tamari, Ioannis Politikos, David A. Knorr, Santosha A. Vardhana, Jennifer C. Young, LeeAnn T. Marcello, Sital Doddi, Sean M. Devlin, Lakshmi V. Ramanathan, Melissa S. Pessin, Erica Dunn, Meighan Palazzo, Christina D. Bravo, Genovefa A. Papanicolaou, Mini Kamboj, Miguel Angel Perales, David J. Chung, Gunjan L. Shah
Journal: Blood Cancer Discovery (2021)

Immune recovery post–cellular therapies is an important predictor of response to the anti–SARS-CoV-2 vaccine and can be used to guide timing of primary vaccination, as well as booster vaccine, after therapy.
Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis
Authors: Vadim Pivniouk, Joao A. Gimenes-Junior, Peace Ezeh, Ashley Michael, Oksana Pivniouk, Seongmin Hahn, Sydney R. VanLinden, Sean P. Malone, Amir Abidov, Dayna Anderson, Justyna Gozdz, Avery DeVries, Fernando D. Martinez, Christian Pasquali, Donata Vercelli
Journal: Journal of Allergy and Clinical Immunology (2021)
Making extra room for carotenoids in plant cells: New opportunities for biofortification
Authors: Salvador Torres-Montilla, Manuel Rodriguez-Concepcion
Journal: Progress in Lipid Research (2021)

Plant carotenoids are essential for photosynthesis and photoprotection and provide colors in the yellow to red range to non-photosynthetic organs such as petals and ripe fruits. They are also the precursors of biologically active molecules not only in plants (including hormones and retrograde signals) but also in animals (including retinoids such as vitamin A). A carotenoid-rich diet has been associated with improved health and cognitive capacity in humans, whereas the use of carotenoids as natural pigments is widespread in the agrofood and cosmetic industries. The nutritional and economic relevance of carotenoids has spurred a large number of biotechnological strategies to enrich plant tissues with carotenoids. Most of such approaches to alter carotenoid contents in plants have been focused on manipulating their biosynthesis or degradation, whereas improving carotenoid sink capacity in plant tissues has received much less attention. Our knowledge on the molecular mechanisms influencing carotenoid storage in plants has substantially grown in the last years, opening new opportunities for carotenoid biofortification. Here we will review these advances with a particular focus on those creating extra room for carotenoids in plant cells either by promoting the differentiation of carotenoid-sequestering structures within plastids or by transferring carotenoid production to the cytosol.
Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR Trial
Authors: Hiddo J. L. Heerspink, Di Xie, George Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Dalane W. Kitzman, Donald Kohan, Hirofumi Makino, John J. V. McMurray, Vlado Perkovic, Peter Rossing, Hans-Henrik Parving, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2021)

Whether early reduction in albuminuria with atrasentan treatment predicts its long-term kidney-protective effect is unknown.To assess the long-term effects on kidney outcomes of atrasentan versus placebo in the SONAR trial, we enrolled patients who had type 2 diabetes and CKD (stage 2-4) and a urinary albumin creatinine ratio (UACR) of 300-5000 mg/g; participants were receiving maximum tolerated renin-angiotensin system inhibition. After 6 weeks exposure to 0.75 mg/day atrasentan (enrichment period), participants were randomized (stratified by UACR response during enrichment, ranging from ≤60% to >0%) to continue atrasentan or transition to placebo. Primary kidney outcome was a composite of sustained serum creatinine doubling or ESKD.UACR response to atrasentan during enrichment persisted throughout the double-blind treatment phase and predicted the primary kidney outcome, whereas UACR levels with placebo remained below pre-enrichment values in the two highest UACR response strata, and exceeded pre-enrichment values in the two lowest strata. As a result, early UACR response to atrasentan during enrichment was also associated with the primary kidney outcome during placebo. Accordingly, the predictive effect of early albuminuria changes during atrasentan was eliminated after placebo correction, leading to a consistent relative risk reduction for the primary kidney outcome with atrasentan compared with placebo, irrespective of the initial UACR response. The difference between atrasentan and placebo in UACR during double-blind treatment was also consistent across UACR response strata.Our findings do not support UACR response as a causal predictor of atrasentan's treatment effect. However, the variable trajectory in UACR with placebo, aspects of the trial design, day-to-day variability in albuminuria, and potential long-lasting effects of atrasentan may have contributed.
Asian American ethnic subgroup disparities in time to surgical treatment for breast cancer in the California Cancer Registry.
Authors: Stephanie Navarro, Yifei Yang, Carol Ochoa, Aaron Mejia, Sue Kim, Lihua Liu, Caryn Lerman, Albert Farias
Journal: Journal of Clinical Oncology (2021)

101 Background: Health risks and outcomes among Asian American patients are not adequately understood when Asians are treated as a homogenous ethnic group. This work is the first to explore trends in time to surgical treatment for breast cancer amongst Asian American ethnic subgroups. Methods: We used data from the population-based California Cancer Registry to identify a cohort of females diagnosed with invasive breast cancer between 2012-2017 in California. Time to surgical treatment was defined as the time elapsed between definitive diagnosis of breast cancer and receipt of surgery. Covariates included individual patient sociodemographic, health history, and tumor characteristics. Multivariable logistic regression was used to determine the odds of receiving surgery within 30 and 90 days of breast cancer diagnosis and multivariable Cox proportional hazards regression was used to analyze the likelihood of shorter time to surgery. A Bonferroni corrected alpha level was used to account for multiple racial/ethnic group comparisons. Results: Of 106,441 breast cancer patients, 57% were non-Hispanic white (NHW), 21% were Hispanic, 14% were Asian (4% Filipino; 3% Chinese; 1% each of Asian Indian or Pakistani (AIP), Vietnamese, Japanese, and Korean; 3% other Asian), and 6% were non-Hispanic black (NHB). Compared to NHWs, Hispanics (OR = 0.86, 99.5% CI = 0.82-0.92) and NHBs (OR = 0.82, 99.5% CI = 0.76-0.90) were less likely to receive surgery within 30 days of breast cancer diagnosis, while Chinese (OR = 1.30, 99.5% CI = 1.17-1.45) and AIPs (OR = 1.24, 99.5% CI = 1.04-1.48) were more likely to receive surgery within 30 days. These trends persisted for Hispanic (OR = 0.87, 99.5% CI = 0.79-0.96), NHB (OR = 0.73, 99.5% CI = 0.63-0.85), and Chinese patients (OR = 1.33, 99.5% CI = 1.04-1.71) when analyzing the likelihood of receiving surgery within 90 days of diagnosis. Compared to NHWs, Hispanics (OR = 0.94, 99.5% CI = 0.92-0.97), NHBs (OR = 0.88, 99.5% CI = 0.85-0.91), and Vietnamese (OR = 0.90, 99.5% CI = 0.83-0.98) were less likely to experience shorter time to surgical treatment, while Chinese (OR = 1.15, 99.5% CI = 1.09-1.21) and AIPs (OR = 1.09, 99.5% CI = 1.01-1.18) were more likely to have shorter time to surgery. Conclusions: In this population-based study of the California Cancer Registry, trends in time to surgical treatment for breast cancer were not consistent for patients belonging to different Asian ethnic subgroups. While Chinese and AIP patients tended to receive surgery sooner than NHW patients, Vietnamese patients face a disparity in receiving timely surgical treatment relative to NHW patients. Further research is needed to fully understand and appropriately target disparities in breast cancer treatment for patients of different Asian American ethnic subgroups.
Analysis of racial disparities in time to treatment initiation and survival among patients with advanced cancers.
Authors: Teresa Maria Zyczynski, Cardinale B. Smith, Ying Zhang, Yi Hao
Journal: Journal of Clinical Oncology (2021)

127 Background: Racial disparities in cancer care have received increased attention in recent years. One previously identified disparity is in the time to treatment initiation (TTI) – a factor closely associated with outcomes. While most research in the US to date has focused on the Medicaid and Medicare populations, this study examined disparities between different racial/ethnic groups in TTI and overall survival (OS) among patients with cancer managed in the community setting. Methods: Using the Flatiron Health electronic health record database, patients diagnosed with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), multiple myeloma (MM), advanced gastroesophageal cancer (aGastric), advanced urothelial cancer (aUL), metastatic renal cell carcinoma (mRCC) or advanced melanoma (aMel) and treated with first-line (1L) therapy, with ≥1 month of follow-up during 2014-2019, were included. Patient characteristics, TTI and outcomes were compared across race/ethnicity groups classified as White, Black, Asian and Hispanic/Latino/Other (Other). Results: A total of 81,543 patients were evaluated (37% aNSCLC, 19% mCRC, 15% mBC, 8% MM, 6% aGastric, 5.2% aUL, 5.0% mRCC and 4.1% aMel); 67% were White, 9% Black, 3% Asian and 11% Other. Overall, TTI was similar across race/ethnicity groups (median range 1.1–1.2 months), and 44% of all patients received treatment ≤30 days post-diagnosis. Overall Survival (months). Median OS varied by tumor and race/ethnicity groups (Table). However, multivariate Cox proportional hazards analysis showed that Asian patients had better OS than Black patients in many cancers (hazard ratio [HR] 0.8 aNSCLC, 0.75 mBC, 0.63 aGastric, 0.59 aUL, 0.81 mCRC, 0.68 mRCC), while White patients had better survival than Black patients in mBC (HR 0.8) and aGastric (HR 0.87). Conclusions: In this real-word analysis, TTI did not differ by race/ethnicity group for any of the cancers examined. However, some differences in OS emerged on multivariate analysis – this was longer in Asian than Black patients in aNSCLC, mBC, mCRC, aGastric, aUL and mRCC, and longer in White than Black patients in mBC and aGastric. Given the small sample size in some groups, further analyses are needed to determine the influence of race/ethnicity on cancer care and outcomes.[Table: see text]
A hierarchical bilayer architecture for complex tissue regeneration
Authors: Min Yu, Dan Luo, Jing Qiao, Jiusi Guo, Danqing He, Shanshan Jin, Lin Tang, Yu Wang, Xin Shi, Jing Mao, Shengjie Cui, Yu Fu, Zixin Li, Dawei Liu, Ting Zhang, Chi Zhang, Zhou Li, Yongsheng Zhou, Yan Liu
Journal: Bioactive Materials (2021)

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro, whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro. After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.
Point-of-care tests to inform antibiotic prescribing
Authors: Alastair D Hay
Journal: BMJ (2021)

The tests have potential but more evidence is needed

Given the global concerns about antibiotic resistance,1 antimicrobial stewardship is essential to preserve the future effectiveness of antibiotics.2 Healthcare practitioners must balance public and patient health, ensuring that only patients who need antibiotics receive them, and that they receive an antibiotic to which their infection is susceptible, at the optimum time, dose, and duration. Whether to prescribe an antibiotic is a key issue for clinicians treating respiratory infections in the community.

Point-of-care tests provide results in time to inform treatment. For respiratory infections, the tests can identify the presence of a microbe345 or measure markers of a host’s response to a microbe, such as C reactive protein or procalcitonin, in finger prick quantities of blood.

The only point-of-care tests currently recommended in the UK are urine dipstick for suspected urinary tract infections by Public Health England6 and C reactive protein for suspected pneumonia by the National Institute for Health and Care Excellence.7 Although dipstick, C reactive protein, and procalcitonin point-of-care tests are widely used internationally, the use of C reactive protein and procalcitonin remains rare in UK primary care.

Existing evidence shows that C reactive protein point-of-care …
Reasons for first-line maintenance therapy discontinuation among patients with newly diagnosed advanced ovarian cancer treated in real-world settings.
Authors: Jinan Liu, Premal H. Thaker, Janvi Sah, Eric M Maiese, Linda Kalilani, Rajesh Mallampati, Jean Hurteau, John Chan
Journal: Journal of Clinical Oncology (2021)

290 Background: PARP inhibitor (PARPi) and bevacizumab have been integrated into the first-line (1L) maintenance therapy for patients (pts) with ovarian cancer (OC). However, due to adverse events, the rate of PARPi maintenance discontinuation was 12% in the SOLO1 clinical trial. We aimed to better understand the rate and cause of maintenance therapy discontinuation in real-world practice. Methods: This retrospective cohort study was conducted using de-identified electronic health record (EHR)–derived data from the nationwide Flatiron Health electronic health database. From January 1, 2016, to February 29, 2020, data were obtained for pts with newly diagnosed stage III/IV epithelial OC who received primary debulking surgery followed by 6–9 cycles of 1L platinum-based chemo or neoadjuvant chemo followed by interval debulking surgery. Index date was the end of 1L systemic therapy. Results: Of 675 pts with stage III/IV OC who underwent primary systemic therapy, 144 (21.3%) received 1L maintenance therapy and were included in the analysis. Mean age was 65.0 y. Most pts were treated in community practice (93.1%), had ECOG score of 0–1 at diagnosis (81.3%), and were shown to be BRCA wild type (66.7%). Bevacizumab was the most common 1L maintenance therapy (n = 69, 47.9%), followed by olaparib (n = 46, 31.9%), paclitaxel (n = 18, 12.5%), rucaparib (n = 10, 6.9%), and gemcitabine (n = 1, 0.7%). Overall, 34 (23.6%) pts discontinued 1L maintenance therapy. The most common reason for discontinuation was disease progression (n = 19, 13.2%), followed by treatment-related toxicity (n = 13, 9.0%; Table). Of 56 pts who received PARPi (olaparib or rucaparib) 1L maintenance therapy, 21 (37.5%) pts discontinued treatment: 11 (19.6%) because of disease progression, 9 (16.0%) treatment-related toxicity, and 1 for other reasons. Conclusions: In pts with advanced OC who received 1L maintenance therapy in clinical practice, disease progression was the most common reason for maintenance therapy discontinuation. The rates of toxicity-related discontinuations were comparable with those reported in clinical trials.[Table: see text]
Cross government strategy needed to reduce health inequalities, says alliance
Authors: Jacqui Wise
Journal: BMJ (2021)

A coalition of health and social care organisations has written to the prime minister to call for an explicit cross-government strategy to reduce health inequalities.

The Inequalities in Health Alliance says this should have clear measurable targets that consider the role of every department and uses every available policy lever to tackle health disparities.

A position paper— The case for a cross-government strategy —from the Royal College of Physicians, which convenes the Inequalities in Health Alliance, highlights real life stories of how people’s health is impacted by non-clinical factors such as poor housing.1

One doctor said that they have a …
T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy
Authors: Shuang Li, Di Zhou, Arlene Sirajuddin, Jian He, Jing Xu, Baiyan Zhuang, Jinghan Huang, Gang Yin, Xiaohan Fan, Weichun Wu, Xiaoxin Sun, Shihua Zhao, Andrew E. Arai, Minjie Lu
Journal: JACC. Cardiovascular imaging (2021)
Microbubble Functionalization with Platelet Membrane Enables Targeting and Early Detection of Sepsis‐Induced Acute Kidney Injury
Authors: Jing Yang, Xiaoyan Miao, Yu Guan, Chaojin Chen, Sufang Chen, Xinmin Zhang, Xue Xiao, Zheng Zhang, Zhengyuan Xia, Tinghui Yin, Ziqing Hei, Weifeng Yao
Journal: Advanced Healthcare Materials (2021)

Abstract The morbidity and mortality of sepsis‐induced acute kidney injury (SAKI) remain high. Early detection using molecular ultrasound imaging may reduce mortality and improve the prognosis. Inspired by the intrinsic relationship between platelets and SAKI, platelet membrane‐coated hybrid microbubbles (Pla‐MBs) are designed for early recognition of SAKI. Pla‐MBs are prepared by ultrasound‐assisted recombination of liposomes and platelets, consisting of inherent platelet membrane isolated from platelets. By coating with platelet membranes, Pla‐MBs are endowed with various adhesive receptors (such as integrin α IIb β 3), providing a benefit for selective adhesion to damaged endothelium in SAKI. In a rat SAKI model, by combining the advantages of molecular ultrasound imaging and platelet membrane, Pla‐MBs display platelet‐mimicking properties and achieve the early targeted diagnosis of SAKI prior to the regular laboratory markers of kidney function. Moreover, the expression of platelet‐binding proteins (von Willebrand factor and fibrinogen) in the kidneys shows consistent results with molecular ultrasound imaging. Together, microbubble functionalization with platelet membranes is diagnostically beneficial for SAKI and might be a promising modality for endothelial injury diseases in the future.
Management of acne vulgaris: summary of NICE guidance
Authors: Jingyuan Xu, Ifigeneia Mavranezouli, Laura Kuznetsov, M Stephen Murphy, Eugene Healy
Journal: BMJ (2021)

### What you need to know Acne vulgaris is the eighth most common disease globally, resulting in >70 000 patients being referred for specialist care in the UK each year.12 While acne vulgaris most often affects adolescents, it is not uncommon in adults and can occur in children. The clinical features vary depending on its severity and its associated psychological impact. Acne vulgaris may persist and lead to pigmentary changes and permanent scarring. This article summarises the guideline from the National Institute for Health and Care Excellence (NICE) on the management of acne vulgaris.3 This guidance was developed with the aim to improve the management of acne vulgaris and reduce sequelae, with a clear framework of referral to more specialised services as appropriate. Throughout the summary and guideline, “acne” refers to acne vulgaris unless otherwise stated. ### How the guideline fits in practice
Minimal Model–Derived Insulin Sensitivity Index Underestimates Insulin Sensitivity in Black Americans
Authors: Andin Fosam, Susan Yuditskaya, Camila Sarcone, Shivraj Grewal, Hubert Fan, Ranganath Muniyappa
Journal: Diabetes Care (2021)

OBJECTIVE To examine the ethnic differences in insulin sensitivity (SI) as measured by the minimal model approach (SI-MM) and the reference method, the euglycemic-hyperinsulinemic clamp (EHC). RESEARCH DESIGN AND METHODS In a prospective study design, thirty Black Americans (BA) were age, sex, and BMI matched with non-Hispanic Whites (NHW). Participants underwent frequently sampled intravenous tolerance test (FSIVGTT) and EHC on 2 separate days during a single visit. RESULTS SI-MM values were significantly lower in BA when compared with NHW (0.035 ± 0.025 vs. 0.058 ± 0.036 [dL/min]/[μU/mL]; P = 0.003). However, there were no ethnic differences in SI measured by EHC (0.028 ± 0.012 vs. 0.035 ± 0.019 [dL/min]/[μU/mL]; P = 0.18). CONCLUSIONS SI-MM systematically underestimates SI in BA when compared with NHW. These findings suggest that studies inferring lower SI in BA based on FSIVGTT and SI-MM should be interpreted cautiously.