tbuckley/cabot-search huggingface dataset:
Porous Silicon Nanocarriers with Stimulus‐Cleavable Linkers for Effective Cancer Therapy
Authors: Yufei Xue, Hua Bai, Bo Peng, Terence Tieu, Jiamin Jiang, Shiping Hao, Panpan Li, Mark Richardson, Jonathan Baell, Helmut Thissen, Anna Cifuentes, Lin Li, Nicolas H. Voelcker
Journal: Advanced Healthcare Materials (2022)

Abstract Porous silicon nanoparticles (pSiNPs) are widely utilized as drug carriers due to their excellent biocompatibility, large surface area, and versatile surface chemistry. However, the dispersion in pore size and biodegradability of pSiNPs arguably have hindered the application of pSiNPs for controlled drug release. Here, a step‐changing solution to this problem is described involving the design, synthesis, and application of three different linker‐drug conjugates comprising anticancer drug doxorubicin (DOX) and different stimulus‐cleavable linkers (SCLs) including the photocleavable linker ( ortho ‐nitrobenzyl), pH‐cleavable linker (hydrazone), and enzyme‐cleavable linker ( β ‐glucuronide). These SCL‐DOX conjugates are covalently attached to the surface of pSiNP via copper (I)‐catalyzed alkyne‐azide cycloaddition (CuAAC, i.e., click reaction) to afford pSiNP‐SCL‐DOXs. The mass loading of the covalent conjugation approach for pSiNP‐SCL‐DOX reaches over 250 µg of DOX per mg of pSiNPs, which is notably twice the mass loading achieved by noncovalent loading. Moreover, the covalent conjugation between SCL‐DOX and pSiNPs endows the pSiNPs with excellent stability and highly controlled release behavior. When tested in both in vitro and in vivo tumor models, the pSiNP‐SCL‐DOXs induces excellent tumor growth inhibition.
Factors Associated With Penicillin Allergy Labels in Electronic Health Records of Children in 2 Large US Pediatric Primary Care Networks
Authors: Margaret G. Taylor, Torsten Joerger, Yun Li, Michael E. Scheurer, Michael E. Russo, Jeffrey S. Gerber, Debra L. Palazzi
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking. <h3>Objective</h3> To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks. <h3>Design, Setting, and Participants</h3> This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021. <h3>Exposures</h3> Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location. <h3>Main Outcomes and Measures</h3> Addition of penicillin allergy label in the electronic medical record. <h3>Results</h3> Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions. <h3>Conclusions and Relevance</h3> In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy–labeling in children is warranted.
RISK OF ISCHEMIC AND BLEEDING ADVERSE EVENTS IN HIGH BLEEDING RISK PATIENTS RECEIVING PERCUTANEOUS CORONARY INTERVENTION: 10 YEAR OUTCOME OF A NATIONWIDE COHORT STUDY
Authors: Jeehoon Kang, Hak Seung Lee, Doyeon Hwang, Jung Kyu Han, Han-mo Yang, Kyung Woo Park, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2022)
Bile multi‐omics analysis classifies lipid species and microbial peptides predictive of carcinoma of gallbladder
Authors: Nupur Sharma, Manisha Yadav, Gaurav Tripathi, Babu Mathew, Vasundhra Bindal, Sanyam Falari, Viniyendra Pamecha, Jaswinder Singh Maras
Journal: Hepatology (2022)

Abstract Background and Aims Histopathological examination is the gold standard for detection of gallstone (GS) or gallbladder carcinoma (CAGB). Bile concentrated in the gallbladder (GB) is expected to recapitulate metagenomics and molecular changes associated with development of CAGB. Approach and Results Bile samples were screened for lipidomics and metaproteome (metagenomics) signatures capable of early detection of cancer in GB anomalies. Analysis of the training cohort ( n = 87) showed that metastability of bile was reduced in CAGB ( p &lt; 0.05). CAGB bile showed significant alteration of lipidome and microbiome as indicated by multivariate partial least squares regression analysis and alpha‐diversity and beta‐diversity indexes ( p &lt; 0.05). Significant reduction of lipid species and increase in bacterial taxa were found to be associated with patients with CAGB, CAGB with GS, and GS ( p &lt; 0.05, log fold change &gt;1.5). A multimodular correlation network created using weighted lipid/metaproteomic correlation network analysis showed striking associations between lipid and metaproteomic modules and functionality. CAGB‐linked metaproteomic modules/functionality directly correlated with lipid modules, species, clinical parameters, and bile acid profile ( p &lt; 0.05). Increased bacterial taxa ( Leptospira , Salmonella enterica , Mycoplasma gallisepticum ) and their functionality showed a direct correlation with lipid classes such as lysophosphatidylinositol, ceramide 1‐phosphate, and lysophosphatidylethanolamine and development of CAGB ( r 2 &gt; 0.85). Lipid/metaproteomic signature–based probability of detection for CAGB was &gt; 90%, whereas that for GS was &gt; 80% ( p &lt; 0.05). Validation of eight lipid species using four machine learning algorithms in two separate cohorts ( n = 38; bile [test cohort 1] and paired plasma [test cohort 2]) showed accuracy (99%) and sensitivity/specificity (&gt;98%) for CAGB detection. Conclusions Bile samples of patients with CAGB showed significant reduction in lipid species and increase in bacterial taxa. Our study identifies a core set of bile lipidome and metaproteome signatures which may offer universal utility for early diagnosis of CAGB.
PROGNOSTIC VALIDITY OF FRAILTY ASSESSMENT TOOLS IN PREDICTION OF MORTALITY AND MAJOR AMPUTATION IN PATIENTS UNDERGOING REVASCULARIZATION FOR LOWER EXTREMITY ARTERIAL DISEASE
Authors: Roozbeh Nikooie, Kim G.E. Smolderen, Mohammed Al-Damluji, Can Meng, Feng Dai, Michael Nanna, Bauer E. Sumpio, Peter Henke, Carlos Mena-Hurtado
Journal: Journal of the American College of Cardiology (2022)
Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar
Authors: Laith J. Abu-Raddad, Hiam Chemaitelly, Houssein H. Ayoub, Sawsan AlMukdad, Hadi M. Yassine, Hebah A. Al-Khatib, Maria K. Smatti, Patrick Tang, Mohammad R. Hasan, Peter Coyle, Zaina Al-Kanaani, Einas Al-Kuwari, Andrew Jeremijenko, Anvar H. Kaleeckal, Ali N. Latif, Riyazuddin M. Shaik, Hanan F. Abdul-Rahim, Gheyath K. Nasrallah, Mohamed Ghaith Al-Kuwari, Adeel A. Butt, Hamad Eid Al-Romaihi, Mohamed H. Al-Thani, Abdullatif Al-Khal, Roberto Bertollini
Journal: New England Journal of Medicine (2022)

Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear.
Abstract P5-08-15: Overcoming mTOR inhibitor resistance by targeting the lysosomal deregulation
Authors: Shengzhe Zhang, Sung Ho Lee, Litong Nie, Youn-Sang Jung, Sohee Jun, Jie Zhang, Esther M Lien, Junjie Chen, Jae-Il Park
Journal: Cancer Research (2022)

Abstract Increasing evidence suggests that the deregulated lysosomes contribute to tumorigenesis and therapeutic resistance. However, its underlying mechanisms remain elusive. Here, we identify transmembrane protein 9 (TMEM9) as a regulator involved in lysosomal metabolism and mammary tumorigenesis. The TMEM9 gene is markedly amplified in breast cancer, correlated with its transcriptional upregulation. We uncovered that Tmem9 knock-out inhibited mammary tumorigenesis in genetically engineered mouse models. Consistently, TMEM9 depletion suppressed the proliferation of breast cancer cells highly expressing TMEM9. Conversely, the ectopic expression of TMEM9 in TMEM9 low breast cancer cells promoted cell proliferation. The lysosome purification and proteomics approach showed that TMEM9 physically and functionally interacts with LAMTOR4, a subunit of the Ragulator complex, to hyperactivate mTOR signaling in breast cancer. Moreover, the combination of TMEM9-v-ATPase inhibitors with mTOR inhibitors exhibited the synergistic growth inhibition of breast cancer cells in vitro and in vivo. Our results reveal that the TMEM9-v-ATPase axis is not only a biomarker for resistance to mTOR inhibition therapy but also a molecular target overcoming mTOR inhibitor resistance. Citation Format: Shengzhe Zhang, Sung Ho Lee, Litong Nie, Youn-Sang Jung, Sohee Jun, Jie Zhang, Esther M Lien, Junjie Chen, Jae-Il Park. Overcoming mTOR inhibitor resistance by targeting the lysosomal deregulation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-15.
PHYSICAL AND PSYCHOSOCIAL EFFECTS OF CARDIAC REHABILITATION PARTICIPATION IN WOMEN COMPARED TO MEN
Authors: Ihab Yassin, Majed Malak, Pavel Hushcha, S. Hammad Jafri, Gisele Bousquet, Lauren Mellett, Lexie Cabral, Lindsay Sonis, Christine Lutfy, Donna M. Polk, Hicham Skali
Journal: Journal of the American College of Cardiology (2022)
BENEFITS OF RIVAROXABAN AFTER LOWER EXTREMITY REVASCULARIZATION FOR SYMPTOMATIC PERIPHERAL ARTERY DISEASE ARE CONSISTENT WITH AND WITHOUT BACKGROUND STATIN THERAPY
Authors: Alexander Heilman, Rupert Bauersachs, Sonia Anand, Manesh R. Patel, Eike S. Debus, Mark Nehler, Connie Ng Hess, Warren H. Capell, Benjamin Osiemo, Judith A. Hsia, Eva Muehlhofer, Lloyd Haskell, Scott D. Berkowitz, Marc P. Bonaca
Journal: Journal of the American College of Cardiology (2022)
Measuring the transformative utopian impulse for planetary health in the age of the Anthropocene: a multi-study scale development and validation
Authors: Frédéric Basso, Dario Krpan
Journal: The Lancet Planetary Health (2022)

BackgroundTransformative utopian impulse for planetary health is people's propensity to have thoughts and engage in actions of which the purpose is to transform the current society into a better one in the future by addressing existing global issues. We aimed to develop a well-validated scale that can measure the transformative utopian impulse for planetary health and uncover its role in societal transformation.MethodsWe developed a scale to measure the transformative utopian impulse for planetary health across 11 studies with 6248 participants from the USA (from the MTurk database) and the UK (from the Prolifico.co database). Participants were eligible take part in the studies if they completed the consent form. Participants who did not pass the seriousness check or did not accurately answer all instructed response items were excluded from statistical analyses. We used exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) to determine the factor structure of the Transformative Utopian Impulse for Planetary Health Scale (TUIPHS). Then we analysed the TUIPHS' nomological network (ie, the relationships between TUIPHS and various constructs ranging from personality traits and values to economic, social, and political attitudes and beliefs). We then examined the scale's incremental predictive validity by testing whether it predicts various attitudes and behaviours relevant to social change beyond scales that measure competing constructs (this part of the study is registered at OSF Registries [https://osf.io/ztj2f]). Finally, we examined the TUIPHS' longitudinal predictive validity by probing whether it predicts people's future support for social change.FindingsData were collected between Oct 8, 2018, and July 6, 2020. We established that TUIPHS has a four-factor structure and can also be scored as a single general factor, indicating that it captures an overarching theoretical construct (ie, the transformative utopian impulse for planetary health). We then showed that the scale is related to various specific individual difference measures that capture diverse aspects of people's propensity to actively engage in thoughts and actions oriented toward the betterment of society. Moreover, TUIPHS predicted, above and beyond 20 competing scales highly correlated (r ≥0·50) with it, a series of 19 self-reported behavioural and attitudinal constructs pertaining to social change. Finally, participants' past TUIPHS scores predicted their support, a few months later, for social movements that aim to build a more just and resilient society than in the current day.InterpretationThis research lays the groundwork for future theoretical and empirical research into the psychological and behavioural processes attached to the transformative utopian impulse for planetary health as a source of transformative social change toward a better way of being and living.FundingThe London School of Economics and Political Science.
THE LEAD IS SHOT: AN UNLIKELY CAUSE OF ICD LEAD FRACTURE AND DEVICE MALFUNCTION
Authors: Christopher Barrett, Muhammad Aftab, Ryan G. Aleong, Alexis Z. Tumolo, Wendy S. Tzou, Michael Rosenberg, John Jason West, Lukasz Patrick Cerbin, James Mann, Syed Rafay Ali Sabzwari, Amneet Sandhu, Matthew Michael Zipse
Journal: Journal of the American College of Cardiology (2022)
MICRORNA 126 AS A SURROGATE MARKER FOR PRIMARY PREVENTION OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE ACROSS DIFFERENT AGE GROUPS IN SUSCEPTIBLE POPULATION
Authors: Arnab Banerjee, Debabrata Roy, Hindol Mazumdar, Rudranil Bhowmik, Sanmoy Karmakar, Abhishek Roy, Kaushik Manna, Navanil Biswas
Journal: Journal of the American College of Cardiology (2022)
EVALUATION OF APPLE WATCH ELECTROCARDIOGRAM TECHNOLOGY TO DETECT ATRIAL FIBRILLATION IN CARDIAC ELECTROPHYSIOLOGY PATIENTS: COMPARING COMPUTER VERSUS PHYSICAN INTERPRETATION IN PATIENTS UNDERGOING RHYTHM CONTROL STRATEGY FOR ATRIAL FIBRILLATION
Authors: Nabeel Saghir, Arjun Aggarwal, Nisha Soneji, Shree Lata Radhakrishnan, Brian Allen, Syed Saad, David Ben-Nun, Hanna Fanous, Samuel Kessel, Kristopher M. Heinzman, Mauricio F. Hong, Thomas K. Kurian
Journal: Journal of the American College of Cardiology (2022)
CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IS ASSOCIATED WITH CARDIOMYOPATHY: A NATIONWIDE COHORT ANALYSIS
Authors: Sahith Reddy Thotamgari, Udhayvir Grewal, Prabandh Reddy Buchhanolla, Aakash Sheth, Akhilesh Babbili, Paari Dominic
Journal: Journal of the American College of Cardiology (2022)
OUTCOME DIFFERENCES BETWEEN PREVALENT USERS VS. NEW USERS OF THE SAME DRUG: WHEN DRUG EFFECT OR SELECTION BIAS CANNOT EXPLAIN POOR OUTCOMES AMONG PREVALENT USERS
Authors: Charles Faselis, Phillip Hong Lam, Prakash C. Deedwania, Ioannis Kanonidis, Evangelos Kanonidis, Amiya Ahmed, Samir Patel, Venkatesh K. Raman, Wen-Chih Wu, Michael Doumas, Richard M. Allman, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2022)
Abstract P5-08-17: Small G protein RALA is a driver and potential therapeutic target in triple negative breast cancer
Authors: Dillon S. Richardson, Matthew W. Cole, Rachel E. Schafer, Jonathan M. Spehar, Sarah A. Steck, Manjusri Das, Arthur W. Lian, Alo Ray, Reena Shakya, Sue E. Knoblaugh, Cynthia D. Timmers, Gina M. Sizemore, Steven T. Sizemore
Journal: Cancer Research (2022)

Abstract Triple Negative Breast Cancer (TNBC) is the leading cause of cancer mortality in women, mostly due to the lack of targeted treatment for this subtype of breast cancer (BC). RALA and RALB are small GTPases implicated in tumor proliferation, survival, and metastasis in a variety of cancers. However, little is known of their roles in breast cancer. Utilizing 3D spheroid invasion assays, we identified that knockout (KO) of RALA greatly reduced the invasion of MDA-MB-231 spheroids in basement membrane extract (BME). Conversely, RALB-KO significantly increased 3D invasion of MDA-MB-231 cells. We further investigated roles for RALA and RALB in TNBC with cell viability assays, transwell assays, and 3D growth assays. Results indicate that KO or depletion of RALA in TNBC cell lines MDA-MB-231 and MDA-MB-468 reduces cell viability and cell migration capabilities in vitro. On the contrary, loss of RALB increased cell migration and viability. Treating TNBC cells with a small molecule inhibitor of both RAL isoforms (BQU57) reduced cell growth in vitro as well as tumor growth and metastasis in vivo. Furthermore, RALA expression, but not RALB expression, was predictive of response to chemotherapy in TNBC patients and RAL inhibitor sensitized TNBC cells to paclitaxel. Combined, these results highlight the importance of the RALs, particularly RALA, as a therapeutic targets in TNBC. Citation Format: Dillon S. Richardson, Matthew W. Cole, Rachel E. Schafer, Jonathan M. Spehar, Sarah A. Steck, Manjusri Das, Arthur W. Lian, Alo Ray, Reena Shakya, Sue E. Knoblaugh, Cynthia D. Timmers, Gina M. Sizemore, Steven T. Sizemore. Small G protein RALA is a driver and potential therapeutic target in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-17.
A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection
Authors: Nanda Kishore Routhu, Sailaja Gangadhara, Lilin Lai, Meredith E. Davis-Gardner, Katharine Floyd, Ayalnesh Shiferaw, Yannic C. Bartsch, Stephanie Fischinger, Georges Khoury, Sheikh Abdul Rahman, Samuel David Stampfer, Alexandra Schäfer, Sherrie M. Jean, Chelsea Wallace, Rachelle L. Stammen, Jennifer Wood, Cohen Joyce, Tamas Nagy, Matthew S. Parsons, Lisa Gralinski, Pamela A. Kozlowski, Galit Alter, Mehul S. Suthar, Rama Rao Amara
Journal: Science Immunology (2022)

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Authors: Jian Liu, Minyang Fu, Manni Wang, Dandan Wan, Yuquan Wei, Xiawei Wei
Journal: Journal of Hematology & Oncology (2022)

Abstract Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc . Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.
Performance of high-frequency ultrasound in the evaluation of skin involvement in cutaneous chronic graft-versus-host disease: A preliminary report
Authors: Elisa Molinelli, Giorgia Mancini, Valerio Brisigotti, Claudia Sapigni, Oriana Simonetti, Attilio Olivieri, Annamaria Offidani
Journal: Journal of the American Academy of Dermatology (2022)