tbuckley/cabot-search huggingface dataset:
Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes
Authors: Yazhen Li, Lu Yang, Yue Hou, Zhenzhen Zhang, Miao Chen, Maoxia Wang, Jin Liu, Jun Wang, Zhihe Zhao, Chaoming Xie, Xiong Lu
Journal: Bioactive Materials (2022)

Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge. Here, a polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment. PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold. The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+ channels. Moreover, the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity. It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages. The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive, ROS-scavenging, anti-inflammatory, and immunomodulatory abilities. This study provides fundamental insights into the synergistical effects of conductivity, osteoinductivity, and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.
Collaboration and Shared Decision-Making Between Patients and Clinicians in Preventive Health Care Decisions and US Preventive Services Task Force Recommendations
Authors: Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael D. Cabana, Aaron B. Caughey, Esa M. Davis, Katrina E. Donahue, Chyke A. Doubeni, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2022)

The US Preventive Services Task Force (USPSTF) works to improve the health of people nationwide by making evidence-based recommendations for preventive services. Patient-centered care is a core value in US health care. Shared decision-making (SDM), in which patients and clinicians make health decisions together, ensures patients’ rights to be informed and involved in preventive care decisions and that these decisions are patient-centered. SDM has a role across the spectrum of USPSTF recommendations. For A or B recommendations (judged by the USPSTF to have high or moderate certainty of a moderate or substantial net benefit at the population level), SDM allows individual patients to decide whether to accept such services based on their personal values and preferences. For C recommendations (indicating at least moderate certainty of a small net benefit at the population level), SDM is critical for individual patients to decide whether the net benefit for them is worthwhile. For D recommendations (reflecting at least moderate certainty of a zero or negative net benefit) or I statements (low certainty of net benefit), clinicians should be prepared to discuss these services if patients ask. More evidence is needed to determine if, in addition to promoting patient-centeredness, SDM reduces inequities in preventive care, as well as to define new strategies to find time for discussion of preventive services in primary care.
Epigenetic regulation of CXCR4 signaling in cancer pathogenesis and progression
Authors: Reem Khaled M.E. Alsayed, Abdul Q. Khan, Fareed Ahmad, Abdul Wahid Ansari, Majid Ali Alam, Jorg Buddenkotte, Martin Steinhoff, Shahab Uddin, Aamir Ahmad
Journal: Seminars in Cancer Biology (2022)

Signaling involving chemokine receptor CXCR4 and its ligand SDF-1/CXL12 has been investigated for many years for its possible role in cancer progression and pathogenesis. Evidence emerging from clinical studies in recent years has further established diagnostic as well as prognostic importance of CXCR4 signaling. CXCR4 and SDF-1 are routinely reported to be elevated in tumors, distant metastases, which correlates with poor survival of patients. These findings have kindled interest in the mechanisms that regulate CXCR4/SDF-1 expression. Of note, there is a particular interest in the epigenetic regulation of CXCR4 signaling that may be responsible for upregulated CXCR4 in primary as well as metastatic cancers. This review first lists the clinical evidence supporting CXCR4 signaling as putative cancer diagnostic and/or prognostic biomarker, followed by a discussion on reported epigenetic mechanisms that affect CXCR4 expression. These mechanisms include regulation by non-coding RNAs, such as, microRNAs, long non-coding RNAs and circular RNAs. Additionally, we also discuss the regulation of CXCR4 expression through methylation and acetylation. Better understanding and appreciation of epigenetic regulation of CXCR4 signaling can invariably lead to identification of novel therapeutic targets as well as therapies to regulate this oncogenic signaling.
Development of Novel Aptamer-Based Targeted Chemotherapy for Bladder Cancer
Authors: Yao Wang, Yang Zhang, Peng-Chao Li, Jiajie Guo, Fan Huo, Jintao Yang, Ru Jia, Juan Wang, Qiju Huang, Dan Theodorescu, Hanyang Yu, Chao Yan
Journal: Cancer Research (2022)

Abstract Bladder cancer is common worldwide, with most patients presenting with nonmuscle invasive disease. Multiple intravesical recurrences lead to reduced quality of life and high costs for patients with this form of bladder cancer. Intravesical chemotherapy aimed at reducing recurrence is the standard-of-care but has significant side effects from nonspecific cytotoxicity to normal urothelium. Importantly, toxicity limits doses that can be administered. Thus, tumor-specific drug targeting could reduce toxicity and enhance effectiveness by allowing higher doses. Here, using cell internalization systematic evolution of ligands by exponential enrichment (SELEX), we identify a novel bladder cancer-specific, chemically modified nucleic acid aptamer that can be preferentially internalized into tumor cells but not normal urothelial cells. The 35-nucleotide B1 aptamer is internalized into bladder cancer cells through clathrin-mediated endocytosis and macropinocytosis. As proof of principle, a B1-guided DNA nanotrain delivery vehicle for epirubicin was constructed as a targeted intravesical chemotherapy. The B1-nanotrain-epirubicin construct exhibited selective cytotoxicity towards bladder cancer cells and outperformed epirubicin in murine orthotopic xenograft models of human bladder cancer. This aptamer-based delivery system makes targeted chemotherapy possible for bladder cancer, providing a compelling rationale for clinical development. Significance: These findings identify a bladder cancer–specific aptamer that can be used for targeted delivery of chemotherapy, potentially reducing toxicity and enhancing therapeutic efficacy.
Blockade of PD-L1/PD-1 signaling promotes osteo-/odontogenic differentiation through Ras activation
Authors: So Mi Jeon, Je Sun Lim, Su Hwan Park, Hyung Joon Kim, Hyung-Ryong Kim, Jong-Ho Lee
Journal: International Journal of Oral Science (2022)

The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
Association of Hearing Impairment and 24-Hour Total Movement Activity in a Representative Sample of US Adults
Authors: Pablo Martinez-Amezcua, Erin E. Dooley, Nicholas S. Reed, Danielle Powell, Bjoern Hornikel, Justin S. Golub, Kelley Pettee Gabriel, Priya Palta
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Lower physical activity (PA) levels have been proposed as a mechanism to explain the association between hearing loss and various adverse outcomes of aging. But whether hearing loss is associated with lower PA is poorly understood. <h3>Objective</h3> To evaluate whether hearing loss is associated with lower levels of PA. <h3>Design, Setting, and Participants</h3> This cross-sectional analysis was conducted in a representative sample of US adults (aged 30-69 years) who participated in the 2011-2012 cycle of the National Health and Nutrition Examination Survey (NHANES). Data analysis was conducted from July to September 2021. <h3>Exposures</h3> Hearing was assessed, in dB, by pure-tone audiometry and summarized as the better hearing ear's pure-tone average (BPTA) of 4 speech frequencies (500, 1000, 2000, and 4000 kHz); a higher BTPA indicates worse hearing. Hearing was also categorized into normal (BPTA ≤25 dB), mild hearing impairment (&gt;25 to 40 dB), and moderate or greater hearing impairment (&gt;40 dB). <h3>Main Outcomes and Measures</h3> Total 24-hour movement activity was measured using wrist accelerometers worn at all times for 7 consecutive days and summarized in monitor-independent movement summary units (MIMS) units (higher MIMS units indicate more movement). The association between BPTA and MIMS units was evaluated using a multivariable-adjusted (demographic characteristics and chronic conditions) piecewise spline regression (knot at 15 dB). Mean differences in MIMS units across hearing categories compared with normal hearing were estimated. <h3>Results</h3> The study included 2490 participants (mean [SE] age, 48.9 [0.3] years; 900 [weighted percentage, 69.3%] White individuals, 1248 [weighted percentage, 50.8%] female participants). Before the knot at 15 dB, we found that each 10-dB higher BPTA was associated with 860.4 (95% CI, 444.8-1276.1) higher MIMS units. Conversely, after the knot, each 10-dB higher BPTA was associated with 458.6 (95% CI, 27.7-889.4) lower MIMS units. The difference in MIMS units across hearing categories was not statistically significant. <h3>Conclusions and Relevance</h3> In this cross-sectional study, in the range of hearing sensitivity of BPTA of 15 dB or greater, worse hearing was associated with lower MIMS units. Lower PA may be a mechanism contributing to the association between hearing impairment and adverse health.
RELATIONSHIP OF CORIN GENE VARIANT WITH BLOOD PRESSURE AND HYPERTENSION AMONG BLACK INDIVIDUALS
Authors: Vibhu Parcha, Marguerite R. Irvin, Leslie Lange, Nicole D. Armstrong, Akhil Pampana, Mariah Meyer, Suzanne Judd, Garima Arora, Pankaj Arora
Journal: Journal of the American College of Cardiology (2022)
microRNA-92a promotes CNS autoimmunity by modulating the regulatory and inflammatory T cell balance
Authors: Mai Fujiwara, Radhika Raheja, Lucien P. Garo, Amrendra K. Ajay, Ryoko Kadowaki-Saga, Sukrut H. Karandikar, Galina Gabriely, Rajesh Krishnan, Vanessa Beynon, Anu Paul, Amee Patel, Shrishti Saxena, Dan Hu, Brian C. Healy, Tanuja Chitnis, Roopali Gandhi, Howard L. Weiner, Gopal Murugaiyan
Journal: Journal of Clinical Investigation (2022)

A disequilibrium between immunosuppressive Tregs and inflammatory IL-17-producing Th17 cells is a hallmark of autoimmune diseases, including multiple sclerosis (MS). However, the molecular mechanisms underlying the Treg and Th17 imbalance in CNS autoimmunity remain largely unclear. Identifying the factors that drive this imbalance is of high clinical interest. Here, we report a major disease-promoting role for microRNA-92a (miR-92a) in CNS autoimmunity. miR-92a was elevated in experimental autoimmune encephalomyelitis (EAE), and its loss attenuated EAE. Mechanistically, miR-92a mediated EAE susceptibility in a T cell-intrinsic manner by restricting Treg induction and suppressive capacity, while supporting Th17 responses, by directly repressing the transcription factor Foxo1. Although miR-92a did not directly alter Th1 differentiation, it appeared to indirectly promote Th1 cells by inhibiting Treg responses. Correspondingly, miR-92a inhibitor therapy ameliorated EAE by concomitantly boosting Treg responses and dampening inflammatory T cell responses. Analogous to our findings in mice, miR-92a was elevated in CD4+ T cells from patients with MS, and miR-92a silencing in patients' T cells promoted Treg development but limited Th17 differentiation. Together, our results demonstrate that miR-92a drives CNS autoimmunity by sustaining the Treg/Th17 imbalance and implicate miR-92a as a potential therapeutic target for MS.
CLO22-091: Malignancy or Not? Role of 18F-FDG PET/CT in Solving the Diagnostic Dilemma in Multiple Myeloma Misdiagnosed as Rheumatoid Arthritis: Pictorial Series
Authors: Surekha Yadav
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-091: Malignancy or Not? Role of 18F-FDG PET/CT in Solving the Diagnostic Dilemma in Multiple Myeloma Misdiagnosed as Rheumatoid Arthritis: Pictorial Series" published on 31 Mar 2022 by National Comprehensive Cancer Network.
ANP SPECIFIC DEFICIENCY AND CARDIOMETABOLIC DISEASE IN MALES IN THE GENERAL COMMUNITY
Authors: Tomoko Ichiki, Valentina Cannone, Christopher Scott, Seethalakshmi Iyer, Jeson Sangaralingham, Kent R. Bailey, Jens P. Goetze, Yoshihisa Tsuji, Richard J. Rodeheffer, John C. Burnett
Journal: Journal of the American College of Cardiology (2022)
INCIDENCE AND PROGNOSIS OF WORSENING RENAL FUNCTION IN PATIENTS WITH HEART FAILURE AND SECONDARY MITRAL REGURGITATION: THE COAPT TRIAL
Authors: Jeremy Kong, Jonathan G. Zaroff, Andrew P. Ambrosy, Ivy Ku, Jacob M. Mishell, Lak Kotinkaduwa, Bjorn Redfors, Nirat Beohar, Gorav Ailawadi, JoAnn Lindenfeld, William T. Abraham, Michael J. Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2022)
MYSTERIOUS LEFT VENTRICULAR OUTFLOW MOBILE MASS BEFORE TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)
Authors: Sherif Roman, Nirmal Guragai, Hamdallah Ashkar, Vanessa Hurtado, Parminder Kaur, Rahul Vasudev, Hartaj Virk, Fayez E. Shamoon
Journal: Journal of the American College of Cardiology (2022)
Cell-Free HPV DNA Provides an Accurate and Rapid Diagnosis of HPV-Associated Head and Neck Cancer
Authors: Giulia Siravegna, Connor J. O'Boyle, Shohreh Varmeh, Natalia Queenan, Alexa Michel, Jarrod Stein, Julia Thierauf, Peter M. Sadow, William C. Faquin, Simon K. Perry, Adam Z. Bard, Wei Wang, Daniel G. Deschler, Kevin S. Emerick, Mark A. Varvares, Jong C. Park, John R. Clark, Annie W. Chan, Vanessa Carlota Andreu Arasa, Osamu Sakai, Jochen Lennerz, Ryan B. Corcoran, Lori J. Wirth, Derrick T. Lin, A. John Iafrate, Jeremy D. Richmon, Daniel L. Faden
Journal: Clinical Cancer Research (2021)

Abstract Purpose: HPV-associated head and neck squamous cell carcinoma (HPV+HNSCC) is the most common HPV-associated malignancy in the United States and continues to increase in incidence. Current diagnostic approaches for HPV+HNSCC rely on tissue biopsy followed by histomorphologic assessment and detection of HPV indirectly by p16 IHC. Such approaches are invasive and have variable sensitivity. Experimental Design: We conducted a prospective observational study in 140 subjects (70 cases and 70 controls) to test the hypothesis that a noninvasive diagnostic approach for HPV+HNSCC would have improved diagnostic accuracy, lower cost, and shorter diagnostic interval compared with standard approaches. Blood was collected, processed for circulating tumor HPV DNA (ctHPVDNA), and analyzed with custom ddPCR assays for HPV genotypes 16, 18, 33, 35, and 45. Diagnostic performance, cost, and diagnostic interval were calculated for standard clinical workup and compared with a noninvasive approach using ctHPVDNA combined with cross-sectional imaging and physical examination findings. Results: Sensitivity and specificity of ctHPVDNA for detecting HPV+HNSCC were 98.4% and 98.6%, respectively. Sensitivity and specificity of a composite noninvasive diagnostic using ctHPVDNA and imaging/physical examination were 95.1% and 98.6%, respectively. Diagnostic accuracy of this noninvasive approach was significantly higher than standard of care (Youden index 0.937 vs. 0.707, P = 0.0006). Costs of noninvasive diagnostic were 36% to 38% less than standard clinical workup and the median diagnostic interval was 26 days less. Conclusions: A noninvasive diagnostic approach for HPV+HNSCC demonstrated improved accuracy, reduced cost, and a shorter time to diagnosis compared with standard clinical workup and could be a viable alternative in the future.
RADIAL AND ULNAR ARTERY ACCESS FOR PERIPHERAL VASCULAR INTERVENTION: A SINGLE CENTER EXPERIENCE
Authors: Allison Aldrich, Allison Lanfear, Talia Meidan, Emily Shih, Srinivasa P. Potluri, Chadi Dib, Karim Al-Azizi, John Kedora, Sameh Sayfo
Journal: Journal of the American College of Cardiology (2022)
Intelligent Paper‐Free Sprayable Skin Mask Based on an In Situ Formed Janus Hydrogel of an Environmentally Friendly Polymer
Authors: Caiyun Cai, Jingyu Tang, Yi Zhang, Weihan Rao, Dinglingge Cao, Wen Guo, Lin Yu, Jiandong Ding
Journal: Advanced Healthcare Materials (2022)

Abstract Traditional skin care masks usually use a piece of paper to hold the aqueous essences, which are not environmentally friendly and not easy to use. While a paper‐free mask is desired, it is faced with a dilemma of moisture holding and rapid release of encapsulated bioactive substances. Herein, a paper‐free sprayable skin mask is designed from an intelligent material—a thermogel which undergoes sol–gel‐suspension transitions upon heating—to solve this dilemma. A synthesized block copolymer of poly(ethylene glycol) and poly(lactide‐ co ‐glycolide) with appropriate ratios can be dissolved in water, and thus easily mixed with a biological substance. The mixture is sprayable. After spraying, a Janus film is formed in situ with a physical gel on the outside and a suspension on the inside facing skin. Thus, both moisture holding and rapid release are achieved. Such a thermogel composed of biodegradable amphiphilic block copolymers loaded with nicotinamide as a skin mask is verified to reduce pigmentation on a 3D pigmented reconstructed epidermis model and further in a clinical study. This work might be stimulating for investigations and applications of biodegradable and intelligent soft matter in the fields of drug delivery and regenerative medicine.
GROUND, INSTANT, OR DECAFFEINATED COFFEE? IMPACT OF DIFFERENT COFFEE SUBTYPES ON INCIDENT ARRHYTHMIA, CARDIOVASCULAR DISEASE AND MORTALITY
Authors: David Chieng, Rodrigo Canovas, Hariharan Sugumar, Louise Segan, Liang-han Ling, Aleksandr Voskoboinik, Ahmed Al-Kaisey, Geoffrey Lee, Sandeep Prabhu, David M. Kaye, Joseph B. Morton, Jonathan M. Kalman, Peter M. Kistler
Journal: Journal of the American College of Cardiology (2022)
THE CURRENT CULTURE OF INTERVENTIONAL CARDIOLOGY: PROGRESSIVELY CHANGING OR STATUS QUO?
Authors: Zarina Sharalaya, Quinn Capers, Ki Park, Nadia Razaq Sutton, Toniya Singh, Sarah Gualano, Joanna Ghobrial, Kyoko Miki, Anne Rzeszut, Claire S. Duvernoy
Journal: Journal of the American College of Cardiology (2022)
National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study
Authors: Megan A Smith, Maddison Sherrah, Farhana Sultana, Philip E Castle, Marc Arbyn, Dorota Gertig, Michael Caruana, C David Wrede, Marion Saville, Karen Canfell
Journal: BMJ (2022)

Abstract Objective To review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population. Design Observational study. Setting Australia. Participants 3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged &lt;40 years had previously been offered vaccination against HPV16 and HPV18. Interventions Primary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up. Main outcome measures Proportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer. Results 54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm. Conclusions Colposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.
68Ga-DOTATATE PET/CT Scan as a Valuable Tool for Diagnosis and Staging of the Rare Entity of Tracheal Paragangliomas
Authors: Robert Nelson, Michael Clemenshaw, Islam Ahmed Shehata Elhelf
Journal: Clinical Nuclear Medicine (2022)

Primary paraganglioma of the trachea is a rare differential among more common tracheal masses. Definitive diagnosis of tracheal masses is obtained via endoscopic biopsy. Utilization of 68Ga-DOTATATE PET/CT is valuable in the workup of these lesions as paragangliomas would have significantly higher radiotracer uptake compared with the more common squamous cell and adenoid cystic carcinomas. This is particularly important in tracheal paragangliomas, which are typically friable and hypervascular with higher risk of significant bleeding on biopsy. In addition, 68Ga-DOTATATE PET/CT can be used to evaluate for local invasion and metastatic disease as a 1-step imaging modality.