tbuckley/cabot-search huggingface dataset:
Ceftriaxone-Resistant Gonorrhea — China, 2022
Authors: Xiaoyu Zhu, Yue Xi, Xiangdong Gong, Shaochun Chen
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis.The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxoneresistant clones, poses a formidable challenge to gonorrhea control.The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance.In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces.The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance.Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively.Only one case of spectinomycin resistance was reported.These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022.Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains.Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.
Interim Effectiveness of Updated 2023–2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19–Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions — VISION Network, September 2023–February 2024
Authors: Ruth Link-Gelles, Elizabeth A.K. Rowley, Malini B. DeSilva, Kristin Dascomb, Stephanie A. Irving, Nicola P. Klein, Shaun J. Grannis, Toan C. Ong, Zachary A. Weber, Katherine E. Fleming-Dutra, Charlene E. McEvoy, Omobosola Akinsete, Daniel Bride, Tamara Sheffield, Allison L. Naleway, Ousseny Zerbo, Bruce Fireman, John Hansen, Kristin Goddard, Brian E. Dixon, Colin Rogerson, William F. Fadel, Thomas Duszynski, Suchitra Rao, Michelle A. Barron, Sarah E. Reese, Sarah W. Ball, Margaret M. Dunne, Karthik Natarajan, Erica Okwuazi, Ami B. Shah, Ryan Wiegand, Mark W. Tenforde, Amanda B. Payne
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.
Understanding exososmes: Part 3—therapeutic + diagnostic potential in dentistry
Authors: Richard J. Miron, Nathan E. Estrin, Anton Sculean, Yufeng Zhang
Journal: Periodontology 2000 (2024)

Abstract Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri‐implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing “remarkable” potential, serving as a valuable tool for clinicians with significant advantages.
Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability — Sickle Cell Data Collection Program, 11 States, 2016–2020
Authors: Mariam Kayle, Audrey L. Blewer, Wei Pan, Jennifer A. Rothman, Carri S. Polick, Joshua Rivenbark, Elliott Fisher, Camila Reyes, John J. Strouse, Shelby Weeks, Jay R. Desai, Angela B. Snyder, Mei Zhou, Ankit Sutaria, Jhaqueline Valle, Sophia S. Horiuchi, Marci K. Sontag, Joshua I. Miller, Ashima Singh, Mahua Dasgupta, Isaac A. Janson, Najibah Galadanci, Sarah L. Reeves, Krista Latta, Isabel Hurden, Shamaree J. Cromartie, Allison P. Plaxco, Ayesha Mukhopadhyay, Matthew P. Smeltzer, Mary Hulihan
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care.A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states.The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived.Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle β-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns.Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes.These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD.Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.
Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines
Authors: Jorge I. F. Salluh, Pedro Póvoa, Abi Beane, Andre Kalil, Cornelius Sendagire, Daniel A. Sweeney, David Pilcher, Eva Polverino, Evelina Tacconelli, Elisa Estenssoro, Jean-Pierre Frat, Julio Ramirez, Luis Felipe Reyes, Oriol Roca, Saad Nseir, Vandack Nobre, Thiago Lisboa, Ignacio Martin-Loeches
Journal: Intensive Care Medicine (2024)
Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice
Authors: Xiaoqian Meng, Linjuan Du, Shuo Xu, Lujun Zhou, Boyan Chen, Yulin Li, Chumao Chen, Huilin Ye, Jun Zhang, Guocai Tian, Xuebing Bai, Ting Dong, Wenzhen Lin, Mengjun Sun, Kecong Zhou, Yan Liu, Wuchang Zhang, Shengzhong Duan
Journal: International Journal of Oral Science (2024)

Abstract Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ + ) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.
FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression
Authors: Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He
Journal: International Journal of Oral Science (2024)

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial-mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8
Protein-altering variants at copy number-variable regions influence diverse human phenotypes
Authors: Margaux L. A. Hujoel, Robert E. Handsaker, Maxwell A. Sherman, Nolan Kamitaki, Alison R. Barton, Ronen E. Mukamel, Chikashi Terao, Steven A. McCarroll, Po-Ru Loh
Journal: Nature Genetics (2024)

Abstract Copy number variants (CNVs) are among the largest genetic variants, yet CNVs have not been effectively ascertained in most genetic association studies. Here we ascertained protein-altering CNVs from UK Biobank whole-exome sequencing data ( n = 468,570) using haplotype-informed methods capable of detecting subexonic CNVs and variation within segmental duplications. Incorporating CNVs into analyses of rare variants predicted to cause gene loss of function (LOF) identified 100 associations of predicted LOF variants with 41 quantitative traits. A low-frequency partial deletion of RGL3 exon 6 conferred one of the strongest protective effects of gene LOF on hypertension risk (odds ratio = 0.86 (0.82–0.90)). Protein-coding variation in rapidly evolving gene families within segmental duplications—previously invisible to most analysis methods—generated some of the human genome’s largest contributions to variation in type 2 diabetes risk, chronotype and blood cell traits. These results illustrate the potential for new genetic insights from genomic variation that has escaped large-scale analysis to date.
Cell-type-specific and disease-associated expression quantitative trait loci in the human lung
Authors: Heini M. Natri, Christina B. Del Azodi, Lance Peter, Chase J. Taylor, Sagrika Chugh, Robert Kendle, Mei-i Chung, David K. Flaherty, Brittany K. Matlock, Carla L. Calvi, Timothy S. Blackwell, Lorraine B. Ware, Matthew Bacchetta, Rajat Walia, Ciara M. Shaver, Jonathan A. Kropski, Davis J. McCarthy, Nicholas E. Banovich
Journal: Nature Genetics (2024)

Abstract Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects. Furthermore, we identified disease interaction eQTLs and demonstrated that this class of associations is more likely to be cell-type-specific and linked to cellular dysregulation in pulmonary fibrosis. Finally, we connected lung disease risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression and implicates context-specific eQTLs as key regulators of lung homeostasis and disease.
Chondrocyte‐Targeted Delivery System of Sortase A‐Engineered Extracellular Vesicles Silencing MMP13 for Osteoarthritis Therapy
Authors: Wenjing Yan, Ying Li, Shuqian Xie, W. Andy Tao, Jing Hu, Haohan Liu, Guiyuan Zhang, Fengying Liu, Yamei Nie, Xue Chen, Xing Zhang, Yufeng Liu, Dong Wei, Changyan Ma, Hao Zhang, Hongtao Xu, Shizhi Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Targeted drug delivery and the reduction of off‐target effects are crucial for the promising clinical application of nucleic acid drugs. To address this challenge, a new approach for treating osteoarthritis (OA) that accurately delivers antisense oligonucleotides (ASO) targeting matrix metalloproteinase‐13 (ASO‐MMP13) to chondrocytes, is developed. Small extracellular vesicles (exos) are ligated with chondrocyte affinity peptide (CAP) using Sortase A and subsequently incubated with cholesterol‐modified ASO‐MMP13 to construct a chondrocyte‐targeted drug delivery exo (CAP‐exoASO). Compared with exos without CAP (ExoASO), CAP‐exoASOs attenuate IL‐1β‐induced chondrocyte damage and prolong the retention time of ASO‐MMP13 in the joint without distribution in major organs following intra‐articular injection. Notably, CAP‐exoASOs decrease MMP13 expression ( P &lt; 0.001) and upregulate COL2A1 expression ( P = 0.006), resulting in reorganization of the cartilage matrix and alleviation of progression in the OA model. Furthermore, the Osteoarthritis Research Society International (OARSI) score of articular cartilage tissues treated with CAP‐exoASO is comparable with that of healthy rats ( P = 0.148). A mechanistic study demonstrates that CAP‐exoASO may reduce inflammation by suppressing the IL‐17 and TNF signaling pathways. Based on the targeted delivery effect, CAP‐exoASOs successfully accomplish cartilage repair and have considerable potential for development as a promising therapeutic modality for satisfactory OA therapy.
Advancing Wearable Biosensors for Congenital Heart Disease: Patient and Clinician Perspectives: A Science Advisory From the American Heart Association
Authors: Animesh Tandon, Jennifer N. Avari Silva, Ami B. Bhatt, Colin K. Drummond, Allison C. Hill, Amanda E. Paluch, Sheradon Waits, Jenny E. Zablah, Kevin C. Harris
Journal: Circulation (2024)

Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations. This science advisory reviews the use of wearables in patients with congenital heart disease, how to improve these technologies for clinicians and patients, and ethical and regulatory considerations. Challenges related to the use of wearables are common to every clinical setting, but specific topics for consideration in congenital heart disease are highlighted.
Real-time feedback improves imagined 3D primitive object classification from EEG
Authors: Attila Korik, Naomi du Bois, Gerard Campbell, Eamonn O’Neill, Laura Hay, Sam Gilbert, Madeleine Grealy, Damien Coyle
Journal: Brain-Computer Interfaces (2024)

Brain-computer interfaces (BCI) enable movement-independent information transfer from humans to computers. Decoding imagined 3D objects from electroencephalography (EEG) may improve design ideation in engineering design or image reconstruction from EEG for application in brain-computer interfaces, neuro-prosthetics, and cognitive neuroscience research. Object-imagery decoding studies, to date, predominantly employ functional magnetic resonance imaging (fMRI) and do not provide real-time feedback. We present four linked studies in a study series to investigate: (1) whether five imagined 3D primitive objects (sphere, cone, pyramid, cylinder, and cube) could be decoded from EEG; and (2) the influence of real-time feedback on decoding accuracy. Studies 1 (N = 10) and 2 (N = 3) involved a single-session and a multi-session design, respectively, without real-time feedback. Studies 3 (N = 2) and 4 (N = 4) involved multiple sessions, without and with real-time feedback. The four studies involved 69 sessions in total of which 26 sessions were online with real-time feedback (15,480 trials for offline and at least 6,840 trials for online sessions in total). We demonstrate that decoding accuracy over multiple sessions improves significantly with biased feedback (p = 0.004), compared to performance without feedback. This is the first study to show the effect of real-time feedback on the performance of primitive object-imagery BCI.
Drug resistance in ovarian cancer: from mechanism to clinical trial
Authors: Ling Wang, Xin Wang, Xueping Zhu, Lin Zhong, Qingxiu Jiang, Ya Wang, Qin Tang, Qiaoling Li, Cong Zhang, Haixia Wang, Dongling Zou
Journal: Molecular Cancer (2024)

Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, “epi-miRNAs”, can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.
Enhancing Tranexamic Acid Penetration through AQP‐3 Protein Triggering via ZIF‐8 Encapsulation for Melasma and Rosacea Therapy
Authors: Jie Tang, Yu Li, Xuefeng Hu, Wei Hua, Haoning Xu, Li Li, Fujian Xu
Journal: Advanced Healthcare Materials (2024)

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.