tbuckley/cabot-search huggingface dataset:
Two Outbreaks of Legionnaires Disease Associated with Outdoor Hot Tubs for Private Use — Two Cruise Ships, November 2022–July 2024
Authors: Sooji Lee, Chris Edens, Troy Ritter, Luis O. Rodriguez, Kara Tardivel, Natalia A. Kozak-Muiznieks, Melisa Willby, Nancy Ortiz, Adam L. Cohen, Jessica C. Smith
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Legionnaires disease is a serious pneumonia caused by Legionella bacteria. During November 2022-June 2024, CDC was notified of 12 cases of Legionnaires disease among travelers on two cruise ships; eight on cruise ship A and four on cruise ship B. CDC, in collaboration with the cruise lines, initiated investigations to ascertain the potential sources of on-board exposure after notification of the second potentially associated case for each ship. Epidemiologic data collected from patient interviews and environmental assessment and sampling results identified private hot tubs on selected cabin balconies as the most likely exposure source. To minimize Legionella growth, both cruise lines modified the operation and maintenance of these devices by removing the heating elements, draining water between uses, and increasing the frequency of hyperchlorination and cleaning. Hot tubs offer favorable conditions for Legionella growth and transmission when maintained and operated inadequately, regardless of location. Private hot tubs on cruise ships are not subject to the same maintenance requirements as are public hot tubs in common areas. Given the range of hot tub-type devices offered as amenities across the cruise industry, to reduce risk for Legionella growth and transmission, it is important for cruise ship water management program staff members to inventory and assess private balcony hot tubs and adapt public hot tub maintenance and operations protocols for use on private outdoor hot tubs.
Genomic Surveillance for SARS-CoV-2 Variants: Circulation of Omicron XBB and JN.1 Lineages — United States, May 2023–September 2024
Authors: Kevin C. Ma, Juan Castro, Anastasia S. Lambrou, Erica Billig Rose, Peter W. Cook, Dhwani Batra, Caelin Cubenas, Laura J. Hughes, Duncan R. MacCannell, Paritra Mandal, Neha Mittal, Mili Sheth, Casey Smith, Amber Winn, Aron J. Hall, David E. Wentworth, Benjamin J. Silk, Natalie J. Thornburg, Clinton R. Paden
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

CDC continues to track the evolution of SARS-CoV-2, including the Omicron variant and its descendants, using national genomic surveillance. This report summarizes U.S. trends in variant proportion estimates during May 2023-September 2024, a period when SARS-CoV-2 lineages primarily comprised descendants of Omicron variants XBB and JN.1. During summer and fall 2023, multiple descendants of XBB with immune escape substitutions emerged and reached >10% prevalence, including EG.5-like lineages by June 24, FL.1.5.1-like lineages by August 5, HV.1 lineage by September 30, and HK.3-like lineages by November 11. In winter 2023, the JN.1 variant emerged in the United States and rapidly attained predominance nationwide, representing a substantial genetic shift (>30 spike protein amino acid differences) from XBB lineages. Descendants of JN.1 subsequently circulated and reached >10% prevalence, including KQ.1-like and KP.2-like lineages by April 13, KP.3 and LB.1-like lineages by May 25, and KP.3.1.1 by July 20. Surges in COVID-19 cases occurred in winter 2024 during the shift to JN.1 predominance, as well as in summer 2023 and 2024 during circulation of multiple XBB and JN.1 descendants, respectively. The ongoing evolution of the Omicron variant highlights the importance of continued genomic surveillance to guide medical countermeasure development, including the selection of antigens for updated COVID-19 vaccines.
Locally Acquired (Autochthonous) Mosquito-Transmitted <i>Plasmodium vivax</i> Malaria — Saline County, Arkansas, September 2023
Authors: Ashleah P. Courtney, Bobby L. Boyanton, Paige V. Strebeck, Keith Blount, Savanna Ledford, Alison D. Ridpath, Kimberly E. Mace, Cherie Smith, Kelley Garner, Catherine Waters, Michael J. Cima, Naveen Patil, Peter D. McElroy, Brian H. Raphael, Sarah G.H. Sapp, Yvonne Qvarnstrom, Audrey Lenhart, Alice Sutcliffe, Theresa M. Dulski, Laura Rothfeldt, Danny Baxter, Monica Baxter, Lisa Collier, Claudia Corredor-Medina, Melissa Green, Stephen Hedges, Leslie Himstedt, Katelyn Lazenby, Laura Leite, Cole Menasco, Meg Mirivel, Emma Rogers, Jennifer Shray, Leah Welker
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

A case of locally acquired (autochthonous) mosquito-transmitted Plasmodium vivax malaria was diagnosed in Arkansas in September 2023. This represents the 10th autochthonous case identified nationally in 2023, after 20 years without recorded local mosquitoborne malaria transmission in the United States. The public health response included case investigation, active case surveillance, mosquito surveillance and control, assessment of medical countermeasures, and clinical and public outreach. Prompt diagnosis and appropriate treatment of malaria can improve clinical outcomes and, in addition to vector control, minimize risk for local transmission. Clinicians should consider malaria among patients who have traveled to countries where malaria is endemic, or with unexplained fever regardless of travel history. Although the risk for autochthonous malaria in the United States remains very low, its reemergence highlights the importance of vectorborne disease preparedness and response. Examples of such efforts include improving awareness among clinicians, access to diagnostics and antimalarial medications, and capacity for mosquito surveillance and control. Collaboration and communication among CDC, health departments, local jurisdictions, clinicians, hospitals, laboratories, and the public can support rapid malaria diagnosis, prevention, and control. Before traveling internationally to areas where malaria is endemic, travelers should consult with their health care provider regarding recommended malaria prevention measures, including chemoprophylaxis and precautions to avoid mosquito bites, to reduce both personal and community risk.
<i>Notes from the Field:</i> First Locally Acquired Dengue Virus Infections — Pasadena, California, October–December 2023
Authors: Matt Feaster, Rudy Patrick, Michael Oshiro, Melody Kuan, Ying-Ying Goh, Manuel Carmona, Sara Y. Tartof, Jason Farned, Tristan Hallum, Andrea J. Lund, Chris Preas, Sharon Messenger, Vicki Kramer, Mary Danforth, Colten Sheridan
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
Association of Medicaid Expansion With Timely Receipt of Treatment and Survival Among Patients With HR-Negative, HER2-Positive Breast Cancer
Authors: Kewei Sylvia Shi, Xu Ji, Changchuan Jiang, Kathryn J. Ruddy, Sharon M. Castellino, K. Robin Yabroff, Xuesong Han
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Hormone receptor (HR)–negative, HER2-positive (also called HER2-enriched) breast cancer has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its association with receipt of care for HR-negative, HER2-positive breast cancer is unknown. We examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment initiation, and survival among nonelderly women newly diagnosed with HR-negative, HER2-positive breast cancer. Patients and Methods: Women aged 18 to 62 years newly diagnosed with HR-negative, HER2-positive breast cancer between 2010 and 2018 were identified from the National Cancer Database. Outcomes included receipt of stage-based guideline-concordant treatment, timely initiation of treatment (&lt;30 days, &lt;60 days, &lt;90 days from diagnosis), and stage-specific 2-year overall survival. A difference-in-differences (DID) analytic approach compared outcome changes following Medicaid expansion in expansion versus nonexpansion states. Multivariable linear probability models were used to estimate treatment outcomes, and flexible parametric survival models were used to evaluate survival, adjusting for sociodemographic and clinical confounders. Results: A total of 31,401 patients were included. Medicaid expansion was associated with an increase of 0.58 percentage points (ppt; 95% CI, 0.01–1.16) in receipt of guideline-concordant treatment overall, a 2.43-ppt (95% CI, 0.68–4.18) increase in initiating guideline-concordant treatment &lt;60 days after diagnosis, and a 1.17-ppt (95% CI, 0.02–2.32) increase in 2-year survival rate. The increase in 2-year survival associated with Medicaid expansion was most prominent for patients with stage III disease (DID, 3.81; 95% CI, 0.82–6.80). Conclusions: Medicaid expansion was associated with improved care and survival for patients with HR-negative, HER2-positive breast cancer, an aggressive cancer type for which prognosis largely depends on access to effective treatment.
Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities
Authors: Harshita Tiwari, Swati Singh, Sonal Sharma, Priyamvada Gupta, Ashish Verma, Amrit Chattopadhaya, Brijesh Kumar, Sakshi Agarwal, Rajiv Kumar, Sanjeev Kumar Gupta, Vibhav Gautam
Journal: Medicinal Research Reviews (2024)

Abstract Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER‐2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal‐like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)‐T cells‐based immunotherapy, phytometabolites‐mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions.
Allocation of Treatment Slots in Elective Mental Health Care—Are Waiting Lists the Ethically Most Appropriate Option?
Authors: Thomas Haustein, Ralf J. Jox
Journal: The American Journal of Bioethics (2024)

Waiting lists are a standard approach to managing excess demand in elective health care. While waiting times are an important policy issue, the ethical validity of the first come, first served (FCFS) principle as such is rarely questioned. Presenting a psychiatric day hospital where all eligible patients have roughly equal claims as a case study, we criticize the reflex use of FCFS for allocation of elective psychiatric care, consider conditions under which this may not be the optimal strategy, and discuss alternatives. We conclude that in our example prioritizing more recent referrals (last come, first served [LCFS]) makes more sense, clinically and ethically. Where several referrals arrive (near-)simultaneously under LCFS, we propose that a higher level of scrutiny be applied to detect possible good reasons for prioritizing one of them. We believe that our observations can be applied to other health care settings that share relevant characteristics with our case.
Decreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism
Authors: Yong Zhao, Shengbo Han, Zhu Zeng, Hai Zheng, Yang Li, Fan Wang, Yan Huang, Yingsong Zhao, Wenfeng Zhuo, Guozheng Lv, Hongda Wang, Guangyu Zhao, Eryang Zhao, Yuhang Hu, Ping Hu, Gang Zhao
Journal: Theranostics (2024)

Resistance to sorafenib remains a major challenge in the systemic therapy of liver cancer. However, the involvement of lipid metabolism-related lncRNAs in this process remains unclear.
Tumor growth suppression in adoptive T cell therapy via IFN-γ targeting of tumor vascular endothelial cells
Authors: Qiaoya Lin, Colleen P Olkowski, Peter L Choyke, Noriko Sato
Journal: Theranostics (2024)

In adoptive T cell therapy (ACT), the direct cytotoxic effects of CD8 T cells on tumor cells, including the release of interferon-gamma (IFN-γ), are considered the primary mechanism for tumor eradication. Cancer antigen escape diminishes the T cell responses, thereby limiting the therapeutic success. The impacts of IFN-γ targeting non-tumor cells in ACT, on the other hand, remains under-investigated. We hypothesized that IFN-γ action on non-tumor cells, particularly tumor vascular endothelial cells within the physiological tumor microenvironment, could influence therapeutic efficacy.
Dual targeting heterodimer PET tracer [<sup>18</sup>F]AlF‑FAPI‑RGD in patients with rheumatoid arthritis: a pilot exploratory study
Authors: Hao Wang, Wei Su, Limeng He, Dongze Wu, Nan Liu, Jing Zhu, Jingjing Zhang, Wei Zhang
Journal: Theranostics (2024)

Fibroblast-like synoviocytes and angiogenesis play crucial roles in the advancement of rheumatoid arthritis (RA). This prospective study aimed to assess the efficacy of [
Enzyme-activatable kidney-targeted dendrimer-drug conjugate for efficient childhood nephrotic syndrome therapy
Authors: Danfei Chen, Junjun Xu, Sha Lv, Xiaoqin Jin, Yuyan Chen, Haifang Cai, Qili Wang, Xiaobo Xuan, Guowei Wang, Weidong Fei, Jian Chen
Journal: Theranostics (2024)

Childhood nephrotic syndrome (NS) is a serious disease affecting the health and quality of life of children, which is characterized by a series of pathophysiological changes due to the increased permeability of the glomerular membrane to plasma proteins. Low renal drug distribution and inefficient cellular uptake, resulting from cellular dysfunctions of filtration and internalization, are the main barriers to drug treatment in childhood NS, leading to deterioration in nephropathy. However, efficient therapeutic methods against childhood NS are still lacking in clinic.
Salivary diagnostics: opportunities and challenges
Authors: Yuxin Li, Yourong Ou, Kexin Fan, Guozhen Liu
Journal: Theranostics (2024)

Saliva contains a diverse array of biomarkers indicative of various diseases. Saliva testing has been a major advancement towards non-invasive point-of-care diagnosis with clinical significance. However, there are challenges associated with salivary diagnosis from sample treatment and standardization. This review highlights the biomarkers in saliva and their role in identifying relevant diseases. It provides an overview and discussion about the current practice of saliva collection and processing, and advancements in saliva detection systems from
HDAC7 drives glioblastoma to a mesenchymal-like state via LGALS3-mediated crosstalk between cancer cells and macrophages
Authors: Shulin Zhao, Rongrong Zhao, Chuanzheng Wang, Caizhi Ma, Zijie Gao, Boyan Li, Yanhua Qi, Wei Qiu, Ziwen Pan, Shaobo Wang, Qindong Guo, Jiawei Qiu, Yang Fan, Xiaofan Guo, Hao Xue, Lin Deng, Gang Li
Journal: Theranostics (2024)

Background: Glioblastoma multiforme (GBM) is an aggressive brain tumour for which current traditional treatment approaches have been unsuccessful, owing to the high genetic heterogeneity and immunosuppressive tumour microenvironment. Methods: Single-cell and spatial transcriptomic data revealed the niche-specific enrichment of mesenchymal-like (MES-like) GBM cells and monocyte-derived macrophages (MDMs); Gain- and loss-of-function assays of HDAC7 was confirmed both in vitro and in vivo assays. Mechanistically, mass spectrum, RNA immunoprecipitation (RIP), and co-immunoprecipitation assays were conducted. Results: We found that HDAC7, which upregulated by TRIM28-mediated sumoylation at the protein levels, inhibited SOX8 expression by mediating H3K27 deacetylation. And the down-regulated SOX8 facilitated the transcriptional activity of JUN, to induce LGALS3 secretion, which then bind to the membrane protein ITGB1 on GSC and MDMs in the autocrine and paracrine manners to facilitate the transformation of the mesenchymal phenotype of GBM and the M2 polarization of MDMs, respectively. In turn, LGALS3 could also secreted by M2 MDMs to promote MES transition of GBM in a paracrine manner, creating a positive feedback loop. In translational medicine, we found that blocking LGALS3 improved the therapeutic sensitivity of HDAC inhibitors. Conclusions: Our findings revealed the role of the novel HDAC7-H3K27ac-SOX8/JUN-LGALS3-ITGB1 axis in maintaining the crosstalk between MES GBM and M2 MDM, highlighting that HDAC7 and LGALS3 may serve as potential prognostic biomarkers and therapeutic targets in GBM.
Characterization of dipyridamole as a novel ferroptosis inhibitor and its therapeutic potential in acute respiratory distress syndrome management
Authors: Xu Chen, Jiapan Shen, Xueqin Jiang, Min Pan, Shuang Chang, Juanjuan Li, Lei Wang, Manli Miao, Xiaoxia Feng, Ling Zhang, Guoqing Shu, Wenjian Liu, Fangzhou Xu, Wentao Zhang, Zhao Ding, Huaiyuan Zong, Weiwei Liu, Dapeng Li, Biao Chen, Min Shao, Guanghe Fei, Xiaojun Zha, Xiaoyun Fan
Journal: Theranostics (2024)

Rationale: Ferroptosis in lung epithelium and endothelium contributes to the pathogenesis of acute respiratory distress syndrome (ARDS), a critical and often fatal condition marked by acute inflammation and elevated pulmonary vascular permeability. Despite this, there are currently no FDA-approved therapeutics specifically targeting ferroptosis for ARDS management. Methods: A screening of 259 FDA-approved drugs was conducted to identify an effective ferroptosis inhibitor in pulmonary epithelial and endothelial cells. The anti-ferroptotic and therapeutic efficacy of this screened drug was rigorously evaluated using two distinct ARDS mouse models (LPS-induced acute lung injury and CLP-induced sepsis) and human airway organoids (hAOs). The regulatory mechanism of this drug on ferroptosis inhibition was investigated via RNA-sequencing, qRT-PCR, western blotting, IF, luciferase reporter assay, chromatin immunoprecipitation assay, limited proteolysis-mass spectrometry assay, cellular thermal shift assay, and drug affinity responsive target stability assay. Furthermore, a proof-of-concept clinical trial was conducted, wherein ARDS patients were administered with the drug as adjunctive therapy. Results: Dipyridamole (DIPY) was identified as a potent inhibitor of ferroptosis in pulmonary epithelial and endothelial cells. DIPY effectively mitigated ferroptosis and pulmonary damage in both mouse models and hAOs, primarily by downregulating heme oxygenase 1 (HMOX1). The transcription factor cAMP responsive element binding protein 1 (CREB1) was identified as a key transactivator of HMOX1, which DIPY effectively downregulated. Mechanistically, DIPY binds to and activates superoxide dismutase 1 (SOD1), which in turn inhibits the CREB1/HMOX1 pathway, thereby suppressing ferroptosis. Notably, the clinical trial further corroborated the therapeutic potential of DIPY in ARDS patients, demonstrating improved outcomes with DIPY adjunctive therapy. Conclusions: These findings provide compelling evidence that DIPY inhibits ferroptosis in pulmonary epithelial and endothelial cells by modulating the SOD1/CREB1/HMOX1 signaling axis and suggest DIPY as a promising therapeutic strategy for ARDS treatment.
BATF2 inhibits the stem cell-like properties and chemoresistance of gastric cancer cells through PTEN/AKT/β-catenin pathway
Authors: Longlong Cao, Kai Weng, Lujie Li, Guangtan Lin, Yuxuan Zhao, Youxin Gao, Xiaobo Huang, Qiyue Chen, Jiabin Wang, Chaohui Zheng, Changming Huang, Jianwei Xie, Ping Li
Journal: Theranostics (2024)

Background: Gastric cancer (GC) ranks as the fifth leading cause of cancer mortality, with cancer stem cells (CSCs) playing a critical role in tumor progression and resistance to chemotherapy. Conventional chemotherapy often fails to effectively target these stem cells. BATF2, a tumor suppressor, is known for its role in gastric cancer, but its influence on cancer stem cell-like properties and chemotherapy response remains unclear. Methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed on 9 gastric cancer samples to evaluate the expression and regulatory function of BATF2. In vitro experiments involving cell cultures, tumor cell spheroids, and organoids were conducted to assess BATF2's impact on 5-Fu sensitivity and its interaction with drug transporters and signaling pathways. In vivo studies, including subcutaneous tumor formation assays, immunohistochemistry, and immunoblotting, were used to validate findings. Results: BATF2 was confirmed as a tumor suppressor in gastric cancer through scRNA-seq analysis. Elevated BATF2 expression correlated with improved outcomes from postoperative chemotherapy in GC patients and increased sensitivity to 5-Fu. BATF2 enhanced 5-Fu responsiveness by inhibiting the ABCG2 drug transporter and promoting PTEN stability, which suppressed AKT phosphorylation. This led to reduced nuclear β-catenin levels and decreased expression of stem cell markers CD44, SOX2, and NANOG, ultimately reducing chemoresistance and stem-like properties in GC cells. Conclusions: BATF2 plays a pivotal role in regulating stem-like characteristics and chemoresistance in gastric cancer through the BATF2/PTEN/AKT/ABCG2 pathway. These findings suggest a novel therapeutic strategy targeting BATF2 to enhance chemotherapy effectiveness in gastric cancer treatment.