tbuckley/cabot-search huggingface dataset:
Long non-coding RNA lung cancer-associated transcript-1 promotes glioblastoma progression by enhancing Hypoxia-inducible factor 1 <b>alpha</b> activity
Authors: Haidong Huang, Hariti Shah, Jing Hao, Jianhong Lin, Richard A Prayson, Liangqi Xie, Shideng Bao, Abhishek A Chakraborty, Eckhard Jankowsky, Jianjun Zhao, Jennifer S Yu
Journal: Neuro-Oncology (2024)

Abstract Background Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside in hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated in GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these lncRNAs may provide new therapeutic strategies to target GSCs under hypoxia. Methods lncRNAs induced by hypoxia in GSCs were identified by RNA-seq. Lung cancer-associated transcript-1 (LUCAT1) expression was assessed by qPCR, RNA-seq, Northern blot, single molecule FISH in GSCs, and interrogated in IvyGAP, The Cancer Genome Atlas, and CGGA databases. LUCAT1 was depleted by shRNA, CRISPR/Cas9, and CRISPR/Cas13d. RNA-seq, Western blot, immunohistochemistry, co-IP, ChIP, ChIP-seq, RNA immunoprecipitation, and proximity ligation assay were performed to investigate mechanisms of action of LUCAT1. GSC viability, limiting dilution assay, and tumorigenic potential in orthotopic GBM xenograft models were performed to assess the functional consequences of depleting LUCAT1. Results A new isoform of Lucat1 is induced by Hypoxia inducible factor 1 alpha (HIF1α) and Nuclear factor erythroid 2-related factor 2 (NRF2) in GSCs under hypoxia. LUCAT1 is highly expressed in hypoxic regions in GBM. Mechanistically, LUCAT1 formed a complex with HIF1α and its co-activator CBP to regulate HIF1α target gene expression and GSC adaptation to hypoxia. Depletion of LUCAT1 impaired GSC self-renewal. Silencing LUCAT1 decreased tumor growth and prolonged mouse survival in GBM xenograft models. Conclusions A HIF1α-LUCAT1 axis forms a positive feedback loop to amplify HIF1α signaling in GSCs under hypoxia. LUCAT1 promotes GSC self-renewal and GBM tumor growth. LUCAT1 is a potential therapeutic target in GBM.
Health-related quality of life and DNA methylation-based aging biomarkers among survivors of childhood cancer
Authors: Noel-Marie Plonski, Yue Pan, Cheng Chen, Qian Dong, Xijun Zhang, Nan Song, Kyla Shelton, John Easton, Heather Mulder, Jinghui Zhang, Geoffrey Neale, Emily Walker, Hui Wang, Rachel Webster, Tara Brinkman, Kevin R Krull, Gregory T Armstrong, Kirsten K Ness, Melissa M Hudson, Qian Li, I-Chan Huang, Zhaoming Wang
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related quality of life (HRQOL). However, associations between DNA methylation–based aging biomarkers and HRQOL have not been evaluated. Methods DNA methylation was generated with Infinium EPIC BeadChip on blood-derived DNA (median for age at blood draw = 34.5 years, range = 18.5-66.6 years), and HRQOL was assessed with age at survey (mean = 32.3 years, range = 18.4-64.5 years) from 2206 survivors in the St Jude Lifetime Cohort. DNA methylation–based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M: beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture 8 domains and physical and mental component summaries. General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA; eg, EAA_GrimAge) or other age-adjusted DNA methylation–based biomarkers (eg, ageadj_DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNA methylation–based surrogate for smoking pack-years. All P values were 2-sided. Results Worse HRQOL was associated with greater EAA_GrimAge (physical component summaries: β = -0.18 years, 95% confidence interval [CI] = -0.251 to -0.11 years; P = 1.85 × 10−5; and 4 individual HRQOL domains), followed by ageadj_DNAmB2M (physical component summaries: β = -0.08 years, 95% CI = -0.124 to -0.037 years; P = .003; and 3 individual HRQOL domains) and ageadj_DNAmADM (physical component summaries: β = -0.082 years, 95% CI = -0.125 to -0.039 years; P = .002; and 2 HRQOL domains). EAA_Hannum (Hannum clock) was not associated with any HRQOL. Conclusions Overall and domain-specific measures of HRQOL are associated with DNA methylation measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes.
Endoscopic treatment of a hepatic abscess arising from a biliary stricture due to intraductal papillary neoplasm of the bile duct
Authors: Kamal M. Hassan, Enad Dawod, Mohammed Hassan, Sanjay M. Salgado, SriHari Mahadev, Reem Z. Sharaiha, Kartik Sampath
Journal: Endoscopy (2024)

Endoscopic ultrasound (EUS)-guided drainage, primarily used for intra-abdominal abscesses/fluid collections, is increasingly used for hepatic abscesses that have been traditionally managed by external drainage or surgery. EUS interventions offer reduced morbidity and potentially lower complication rates. We present a case showcasing the efficacy and safety of EUS-guided drainage in treating a complex hepatic abscess ([Video 1]).
Efficacy of a novel drill dilator in overcoming severe biliary strictures with balloon enteroscopy
Authors: Haruka Toyonaga, Tsuyoshi Hayashi, Masayo Motoya, Toshifumi Kin, Kuniyuki Takahashi, Akio Katanuma
Journal: Endoscopy (2024)

In patients with altered anatomy, biliary strictures are widely overcome using balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP). As the balloon enteroscope has a small-diameter channel and scope maneuverability is poor, severe biliary strictures are often difficult to overcome. In such cases, dilation has previously been achieved using screw-type stent retrievers [1] [2]. Recently, however, a novel drill dilator (Tornus ES; Asahi Intecc Co., Ltd., Aichi, Japan) has been developed specifically for penetrating and dilating strictures [3] [4] [5].
Endoscopic membranectomy for congenital duodenal stenosis in an adult
Authors: Ran Chen, Shiya Hong, Zhi Ni, Qingyong Zhang, Xiaoqing Huang, Lan Lin, Rongchun Zhang
Journal: Endoscopy (2024)

A 17-year-old girl with Down syndrome (body mass index 15kg/m2) was admitted to our department because of recurrent bilious vomiting since birth. Double-bubble sign on ultrasound and upper gastrointestinal imaging ([Fig. 1]) indicated obvious dilation of the duodenum and stomach. Congenital stricture of the duodenum is mainly classified into four types ([Fig. 2]) [1]. Gastroscopy confirmed a membranous duodenal stenosis (Type Ib), with an opening of approximately 1 mm in diameter, and the duodenal papilla was located directly above the diaphragm. We performed membrane radial incision ([Video 1]).
Multiple snares-assisted endoscopic full-thickness resection of a giant submucosal tumor at the esophagogastric junction
Authors: Jiyu Zhang, Miao Shi, Dan Liu, Lixia Zhao, Bingrong Liu
Journal: Endoscopy (2024)

A 26-year-old woman presented to our hospital with intermittent dysphagia lasting 1 month. A contrast-enhanced computed tomography (CT) scan revealed a low-density accumulation at the esophagogastric junction, extending from the mediastinum to the abdominal cavity ([Fig. 1] a). Endoscopic examination displayed a large submucosal bulge with a smooth mucosal surface, located 31 cm from the incisors ([Fig. 1] b). Three-dimensional reconstruction techniques were utilized to assess the size and pinpoint the precise location of the lesion ([Fig. 1] c). Endoscopic ultrasound confirmed its origin from the muscularis propria, showing hypoechoic changes ([Fig. 1] d).
Progress towards the UNAIDS 95-95-95 targets in the Fifth Botswana AIDS Impact Survey (BAIS V 2021): a nationally representative survey
Authors: Madisa Mine, Kristen A Stafford, Rebecca L Laws, Reson Marima, Phenyo Lekone, Dinah Ramaabya, Kgomotso Makhaola, Hetal K Patel, Prichard Mapondera, Floris Wray-Gordon, Chinedu Agbakwuru, Lillian Okui, Susan Matroos, Eden Onyadile, Julia Ngidi, Alash'le Abimiku, Khuteletso Bagapi, Bornapate Nkomo, Stephane M Bodika, Kaylee J Kim, Mirna Moloney, Andrew Mitchell, Akipu Ehoche, Faith L Ussery, Steven Y Hong, Stella Keipeile, Matshelo Matlhaga, Rapetse Mathumo, Robert Selato, Manhattan E Charurat, Andrew C Voetsch
Journal: The Lancet HIV (2024)
The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis
Authors: Tian Tang, Ying Zhu, Yuan-Yuan Zhang, Jin-Jin Chen, Jian-Bo Tian, Qiang Xu, Bao-Gui Jiang, Guo-Lin Wang, Nick Golding, Max L Mehlman, Chen-Long Lv, Simon I Hay, Li-Qun Fang, Wei Liu
Journal: The Lancet Microbe (2024)
Rationally Designed Benzobisthiadiazole‐Based Covalent Organic Framework for High‐Performance NIR‐II Fluorescence Imaging‐Guided Photodynamic Therapy
Authors: Xian Zhang, You Dou, Shuang Liu, Peiyao Chen, Yating Wen, Junrong Li, Yao Sun, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Although being applied as photosensitizers for photodynamic therapy, covalent organic frameworks (COFs) fail the precise fluorescence imaging in vivo and phototherapy in deep-tissue, due to short excitation/emission wavelengths. Herein, this work proposes the first example of NIR-II emissive and benzobisthiadiazole-based COF-980. Comparing to its ligands, the structure of COF-980 can more efficiently reducing the energy gap (ΔE
Within-episode repeat antibiotic prescriptions in patients with respiratory tract infections: A population-based cohort study
Authors: Arief Lalmohamed, Roderick P. Venekamp, Albert Bolhuis, Patrick C. Souverein, Janneke H.H.M. van de Wijgert, Martin C. Gulliford, Alastair D. Hay
Journal: Journal of Infection (2024)

BackgroundAntimicrobial stewardship interventions mainly focus on initial antibiotic prescriptions, with few considering within-episode repeat prescriptions. We aimed to describe the magnitude, type and determinants of within-episode repeat antibiotic prescriptions in patients presenting to primary care with respiratory tract infections (RTIs).MethodsWe conducted a population-based cohort study among 530 sampled English general practices within the Clinical Practice Research Datalink (CPRD). All individuals with a primary care RTI consultation for which an antibiotic was prescribed between March 2018 and February 2022. Main outcome measurement was repeat antibiotic prescriptions within 28 days of a RTI visit stratified by age (children vs. adults) and RTI type (lower vs. upper RTI). Multivariable logistic regression and principal components analyses were used to identify risk factors and patient clusters at risk for within-episode repeat prescriptions.Findings905,964 RTI episodes with at least one antibiotic prescription were identified. In adults, 19.9% (95% CI 19.3-20.5%) had at least one within-episode repeat prescription for a lower RTI, compared to 10.5% (95% CI 10.3-10.8%) for an upper RTI. In children, this was around 10% irrespective of RTI type. The majority of repeat prescriptions occurred a median of 10 days after the initial prescription and was the same antibiotic class in 48.3% of cases. Frequent RTI related GP visits and prior within-RTI-episode repeat antibiotic prescriptions were main factors associated with repeat prescriptions in both adults and children irrespective of RTI type. Young (<2 years) and older (65+) age were associated with repeat prescriptions. Among those aged 2-64 years, allergic rhinitis, COPD and oral corticosteroids were associated with repeat prescriptions.InterpretationsRepeat within-episode antibiotic use accounts for a significant proportion of all antibiotics prescribed for RTIs, with same class antibiotics unlikely to confer clinical benefit and is therefore a prime target for future antimicrobial stewardship interventions.
An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure
Authors: Wei Liu, Wenhua You, Zhenwei Lan, Yijiu Ren, Shuangshu Gao, Shuchao Li, Wei-Wei Chen, Chunyu Huang, Yong Zeng, Nengming Xiao, Zeshuai Wang, Huikang Xie, Huan Ma, Yun Chen, Guangsuo Wang, Chang Chen, Hanjie Li
Journal: Cell Reports Medicine (2024)

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8+ T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4+ T cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4+ T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. Inhibiting TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The anti-tumoral effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes an anti-tumoral role of the Tfh-dependent TLS in the development of LUAD.
Biomimetic MicroRNAs‐Selenium‐Nanocomposites for Targeted and Combined Hyperlipidemia Therapy
Authors: Tong Li, Libing Liu, Kongdi Zhu, Yun Luo, Xin Huang, Yulan Dong, Jiaqiang Huang
Journal: Advanced Healthcare Materials (2024)

Hyperlipidemia is considered as a high-risk factor for leading to coronary heart disease. MicroRNA-148a-3p (miR-148a-3p) inhibitor is a potential therapeutic target to bind low-density lipoprotein cholesterol receptors (LDLR) for decreasing the levels of low-density lipoprotein cholesterol in plasma. However, the therapeutic effects are not ideal in the clinical translation of nucleic acids treatment, owing to the short circulation time in vivo. Therefore, a platelet membrane (PM) cloaks Se nanoparticles (SeNPs) delivery system with chitosan (CS) modifies and miR-148a-3p inhibitors encapsulated is designed (PM/CS-SeNPs/miR). The PM/CS-SeNPs/miR shows a uniform shell-core structure with a particle size of ≈90 nm. Co-delivering miR-148a-3p inhibitors and Se effectively alleviate hyperlipidemia via LDLR pathway and Toll-Like Receptor 4 (TLR-4)/NF-κB signaling pathway, respectively. Furthermore, coated by PM, PM/CS-SeNPs/miR successfully prolong circulation time to 48 h in vivo and quickly target to liver with no toxicity. This dual combination therapy with miRNAs and Se based on nanoparticles targeted delivery presents a high-performance strategy for precise hyperlipidemia treatment.
<i>HER2</i> Gene Expression Levels Are Predictive and Prognostic in Patients With Metastatic Colorectal Cancer Enrolled in CALGB/SWOG 80405
Authors: Francesca Battaglin, Fang-Shu Ou, Xueping Qu, Howard S. Hochster, Donna Niedzwiecki, Richard M. Goldberg, Robert J. Mayer, Karam Ashouri, Tyler J. Zemla, Charles D. Blanke, Alan P. Venook, Omar Kabbarah, Heinz-Josef Lenz, Federico Innocenti
Journal: Journal of Clinical Oncology (2024)

The phase III Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial found no difference in overall survival (OS) in patients with metastatic colorectal cancer receiving first-line chemotherapy in combination with either bevacizumab or cetuximab. We investigated the potential prognostic and predictive value of
Disparities Between Teleretinal Imaging Findings and Patient-Reported Diabetic Retinopathy Status and Follow-Up Eye Care Interval: A 10-Year Prospective Study
Authors: Paolo S. Silva, Jerry D. Cavallerano, Jennifer K. Sun, Ann M. Tolson, Dorothy Tolls, Martin J. Abrahamson, Lloyd M. Aiello, Lloyd Paul Aiello
Journal: Diabetes Care (2024)

OBJECTIVE To assess self-reported awareness of diabetic retinopathy (DR) and concordance of eye examination follow-up compared with findings from concurrent retinal images. RESEARCH DESIGN AND METHODS We conducted a prospective observational 10-year study of 26,876 consecutive patients with diabetes who underwent retinal imaging during an endocrinology visit. Awareness and concordance were evaluated using questionnaires and retinal imaging. RESULTS Awareness information and gradable images were available in 25,360 patients (94.3%). Severity of DR by imaging was as follows: no DR (n = 14,317; 56.5%), mild DR (n = 6,805; 26.8%), or vision-threatening DR (vtDR; n = 4,238; 16.7%). In the no, mild, and vtDR groups, 96.7%, 88.5%, and 54.9% of patients, respectively, reported being unaware of any prior DR. When DR was present, reporting no prior DR was associated with shorter diabetes duration, milder DR, last eye examination &amp;gt;1 year before, no dilation, no scheduled appointment, and less specialized provider (all P &amp;lt; 0.001). Among patients with vtDR, 41.2%, 58.1%, and 64.2% did not report being aware of any DR and follow-up was concordant with current DR severity in 66.7%, 41.3%, and 25.4% (P &amp;lt; 0.001) of patients when prior examination was performed by a retinal specialist, nonretinal ophthalmologist, or optometrist (P &amp;lt; 0.001), respectively. CONCLUSIONS Substantial discrepancies exist between DR presence, patient awareness, and concordance of follow-up across all DR severity levels. These discrepancies are present across all eye care provider types, with the magnitude influenced by provider type. Therefore, patient self-report should not be relied upon to reflect DR status. Modification of medical care and education models may be necessary to enhance retention of ophthalmic knowledge in patients with diabetes and ensure accurate communication between all health care providers.
Thrombin receptor activating peptide-6 decreases acute graft-versus-host disease through activating GPR15
Authors: Cong Liu, Qiu Lan, Shuo Cao, Fei Zheng, Yiwen Liang, Jingyi Shen, Ying Wang, Takayuki Ikezoe, Kailin Xu, Bin Pan
Journal: Leukemia (2024)
Removal of an embedded gastric fishbone by traction-assisted endoscopic full-thickness resection
Authors: Shuzhen Chen, Songsong Ying, Cailian Xian, Yongqiang Li, Wenyan Jiang
Journal: Endoscopy (2024)

A 65-year-old man was referred to our hospital with a half-year history of upper abdominal pain. Endoscopy showed a submucosal eminence on the anterior wall of the gastric antrum ([Fig. 1] a). Endoscopic ultrasonography (EUS) revealed a hyperechoic lesion in the gastric submucosa ([Fig. 2]). A computed tomography (CT) scan showed a long, high density shadow in the gastric antrum, locally protruding into the serosal cavity ([Fig. 3]). Emergency endoscopy was performed with the patient under general anesthesia and with endotracheal intubation ([Video 1]).
2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction
Authors: Thomas M. Maddox, James L. Januzzi, Larry A. Allen, Khadijah Breathett, Sara Brouse, Javed Butler, Leslie L. Davis, Gregg C. Fonarow, Nasrien E. Ibrahim, JoAnn Lindenfeld, Frederick A. Masoudi, Shweta R. Motiwala, Estefania Oliveros, Mary Norine Walsh, Alan Wasserman, Clyde W. Yancy, Quentin R. Youmans
Journal: Journal of the American College of Cardiology (2024)
Myelodysplastic neoplasms dissected into indolent, leukaemic and unfavourable subtypes by computational clustering of haematopoietic stem and progenitor cells
Authors: Margot F van Spronsen, Sofie Van Gassen, Carolien Duetz, Theresia M Westers, Yvan Saeys, Arjan A van de Loosdrecht
Journal: Leukemia (2024)

Abstract Myelodysplastic neoplasms (MDS) encompass haematological malignancies, which are characterised by dysplasia, ineffective haematopoiesis and the risk of progression towards acute myeloid leukaemia (AML). Myelodysplastic neoplasms are notorious for their heterogeneity: clinical outcomes range from a near-normal life expectancy to leukaemic transformation or premature death due to cytopenia. The Molecular International Prognostic Scoring System made progress in the dissection of MDS by clinical outcomes. To contribute to the risk stratification of MDS by immunophenotypic profiles, this study performed computational clustering of flow cytometry data of CD34 + cells in 67 MDS, 67 AML patients and 49 controls. Our data revealed heterogeneity also within the MDS-derived CD34 + compartment. In MDS, maintenance of lymphoid progenitors and megakaryocytic-erythroid progenitors predicted favourable outcomes, whereas expansion of granulocyte-monocyte progenitors increased the risk of leukaemic transformation. The proliferation of haematopoietic stem cells and common myeloid progenitors with downregulated CD44 expression, suggestive of impaired haematopoietic differentiation, characterised a distinct MDS subtype with a poor overall survival. This exploratory study demonstrates the prognostic value of known and previously unexplored CD34 + populations and suggests the feasibility of dissecting MDS into a more indolent, a leukaemic and another unfavourable subtype.
Endoscopic ultrasound-guided gallbladder drainage using a forward-viewing echoendoscope after Billroth II gastrectomy
Authors: Yuichiro Tozuka, Kazuya Sugimori, Haruo Miwa, Takashi Kaneko, Makoto Ueno, Junji Furuse, Shin Maeda
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is effective for treating cholecystitis [1] [2]; however, its application is challenging in patients with surgically altered anatomy [3]. In such patients, the forward-viewing echoendoscope (FV-EUS) is useful [4]. Here, we report a case of a patient who underwent EUS-GBD using FV-EUS after Billroth II gastrectomy.
Transmembrane domain–driven PD-1 dimers mediate T cell inhibition
Authors: Elliot A. Philips, Jia Liu, Audun Kvalvaag, Alexander M. Mørch, Anna S. Tocheva, Charles Ng, Hong Liang, Ian M. Ahearn, Ruimin Pan, Christina C. Luo, Alexander Leithner, Zhihua Qin, Yong Zhou, Antonio Garcia-España, Adam Mor, Dan R. Littman, Michael L. Dustin, Jun Wang, Xiang-Peng Kong
Journal: Science Immunology (2024)

Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers, but PD-1 has been considered monomeric. Here, we show that PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions and that propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor immunity, cytotoxic T cell function, and autoimmune tissue destruction. These observations contribute to our understanding of the PD-1 axis and how it can potentially be manipulated for improved treatment of cancer and autoimmune diseases.
Peroral choledochoscope-assisted removal of residual guidewire embedded in the mucous membrane of the pancreatic duct
Authors: Yaoting Li, Lichao Zhang, Baoru Zhang, Tingting Yu, Yankun Hou, Jiao Tian, Senlin Hou
Journal: Endoscopy (2024)

A 36-year-old man underwent endoscopic retrograde cholangiopancreatography (ERCP) at a local hospital for chronic pancreatitis, after which the broken end of a guidewire remained in the pancreatic duct. The patient had intermittent postoperative abdominal discomfort and was referred to our hospital.