tbuckley/cabot-search huggingface dataset:
Conversion practice recall and mental health symptoms in sexual and gender minority adults in the USA: a cross-sectional study
Authors: Nguyen K Tran, Elle Lett, Barbara Cassese, Carl G Streed, David J Kinitz, Shalonda Ingram, Karalin Sprague, Zubin Dastur, Micah E Lubensky, Annesa Flentje, Juno Obedin-Maliver, Mitchell R Lunn
Journal: The Lancet Psychiatry (2024)
Inhibition of ACSS2 triggers glycolysis inhibition and nuclear translocation to activate SIRT1/ATG5/ATG2B deacetylation axis, promoting autophagy and reducing malignancy and chemoresistance in ovarian cancer
Authors: Jiang Yang, Haoyu Wang, Bingshu Li, Jingchun Liu, Xiaoyi Zhang, Ying Wang, Jiaxin Peng, Likun Gao, Xinqi Wang, Siyuan Hu, Wenyi Zhang, Li Hong
Journal: Metabolism (2024)
Maternal and pregnancy factors contributing to the association between area deprivation and infant mortality in England: a retrospective cohort study
Authors: Frederick K Ho, Max Allan, Hui Shao, Kenneth K C Man, Bhautesh D Jani, Donald Lyall, Claire Hastie, Michael Fleming, Daniel Mackay, John G F Cleland, Christian Delles, Ruth Dundas, Jim Lewsey, Patrick Ip, Ian Wong, Paul Welsh, Anna Pearce, Charlotte M Wright, Helen Minnis, S Vittal Katikireddi, Jill P Pell
Journal: The Lancet Regional Health - Europe (2024)

Socioeconomic inequality in infant mortality in the UK is rising. This study aims to identify contributory maternal and pregnancy factors that can explain the known association between area deprivation and infant mortality.
Sexual Health and Quality of Life in Patients With Low-Risk Early-Stage Cervical Cancer: Results From GCIG/CCTG CX.5/SHAPE Trial Comparing Simple Versus Radical Hysterectomy
Authors: Sarah E. Ferguson, Lori A. Brotto, Janice Kwon, Vanessa Samouelian, Gwenael Ferron, Amandine Maulard, Cor de Kroon, Willemien Van Driel, John Tidy, Karin Williamson, Sven Mahner, Stefan Kommoss, Frederic Goffin, Karl Tamussino, Brynhildur Eyjolfsdottir, Jae-Weon Kim, Noreen Gleeson, Dongsheng Tu, Lois Shepherd, Marie Plante
Journal: Journal of Clinical Oncology (2024)

PURPOSE Simple hysterectomy and pelvic node assessment (SHAPE) is a phase III randomized trial (ClinicalTrials.gov identifier: NCT01658930 ) reporting noninferiority of simple compared with radical hysterectomy for oncologic outcomes in low-risk cervical cancer. This study presents secondary outcomes of sexual health and quality of life (QOL) of the SHAPE trial. METHODS Participants were randomly assigned to receive either radical or simple hysterectomy. Sexual health was assessed up to 36 months postoperatively using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised and QOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer-Specific Module (QLQ-CX24) questionnaires. RESULTS Among participants with at least one QOL measure, clinical and pathologic characteristics were balanced and with no differences in preoperative baseline scores for sexual health or QOL between groups. FSFI total score met the cutoff for dysfunction up to 6 months ( P = .02) in the radical hysterectomy group. Group differences favored simple hysterectomy for FSFI subscales: desire and arousal at 3 months ( P ≤ .001) and pain and lubrication up to 12 months ( P ≤ .018). Both groups met the cutoff for sexual distress but was higher in radical hysterectomy at 3 months ( P = .018). For QLQ-CX24, symptom experience was significantly better up to 24 months ( P = .031) and body image better at 3, 24, and 36 months ( P ≤ .01) for simple hysterectomy. Sexual-vaginal functioning was significantly better up to 24 months ( P ≤ .022) and more sexual activity up to 36 months ( P = .024) in the simple hysterectomy arm. Global health status was significantly higher at 36 months for simple hysterectomy ( P = .025). CONCLUSION Simple hysterectomy was associated with lower rates of sexual dysfunction than radical hysterectomy, with a lower proportion of women having sustained sexual-vaginal dysfunction. These results further support the benefit of surgical de-escalation for low-risk cervical cancer.
Efficacy and Safety of Roxadustat for Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: A Randomized, Open-Label, Active-Controlled Phase III Study
Authors: Shun Lu, Jiong Wu, Jin Jiang, Qisen Guo, Yan Yu, Yu Liu, Hua Zhang, Ling Qian, Xiumei Dai, Yanyan Xie, Ting Fu, Tyson Lee, Yan Lu, Rui Ma, Mark D. Eisner
Journal: Journal of Clinical Oncology (2024)

PURPOSE We evaluated the efficacy and safety of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies receiving multicycle treatments of chemotherapy. PATIENTS AND METHODS In this open-label, noninferiority phase III study conducted at 44 sites in China, 159 participants age ≥18 years with CIA nonmyeloid malignancy and CIA were randomly assigned (1:1) to oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting dosages were 100, 120, and 150 mg three times a week for participants weighing 40-&lt;50, 50-60, and &gt;60 kg, respectively. rHuEPO-α starting dosage for all participants was 150 IU/kg three times a week. Both roxadustat and rHuEPO-α dosages could be modified. The primary end point was least-squares mean (LSM) change in hemoglobin (Hb) concentration from baseline to the concentration averaged over weeks 9-13. RESULTS Of the 159 participants randomly assigned, 140 were included in the per-protocol set (roxadustat, n = 78; rHuEPO-α, n = 62). The LSM (95% two-sided CI) change from baseline to weeks 9-13 in Hb concentration was 17.1 (13.58 to 20.71) g/L with roxadustat and 15.4 (11.34 to 19.50) g/L with rHuEPO-α (mean difference [95% CI], 1.7 [–3.39 to 6.84]). The lower bound of the one-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined noninferiority margin of ‒6.6 g/L, establishing noninferiority. Noninferiority was supported by five of six key secondary end points. Rates of adverse events were generally comparable between treatments and consistent with previous findings. CONCLUSION Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance.
Impact of an Epstein-Barr Virus Serology-Based Screening Program on Nasopharyngeal Carcinoma Mortality: A Cluster-Randomized Controlled Trial
Authors: Wen-Jie Chen, Xia Yu, Yu-Qiang Lu, Ruth M. Pfeiffer, Wei Ling, Shang-Hang Xie, Zhi-Cong Wu, Xue-Qi Li, Yu-Ying Fan, Biao-Hua Wu, Kuang-Rong Wei, Hui-Lan Rao, Qi-Hong Huang, Xiang Guo, Ying Sun, Jun Ma, Qing Liu, Allan Hildesheim, Ming-Huang Hong, Yi-Xin Zeng, Ming-Fang Ji, Zhiwei Liu, Su-Mei Cao
Journal: Journal of Clinical Oncology (2024)

PURPOSE Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population. METHODS Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538 ). RESULTS A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856). CONCLUSION In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.
Clinical effectiveness of DREAMS START (Dementia Related Manual for Sleep; Strategies for Relatives) versus usual care for people with dementia and their carers: a single-masked, phase 3, parallel-arm, superiority randomised controlled trial
Authors: Penny Rapaport, Sarah Amador, Mariam O Adeleke, Julie A Barber, Sube Banerjee, Georgina Charlesworth, Chris Clarke, Colin A Espie, Lina Gonzalez, Rossana Horsley, Rachael Hunter, Simon D Kyle, Monica Manela, Malgorzata Raczek, Zuzana Walker, Lucy Webster, Hang Yuan, Gill Livingston
Journal: The Lancet Healthy Longevity (2024)
Atherosclerotic Cardiovascular Diseases Are Associated With Incident Metastatic and Nonmetastatic Cancer
Authors: Tal Caller, Alexander Fardman, Yariv Gerber, Yonatan Moshkovits, Shmuel Tiosano, Alon Kaplan, Maia Kalstein, Gabriella Bayshtok, Tomer Itkin, Abraham Avigdor, Nili Naftali-Shani, Jonathan Leor, Elad Maor
Journal: JACC CardioOncology (2024)
Net Clinical Benefit of 12-Month Over 3-Month Edoxaban in Cancer-Associated Isolated Distal Deep Vein Thrombosis
Authors: Yuji Nishimoto, Yugo Yamashita, Takeshi Morimoto, Nao Muraoka, Michihisa Umetsu, Takuma Takada, Yoshito Ogihara, Tatsuya Nishikawa, Nobutaka Ikeda, Yukihito Sato, Takahisa Yamada, Takeshi Kimura
Journal: JACC CardioOncology (2024)
Papillary Craniopharyngioma: an integrative and comprehensive review
Authors: Ruth Prieto, Tareq A Juratli, Evan D Bander, Sandro Santagata, Laura Barrios, Priscilla K Brastianos, Theodore H Schwartz, José M Pascual
Journal: Endocrine Reviews (2024)

Abstract Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as World Health Organization grade 1, characterized by nonkeratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular cysts with a cauliflower-like excrescence. PCPs primarily occur in adults (95%), with increased frequency in males (60%), and predominantly affect the hypothalamus. Over 80% of these tumors are located in the third ventricle, expanding either above an anatomically intact infundibulum (strictly third ventricle tumors) or within the infundibulo-tuberal region of the third ventricle floor. Clinical manifestations commonly include visual deficits and a wide range of psychiatric disturbances (45% of patients), such as memory deficits and odd behavior. Magnetic resonance imaging can identify up to 50% of PCPs by the presence of a basal duct-like recess. Surgical management is challenging, requiring complex approaches to the third ventricle and posing significant risk of hypothalamic injury. The endoscopic endonasal approach allows radical tumor resection and yields more favorable patient outcomes. Of intriguing pathogenesis, over 90% of PCPs harbor the somatic BRAFV600E mutation, which activates the mitogen-activated protein kinase signaling pathway. A phase 2 clinical trial has demonstrated that PCPs respond well to proto-oncogene B-Raf/MAPK/ERK kinase inhibitors. This comprehensive review synthesizes information from a cohort of 560 well-described PCPs and 99 large CP series including PCP cases published from 1856 to 2023 and represents the most extensive collection of knowledge on PCPs to date.
The incidence of postoperative periprosthetic femoral fracture following total hip replacement: An analysis of UK National Joint Registry and Hospital Episodes statistics data
Authors: Jonathan Nicholas Lamb, Jonathan Thomas Evans, Samuel Relton, Michael Richard Whitehouse, J Mark Wilkinson, Hemant Pandit
Journal: PLoS Medicine (2024)

Background Postoperative periprosthetic femoral fracture (POPFF) after total hip replacement (THR) requires complex surgery and is associated with a high morbidity, mortality, and cost. Although the United Kingdom based National Joint Registry (NJR) captures over 95% of THRs treated with revision, before June 2023 it did not capture POPFF treated with fixation. We aimed to estimate the incidence and epidemiology of POPFF treated with either surgery in England. Methods and findings We performed a retrospective analysis of a mandatory, prospective database (NJR) linked to Hospital Episode Statistics (HES). All linkable primary THRs between 01/01/2004 and 31/12/2020 were included. Revision or fixation of POPFF were identified using a combination of procedural and diagnosis codes. We identified 809,832 THRs representing 5,542,332 prosthesis years at risk. A total of 5,100 POPFF were identified that had been surgically treated by revision, fixation, or both, and 2,831 of these fractures were treated with fixation alone, meaning 56% were not represented with revision data alone. The incidence of POPFF needing surgery was 0.92 (95% CI 0.90, 0.95) per 1,000 prostheses years. This incidence was higher in patients over the age of 70 at the time of primary THR (1.31 [95% CI 1.26, 1.35] per 1,000 prostheses years) and for patients who underwent THR for hip fracture (2.19 [95% CI 1.97, 2.42] per 1,000 prostheses years). This incidence appears to be increasing year on year. The cumulative probability of sustaining a POPFF within 10 years of THR was 1% and over 15% of patients died within 1 year of surgery for a POPFF. Conclusions To date, the incidence of POPFF may have been underestimated with over 50% of cases missed if the case identification in this study is correct. After including these cases, we observed that POPFF is the largest reason for major reoperation following THR and patients sustaining these injuries have a high risk of death. The prevention and treatment of POPFF and requires further resource allocation and research.
Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury
Authors: S Farshid Moussavi-Harami, Simon J Cleary, Mélia Magnen, Yurim Seo, Catharina Conrad, Bevin C English, Longhui Qiu, Kristin M Wang, Clare L Abram, Clifford A Lowell, Mark R Looney
Journal: Journal of Clinical Investigation (2024)

The acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality and neutrophils are critical to its pathogenesis. Neutrophil activation is closely regulated by inhibitory tyrosine phosphatases including Src homology region 2 domain containing phosphatase-1 (Shp1). Here, we report that loss of neutrophil Shp1 in mice produced hyperinflammation and lethal pulmonary hemorrhage in sterile inflammation and pathogen-induced models of acute lung injury (ALI) through a Syk kinase-dependent mechanism. We observed large intravascular neutrophil clusters, perivascular inflammation, and excessive neutrophil extracellular traps in neutrophil-specific Shp1 knockout mice suggesting an underlying mechanism for the observed pulmonary hemorrhage. Targeted immunomodulation through the administration of a Shp1 activator (SC43) reduced agonist-induced reactive oxygen species in vitro and ameliorated ALI-induced alveolar neutrophilia and NETs in vivo. We propose that the pharmacologic activation of Shp1 has the potential to fine-tune neutrophil hyperinflammation that is central to the pathogenesis of ARDS.
Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system
Authors: Tianxu Liu, Jian Li, Xin Yin, Fengmin Lu, Hui Zhao, Lin Wang, Cheng-Feng Qin
Journal: Gut (2024)

Background Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. Objective This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA). Design In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar −/− mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&amp;E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model. Results On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model. Conclusion This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo.
High-dose IV ascorbic acid therapy in CCUS patients with TET2 mutations
Authors: Zhuoer Xie, Jenna Fernandez, Terra L Lasho, Christy M. Finke, Michelle Amundson, Kristen McCullough, Betsy LaPlant, Abhishek A Mangaonkar, Naseema Gangat, Kaaren K Reichard, Michelle Ann Elliott, Thomas E. Witzig, Mrinal M. Patnaik
Journal: Blood (2024)
Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD
Authors: Fu-Shun Yen, Chih-Cheng Hsu, James Cheng-Chung Wei, Fuu-Jen Tsai, Yuhan Huang, Teng-Shun Yu, Chii-Min Hwu
Journal: Thorax (2024)

Background Clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary outcomes and mortality between GLP-1 RA use and no use in patients with type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD). Methods The study identified 8060 matched GLP-1 RA users and non-users from Taiwan’s National Health Insurance Research Database from 1 January 2008 to 31 December 2019. Cox proportional hazards models were used to determine the risk of cardiopulmonary outcomes between GLP-1 RA users and non-users. Results The mean follow-up time was 2.51 and 2.46 years for GLP-1 RA users and non-users, respectively. In the matched cohorts, GLP-1 RA users had a significantly lower risk of mortality (adjusted HR (aHR) 0.46, 95% CI 0.38 to 0.56), cardiovascular events (aHR 0.73, 95% CI 0.65 to 0.82), non-invasive positive pressure ventilation (aHR 0.66, 95% CI 0.47 to 0.93), invasive mechanical ventilation (aHR 0.64, 95% CI 0.51 to 0.8) and bacterial pneumonia (aHR 0.76, 95% CI 0.65 to 0.88) than GLP-1 RA non-users. The subsequent analyses for various subgroup and medication duration also showed that GLP-1 RA was associated with a significantly lower risk of mortality, cardiovascular events, ventilation support and bacterial pneumonia than non-GLP-1 RA. Conclusion This nationwide cohort study showed that GLP-1 RA had a lower risk of cardiopulmonary outcomes and all-cause mortality than non-GLP-1 RA in patients with T2D and COPD. GLP-1 RA may help manage diabetes in people with COPD.
p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus
Authors: Guodong Lian, Ermanno Malagola, Chengguo Wei, Qiongyu Shi, Junfei Zhao, Masahiro Hata, Hiroki Kobayashi, Yosuke Ochiai, Biyun Zheng, Xiaofei Zhi, Feijing Wu, Ruhong Tu, Osmel Companioni Nápoles, Wenjing Su, Leping Li, Changqing Jing, Man Chen, Leah Zamechek, Richard Friedman, Karol Nowicki-Osuch, Michael Quante, Jianwen Que, Timothy C Wang
Journal: Gut (2024)

Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r + cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo. Results The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation towards metaplasia, but only amidst chronic injury. In L2-IL1β mice, p53 mutation increased progenitors expansion and lineage-tracing with a shift from metaplasia to dysplasia. scRNA-seq revealed dysplastic cells arise directly from mutant progenitors rather than progressing through metaplasia. In vitro, p53 mutation enhanced BE progenitors’ organoid-forming efficiency, growth, DNA damage resistance and progression to aneuploidy. Sorted metaplastic cells grew poorly with no progression to dysplasia, while mutant progenitors gave rise to dysplasia in orthotopic transplantation. Computational analyses indicated that p53 mutation inhibited stem cell differentiation through Notch activation. Conclusions p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia.
Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma
Authors: Yang Liu, Junyan Wu, Hinda Najem, Yiyun Lin, Lizhi Pang, Fatima Khan, Fei Zhou, Heba Ali, Amy B Heimberger, Peiwen Chen
Journal: Journal of Clinical Investigation (2024)

Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression and therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) and olfactomedin like-3 (OLFML3) as essential macrophage and microglia chemokines, respectively, in GBM. Here, single-cell transcriptomics and multiplex sequential immunofluorescence followed by functional studies demonstrate that macrophages negatively correlate with microglia in the GBM tumor microenvironment. LOX inhibition in PTEN-deficient GBM cells upregulates OLFML3 expression via the NF-κB-PATZ1 signaling pathway, inducing a compensatory increase of microglia infiltration. Dual targeting macrophages and microglia via inhibition of LOX and the CLOCK-OLFML3 axis generates potent anti-tumor effects and offers a complete tumor regression in more than 60% of animals when combined with anti-PD1 therapy in PTEN-deficient GBM mouse models. Thus, our findings provide a translational triple therapeutic strategy for this lethal disease.