bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for imaging abnormalities after the first febrile urinary tract infection in infants ≤3 months old: a retrospective cohort study
Authors: Chong Siew Le , Leow Esther Huimin , Yap Celeste Jia Ying , Chao Sing Ming , Ganesan Indra , Ng Yong Hong 
Published: January 2023

ObjectivesTo assess the association of clinical factors and investigation results (blood and urine) with imaging abnormalities (ultrasound of the kidneys, ureters and bladder; dimercaptosuccinic acid scan; and/or micturating cystourethrogram) and recurrent urinary tract infections (UTIs) in infants ≤3 months old presenting with their first febrile UTI.MethodsWe conducted a retrospective cohort study of infants ≤3 months old with first febrile UTI admitted from 2010 to 2016. Multivariable logistic regression model was used to analyse the association of imaging abnormalities and recurrent UTI with covariates selected a priori: age at presentation, maximum temperature, duration of illness at presentation, interval between start of antibiotics and fever resolution, C-reactive protein, total white cell count on the full blood count, bacteraemia, white cell count on the urinalysis and non-Escherichia coligrowth in the urine culture (non-E. coliUTI).ResultsThere were 190 infants but 12 did not undergo any imaging. Median age at presentation was 63 days (IQR 41–78). Twenty-four patients had imaging abnormalities. Non-E. coliUTI (adjusted OR (aOR) 5.01, 95% CI 1.65 to 15.24, p=0.004) was independently associated with imaging abnormalities, while bacteraemia (aOR 4.93, 95% CI 1.25 to 19.43, p=0.022) and non-E. coliUTI (aOR 5.06, 95% CI 1.90 to 13.48, p=0.001) were independently associated with recurrent UTI.ConclusionNon-E. coliUTI at the first febrile UTI in infants ≤3 months old may be useful in predicting imaging abnormalities while bacteraemia and non-E. coliUTI may be useful to predict recurrent UTI.
Subcostal transversus abdominis plane block for postoperative analgesia in liver transplant recipients: a before-and-after study
Authors: Assefi Mona , Trillaud Emma , Vezinet Corinne , Duceau Baptiste , Baron Elodie , Pons Stephanie , Clavieras Noemie , Quemeneur Cyril , Selves Agathe , Scatton Olivier , Monsel Antoine , Constantin Jean-Michel 
Published: January 2023

IntroductionPostoperative pain management after orthotopic liver transplantation is complex due to impaired liver function and frequent acute kidney dysfunction. Subcostal transversus abdominis plane (TAP) block may be of interest in this population. The aim of this study was to evaluate the impact of subcostal TAP block on opioid consumption after liver transplantation.MethodsWe conducted a before-and-after single center study. During the first period, we included patients whom did not receive an analgesic TAP block. During the second period, we included those with bilateral ultrasound-guided subcostal TAP block (20 mL ropivacaïne 0.2% each side). Patients requiring sedation within 48 hours of surgery as well as patients with combined liver and kidney transplants or skin-only closures were excluded. The primary outcome was cumulative oral morphine consumption within 48 hours after surgery. Secondary outcomes included pain scores and TAP block-related complications.ResultsA total of 132 patients were included in the non-TAP block group and 78 patients in the TAP block group. The median oral morphine equivalent consumption (IQR) within 48 hours following surgery was 74 mg (39; 112) for the non-TAP block group and 50 mg (20; 80) for the TAP block group (p<0.001). There was no difference in pain scores between the two groups. No complications related to the TAP block were reported.ConclusionSubcostal TAP block appears to have a small opioid reducing effect after orthotopic liver transplantation surgery.
Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial)
Authors: Vanneste Thibaut , Belba Amy , Kallewaard Jan Willem , van Kuijk Sander M J , Gelissen Marloes , Emans Peter , Bellemans Johan , Smeets Kristof , Terwiel Chris , Van Boxem Koen , Sommer Micha , Van Zundert Jan 
Published: January 2023

BackgroundRadiofrequency (RF) treatment of the genicular nerves has the potential to reduce chronic knee pain due to osteoarthritis or persistent postsurgical pain, however, a direct comparison between the two main modalities used, conventional and cooled, is lacking.MethodsThis double blind, non-inferiority, pilot, randomized controlled trial compared the effects of cooled and conventional RF in chronic knee pain patients suffering from osteoarthritis or persistent postsurgical pain after total knee arthroplasty. Patients were randomized following a 1:1 rate. The primary outcome was the proportion of patients with ≥50% pain reduction at 3 months postintervention. Other outcomes were knee pain, functionality, quality of life, emotional health, and adverse events up to 6 months postintervention. Conventional RF treatment was tested for non-inferiority to cooled in reducing knee pain at 3 months follow-up.ResultsForty-nine of 70 patients were included, of which 47 completed a 3-month follow-up. The primary outcome was achieved in 4 of 23 patients treated with conventional RF (17%) vs in 8 of 24 with cooled (33%) (p=0,21). Results from the non-inferiority comparison were inconclusive in relation to the non-inferiority margin. There was no statistically significant difference between secondary outcomes. There were no serious adverse events.ConclusionsBoth conventional and cooled RF treatment reduced pain in the osteoarthritis and persistent postsurgical pain population. This pilot study did not demonstrate statistically significant differences in the proportion of patients experiencing ≥50% pain reduction between techniques. The non-inferiority analysis was inconclusive. These results warrant further research.Trial registration numberNCT03865849.
Acute right insular ischaemic lesions and poststroke left ventricular dysfunction
Authors: Winder Klemens , Villegas Millar Carolina , Siedler Gabriela , Knott Michael , Dörfler Arnd , Engel Anna , Achenbach Stephan , Hilz Max J , Kallmünzer Bernd , Schwab Stefan , Seifert Frank , Fröhlich Kilian 
Published: January 2023

IntroductionMyocardial injury related to acute ischaemic stroke is common even without primary cardiac disease. We intended to determine associations between values of left ventricular ejection fraction (LVEF) and ischaemic stroke lesion sites.MethodsOf a local database, patients with acute first-ever ischaemic stroke confirmed by brain imaging but without pre-existing heart disease were included. The cardiac morphology and LVEF were obtained from transthoracic or transesophageal echocardiography, and impaired LVEF was categorised as mild (35%–50%), moderate (34%–25%) and severe (<25%). Patient age, stroke severity, ischaemic lesion volume, prevalence of troponin I increase (>0.1 ng/mL), atrial fibrillation and cardiac wall motion abnormalities were assessed and compared between patients with and without impaired LVEF after stroke (significance: p<0.05). A multivariate voxelwise lesion analysis correlated LVEF after stroke with sites of ischaemic lesions.ResultsOf 1209 patients who had a stroke, 231 (mean age 66.3±14.0 years) met the inclusion criteria; 40 patients (17.3%) had an impaired LVEF after stroke. Patients with impaired LVEF had higher infarct volumes (53.8 mL vs 30.0 mL, p=0.042), a higher prevalence of troponin increase (17.5% vs 4.2%, p=0.006), cardiac wall motion abnormalities (42.5% vs 5.2%, p<0.001) and atrial fibrillation (60.0% vs 26.2%, p<0.001) than patients with LVEF of >50%. The multivariate voxelwise lesion analysis yielded associations between decreased LVEF and damaged voxels in the insula, amygdala and operculum of the right hemisphere.ConclusionOur imaging analysis unveils a prominent role of the right hemispheric central autonomic network, especially of the insular cortex, in the brain–heart axis. Our results support preliminary evidence that acute ischaemic stroke in distinct brain regions of the central autonomic network may directly impair cardiac function and thus further supports the concept of a distinct stroke-heart syndrome.
Using a Clinical Decision Support System to Improve Anticoagulation in Patients with Nonvalve Atrial Fibrillation in China’s Primary Care Settings: A Feasibility Study
Authors: Ru Xueying , Wang Tianhao , Zhu Lan , Ma Yunhui , Qian Liqun , Sun Huan , Pan Zhigang 
Published: January 2023

Background. To primarily investigate the effect of using a clinical decision support system (CDSS) in community health centers in Shanghai, China, on the proportion of patients prescribed guideline-directed antithrombotic therapy. This study also gauged the general practitioner (GP)’s acceptance of the CDSS who worked in the atrial fibrillation (AF) special consulting room of the CDSS group. Methods. This was a prospective cohort study that included a semistructured interview and a feasibility study for a cluster-randomized controlled trial. Eligible patients who sought medical care in the AF special consulting rooms in two community health centers in Shanghai, China, between April 1, 2020, and October 1, 2020, were enrolled, and their medical records from the enrollment date, up to October 1, 2021, were extracted. Based on whether the GPs in the AF special consulting rooms of the two sites used the CDSS or not, we classified the two sites as a software group and a control group. The CDSS could automatically assess the risks of stroke and bleeding and provide suggestions on treatment, follow-up, adjustment of anticoagulants or dosage, and other items. The primary outcome was the proportion of patients prescribed guideline-directed antithrombotic therapy. We also conducted a semistructured interview with the GP in the AF special consulting rooms of the software group regarding the acceptance of the CDSS and suggestions on the optimization of the CDSS and the study protocol of the cluster-randomized controlled trial in the future. Results. Eighty-four patients completed the follow-up. The mean age of these subjects was 75.71 years, the median time of clinical visits was six times per person, and the follow-up duration was 15 months. The basic demographics were similar between the two groups, except for age (t = 2.109,

p

= 0.038) and the HAS-BLED score (χ2 = 4.363,

p

= 0.037). The primary outcome in the software group was 8.071 times higher than that in the control group (adjusted odds ratio (OR) = 8.071, 95% confidence interval (2.570–25.344),

p

< 0.001). The frequency of consultation between groups was not significantly different (

p

= 0.981). It seemed that the incidence of adverse clinical events in the software group was lower than that in the control group. The main reason for dropouts in both groups was “following up in other hospitals.” The GP in the AF special consulting rooms of the software group accepted the CDSS well. Conclusions. The findings indicated that it was feasible to further promote the CDSS in the study among community health centers in China. The use of the CDSS might improve the proportion of patients prescribed guideline-directed antithrombotic therapy. The GP in the AF special consulting room of the software group showed a positive attitude toward the CDSS.
Inference on the Genetic Architecture of Breast Cancer Risk
Authors: Yasui Yutaka , Letsou William , Wang Fan , Im Cindy , Sapkota Yadav , Wang Zhaoming , Salehabadi Sedigheh Mirzaei , Baedke Jessica L. , Moon Won Jong , Liu Qi , Robison Leslie L. , Martinez Jose Miguel 
Published: January 2023

Abstract

Background:
What are the major determinants of women's breast cancer risk? Rare mutations such as those in the BRCA1/2 genes, polygenic scores of common alleles identified by genome-wide association studies, or nongenetic factors?

Methods:
The population-based Nordic Twin Study of Cancer, with 3,933 breast cancer cases among 21,054 monozygotic (MZ) and 30,939 dizygotic (DZ) female twin pairs, provides three key clues to this question: (i) the average lifetime risk, approximately 8%, does not differ by twin zygosity; (ii) the mean time interval between diagnoses when both twins develop disease (i.e., disease concordance) also does not differ by zygosity; but, (iii) conditioning on one twin having developed disease, the incidence rate in the co-twin is approximately 1% per year if the pair is MZ and 0.5% per year if DZ.

Results:
Assuming that nongenetic risk factors are shared similarly between twins regardless of zygosity, we can draw two conclusions from (i) to (iii).

Conclusions:
First, (i) and (iii) imply that the chief determinant of risk is in the germline DNA, because the conditional incidence rate is several-fold higher than the average risk (8% lifetime) in MZ twins but only half as much in DZ twins. Second, the seeming inconsistency between the two-fold conditional incidence rate (iii) and the equality of the mean inter-twin disease intervals in disease concordance (ii) can be resolved if the risk factors in the germline DNA are rare variants, not common variants.

Impact:
This paper details simple deductive reasoning for these conclusions and draws a critical inference regarding breast cancer etiology.
See related In the Spotlight, p. 1477
Abstract B009: A liver-tropic BCL-xL PROTAC effectively clears senescent hepatocytes and prevents NASH-driven HCC in mice
Authors: Yang Yang , Jn-Simon Natacha , Hu Wanyi , Zhang Peiyi , Zheng Guangrong , Pi Liya , He Yonghan , Zhou Daohong 
Published: January 2023

Abstract
Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we reported the discovery of 753b, a BCL-xL proteolysis targeting chimera (PROTAC), as a potent and liver-tropic senolytic. We found that 753b can selectively clear senescent hepatocytes in aged mice and the STAM mice even though it can potently kill various SnCs in vitro. This is in part because 753b is enriched in the liver after its administration by ip injection. Moreover, 753b treatment can effectively reduce the development of non-alcoholic steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma (HCC) in the STAM mice. These findings suggest that 753b has the potential to be developed as a novel therapeutic for NAFLD and NASH-driven HCC.
Citation Format: Yang Yang, Natacha Jn-Simon, Wanyi Hu, Peiyi Zhang, Guangrong Zheng, Liya Pi, Yonghan He, Daohong Zhou. A liver-tropic BCL-xL PROTAC effectively clears senescent hepatocytes and prevents NASH-driven HCC in mice [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B009.
Abstract B020: Pre-malignant plasma cells exhibit a senescence-like phenotype and accumulation of transposable elements
Authors: Borges Gabriel Alvares , Guilatco Angelo Jose , Hachfeld Christine M. , Ruan Ming , Royzenblat Sonya , Xu Ming , Edwards Claire M. , Diaz-delCastillo Marta , Andersen Thomas L. , Kourelis Taxiarchis , Tchkonia Tamar , Kirkland James L. , Drake Matthew T. , Weivoda Megan 
Published: January 2023

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR012) of the Conference Proceedings.
Citation Format: Gabriel Alvares Borges, Angelo Jose Guilatco, Christine M. Hachfeld, Ming Ruan, Sonya Royzenblat, Ming Xu, Claire M. Edwards, Marta Diaz-delCastillo, Thomas L. Andersen, Taxiarchis Kourelis, Tamar Tchkonia, James L. Kirkland, Matthew T. Drake, Megan Weivoda. Pre-malignant plasma cells exhibit a senescence-like phenotype and accumulation of transposable elements [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B020.
Abstract IA012: Age related changes in the tumor microenvironment drive tumor progression
Authors: Stewart Sheila A. 
Published: January 2023

Abstract
The stromal compartment plays a pivotal role in tumor progression. This is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells and its expression levels correlate with poor prognosis. Using clinically relevant breast cancer metastasis models, we show that orally administered, small-molecule inhibitors of p38MAPKα or its downstream kinase, MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. Further we found that this effect is mediated by inhibition of the p38MAPKα pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, we also found that these inhibitors reduced tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity for cancer patients that drastically impacts their quality of life. Mechanistic studies revealed that p38MAPKα’s ability to limit tumor growth within the bone is dependent on CD4 T cells and macrophages. To determine which cell types within the bone contribute to tumor growth and bone loss, we carried out single cell RNA-sequencing of stromal cells located within the bone metastatic lesion and cells outside the lesion. We found numerous differences that could explain how the stromal compartment contributes to tumor progression and bone loss and how inhibition of p38MAPKα or MK2 contribute. These data underscore the vital role stromal-derived factors play in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss.
Citation Format: Sheila A. Stewart. Age related changes in the tumor microenvironment drive tumor progression [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA012.
Abstract A023: OGT/CDK5/ACSS2 axis regulates breast cancer brain metastatic growth
Authors: Esquea Emily , Ciraku Lorela , Minh Giang Le , Reginato Mauricio 
Published: January 2023

Abstract
Brain metastases (BMs) in breast cancer patients is considered an end-stage event, with no effective drug treatment and a median survival after diagnosis measured in months. Currently, there are no effective drug treatment for BM patients, thus there is an urgent need to develop novel treatment strategies. Breast cancers that metastasize to the brain must adapt to lack of lipid availability in the brain environment and are highly dependent on fatty acid synthesis for growth and survival. However, the signaling pathways that regulate precursors of fatty acid synthesis and lipid metabolism in breast cancer brain metastatic (BCBM) tumors are not known. Here, we show that BCBM cells can generate acetyl-CoA, a major metabolite feeding lipid biosynthesis, via phosphorylation of acetyl-CoA synthetase 2 (ACSS2) by the cyclin-dependent kinse-5 (CDK5) regulated by the nutrient sensor O-GlcNAc transferase (OGT). Breast cancer cells selected to metastasize to the brain contain higher levels of O-GlcNAcylation, OGT. and ACSS2-Ser267 phosphorylation compared to parental cells, and we show that human breast cancer brain metastatic patient samples contain elevated ACSS2-Ser-267 levels. Additionally, overexpression of the OGT, CDK5, or ACSS2-S267D phospho-mimetic mutant confers a growth advantage of breast cancer cells in the brain in vivo. Importantly, we show that ACSS2 is required for breast cancer growth in the brain but not in the mammary fat pad. Transcriptome analysis shows that ACSS2 regulates E2F-regulated genes and E2F1 protein levels in breast cancer cells. Pharmacologically targeting the CDK5 or ACSS2 with respective small molecule inhibitors reduces tumor growth in orthotopic ex vivo brain slice model. These results suggest a crucial role for OGT/CDK5/ACSS2 signaling axis to regulate lipid metabolism in BCBM cells and identify CDK5 and ACSS2 as novel therapeutic targets for treatment of breast cancer brain metastatic growth.
Citation Format: Emily Esquea, Lorela Ciraku, Giang Le Minh, Mauricio Reginato. OGT/CDK5/ACSS2 axis regulates breast cancer brain metastatic growth [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A023.
Abstract A037: PROTACs as emergent treatment modality of metastatic prostate cancer. [R
Authors: Bhavar Prashant Kashinath , Surampudi Uday Kumar , Sarma Partha Pratim , Katike Satish , Gandham Adilakshmi 
Published: January 2023

Abstract
Prostate cancer is one of the most commonly diagnosed and fourth leading cause of cancer death in men, with low survival rates for metastatic cancers. Androgen receptor (AR) is one of the most altered Oncogenes in castration-resistant prostate cancer (mCRPC). Suppression of AR signalling is one of the common strategies to treat prostate cancer. Androgen deprivation therapy (ADT) has been the backbone therapy for decades and demonstrated survival benefit when used alongside other therapies including Docetaxel, cabazitaxel or hormone based anti-androgen therapies such as Enzalutamide, abiraterone, darolutamide, and apalutamide. Unfortunately, amplification or mutation in AR gene along with its associated pathway such as alteration of PI3K pathway or upregulation of MYC oncogene drive mCRPC cell proliferation and confers resistance to existing therapies. To overcome such resistance mechanisms, targeted therapy towards Androgen receptor has emerged, where ligand conjugated small molecule inhibitors using proteolysis targeting chimera (PROTAC) strategy, could effectively downregulate the AR expression. Several PROTACs as ‘Androgen Receptor Degraders (ARD)’ are showing promising activity in early-stage clinical studies. Although a promising strategy, challenges exist for its development in future; given that finding the most appropriate protein-protein interaction is essential to find optimal ligand to successfully design PROTAC. Similarly, challenges to optimize safety and efficacy of PROTACs in the clinic, also remain to be addressed. Here we aim to provide comprehensive review, including patent landscape of the therapeutic benefits of using PROTACs and its future development prospect in context to metastatic prostate cancer.
Citation Format: Prashant Kashinath Bhavar, Uday Kumar Surampudi, Partha Pratim Sarma, Satish Katike, Adilakshmi Gandham. PROTACs as emergent treatment modality of metastatic prostate cancer. [R [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A037.