bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Magnetic Resonance Imaging of Dysregulated Zinc Secretion Detects Early Pancreatic Ductal Adenocarcinoma Lesions and Response to KRASG12D Inhibitor Treatment
Authors: Jordan Veronica Clavijo , Sojoodi Mozhdeh , Moloudi Farzad , Gonzalez-Pagan Patricia , Jin Manyu , Pantazopoulos Pamela , French Ethan , Whittier Jonah Weigand , Rotile Nicholas , Tavallai Mehrad , Hallin Jill , Ramsay Ian , Gale Eric M , Barrett Stephen C. , El-Bardeesy Nabeel , Qadan Motaz , Tanabe Kenneth K. , Caravan Peter 
Published: September 2024

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, primarily due to late-stage diagnosis and limited treatment options. Zinc homeostasis is markedly dysregulated in PDAC and this dysregulation can be probed by administering a secretagogue to stimulate zinc secretion (SSZS) in the exocrine pancreas and imaging this secretion with a zinc sensitive MRI probe. This study demonstrates the potential of SSZS MRI for early detection, monitoring treatment response, and assessing recurrence after treatment withdrawal in PDAC. Our approach relies on interrogating the pancreas, circumventing the challenge of locating small, elusive tumors. By SSZS MRI, we detected PDAC by observing the unique zinc hypersecretory activity of the pancreas when malignancy is present. We observed dysregulation of zinc transporters in both human and mouse pancreas containing PDAC and confirmed secretagogue-stimulated zinc secretion in vitro and in vivo. We found that combining secretagogues such as secretin and caerulein maximized zinc secretion and as such MRI signal in the pancreas. Notably, SSZS MRI detected treatment responses to KRAS G12D inhibition within 3-5 days and identified cancer recurrence as early as one day post-treatment withdrawal. Additionally, secretagogue stimulation improved treatment responses and delayed recurrence in both treatment models. These findings suggest that SSZS MRI could significantly enhance PDAC diagnosis and management, providing a novel, non-invasive imaging modality to improve patient outcomes.STATEMENT OF SIGNIFICANCEThis study demonstrates the utility of secretagogue-stimulated zinc secretion (SSZS) MRI in detecting pancreatic ductal adenocarcinoma (PDAC) at early stages, monitoring treatment responses, and assessing cancer recurrence, thereby offering a promising non-invasive imaging modality to improve PDAC patient management and outcomes.
Multi-task benchmarking of single-cell multimodal omics integration methods
Authors: Liu Chunlei , Ding Sichang , Kim Hani Jieun , Long Siqu , Xiao Di , Ghazanfar Shila , Yang Pengyi 
Published: September 2024

AbstractSingle-cell multimodal omics technologies have empowered the profiling of complex biological systems at a resolution and scale that were previously unattainable. These biotechnologies have propelled the fast-paced innovation and development of data integration methods, leading to a critical need for their systematic categorisation, evaluation, and benchmark. Navigating and selecting the most pertinent integration approach poses a significant challenge, contingent upon the tasks relevant to the study goals and the combination of modalities and batches present in the data at hand. Understanding how well each method performs multiple tasks, including dimension reduction, batch correction, cell type classification and clustering, imputation, feature selection, and spatial registration, and at which combinations will help guide this decision. This study aims to develop a much-needed guideline on choosing the most appropriate method for single-cell multimodal omics data analysis through a systematic categorisation and comprehensive benchmarking of current methods.
PGR5 promotes energy-dependent non-photochemical quenching to enable efficient C4photosynthesis under fluctuating light
Authors: Woodford Russell , Watkins Jacinta , Moore Marten , Nix Samuel J. , Yee Suyan , Chan Kai Xun , Pogson Barry , von Caemmerer Susanne , Furbank Robert T. , Ermakova Maria 
Published: September 2024

AbstractPROTON GRADIENT REGULATION 5 (PGR5) is essential for generating proton motive force across thylakoid membranes in C3plants and supporting photoprotection under fluctuating light conditions. It is proposed that this function is achieved by regulating cyclic electron flow around Photosystem I. During the evolutionary transition from C3to C4photosynthesis, the leaf abundance of PGR5 has increased, coinciding with a rise in the cyclic electron flow rate. To investigate the contribution of PGR5 to photoprotection in C4photosynthesis, we generated model C4monocotSetaria viridiswith nullpgr5alleles. We show that plants lacking PGR5 struggle to establish proton motive force and energy-dependent non-photochemical quenching (qE) at higher irradiances during instantaneous measurements. This leads to a progressive decline in maximum Photosystem I activity when leaves are exposed to repeated cycles of high irradiance. Additionally, plants without PGR5 exhibit severely reduced growth and photosynthesis compared to wild type plants when grown under fluctuating daylight but not under constant daylight. In the absence of PGR5, a slower-relaxing, zeaxanthin-dependent form of non-photochemical quenching supports growth under fluctuating light, albeit at the cost of reduced photochemical efficiency and assimilation rate. Our findings underscore the role of PGR5 in enabling efficient C4photosynthesis under fluctuating light by establishing proton motive force for the rapid upregulation of qE and preventing photodamage to the electron transport machinery. This study highlights the importance of various non-photochemical quenching mechanisms for C4photosynthesis and emphasises the role of PGR5 in the evolution of C4plants.
Integration of Group A Streptococcus Rapid Tests with the Open Fluidic CandyCollect Device
Authors: Sanchez J. Carlos , Robertson Ingrid H. , Shinkawa Victoria A. M. , Su Xiaojing , Tu Wan-chen , Robinson Timothy R. , Chang Megan M. , Blom Andrea , Alfaro Elena , Hatchett Daniel B. , Olanrewaju Ayokunle O. , Wald Ellen R. , DeMuri Gregory P. , Berthier Erwin , Thongpang Sanitta , Theberge Ashleigh B. 
Published: September 2024

AbstractThe CandyCollect device is a lollipop-inspired open fluidic oral sampling device designed to provide a comfortable user sampling experience. We demonstrate that the CandyCollect device can be coupled with a rapid antigen detection test (RADT) kit designed for Group A Streptococcus (GAS). Throughin vitroexperiments with pooled saliva spiked withStreptococcus pyogeneswe tested various reagents and elution volumes to optimize the RADT readout from CandyCollect device samples. The resulting optimized protocol uses the kit-provided reagents and lateral flow assay (LFA) while replacing the kit’s pharyngeal swab with the CandyCollect device, reducing the elution solution volume, and substituting the tube used for elution to accommodate the CandyCollect device. Positive test results were detected by eye with bacterial concentrations as low as the manufacturer’s “minimal detection limit” - 1.5×105CFU/mL. LFA strips were also scanned and quantified with image analysis software to determine the signal-to-baseline ratio (SBR) and categorize positive test results without human bias. We tested our optimized protocol for integrating CandyCollect and RADT using CandyCollect clinical samples from pediatric patients (n=6) who were previously diagnosed with GAS pharyngitis via pharyngeal swabs tested with RADT as part of their clinical care. The LFA results of these CandyCollect devices and interspersed negative controls were determined by independent observers, with positive results obtained in four of the six participants on at least one LFA replicate. Taken together, our results show that CandyCollect devices from children with GAS pharyngitis can be tested using LFA rapid tests.Table of Contents/Abstract Figure
Serum, Cell-Free, HPV-Human DNA Junction Detection and HPV Typing for Predicting and Monitoring Cervical Cancer Recurrence
Authors: Van Arsdale Anne , Mescheryakova Olga , Gallego Sonia , Maggi Elaine C. , Harmon Bryan , Kuo Dennis Y.S. , Van Doorslaer Koenraad , Einstein Mark H. , Haas Brian J. , Montagna Cristina , Lenz Jack 
Published: September 2024

AbstractAlmost all cervical cancers are caused by human papillomaviruses (HPVs). In most cases, HPV DNA is integrated into the human genome. We found that tumor-specific, HPV-human DNA junctions are detectable in serum cell-free DNA of a fraction of cervical cancer patients at the time of initial treatment and/or at six months following treatment. Retrospective analysis revealed these junctions were more frequently detectable in women in whom the cancer later recurred. We also found that cervical cancers caused by HPV types outside of phylogenetic clade α9 had a higher recurrence frequency than those caused by α9 types in both our study and The Cancer Genome Atlas cervical cancer database, despite the higher prevalence of α9 types including HPV16 in cervical cancer. Thus, HPV-human DNA junction detection in serum cell-free DNA and HPV type determination in tumor tissue may help predict recurrence risk. Screening serum cell-free DNA for junctions may also offer an unambiguous, non-invasive means to monitor absence of recurrence following treatment.
Performance of Deep Learning Models in Predicting the Nugent Score to Diagnose Bacterial Vaginosis
Authors: Watanabe Naoki , Watari Tomohisa , Akamatsu Kenji , Miyatsuka Isao , Otsuka Yoshihito 
Published: September 2024

ABSTRACTThe Nugent score is a commonly used tool for diagnosing bacterial vaginosis; however, its accuracy depends on the skills of laboratory technicians. We aimed to evaluate the performance of deep learning models in predicting the Nugent score, with the goal of improving diagnostic consistency and accuracy. A total of 1,510 vaginal images collected from a hospital in Japan between 2021 and 2023 were assessed. Each image was annotated by laboratory technicians into one of four categories based on the Nugent score—normal vaginal flora, absence of vaginal flora, altered vaginal flora, or bacterial vaginosis. Deep learning models were developed to predict these categories, and their performance was evaluated by comparing the predicted scores with technician annotations. A high magnification model was further optimized and evaluated using an independent test set of 106 images to assess its performance relative to that of the technicians. The deep learning models demonstrated an accuracy of 84% at low magnification and 89% at high magnification in predicting the Nugent score categories. After optimization, the high magnification model achieved 94% accuracy, surpassing the average 92% accuracy of the technicians. The agreement between deep learning model predictions and technician annotations was 92% for normal vaginal flora, 100% for absence of vaginal flora, 91% for altered vaginal flora, and 100% for bacterial vaginosis. The deep learning models demonstrated accuracy comparable to that of laboratory technicians, which indicates their potential utility in improving the diagnostic accuracy of bacterial vaginosis.IMPORTANCEBacterial vaginosis is a global health issue affecting women, causing symptoms such as abnormal vaginal discharge and discomfort. The Nugent score is the standard method for diagnosing bacterial vaginosis and is based on manual interpretation of Gram-stained vaginal smears. However, this method relies on the skill and experience of trained professionals, leading to variability in results and challenges in facilities with limited access to such experts. This poses significant challenges for settings with limited access to experienced technicians. The deep learning models developed in this study predict the Nugent score with high accuracy; thus, they can be used to standardize the diagnosis of bacterial vaginosis, reduce observer variability, and enable reliable diagnosis even in settings without experienced personnel. Although larger scale validation is needed, our results suggest that deep learning models may represent a new approach for the diagnosis of bacterial vaginosis.
Randomized dose-response trial of n-3 fatty acids in hormone receptor negative breast cancer survivors—impact on breast adipose oxylipin and DNA methylation patterns
Authors: Frankhouser David E. , DeWess Todd , Snodgrass Isabel F. , Cole Rachel M. , Steck Sarah , Thomas Danielle , Kalu Chidimma , Belury Martha A. , Clinton Steven K. , Newman John W. , Yee Lisa D. 
Published: September 2024

AbstractBackgroundIncreasing evidence suggests the unique susceptibility of estrogen receptor and progesterone receptor negative (ERPR-) breast cancer to dietary fat amount and type. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may modulate breast adipose fatty acid profiles and downstream bioactive metabolites to counteract pro-inflammatory, pro-carcinogenic signaling in the mammary microenvironment.ObjectiveTo determine effects of ∼1 to 5 g/d EPA+DHA over 12 months on breast adipose fatty acid and oxylipin profiles in women with ERPR(−) breast cancer, a high-risk molecular subtype.MethodsWe conducted a 12-month randomized controlled, double-blind clinical trial of ∼5g/d vs ∼1g/d DHA+EPA supplementation in women within 5 years of completing standard therapy for ERPR(−) breast cancer Stages 0-III. Blood and breast adipose tissue specimens were collected every 3 months for biomarker analyses including fatty acids by gas chromatography, oxylipins by LC-MS/MS, and DNA methylation by reduced-representation bisulfite sequencing (RRBS).ResultsA total of 51 participants completed the 12-month intervention. Study treatments were generally well-tolerated. While both doses increased n-3 PUFAs from baseline in breast adipose, erythrocytes, and plasma, the 5g/d supplement was more potent (n =51, p <0.001). The 5g/d dose also reduced plasma triglycerides from baseline (p =0.008). Breast adipose oxylipins at 0, 6, and 12 months showed dose-dependent increases in unesterified and esterified DHA and EPA metabolites (n =28). Distinct DNA methylation patterns in adipose tissue after 12 months were identified, with effects unique to the 5g/d dose group (n =17).ConclusionsOver the course of 1 year, EPA+DHA dose-dependently increased concentrations of these fatty acids and their derivative oxylipin metabolites, producing differential DNA methylation profiles of gene promoters involved in metabolism-related pathways critical to ERPR(−) breast cancer development and progression. These data provide evidence of both metabolic and epigenetic effects of n-3 PUFAs in breast adipose tissue, elucidating novel mechanisms of action for high-dose EPA+DHA-mediated prevention of ERPR(−) breast cancer.Clinicaltrials.gov identifierNCT02295059
Prevalence and real-world effectiveness of popular smoking cessation aids in England: a population-based study
Authors: Jackson Sarah E. , Brown Jamie , Buss Vera , Shahab Lion 
Published: September 2024

AbstractImportanceA wide range of medications, non-combustible nicotine products, behavioural support, and alternative treatments are available in England to help people stop smoking. Understanding their effectiveness in the real world can support informed decision-making.ObjectivesTo provide up-to-date estimates of the prevalence and real-world effectiveness of different smoking cessation aids and explore moderation of effectiveness by socioeconomic position.DesignPopulation-based survey, 2006-2024.SettingEngland.Participants25,094 adults (≥16y) who reported having tried to quit smoking in the past year.Main outcomes and measuresThe outcome variable was self-reported continuous abstinence from the start of the most recent quit attempt up to the time of survey. Independent variables were use (yes/no) of the following aids in the most recent attempt: nicotine replacement therapy (NRT) obtained on prescription or over-the-counter; varenicline; bupropion; e-cigarettes; face-to-face behavioural support; telephone support; written self-help materials; websites; smartphone apps; hypnotherapy; Allen Carr’s Easyway method; heated tobacco products (HTPs); nicotine pouches. Covariates included sociodemographic characteristics and features of the quit attempt.ResultsWe analysed data from 25,094 participants (mean [SD] age = 38.7y [15.3]; 48.5% women). In 2023/24, the most used aids were e-cigarettes (40.2%) and over-the-counter NRT (17.3%); 40.8% of quit attempts were unaided. While e-cigarette use was associated with higher odds of abstinence after adjustment for use of other aids and covariates (OR=1.95 [1.74-2.17]), use of over-the-counter NRT was not (OR=1.03 [0.93-1.15]). Other aids positively associated with abstinence were websites (used by 4.6% in 2023/24; OR=1.43 [1.03-1.98]), prescription NRT (4.5%; OR=1.33 [1.12-1.58]), varenicline (1.1%; OR=1.80 [1.50-2.18]), and HTPs (0.7%; OR=2.37 [1.24-4.51]). Face-to-face behavioural support (used by 2.2% in 2023/24) was also associated with higher odds of abstinence among those from less advantaged (OR=1.59 [1.19-2.14]) but not more advantaged social grades (OR=0.91 [0.65-1.29]). There was not clear evidence of a benefit of any other aid, although some analyses were inconclusive.Conclusions and relevanceA range of effective smoking cessation aids are available in England, but many people try to quit using less effective forms of support or none at all. Quit success rates could be improved by encouraging people to use more effective methods.
Allelic effects onKLHL17expression likely mediated by JunB/D underlie a PDAC GWAS signal at chr1p36.33
Authors: Connelly Katelyn E. , Hullin Katherine , Abdolalizadeh Ehssan , Zhong Jun , Eiser Daina , O’Brien Aidan , Collins Irene , Das Sudipto , Duncan Gerard ,   Pancreatic Cancer Cohort Consortium,   Pancreatic Cancer Case-Control Consortium, Chanock Stephen J. , Stolzenberg-Solomon Rachael Z. , Klein Alison P. , Wolpin Brian M. , Hoskins Jason W. , Andresson Thorkell , Smith Jill P. , Amundadottir Laufey T. 
Published: September 2024

AbstractPancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the U.S. Both rare and common germline variants contribute to PDAC risk. Here, we fine-map and functionally characterize a common PDAC risk signal at 1p36.33 (tagged by rs13303010) identified through a genome wide association study (GWAS). One of the fine-mapped SNPs, rs13303160 (r2=0.93 in 1000G EUR samples, OR=1.23,Pvalue=2.74×10−9) demonstrated allele-preferential gene regulatory activityin vitroand allele-preferential binding of JunB and JunDin vitroandin vivo. Expression Quantitative Trait Locus (eQTL) analysis identifiedKLHL17as a likely target gene underlying the signal. Proteomic analysis identified KLHL17 as a member of the Cullin-E3 ubiquitin ligase complex in PDAC-derived cells.In silicodifferential gene expression analysis of the GTExv8 pancreas data suggested an association between lower KLHL17 (risk associated) and pro-inflammatory pathways. We hypothesize that KLHL17 may mitigate inflammation by recruiting pro-inflammatory proteins for ubiquitination and degradation thereby influencing PDAC risk.
Statin uses and skeletal muscle-related phenotypes: insights from epidemiological and Mendelian randomization analyses
Authors: Tang Fan , Chen Zhanchao , Qiu Hongbing , Liu Yige , Shen Yanjiao , Zhang Yiying , Wang Shanjie , Yu Bo 
Published: September 2024

AbstractBackgroundThe association between statin use and skeletal muscle-related side effects is always controversial. This study aimed to comprehensively investigate the associations between statin use and muscle-related phenotypes including sarcopenia, sarcopenic obesity, serum lactate dehydrogenase (LDH), and musculoskeletal pain symptoms among adults with indications for statin use for secondary prevention (cardiovascular disease, diabetes, or hyperlipidemia).MethodsThis cross-sectional study included 22,549 patients aged ≥20 years with cardiovascular disease, diabetes, or hyperlipidemia. Weighted generalized linear regression analysis and propensity score matching methods were used to estimate the associations between the use of statins or other lipid-lowering agents and skeletal muscle-related phenotypes. Mendelian randomization (MR) analysis was additionally used to verify the causal relationship between statin use and skeletal muscle-related phenotypes.ResultsThe weighted mean age was 59 years, 50.3% were male, and 37.6% (n=8,481) received statin treatment. In the unadjusted model, compared with adults without any lipid-lowering drugs, statin use was associated with a higher likelihood of sarcopenia (appendicular skeletal muscle mass [ASM]/Body mass index [BMI] OR 1.35 (95%CI 1.12 to 1.62, p < 0.001), ASM/weight [Wt] OR 1.86 (95%CI 1.62 to 2.13, p < 0.001), max HGS β -3.01 (95% CI -3.97 to -2.06, p < 0.001), relative HGS β -0.23 (95% CI -0.30 to -0.17, p < 0.001) and combined HGS β -5.90 (95% CI -7.86 to -3.93, p < 0.001)), sarcopenic obesity (ASM/height squared [Ht2] and body fat percentage definition [OR 1.36 (95% CI 1.13 to 1.63, p < 0.001]). After multivariable adjustment or propensity score match, the independent associations of statin use with sarcopenia, sarcopenic obesity, HGS, LDH, and musculoskeletal pain became nonsignificant. Stepwise regression suggested that age was the predominant confounding factor for the associations. MR analysis also revealed no significant causality between statin use and skeletal muscle-related phenotypes.ConclusionsOur epidemiological and MR analyses did not support the causality between statin use and skeletal muscle-related phenotypes. A higher likelihood of skeletal muscle-related adverse phenotypes in statin users may be attributed to age. Future studies should further explore the biological factors that may affect statin-related muscle phenotypes to provide evidence for the safety of statins.
Effects of a Cardiac and Psychosocial Rehabilitation Program on Anxiety, Depression, Self-Efficacy, Quality of Life, and Exercise Capacity in Young Adults With Fontan Circulation: A Randomized Controlled Trial
Authors: Moon Ju Ryoung , Huh June , Song Jinyoung , Kang I-Seok , Park Goeun , Kim Kyunga , Sung Jidong , Chang Sung-A , Park Seung Woo , Yang Ji-Hyuk , Jun Tae-Gook 
Published: September 2024

ABSTRACTBACKGROUNDYoung adults with Fontan circulation (FC) face psychosocial, physical, and environmental challenges and are vulnerable to emotional distress. They need holistic intervention programs to face these problems and enhance their quality of life. This study developed and evaluated a cardiac and psychosocial rehabilitation (CPR) program for young adults with FC.METHODS AND RESULTSThirty-eight young adults with FC aged 18–23 years were prospectively recruited from an outpatient clinic and randomized into a CPR group (n = 12) that underwent eight weekly group-based sessions combining a psychosocial program based on cognitive behavioral therapy with home-based cardiac rehabilitation (CR), a CR group (n = 12) that received only home-based CR, and a usual care control group (n = 12). The study assessed CPR program effectiveness based on the Hospital Anxiety and Depression Scale, self-efficacy, quality of life, and exercise capacity testing at three time points: pre-intervention, post-intervention, and four weeks post-intervention. Participants’ average ages were 19.75 (2.28), 19.65 (1.79), and 20.38 (1.85) years in the CPR, CR, and control groups, respectively; 50% (CPR group) to 53.8% (CR and control groups) of the participants were male. After eight weeks, depression and anxiety decreased, whereas self-efficacy and quality of life increased in the CPR group compared with the CR and control groups. The groups showed no differences in exercise capacity.CONCLUSIONCPR can be part of an intervention for alleviating psychological distress and improving self-efficacy in young adults with FC. Efforts should be made to increase the efficacy of home-based CR.