bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C072: Andrographolide exhibits anti-cancer activity via restoring DNMT3B-suppressed ZNF382 expression in pancreatic cancer
Authors: Zhuang Kai-Ru , Chan Hsin-Yu , Chen Chian-Feng , Fu Shu-Ling 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy. Due to the lack of early diagnosis and the limited response to current clinical treatments, PDAC has a high recurrence rate and a poor 5-year survival rate. Andrographolide, a labdane diterpenoid compound and the main active ingredient found in the medicinal plant Andrographis paniculata, is known for its anti-cancer effects against a variety of cancer types. Nevertheless, there are few studies on the anti-cancer activity and underlying mechanism of andrographolide against PDAC. We recently found that andrographolide suppressed cell viability, proliferation and migration abilities of PDAC cells, as well as impaired tumor growth in vivo. Notably, andrographolide induced the mRNA and protein expression of Zinc finger protein 382 (ZNF382) in PDAC cells. ZNF382 functions as a transcription repressor but its biological function in pancreatic cancer remains unclear. Through analysis of pancreatic adenocarcinoma (PAAD) patient data from TCGA, the expression of ZNF382 is lower in tumor samples than in normal tissues, and patients with higher ZNF382 expression showed better overall survival rates. Recently, we confirmed that ZNF382 expression was significantly decreased in clinical tumor tissues compared with matched normal tissues in 9 out of 10 pancreatic cancer patients. In addition, we demonstrated that overexpression of ZNF382 inhibited malignant phenotypes of PDAC cells and suppressed tumor growth in mice. Based on TCGA database analysis, the ZNF382 promoter is hypermethylated in primary pancreatic tumors, and this hypermethylation pattern correlates with its low expression. We further showed that andrographolide treatment inhibited the expression of DNA methyltransferase 3 beta (DNMT3B) and promoted the demethylation of ZNF382 promoter in PDAC cells. Notably, overexpression of DNMT3B attenuated both the andrographolide-induced expression of ZNF382 and its associated anti-cancer effects. In summary, our findings indicate that ZNF382 serves as a tumor suppressor in pancreatic cancer and suggest that andrographolide exerts its anticancer effects in pancreatic cancer through the suppression of DNMT3B-dependent DNA methylation, leading to the reactivation of ZNF382 expression.
Citation Format: Kai-Ru Zhuang, Hsin-Yu Chan, Chian-Feng Chen, Shu-Ling Fu. Andrographolide exhibits anti-cancer activity via restoring DNMT3B-suppressed ZNF382 expression in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C072.
Abstract C113: The mitochondrial calcium uniporter supports epithelial to mesenchymal transition of pancreatic ductal adenocarcinoma
Authors: Weissenrieder Jillian S. , Pitarresi Jason , Weinmann Natalie , Drager Rebecca , Paudel Usha , Rustgi Anil , Stanger Ben , Foskett J. Kevin 
Published: January 2024

Abstract
In spite of many new developments in cancer treatments and targeted therapies over the past few decades, outcomes for pancreatic ductal adenocarcinoma (PDAC) patients continue to be poor. Calcium signaling and mitochondrial function are known to contribute to cancer outcomes in many paradigms, yet much remains unknown in the context of PDAC. The mitochondrial Ca2+ uniporter, MCU, is the main route by which mitochondria can take up Ca2+ into the mitochondrial matrix, where it drives metabolic activity in the tricarboxylic acid cycle and promotes ATP synthesis by the electron transport chain. Our previous work suggests that Ca2+ flux from the endoplasmic reticulum (ER) into the mitochondria at mitochondria-associated membranes (MAMs) may be important to drive malignancy. Here, we show that MCU expression is associated with poor outcomes in PDAC patients and disease progression in murine organoid models of cancer development. Further, deletion of Mcu in murine KPC cells results in ablation of mitochondrial Ca2+ uptake, which reduces growth, proliferation, and clonogenicity. Tumor growth and metastatic colonization are also reduced in orthotopic implantation models, with some KPCY-McucKO models failing to develop primary lesions. This suggests that MCU, and thus mitochondrial Ca2+, play an important role in tumor growth. Critically, we here elucidate a heretofore unknown relationship between ER-to-mitochondrial Ca2+ flux through Mcu and epithelial to mesenchymal transition (EMT), an important process that contributes to poor outcomes in PDAC. To this end, McucKO associates with reduced basal Snail expression and reduced TGFβ secretion, and McucKO clones have a more epithelial morphology than their isogenic, Mcu-expressing counterparts. Both stable expression of Snail and treatment with TGFβ are able to rescue growth, mobility, and clonogenic deficits in McucKO cell lines to levels comparable to isogenic, Mcu-expressing cell lines. Uptake assays, metabolomics, isotope tracing, and mRNA-Seq have enabled us to elucidate metabolic and transcriptional rewiring induced by Snail and TGFβ treatment which may promote cell survival and proliferation despite the lack of Mcu. This work has important implications for potential targeting of Ca2+ signaling in the context of PDAC.
Citation Format: Jillian S. Weissenrieder, Jason Pitarresi, Natalie Weinmann, Rebecca Drager, Usha Paudel, Anil Rustgi, Ben Stanger, J. Kevin Foskett. The mitochondrial calcium uniporter supports epithelial to mesenchymal transition of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C113.
Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts
Authors: Pattalachinti Vinay K. , Ito Ichiaki , Chowdhury Saikat , Yousef Abdelrahman , Gu Yue , Gunes Betul Beyza , Salle Emma R. , Taggart Melissa W. , Fournier Keith , Fowlkes Natalie W. , Shen John Paul 
Published: January 2024

Abstract

Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implanted in the flank. Comparing the tumor-specific transcriptome (excluding stromal transcription), the peritoneal microenvironment relatively upregulated genes related to proliferation, including MKI67 and EXO1. Peritoneal tumors were also enriched for proliferative gene sets, including E2F and Myc Targets. Proteomic studies found a 2.5-fold increased ratio of active-to-inactive phosphoforms of the YAP oncoprotein in peritoneal tumors, indicating downregulation of Hippo signaling.

Implications:
The peritoneal microenvironment promotes growth of appendiceal tumors and expression of proliferative pathways in PDXs.
Optimal Minimal Stent Area and Impact of Stent Underexpansion in Left Main Up-Front 2-Stent Strategy
Authors: Kim Ju Hyeon , Kang Do-Yoon , Ahn Jung-Min , Kweon Jihoon , Choi Yeonwoo , Kim Hoyun , Lee Jinho , Chae Jihye , Kang Soo-Jin , Park Duk-Woo , Park Seung-Jung 
Published: January 2024

BACKGROUND:
We previously reported the use of minimal stent area to predict angiographic in-stent restenosis after drug-eluting stent implantation for unprotected left main (LM) disease. We aimed to evaluate the optimal minimal stent area criteria for up-front LM 2-stenting based on long-term clinical outcomes.

METHODS:
We identified 292 consecutive patients with LM bifurcation stenosis who were treated using the crush technique. The final minimal stent area was measured in the ostial left anterior descending artery (LAD), ostial left circumflex artery (LCX), and distal LM. The primary outcome was 5-year major adverse cardiac events, including all-cause death, myocardial infarction, and target lesion revascularization.

RESULTS:

The minimal stent area cutoff values that best predicted the 5-year major adverse cardiac events were 11.8 mm
2
for distal LM (area under the curve, 0.57;
P
=0.15), 8.3 mm
2
for LAD ostium (area under the curve, 0.62;
P
=0.02), and 5.7 mm
2
for LCX ostium (area under the curve, 0.64;
P
=0.01). Using these criteria, the risk of 5-year major adverse cardiac events was significantly associated with stent underexpansion in the LAD ostium (hazard ratio, 3.14; [95% CI, 1.23–8.06];
P
=0.02) and LCX ostium (hazard ratio, 2.60 [95% CI, 1.11–6.07];
P
=0.03) but not in the distal LM (hazard ratio, 0.81 [95% CI, 0.34–1.91];
P
=0.63). Patients with stent underexpansion in both ostial LAD and LCX had a significantly higher rate of 5-year major adverse cardiac events than those with no or 1 underexpanded stent of either ostium (
P
<0.01).

CONCLUSIONS:
Stent underexpansion in the LAD and LCX ostium was significantly associated with long-term outcomes in patients who underwent up-front 2-stenting for LM bifurcation stenosis.
Deployment of Point‐of‐Care Echocardiography to Improve Cardiac Diagnostic Access Among American Indians
Authors: de Loizaga Sarah , Benashley LeCario , Hoekzema Jacob , Ahmed Nahreen , Alexander Craig , Bolger Ann , Evers Patrick D. , Hill Garick D. , Nakagaayi Doreen , Nashio J. T. , Nunes Maria Carmo Pereira , Sable Craig , Tacuri Luz Marina , Danforth Kristen , Beaton Andrea , Close Ryan 
Published: January 2024

Background
American Indians face significant barriers to diagnosis and management of cardiovascular disease. We sought to develop a real‐world implementation model for improving access to echocardiography within the Indian Health Service, the American Indian Structural Heart Disease Partnership.

Methods and Results
The American Indian Structural Heart Disease Partnership was implemented and evaluated via a 4‐step process of characterizing the system where it would be instituted, building point‐of‐care echocardiography capacity, deploying active case finding for structural heart disease, and evaluating the approach from the perspective of the clinician and patient. Data were collected and analyzed using a parallel convergent mixed methods approach. Twelve health care providers successfully completed training in point‐of‐care echocardiography. While there was perceived usefulness of echocardiography, providers found it difficult to integrate screening point‐of‐care echocardiography into their workday given competing demands. By the end of 12 months, 6 providers continued to actively utilize point‐of‐care echocardiography. Patients who participated in the study felt it was an acceptable and effective approach. They also identified access to transportation as a notable challenge to accessing echocardiograms. Over the 12‐month period, a total of 639 patients were screened, of which 36 (5.6%) had a new clinically significant abnormal finding.

Conclusions
The American Indian Structural Heart Disease Partnership model exhibited several promising strategies to improve access to screening echocardiography for American Indian populations. However, competing priorities for Indian Health Service providers' time limited the amount of integration of screening echocardiography into outpatient practice. Future endeavors should explore community‐based solutions to develop a more sustainable model with greater impact on case detection, disease management, and improved outcomes.
Using Artificial Intelligence for Rheumatic Heart Disease Detection by Echocardiography: Focus on Mitral Regurgitation
Authors: Brown Kelsey , Roshanitabrizi Pooneh , Rwebembera Joselyn , Okello Emmy , Beaton Andrea , Linguraru Marius George , Sable Craig A. 
Published: January 2024

Background
Identification of children with latent rheumatic heart disease (RHD) by echocardiography, before onset of symptoms, provides an opportunity to initiate secondary prophylaxis and prevent disease progression. There have been limited artificial intelligence studies published assessing the potential of machine learning to detect and analyze mitral regurgitation or to detect the presence of RHD on standard portable echocardiograms.

Methods and Results

We used 511 echocardiograms in children, focusing on color Doppler images of the mitral valve. Echocardiograms were independently reviewed by an expert adjudication panel. Among 511 cases, 229 were normal, and 282 had RHD. Our automated method included harmonization of echocardiograms to localize the left atrium during systole using convolutional neural networks and RHD detection using mitral regurgitation jet analysis and deep learning models with an attention mechanism. We identified the correct view with an average accuracy of 0.99 and the correct systolic frame with an average accuracy of 0.94 (apical) and 0.93 (parasternal long axis). It localized the left atrium with an average Dice coefficient of 0.88 (apical) and 0.9 (parasternal long axis). Maximum mitral regurgitation jet measurements were similar to expert manual measurements (
P
value=0.83) and a 9‐feature mitral regurgitation analysis showed an area under the receiver operating characteristics curve of 0.93, precision of 0.83, recall of 0.92, and F1 score of 0.87. Our deep learning model showed an area under the receiver operating characteristics curve of 0.84, precision of 0.78, recall of 0.98, and F1 score of 0.87.

Conclusions
Artificial intelligence has the potential to detect RHD as accurately as expert cardiologists and to improve with more data. These innovative approaches hold promise to scale echocardiography screening for RHD.
The effect of cerebellar TMS on error processing: A combined single-pulse TMS and ERP study
Authors: Berlijn Adam M. , Huvermann Dana M. , Groiss Stefan J. , Schnitzler Alfons , Mittelstaedt Manfred , Bellebaum Christian , Timmann Dagmar , Minnerop Martina , Peterburs Jutta 
Published: January 2024

AbstractThe present study investigated temporal aspects of cerebellar contributions to the processing of performance errors as indexed by the error-related negativity (ERN) in the response-locked event-related potential (ERP). We co-registered EEG and applied single-pulse transcranial magnetic stimulation (spTMS) to the left posterolateral cerebellum and an extra-cerebellar control region (vertex) while healthy adult volunteers performed a Go/Nogo Flanker Task. In Go trials, TMS pulses were applied at four different time points, with temporal shifts of -100 ms, -50 ms, 0 ms, or +50 ms relative to the individual error latency (IEL, i.e., individual ERN peak latency + median error response time). These stimulation timings were aggregated into early (-100 ms, -50 ms) and late (0 ms, +50 ms) stimulation for the analysis. In Nogo trials, TMS pulses occurred 0 ms, 100 ms, or 300 ms after stimulus onset. Mixed linear model analyses revealed that cerebellar stimulation did not affect error rates overall. No effects were found for response times. As hypothesized, ERN amplitudes were decreased for cerebellar stimulation. No significant differences were found for the error positivity (Pe). Similar to TMS application to probe cerebellar-brain inhibition in the motor domain, the inhibitory tone of the cerebellar cortex may have been disrupted by the pulses. Reduced inhibitory output of the cerebellar cortex may have facilitated the processing of error information for response selection, which is reflected in a decreased ERN.
The GLM-spectrum: A multilevel framework for spectrum analysis with covariate and confound modelling
Authors: Quinn Andrew J. , Atkinson Lauren Z. , Gohil Chetan , Kohl Oliver , Pitt Jemma , Zich Catharina , Nobre Anna C. , Woolrich Mark W. 
Published: January 2024

AbstractThe frequency spectrum is a central method for representing the dynamics within electrophysiological data. Some widely used spectrum estimators make use of averaging across time segments to reduce noise in the final spectrum. The core of this approach has not changed substantially since the 1960s, though many advances in the field of regression modelling and statistics have been made during this time. Here, we propose a new approach, the General Linear Model (GLM) Spectrum, which reframes time averaged spectral estimation as multiple regression. This brings several benefits, including the ability to do confound modelling, hierarchical modelling, and significance testing via non-parametric statistics. We apply the approach to a dataset of EEG recordings of participants who alternate between eyes-open and eyes-closed resting state. The GLM-Spectrum can model both conditions, quantify their differences, and perform denoising through confound regression in a single step. This application is scaled up from a single channel to a whole head recording and, finally, applied to quantify age differences across a large group-level dataset. We show that the GLM-Spectrum lends itself to rigorous modelling of within- and between-subject contrasts as well as their interactions, and that the use of model-projected spectra provides an intuitive visualisation. The GLM-Spectrum is a flexible framework for robust multilevel analysis of power spectra, with adaptive covariate and confound modelling.
Nutritive value of cereal grains, protein meals and by-products for yellow mealworms
Authors: Pascual J.J. , Fasce B. , Martı́nez-de-Pablo A. , Andrade C. , López M.C. , Cambra-López M. 
Published: January 2024

Abstract
Nutritive value of raw materials is needed to formulate diets that fulfil the requirements of the yellow mealworms. The objective of this study was to determine the nutritional value of six raw materials commonly used in yellow mealworm feeding (barley grain, corn grain, hominy feed, wheat bran, corn gluten feed and soybean meal) and to propose prediction equations for the nutritive value of raw materials from their chemical composition. From Monday to Friday 5 g of raw material and 20 g of gel (source of water and micronutrients) were daily supplied. After two days of fasting, frass was collected. This procedure was repeated for 6 weeks. During this period, the initial and final weight of the larvae, the consumption of the raw material offered, and the production of faeces were controlled. Raw materials and faeces were analysed for dry matter (DM), ashes, crude protein (CP), ether extract, acid detergent fibre (ADF) and gross energy (GE), from which their coefficients of digestibility were determined. The digestible energy (DE) content of the raw materials was 13.8, 14.2, 11.6, 8.7, 6.9, 11.3 MJ DE/kg DM and the digestible protein (DP) was 61, 52, 48, 74, 70 and 242 g DP/kg DM for the barley grain, corn grain, hominy feed, wheat bran, corn gluten feed and soybean meal, respectively. DE content of raw materials was closely correlated with their content on ashes, starch and ADF (−0.83, +0.69 and −0.65, respectively; ), while DP content was mainly correlated with their content on CP, starch and ether extract (+0.95, +0.60 and −0.69, respectively; ). It can be concluded that mealworms have a good ability to utilize cereal starch, wheat bran diets should be complemented with digestible carbohydrates and protein sources, and soybean meal may be a good source of vegetable protein for mealworms.
Divine Style
Authors: Dobbs-Allsopp F. W. 
Published: January 2024

In exploring the seminal works of Walt Whitman, the great American poet, many commentators have acknowledged the underlying influence of The King James Bible. However, a study has yet to elucidate the precise manner in which the Bible has shaped Whitman’s poetic style.
This is the deficit that F. W. Dobbs-Allsopp seeks to address in his new piece of literary scholarship: 'Divine Style: Walt Whitman and the King James Bible'. Dobbs-Allsopp, Professor of Old Testament at Princeton Theological Seminary, explicitly approaches Whitman from the perspective of a biblical scholar.
Utilising his wealth of expertise in this field, he constructs a compelling, erudite and methodical argument for the King James Bible’s importance in the evolution of Whitman’s style – from his signature long lines to the prevalence of parallelism and tendency towards parataxis in his works.
'Divine Style' focuses on Whitman’s output in the years preceding the release of his 1855 opus 'Leaves of Grass' through the general period of the book’s first three editions. In this, Dobbs-Allsopp’s exploration of the period is exhaustive – covering not just Leaves of Grass but recently recovered notebooks, newly digitised manuscripts and additions to the corpus, such as the novel 'Life and Adventures of Jack Engle'.
This is a work of careful, detailed scholarship, offering an authoritative commentary that will be a valuable resource for students of Whitman, biblical scholars and scholars of literature more generally.
Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis
Authors: Yoshida Michihiko , Yanagimoto Hiroaki , Tsugawa Daisuke , Akita Masayuki , Urade Takeshi , Nanno Yoshihide , Fukushima Kenji , Gon Hidetoshi , Komatsu Shohei , Asari Sadaki , Kido Masahiro , Toyama Hirochika , Ajiki Tetsuo , Fukumoto Takumi 
Published: January 2024

Introduction Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. Methods We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. Results After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. Discussion S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.