bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA011: Understanding field carcinogenesis in obesity-related endometrial cancer
Authors: Chandler Ronald 
Published: March 2024

Abstract
Over the last decade, endometrial cancer (EC) incidence has increased at an average rate of 0.8% each year. Although cancer death rates decreased during this time, EC showed the greatest increase in cancer death among women. Public awareness of EC remains low, and EC research remains underfunded relative to its societal burden. While most women with EC are post-menopausal, up to 30% of cases occur in pre-menopausal women under 50 years of age, with obesity being a major risk factor. More than half of all EC is associated with obesity. Obesity is also a leading risk factor for benign endometrial hyperplasia, which is considered the precursor lesion to EC. Like other cancers, the causes of EC are multifactorial, with obesity and somatic mutations playing causal roles. By 2030, half of all adult women in the U.S. are expected to be classified as obese. Therefore, EC incidence is expected to increase. If detected early, EC can be cured with surgical hysterectomy, but this solution is not ideal for all women. Intentional weight loss can lower endometrial cancer risk in obese women, but certain barriers prevent obese, at-risk women from losing weight or maintaining healthy lifestyles while living in obesogenic environments. There is a critical need to understand the biological mechanisms underlying EC pathogenesis in at-risk obese women. Although EC is thought to arise from a hyperplastic endometrial epithelium, our previous findings suggest that high-fat diet induced obesity affects other cell types within the endometrial microenvironment, including endometrial stroma and immune cells, in the absence of histopathological change. Common EC somatic mutations can also arise in the absence of histopathological change or occur in cases of benign disease. Our overarching hypothesis is that a normal appearing endometrium may accrue cell-context dependent alterations in response to obesity and somatic mutations across a pre-malignant tissue field that are predictive of malignant transformation. This presentation will highlight our recent work on the combined molecular and phenotypic effects of obesity and common EC driver mutations on the endometrial tissue field. The identification of high-value molecular targets across the endometrial pre-malignant field may inform new early detection and prevention strategies for EC.
Citation Format: Ronald Chandler. Understanding field carcinogenesis in obesity-related endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA011.
Abstract IA013: Unique metabolic changes in Lynch syndrome-associated endometrial cancer
Authors: Yates Melinda S. 
Published: March 2024

Abstract
Lynch syndrome-associated endometrial cancers (ECs) are defined by germline mutations in DNA mismatch repair genes, including MSH2, MSH6, PMS2, and MLH1. Lynch syndrome (LS) tumors have received increased attention in the therapeutic context as these tumors are microsatellite instable and often reflect increased immune cell infiltration and enhanced response to immunotherapy. However, relatively little attention has been paid to pathogenesis of LS ECs. Women with LS represent an at-risk population who could benefit from cancer interception strategies due to a 60% cumulative lifetime risk of developing EC. We developed a mouse model of MSH2 loss targeted to the uterus to evaluate EC pathogenesis, with the goal of elucidating mechanisms that alter disease penetrance for women with hereditary risk for EC development. Our Progesterone Receptor-Cre Msh2f lox/flox mice (abbreviated Msh2KO) develop ECs that closely mimic human EC. Whole transcriptome profiling of Msh2KO EC and Msh2KO normal endometrium compared to wild-type endometrium identified “Mitochondrial dysfunction” as a significantly altered pathway in Msh2 deficiency, prompting our in-depth evaluation of mitochondrial alterations in Msh2KO mice, MSH2-deficient cell lines, and LS-associated EC patient specimens. We will discuss the impact of MSH2 deficiency across multiple measures of mitochondrial content, integrity, function, and metabolomic analyses in ECs using preclinical models and human tissue studies. Overall, our studies reveal that MSH2-deficient EC is characterized by mitochondrial DNA damage, mitochondrial content reduction, and decreased mitochondrial function. In addition, decreased mitochondrial respiration for energy production facilitates metabolic reprogramming toward glycolysis. We are conducting further studies to define mechanisms underlying mitochondrial defects due to MSH2 loss and opportunities for intervention. Mitochondrial and metabolic aberrations could serve as novel biomarkers for EC development and targets for cancer prevention in women with LS.
Citation Format: Melinda S. Yates. Unique metabolic changes in Lynch syndrome-associated endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA013.
Abstract IA016: Molecular diversity of uterine serous carcinoma
Authors: Santin Alessandro D. 
Published: March 2024

Abstract
Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer with a high recurrence rate and poor prognosis disproportionately affecting black women. Whole-exome-sequencing analysis revealed that up to 10% of USC harbor features of ultra/hypermutation due to a deficiency of polymerase e (POLE) and/or mismatched-repair genes (MMRd). These tumors are notable for having a high number of single nucleotide variants (SNV), no LOH segments or copy-number variants (CNV) and a peculiar genetic signature characterized by an increased rate of C &gt; A transversions. In contrast, the overwhelming majority of USC (~ 90%) are POLE/MMR proficient, have a low number of SNV and demonstrate alteration in genes including TP53, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling-complex, and TAF1, an element of the core TFIID transcriptional machinery are also detected in a significant number of USC. Somatic CNVs, a sign of genomic instability, are identified in the majority of USC with multiple copy number gains and copy number losses, with the most frequent events taking place in pathways similar to those found from analysis of SNVs. In addition to loss of TP53, frequent deletion of a small segment of chromosome 19 containing MBD3, a member of the NuRD-chromatin-modification-complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (encoding for the HER2/neu receptor) and CCNE1 (a target of FBXW7-mediated ubiquitination) are commonly detected. Overall, these findings suggest that both somatic point mutations (SNV) and somatic CNV play a major role in the pathogenesis of USC. Importantly, the frequent mutation of DNA damage, chromatin remodeling, cell cycle and cell proliferation pathways in USC including the overexpression/amplification of HER2/neu, CCNE1 and the tumor-associated calcium signal transducer 2 (TACSTD2/TROP2) genes, suggest novel targets for therapy against this lethal variant of endometrial cancer.
Citation Format: Alessandro D. Santin. Molecular diversity of uterine serous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA016.
Figure S4 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M. 
Published: March 2024

<p>Figure S4: Deficiency of PPARγ in CSF1R- or CD11c-expressing cells suppresses tumor growth. </p>
Figure S2 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M. 
Published: March 2024

<p>Figure S2: Innate immune cells are regulated by GM-CSF and contributes to tumorigenesis.</p>
A Pilot Study on Patient-specific Computational Forecasting of Prostate Cancer Growth during Active Surveillance Using an Imaging-informed Biomechanistic Model
Authors: Lorenzo Guillermo , Heiselman Jon S. , Liss Michael A. , Miga Michael I. , Gomez Hector , Yankeelov Thomas E. , Reali Alessandro , Hughes Thomas J.R. 
Published: March 2024

Abstract

Active surveillance (AS) is a suitable management option for newly diagnosed prostate cancer, which usually presents low to intermediate clinical risk. Patients enrolled in AS have their tumor monitored via longitudinal multiparametric MRI (mpMRI), PSA tests, and biopsies. Hence, treatment is prescribed when these tests identify progression to higher-risk prostate cancer. However, current AS protocols rely on detecting tumor progression through direct observation according to population-based monitoring strategies. This approach limits the design of patient-specific AS plans and may delay the detection of tumor progression. Here, we present a pilot study to address these issues by leveraging personalized computational predictions of prostate cancer growth. Our forecasts are obtained with a spatiotemporal biomechanistic model informed by patient-specific longitudinal mpMRI data (T2-weighted MRI and apparent diffusion coefficient maps from diffusion-weighted MRI). Our results show that our technology can represent and forecast the global tumor burden for individual patients, achieving concordance correlation coefficients from 0.93 to 0.99 across our cohort (n = 7). In addition, we identify a model-based biomarker of higher-risk prostate cancer: the mean proliferation activity of the tumor (P = 0.041). Using logistic regression, we construct a prostate cancer risk classifier based on this biomarker that achieves an area under the ROC curve of 0.83. We further show that coupling our tumor forecasts with this prostate cancer risk classifier enables the early identification of prostate cancer progression to higher-risk disease by more than 1 year. Thus, we posit that our predictive technology constitutes a promising clinical decision-making tool to design personalized AS plans for patients with prostate cancer.

Significance:
Personalization of a biomechanistic model of prostate cancer with mpMRI data enables the prediction of tumor progression, thereby showing promise to guide clinical decision-making during AS for each individual patient.
Redescription of Xiphinema artemisiae Chizhov, Tiev & Turkina, 1986 (Dorylaimida: Longidoridae): new occurrence in Iran
Authors: Fekrat Farnaz , Ghaderi Reza , Pourjam Ebrahim , Castillo Pablo , Pedram Majid 
Published: March 2024

Summary
A population of Xiphinema artemisiae was recovered from Iran, representing the first report after its original description from a meadow pasture in northern Caucasus, Russia. The Iranian population was recovered from the rhizosphere of grasses in the Damavand region, Tehran province. The females of the recovered populations are characterised by a lip region separated from the rest of body by a depression, a 5.1-5.6 mm long body, a 129-138 μm long odontostyle, 76-85 μm long odontophore, a uterus having a pseudo-Z-organ and crystalloid bodies observed in some specimens, and a short, rounded, dorsally more convex tail with a subcentral mucron, four juvenile developmental stages (the first stage was not recovered) and functional males. The Iranian population is morphologically and morphometrically similar to the type population and minor morphological differences can be attributed to geographical interpopulation differences. Molecular phylogenetic relationships of the Iranian population of X. artemisiae with other species were reconstructed using sequences of three genomic ribosomal markers, viz. small, large subunit D2-D3 and internal transcribed spacer (SSU, LSU D2-D3 and ITS) rDNA.
Hip abductor strengthening vs iliotibial band stretching exercises in conventional knee osteoarthritis rehabilitation: a comparative trial
Authors: Mehla P. , Joshi S. , Pawalia A. , Gera C. 
Published: March 2024

Abstract
The aim of this study is to compare the effect of hip abductor and iliotibial band (ITB) exercises for patients of knee osteoarthritis (OA). 60 patients with knee OA were randomly divided into three groups. Group A received hip abductor strengthening along with quadriceps strengthening exercises, Group B received iliotibial band stretching along with quadriceps strengthening exercises and Group C received conventional knee exercises. The treatment duration was three sessions per week in alternate days for 3 weeks. The outcome measures were pain, physical performance and quality of life, which were evaluated at the baseline and after 3 week of intervention with the visual analogue scale, chair sit to stand test and knee injuries and osteoarthritis outcome score questionnaire. All the three groups showed statistically significant improvement in pain, physical performance and quality of life in patients with knee OA. Hip abductor strengthening exercises group showed more significant improvement in pain, physical performance and quality of life than the Iliotibial band stretching exercises group. The results of the study suggest that the hip abductor strengthening exercises can be more effective than iliotibial band stretching exercises in reducing pain, improving quality of life and physical performance in patients with knee osteoarthritis. But we can also use iliotibial band stretching exercises with other interventions in case of knee OA because iliotibial band stretching exercises also gives result in reduction of pain, symptoms and improvement in physical performance and quality of life.
Clinical trial registry of India No. CTRI/2023/06/054225
Continuity and Change in the Role of Mysticism Under the Islamic Republic of Iran
Authors: Machlis Elisheva 
Published: March 2024

Abstract
The current study will evaluate the role of ‘irfān [the inner perception of knowledge; combining elements of philosophy, theosophy, mysticism and Shi‘i thought] within the Islamic Republic of Iran as a significant component of Iran’s cultural heritage. It will focus on several prominent clerics and intellectuals who represent the regime’s diverse political factions. This article will demonstrate that under the Islamic Republic, ‘irfān evolved from a marginalized area to a central phenomenon and became a tool to debate the political direction of the state and the relationship between its revolutionary and republican elements. While mysticism in the service of politics was more wide-spread among the reformist camp, ardent supporters of the regime resorted to ‘irfān to enhance an exclusive perception of authority based on the rule of the Supreme Jurist. It also created a shared spiritual basis among the Islamic State’s diverse voices. The result was a new blend between mysticism, philosophy, Western thought, politics, Islamic law, and even messianism, within an inter-connectivity between the mystical path and the Shari‘a. Consequently, a complex understanding of ‘irfān has to take into consideration the multiple fusions between Islamic mysticism and other trends and evaluate the result in a specific socio-political context.
Expecting the Future: Entropy-Based Predictions in Time Perception
Authors: Clarke Jason , Tyler Becky 
Published: March 2024

Abstract
What cognitive mechanisms underlie the human experience of time’s directionality, often described as the psychological arrow of time? This study explores this question by examining the role of visual entropy, a measure of disorder within a system, in shaping our perception of time. Grounded in the second law of thermodynamics and predictive processing frameworks, we hypothesised that the human cognitive system expects an increase in visual entropy over time and that violations of this expectation (prediction errors) would lead to a relative overestimation of perceived duration. Participants reproduced the duration of computer-generated animations depicting three-dimensional greyscale shapes shattering from wholes into parts (low to high entropy) or the reverse (high to low entropy) presented at different lengths (500, 1000, 1500, and 2000 milliseconds). The results revealed a significant interaction: while forward animations (low to high entropy) were perceived as longer at the shortest duration (500 ms), backward animations (high to low entropy) were overestimated at longer durations (1500 and 2000 ms). This pattern suggests an initial reliance on high-precision expectations for shorter stimuli, with a shift towards increased weighting of prediction errors for longer durations, leading to the overestimation of entropy-reversed stimuli. These results align with predictive processing frameworks, indicating that the brain dynamically reconciles incoming sensory data with prior expectations of entropy progression, thereby shaping our subjective experience of temporal directionality. This research introduces a novel paradigm for examining time perception and supports the application of predictive processing theories in understanding the cognitive and neural underpinnings of temporal experience.
Understanding the Geopolitical Implications of the Impending Religious Power Vacuum in Tibet
Authors: Ba Jonathan 
Published: March 2024

Abstract
Despite being the smallest branch of Buddhism worldwide, Vajrayana Buddhism is the majority religion in Tibet, Mongolia, and Bhutan, where it wields significant religious and political power. This power has traditionally been concentrated among a small number of lamas, most notably the Dalai Lama, who upon their passing are replaced by a successor in accordance with traditional rituals. Since Tibet came under control of China in 1950, the Chinese Communist Party has sought to gain complete control over Tibetan Vajrayana Buddhism, coopting these leadership institutions by installing its own puppet lamas. However, the flight of the current Dalai Lama from the Tibetan capital Lhasa in 1959 led to the exodus of Tibetans to India, where a government-in- exile was established in Dharamsala. This government, which derives its legitimacy from the Dalai Lama, represents the interests of the Tibetan people, including challenging Chinese rule over Tibet. The current Dalai Lama is now an octogenarian, and his passing will create a religious power vacuum at the core of Vajrayana Buddhism. This paper explores several possible outcomes of this religious power vacuum, and whether Vajrayana Buddhism can maintain its integrity and autonomy moving forward.
Impact of sarcopenia on outcomes of bladder cancer undergoing radical cystectomy: A systematic review and meta-analysis
Authors: Qin Fanyi , Wu Jiacheng 
Published: March 2024

Objective To provide synthesized evidence on the association between sarcopenia and risk of mortality, recurrence and postoperative complications in patients with bladder cancer and undergoing radical cystectomy (RC). Methods Only studies with observational design that investigated the association between sarcopenia and outcomes of interest among patients with bladder cancer undergoing RC were included. The outcomes of interest were mortality, recurrence, and postoperative complications. The systematic search was conducted using three large databases, that is, PubMed, EMBASE, and Scopus. A random effects model was used for the analysis and pooled effect sizes were reported as odds ratio (OR) or hazards ratio (HR) along with 95% confidence intervals (CIs). Results A total of 21 studies with 4997 patients were included. Compared to non-sarcopenic subjects, those with sarcopenia had increased risk of all-cause mortality (HR 1.45, 95% CI: 1.32, 1.61), cancer-specific mortality (HR 1.74, 95% CI: 1.49, 2.03) and a lower recurrence free survival (HR 1.84, 95% CI: 1.30, 2.62). Patients with sarcopenia also had higher risk of developing complications within 90 days postoperatively (OR 1.77, 95% CI: 1.23, 2.55). Conclusion Sarcopenia among patients with bladder cancer and managed using RC is associated with adverse survival outcomes and an increased risk of postoperative complications.
Transcranial direct current stimulation for upper extremity motor dysfunction in poststroke patients: A systematic review and meta-analysis
Authors: Tang Xian , Zhang Nan , Shen Zhiyuan , Guo Xin , Xing Jun , Tian Shujuan , Xing Yuan 
Published: March 2024

Objective To evaluate the efficacy and safety of transcranial direct current stimulation in poststroke patients with upper extremity motor dysfunction using a systematic review and meta-analysis. Data Sources We searched the Web of Science, Cochrane Library, EMBASE, and PubMed for randomized controlled trials investigating the effects of both active and sham stimulation up until January 27, 2024. Review Methods Efficacy, including the upper extremity Fugl–Meyer Assessment, Action Research Arm Test, Barthel Index, and safety, were assessed. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool and the Physiotherapy Evidence Database Scale. Meta-analysis was performed using the RevMan 5.4 software. Results Forty-four studies with 1555 participants were included. Transcranial direct current stimulation proved effective in improving upper extremity motor function (standardized mean difference = 0.22, 95% confidence interval: 0.12–0.32, P < 0.001) and Barthel Index (mean difference = 4.65, 95% confidence interval: 2.82–6.49, P < 0.001). Subgroup analysis revealed the highest transcranial direct current stimulation efficacy in patients with subacute stroke. Both anodal and cathodal stimulation were effective against upper extremity motor dysfunction. C3/C4 was the most effective stimulus target. Optimal stimulation parameters included stimulus current densities <0.057 mA/cm2 for 20–30 min and <30 sessions. Adverse effects and dropouts during follow-up showed that transcranial direct current stimulation is safe and feasible. Conclusions Our findings suggest that both anodal and cathodal stimulation were significantly effective in subacute stroke patients, particularly when preceding other treatments and when C3/C4 is targeted.