bluuebunny/crossref_metadata_2025_split huggingface dataset:
Priorities to Promote Participant Engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network
Authors: Schuster Anne LR. , Crossnohere Norah L. , Bachini Melinda , Blair Cindy K. , Carpten John D. , Claus Elizabeth B. , Colditz Graham A. , Ding Li , Drake Bettina F. , Fields Ryan C. , Janeway Katherine A. , Kwan Bethany M. , Lenz Heinz-Josef , Ma Qin , Mishra Shiraz I. , Paskett Electra D. , Rebbeck Timothy R. , Ricker Charité , Stern Mariana C. , Sussman Andrew L. , Tiner Jessica C. , Trent Jeffrey M. , Verhaak Roel GW. , Wagle Nikhil , Willman Cheryl , Bridges John FP. ,   for the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network
Published: February 2023

AbstractBackground:Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research.Methods:PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities.Results:Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants.Conclusions:PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries.Impact:Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement.
Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies
Authors: Argirion Ilona , Pfeiffer Ruth M. , Proietti Carla , Coghill Anna E. , Yu Kelly J. , Middeldorp Jaap M. , Sarathkumara Yomani D. , Hsu Wan-Lun , Chien Yin-Chu , Lou Pei-Jen , Wang Cheng-Ping , Rothman Nathaniel , Lan Qing , Chen Chien-Jen , Mbulaiteye Sam M. , Jarrett Ruth F. , Glimelius Ingrid , Smedby Karin E. , Hjalgrim Henrik , Hildesheim Allan , Doolan Denise L. , Liu Zhiwei 
Published: February 2023

Abstract

Background:
Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL).

Methods:
Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models.

Results:
IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.

Conclusions:
Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis.

Impact:
Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma
Authors: Limberg Jessica , Egan Caitlin E. , Gray Katherine D. , Singh Mandeep , Loewenstein Zachary , Yang Yanping , Riascos Maria Cristina , Al Asadi Hala , Safe Parima , El Eshaky Steve , Liang Heng , Ullmann Timothy M. , Wang Weibin , Li Wei , Zhang Tuo , Xiang Jenny , Stefanova Dessislava , Jin Moonsoo M. , Zarnegar Rasa , Fahey Thomas J. , Min Irene M. 
Published: February 2023

Abstract

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer.

Implications:
Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.
Autoantibodies Drive Heart Damage Caused by Concomitant Radiation and PD-1 Blockade
Authors: Yan Bo , Hooper D. Craig , Yuan Zhiyong , Wang Changli , Chen Yulong , Lu Bo 
Published: February 2023

AbstractConcurrent PD-1 blockade and thoracic radiotherapy is being investigated in clinical trials for locally advanced, non–small cell lung cancer and small cell lung cancer, despite a potential overlapping risk of cardiotoxicity. Our prior studies demonstrate that cardiotoxicity from concurrent cardiac irradiation and anti–PD-1 administration in a mouse model is CD8+ T-cell dependent. The objective of this study was to determine whether humoral immunity contributed to the observed cardiac tissue damage, as measured by creatine kinase MB and cardiac troponin 1 release and decline in cardiac function. In the current study, we demonstrate the presence of cardiac autoantibodies, which were essential for the occurrence of cardiotoxicity from the combined therapy. Mice subjected to cardiac irradiation, while being treated with anti–PD-1, developed high levels of antibodies that reacted with cardiac tissues in vivo and cardiac antigens in vitro. Moreover, mice deficient in B cells were protected against cardiotoxicity, whereas the transfer of autoantibody-containing sera from mice that had received combined treatment reproduced the same pathologic phenotype in mice exposed to cardiac irradiation but was not observed in normal recipients. The cardiotoxic effect of the sera, which associated with CD8+ T-cell accumulation in cardiac tissue, was limited by IgG depletion. In conclusion, concurrent cardiac irradiation and PD-1 blockade leads to production of cardiac autoantibodies, likely due to antigen exposure within the irradiated cardiac tissues, which play a key role in the resulting cardiotoxicity.
Tumor-derived GCSF Alters Tumor and Systemic Immune System Cell Subset Composition and Signaling
Authors: Matos Israel , Barvalia Maunish , Chehal Manreet K. , Robertson A. Gordon , Kulic Iva , Silva Jessica A.F.D. , Ranganathan Abhinandan , Short Amy , Huang Yu-Hsuan , Long Erin , Priatel John J. , Dhanji Salim , Nelson Brad H. , Krebs Danielle L. , Harder Kenneth W. 
Published: February 2023

While immunotherapies such as immune checkpoint blockade and adoptive T-cell therapy improve survival for a subset of human malignancies, many patients fail to respond. Phagocytes including dendritic cells (DC), monocytes, and macrophages (MF) orchestrate innate and adaptive immune responses against tumors. However, tumor-derived factors may limit immunotherapy effectiveness by altering phagocyte signal transduction, development, and activity. Using Cytometry by Time-of-Flight, we found that tumor-derived GCSF altered myeloid cell distribution both locally and systemically. We distinguished a large number of GCSF-induced immune cell subset and signal transduction pathway perturbations in tumor-bearing mice, including a prominent increase in immature neutrophil/myeloid-derived suppressor cell (Neut/MDSC) subsets and tumor-resident PD-L1+ Neut/MDSCs. GCSF expression was also linked to distinct tumor-associated MF populations, decreased conventional DCs, and splenomegaly characterized by increased splenic progenitors with diminished DC differentiation potential. GCSF-dependent dysregulation of DC development was recapitulated in bone marrow cultures in vitro, using medium derived from GCSF-expressing tumor cell cultures. Importantly, tumor-derived GCSF impaired T-cell adoptive cell therapy effectiveness and was associated with increased tumor volume and diminished survival of mice with mammary cancer. Treatment with neutralizing anti-GCSF antibodies reduced colonic and circulatory Neut/MDSCs, normalized colonic immune cell composition and diminished tumor burden in a spontaneous model of mouse colon cancer. Analysis of human colorectal cancer patient gene expression data revealed a significant correlation between survival and low GCSF and Neut/MDSC gene expression. Our data suggest that normalizing GCSF bioactivity may improve immunotherapy in cancers associated with GCSF overexpression.Significance:Tumor-derived GCSF leads to systemic immune population changes. GCSF blockade restores immune populations, improves immunotherapy, and reduces tumor size, paralleling human colorectal cancer data. GCSF inhibition may synergize with current immunotherapies to treat GCSF-secreting tumors.
How Well Does Non-mass Enhancement Correlate With DCIS/Invasive Cancer?
Authors: Huang Kai , Dufresne Maria , Baksh Mizba , Nussbaum Samuel , Abbaszadeh Kasbi Ali , Mohammed Ashary , Advani Pooja , Morozov Andrey , Bagaria Sanjay , McLaughlin Sarah , Gabriel Emmanuel 
Published: February 2023

Introduction Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology. Methods This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology. Results From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT. Conclusions Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach.
Impact of Frailty on Patient Outcomes after Hartmann’s Reversal: A NSQIP Analysis
Authors: Kooragayala Keshav , Lou Johanna , Butchy Virginia , Balakrishnan Archana , Sandilos Georgianna , Kwiatt Michael , Giugliano Danica , McClane Steven 
Published: February 2023

Background Colostomy reversal is a common procedure. Patients often have baseline comorbidities associated with postoperative morbidity. We utilized a modified frailty index (mFI-5) to predict postoperative complications. Methods Patients who underwent elective, open Hartmann’s reversal were queried from the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified to low, medium, or high frailty groups. Statistical analysis was performed using chi-squared, ANOVA, and logistic regression. Results There were 9272 patients with Hartmann’s reversal. 48.78%, 30.31%, and 12.89% had low, moderate, or high frailty, respectively. High frailty was associated with cardiac arrest, myocardial infarction, reintubation, prolonged intubation, early reoperation, and mortality. After multivariate analysis, high frailty was associated with prolonged intubation (OR 3.147, P = .001), reintubation (OR 2.548, P = .002), and reoperation (OR 1.67, P < .001). Conclusions Frailty was associated with greater risk of postoperative complications in patients undergoing Hartmann’s reversal. Frailty may be a useful adjunct to stratify for patients who are at risk for postoperative complications.
Levels of elements in selected food substances that support usage in the management and treatment of erectile dysfunction
Authors: Lartey Michael , Frimpong-Manso Samuel , Amoah Stephen O , Boamah Daniel , Mohammed Awan Abdul Rashid 
Published: February 2023

Background The use of fruits and vegetables for the management and treatment of erectile dysfunction has gained popularity due to the cheaper cost, accessibility and perceived absence of side effects. Much of the work done on plant-based aphrodisiacs has focused on the phytochemistry of secondary metabolites. Aim This work sought to analyze selected fruits and vegetables that are commonly used in the management of erectile dysfunction in Ghana and quantify the levels of some micro- and macro-elements necessary for good penile health in order to determine the usefulness or otherwise of the selected produce. Methods Energy-dispersive X-ray fluorescence spectroscopy was used to detect and quantify the levels of potassium (K), calcium (Ca), selenium (Se), magnesium (Mg), iron (Fe), and zinc (Zn) in carrot roots, cucumber fruit, garlic bulb, ginger rhizome, nutmeg fruit, sweet potato tuber, tiger nut tuber and watermelon fruit. Results The analysis revealed the presence of K, Ca, Mg, Fe and Zn. Levels of Se were below detection. The concentration of K was the highest in each of the food substances. However, in terms of recommended daily allowance, Mg had the highest contribution. Cucumber fruit and the rind of watermelon fruit had the highest levels of micro- and macro-elements implicated in erectile dysfunction. Conclusion The potential use of these foods to treat and manage erectile dysfunction may not only be due to the presence of phytochemicals alone but also the presence of significant levels of micro- and macro-elements required for good penile health.
Determinants of perinatal mortality at tertiary hospitals in East Wollega, Western Ethiopia: a case–control study
Authors: Oljira Rut , Merdassa Elias , Kejela Gemechu , Fentahun Firehiwot , Tilahun Temesgen 
Published: February 2023

Objective This study was performed to determine predisposing factors of perinatal mortality among deliveries at tertiary hospitals in East Wollega, Western Ethiopia. Methods This institutional-based unmatched retrospective case–control study involved 810 samples (270 perinatal deaths and 540 controls) selected from the study hospitals. For each case, two controls were selected. Data were collected using a pretested structured questionnaire. Data were entered into EpiData Version 3.1 and exported to SPSS Version 25 for analysis. Descriptive analysis and logistic regression were performed. The adjusted odds ratio with 95% confidence interval was calculated, and statistical significance was declared at a P-value of <0.05. Results The statistical analysis revealed the following independent determinants of perinatal mortality: rural residence, lack of antenatal care, preterm delivery, induction of labor, presence of obstetric complications, breech presentation, shoulder presentation, low birth weight, congenital malformation, and not using a partograph. Conclusion Given the determinant factors of perinatal mortality in the study area, health facilities are recommended to implement appropriate antenatal care, intrapartum care, and neonatal care to prevent perinatal mortality. They are also advised to use partographs and ensure better access to antenatal care facilities.
Using an Affordable Motion Capture System to Evaluate the Prognostic Value of Drop Vertical Jump Parameters for Noncontact ACL Injury
Authors: Corban Jason , Karatzas Nicolaos , Zhao Kevin Y. , Babouras Athanasios , Bergeron Stephane , Fevens Thomas , Rivaz Hassan , Martineau Paul A. 
Published: February 2023

Background: Knee kinematic parameters during a drop vertical jump (DVJ) have been demonstrated to be associated with increased risk of noncontact anterior cruciate ligament (ACL) injury. However, standard motion analysis systems are not practical for routine screening. Affordable and practical motion sensor alternatives exist but require further validation in the context of ACL injury risk assessment. Purpose/Hypothesis: To prospectively study DVJ parameters as predictors of noncontact ACL injury in collegiate athletes using an affordable motion capture system (Kinect; Microsoft). We hypothesized that athletes who sustained noncontact ACL injury would have larger initial and peak contact coronal abduction angles and smaller peak flexion angles at the knee during a DVJ. Study Design: Case-control study; Level of evidence, 3. Methods: 102 participants were prospectively recruited from a collegiate varsity sports program. A total of 101 of the 102 athletes (99%) were followed for an entire season for noncontact ACL injury. Each athlete performed 3 DVJs, and the data were recorded using the motion capture system. Initial coronal, peak coronal, and peak sagittal angles of the knee were identified by our software. Results: Five of the 101 athletes sustained a noncontact ACL injury. Peak coronal angles were significantly greater and peak sagittal flexion angles were significantly smaller in ACL-injured athletes ( P = .049, P = .049, respectively). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve of 0.88, 0.92, and 0.90 for initial coronal, peak coronal, and peak sagittal angle, respectively. An initial coronal angle cutoff of 2.96° demonstrated 80% sensitivity and 72% specificity, a peak coronal angle cutoff of 6.16° demonstrated 80% sensitivity and 72% specificity, and a peak sagittal flexion cutoff of 93.82° demonstrated 80% sensitivity and 74% specificity on the study cohort. Conclusion: Increased peak coronal angle and decreased peak sagittal angle during a DVJ were significantly associated with increased risk for noncontact ACL injury. Based on ROC analysis, initial coronal angle showed good prognostic ability, whereas peak coronal angle and peak sagittal flexion provided excellent prognostic ability. Affordable motion capture systems show promise as cost-effective and practical options for large-scale ACL injury risk screening.
Self-catalytic phthalonitrile polymer with improved processing performance and long-term thermal stability
Authors: Zhang Xinyang , Wang Xinyang , Zhang Shuo , Wu Minjie , Rong Jianxin , Han Wenshuang , Zhao Tao , Yu Xiaoyan , Zhang Qingxin 
Published: February 2023

Phthalonitrile monomer with alkyl, pyrimidine, and amino is successfully prepared by nucleophilic substitution. The monomer is cured by autocatalysis of active hydrogen in the amino group, in order to obtain polymers through different temperature procedures. The low melting point (96°C) and curing kinetics of the monomer are analyzed by DSC, which manifest a processing window of 163°C. With lower energy barriers to overcome, the apparent activation energy ( E a) is 59.6 kJ mol−1 after fitting and calculating, signifying that the monomers are easier to process into polymers. This study focuses on the usefulness of the polymer, especially the long-term thermal stability by the comparison of numerous commonly used polymers. The consequence demonstrates that the polymer could be used for long periods at 300°C, keeping weight loss within 5 wt.% for 6 h. The advantage of long-term usage at high temperatures has not been proved in previous works on phthalonitrile polymer. Moreover, the thermal and thermal-mechanical stability are examined through TGA and DMA. The results indicate preferable thermal properties, that the glass transition temperature is up to 400°C.