bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR009: An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas
Authors: Falvo David J. , Grimont Adrien , Zumbo Paul , Yang Julie L. , Osterhoudt Alexa , Pan Grace , Rendeiro Andre F. , Wilkinson John E. , Dündar Friederike , Elemento Olivier , Yantiss Rhonda K. , Betel Doron , Koch Richard , Chandwani Rohit 
Published: November 2022

Abstract
Inflammation is essential to the disruption of tissue homeostasis, and, in the pancreas, can destabilize the identity of terminally differentiated acinar cells. A longstanding question has been whether a history of past injuries instructs subsequent homeostatic responses to future stimuli – despite being distantly separated in time. Thus, we employ here Mist1-CreERT2; LSL-tdTomato lineage-tracing mice to investigate the long-term effects of a transient inflammatory episode on pancreatic tissue homeostasis. We delineate the chromatin dynamics that accompany the cycle of metaplasia and regeneration following pancreatitis, and reveal that the pancreatic acinar cell compartment durably retains specific inflammation-induced epigenetic changes even 18-weeks after exposure to the original inflammatory stimulus. We observe that despite histologic resolution of pancreatitis, acinar cells fail to return to their molecular baseline after several months, representing an incomplete cell fate decision. Motif analysis demonstrates the enrichment of AP-1/Fra1 motifs at these persistently accessible memory regions—a transcriptional effector activated downstream of the Ras/MAPK pathway. This epigenetic memory controls lineage plasticity, with diminished metaplasia in response to a second inflammatory insult but increased tumorigenesis with an oncogenic Kras mutation. We demonstrate that pancreatic acinar cells exhibit rapid malignant transformation upon re-challenge with oncogenic stress via inflammatory memory recall, with robust reactivation of genes associated with differentially accessible memory regions. Together, our findings define the dynamics and recall of an epigenetic memory of inflammation that impacts cell fate decisions in a context-dependent manner.
Citation Format: David J. Falvo, Adrien Grimont, Paul Zumbo, Julie L. Yang, Alexa Osterhoudt, Grace Pan, Andre F. Rendeiro, John E. Wilkinson, Friederike Dündar, Olivier Elemento, Rhonda K. Yantiss, Doron Betel, Richard Koch, Rohit Chandwani. An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR009.
Abstract PR023: Targeting gemcitabine resistance in pancreatic cancer
Authors: Beutel Alica Katrin , Singh Rima , Anaraki Cecily , Tong Gregory , Martinez Thomas , Kleger Alexander , Jutric Zeljka , Halbrook Christopher James 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a devastating 5-year survival rate of 11%. A lack of durable responses to standard-of-care chemotherapy combinations renders its treatment particularly challenging and largely contributes to the devastating prognosis. Gemcitabine, a pyrimidine anti-metabolite, is a cornerstone in PDAC therapy, but resistance remains a major hurdle. Multiple mechanisms of chemoresistance have been suggested to be mediated by rewired metabolism in PDAC cells. Accordingly, we hypothesize that metabolic reprogramming can be targeted to re-sensitize PDAC tumors to anti-metabolite chemotherapy. To define the spectrum of targetable metabolic and transcriptomic programs that drive cell-intrinsic resistance to gemcitabine, we established organoids from treatment-naïve PDAC patients. Gemcitabine high versus low responders, as assessed by dose response viability assays, were selected for metabolomic profiling and RNA sequencing. To define real-time reprogramming during the acquisition of resistance, we generated gemcitabine resistant murine pancreatic cancer cell lines and collected a time course series of metabolomic and transcriptomic datasets of sensitive, intermediate resistant and resistant cells. Integration of these dataset through a systems biology approach to define primary and de novo resistance is being used to characterize metabolic gemcitabine resistance mechanisms. These are functionally validated to provide novel approaches to re-sensitize resistant PDAC cells to gemcitabine in vitro and in vivo. The improvement of current chemotherapy combinations represents a promising approach, with potential to immediately translate into a clinical benefit and improve survival in this deadly disease.
Citation Format: Alica Katrin Beutel, Rima Singh, Cecily Anaraki, Gregory Tong, Thomas Martinez, Alexander Kleger, Zeljka Jutric, Christopher James Halbrook. Targeting gemcitabine resistance in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR023.
Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion
Authors: Saemann Lars , Kohl Matthias , Veres Gábor , Korkmaz‐Icöz Sevil , Großkopf Anne , Karck Matthias , Simm Andreas , Wenzel Folker , Szabó Gábor 
Published: November 2022

Background
Hearts procured from circulatory death donors (DCD) are predominantly maintained by machine perfusion (MP) with normothermic donor blood. Currently, DCD heart function is evaluated by lactate and visual inspection. We have shown that MP with the cardioplegic, crystalloid Custodiol‐N solution is superior to blood perfusion to maintain porcine DCD hearts. However, no method has been developed yet to predict the contractility of DCD hearts after cardioplegic MP. We hypothesize that the shift of microvascular flow during continuous MP with a cardioplegic preservation solution predicts the contractility of DCD hearts.

Methods and Results

In a pig model, DCD hearts were harvested and maintained by MP with hypothermic, oxygenated Custodiol‐N for 4 hours while myocardial microvascular flow was measured by Laser Doppler Flow (LDF) technology. Subsequently, hearts were perfused with blood for 2 hours, and left ventricular contractility was measured after 30 and 120 minutes. Various novel parameters which represent the LDF shift were computed. We used 2 combined LDF shift parameters to identify bivariate prediction models. Using the new prediction models based on LDF shifts, highest
r
2
for end‐systolic pressure was 0.77 (
P
=0.027), for maximal slope of pressure increment was 0.73 (
P
=0.037), and for maximal slope of pressure decrement was 0.75 (
P
=0.032) after 30 minutes of reperfusion. After 120 minutes of reperfusion, highest
r
2
for end‐systolic pressure was 0.81 (
P
=0.016), for maximal slope of pressure increment was 0.90 (
P
=0.004), and for maximal slope of pressure decrement was 0.58 (
P
=0.115). Identical prediction models were identified for maximal slope of pressure increment and for maximal slope of pressure decrement at both time points. Lactate remained constant and therefore was unsuitable for prediction.

Conclusions
Contractility of DCD hearts after continuous MP with a cardioplegic preservation solution can be predicted by the shift of LDF during MP.
Drug-Induced Rhinitis: Narrative Review
Authors: Alromaih Saud , Alsagaf Lamya , Aloraini Nouf , Alrasheed Abdulaziz , Alroqi Ahmad , Aloulah Mohammad , Alsaleh Saad , Alhawassi Tariq 
Published: November 2022

Objectives Rhinitis, one of the most common inflammatory conditions of the nasal mucosa, is known to affect a large proportion of people worldwide. It is generally classified into allergic and non-allergic types and both are associated with several unpleasant symptoms. Several medications prescribed for different medical conditions can cause unpleasant rhinitis as an adverse effect, which is known as drug-induced non-allergic rhinitis. The aims of this article were to review the literature to identify drugs that could induce rhinitis, prevalence of drug-induced rhinitis, and the associated pathogenic mechanisms if known. Methods Literature search screening for eligible papers published up to December 31st, 2021, in Medline (via PubMed) and Embase was conducted. The search included the following combination of keywords and terms: rhinitis, sneezing, congestion, allergic, non-allergic, rhinorrhea, vasomotor, medication, drug-induced. Results The review findings suggest that 12 subtypes of drugs potentially could induce rhinitis. Based on their mechanisms of action, the pathogenic causes for the induction of rhinitis have been recognized for some drugs, while others remain unknown. Conclusion Awareness of the list of drugs that reportedly induce non-allergic nasal symptoms, along with taking the patient’s medication history, is important in the diagnosis of rhinitis.
Ethics, virtues and xenotransplantation
Authors: George Andrew JT 
Published: November 2022

Early in 2022 the first pig to human cardiac xenotransplant was performed. The graft initially performed well, and rejection was well controlled. However, the graft failed, and the patient died 60 days after the procedure. The ethical issues relating to xenotransplantation include the risk/benefit to the individual, the risk of porcine-derived infectious agents crossing into humans, animal welfare and rights, issues of human and animal identity and concerns relating to fair allocation of organs and appropriate use of resources. These ethical issues are often addressed using emotional arguments, or through consequentialist or deontological lens. An alternative is to use approaches based on virtue ethics to understand the moral purpose ( telos) of the research and the virtues (character traits) needed to be a good research clinician. In this review we will consider the virtues of justice, courage, temperance and practical wisdom, as well as the role of clinical curiosity, and their application to xenotransplantation. This provides an alternative approach for the clinical academic and others involved in the research to reflect on their practice.
A systematic review of mood and depression measures in people with severe cognitive and communication impairments following acquired brain injury
Authors: Rose Alexandra E. , Cullen Breda , Crawford Sarah , Evans Jonathan J. 
Published: November 2022

Aim A systematic review to identify which mood and depression measures are valid for use with people with severe cognitive and communication impairments following severe acquired brain injury. Method A systematic search of Cochrane, Web of Science, Ovid, and EBSCOhost was performed in March 2020, July 2021, and September 2022. The search focused on self-report and observer-rated assessment tools used to assess mood, depression, and/or distress in those described as having a severe acquired brain injury. Psychometric properties were extracted using the Consensus-based standards for the selection of health measurement instruments (COSMIN) risk of bias checklist. Qualitative synthesis was performed on extracted patient data. Results Nineteen papers detailing the psychometric properties of 25 measures were included, involving 2,914 participants. Nine papers provided details confirming the severity of participants’ cognitive and communication impairments. The remaining papers described including severely injured participants but provided limited details so that precise level of severity could not be confirmed. Only one paper showed evidence of adequate psychometric properties and included those with severe cognitive impairments in a study of two observer-rated measures, the Stroke Aphasia Depression Questionnaire (10 items) and the Aphasia Depression Rating Scale. Conclusions Due to the exclusion of individuals with severe cognitive and communication consequences following brain injury, no studies using self-report measures showed adequate validity evidence to recommend their use in this population. A small study using two observer-rated scales included those with severe cognitive impairments and showed satisfactory evidence that these measures can be validly used with this population.
Effectiveness of vortioxetine in patients with major depressive disorder and co-morbid generalized anxiety disorder in routine clinical practice: A subgroup analysis of the RELIEVE study
Authors: Almeida Susana S , Christensen Michael Cronquist , Simonsen Kenneth , Adair Michael 
Published: November 2022

Background: Generalized anxiety disorder (GAD) is commonly co-morbid with major depressive disorder (MDD) and is associated with greater functional impairment and poorer treatment outcomes than MDD alone. However, studies on treatment with drugs for depression in patients with MDD and co-morbid GAD are limited. Aims: To examine the effectiveness of vortioxetine treatment in patients with MDD and co-morbid GAD in a subgroup analysis of the real-world RELIEVE study. Methods: The analysis included outpatients diagnosed with MDD and co-morbid GAD who initiated vortioxetine treatment at their physician’s discretion in the 24-week, observational RELIEVE study. Primary outcome was patient functioning (Sheehan Disability Scale (SDS)) after 12 and 24 weeks of vortioxetine treatment; secondary outcomes included depression severity (9-item Patient Health Questionnaire (PHQ-9)), cognitive symptoms (5-item Perceived Deficits Questionnaire – Depression (PDQ-D-5)) and cognitive performance (Digit Symbol Substitution Test (DSST)). Results: Overall, 180 patients with MDD and co-morbid GAD were included in the analysis. Following vortioxetine initiation, clinically significant improvements in patient functioning (SDS total score) were observed at week 12 (least-squares (LS) mean reduction from baseline, 7.5 points), sustained through week 24 (9.2 points) (both p < 0.0001). LS mean PHQ-9, PDQ-D-5 and DSST scores improved by 7.9, 4.8 and 7.4 points at week 24, respectively (all p < 0.0001 vs baseline). Adverse events were reported by 33.9% of patients (most commonly nausea, 13.3%). Conclusions: In routine clinical practice, vortioxetine was associated with clinically meaningful, sustained improvements in functioning, and depressive and cognitive symptoms, in patients with MDD and co-morbid GAD. Clinical Trials Registry Name and Identifier: Real-life Effectiveness of Vortioxetine in Depression (RELIEVE) (NCT03555136) https://clinicaltrials.gov/ct2/show/NCT03555136
Prediction of homologous recombination deficiency from cancer gene expression data
Authors: Kang Jun , Lee Jieun , Lee Ahwon , Lee Youn Soo 
Published: November 2022

Objective Homologous recombination deficiency (HRD) is the main mechanism of tumorigenesis in some cancers. HRD causes abnormal double-strand break repair, resulting in genomic scars. Some scoring HRD tests have been approved as companion diagnostics of polyadenosine diphosphate-ribose polymerase (PARP) inhibitor treatment. This study aimed to build an HRD prediction model using gene expression data from various cancer types. Methods The cancer genome atlas data were used for HRD prediction modeling. A total of 10,567 cases of 33 cancer types were included, and expression data from 5128 out of 20,502 genes were included as predictors. A penalized logistic regression model was chosen as a modeling technique. Results The area under the curve of the receiver operating characteristic curve of HRD status prediction was 0.98 for the training set and 0.93 for the test set. The accuracy of HRD status prediction was 0.93 for the training set and 0.88 for the test set. Conclusions Our study suggests that the HRD prediction model based on penalized logistic regression using gene expression data can be used to select patients for treatment with PARP inhibitors.
Tuberculin skin test versus QuantiFERON-TB gold in-tube for latent tuberculosis screening in people living with HIV in a resource-limited setting
Authors: José Raúl Nieto-Saucedo , Joshua Saldaña-Villanueva , Adriana Villafuerte-García , Eva Gutiérrez-Delgado , la Torre-Gutiérrez Hector De , Liz Jovanna Martínez-Navarro , Alejandro Ernesto Macías-Hernández , Juan Luis Mosqueda-Gómez 
Published: November 2022

Objective To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV). Methods A cross-sectional study was carried out between 2017–2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST. Results A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8 years. The median time since HIV diagnosis was 5 years (IQR 2–10), with a median CD4+ count of 541 (IQR 340–757) cells/mm3. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST ( p = .003). Conclusion There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.
A Gendered EU Settlement Scheme: Intersectional Oppression of Immigrant Women in a Post-Brexit Britain
Authors: Yong Adrienne 
Published: November 2022

The EU Settlement Scheme (EUSS) is a transitory immigration regime rolled out by the Home Office as part of the measures for the UK withdrawing from the EU. More can be said about whether the EUSS can truly be hailed an overall “success”, as per official Government messaging, several years after its initial introduction. This paper evaluates this by considering two case studies of vulnerable immigrant women required to apply to the Scheme to successfully remain in the UK after the transition period: those at risk of or facing violence against women and girls (VAWG), and non-EU family members (NEFMs) of EU citizens. Using the theories of intersectionality and vulnerability, the paper outlines how gender and immigration status intersect to make women more vulnerable by virtue of the legal framework of the EUSS and its criteria, arguing that it entrenches intersectional oppression faced uniquely by these women.
Earnings differentials associated with sexual orientation in the Pakistan labour market
Authors: Wahid Abdul , Mantell Edmund H , Kowalewski Oskar 
Published: November 2022

AbstractThis study addresses the question of whether self-identified LGBT status has some power to explain differences between the earnings of male LGTB workers and their occupational counterpart non-LGBT male workers in the Pakistan labour market. The Pakistan labour market is known to be ‘traditional’ in the sense that its operations and the attitudes of participants reflect the confluence of various sociological, political, religious, cultural and patriarchal systems. However, the quantitative significance, if any, of overt sexual orientation and its correlation with earnings remains unclear. This study addresses that question. We find that employed male workers in our sample who are known to be (or thought by employers to be) members of the LGBT community experience significant earnings disadvantages relative to counterpart heterosexual workers.
JC Polyoma Virus as a Possible Risk Factor for Prostate Cancer Development - Immunofluorescence and Molecular Based Case Control Study
Authors: Gorish Babbiker M. T. 
Published: November 2022

Background In vitro studies have produced conflicting results about the significance of the JC Polyoma Virus (JCV) in the human cancers. Objectives Our study aims to detect the presence of JCV Large T antigen (LTag) together with viral load quantitation in the prostate tumor samples to assess if JCV harbors risk factor for prostate cancer (PCa). Method This was a case control-based study. A total of 110 patients participated in this study, including 55 patients with PCa and another 55 patients with benign prostatic hyperplasia (BPH) as cases and controls, respectively. Tissue, blood and urine samples were collected from each participant. Tissues samples were analyzed for the presence of JCV Ltag using a direct immunofluorescence assay (IF). Only positive IF tested samples were subjected to viral quantitation assay. Data were collected and managed using SPSS version 20. Result The JCV LTag in the cases group was 23.63% (13/55) which was higher than that of the controls group 5.45% (3/55) with a P. value of .006 and O.R of 5.76. The mean of viral load was significantly higher among cases tissue specimens 20156 ± 5450 copies/ml compared to controls group 6378 ± 2456copies/ml with P-value of .002. The virus was detected in 11/13 (84.6%) urine samples of cases with a mean viral load of 14068 ± 4590 copies/ml compared to 2/3 (66.6%) of controls viral load 2534 ± 1267 copies/ml. Conclusion In conclusion, a higher JCV LTag with more viral load were detected in cases group compared to controls. Our findings support a strong relationship between JCV infection and the probability of developing PCa.
Experimental and numerical vibration analysis of surface mechanical attrition treatment
Authors: Yarar Eser , Ertürk A Tamer , Açıkgöz Çağatay , Karabay Sedat 
Published: November 2022

The surface mechanical attrition treatment creates a nanocrystal layer with improved mechanical properties without changing the surface chemistry. Vibration produces residual stresses in a layer close to the surface by successive impacts on the material surface. Vibration treatments represent a “green” alternative to surface treatments without the use of chemicals and high temperatures. Depending on the operating frequency and amplitude of a particular vibration platform, the most decisive parameter to be controlled for the efficiency of the application is the velocity. Vibration platforms in the SMAT process are ultrasonic and mechanically based platforms. This work presents a vibration platform where velocity is below 1 m/s, which is the lowest operating speed defined in the SMAT process. This work includes both analytical and numerical solutions to the natural frequency values of the vibrating table. The operating conditions were determined by finding the natural frequency values. The amplitude, velocity, and acceleration relations of the vibrating table that will occur during the process were found using the frequency response analysis method. ANSYS and MATLAB were used for numerical and analytical solutions, respectively. Numerical and analytical results were in agreement with the experimental modal analysis.