bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 905: A novel bioluminescent bioassay platform for the discovery and development of engineered T cell therapies for cancer
Authors: Grailer Jamison , Slater Michael , Hartnett Jim , Fan Frank , Cong Mei 
Published: April 2023

Abstract
Adoptive transfer of T cells genetically modified to express antigen receptor transgenes has shown promise for the treatment of cancer. Both chimeric antigen receptors (CARs) and transgenic T cell receptors (TCRs) have been used to redirect T cells in preclinical and clinical studies. TCR Therapy (TCR-T) can target essentially any tumor antigen via the major histocompatibility (MHC) system. However, the development of novel tumor antigen specific TCRs is hampered by the lack of easy-to-use model systems and sensitive readouts to facilitate candidate screening and development. Particularly, determination of transgenic TCR activation in primary and immortalized T cells is confounded by the presence of endogenous TCR expression which results in mixed alpha/beta TCR pairings and compression of assay readouts. Herein, we describe the development of a novel cell-based TCR knockout (TCR-KO) reporter assay platform for the development and characterization of novel TCR candidates. CRISPR/Cas9 was used to knockout the endogenous TCR chains in a T cell line that stably expresses a luciferase reporter gene responsive to TCR activation. Reintroduction of a transgenic TCR into the TCR-KO reporter cells results in robust antigen-specific reporter activation compared to parental reporter cells. The further development of CD4/CD8 double-positive and double-negative versions enable low and functional high avidity TCR screening with or without MHC bias. Furthermore, stable TCR-expressing reporter cells generated from TCR-KO reporter cells exhibit sufficient sensitivity and robustness for safety and specificity studies of lead TCR candidates. Together, our data demonstrate that TCR-KO reporter cells can be a useful tool for the discovery, characterization, and deployment of T cell immunotherapy.
Citation Format: Jamison Grailer, Michael Slater, Jim Hartnett, Frank Fan, Mei Cong. A novel bioluminescent bioassay platform for the discovery and development of engineered T cell therapies for cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 905.
Abstract 958: Signal transduction pathway activity of TGF-β and Hedgehog as possible response predictors to checkpoint inhibition in patients with advanced melanoma; a retrospective cohort study
Authors: vanRavensteijn Stefan G. , Taurello Daniele V. , Amir Avital , Wesseling Yvonne J. , vanBrussel Anne G. , Keizer Diederick M. , Verheul Henk M. , Bol Kalijn F. 
Published: April 2023

Abstract
Introduction: Although immunotherapy is highly effective in patients with melanoma, not all patients respond equally well to immune checkpoint inhibition (ICI). Preclinical data indicate that TGF-β pathway activity mediates immune evasion by tumor T cell exclusion and may therefore be predictive for response. Recently, a new mRNA-based methodology has been developed to measure and quantify signal transduction pathway (STP) activities in tissue. This study was initiated to characterize the STPs in advanced melanoma samples to better understand the role of STPs in immune check point efficacy.
Method: The OncoSIGNal pathway activity profiling PCR test (InnoSIGN) was used to measure the activity of 8 different STPs (AR, PI3K, MAPK, Hedgehog (HH), TGF-β, Notch, NFkB and JAK-STAT1/2) in biopsies (FFPE) from patients with advanced melanoma (n=34) and expressed on a scale from 0 -100. A biopsy of a metastatic site was obtained prior start of ICI therapy (nivolumab or pembrolizumab). These samples were analyzed for STP activity and related to progression-free survival (PFS). Also, STP activities were compared between responders (n=15; partial or complete response) and non-responders (n=19; defined as progression within 6 months).
Results: The mean HH score of responders versus non-responders was 35.7 + 6.1 vs 41.6 + 8.7 (p=0.038), while TGF-β scores were 53.9 + 6.2 vs 56.8 + 8.2 (p=0.265), respectively. Cox regression analysis showed a hazard ratio of 1-1.1 for PFS of both HH and TGF-β (HH: p=0.032) (TGF-β: p=0.071). Kaplan Meier curves indicated a better PFS for lower HH activity at a threshold of 46 (p&lt; 0.001) and lower MAPK activity at a threshold of 47.3 (p= 0.041). No relation with PFS was detected for TGF-β activity. No statistically significant differences were observed in STP activity between different metastatic locations ((sub)cutaneous, lymph node or visceral metastases).
Conclusion: Signal transduction pathway activity of metastatic samples, taken prior start of ICI therapy, from patients with advanced melanoma, suggest that TGF-β did not correlate with response nor PFS but increased HH and MAPK STP activity may relate towards a worse PFS from ICI therapy.
Citation Format: Stefan G. vanRavensteijn, Daniele V. Taurello, Avital Amir, Yvonne J. Wesseling, Anne G. vanBrussel, Diederick M. Keizer, Henk M. Verheul, Kalijn F. Bol. Signal transduction pathway activity of TGF-β and Hedgehog as possible response predictors to checkpoint inhibition in patients with advanced melanoma; a retrospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 958.
Supplemental Table S2 from BRCA1-Associated RING Domain-1 (BARD1) Loss and GBP1 Expression Enhance Sensitivity to DNA Damage in Ewing Sarcoma
Authors: Maurer Lisa M. , Daley Jessica D. , Mukherjee Elina , Venier Rosemarie E. , Julian Claire M. , Bailey Nathanael G. , Jacobs Michelle F. , Kumar-Sinha Chandan , Raphael Haley , Periyapatna Nivitha , Weiss Kurt , Janeway Katherine A. , Mody Rajen , Lucas Peter C. , McAllister-Lucas Linda M. , Bailey Kelly M. 
Published: April 2023

<p>Prevalence of somatic DNA damage repair gene variants in Ewing cell lines included in original studies of PARP inhibition.</p>
Tourists’ Service Satisfaction of the Selected Amusement Parks in Subic Bay Freeport Zone
Authors: Abrajano Rhia May C. , Fernandez Grace , Salazar Glenn 
Published: April 2023

This descriptive-survey research determined the tourists’ service satisfaction of the selected amusement parks in Subic Bay Freeport Zone, Olongapo City. A total of 90 respondents served as the participants of the study. The researchers assessed the levels of satisfaction of amusement parks guests based on their perceptions. Guests were asked on how they can describe their satisfaction levels based on entertainments offered by the parks, staffs, safety and security, and cleanliness of each park. Entertainment wise, Amusement Park C was perceived by its guests as the most entertaining parks among the selected the amusement parks in the Freeport. Its adventurous and thrilling activities and wide vast forest area makes it more entertaining. The staffs of the Amusement Park A were given the highest rating by its guests compared to other selected amusement parks in the Freeport. Their staffs were considered by most of its guests as accommodating, informative and are always ready to serve the guests with all their requests. Safety and security were highly prioritized by the Amusement Park B management and it was confirmed by its guests based on their perception. This research find out that Amusement Park B and all its parks inside its area were considered by its guests as safe and secured as compared to its competitors in the Freeport. Few machines and technical rides inside the Amusement Park B made it safer for its guests. It was able to fully maximize nature for tourism and entertainment purposes. The highest rating for cleanliness, one of the several important factors that affects the levels of satisfaction of the guests, was given by the respondents to Amusement Park B. This gave the said amusement park the highest overall rating. The study recommends to conduct benchmarking or comparative studies of Freeport amusement parks with other amusement parks in the country. This shall focus on enhancing the tourism industry in the Freeport by learning new ways to make its tourism industry a truly world class.
Prognostic Value of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging for Predicting Venous Thromboembolism in Children With Lymphoma
Authors: Beall Maren , Deep Kyra , Tram Nguyen K. , Nabavinia Mahboubeh , Janse Sarah A. , Chou Ting-Heng , Hardisky Dariya , Bobbey Adam J. , Kerlin Bryce A. , Audino Anthony N. , Stacy Mitchel R. 
Published: April 2023

Background:
Positron emission tomography (PET)/computed tomography (CT) imaging can detect changes in arterial inflammation, but has not been used to evaluate chemotherapy-induced venous inflammation or assess risk for venous thromboembolism (VTE) in pediatric oncology. Therefore, the purpose of this study was to evaluate the prognostic value of fluorine-18-fluorodeoxyglucose PET/CT imaging of venous inflammation for predicting VTE occurrence in the 12 months after lymphoma diagnosis in pediatric, adolescent, and young adult patients.

Methods:
Pediatric, adolescent, and young adult patients with lymphoma diagnoses (n=71) who underwent whole-body PET/CT imaging at initial staging of disease and first therapeutic follow-up were retrospectively evaluated for serial changes in lower extremity venous uptake of fluorine-18-fluorodeoxyglucose. PET/CT images were used to segment and quantify serial changes in fluorine-18-fluorodeoxyglucose uptake for veins of interest (ie, popliteal and femoral). Incidence of VTE was assessed for 12 months after lymphoma diagnosis.

Results:

PET/CT detected a significantly higher inflammatory response in the femoral (
P
=0.012) and popliteal (
P
=0.013) veins of patients who experienced a VTE event compared with those who remained VTE free in the 12 months after diagnosis. The area under the curve values for receiver operator characteristics analyses were 0.76 (femoral vein) and 0.77 (popliteal vein) based on incidence of VTE occurrence. Univariate analyses demonstrated that PET/CT-derived changes in femoral (
P
=0.008) and popliteal (
P
=0.002) vein inflammation were significantly associated with VTE-free survival at 12 months after diagnosis.

Conclusions:
Fluorine-18-fluorodeoxyglucose PET/CT imaging detects treatment-induced venous toxicity that may provide insight into risk of VTE events in pediatric and adolescent and young adult patients with lymphoma.
The Graffiti Marking Polis Ownership from the Excavations of Olbian Agora in the 1960s and 1970s
Authors: Bekhter Anastasia , Il’ina Yuliya 
Published: April 2023

Abstract
The article publishes eleven graffiti from the Olbian Agora, marking pottery owned by the polis (Yu.G. Vinogradov has published photos of six objects). On one of the vessels the word πόλεως̣ is written in its full form, on the others it is represented by abbreviations ΠΟ and ΠΟΛΕ. The collection includes ten imported black-glazed vessels of Attic production (the location of four of them is currently unknown, the description is given on the basis of archival photos) and a red-slip fish dish, supposedly of local production. On the basis of the archaeological context, the typology of pottery and paleography, the graffiti can be dated to the first half of the 5th century BC.
Raylessness and paedomorphosis: losses and gains of xylem rays en route from procambium to vascular cambium
Authors: Frankiewicz Kamil E. , Oskolski Alexei A. 
Published: April 2023

Summary
A recurring motif of Carlquist’s work is the identification of traits typical for primary xylem of angiosperms as a whole, but found in the secondary xylem of certain species. These traits together make up the ‘Carlquistian syndrome’. Convergent occurrence of the syndrome in plants with similar habits suggests its adaptive value. One of its components — raylessness — has received the most attention and has been regarded as the result of selection favouring stem rigidity. However, how raylessness (or the Carlquistian syndrome in general) arises ontogenetically has been little studied. Here, we report that in some plants secondary xylem resembles primary xylem of the same individual, and not that of angiosperms in general as observed by Carlquist. Based on literature and microslide surveys, we identified this prolongation of primary xylem patterns into secondary xylem in most major clades of non-monocot angiosperms, including magnoliids, asterids and rosids.
Molecular phylogenetics and diversity of the Himalayan shrew ( Soriculus nigrescens Gray, 1842) (Eulipotyphla, Soricidae) in Southwest China
Authors: JIANG HAIJUN , FU CHANGKUN , TANG KEYI , LI FENGJUN , FAIZ ABU UL HASSAN , GUO KEJI , LIU SHAOYING , CHEN SHUNDE 
Published: April 2023

The Himalayan shrew, Soriculus nigrescens Gray, 1842, belongs to the monotypic genus Soriculus, which is distributed mainly in the Himalayan region. Previous authors have studied its classification based on morphological and molecular data. However, no comprehensive study of the diversity and phylogeny of this species has been performed. In this study, we investigated the molecular phylogeny, genetic diversity, and species divergence of S. nigrescens based on one mitochondrial gene and three nuclear genes. A total of 124 samples from 27 sites in Southwest China were analyzed. Our molecular phylogenetic analyses and species divergence reveal non-monophyly of Soriculus, potentially representing two genera and three clades. Populations from Yunnan (Clade YN) represent the subspecies S. n. minors and should recover the full species status. Populations from Himalayas (Clade A) represent the species S. nigrescens, while populations from southeastern Nyenchen Tanglha Mountains and southern Himalayas (Clade B) represent a new cryptic and unnamed species. Species delimitation analyses and deep genetic distance analysis clearly support the species status of these three evolving clades. The putative new genus and cryptic species should be studied and identified in the future using a more extensive sampling combined with a comprehensive morphological and phylogenetic analysis.
The correlation between women’s various gynaecological diseases to ovarian cancer in Sulaimaniyah City, Iraq
Authors: Karim Soz Mustafa Hagi , Fattah Chro Najmadin 
Published: April 2023

Objective To assess the relationship between benign gynaecological disorders and ovarian cancer (OC). Methods This retrospective observational study enrolled female patients with histologically-confirmed primary OC. Clinical and demographic data were collected using a questionnaire. Blood samples were analysed for tumour biomarker levels including cancer antigen (CA)-125, CA19-9, carcinoembryonic antigen, β human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH) using enzyme-linked immunosorbent assays. Results A total of 100 female patients were enrolled in the study. Of these, 44 patients had simple ovarian cysts (44%), 22 had uterine fibroids (22%), 15 had adenomyosis (15%), 13 had pelvic inflammatory disease (13%) and six had endometriosis (6%). There was a significant association between high grade serous OC histology with both benign ovarian and uterine diseases. There was a significant association between both adenomyosis and uterine fibroids and high grade OC. There was also a significant association between endometriosis and stages III/IV OC. With regard to tumour biomarkers, there was a significant association between β-hCG and LDH biomarkers and benign uterine tumours. Conclusion Benign gynaecological diseases are accompanied by the high risk of the development of OC. Common benign gynaecological diseases associated with OC were uterine fibroids and adenomyosis.
Elective Ambulatory Unit: Experience of Local Anesthetic Only Surgery During the Pandemic
Authors: Jeans Edward , Talwalkar Sumedh , Gebrye Tadesse , Yeowell Gillian , Fatoye Francis , Hayton Mike 
Published: April 2023

Background: The second COVID-19 wave severely limited access to elective surgery. Methods: Between December 2020 and May 2021, 530 patients underwent a procedure in the elective ambulatory unit (EAU), a walk-in and walk-out model of surgery, and we used a prepandemic cohort of day-case patients for comparison. Results: We have had no confirmed cases of COVID-19 transmission on-site. The infection rate for EAU and day-case units for carpal tunnel decompression was 1.36% and 2%, respectively, and this difference was not significant, P = .696. Patient satisfaction was excellent at 9.8 of 10. The waiting time from primary care referral to carpal tunnel decompression was cut from 36 weeks to 12 weeks during the study period. Significant benefit in efficiency and cost saving was also found. Conclusion: Elective ambulatory unit provides a template to perform high-volume low-complexity hand and wrist surgery in a safe, efficient, and cost-effective manner.
Anterior Tibiotalar Fat Pad Involvement in Ankle Osteoarthritis: MRI Features in Patients 1 Year After a Lateral Ankle Sprain
Authors: Arnaert Stijn , Byttebier Paul , Van Rossom Sam , Vereecke Evie , Jonkers Ilse , Oei Edwin , Bierma-Zeinstra Sita M.A. , Lories Rik , van Middelkoop Marienke , Clockaerts Stefan 
Published: April 2023

Objective To investigate the characteristics of the anterior tibiotalar fat pad (ATFP) in the ankle joint in a population of patients 1 year after an ankle sprain and its correlation with systemic factors and local articular pathology. Design The study is a secondary analysis of an observational case-control study. We included 206 patients who were followed 6-12 months after ankle sprain. T1 MRI scans were assessed for signal intensity and area of ATFP by mapping the fat pad using dedicated imaging software (Mimics 18.0). Quantitative values of intensity and area were generated. Linear regression analysis was used to examine the association between both local and systemic factors and the ATFP. Variables with a P value <0.2 were entered in 5 stepwise multivariate models: (1) age-sex-body mass index (BMI); (2) anamnesis; (3) physical examination; (4) radiographic findings; and (5) MRI findings. Predictors in these separate models were entered in the final model. Results The final multivariate model showed a significant positive association between age ( P = 0.04; 95% confidence interval [CI] = 1.13 ± 1.06), BMI ( P = 0.05; 95% CI = 3.61 ± 3.53), and sex ( P < 0.01; 95% CI = −49.26 ± 30.04) with T1 intensity. The final model also showed a significant negative association between age ( P < 0.01; 95% CI = −0.57 ± 0.34), diffuse cartilage loss in the lateral talus ( P = 0.03; 95% CI = −0.71 ± 0.63), and Kellgren and Lawrence score in the tibiotalar joint ( P < 0.01; 95%CI = −21.61 ± 7.24) and ATFP area. A positive association was found between BMI ( P < 0.01; 95% CI = 2.25 ± 1.15) and ATFP area. Conclusion This study demonstrates a correlation between ATFP and both systemic factors and local pathology in the ankle joint.
Observational Study Examining Kidney Transplantation Outcomes Following Donation From Individuals That Died of Drug Toxicity in British Columbia, Canada
Authors: Xie Max Wenheng , Kennan Sean Patrick , Slaunwhite Amanda , Rose Caren 
Published: April 2023

Background: The illicit drug toxicity (overdose) crisis has worsened across Canada, between 2016 and 2021 more than 28 000 individuals have died of drug toxicity. Organ donation from persons who experience drug toxicity death has increased in recent years. Objective: This study examines whether graft loss after kidney transplantation differed by donor cause of death. Design: Retrospective cohort. Setting: Provincial transplant program of British Columbia, Canada. Patients: Transplant recipients who received kidney transplantation from deceased donors aged 12 to 70 years between 2013 and 2019 (N = 1012). Measurements: Transplant recipient all cause graft loss (graft loss due to any cause including death) was compared by donor cause of death from drug toxicity or other. Methods: Five-year Kaplan-Meier estimates of all-cause graft survival, and 3-year complete as well as stratified inverse probability of treatment weighted Cox proportional hazards models were conducted. Results: Drug toxicity death donors donated to 25% (252/1012) of kidney transplantations. Drug toxicity death donors were more likely to be young, white, males, with fewer comorbidities such as diabetes or hypertension but were more likely to have a terminal serum creatinine ≥1.5 mg/dL or be hepatitis C virus (HCV) positive. Unadjusted 5-year estimate of all-cause graft survival was 97% for recipients of drug toxicity donor kidneys and 83% for recipients of non-drug toxicity donor kidneys ( P < .001). Recipients of drug toxicity death donor kidneys had decreased risk of all cause graft loss compared to recipients of non-drug toxicity death donor kidneys (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.12-0.77, P = .012). This is primarily due to the reduced risk of all-cause graft loss for recipients of younger (≤35 years) drug toxicity death donor kidneys (HR: 0.05, 95% CI: 0.00-0.55, P = .015). Limitations: Potential selection bias, potential unmeasured confounding. Conclusions: Donation after drug toxicity death is safe and should be considered more broadly to increase deceased donor kidney donation.
Determining the Time Required to Achieve Clinically Significant Outcomes on the PROMIS Upper Extremity Questionnaire After Arthroscopic Rotator Cuff Repair
Authors: Polce Evan M. , Vadhera Amar S. , Fu Michael C. , Singh Harsh , Haunschild Eric D. , Garrigues Grant E. , Yanke Adam B. , Forsythe Brian , Cole Brian J. , Verma Nikhil N. 
Published: April 2023

Background: Clinically significant outcome (CSO) thresholds for the Patient-Reported Outcome Measurement Information System–Upper Extremity (PROMIS–UE) score have been previously defined after arthroscopic rotator cuff repair (RCR). However, the time required to achieve CSOs for the PROMIS–UE score is unknown. Purpose: To (1) determine the time required to achieve the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and Patient Acceptable Symptom State (PASS) score thresholds after RCR for the PROMIS–UE questionnaire and (2) identify patient factors associated with earlier or delayed achievement of these clinical benchmarks. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively maintained institutional database was retrospectively reviewed for consecutive patients who underwent RCR between January 2018 and January 2019. Patients were included if they completed the PROMIS–UE questionnaire both preoperatively and at standardized postoperative time intervals: 5 to 7 months (6-month time point), 11 to 13 months (1-year time point), and ≥23 months (2-year time point). Kaplan-Meier survival curves with interval censoring were used to define the cumulative percentage of patients who achieved the MCID, SCB, and PASS. Patient variables associated with earlier or delayed achievement of the MCID, SCB, and PASS were determined using Weibull parametric survival regression analysis. Results: Included were 105 patients undergoing RCR (age, 57.3 ± 10.3 years; body mass index, 31.5 ± 6.1 kg/m2). By 2-year follow-up, the cumulative percentage of patients achieving the MCID, SCB, and PASS was 86.7%, 76.2%, and 74.3%, respectively. The mean time required to reach the MCID, SCB, and PASS score thresholds was 9.5 ± 3.8, 10.3 ± 4.4, and 9.8 ± 4.6 months, respectively. Factors associated with delayed achievement of CSOs included greater baseline PROMIS–UE score (MCID and SCB) and workers’ compensation insurance (PASS). Greater baseline PROMIS–UE scores were associated with earlier achievement of the PASS. Conclusion: Most patients achieved CSOs for the PROMIS–UE within 12 months of RCR. Patient-specific factors found to be associated with earlier or delayed achievement of CSOs can be used to inform patient discussions on the expected timeline for recovery after RCR.