bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 international border surveillance at Toronto’s Pearson Airport: a cohort study
Authors: Goel Vivek , Bulir David , De Prophetis Eric , Jamil Munaza , Rosella Laura C , Mertz Dominik , Regehr Cheryl , Smieja Marek 
Published: July 2021

ObjectivesThe primary objective was to estimate the positivity rate of air travellers coming to Toronto, Canada in September and October 2020, on arrival and on day 7 and day 14. The secondary objectives were to estimate the degree of risk based on country of origin and to assess knowledge and attitudes towards COVID-19 control measures and subjective well-being during the quarantine period.DesignProspective cohort of arriving international travellers.SettingToronto Pearson Airport Terminal 1, Toronto, Canada.ParticipantsParticipants of this study were passengers arriving on international flights. Inclusion criteria were those aged 18 or older who had a final destination within 100 km of the airport, spoke English or French, and provided consent. Excluded were those taking a connecting flight, had no internet access, exhibited symptoms of COVID-19 on arrival or were exempted from quarantine.Main outcome measuresPositive for SARS-CoV-2 virus on reverse transcription PCR with self-administered oral-nasal swab and general well-being using the WHO-5 Well-being Index.ResultsOf 16 361 passengers enrolled, 248 (1.5%, 95% CI 1.3% to 1.7%) tested positive. Of these, 167 (67%) were identified on arrival, 67 (27%) on day 7, and 14 (6%) on day 14. The positivity rate increased from 1% in September to 2% in October. Average well-being score declined from 19.8 (out of a maximum of 25) to 15.5 between arrival and day 7 (p<0.001).ConclusionsA single arrival test will pick up two-thirds of individuals who will become positive by day 14, with most of the rest detected on the second test on day 7. These results support strategies identified through mathematical models that a reduced quarantine combined with testing can be as effective as a 14-day quarantine.
Does admission order form design really matter? A reduction in urea blood test ordering
Authors: Mathura Pamela , Boettger Cole , Hagtvedt Reidar , Suranyi Yvonne , Kassam Narmin 
Published: July 2021

IntroductionLaboratory blood testing is one of the most high-volume medical procedures and continues to increase steadily with instances of inappropriate testing resulting in significant financial implications. Studies have suggested that the design of a standard hospital admission order form and laboratory request forms influence physician test ordering behaviour, reducing inappropriate ordering and promoting resource stewardship.Aim/methodTo redesign the standard medicine admission order form-laboratory request section to reduce inappropriate blood urea nitrogen (BUN) testing.ResultsA redesign of the standard admission order form used by general internal medicine physicians and residents in two large teaching hospitals in one health zone in Alberta, Canada led to a significant step reduction in the ordering of the BUN test on hospital admission.ConclusionsRedesigning the standard medicine admission order form-laboratory request section can have a beneficial effect on the reduction in BUN ordering altering physician ordering patterns and behaviour.
New insight on the role of liraglutide in alleviating dexamethasone-induced pancreatic cytotoxicity via improving redox status, autophagy flux, and PI3K/Akt/Nrf2 signaling
Authors: Elseady Walaa S. , Abd Ellatif Rasha A. , Estfanous Remon S. , Emam Marwa N. , Keshk Walaa A. 
Published: July 2021

Chronic glucocorticoids therapy is commonly complicated by steroid diabetes, although the underlying mechanisms are still elusive. Liraglutide, a glucagon-like peptide-1, was initially found to induce glycemic control and recently it was found to have many pleotropic effects; however, its role in pancreas remains unknown. The present study aims to estimate the protective role of liraglutide on dexamethasone-induced pancreatic cytotoxicity and hyperglycemia, highlighting the possible underlying biochemical, molecular, and cellular mechanisms. Twenty-eight male Wistar rats were involved in this study and were randomly divided into four groups. Group III and IV were treated with 1 mg/kg dexamethasone daily for 10 days. Group II and IV were treated with liraglutide in a dose of 0.8 mg/kg per day for 2 weeks. Pancreatic caspase-9, nuclear factor erythroid 2–related factor 2 (Nrf2), phospho-protein kinase-B (pAkt), and sequestrome 1 (p62) levels were assessed by immunoassay. Moreover, phosphoinositide 3-kinase (PI3K) expression by real-time PCR, microtubule-associated protein light chain 3 (LC3B) expression by immunohistochemistry, glycemic status, β-cell function by homoeostasis model assessment (HOMA) β index, and pancreatic redox status were assessed. Liraglutide improved blood glucose level, β-cell function, pancreatic caspase-9 level, redox status, and autophagy. Additionally, it increased pancreatic PI3K, pAkt, and Nrf2 levels. Moreover, preservation of pancreatic histological and the ultrastructural morphological features of β- and α-cells were observed. In conclusion, liraglutide protected against dexamethasone-induced pancreatic injury and hyperglycemia and decelerated the progression towards steroid diabetes via activating PI3K/Akt/Nrf2 signaling and autophagy flux pathways.
Machine Learning Based Assembly of Fragments of Ancient Papyrus
Authors: Abitbol Roy , Shimshoni Ilan , Ben-Dov Jonathan 
Published: July 2021

The task of assembling fragments in a puzzle-like manner into a composite picture plays a significant role in the field of archaeology as it supports researchers in their attempt to reconstruct historic artifacts. In this article, we propose a method for matching and assembling pairs of ancient papyrus fragments containing mostly unknown scriptures.
Papyrus paper is manufactured from papyrus plants and therefore portrays typical thread patterns resulting from the plant’s stems. The proposed algorithm is founded on the hypothesis that these thread patterns contain unique local attributes such that nearby fragments show similar patterns reflecting the continuations of the threads. We posit that these patterns can be exploited using image processing and machine learning techniques to identify matching fragments. The algorithm and system which we present support the quick and automated classification of matching pairs of papyrus fragments as well as the geometric alignment of the pairs against each other.
The algorithm consists of a series of steps and is based on deep-learning and machine learning methods. The first step is to deconstruct the problem of matching fragments into a smaller problem of finding thread continuation matches in local edge areas (squares) between pairs of fragments. This phase is solved using a convolutional neural network ingesting raw images of the edge areas and producing local matching scores. The result of this stage yields very high recall but low precision. Thus, we utilize these scores in order to conclude about the matching of entire fragments pairs by establishing an elaborate voting mechanism. We enhance this voting with geometric alignment techniques from which we extract additional spatial information. Eventually, we feed all the data collected from these steps into a Random Forest classifier in order to produce a higher order classifier capable of predicting whether a pair of fragments is a match.
Our algorithm was trained on a batch of fragments which was excavated from the Dead Sea caves and is dated circa the 1st century BCE. The algorithm shows excellent results on a validation set which is of a similar origin and conditions. We then tried to run the algorithm against a real-life set of fragments for which we have no prior knowledge or labeling of matches. This test batch is considered extremely challenging due to its poor condition and the small size of its fragments. Evidently, numerous researchers have tried seeking matches within this batch with very little success. Our algorithm performance on this batch was sub-optimal, returning a relatively large ratio of false positives. However, the algorithm was quite useful by eliminating 98% of the possible matches thus reducing the amount of work needed for manual inspection. Indeed, experts that reviewed the results have identified some positive matches as potentially true and referred them for further investigation.
Optimal PSA Threshold for Obtaining MRI-Fusion Biopsy in Biopsy-Naïve Patients
Authors: Wang Luke L. , Henslee Brandon L. , Sam Peter B. , LaGrange Chad A. , Boyle Shawna L. 
Published: July 2021

Objective. The study investigates the prostate-specific antigen threshold for adding targeted, software-based, magnetic resonance imaging-ultrasound fusion biopsy during a standard 12-core biopsy in biopsy-naïve patients. It secondarily explores whether the targeted biopsy is necessary in setting of abnormal digital rectal examination. Methods. 260 patients with suspected localized prostate cancer with no prior biopsy underwent prostate magnetic resonance imaging and were found to have Prostate Imaging Reporting and Data System score

≥

3 lesion(s). All 260 patients underwent standard 12-core biopsy and targeted biopsy during the same session. Clinically significant cancer was Gleason

≥

3 + 4. Results. Percentages of patients with prostate-specific antigen 0–1.99, 2–3.99, 4–4.99, 5–5.99, 6–9.99, and

≥

10 were 3.0%, 4.7%, 20.8%, 16.9%, 37.7%, and 16.9%, respectively. Cumulative frequency of clinically significant prostate cancer increased with the addition of targeted biopsy compared with standard biopsy alone across all prostate-specific antigen ranges. The difference in clinically significant cancer detection between targeted plus standard biopsy compared to standard biopsy alone becomes statistically significant at prostate-specific antigen >4.3 (

p
=
0.031

). At this threshold, combination biopsy detected 20 clinically significant prostate cancers, while standard detected 14 with 88% sensitivity and 20% specificity. Excluding targeted biopsy in setting of a positive digital rectal exam would save 12.3% magnetic resonance imaging and miss 1.8% clinically significant cancers in our cohort. Conclusions. In biopsy-naïve patients, at prostate-specific antigen >4.3, there is a significant increase in clinically significant prostate cancer detection when targeted biopsy is added to standard biopsy. Obtaining standard biopsy alone in patients with abnormal digital rectal examinations would miss 1.8% clinically significant cancers in our cohort.
Nursing Observation on the Clinical Efficacy and Toxicity of Lobaplatin Compared with Cisplatin in the Treatment of Locally Advanced Hypopharyngeal Carcinoma Based on Intelligent CT Imaging
Authors: Li Yunyan , Yang Guangrun , Li Mengmeng , Tong Xu 
Published: July 2021

With the acceleration of people’s life rhythm, the incidence of hypopharyngeal cancer has generally increased. This study mainly explores the clinical efficacy and toxicity of lobaplatin compared with cisplatin in the treatment of locally advanced hypopharyngeal carcinoma based on intelligent CT imaging. Group A received lobaplatin combined with docetaxel induction chemotherapy for 2 cycles after cisplatin combined with intensity-modulated radiotherapy. Lobaplatin was added to the patient, then, 200 ml of 5% glucose was added, and the patient was injected intravenously for 1.8 hours. After 2 cycles of induction chemotherapy, simultaneous lobaplatin chemotherapy was performed every week for 5 weeks (10 mg/week), and the efficacy was evaluated after 4 consecutive courses of treatment. Group B received cisplatin combined with docetaxel induction chemotherapy after 2 cycles of cisplatin combined with intensity-modulated radiotherapy. Group C was the control group and was not treated with cisplatin or docetaxel. Stomach protection treatment was given in time throughout the treatment process. All patients underwent normal CT (NCCT) and enhanced CT (CECT) examinations before treatment. We extracted 5 mm plain scan CTQNCCT and enhanced CT (CECT) digital DICOM images from the PACS system for omics feature selection. Toxic and side effects are rated in different degrees according to the evaluation criteria of the National Cancer Institute (NCD) common adverse events. Blood routine and liver and kidney function tests were checked every week, and the medication was stopped immediately if there is a serious reaction. In addition, in vitro cell culture was set up to test the inhibitory effect of cisplatin and lobaplatin on the proliferation of cancer cells. The incidence of digestive tract reaction was 13.0% in the A plan group and 58.3% in the B plan group. The A group was lower than the B group, and the difference was statistically significant (

P
=
0.001

< 0.05). Compared with cisplatin, lobaplatin has a milder gastrointestinal reaction, and there is no common hepatic and renal toxicity of cisplatin. This study is helpful to provide guidance for the clinical efficacy of locally advanced hypopharyngeal cancer treatment.
AP-2α–Mediated Activation of E2F and EZH2 Drives Melanoma Metastasis
Authors: White Jeffrey R. , Thompson Dakota T. , Koch Kelsey E. , Kiriazov Boris S. , Beck Anna C. , van der Heide Dana M. , Grimm Benjamin G. , Kulak Mikhail V. , Weigel Ronald J. 
Published: July 2021

Abstract

In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, is controversial as some findings have suggested tumor suppressor activity while other studies have shown high TFAP2A expression in node-positive melanoma associated with poor prognosis. Here we demonstrate that AP-2α facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2. A BioID screen found that AP-2α interacts with members of the nucleosome remodeling and deacetylase (NuRD) complex. Loss of AP-2α removed activating chromatin marks in the promoters of EZH2 and other E2F target genes through activation of the NuRD repression complex. In melanoma cells, treatment with tazemetostat, an FDA-approved and highly specific EZH2 inhibitor, substantially reduced anchorage-independent colony formation and demonstrated heritable antimetastatic effects, which were dependent on AP-2α. Single-cell RNA sequencing analysis of a metastatic melanoma mouse model revealed hyperexpansion of Tfap2aHigh/E2F-activated cell populations in transformed melanoma relative to progenitor melanocyte stem cells. These findings demonstrate that melanoma metastasis is driven by the AP-2α/EZH2 pathway and suggest that AP-2α expression can be used as a biomarker to predict responsiveness to EZH2 inhibitors for the treatment of advanced melanomas.

Significance:
AP-2α drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors.
Imaging Early Response to Checkpoint Inhibition
Authors: Cullen Quinlan , Keshari Kayvan R. 
Published: July 2021

Abstract
Immune checkpoint blockade therapy has achieved remarkable clinical success, but these promising results have been limited to a minority of patients. Thus far, efforts to establish a predictive biomarker or accurately assess early response to treatment have been fruitless. In this issue of Cancer Research, Saida and colleagues utilized advanced molecular imaging modalities to assess changes in the tumor microenvironment that correlate with tumor response to immune checkpoint blockade therapy in vivo. This study suggests a combination of imaging biomarkers with potential for delineating clinical response to immunotherapy.
See related article by Saida et al., p. 3693
Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P. , Chen Gregory M. , Allen David Hottman , Zhang Ruitao , Xu Jason , Chen Chia-Hui , Hu Yuxuan , Tasian Sarah K. , Tan Kai 
Published: July 2021

Abstract

Purpose:
Systems biology approaches can identify critical targets in complex cancer signaling networks to inform new therapy combinations that may overcome conventional treatment resistance.

Experimental Design:
We performed integrated analysis of 1,046 childhood B-ALL cases and developed a data-driven network controllability-based approach to identify synergistic key regulator targets in Philadelphia chromosome–like B-acute lymphoblastic leukemia (Ph-like B-ALL), a common high-risk leukemia subtype associated with hyperactive signal transduction and chemoresistance.

Results:
We identified 14 dysregulated network nodes in Ph-like ALL involved in aberrant JAK/STAT, Ras/MAPK, and apoptosis pathways and other critical processes. Genetic cotargeting of the synergistic key regulator pair STAT5B and BCL2-associated athanogene 1 (BAG1) significantly reduced leukemia cell viability in vitro. Pharmacologic inhibition with dual small molecule inhibitor therapy targeting this pair of key nodes further demonstrated enhanced antileukemia efficacy of combining the BCL-2 inhibitor venetoclax with the tyrosine kinase inhibitors ruxolitinib or dasatinib in vitro in human Ph-like ALL cell lines and in vivo in multiple childhood Ph-like ALL patient-derived xenograft models. Consistent with network controllability theory, co-inhibitor treatment also shifted the transcriptomic state of Ph-like ALL cells to become less like kinase-activated BCR-ABL1–rearranged (Ph+) B-ALL and more similar to prognostically favorable childhood B-ALL subtypes.

Conclusions:
Our study represents a powerful conceptual framework for combinatorial drug discovery based on systematic interrogation of synergistic vulnerability pathways with pharmacologic inhibitor validation in preclinical human leukemia models.
Abstract 1009: Combination Niraparib and Metformin synergistically inhibits endometrial cancer cell growth and metastasis
Authors: Gan Qiyu , Cheng Jingxin , Chen Rui , Bie Yachun , Wang Guozeng , Chang Linlin 
Published: July 2021

Abstract
Backgroud Endometrial Carcinoma (EC) is the most common gynecological malignancy among women. Even with a favorable prognosis, cure is still elusive with recurrence, chemotherapy resistance and poor outcome. Poly ADP-ribose polymerase inhibitors (PARPi) have been emerged as promising cancer therapeutics, especially for tumors with deficient homologous recombination (HR) repair. Niraparib for example is well established for ovarian cancer. Metformin, an antidiabetic drug, has been reported to be a new adjunctive strategy for different cancer types, including endometrial cancer. While the effect of Niraparib for EC as monotherapy or in combination with Metformin is still unknown.
Method Here we used two types of endometrial cancer cell lines Ishikawa and HEC-1B to detect the effect of Niraparib as monotherapy or in combination with Metformin on cell proliferation, apoptosis, invasion and metastasis. The 50% Inhibitory concentration (IC50) was assessed, and transwell, Annexin V staining, clonogenic assay were applied. Also, western blotting was performed to determine the expression of proteins involved, such as Bax, Caspase-3, Bcl-2, p-AKT, RAD51, γ-H2AX and so on.
Results Our study demonstrated that Niraparib inhibited endometrial cell growth in both Ishikawa and HEC-1B cell lines with IC50 0.024umol/L and 0.127umol/L separately. The invasion and metastasis were also suppressed. Annexin V staining showed that Niraparib could significantly promoted apoptosis, which was largely enhanced by Metformin combination therapy (p&lt;0.01). Accordingly, the apoptosis-related proteins Bax, Caspase-3, and DNA damage-related protein RAD51, γ-H2AX were increased, while proliferation-related protein p-AKT, anti-apoptosis-related protein Bcl-2, invasion and metastasis-related protein E-cadherin were decreased, as confirmed by western blotting.
Conclusion Niraparib shows the anticancer effect on endometrial cancer cell through inhibiting the cell viability, metastasis and inducing apoptosis, which is significantly enhanced by the combination with Metformin. Our results provide preclinical evidence that the combination of these well-establised drugs may warrant further clinical investigation for endometrial cancer treatment.
Citation Format: Qiyu Gan, Jingxin Cheng, Rui Chen, Yachun Bie, Guozeng Wang, Linlin Chang. Combination Niraparib and Metformin synergistically inhibits endometrial cancer cell growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1009.
Abstract 1015: mTOR inhibitor induces non-apoptotic, autophagy dependent cell death (ADCD) in TP53 mutant HNSCC
Authors: Alam Md Maksudul , Fermin Janmaris Marin , Spiller Patrick T. , Dorr Channing , Rong Xiaohua , Medlin Tara-Moore , Khandelwal Alok R. , Nathan Cherie-Ann 
Published: July 2021

Abstract
TP53 is the most frequently mutated gene in Head and Neck Squamous Cell Carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis. A phase II multi-institutional clinical trial, determined that, adjuvant therapy with an mTOR inhibitor significantly increased 2-year progression free survival (PFS) in patients with p53 mutant tumors. Previous studies have shown that mutant p53 causes sustained activation of PI3K/AKT/mTOR pathway in cancer. We investigated the mechanism by which the mTOR inhibitor CCI-779 inhibits cell growth of TP53 mutant HNSCC in vitro. HPV-negative HNSCC cell lines harboring TP53 mutations at different positions were treated with CCI-779.CCI-779 significantly reduced cell viability and colony forming ability of all the cell lines tested. CCI-779 did not induce apoptosis or cell cycle arrest in these cells. However, the reduction in cell viability was associated with increase in autophagy as demonstrated by increased levels of LC3-II. The autophagy inhibitors, 3-methyl adenine (3-MA) and ULK-101 restored the cell viability by inhibiting CCI-779 induced autophagy. Therefore, we postulate that CCI-779 induces nonapototic autophagy dependent cell death (ADCD) in HPV-negative TP53 mutant HNSCC cell lines. CCI-779 induced autophagy is accompanied by increased level of ULK1 and Beclin1 as well as increased phosphorylation of ULK1 at Serine 555. However, ULK101 (ULK1 inhibitor) and 3-MA (PI3K inhibitor) when combined with CCI-779 reduced the level of both total and phosphorylated levels of ULK1, which resulted in inhibition of autophagy and improved cell viability. However, combination of CCI-779 and bafilomycin A1 treatment showed increased level of LC3-II, ULK1 and phospho-ULK1 (S555) with concomitant decrease in cell viability. Our data suggests that rapalog induces ADCD by facilitating autophagy initiation through the stabilization and activation of ULK1. Moreover our data demonstrated that CCI-779 mediated activation of ULK1 is associated with down regulation of mTORC1 but not mTORC2 signaling. This is a novel mechanism of how rapalogues induce ADCD through the stabilization/activation of ULK1 in HPV-negative TP53 mutant HNSCC cells. Together these data highlight the importance of how mTORi can be used to accelerate tumor cell death in HPV-negative TP53 mutant HNSCC.
Citation Format: Md Maksudul Alam, Janmaris Marin Fermin, Patrick T. Spiller, Channing Dorr, Xiaohua Rong, Tara-Moore Medlin, Alok R. Khandelwal, Cherie-Ann Nathan. mTOR inhibitor induces non-apoptotic, autophagy dependent cell death (ADCD) in TP53 mutant HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1015.