bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines
Authors: Bücke Philipp , Jung Simon , Kaesmacher Johannes , Goeldlin Martina B , Horvath Thomas , Prange Ulrike , Beyeler Morin , Fischer Urs , Arnold Marcel , Seiffge David J , Meinel Thomas R 
Published: May 2024

Introduction: This study aimed to report the safety and efficacy of off-label intravenous thrombolysis (IVT) with alteplase after sequentially liberalizing our institutional guidelines allowing IVT for patients under direct oral anticoagulants (DOACs) regardless of plasma levels, time of last intake, and without prior anticoagulation reversal therapy. Patients and methods: We utilized the target-trial methodology to emulate hypothetical criteria of a randomized controlled trial in our prospective stroke registry. Consecutive DOAC patients (06/2021–11/2023) otherwise qualifying for IVT were included. Safety and efficacy outcomes (symptomatic intracranial hemorrhage [ICH], any radiological ICH, major bleeding, 90-day mortality, 90-day good functional outcome [mRS 0–2 or return to baseline]) were assessed using inverse-probability-weighted regression-adjustment comparing patients with versus without IVT. Results: Ninety eight patients fulfilled the target-trial criteria. IVT was given in 49/98 (50%) patients at a median of 178 (interquartile range 134–285) min after symptom onset with median DOAC plasma level of 77 ng/ml (15 patients had plasma levels > 100 ng/ml; 25/49 [51%] were treated within 12 h after last DOAC ingestion). Endovascular therapy was more frequent in patients without IVT (73% vs 33%). Symptomatic ICH occurred in 0/49 patients receiving IVT and 2/49 patients without IVT (adjusted difference −2.5%; 95% CI −5.9 to 0.8). The rates of any radiological ICH were comparable. Patients receiving IVT were more likely to have good functional outcomes. Discussion and conclusion: After liberalizing our approach for IVT regardless of recent DOAC intake, we did not experience any safety concerns. The association of IVT with better functional outcomes warrants prospective randomized controlled trials.
Post-Overdose Extended-Release Buprenorphine Initiation Facilitated by a Partnership Between Emergency Medical Services and an Outpatient Substance Use Disorder Observation Unit
Authors: Taylor Jessica L. , Gott Jacqueline , Weisenthal Karrin , Colicchio Paige , Dyer Sophia , Komaromy Miriam S. 
Published: May 2024

Background: People who experience a nonfatal opioid overdose and receive naloxone are at high risk of subsequent overdose death but experience gaps in access to medications for opioid use disorder. The immediate post-naloxone period offers an opportunity for buprenorphine initiation. Limited data indicate that buprenorphine administration by emergency medical services (EMS) after naloxone overdose reversal is safe and feasible. We describe a case in which a partnership between a low-barrier substance use disorder (SUD) observation unit and EMS allowed for buprenorphine initiation with extended-release injectable buprenorphine after naloxone overdose reversal. Case: A man in his 40’s with severe opioid use disorder and numerous prior opioid overdoses experienced overdose in the community. EMS was activated and he was successfully resuscitated with intranasal naloxone, administered by bystanders and EMS. He declined emergency department (ED) transport and consented to transport to a 24/7 SUD observation unit. The patient elected to start buprenorphine due to barriers attending opioid treatment programs daily. His largest barrier was unsheltered homelessness. His severe opioid withdrawal symptoms were successfully treated with 16/4 mg sublingual buprenorphine/naloxone and 300 mg extended-release injectable buprenorphine (XR-buprenorphine), without precipitated withdrawal. Two weeks later, he reported no interval fentanyl use. Discussion: We describe the case of a patient successfully initiated onto XR-buprenorphine in the immediate post-naloxone period via a partnership between an outpatient low-barrier addiction programs and EMS. Such partnerships offer promise in expanding buprenorphine access and medication choice, particularly for the high-risk population of patients who decline ED transport.
Deep PIM kinase substrate profiling reveals new rational cotherapeutic strategies for acute myeloid leukemia
Authors: Joglekar Tejashree , Chin Alexander , Voskanian-Kordi Alin , Baek Seungchul , Raja Azim , Rege Apurv , Huang Weiliang , Kane Maureen , Laiho Marikki , Webb Thomas R. , Fan Xiaoxuan , Rubenstein Michael , Bieberich Charles J. , Li Xiang 
Published: May 2024

Abstract
Provirus integration site for Moloney murine leukemia virus (PIM) family serine/threonine kinases perform protumorigenic functions in hematologic malignancies and solid tumors by phosphorylating substrates involved in tumor metabolism, cell survival, metastasis, inflammation, and immune cell invasion. However, a comprehensive understanding of PIM kinase functions is currently lacking. Multiple small-molecule PIM kinase inhibitors are currently being evaluated as cotherapeutics in patients with cancer. To further illuminate PIM kinase functions in cancer, we deeply profiled PIM1 substrates using the reverse in-gel kinase assay to identify downstream cellular processes targetable with small molecules. Pathway analyses of putative PIM substrates nominated RNA splicing and ribosomal RNA (rRNA) processing as PIM-regulated cellular processes. PIM inhibition elicited reproducible splicing changes in PIM-inhibitor–responsive acute myeloid leukemia (AML) cell lines. PIM inhibitors synergized with splicing modulators targeting splicing factor 3b subunit 1 (SF3B1) and serine-arginine protein kinase 1 (SRPK1) to kill AML cells. PIM inhibition also altered rRNA processing, and PIM inhibitors synergized with an RNA polymerase I inhibitor to kill AML cells and block AML tumor growth. These data demonstrate that deep kinase substrate knowledge can illuminate unappreciated kinase functions, nominating synergistic cotherapeutic strategies. This approach may expand the cotherapeutic armamentarium to overcome kinase inhibitor–resistant disease that limits durable responses in malignant disease.
Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry
Authors: Brink Mirian , Huisman Francien , Meeuwes Frederik O. , van der Poel Marjolein W. M. , Kersten Marie José , Wondergem Mariëlle , Böhmer Lara , Woei-A-Jin F. J. Sherida H. , Visser Otto , Oostvogels Rimke , Jansen Patty M. , Diepstra Arjan , Snijders Tjeerd J. F. , Huls Gerwin , Vermaat Joost S. P. , Plattel Wouter J. , Nijland Marcel 
Published: May 2024

Abstract
Optimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK–) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK– ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% received salvage chemotherapy, 20% received brentuximab vedotin (BV), and 36% received other treatment. In third-line treatment, BV was most commonly used (38%). ORR after second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. The risk of second relapse was negatively affected by early relapse (&lt;12 months after diagnosis), whereas BV reduced this risk compared with salvage chemotherapy. Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for patients with R/R T-NHL treated with BV compared with patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for patients with R/R T-NHL is challenged.
The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas
Authors: Bhansali Rahul S. , Ellin Fredrik , Relander Thomas , Cao Miao , Li Wenrui , Long Qi , Ganesan Nivetha , Stuver Robert , Horwitz Steven M. , Wudhikarn Kitsada , Hwang Steven R. , Bennani N. Nora , Chavez Julio , Sokol Lubomir , Saeed Hayder , Duan Frank , Porcu Pierluigi , Pullarkat Priyanka , Mehta-Shah Neha , Zain Jasmine M. , Ruiz Miguel , Brammer Jonathan E. , Prakash Rishab , Iyer Swaminathan P. , Olszewski Adam J. , Major Ajay , Riedell Peter A. , Smith Sonali M. , Goldin Caroline , Haverkos Bradley , Hu Bei , Zhuang Tony Z. , Allen Pamela B. , Toama Wael , Janakiram Murali , Brooks Taylor R. , Jagadeesh Deepa , Hariharan Nisha , Goodman Aaron M. , Hartman Gabrielle , Ghione Paola , Fayyaz Fatima , Rhodes Joanna M. , Chong Elise A. , Gerson James N. , Landsburg Daniel J. , Nasta Sunita D. , Schuster Stephen J. , Svoboda Jakub , Jerkeman Mats , Barta Stefan K. 
Published: May 2024

Abstract
Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse–enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.
Protein features fusion using attributed network embedding for predicting protein-protein interaction
Authors: Cao Mei-Yuan , Zainudin Suhaila , Daud Kauthar Mohd 
Published: May 2024

Abstract
Background
Protein-protein interactions (PPIs) hold significant importance in biology, with precise PPI prediction as a pivotal factor in comprehending cellular processes and facilitating drug design. However, experimental determination of PPIs is laborious, time-consuming, and often constrained by technical limitations.

Methods
We introduce a new node representation method based on initial information fusion, called FFANE, which amalgamates PPI networks and protein sequence data to enhance the precision of PPIs’ prediction. A Gaussian kernel similarity matrix is initially established by leveraging protein structural resemblances. Concurrently, protein sequence similarities are gauged using the Levenshtein distance, enabling the capture of diverse protein attributes. Subsequently, to construct an initial information matrix, these two feature matrices are merged by employing weighted fusion to achieve an organic amalgamation of structural and sequence details. To gain a more profound understanding of the amalgamated features, a Stacked Autoencoder (SAE) is employed for encoding learning, thereby yielding more representative feature representations. Ultimately, classification models are trained to predict PPIs by using the well-learned fusion feature.

Results
When employing 5-fold cross-validation experiments on SVM, our proposed method achieved average accuracies of 94.28%, 97.69%, and 84.05% in terms of Saccharomyces cerevisiae, Homo sapiens, and Helicobacter pylori datasets, respectively.

Conclusion
Experimental findings across various authentic datasets validate the efficacy and superiority of this fusion feature representation approach, underscoring its potential value in bioinformatics.
Genomic regions, candidate genes, and pleiotropic variants associated with physiological and anatomical indicators of heat stress response in lactating sows
Authors: de Oliveira Letícia Fernanda , Veroneze Renata , Sousa Katiene Régia Silva , Mulim Henrique A. , Araujo André Campelo , Huang Yijian , Johnson Jay S. , Brito Luiz F. 
Published: May 2024

Abstract
Background
Heat stress (HS) poses significant threats to the sustainability of livestock production. Genetically improving heat tolerance could enhance animal welfare and minimize production losses during HS events. Measuring phenotypic indicators of HS response and understanding their genetic background are crucial steps to optimize breeding schemes for improved climatic resilience. The identification of genomic regions and candidate genes influencing the traits of interest, including variants with pleiotropic effects, enables the refinement of genotyping panels used to perform genomic prediction of breeding values and contributes to unraveling the biological mechanisms influencing heat stress response. Therefore, the main objectives of this study were to identify genomic regions, candidate genes, and potential pleiotropic variants significantly associated with indicators of HS response in lactating sows using imputed whole-genome sequence (WGS) data. Phenotypic records for 18 traits and genomic information from 1,645 lactating sows were available for the study. The genotypes from the PorcineSNP50K panel containing 50,703 single nucleotide polymorphisms (SNPs) were imputed to WGS and after quality control, 1,622 animals and 7,065,922 SNPs were included in the analyses.

Results
A total of 1,388 unique SNPs located on sixteen chromosomes were found to be associated with 11 traits. Twenty gene ontology terms and 11 biological pathways were shown to be associated with variability in ear skin temperature, shoulder skin temperature, rump skin temperature, tail skin temperature, respiration rate, panting score, vaginal temperature automatically measured every 10 min, vaginal temperature measured at 0800 h, hair density score, body condition score, and ear area. Seven, five, six, two, seven, 15, and 14 genes with potential pleiotropic effects were identified for indicators of skin temperature, vaginal temperature, animal temperature, respiration rate, thermoregulatory traits, anatomical traits, and all traits, respectively.

Conclusions
Physiological and anatomical indicators of HS response in lactating sows are heritable but highly polygenic. The candidate genes found are associated with important gene ontology terms and biological pathways related to heat shock protein activities, immune response, and cellular oxidative stress. Many of the candidate genes with pleiotropic effects are involved in catalytic activities to reduce cell damage from oxidative stress and cellular mechanisms related to immune response.
Comprehensive identification of maize ZmE2F transcription factors and the positive role of ZmE2F6 in response to drought stress
Authors: Cao Yang , Wang Kexin , Lu Fengzhong , Li Qi , Yang Qingqing , Liu Bingliang , Muhammad Hayderbinkhalid , Wang Yingge , Fu Fengling , Li Wanchen , Yu Haoqiang 
Published: May 2024

Abstract
Background
The early 2 factor (E2F) family is characterized as a kind of transcription factor that plays an important role in cell division, DNA damage repair, and cell size regulation. However, its stress response has not been well revealed.

Results
In this study, ZmE2F members were comprehensively identified in the maize genome, and 21 ZmE2F genes were identified, including eight E2F subclade members, seven DEL subfamily genes, and six DP genes. All ZmE2F proteins possessed the DNA-binding domain (DBD) characterized by conserved motif 1 with the RRIYD sequence. The ZmE2F genes were unevenly distributed on eight maize chromosomes, showed diversity in gene structure, expanded by gene duplication, and contained abundant stress-responsive elements in their promoter regions. Subsequently, the ZmE2F6 gene was cloned and functionally verified in drought response. The results showed that the ZmE2F6 protein interacted with ZmPP2C26, localized in the nucleus, and responded to drought treatment. The overexpression of ZmE2F6 enhanced drought tolerance in transgenic Arabidopsis with longer root length, higher survival rate, and biomass by upregulating stress-related gene transcription.

Conclusions
This study provides novel insights into a greater understanding and functional study of the E2F family in the stress response.
SEEI: spherical evolution with feedback mechanism for identifying epistatic interactions
Authors: Tang De-yu , Mao Yi-jun , Zhao Jie , Yang Jin , Li Shi-yin , Ren Fu-xiang , Zheng Junxi 
Published: May 2024

Abstract
Background
Detecting epistatic interactions (EIs) involves the exploration of associations among single nucleotide polymorphisms (SNPs) and complex diseases, which is an important task in genome-wide association studies. The EI detection problem is dependent on epistasis models and corresponding optimization methods. Although various models and methods have been proposed to detect EIs, identifying EIs efficiently and accurately is still a challenge.

Results
Here, we propose a linear mixed statistical epistasis model (LMSE) and a spherical evolution approach with a feedback mechanism (named SEEI). The LMSE model expands the existing single epistasis models such as LR-Score, K2-Score, Mutual information, and Gini index. The SEEI includes an adaptive spherical search strategy and population updating strategy, which ensures that the algorithm is not easily trapped in local optima. We analyzed the performances of 8 random disease models, 12 disease models with marginal effects, 30 disease models without marginal effects, and 10 high-order disease models. The 60 simulated disease models and a real breast cancer dataset were used to evaluate eight algorithms (SEEI, EACO, EpiACO, FDHEIW, MP-HS-DHSI, NHSA-DHSC, SNPHarvester, CSE). Three evaluation criteria (pow1, pow2, pow3), a T-test, and a Friedman test were used to compare the performances of these algorithms. The results show that the SEEI algorithm (order 1, averages ranks = 13.125) outperformed the other algorithms in detecting EIs.

Conclusions
Here, we propose an LMSE model and an evolutionary computing method (SEEI) to solve the optimization problem of the LMSE model. The proposed method performed better than the other seven algorithms tested in its ability to identify EIs in genome-wide association datasets. We identified new SNP–SNP combinations in the real breast cancer dataset and verified the results. Our findings provide new insights for the diagnosis and treatment of breast cancer.
Availability and implementation: https://github.com/scutdy/SSO/blob/master/SEEI.zip.
Potential fungicidal and antiaflatoxigenic effects of cinnamon essential oils on Aspergillus flavus inhabiting the stored wheat grains
Authors: Gwad Manar M. Abdel , El-Sayed Ashraf S. A. , Abdel-Fattah Gamal M. , Abdelmoteleb Mohamed , Abdel-Fattah Ghada G. 
Published: May 2024

AbstractWheat is one of the essential crops for the human and animal nutrition, however, contamination with aflatoxigenic fungi, due to the improper storage conditions and high humidity, was the main global threats. So, preventing the growth of aflatoxigenic fungi in stored wheat grains, by using different essential oils was the main objective of this work. Aspergillus flavus EFBL-MU12 PP087400, EFBL-MU23 PP087401 and EFBL-MU36 PP087403 isolates were the most potent aflatoxins producers inhabiting wheat grains. The effect of storage conditions of wheat grains “humidity, temperature, incubation period, and pH” on growth of A. flavus, was assessed by the response surface methodology using Plackett-Burman design and FCCD. The highest yield of aflatoxins EFBL-MU12 B1 and B2 by A. flavus grown on wheat grains were 145.3 and 7.6 μg/kg, respectively, at incubation temperature 35°C, 16% moisture contents, initial pH 5.0, and incubated for 14 days. The tested oils had a powerful antifungal activity for the growth and aflatoxins production by A. flavus in a concentration-dependent manner. Among these oils, cinnamon oil had the highest fungicidal activity for A. flavus at 0.125%, with about 85-90 % reduction to the aflatoxins B1 and B2, conidial pigmentation and chitin contents on wheat grains. From the SEM analysis, cinnamon oils had the most deleterious effect on A. flavus with morphological aberrations to the conidial heads, vegetative mycelia, alteration in conidiophores identity, hyphae shrank, and winding. To emphasize the effect of the essential oils on the aflatoxins producing potency of A. flavus, the molecular expression of the aflatoxins biosynthetic genes was estimated by RT-qPCR. The molecular expression of nor-1, afLR, pKsA and afLJ genes was suppressed by 94-96%, due to cinnamon oil at 0.062% compared to the control. Conclusively, from the results, cinnamon oils followed by the peppermint oils displayed the most fungicidal activity for the growth and aflatoxins production by A. flavus grown on wheat grains.