bluuebunny/crossref_metadata_2025_split huggingface dataset:
The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy
Authors: Wang Hua , Zhou Xiaowen , Li Chenbei , Yan Shuxiang , Feng Chengyao , He Jieyu , Li Zhihong , Tu Chao 
Published: October 2022

AbstractPediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements and considerations, treatment strategies and drugs for pediatric cancers have been so far scarcely studied. It is well known that tumor cells tend to progressively evade cell death pathways, which is known as apoptosis resistance, one of the hallmarks of cancer, dominating tumor drug resistance. Recently, treatments targeting nonapoptotic cell death have drawn great attention. Pyroptosis, a newly specialized form of cell death, acts as a critical physiological regulator in inflammatory reaction, cell development, tissue homeostasis and stress response. The action in different forms of pyroptosis is of great significance in the therapy of pediatric cancers. Pyroptosis could be induced and consequently modulate tumorigenesis, progression, and metastasis if treated with local or systemic therapies. However, excessive or uncontrolled cell death might lead to tissue damage, acute inflammation, or even cytokine release syndrome, which facilitates tumor progression or recurrence. Herein, we aimed to describe the molecular mechanisms of pyroptosis, to highlight and discuss the challenges and opportunities for activating pyroptosis pathways through various oncologic therapies in multiple pediatric neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, and brain tumors.
Evaluating a tool to improve engagement and recruitment of under-served groups in trials
Authors: Morris Lydia , Dumville Jo , Treweek Shaun , Miah Nasima , Curtis Ffion , Bower Peter 
Published: October 2022

Abstract
Background
Despite substantial awareness that certain groups (e.g. ethnic minorities) are under-represented and under-served in trials, limited progress has been made in addressing this. As well as a public service and ethical duty to recruit and engage under-served groups in relevant research, importantly, there are clear scientific benefits, for example, increased generalisability.
The key aims of the current study were to explore the following: general barriers and facilitators to enhancing the recruitment of under-served groups into trials, the usability and value of a specific tool (INCLUDE Ethnicity Framework) to support engagement and recruitment of under-served groups, and ways of engaging diverse patient, public and community involvement and engagement (PCIE) groups.

Methods
Firstly, researchers completed a brief survey in relation to a specific trial in which they were involved (N = 182, 38% response rate). A second stage involved sampling survey respondents and asking them to complete the INCLUDE Ethnicity Framework and then a remote semi-structured interview (N = 15). Qualitative data were analysed using thematic analysis. Finally, we conducted a consultation process with PCIE contributors primarily to develop guidelines for discussing the INCLUDE Ethnicity Framework with PCIE representatives.

Results
Researchers recognised the importance of increasing engagement and recruitment of under-served groups within trials, but varied in their knowledge, ability and commitment to implementation in practice. The INCLUDE Ethnicity Framework was described by some as raising their awareness of how inclusion could be improved. Respondents highlighted a need for shared resources and wider structural change to facilitate such engagement. PCIE was identified, in the survey and interviews, as the most common method of trying to improve recruitment of under-served groups. However, researchers also commonly highlighted that PCIE groups were sometimes not very diverse.

Conclusions
There is a need for researchers to consider the funding and time resources required for diverse and inclusive recruitment to trials and for funders to enable this. The INCLUDE Ethnicity Framework can help to raise awareness of inclusion challenges. This study indicates that it is important to take proactive steps to involve relevant under-served groups in PCIE and practical suggestions are made to facilitate this.
Emergency department-based, nurse-initiated, serious illness conversation intervention for older adults: a protocol for a randomized controlled trial
Authors: Prachanukool Thidathit , Block Susan D. , Berry Donna , Lee Rachel S. , Rossmassler Sarah , Hasdianda Mohammad A. , Wang Wei , Sudore Rebecca , Schonberg Mara A. , Tulsky James A. , Ouchi Kei 
Published: October 2022

AbstractBackgroundVisits to the emergency department (ED) are inflection points in patients’ illness trajectories and are an underutilized setting to engage seriously ill patients in conversations about their goals of care. We developed an intervention (ED GOAL) that primes seriously ill patients to discuss their goals of care with their outpatient clinicians after leaving the ED. The aims of this study are (i) to test the impact ofED GOALadministered by trained nurses on self-reported, advance care planning (ACP) engagement after leaving the ED and (ii) to evaluate whetherED GOALincreases self-reported completion of serious illness conversation and other patient-centered outcomes.MethodsThis is a two-armed, parallel-design, single-blinded, randomized controlled trial of 120 seriously ill older adults in two academic and one community EDs in Boston, MA. Participants are English-speaking adults 50 years and older with a serious life-limiting illness with a recent ED visit. Patients with a valid MOLST (medical order for life-sustaining treatment) form or other documented goals of care within the last 3 months are excluded. We enroll the caregivers of patients with cognitive impairment. Patients are assigned to the intervention or control group using block randomization. A blinded research team member will perform outcome assessments. We will assess (i) changes in ACP engagement within 6 months and (ii) qualitative assessments of the effect ofED GOAL.DiscussionIn seriously ill older adults arriving in the ED, this randomized controlled trial will test the effects ofED GOALon patients’ self-reported ACP engagement, EMR documentation of new serious illness conversations, and improving patient-centered outcomes.Trial registrationClinicalTrials.govidentifier: NCT05209880
Insights into an NEk2 inhibitory profile of nitidine chloride by molecular docking and biological evaluation
Authors: Li Danni , Lu Jiahao , Zhang Qiying , Zhou Yuzhu , Li Long , Zhu Hua , Li Tong 
Published: October 2022

AbstractDeregulation of NEK2(NIMA-related serine/threonine 2) confers chemotherapeutic resistance to apoptosis and is closely correlated with poor prognosis in hepatocellular carcinoma (HCC). Here, we find that nanoparticles are prepared through hemisynthesis from natural nitidine chloride (NC) with enhanced antitumor activity. Nitidine chloride nanoparticle (TPGS-FA/NC) treatment show good therapy effect in Li-7 hepatocellular carcinoma cells. Additionally, molecular docking technologies are aimed at NEK2 protein (PDB ID: 6SGD) to analyze the detailed binding interactions with the potent target. NC participates in interactions with Asp159 residue. These studies advance the understanding of the modification of nitidine chloride substituent and provide useful drug design information for liver cancer treatment.
Volatile chemical composition of Octoblepharum albidum Hedw. (Bryophyta) from the Brazilian Amazon
Authors: Alves Raynon Joel Monteiro , Miranda Thyago Gonçalves , Pinheiro Rafaela Oliveira , de Souza Pinheiro Wandson Braamcamp , Andrade Eloisa Helena de Aguiar , Tavares-Martins Ana Cláudia Caldeira 
Published: October 2022

AbstractBryophytes have a variety of bioactive compounds that can be used in biotechnological processes. The objective of this study was to know the volatile chemical composition of Octoblepharum albidum Hedw. from the Amazon and investigate its association with possible bioactive effects on insects. The volatile concentrate of O. albidum was obtained by micro-scale simultaneous distillation–extraction and analyzed by gas chromatography coupled to mass spectrometry and the identification of the compounds was based on system libraries and specialized literature. Twelve organic compounds (92.44% of the total) were identified. Hexadecanoic acid, oleic acid, E-isoeugenol, 1-octen-3-ol, and stearic acid were the major compounds. Most of the compounds have already been reported from bryophytes, while others have an unprecedented occurrence in the group. All identified compounds have biological activities reported in the literature and may participate in plant defense mechanisms against insects, causing mortality or developmental inhibition. In this study, we describe for the first time the volatile chemical composition of O. albidum from Brazil and provide evidence that this species is a source of bioactive compounds. The identified compounds have been reported in the literature to cause mortality or affect the biological parameters of insects, what suggests the possibility of their usage in the formulation of bioinsecticides.
Historical records of plant-insect interactions in subarctic Finland
Authors: Zoller Leana , Knight Tiffany M. 
Published: October 2022

Abstract
Objectives
Historical ecological records document the diversity and composition of communities decades or centuries ago. They can provide a valuable benchmark for comparisons with modern communities. Historical datasets on plant-animal interactions allow for modern comparisons that examine the stability of species and interaction networks over long periods of time and in response to anthropogenic change. Here we present a curated dataset of interactions between plants and insects in subarctic Finland, generated from digitizing a historical document from the late 19th century and updating the taxonomy using currently accepted nomenclature.

Data description
The resulting dataset contains 654 records of plant-insect interactions observed during the years 1895–1900, and includes 498 unique interactions between 86 plant species and 173 insect taxa. Syrphidae, Apidae and Muscidae were the insect families involved in most interactions, and interactions were most observed with the plant species Angelica archangelica, Salix caprea, and Chaerophyllum prescottii. Interaction data are available as csv-file and provide a valuable resource on plant-insect interactions over 120 years ago in a high latitude ecosystem that is undergoing rapid climate change.
Direct sequencing of β-globin gene reveals a rare combination of two exonic and two intronic variants in a β-thalassemia major patient: a case report
Authors: Chauhan Waseem , Fatma Rafat , Zaka-ur-Rab Zeeba , Afzal Mohammad 
Published: October 2022

Abstract
Background
Due to indels in the β-globin gene, patients with β-thalassemia major exhibit a range of severity, with genotype β0β0 > β0β+ > β+β+, according to the production level of the β-globin chain. More than 300 mutations have been identified in the β-globin gene.

Case presentation
In this case study, we report a compound heterozygous condition with a rare concoction of four different variants (CD 3(T > C), CD41/42 (-CTTT), IVS II-16 (G > C), and IVS II-666 (C > T) in a single β-globin gene. A regular transfusion-dependent 4-year-old male patient from India was included in the study. Augmented direct sequencing of the β-globin gene helped reveal the presence of an unusual combination of different variants in a single gene. This patient clinically presented as β-thalassemia major and was genotypically considered as β0β+, although CD41/42(-CTTT) was the only causative/pathogenic mutation in the disease severity.

Conclusion
Although CD41/42-(CTTT) is the only pathogenic variant among the four variants, the clinical complications of such a combination of variants (pathogenic and benign) is not well understood. Intronic mutations may have the ability to modify clinical characteristics. The variants must therefore be reclassified using additional mRNA splicing and expression-based studies. Additionally, these types of combinations may have significance in studying population migration around the world.
Blood donor biobank and HLA imputation as a resource for HLA homozygous cells for therapeutic and research use
Authors: Clancy Jonna , Hyvärinen Kati , Ritari Jarmo , Wahlfors Tiina , Partanen Jukka , Koskela Satu 
Published: October 2022

Abstract
Background
Allogeneic therapeutic cells may be rejected if they express HLA alleles not found in the recipient. As finding cell donors with a full HLA match to a recipient requires vast donor pools, the use of HLA homozygous cells has been suggested as an alternative. HLA homozygous cells should be well tolerated by those who carry at least one copy of donor HLA alleles. HLA-A-B homozygotes could be valuable for HLA-matched thrombocyte products. We evaluated the feasibility of blood donor biobank and HLA imputation for the identification of potential cell donors homozygous for HLA alleles.

Methods
We imputed HLA-A, -B, -C, -DRB1, -DQA1, -DQB1 and -DPB1 alleles from genotypes of 20,737 Finnish blood donors in the Blood Service Biobank. We confirmed homozygosity by sequencing HLA alleles in 30 samples and by examining 36,161 MHC-located polymorphic DNA markers.

Results
Three hundred and seventeen individuals (1.5%), representing 41 different haplotypes, were found to be homozygous for HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 alleles. Ten most frequent haplotypes homozygous for HLA-A to -DQB1 were HLA-compatible with 49.5%, and three most frequent homozygotes to 30.4% of the Finnish population. Ten most frequent HLA-A-B homozygotes were compatible with 75.3%, and three most frequent haplotypes to 42.6% of the Finnish population. HLA homozygotes had a low level of heterozygosity in MHC-located DNA markers, in particular in HLA haplotypes enriched in Finland.

Conclusions
The present study shows that HLA imputation in a blood donor biobank of reasonable size can be used to identify HLA homozygous blood donors suitable for cell therapy, HLA-typed thrombocytes and research. The homozygotes were HLA-compatible with a large fraction of the Finnish population. Regular blood donors reported to have positive attitude to research donation appear a good option for these purposes. Differences in population frequencies of HLA haplotypes emphasize the need for population-specific collections of HLA homozygous samples.
Identification of a new way to induce differentiation of dermal fibroblasts into vascular endothelial cells
Authors: Cui XiaoLing , Wang XiaoTan , Wen Jie , Li Xiao , Li Nan , Hao XuXiao , Zhao BaoXiang , Wu Xunwei , Miao JunYing 
Published: October 2022

Abstract
Background
Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs.

Methods
In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs.

Results
Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB).

Conclusions
Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.
Unrelated cord blood transplantation vs. HLA-matched sibling transplantation for adults with B-cell acute lymphoblastic leukemia in complete remission: superior OS for patients with long-term survival
Authors: Sun Guangyu , Tang Baolin , Song Kaidi , Wu Yue , Tu Meijuan , Wan Xiang , Yao Wen , Geng Liangquan , Qiang Ping , Zhu Xiaoyu 
Published: October 2022

Abstract
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for adult acute lymphoblastic leukemia (ALL). For patients who lack a human leukocyte antigen (HLA)-matched sibling donor, unrelated cord blood (UCB) is an alternative graft option. Previous studies have focused mainly on all T- and B-cell ALL (B-ALL) patients, while data related specifically to adult B-ALL patients after UCB transplantation (UCBT) are scarce.

Methods
We retrospectively compared the outcomes of UCBT and HLA-matched sibling transplantation (MST) in the treatment of adult B-ALL patients in complete remission (CR) at our center. From June 2006 to December 2020, 156 adult B-ALL patients who achieved CR before transplantation were enrolled. The main clinical outcomes of UCBT and MST were analyzed.

Results
Hematopoietic recovery was significantly faster in MST recipients than in UCBT recipients. Higher incidences of grades II-IV and III-IV acute graft-versus host disease (aGVHD) were found in UCBT recipients (P < 0.001 and = 0.03), while a lower incidence of extensive chronic GVHD (cGVHD) was found in UCBT recipients (P < 0.001). The cumulative incidences of 2-year non-relapse mortality (NRM), 2-year relapse, 5-year disease-free survival (DFS) and 5-year GVHD-free relapse-free survival (GRFS) were comparable between MST and UCBT recipients. The overall survival (OS) during the first 700 days was similar between the MST and UCBT groups, while the OS of patients with a survival time of more than 700 days in the UCBT group was better than that in the MST group according to multivariate analysis (P = 0.03).

Conclusions
Our study shows that when treating adult B-ALL patients in CR, UCBT can achieve comparable effects as MST, may provide superior OS for patients with long-term survival, and should be considered a good alternative.
Enteric neurosphere cells injected into rectal submucosa might migrate caudorostrally to reconstitute enteric ganglia along the entire length of postnatal colon
Authors: Chen Jeng-Chang 
Published: October 2022

Abstract
Background
In enteric neural stem cell (ENSC) therapy for enteric neuropathy, the gut is ostensibly accessible via laparotomy, laparoscopy or endoscopy, whereas its elongated configuration and multilayered structures substantially complicate the targeting of ENSC delivery. This study aimed to evaluate the feasibility of ENSC delivery via trans-anal rectal submucosal injection.

Methods
ENSC transplantation was conducted in an immunologically compatible model of FVB/NCrl-Tg(Pgk1-EGFP)01Narl into FVB/N murine strain combination. Enteric neurospheres were mass-produced by the cultivation of dispersed enterocytes harvested from gestational day 14 FVB/NCrl-Tg(Pgk1-EGFP)01Narl murine fetuses. Dissociated neurosphere cells were injected into rectal submucosa of adult FVB/N mice after artificial prolapse of rectal mucosa. Ganglion reconstitution in recipients’ colon was examined by immunohistochemcal and immunofluorescence staining.

Results
Cell spreading and ganglion assembly in recipients’ colorectum were examined one week after transplantation. Donor ENSCs migrated rostrally within the colonic wall to intermuscularly repopulate the neighboring colorectum and assemble myenteric ganglia. It contributed to a chimeric state of myenteric plexuses with donor-origin ganglia of 41.2–67.5%. Two months later, transplanted ENSCs had undergone long-distance caudorostral migration almost up to the cecum to reconstitute myenteric and submucosal ganglia along the entire length of the colon.

Conclusion
This proof-of-principle study provided a viable justification for minimally invasive rectal ENSC transplantation to create long-term and long-range reconstitution of enteric ganglia. It opens up the new approach to ENSC delivery in laboratory animals and casts light on the feasibility of replacing damaged or replenishing missing enteric neurons by trans-anal rectal ENSC transplantation.
Modification and application of highly active alkaline pectin lyase
Authors: Li Pi-Wu , Ma Jun , Wei Xiao-Feng , Zhang Zi-Yang , Wang Rui-Ming , Xiao Jing , Wang Jun-Qing 
Published: October 2022

AbstractAlkaline pectate lyase has developmental prospects in the textile, pulp, paper, and food industries. In this study, we selected BacPelA, the pectin lyase with the highest expression activity from Bacillus clausii, modified and expressed in Escherichia coli BL21(DE3). Through fragment replacement, the catalytic activity of the enzyme was significantly improved. The optimum pH and temperature of the modified pectin lyase (PGLA-rep4) were 11.0 and 70 °C, respectively. It also exhibited a superior ability to cleave methylated pectin. The enzyme activity of PGLA-rep4, measured at 235 nm with 0.2% apple pectin as the substrate, was 554.0 U/mL, and the specific enzyme activity after purification using a nickel column was 822.9 U/mg. After approximately 20 ns of molecular dynamics simulation, the structure of the pectin lyase PGLA-rep4 tended to be stable. The root mean square fluctuation (RMSF) values at the key catalytically active site, LYS168, were higher than those of the wildtype PGLA. In addition, PGLA-rep4 was relatively stable in the presence of metal ions. PGLA-rep4 has good enzymatic properties and activities and maintains a high pH and temperature. This study provides a successful strategy for enhancing the catalytic activity of PGLA-rep4, making it the ultimate candidate for degumming and various uses in the pulp, paper, and textile industries.