bluuebunny/crossref_metadata_2025_split huggingface dataset:
The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway
Authors: Zhu Juanjuan , Wen Yuan , Zhang Qiuling , Nie Fei , Cheng Mingliang , Zhao Xueke 
Published: March 2022

Abstract
Background
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and has no safe and effective drug for treatment. We have previously reported the function of blueberry, but the effective monomer and related molecular mechanism remain unclear.

Methods
The monomer of blueberry was examined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The NASH cell model was constructed by exposing HepG2 cells to free fatty acids. The NASH mouse model was induced by a high-fat diet for 12 weeks. NASH cell and mouse models were treated with different concentrations of blueberry monomers. The molecular mechanism was studied by Oil Red O staining, ELISA, enzyme activity, haematoxylin–eosin (H&E) staining, immunohistochemistry, immunofluorescence, western blot, RNA sequencing, and qRT-PCR.

Results
We identified one of the main monomer of blueberry as tectorigenin (TEC). Cyanidin-3-O glucoside (C3G) and TEC could significantly inhibit the formation of lipid droplets in steatosis hepatocytes, and the effect of TEC on the formation of lipid droplets was significantly higher than that of C3G. TEC can promote cell proliferation and inhibit the release of inflammatory mediators in NASH cell model. Additionally, TEC administration provided a protective role against high-fat diets induced lipid damage, and suppressed lipid accumulation. In NASH mouse model, TEC can activate autophagy, inhibit pyroptosis and the release of inflammatory mediators. In NASH cell model, TEC inhibited pyroptosis by stimulating autophagy. Then, small RNA sequencing revealed that TEC up-regulated the expression of tRF-47-58ZZJQJYSWRYVMMV5BO (tRF-47). The knockdown of tRF-47 blunted the beneficial effects of TEC on NASH in vitro, including inhibition of autophagy, activation of pyroptosis and release of inflammatory factors. Similarly, suppression of tRF-47 promoted the lipid injury and lipid deposition in vivo.

Conclusions
These results demonstrated that tRF-47-mediated autophagy and pyroptosis plays a vital role in the function of TEC to treat NASH, suggesting that TEC may be a promising drug for the treatment of NASH.
DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity
Authors: Cendrowicz Ewa , Jacob Lisa , Greenwald Shirley , Tamir Ami , Pecker Iris , Tabakman Rinat , Ghantous Lucy , Tamir Liat , Kahn Roy , Avichzer Jasmine , Aronin Alexandra , Amsili Shira , Zorde-Khvalevsky Elina , Gozlan Yosi , Vlaming Martijn , Huls Gerwin , van Meerten Tom , Dranitzki Michal Elhalel , Foley-Comer Adam , Pereg Yaron , Peled Amnon , Chajut Ayelet , Bremer Edwin 
Published: March 2022

Abstract
Background
Treatment of Diffuse Large B Cell Lymphoma (DLBCL) patients with rituximab and the CHOP treatment regimen is associated with frequent intrinsic and acquired resistance. However, treatment with a CD47 monoclonal antibody in combination with rituximab yielded high objective response rates in patients with relapsed/refractory DLBCL in a phase I trial. Here, we report on a new bispecific and fully human fusion protein comprising the extracellular domains of SIRPα and 4-1BBL, termed DSP107, for the treatment of DLBCL. DSP107 blocks the CD47:SIRPα ‘don’t eat me’ signaling axis on phagocytes and promotes innate anticancer immunity. At the same time, CD47-specific binding of DSP107 enables activation of the costimulatory receptor 4-1BB on activated T cells, thereby, augmenting anticancer T cell immunity.

Methods
Using macrophages, polymorphonuclear neutrophils (PMNs), and T cells of healthy donors and DLBCL patients, DSP107-mediated reactivation of immune cells against B cell lymphoma cell lines and primary patient-derived blasts was studied with phagocytosis assays, T cell activation and cytotoxicity assays. DSP107 anticancer activity was further evaluated in a DLBCL xenograft mouse model and safety was evaluated in cynomolgus monkey.

Results
Treatment with DSP107 alone or in combination with rituximab significantly increased macrophage- and PMN-mediated phagocytosis and trogocytosis, respectively, of DLBCL cell lines and primary patient-derived blasts. Further, prolonged treatment of in vitro macrophage/cancer cell co-cultures with DSP107 and rituximab decreased cancer cell number by up to 85%. DSP107 treatment activated 4-1BB-mediated costimulatory signaling by HT1080.4-1BB reporter cells, which was strictly dependent on the SIRPα-mediated binding of DSP107 to CD47. In mixed cultures with CD47-expressing cancer cells, DSP107 augmented T cell cytotoxicity in vitro in an effector-to-target ratio-dependent manner. In mice with established SUDHL6 xenografts, the treatment with human PBMCs and DSP107 strongly reduced tumor size compared to treatment with PBMCs alone and increased the number of tumor-infiltrated T cells. Finally, DSP107 had an excellent safety profile in cynomolgus monkeys.

Conclusions
DSP107 effectively (re)activated innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.
Calorie restriction improves metabolic state independently of gut microbiome composition: a randomized dietary intervention trial
Authors: Sowah Solomon A. , Milanese Alessio , Schübel Ruth , Wirbel Jakob , Kartal Ece , Johnson Theron S. , Hirche Frank , Grafetstätter Mirja , Nonnenmacher Tobias , Kirsten Romy , López-Nogueroles Marina , Lahoz Agustín , Schwarz Kathrin V. , Okun Jürgen G. , Ulrich Cornelia M. , Nattenmüller Johanna , von Eckardstein Arnold , Müller Daniel , Stangl Gabriele I. , Kaaks Rudolf , Kühn Tilman , Zeller Georg 
Published: March 2022

AbstractBackgroundThe gut microbiota has been suggested to play a significant role in the development of overweight and obesity. However, the effects of calorie restriction on gut microbiota of overweight and obese adults, especially over longer durations, are largely unexplored.MethodsHere, we longitudinally analyzed the effects of intermittent calorie restriction (ICR) operationalized as the 5:2 diet versus continuous calorie restriction (CCR) on fecal microbiota of 147 overweight or obese adults in a 50-week parallel-arm randomized controlled trial, the HELENA Trial. The primary outcome of the trial was the differential effects of ICR versus CCR on gene expression in subcutaneous adipose tissue. Changes in the gut microbiome, which are the focus of this publication, were defined as exploratory endpoint of the trial. The trial comprised a 12-week intervention period, a 12-week maintenance period, and a final follow-up period of 26 weeks.ResultsBoth diets resulted in ~5% weight loss. However, except forLactobacillalesbeing enriched after ICR, post-intervention microbiome composition did not significantly differ between groups. Overall weight loss was associated with significant metabolic improvements, but not with changes in the gut microbiome. Nonetheless, the abundance of theDoreagenus at baseline was moderately predictive of subsequent weight loss (AUROC of 0.74 for distinguishing the highest versus lowest weight loss quartiles). Despite the lack of consistent intervention effects on microbiome composition, significant study group-independent co-variation between gut bacterial families and metabolic biomarkers, anthropometric measures, and dietary composition was detectable. Our analysis in particular revealed associations between insulin sensitivity (HOMA-IR) andAkkermansiaceae,Christensenellaceae, andTanerellaceae. It also suggests the possibility of a beneficial modulation of the latter two intestinal taxa by a diet high in vegetables and fiber, and low in processed meat.ConclusionsOverall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction.Trial registrationThe trial, including the present microbiome component, was prospectively registered atClinicalTrials.govNCT02449148on May 20, 2015.
Glucose-6-phosphate dehydrogenase deficiency presenting with rhabdomyolysis in a patient with coronavirus disease 2019 pneumonia: a case report
Authors: Yu Regina , Chen Chien-Rong , Evans Darci , Qing Xin , Gotesman Moran , Chandramohan Gangadarshni , Kallay Thomas , Lin Henry J. , Pedigo Tiffany P. 
Published: March 2022

Abstract
Background
Glucose-6-phosphate dehydrogenase deficiency is a rarely recognized predisposing factor for rhabdomyolysis. Rhabdomyolysis with coronavirus disease 2019 has been increasingly seen during the pandemic. We report the uncommon occurrence of coronavirus disease 2019 pneumonia, severe rhabdomyolysis, and acute renal failure in the setting of glucose-6-phosphate dehydrogenase deficiency.

Case presentation
A 19-year-old African American male presented with myalgias, diaphoresis, and dark urine. Testing for severe acute respiratory syndrome coronavirus 2 was positive. He had severe rhabdomyolysis with creatine kinase levels up to 346,695 U/L. He was oliguric and eventually required hemodialysis. Progressive hypoxemia, methemoglobinemia, and hemolytic anemia occurred following one dose of rasburicase for hyperuricemia. Glucose-6-phosphate dehydrogenase deficiency was diagnosed. Full recovery followed a single volume exchange transfusion and simple packed red blood cell transfusions.

Conclusions
Glucose-6-phosphate dehydrogenase deficiency may predispose individuals to rhabdomyolysis due to severe acute respiratory syndrome coronavirus 2, presumably due to altered host responses to viral oxidative stress. Early screening for glucose-6-phosphate dehydrogenase deficiency can be useful for management of patients with rhabdomyolysis.
Parental divorce and nicotine addiction in Lebanese adolescents: the mediating role of child abuse and bullying victimization
Authors: Sanayeh Elie Bou , Iskandar Katia , Fadous Khalife Marie-Claude , Obeid Sahar , Hallit Souheil 
Published: March 2022

Abstract
Background
Lebanon ranks first amongst Middle-Eastern countries in terms of cigarette and waterpipe smoking. Understanding the mediating factors for nicotine addiction in adolescents who have experienced parental divorce is vital to take effective measures that will help in lowering its prevalence in our community. The objective of this study was to investigate the association between the increasingly concerning parental divorce and nicotine addiction in Lebanese adolescents while taking into consideration the plausible mediating effect of abuse and bullying victimization.

Methods
This was a cross-sectional survey-based study that was conducted between January and May 2019. A total of 1810 adolescents aged between 14 and 17 years was enrolled from 16 Lebanese schools. Linear regressions taking the cigarette and waterpipe dependence scores as dependent variables were conducted respectively, using the SPSS software. PROCESS v3.4 model 4 was used for mediation analysis.

Results
A total of 11.9% of the enrolled participants had divorced parents. Higher cigarette and waterpipe dependence were found in adolescents whose parents were divorced compared to those living together. More child psychological abuse, having divorced parents vs living together, and more child physical abuse were significantly associated with higher cigarette dependence. More child psychological and physical, and having divorced parents vs living together were significantly associated with more waterpipe dependence. In addition, all forms of abuse (except neglect) and bullying victimization had a partially mediating effect in the associations between parental divorce and nicotine dependence (cigarette and waterpipe) in adolescents.

Conclusion
This study results may serve as a first step towards enrolling separated parents and their children in special prevention programs to help them create a protective and supportive environment.
Design, synthesis, and biological evaluation of chalcones for anticancer properties targeting glycogen synthase kinase 3 beta
Authors: Ahn Seunghyun , Truong Vi Nguyen-Phuong , Kim Beomsoo , Yoo Miri , Lim Yoongho , Cho Somi Kim , Koh Dongsoo 
Published: March 2022

AbstractChalcones compounds have been investigated to exhibit anticancer activity through various physiological modes of action. In order to develop chalcone compounds with novel anticancer-related modes of action, diverse chalcone compounds were designed and synthesized. Variously substituted poly-methoxy chalcone compounds1–17were prepared, and their structures were identified using high-resolution mass spectrometry (HR/MS) and nuclear magnetic resonance (NMR) experiments. Long-term survival clonogenic assay was applied to evaluate their anti-cancer abilities and revealed that their GI50 values ranged between 1.33 and 172.20 μM. When MCF-7SC cells were treated with various concentrations of compound14, reduced cell viability and induced apoptosis in MCF-7SC cells were observed in a dose-dependent manner. Wound healing assay demonstrated that compound14prevented the MCF7-SC migrated cells at non-lethal concentrations after 12 and 24 h of exposure. The efficiency of compound14on the levels of Epithelial-mesenchymal transition (EMT) markers was accessed by the western blot analysis. For the concrete understanding of anticancer properties at the molecular level, in vitro kinase assays on 12 cancer related proteins were carried out. Glycogen synthase kinase 3 beta (GSK3β) was most effectively inhibited by compound14with 89% inhibitory activity at 10 µM against GSK3β. The binding mode of compound14with GSK3β was reinforced through in silico experiments, which demonstrated compound14binds with GSK3β at binding affinity ranged between − 7.5 kcal/mol and − 6.8 kcal/mol. SwissADME analysis provided the druggability and leadlikeness of compound14, which unveiled drug development possibilities of chalcone compound14.
METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression
Authors: Guo Yu-qing , Wang Qiang , Wang Jun-guo , Gu Ya-jun , Song Pan-pan , Wang Shou-yu , Qian Xiao-yun , Gao Xia 
Published: March 2022

Abstract
Background
N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC).

Methods
The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo.

Results
M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression.

Conclusions
METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.
Examining key factors impact on health science students’ intentions to adopt genetic and pharmacogenomics testing: a comparative path analysis in two different healthcare settings
Authors: Koufaki Margarita-Ioanna , Siamoglou Stavroula , Patrinos George P. , Vasileiou Konstantinos 
Published: March 2022

Abstract
Background
There is an increasing interest worldwide in investigating healthcare stakeholders’ perceptions and intentions to adopt pharmacogenomics (PGx) into clinical practice. However, the existing inquiries based on well-established theories and models that interpret their intentions to implement PGx are scarce. This study is the first that examines the impact of selected factors on health science students’ intention to adopt genetic testing applications using the technology acceptance model while it compares two different cultural groups: Greeks (Europe; Christian) and Malays (Asia; Muslim).

Results
Malay students were more persuaded about benefits of genomics for drug management compared to their Greek counterparts. However, participants from both countries appear to be particularly convinced about the benefits of genomics on disease management. Moreover, students from both countries considered the potential misuse of genetic information by corporate or government bodies as their most important concern; Greek students appeared to be considerably less worried than Malay about other probable hazards such as the deficient protection of privacy and confidentiality, which could be attributed to their religious background. Participants from both samples expressed very positive attitudes towards genetic research and testing and their favourable intentions to adopt genetic testing for personal use. Exploratory factors analysis and path analysis yielded quite similar results for both samples. Path analysis revealed that the factors of attitudes, concerns, drug management benefits and disease management benefits significantly influenced students’ intentions to adopt genetic testing for personal use, with attitudes being the most inspirational factor with rather high impact, while training did not seem to affect participant’s intentions. The squared multiple correlation of both models was quite satisfactory reaching to 0.55 for the Malaysian sample.

Conclusion
Similarities in the results of the two groups along with the relevant validity and reliability tests indicate that the proposed model is a good fit for future studies to interpret stakeholders’ intentions to adopt genetic testing. Therefore, it can provide a promising and reliable basis for future model development to explain the relationships between intentions to adopt genetic testing and its predictors.
The relations between executive functions and occupational functioning in individuals with bipolar disorder: a scoping review
Authors: Koene Juul , Zyto Susan , van der Stel Jaap , van Lang Natasja , Ammeraal Marion , Kupka Ralph W. , van Weeghel Jaap 
Published: March 2022

Abstract
Background
Patients with bipolar disorder experience impairments in their occupational functioning, despite remission of symptoms. Previous research has shown that neurocognitive deficits, especially deficits in executive functions, may persist during euthymia and are associated with diminished occupational functioning.

Objectives
The aim of this scoping review was to identify published studies that report on the relationships between executive functions and occupational functioning in BD to review current knowledge and identify knowledge gaps. In addition to traditional neuropsychological approaches, we aimed to describe executive functioning from a self-regulation perspective, including emotion regulation.

Methods
We applied the methodological framework as described by Arksey and O’Malley (Int J Soc Res Methodol Theory Pract 8:19–32, 2005) and Levac et al. (Implement Sci 5:1–9, 2010). We searched PubMed and psycINFO for literature up to November 2021, after which we screened papers based on inclusion criteria. Two reviewers independently performed the screening process, data charting process, and synthesis of results.

Results
The search yielded 1202 references after deduplication, of which 222 remained after initial screening. The screening and inclusion process yielded 82 eligible papers in which relationships between executive functions and occupational functioning are examined.

Conclusion
Neurocognitive deficits, including in executive functions and self-regulation, are associated with and predictive of diminished occupational functioning. Definitions and measurements for neurocognitive functions and occupational functioning differ greatly between studies, which complicates comparisons. Studies on functional remediation show promising results for improving occupational functioning in patients with BD. In research and clinical practice more attention is needed towards the quality of work functioning and the various contexts in which patients with BD experience deficits.
Application of double-negative T cells in haematological malignancies: recent progress and future directions
Authors: Chen Xingchi , Wang Dongyao , Zhu Xiaoyu 
Published: March 2022

AbstractHaematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3+CD4−CD8−) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.