bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of glycans in platelet and megakaryocyte biology
Authors: Falet Hervé , Rivadeneyra Leonardo , Hoffmeister Karin M. 
Published: January 2022

Abstract
Humans produce and remove 1011 platelets daily to maintain a steady-state platelet count. The tight regulation of platelet production and removal from the blood circulation prevents anomalies in both processes from resulting in reduced or increased platelet count, often associated with the risk of bleeding or overt thrombus formation, respectively. This review focuses on the role of glycans, also known as carbohydrates or oligosaccharides, including N- and O-glycans, proteoglycans, and glycosaminoglycans, in human and mouse platelet and megakaryocyte physiology. Based on recent clinical observations and mouse models, we focused on the pathologic aspects of glycan biosynthesis and degradation and their effects on platelet numbers and megakaryocyte function.
Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma
Authors: Trasanidis Nikolaos , Katsarou Alexia , Ponnusamy Kanagaraju , Shen Yao-An , Kostopoulos Ioannis V. , Bergonia Bien , Keren Keren , Reema Paudel , Xiao Xiaolin , Szydlo Richard M. , Sabbattini Pierangela M. R. , Roberts Irene A. G. , Auner Holger W. , Naresh Kikkeri N. , Chaidos Aristeidis , Wang Tian-Li , Magnani Luca , Caputo Valentina S. , Karadimitris Anastasios 
Published: January 2022

Abstract
Understanding the biological and clinical impact of copy number aberrations (CNAs) on the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring an adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chromosome 1 (chr1q) portend high-risk MM disease, the underpinning molecular etiology remains elusive. Here, with reference to the 3-dimensional (3D) chromatin structure, we integrate multi-omics data sets from patients with MM with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM. Prominent among these genes, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed superenhancers, PBX1 directly regulates critical oncogenic pathways and a FOXM1-dependent transcriptional program. Together, PBX1 and FOXM1 activate a proliferative gene signature that predicts adverse prognosis across multiple types of cancer. Notably, pharmacological disruption of the PBX1-FOXM1 axis with existing agents (thiostrepton) and a novel PBX1 small molecule inhibitor (T417) is selectively toxic against chr1q-amp myeloma and solid tumor cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes, and proposes novel CNA-targeted therapy strategies in MM and other types of cancer.
Day 30 SUVmax predicts progression in patients with lymphoma achieving PR/SD after CAR T-cell therapy
Authors: Al Zaki Ajlan , Feng Lei , Watson Grace , Ahmed Sairah A. , Mistry Haleigh , Nastoupil Loretta J. , Hawkins Misha , Nair Ranjit , Iyer Swaminathan P. , Lee Hun J. , Steiner Raphael E. , Flowers Christopher R. , Shpall Elizabeth J. , Kebriaei Partow , Neelapu Sattva S. , Westin Jason R. , Strati Paolo 
Published: January 2022

Abstract
About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P &lt; .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.
Fine-Tuning of the Grain Size by Alternative Splicing of GS3 in Rice
Authors: Liu Lei , Zhou Ying , Mao Feng , Gu Yujuan , Tang Ziwei , Xin Yi , Liu Fuxia , Tang Tang , Gao Hui , Zhao Xiangxiang 
Published: January 2022

AbstractGrain size is subtly regulated by multiple signaling pathways in rice. Alternative splicing is a general mechanism that regulates gene expression at the post-transcriptional level. However, to our knowledge, the molecular mechanism underlying grain size regulation by alternative splicing is largely unknown. GS3, the first identified QTL for grain size in rice, is regulated at the transcriptional and post-translational level. In this study, we identified that GS3 is subject to alternative splicing. GS3.1 and GS3.2, two dominant isoforms, accounts for about 50% and 40% of total transcripts, respectively. GS3.1 encodes the full-length protein, while GS3.2 generated a truncated proteins only containing OSR domain due to a 14 bp intronic sequence retention. Genetic analysis revealed that GS3.1 overexpressors decreased grain size, but GS3.2 showed no significant effect on grain size. Furthermore, we demonstrated that GS3.2 disrupts GS3.1 signaling by competitive occupation of RGB1. Therefore, we draw a conclusion that the alternative splicing of GS3 decreases the amount of GS3.1 and GS3.2 disrupts the GS3.1 signaling to inhibit the negative effects of GS3.1 to fine-tune grain size. Moreover, the mechanism is conserved in cereals rather than in Cruciferae, which is associated with its effects on grain size. The results provide a novel, conserved and important mechanism underlying grain size regulation at the post-transcriptional level in cereals.
Predicting combinations of drugs by exploiting graph embedding of heterogeneous networks
Authors: Song Fei , Tan Shiyin , Dou Zengfa , Liu Xiaogang , Ma Xiaoke 
Published: January 2022

AbstractBackgroundDrug combination, offering an insight into the increased therapeutic efficacy and reduced toxicity, plays an essential role in the therapy of many complex diseases. Although significant efforts have been devoted to the identification of drugs, the identification of drug combination is still a challenge. The current algorithms assume that the independence of feature selection and drug prediction procedures, which may result in an undesirable performance.ResultsTo address this issue, we develop a novelSemi-supervisedHeterogeneousNetworkEmbedding algorithm (called SeHNE) to predict the combination patterns of drugs by exploiting the graph embedding. Specifically, the ATC similarity of drugs, drug–target, and protein–protein interaction networks are integrated to construct the heterogeneous networks. Then, SeHNE jointly learns drug features by exploiting the topological structure of heterogeneous networks and predicting drug combination. One distinct advantage of SeHNE is that features of drugs are extracted under the guidance of classification, which improves the quality of features, thereby enhancing the performance of prediction of drugs. Experimental results demonstrate that the proposed algorithm is more accurate than state-of-the-art methods on various data, implying that the joint learning is promising for the identification of drug combination.ConclusionsThe proposed model and algorithm provide an effective strategy for the prediction of combinatorial patterns of drugs, implying that the graph-based drug prediction is promising for the discovery of drugs.
The effect of group-based education on gastrointestinal symptoms and quality of life in patients with celiac disease: randomized controlled clinical trial
Authors: Akbari Namvar Zahra , Mahdavi Reza , Shirmohammadi Masood , Nikniaz Zeinab 
Published: January 2022

Abstract
Background
In this trial, we investigated the effect of a group-based education program on gastrointestinal (GI) symptoms and quality of life (QOL) in patients with celiac disease (CD).

Method
In the present study, 130 patients with CD who were on a GFD for at least 3 months, randomly assigned to receive group-based education (n = 66) or routine education in the celiac clinic (n = 64) for 3 months. We assessed gastrointestinal symptoms and quality of life using the gastrointestinal symptom rating scale (GSRS) questionnaire and SF-36 questionnaire at baseline and 3 months after interventions.

Results
The mean age of the participants was 37.57 ± 9.59 years. There were no significant differences between the two groups regarding the baseline values. Results showed that the mean score of total GSRS score in the intervention group was significantly lower compared with the control group 3 months post-intervention (p = 0.04). Also, there was a significant difference in the mean score of SF-36 between the two groups 3 months post-intervention (p = 0.02).

Conclusion
Results showed that group-based education was an effective intervention in patients with celiac disease to improve gastrointestinal symptoms and quality of life.
Trial registration IRCT code: IRCT20080904001197N21; registration date: 5/23/2019.
Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy
Authors: Liu Youxia , Li Hongfen , Yu Huyan , Wang Fanghao , Jia Junya , Yan Tiekun 
Published: January 2022

Abstract
Background
The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN).

Methods
This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs).

Results
The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1.

Conclusions
The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.
Development and validation of preconception care improvement scale (PCIS) in a resource-limited setting
Authors: Teshome Firanbon , Birhanu Zewdie , Kebede Yohannes 
Published: January 2022

AbstractBackgroundPreconception care helps to close the gaps in a continuum of care. It is of paramount importance to reduce maternal and child adverse pregnancy outcomes, increase the utilization of services such as antenatal care, skilled delivery care, and post-natal care, and improve the lives of future generations. Therefore, a validated instrument is required. The purpose of this study was to develop and validate the preconception care improvement scale (PCIS) in a resource-limited setting.MethodsA mixed-method study was carried out from 02, March to 10, April 2019 in Manna district, Oromia region, Ethiopia to test the reliability and validity of the scale. Items were generated from literatures review, in-depth interviews with different individuals, and focused group discussions with women of reproductive age groups. A pretested structured questionnaire was used and a survey was conducted among 623 pregnant women in the district. The collected data were entered into EPI-data version 3.1 software and exported to SPSS version 23 software and data were analyzed for internal consistency and validity using reliability analysis and factor analysis.ResultsThe PCIS has 17 items loaded into six factors: Substance-related behaviors, screening for common non-communicable and infectious diseases, micronutrient supplementation and vaccination, seeking advice, decision and readiness for conception, and screening for sexually transmitted diseases. Factor analysis accounted for 67.51% of the observed variance. The internal consistency (Cronbach’s alpha) of the scale was 0.776. Diversified participants of the qualitative study and experts’ discussions assured the face and content validity of the scale. Factor loading indicated the convergent validity of the scale. Three of the PCIS subscale scores had a positive and significant association with the practice of preconception care and antenatal care visits, which confirmed the predictive validity of the scale.ConclusionThe PCIS exhibited good reliability, face validity, content validity, convergent validity, and predictive validity. Thus, the scale is valid and helps to improve preconception care, especially in resource-limited settings.
Quantile regression analysis of the association between parental rearing and interpersonal sensitivity in Chinese adolescents
Authors: Zhang Yafeng , Tian Wei , Xin Yuqi , Zhou Quan , Yan Guangcan , Zhou Jianqiu , Wang Bin , Tao Yuchun , Fan Lihua , Wang Limin 
Published: January 2022

AbstractBackgroundParental rearing is well documented as an important influencing factor of interpersonal sensitivity (IS). However, little research has focused on the extent by which various aspects of parental rearing in fluence IS. This study aimed to analyze the effects of parental rearing on IS, using quantile regression. We analyzed the extent of the influence of parental rearing on IS by quantile regression to provide definitive evidence on the family education of adolescents with IS problems.MethodsThe multiple cross-sectional studies were conducted among 3345 adolescents from Harbin, China, in 1999, 2006, 2009 and 2016. Furthermore, a multistage sampling method (stratified random cluster) was used to select participants. IS was assessed using a subscale of the Symptom Checklist-90-Revision. Perceived parental rearing was assessed using the Egna Minnen av. Barndoms Uppfostran. The ordinary least squares (OLS) linear regression was used to determine the average effect of parental rearing on IS. The quantile regression was conducted to examine the established associations and to further explain the association.ResultsPaternal emotional warmth was found to be associated with IS across the quantile, especially after the 0.6 quantiles; however, this association was not found for maternal emotional warmth. Paternal punishment was associated with IS at the 0.22–0.27 and 0.60 quantile; however, maternal punishment had no significant effect on IS. QR method found that paternal overinvolvement was associated with IS at the 0.48–0.65 quantiles, but paternal overprotection was associated with IS across the quantile; however, maternal overinvolvement and overprotection was positively correlated with IS at the 0.07–0.95 quantiles. The correlation between paternal rejection and IS was found at the 0.40–0.75 and > 0.90 quantiles; maternal rejection was associated with IS within the 0.05–0.92 quantiles.ConclusionsParental rearing practices predict different magnitudes of IS at varying levels. This study provides suggestions for parents to assess purposefully and systematically, intervene, and ameliorate adolescent IS problems. We also highlight the role of paternal rearing in children’s IS problems, providing new ideas for family education.
Neurapraxia in patients with trigeminal neuralgia but no identifiable neurovascular conflict during microvascular decompression: a retrospective analysis of 26 cases
Authors: Li Juan , Zhou Min , Wang Yuhai , Kwok Sze Chai , Yin Jia 
Published: January 2022

Abstract
Background
Microvascular decompression (MVD) is the first choice in patients with classic trigeminal neuralgia (TGN) that could not be sufficiently controlled by pharmacological treatment. However, neurovascular conflict (NVC) could not be identified during MVD in all patients. To describe the efficacy and safety of treatment with aneurysm clips in these situations.

Methods

A total of 205 patients underwent MVD for classic TGN at our center from January 1, 2015 to December 31, 2019. In patients without identifiable NVC upon dissection of the entire trigeminal nerve root, neurapraxia was performed using a Yasargil temporary titanium aneurysm clip (force: 90 g) for 40 s (or a total of 60 s if the process must be suspended temporarily due to bradycardia or hypertension).

Results
A total of 26 patients (median age: 64 years; 15 women) underwent neurapraxia. Five out of the 26 patients received prior MVD but relapsed. Immediate complete pain relief was achieved in all 26 cases. Within a median follow-up of 3 years (range: 1.0–6.0), recurrence was noted in 3 cases (11.5%). Postoperative complications included hemifacial numbness, herpes labialis, masseter weakness; most were transient and dissipated within 3–6 months.

Conclusions
Neurapraxia using aneurysm clip is safe and effective in patients with classic TGN but no identifiable NVC during MVD. Whether this method could be developed into a standardizable method needs further investigation.
Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study
Authors: Inaishi Jun , Saisho Yoshifumi , Watanabe Yuusuke , Tsuchiya Tami , Sasaki Hironobu , Masaoka Tatsuhiro , Itoh Hiroshi 
Published: January 2022

Abstract
Background
We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking.

Methods
Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching.

Results
HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05).

Conclusions
Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW.

Trial registration
Clinical trial registry number; UMIN000016390 and jRCTs031180320.
Approval date of Registry and the Registration: December 12, 2014.
Dignity therapy intervention fidelity: a cross-sectional descriptive study with older adult outpatients with cancer
Authors: Schoppee Tasha M. , Scarton Lisa , Bluck Susan , Yao Yingwei , Keenan Gail , Samuels Virginia , Fitchett George , Handzo George , Chochinov Harvey M. , Emanuel Linda L. , Wilkie Diana J. 
Published: January 2022

Abstract
Objectives
Intervention fidelity is imperative to ensure confidence in study results and intervention replication in research and clinical settings. Like many brief protocol psychotherapies, Dignity Therapy lacks sufficient evidence of intervention fidelity. To overcome this gap, our study purpose was to examine intervention fidelity among therapists trained with a systematized training protocol.

Methods
For preliminary fidelity evaluation in a large multi-site stepped wedge randomized controlled trial, we analyzed 46 early transcripts of interviews from 10 therapists (7 female; 7 White, 3 Black). Each transcript was evaluated with the Revised Dignity Therapy Adherence Checklist for consistency with the Dignity Therapy protocol in terms of its Process (15 dichotomous items) and Core Principles (6 Likert-type items). A second rater independently coded 26% of the transcripts to assess interrater reliability.

Results
Each therapist conducted 2 to 10 interviews. For the 46 scored transcripts, the mean Process score was 12.4/15 (SD = 1.2), and the mean Core Principles score was 9.9/12 (SD = 1.8) with 70% of the transcripts at or above the 80% fidelity criterion. Interrater reliability (Cohen’s kappa and weighted kappa) for all Adherence Checklist items ranged between .75 and 1.0. For the Core Principles items, Cronbach’s alpha was .92.

Conclusions
Preliminary findings indicate that fidelity to Dignity Therapy delivery was acceptable for most transcripts and provide insights for improving consistency of intervention delivery. The systematized training protocol and ongoing monitoring with the fidelity audit tool will facilitate consistent intervention delivery and add to the literature about fidelity monitoring for brief protocol psychotherapeutic interventions.