bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid artery dissection in Hutchinson-Gilford Progeria: a case report
Authors: González-Maestro Víctor , Monteagudo-Vilavedra Einés , Rodríguez-Antuña Jorge , Lendoiro-Fuentes Marta , Gómez María Soledad Brage , Miño Elena Maside
Published: March 2022

Background

Strokes in the paediatric age group have their own epidemiology and aetiology and are frequently misdiagnosed. As in the adult population, they present some risk factors that must be identified. Cerebral arteriopathies as a cause of paediatric ischaemic stroke present a very diverse aetiology and morphology.

In this article we report a paediatric stroke in a patient who was diagnosed during his first months of life of Hutchinson-Gilford´s Progeria (HGP). This is a rare genetic condition caused by mutations in the LMNA gene, producing an aberrant lamin A protein. The disease leads to premature aging, and cardiovascular complications are the first cause of morbidity and mortality in these patients.

Case presentation

We report the case of a 5-year-old patient with HGP (missense mutation—de novo—c.1822G > A in heterozygosis, LMNA gene). The patient was diagnosed during his first year of life and presented distinct phenotypical features. No other relevant comorbidities were present.

He was admitted to the emergency department for right hemiparesis with at least 4 h of evolution, with inability to open the hand and slight decrease in the level of consciousness (pedNIHSS 5–6). Cranial-CT and angio-CT showed findings indicative of left carotid dissection. Consensus was reached on conservative medical management with anticoagulation and antiplatelet therapy. In the first few days, the patient had a favourable evolution with resolution of the right lower limb hemiparesis and, one month after discharge, of the hand paresis.

Conclusions

The clinical manifestations, the vascular phenotype of the genetic mutation and the location of the radiological signs on a specific vascular morphology are indicative of carotid dissection. Spontaneous dissections occur under a predisposing risk factor or disease and are an exceptional finding in patients with HGP.
Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults
Authors: Wang Zuxing , Chen Lili , Xiao Jun , Jiang Fugui , Min Wenjiao , Liu Shuyun , Wang Yunqiong , Qi Mengsha
Published: March 2022

Background

The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior.

Methods

A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis.

Results

Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594–0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor.

Conclusion

Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.
Evaluating scenarios for school reopening under COVID19
Authors: Baxter Arden , Oruc Buse Eylul , Asplund John , Keskinocak Pinar , Serban Nicoleta
Published: March 2022

Background

Thousands of school systems have struggled with the decisions about how to deliver education safely and effectively amid the COVID19 pandemic. This study evaluates the public health impact of various school reopening scenarios (when, and how to return to in-person instruction) on the spread of COVID19.

Methods

An agent-based simulation model was adapted and used to project the impact of various school reopening strategies on the number of infections, hospitalizations, and deaths in the state of Georgia during the study period, i.e., February 18th-November 24th, 2020. The tested strategies include (i) schools closed, i.e., all students receive online instruction, (ii) alternating school day, i.e., half of the students receive in-person instruction on Mondays and Wednesdays and the other half on Tuesdays and Thursdays, (iii) alternating school day for children, i.e., half of the children (ages 0-9) receive in-person instruction on Mondays and Wednesdays and the other half on Tuesdays and Thursdays, (iv) children only, i.e., only children receive in-person instruction, (v) regular, i.e., all students return to in-person instruction. We also tested the impact of universal masking in schools.

Results

Across all scenarios, the number of COVID19-related deaths ranged from approximately 8.8 to 9.9 thousand, the number of cumulative infections ranged from 1.76 to 1.96 million for adults and 625 to 771 thousand for children and youth, and the number of COVID19-related hospitalizations ranged from approximately 71 to 80 thousand during the study period. Compared to schools reopening August 10 with a regular reopening strategy, the percentage of the population infected reduced by 13%, 11%, 9%, and 6% in the schools closed, alternating school day for children, children only, and alternating school day reopening strategies, respectively. Universal masking in schools for all students further reduced outcome measures.

Conclusions

Reopening schools following a regular reopening strategy would lead to higher deaths, hospitalizations, and infections. Hybrid in-person and online reopening strategies, especially if offered as an option to families and teachers who prefer to opt-in, provide a good balance in reducing the infection spread compared to the regular reopening strategy, while ensuring access to in-person education.
Typical antipsychotics is associated with increased risk of severe exacerbation in asthma patients: a nationwide population-based cohort study
Authors: Kuo Chin-Wei , Yang Szu-Chun , Shih Yu-Fen , Liao Xin-Min , Lin Sheng-Hsiang
Published: March 2022

Background

Severe asthma exacerbation reduces patients’ quality of life, results in visits to the emergency department (ED) and hospitalization, and incurs additional medical costs. Antipsychotics block receptors with bronchodilation function; however, the association between antipsychotic use and severe asthma exacerbation is unknown. This study aimed to investigate the effects of antipsychotics on asthma-related ED visits and hospitalizations.

Methods

A case-crossover design was used in this study. Using the 2003–2017 Taiwan National Health Insurance Reimbursement Database, we established a cohort of 18,657 adults with asthma exacerbation leading to ED visits or hospitalization. Univariate and multivariate conditional logistic regressions were conducted to explore the association between antipsychotic use and severe asthma exacerbation. Subgroup analyses of different classes, doses, receptor functions of antipsychotics, different psychiatric disease, and sensitivity analyses of excluding patients with schizophrenia were also performed.

Results

Antipsychotic use was associated with a higher risk of severe asthma exacerbation (adjusted odds ratio [OR]: 1.27; 95% confidence interval [CI] 1.05–1.54; P = 0.013) compared with no use of antipsychotics. The use of typical antipsychotics increased the risk of severe asthma exacerbation (adjusted OR: 1.40, 95% CI 1.10–1.79, P = 0.007), whereas the use of atypical antipsychotics did not. These results did not change after the exclusion of patients with schizophrenia. There was a dose-dependent effect of antipsychotics (trend test, P = 0.025). Antipsychotics that block the M2 muscarinic or D2 dopaminergic receptors were associated with an increased risk of severe asthma exacerbation (adjusted OR: 1.39, 95% CI 1.10–1.76, P = 0.007 and adjusted OR: 1.33, 95% CI 1.08–1.63, P = 0.008, respectively). However, use of antipsychotics did not increase risk of severe asthma exacerbation in patients with psychiatric disorder.

Conclusions

The use of typical antipsychotics is associated with a dose-dependent increased risk of severe asthma exacerbation, especially for patients without psychiatric disorders. Further research on the impact of typical antipsychotics on asthma exacerbation is warranted.
Exploration of induced sputum BIRC3 levels and clinical implications in asthma
Authors: Du Lijuan , Xu Changyi , Zeng Zhimin , Chen Fengjia , Tang Kun , Liang Yuxia , Guo Yubiao
Published: March 2022

Background

Baculoviral IAP repeat-containing 3 (BIRC3) which encodes a member of the IAP family of proteins upregulated in the asthma expression profile dataset. However, there was few research on studying the clinical implication of BIRC3 in asthma.

Objective

To validate BIRC3 expression and its clinical implications in induced sputum of asthma.

Methods

Based on the GSE76262 (118 asthma cases and 21 healthy controls) dataset, differentially expressed genes were screened using R software. Subsequently, BIRC3 mRNA and protein were clinically verified in induced sputum samples through quantitative real‐time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Besides, the correlations between BIRC3 expression and asthmatic eosinophilic/allergic inflammation indicators (FeNO, IgE, and EOS%), pulmonary function (FEV1, FEV1% pred, FVC% pred, and FEV1/FVC), and inflammatory cytokines (IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP) were analyzed. Finally, BIRC3 mRNA was detected in human primary bronchial epithelial cells stimulated by cytokines (IL-4 or IL-13).

Results

BIRC3 was screened as a candidate gene in the GSE76262, which was highly expressed in asthma. Highly expressed BIRC3 was positively correlated with eosinophilic and allergic indicators, including FeNO, blood eosinophil, and serum IgE. Moreover, BIRC3 protein was positively associated with inflammation cytokines, like IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP, while negatively correlated with FEV1, FEV1%pred, FVC% pred, and FEV1/FVC. Furthermore, the expression of BIRC3 could be induced in primary bronchial epithelial cells treated by cytokines IL-4 or IL-13.

Conclusions

BIRC3 significantly increased in induced sputum of asthma and positively correlated with airway eosinophilic and peripheral blood allergic inflammation, type 2 cytokines, and airway obstruction. Increased BIRC3 might be involved in the pathogenesis of asthma by affecting the eosinophilic and allergic inflammation.
Comprehensive analysis of pedicle screw implantation in the C7 vertebra using computed tomography-based three-dimensional models
Authors: Liu Huan , Zhou Zhi-Yong , Wei Jia-Xu , Zhang Ming , Bai Meng , Huang Ai-Bing
Published: March 2022

Background

From a biomechanical point of view, pedicle screws (PS) are better than other kinds of screws for implantation in the seventh cervical vertebra (C7). However, the application of PS is limited because of the high risk of severe complications. It is essential to define the optimal entry point and trajectory. The aim of this study was to comprehensively analyze the starting point and trajectory for C7 PS insertion using three dimensional (3D) models.

Methods

Overall, 60 subjects aged 18 to 67 years old were included. All CT images were used to construct 3D computer models of the C7 vertebrae. A new coordinate system was established for the next evaluation. The pedicle axis was calculated with respect to the entire pedicle; then, the ideal entry point, screw diameter and length, sagittal angle and lateral angle were assessed.

Results

All the ideal entry points were located at the medial superior to lateral notch (LN), and the mean distance between the entry point and LN was 5.86 ± 1.67 mm in the horizontal direction and 3.47 ± 1.57 mm in the vertical direction. The mean distance between the entry point and the middle point of the inferior edge of the C6 articular process (MP) was 0.74 ± 1.83 mm in the horizontal direction. The mean sagittal angle of the pedicle axis was 90.42°, and the mean pedicle transverse angle was 30.70°. The average diameter and length of the PS were 6.51 ± 0.76 mm and 31.58 ± 4.40 mm, respectively.

Conclusions

This study provided a novel method to calculate the ideal starting point and trajectory for C7 PS insertion. These measurements may be helpful for preoperative planning. It is recommended that 3D CT imaging is used preoperatively to carefully evaluate the anatomy of each individual.
The characteristics of husbands and violence against women in Wuhan, China: a cross-sectional study
Authors: Chang Xuening , Yang Yifan , Li Ruizhen
Published: March 2022

Objective

To explore the prevalence and correlation between husbands and lifetime domestic violence (DV) among women in Wuhan, China.

Methods

A cross-sectional study was conducted in a community health center in Wuhan from June 2015 to December 2015. A total of 1015 women who came to the center for gynecological examination were selected through a random sampling. They were assessed using the WHO Violence Against Women Instrument to evaluate the prevalence of DV. The chi-square test, the Wilcoxon rank test, and unadjusted and adjusted logistic regression analyses were used to analyze the possible risk or protective factors for DV.

Results

The lifetime prevalence of DV was 29.36% (298/1015). The risk factors included heavy physical labor (OR 3.54, 95% CI 1.63–7.77), long-term drinking (OR 1.60, 95% CI 1.19–2.14), overweight or obesity (OR 1.36, 95% CI 1.01–1.88) and long-term smoking (OR 1.03, 95% CI 1.01–1.04). Higher education was a protective factor (OR 0.80, 95% CI 0.66–0.96).

Conclusion

Women whose husbands had lower education, performed heavy physical labor, were long-term alcohol consumers, had overweight or obesity, and were long-term smokers were vulnerable to lifetime DV.
Chinese ICU physicians’ knowledge of antibiotic pharmacokinetics/pharmacodynamics (PK/PD): a cross-sectional survey
Authors: Mao Wenchao , Lu Difan , Zhou Jia , Zhen Junhai , Yan Jing , Li Li ,   Zhejiang Provincial Critical Care Clinical Research Group
Published: March 2022

Background

Patients with sepsis have a high mortality rate, accumulated evidences suggest that an optimal antibiotic administration strategy based on pharmacokinetics/pharmacodynamics (PK/PD) can improve the prognosis of septic patients. Therefore, we assessed Chinese intensive care unit (ICU) physicians’ knowledge about PK/PD.

Methods

In December 2019, we designed a questionnaire focused on Chinese ICU physicians’ knowledge about PK/PD and collected the questionnaires after 3 months. The questionnaire was distributed via e-mail and WeChat, and was distributed to ICU doctors in 31 administrative regions of China except Hong Kong, Macao and Taiwan. The passing score was corrected by the Angoff method, and the ICU physicians’ knowledge about PK/PD was analysed accordingly.

Results

We received a total of 1,309 questionnaires and retained 1,240 valid questionnaires. The passing score was 90.8, and the overall pass rate was 56.94%. The pass rate for tertiary and secondary hospitals was 59.07% and 37.19%, respectively. ICU physicians with less than 5 years of work experience and resident physician accounted for the highest pass rate, while those with between 5 to 10 years of work experience and attending accounted for the lowest pass rate. The majority of participants in the Chinese Critical Care Certified Course (5C) were from Jiangsu and Henan provinces, and they had the highest average scores (125.8 and 126.5, respectively). For Beijing and Shanghai, the average score was only 79.4 and 90.9, respectively.

Conclusions

Chinese ICU physicians’ knowledge about PK/PD is unsatisfactory. Therefore, it is essential to strengthen ICU physicians’ knowledge about PK/PD.
Predictive validity of the Stopping Elderly Accidents, Deaths & Injuries (STEADI) program fall risk screening algorithms among community-dwelling Thai elderly
Authors: Loonlawong Sriprapa , Limroongreungrat Weerawat , Rattananupong Thanapoom , Kittipimpanon Kamonrat , Saisanan Na Ayudhaya Wanvisa , Jiamjarasrangsi Wiroj
Published: March 2022

Background

Fall risk screening using multiple methods was strongly advised as the initial step for preventing fall. Currently, there is only one such tool which was proposed by the U.S. Centers for Disease Control and Prevention (CDC) for use in its Stopping Elderly Accidents, Death & Injuries (STEADI) program. Its predictive validity outside the US context, however, has never been investigated. The purpose of this study was to determine the predictive validity (area under the receiver operating characteristic curve: AUC), sensitivity, and specificity of the two-step sequential fall-risk screening algorithm of the STEADI program for Thai elderly in the community.

Methods

A 1-year prospective cohort study was conducted during October 2018–December 2019. Study population consisted of 480 individuals aged 65 years or older living in Nakhon Ratchasima Province, Thailand. The fall risk screening algorithm composed of two serial steps. Step 1 is a screening by the clinician’s 3 key questions or the Thai Stay Independent brochure (Thai-SIB) 12 questions. Step 2 is a screening by 3 physical fitness testing tools including Time Up and Go test (TUG), 30-s Chair Stand, and 4-stage balance test. Participants were then followed for their fall incidents. Statistical analyses were conducted by using Cox proportional hazard model. The AUC, sensitivity, specificity, and other relevant predictive validity indices were then estimated.

Results

The average age of the participants was 73.3 ± 6.51 years (range 65–95 years), and 52.5% of them were female. The screening based on the clinician’s 3 key questions in Step 1 had a high AUC (0.845), with the sensitivity and specificity of 93.9% (95% CI 88.8, 92.7) and 75.0% (95% CI 70.0, 79.6), respectively. Appropriate risk categorization however differed slightly from the original STEADI program.

Conclusions

With some modification, the fall risk screening algorithm based on the STEADI program was applicable in Thai context.
TCN1 is a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma
Authors: Li Haining , Guo Liping , Cai Zhigang
Published: March 2022

Background

Around the world, lung cancer is the leading cause of cancer-related death. Lung adenocarcinomas are among the most common diagnosed forms of lung cancer, whose overall survival has not improved significantly, which makes finding an effective therapeutic target vital. Transcobalamin (TCN1) is a vitamin B12-binding protein which regulates cobalamin homeostasis. In tumor tissues, TCN1 is expressed highly, and its expression is correlated with cancer aggressiveness and poor prognosis according to recent studies and bioinformatic analyses. However, its effect on lung adenocarcinoma (LUAD) is unknown.

Methods

We evaluated whether TCN1 shows diagnostic and prognostic value in LUAD using bioinformatic analysis. In particular, various databases and analysis tools were used to determine TCN1’s relationship with LUAD, including TCGA, GTEx, GEO, STRING, and TISIDB.

Results

As compared to normal lung tissue, the level of TCN1 expression in LUAD tissues was significantly higher (P < 0.001). TCN1 also had a good ability to distinguish lung adenocarcinoma from non-lung adenocarcinoma samples [area under the curve (AUC) = 0.788]. According to univariate Cox statistics, high expression levels of TCN1 correlate with poor overall survival (OS) in LUAD (P < 0.001). Moreover, based on a multivariate Cox analysis, TCN1 expression was independently correlated with OS (P = 0.011). GO/KEGG and GSEA indicated enrichment in epidermal cell differentiation (P < 0.0005), keratinocyte differentiation (P < 0.0005), neuroactive ligand–receptor interaction (P < 0.0005), epithelial–mesenchymal transition (P = 0.029, FDR = 0.023) and TNFA signaling via NFKB (P = 0.029, FDR = 0.023). Furthermore, TCN1 is associated with immune infiltration based on an analysis of immune cell infiltration.

Conclusions

In summary, TCN1 could be used as a prognostic and diagnostic biomarker and provide deeper perspectives for the development of therapies and prognostic markers in LUAD.
Untargeted metabolomics analysis of esophageal squamous cell cancer progression
Authors: Yang Tao , Hui Ruting , Nouws Jessica , Sauler Maor , Zeng Tianyang , Wu Qingchen
Published: March 2022

90% of esophageal cancer are esophageal squamous cell carcinoma (ESCC) and ESCC has a very poor prognosis and high mortality. Nevertheless, the key metabolic pathways associated with ESCC progression haven’t been revealed yet. Metabolomics has become a new platform for biomarker discovery over recent years. We aim to elucidate dominantly metabolic pathway in all ESCC tumor/node/metastasis (TNM) stages and adjacent cancerous tissues. We collected 60 postoperative esophageal tissues and 15 normal tissues adjacent to the tumor, then performed Liquid Chromatography with tandem mass spectrometry (LC–MS/MS) analyses. The metabolites data was analyzed with metabolites differential and correlational expression heatmap according to stage I vs. con., stage I vs. stage II, stage II vs. stage III, and stage III vs. stage IV respectively. Metabolic pathways were acquired by Kyoto Encyclopedia of Genes and Genomes. (KEGG) pathway database. The metabolic pathway related genes were obtained via Gene Set Enrichment Analysis (GSEA). mRNA expression of ESCC metabolic pathway genes was detected by two public datasets: gene expression data series (GSE)23400 and The Cancer Genome Atlas (TCGA). Receiver operating characteristic curve (ROC) analysis is applied to metabolic pathway genes. 712 metabolites were identified in total. Glycerophospholipid metabolism was significantly distinct in ESCC progression. 16 genes of 77 genes of glycerophospholipid metabolism mRNA expression has differential significance between ESCC and normal controls. Phosphatidylserine synthase 1 (PTDSS1) and Lysophosphatidylcholine Acyltransferase1 (LPCAT1) had a good diagnostic value with Area under the ROC Curve (AUC) > 0.9 using ROC analysis. In this study, we identified glycerophospholipid metabolism was associated with the ESCC tumorigenesis and progression. Glycerophospholipid metabolism could be a potential therapeutic target of ESCC progression.
Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis
Authors: Chen Qi , Liang Xi , Wu Tianzhou , Jiang Jing , Jiang Yongpo , Zhang Sheng , Ruan Yanyun , Zhang Huaping , Zhang Chao , Chen Peng , Lv Yuhang , Xin Jiaojiao , Shi Dongyan , Chen Xin , Li Jun , Xu Yinghe
Published: March 2022

Background

Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis.

Methods

A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules.

Results

Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log2 fold change| > 1.5, adjusted P value < 0.05 and variable importance in the projection (VIP) > 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the derivation results (area under the receiver operating characteristic curve (AUROC): 0.81–0.96/0.62–1.00). The pentose phosphate pathway was found to be related to sepsis-associated encephalopathy. Phenylalanine metabolism was associated with sepsis-associated acute kidney injury. The key molecular alterations of the multiomics network in sepsis compared to normal controls implicate acute inflammatory response, platelet degranulation, myeloid cell activation involved in immune response and phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis.

Conclusions

Integrated analysis of untargeted metabolomics and proteomics revealed characteristic metabolite and protein alterations in sepsis, which were mainly involved in inflammation-related pathways and amino acid metabolism. This study depicted the pathological characteristics and pathways involved in sepsis and potential therapeutic targets.
Superior physical and mental health of healthy volunteers before and five years after mobilized stem cell donation
Authors: Heyn J. , Bräuninger S. , Dimova-Dobreva M. , Mathieson N. , Koptelova N. , Kolpakova A. , Seidl C. , Reinhardt P. , Tsamadou C. , Schrezenmeier H. , Nakov R. , Seifried E. , Bonig H.
Published: March 2022

Background

Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally.

Methods

We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire.

Results

Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time.

Conclusions

HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation.

Trial registration National Clinical Trial NCT01766934
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

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

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

Background

The 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.

Methods

Here, 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.

Results

Both 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.

Conclusions

Overall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction.

Trial registration

The 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

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

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

Chalcones 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

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

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

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.