bluuebunny/crossref_metadata_2025 huggingface dataset:
Untargeted metabolomic analysis reveals different metabolites associated with response to mepolizumab and omalizumab in asthma
Authors: Nopsopon Tanawin , Chen Yulu , Chen Qingwen , Wheelock Craig E. , Weiss Scott. T. , McGeachie Michael , Lasky-Su Jessica , Akenroye Ayobami
Published: April 2024

Background

There is limited evidence on biomarkers associated with response to the monoclonal antibodies currently approved for asthma treatment. We sought to identify circulatory metabolites associated with response to treatment with mepolizumab or omalizumab.

Methods

We conducted global metabolomic profiling of pre-treatment plasma samples from 100 patients with moderate-to-severe asthma who initiated mepolizumab (n=31) or omalizumab (n=69). The primary outcome was the change in exacerbations within 12 months of therapy. Negative binomial models were used to assess the association between each metabolite and exacerbations, adjusting for age, sex, body mass index, baseline exacerbations and inhaled corticosteroid use. Chemical similarity enrichment analysis (ChemRICH) was conducted to identify chemical subclasses associated with treatment response.

Results

The mean age of the mepolizumab group was 58.7 years with on average 2.9 exacerbations over the year prior to initiation of biologic therapy. The mean age in the omalizumab group was 48.8 years with 1.5 exacerbations in the preceding year. Patients with higher levels of two tocopherol metabolites were associated with more exacerbations on mepolizumab (δ-carboxyethyl hydroxychroman (CEHC) (p=2.65E-05, false discovery rate (FDR=0.01) and δ-CEHC glucuronide (p=2.47E-06, FDR=0.003)). Higher levels of six androgenic steroids, three carnitine metabolites and two bile acid metabolites were associated with decreased exacerbations in the omalizumab group. In enrichment analyses, xanthine metabolites (cluster FDR=0.0006) and tocopherol metabolites (cluster FDR=0.02) were associated with worse mepolizumab response, while androgenic steroids (cluster FDR=1.9E-18), pregnenolone steroids (cluster p=3.2E-07, FDR=1.4E-05) and secondary bile acid metabolites (cluster p=0.0003, FDR=0.006) were the top subclasses associated with better omalizumab response.

Conclusion

This study identifies distinct metabolites associated with response to mepolizumab and omalizumab, with androgenic steroids associated with response to both mepolizumab and omalizumab.
Control of false discoveries in grouped hypothesis testing for eQTL data
Authors: Rudra Pratyaydipta , Zhou Yi-Hui , Nobel Andrew , Wright Fred A.
Published: April 2024

Background

Expression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches.

Results

In an empirical Bayesian setting, we propose a new method to control the false discovery rate (FDR) for grouped hypotheses. Here, each gene forms a group, with SNPs annotated to the gene corresponding to individual hypotheses. The heterogeneity of effect sizes in different groups is considered by the introduction of a random effects component. Our method, entitled Random Effects model and testing procedure for Group-level FDR control (REG-FDR), assumes a model for alternative hypotheses for the eQTL data and controls the FDR by adaptive thresholding. As a convenient alternate approach, we also propose Z-REG-FDR, an approximate version of REG-FDR, that uses only Z-statistics of association between genotype and expression for each gene-SNP pair. The performance of Z-REG-FDR is evaluated using both simulated and real data. Simulations demonstrate that Z-REG-FDR performs similarly to REG-FDR, but with much improved computational speed.

Conclusion

Our results demonstrate that the Z-REG-FDR method performs favorably compared to other methods in terms of statistical power and control of FDR. It can be of great practical use for grouped hypothesis testing for eQTL analysis or similar problems in statistical genomics due to its fast computation and ability to be fit using only summary data.
HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes
Authors: He Lixia , Feng Xue , Hu Chunli , Liu Shuang , Sheng Hui , Cai Bei , Ma Yun
Published: April 2024

Background

Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function.

Result

It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter.

Conclusion

Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.
Developmentally dependent reprogramming of the Arabidopsis floral transcriptome under sufficient and limited water availability
Authors: Ma Xinwei , Wang Jun , Su Zhao , Ma Hong
Published: April 2024

Background

Environmental stresses negatively impact reproductive development and yield. Drought stress, in particular, has been examined during Arabidopsis reproductive development at morphological and transcriptomic levels. However, drought-responsive transcriptomic changes at different points in reproductive development remain unclear. Additionally, an investigation of the entire transcriptome at various stages during flower development is of great interest.

Results

Here, we treat Arabidopsis plants with well-watered and moderately and severely limiting water amounts when the first flowers reach maturity and generate RNA-seq datasets for early, middle, and late phases during flower development at 5, 6, and 7 days following treatment. Under different drought conditions, flowers in different developmental phases display differential sets of drought-responsive genes (DTGs), including those that are enriched in different GO functional categories, such as transcriptional regulation and response to stresses (early phase), lipid storage (middle phase), and pollen and seed development and metabolic processes (late phase). Some gene families have different members induced at different floral phases, suggesting that similar biochemical functions are carried out by distinct members. Developmentally-regulated genes (DVGs) with differential expression among the three floral phases belong to GO terms that are similar between water conditions, such as development and reproduction, metabolism and transport, and signaling and stress response. However, for different water conditions, such similar GO terms correspond to either distinct gene families or different members of a gene family, suggesting that drought affects the expression of distinct families or family members during reproductive development. A further comparison among transcriptomes of tissues collected on different days after treatment identifies differential gene expression, suggesting age-related genes (ARGs) might reflect the changes in the overall plant physiology in addition to drought response and development.

Conclusion

Together, our study provides new insights into global transcriptome reprogramming and candidate genes for drought response, flower development, aging and coordination among these complex biological processes.
Exploring the synergistic effects of indole acetic acid (IAA) and compost in the phytostabilization of nickel (Ni) in cauliflower rhizosphere
Authors: Khan Raheel , Sarwar Muhammad Junaid , Shabaan Muhammad , Asghar Hafiz Naeem , Zulfiqar Usman , Iftikhar Irfan , Aijaz Nazish , Haider Fasih Ullah , Chaudhary Talha , Soufan Walid
Published: April 2024

Heavy metals (HMs) contamination, owing to their potential links to various chronic diseases, poses a global threat to agriculture, environment, and human health. Nickel (Ni) is an essential element however, at higher concentration, it is highly phytotoxic, and affects major plant functions. Beneficial roles of plant growth regulators (PGRs) and organic amendments in mitigating the adverse impacts of HM on plant growth has gained the attention of scientific community worldwide. Here, we performed a greenhouse study to investigate the effect of indole-3-acetic acid (IAA @ 10− 5 M) and compost (1% w/w) individually and in combination in sustaining cauliflower growth and yield under Ni stress. In our results, combined application proved significantly better than individual applications in alleviating the adverse effects of Ni on cauliflower as it increased various plant attributes such as plant height (49%), root length (76%), curd height and diameter (68 and 134%), leaf area (75%), transpiration rate (36%), stomatal conductance (104%), water use efficiency (143%), flavonoid and phenolic contents (212 and 133%), soluble sugars and protein contents (202 and 199%), SPAD value (78%), chlorophyll ‘a and b’ (219 and 208%), carotenoid (335%), and NPK uptake (191, 79 and 92%) as compared to the control. Co-application of IAA and compost reduced Ni-induced electrolyte leakage (64%) and improved the antioxidant activities, including APX (55%), CAT (30%), SOD (43%), POD (55%), while reducing MDA and H2O2 contents (77 and 52%) compared to the control. The combined application also reduced Ni uptake in roots, shoots, and curd by 51, 78 and 72% respectively along with an increased relative production index (78%) as compared to the control. Hence, synergistic application of IAA and compost can mitigate Ni induced adverse impacts on cauliflower growth by immobilizing it in the soil.
Mortality and its predictors in abdominal injury across sub-Saharan Africa: systematic review and meta-analysis
Authors: Endeshaw Destaw , Delie Amare Mebrat , Adal Ousman , Tareke Abiyu Abadi , Bogale Eyob Ketema , Anagaw Tadele Fentabel , Tiruneh Misganaw Guadie , Fenta Eneyew Talie
Published: April 2024

Background

Abdominal injuries exert a significant impact on global morbidity and mortality. The aggregation of mortality data and its determinants across different regions holds immense importance for designing informed healthcare strategies. Hence, this study assessed the pooled mortality rate and its predictors across sub-Saharan Africa.

Method

This meta-analysis employed a comprehensive search across multiple electronic databases including PubMed, Africa Index Medicus, Science Direct, and Hinari, complemented by a search of Google Scholar. Subsequently, data were extracted into an Excel format. The compiled dataset was then exported to STATA 17 statistical software for analysis. Utilizing the Dersimonian-Laird method, a random-effect model was employed to estimate the pooled mortality rate and its associated predictors. Heterogeneity was evaluated via the I2 test, while publication bias was assessed using a funnel plot along with Egger's, and Begg's tests.

Result

This meta-analysis, which includes 33 full-text studies, revealed a pooled mortality rate of 9.67% (95% CI; 7.81, 11.52) in patients with abdominal injuries across sub-Saharan Africa with substantial heterogeneity (I2 = 87.21%). This review also identified significant predictors of mortality. As a result, the presence of shock upon presentation demonstrated 6.19 times (95% CI; 3.70-10.38) higher odds of mortality, followed by ICU admission (AOR: 5.20, 95% CI; 2.38-11.38), blunt abdominal injury (AOR: 8.18, 95% CI; 4.97-13.45), post-operative complications (AOR: 8.17, 95% CI; 4.97-13.44), and the performance of damage control surgery (AOR: 4.62, 95% CI; 1.85-11.52).

Conclusion

Abdominal injury mortality is notably high in sub-Saharan Africa. Shock at presentation, ICU admission, blunt abdominal injury, postoperative complications, and use of damage control surgery predict mortality. Tailored strategies to address these predictors could significantly reduce deaths in the region.
Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit
Authors: Iacovelli Alessandra , Oliva Alessandra , Mirabelli Flavio Marco , Giannone Silvia , Laguardia Marianna , Morviducci Matteo , Nicolardi Maria Luisa , Repaci Emma , Sanzari Maria Teresa , Leanza Cristiana , Raponi Giammarco , Mastroianni Claudio , Palange Paolo
Published: April 2024

Background

COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients.

Materials and methods

This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients.

Results

Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155–314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12–31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75–4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12–4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19–5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47–5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20–26.92), p = 0.035]. No differences were observed in hematological cohort.

Conclusion

CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.
A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy
Authors: Kaburagi Kei , Hagiwara Yuta , Tachikawa Keiji , Miyake Noriko , Akiyama Hisanao , Kawai Yosuke , Omae Yosuke , Tokunaga Katsushi , Yamano Yoshihisa , Shimizu Takahiro , Mitsuhashi Satomi
Published: April 2024

Background

Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left–right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy.

Case presentation

We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left–right body axis.

Conclusions

Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.
Competent blastocyst and receptivity endometrium improved clinical pregnancy in fresh embryo transfer cycles: a retrospective cohort study
Authors: Wang Longmei , Qiu Pingping , Jiang Lizhi , Li Ping , Jiang Yufei
Published: April 2024

Background

Embryo quality is usually regarded as a key predictor of successful implantation and clinical pregnancy potential. The identification of embryos that have the capacity to implant and result in a healthy pregnancy is a crucial part of in vitro fertilization (IVF). Usually, morphologically high-quality embryos are chosen for embryo transfer in IVF treatment. The aim of this study was to assess the association between the available blastocyst formation rate and the clinical pregnancy outcome following the first fresh embryo transfer cycle and provide systematic individual treatment to adjust endometrial receptivity for the next transfer cycle.

Methods

This retrospective, single-center study included 512 fresh embryo transfers conducted between 11/2019 and 08/2021, which consisted of 385 cleavage-stage (Day 3) and 127 blastocyst-stage (Day 5) embryo transfers. The two groups were divided into a clinical pregnancy group and a nonclinical pregnancy group for comparison. The association between the available blastocyst formation rate and the clinical pregnancy rate in the Day 3 and Day 5 transfer groups were considered.

Results

In the Day 3 group, there were 275 clinical pregnancies, and the clinical pregnancy rate was 71.43%. Although the two pronuclei (2PN) oocyte rate and available embryo rate at Day 3 were significantly higher in the clinical pregnancy group than the nonclinical pregnancy group (P < 0.05), the blastocyst formation rate and the available blastocyst formation rate were not significantly different between the clinical pregnancy group and the nonclinical pregnancy group (P > 0.05). In the Day 5 group, there were 81 clinical pregnancies, and the clinical pregnancy rate was 63.78%. No baseline characteristics showed any obvious differences between the clinical pregnancy group and nonclinical pregnancy group (P > 0.05). The blastocyst formation rate in the nonclinical pregnancy group was higher than that in the clinical pregnancy group, but the difference was not statistically significant (81.06% vs. 77.03%, P = 0.083). Interestingly, the available blastocyst formation rate and the Day 5 available blastocyst formation rate were significantly higher in the nonclinical pregnancy group than the clinical pregnancy group (66.19% vs. 60.79%, P = 0.014; 54.58% vs. 46.98%, P = 0.007).

Conclusions

In fresh cycles, the available blastocyst formation rate was not associated with the clinical pregnancy outcome for Day 3 embryo transfers, and the available blastocyst formation rate was not positively correlated with the clinical pregnancy outcome for Day 5 embryo transfers.
Validity and reliability of the Turkish version of the transition of primiparas becoming mothers scale
Authors: Kirbaş Zila Özlem , Odabaşi Aktaş Elif , Özkan Hava
Published: April 2024

Background

The transition to motherhood is an important life event in a woman’s life and represents an important developmental process that brings physical, psychological and social changes to gain a new role. However, research on the transition to motherhood in Turkish society is scarce. There is a need for a comprehensive, practical and reliable tool to evaluate the transition to motherhood in primiparous mothers. This study evaluated the reliability and validity of the Turkish version of the Transition of Primiparous Becoming Mothers Scale (TMP-S) to evaluate the transition process of primiparous mothers to motherhood.

Methods

This methodological research was carried out in obstetrics and gynecology outpatient clinics, pediatric outpatient clinics, and family health centers of a hospital in Türkiye. The sample consisted of primiparous mothers of 0 to 6- month-old babies who visited clinics and family health centers for routine postnatal examinations (n ​​= 305). After evaluating the language equivalence and content validity of the scale, test-retest reliability, internal consistency and construct validity were examined. Factor analysis, Pearson’s correlation, retest reliability, and Cronbach’s alpha were employed to evaluate structural validity and reliability.

Results

The final TPM-S had two dimensions with 25 items. Exploratory factor analysis revealed a two-factor solution, which accounted for 59.276% of the variance. Confirmatory factor analysis showed that the model fit of the two-factor model also reached a satisfactory model ft after modification. The comparative fit index was 0.894, the Tucker‒Lewis index was 0.882, and the root mean square error of approximation was 0.079. The content validity index of the scale ranged from 0.56 ~ 0.77. The Cronbach’s alpha coefficient was 0.93 for the total scale, and the test–retest reliability was 0.96.

Conclusions

It is a valid and reliable tool for evaluating the transition to motherhood among primiparous mothers of 0 to 6 month-old babies in Türkiye. Turkish researchers and healthcare professionals can routinely apply this measurement tool to primiparous mothers in the first six months after birth to evaluate their transition to motherhood.
Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects
Authors: Duan Lewei , Liu Zheng , Wan Fangning , Dai Bo
Published: April 2024

Background

Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects.

Methods

An extensive PubMed search was conducted until February 26, 2023, with the search term “prostate”, “whole-mount”, “large format histology”, which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding.

Results

WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region.

Conclusions

WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.
The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung
Authors: Kong Chao , Yin Xiaoyan , Zou Jingmin , Ma Changsheng , Liu Kai
Published: April 2024

Objective

To explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma.

Methods

Retrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness.

Results

In univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group).

Conclusions

Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.
Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC
Authors: Zhou Lijie , Zeng Youmiao , Liu Yuanhao , Du Kaixuan , Luo Yongbo , Dai Yiheng , Pan Wenbang , Zhang Lailai , Zhang Lei , Tian Fengyan , Gu Chaohui
Published: April 2024

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.
Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach
Authors: Ciora Octavia-Andreea , Seegmüller Tanja , Fischer Johannes S. , Wirth Theresa , Häfner Friederike , Stoecklein Sophia , Flemmer Andreas W. , Förster Kai , Kindt Alida , Bassler Dirk , Poets Christian F. , Ahmidi Narges , Hilgendorff Anne
Published: April 2024

Background

Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles.

Methods

Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR (“Attention to Infants at Respiratory Risks”) and NEuroSIS (“Neonatal European Study of Inhaled Steroids”). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques.

Results

First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters).

Conclusions

By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies.

Trial registration

AIRR: DRKS.de, DRKS00004600, 28/01/2013. NEuroSIS: ClinicalTrials.gov, NCT01035190, 18/12/2009.
Association between dietary selenium and zinc intake and risk of dilated cardiomyopathy in children: a case-control study
Authors: Aryafar Maryam , Mahdavi Mohammad , Shahzadi Hossein , Ranjbar Yeganeh Rajabpour , Sohouli Mohammad Hassan , Afzal Sina , Tehrani Asal Neshatbini , Fotros Danial , Daftari Ghazal
Published: April 2024

Background

Dilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients.

Methods

A total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP.

Results

After fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057–0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035–0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively.

Conclusions

This study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention.
Effect of the COVID-19 pandemic on utilization of essential health services in Iran evidence from an interrupted time series analysis
Authors: Ranjbar Mohammad , Mousavi Seyed Masood , Madadizadeh Farzan , Dargani Nahid Hosseini , Iraji Samaneh , Angell Blake , Assefa Yibeltal
Published: April 2024

Background

The COVID-19 disrupted the provision of essential health services in numerous countries, potentially leading to outbreaks of deadly diseases. This study aims to investigate the effect of the COVID-19 pandemic on the utilization of essential health services in Iran.

Methods

An analytical cross-sectional study was conducted using interrupted time series (ITS) analysis. Data about five indicators, including 'childhood vaccination, infant care, hypertension screening, diabetes screening, and breast cancer screening,' were obtained from the electronic health record System in two-time intervals: 15 months before (November 2018 to January 2020) and 15 months after (January 2020 to May 2021) the onset of the COVID-19 pandemic. The data were analyzed by utilizing ITS. In addition, a Poisson model was employed due to the usage of count data. The Durbin-Watson (DW) test was used to identify the presence of lag-1 autocorrelation in the time series data. All statistical analysis was performed using R 4.3.1 software, considering a 5% significance level.

Results

The ITS analysis showed that the COVID-19 pandemic significantly affected the utilization of all essential health services (P < 0.0001). The utilization of hypertension screening (RR = 0.51, p < 0.001), diabetes screening (RR = 0.884, p < 0.001), breast cancer screening (RR = 0.435, p < 0.001), childhood vaccination (IRR = 0.947, p < 0.001), and infant care (RR = 1.666, p < 0.001), exhibited a significant decrease in the short term following the pandemic (P < 0.0001). However, the long-term trend for all service utilization, except breast cancer screening (IRR = 0.952, p < 0.001), demonstrated a significant increase.

Conclusions

The COVID-19 pandemic affected utilization of essential health care in Iran. It is imperative to utilize this evidence to develop policies that will be translated into targeted planning and implementation to sustain provision and utilization of essential health services during public health emergencies. It is also vital to raise awareness and public knowledge regarding the consequences of interruptions in essential health services. In addition, it is important to identify the supply- and demand-side factors contributing to these disruptions.
Change in general and domain-specific physical activity during the transition from primary to secondary education: a systematic review
Authors: Spruijtenburg Gwennyth E. , van Abswoude Femke , Adams Imke L. J. , Platvoet Sebastiaan W. J. , de Niet Mark , Steenbergen Bert
Published: April 2024

Background

Knowledge of changes in the domains of physical activity (PA) during the transition period from primary to secondary education and the factors associated with these changes, are prerequisites for the design of effective PA promotion strategies. Therefore, the first aim of this study was to systematically review changes in general, leisure-time, school, transport, work, and home PA across the transition from primary to secondary education. The second aim was to systematically review the individual, social, and physical environmental factors that were associated with these changes.

Methods

Records published up until September 2023 were retrieved from five electronic databases. We included longitudinal and cross-sectional studies that investigated general or domain-specific PA from 2 years before to 2 years after the transition from primary to secondary education. Information on source, study characteristics, sample characteristics, PA, and factors were extracted from the papers included. We reported the direction of change in general and domain-specific PA and the direction of association of the factors with change in general and domain-specific PA.

Results

Forty-eight papers were included in the study. The evidence on changes in PA and associated factors was greatest for general PA. A limited number of the studies investigated the separate domains of leisure-time, school, and transport. Most studies on general and school PA reported a decline in PA, but there were no consistent results for the domains of leisure-time and transport. With respect to the associated factors, evidence was predominantly found for individual factors and to a lesser degree for physical environmental and social environmental factors. None of the factors were consistently associated with changes in general or domain-specific PA during the school transition.

Conclusions

For the design of targeted PA promotion strategies, further studies are warranted to explore changes in the specific domains of PA across the transition from primary to secondary education, especially in the domains of leisure-time, transport, home, and work PA. In addition, the interactions between factors at different socioecological levels to influence changes in PA need to be addressed more in the future.

Trial registration

PROSPERO CRD42020190204.
Impact of training on knowledge, confidence and attitude amongst community health volunteers in the provision of community-based palliative care in rural Kenya
Authors: Elias Hussein , Kisembe Evelyne , Nyariki Sarah , Kiplimo Ivan , Amisi James , Boit Juli , Tarus Allison , Mohamed Naseem , Cornetta Kenneth
Published: April 2024

Objectives

Existing literature suggests multiple potential roles for community health volunteers (CHVs) in the provision of palliative care (PC) in low- and middle-income countries. In Kenya the role of CHV in the provision of PC has not been reported. The objective of this study was to assess knowledge, confidence, attitude, and clinical practice of community health volunteers after attending a novel palliative care (PC) training program.

Methods

A total of 105 CHVs participated in a 3-day in person training followed by a 1-month in person and telephone observation period of the palliative care activities in the community. Structured questionnaires were used pre- and post-training to assess knowledge acquisition, impact on practice, and content delivery. A mixed method study design was conducted 12-month post training to assess impact on clinical practice.

Results

Immediately after training, CHV provided positive ratings on relevance and content delivery. In the month following training, CHVs evaluated 1,443 patients, referred 154, and conducted 110 and 129 tele consults with the patients and PC providers respectively. The follow up survey at 12 months revealed improved knowledge and confidence in various domains of palliative care including symptom and spiritual assessment and provision of basic nursing and bereavement care. Focus group discussions revealed the CHVs ability to interpret symptoms, make referrals, improved communication/ interpersonal relationships, spiritual intervention, patient comfort measures and health care practices as newly learned and practiced skills.

Conclusions

We noted improved knowledge, new skills and change in practice after CHVs participation in a novel training curriculum. CHVs can make important contributions to the PC work force and be first line PC providers in the community as part of larger hub and spoke care model.
“Being an informal caregiver – strengthening resources”: mixed methods evaluation of a psychoeducational intervention supporting informal caregivers in palliative care
Authors: Theißen Tabea , Ullrich Anneke , Oechsle Karin , Wikert Julia , Bokemeyer Carsten , Schieferdecker Aneta
Published: April 2024

Background

Informal caregivers are key support for patients with progressive incurable diseases. However, their own needs often remain unmet. Therefore, we developed, manualised and implemented the intervention “Being an informal caregiver – strengthening resources” aiming to support and empower informal caregivers by addressing relevant information-related, physical, psychological and social needs.

Methods

In this pilot study, we evaluated the acceptance and experiences with this psychoeducational intervention. The study was conducted over two years (2019-2021). Informal caregivers were recruited from the University Medical Centre Hamburg-Eppendorf and the metropolitan region of Hamburg, Germany. The intervention was aimed at adult persons who identified themselves as an informal caregiver to an adult patient with a progressive incurable cancer and non-cancer disease. For the evaluation we used a mixed methods approach, combining a longitudinal questionnaire survey (pre-intervention, after each module, 3-months follow-up) and semi-structured interviews post-intervention. Quantitative data were analysed using descriptive statistics and a paired t-Test, interviews were analysed based on the qualitative content analysis according to Mayring. Results were triangulated using a convergent triangulation design.

Results

Of 31 informal caregivers who received the intervention, 25 returned the follow-up questionnaire and 20 informal caregivers were interviewed. Triangulated results showed a high satisfaction with the implementation of the intervention. Of a broad range of subjective benefits, gaining knowledge, self-awareness and self-efficacy were most apparent. Informal caregivers reported improved preparedness, awareness of own needs as well as confidence regarding handling own emotions and interacting with the ill person. However, implementing the learned skills into daily life can be challenging due to internal and external factors. Motivations and challenges for participating as well as potential for improvement were identified.

Conclusions

This pilot study showed an overall positive evaluation and several subjective benefits of the psychoeducational intervention “Being an informal caregiver – strengthening resources”. Further research is needed to measure the efficacy of this intervention on informal caregivers’ outcomes. Therefore, a multicentre randomized prospective study is planned.
Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma
Authors: Liu Suqing , Zhang Yaohua , Zhu Xiaohua , He Shan , Liu Xiao , Lv Xiang , Zuo Fuguo , Wu Jinfeng
Published: April 2024

Background

The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms.

Methods

The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue.

Results

HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors.

Conclusions

HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.
Application of artificial intelligence-assisted image diagnosis software based on volume data reconstruction technique in medical imaging practice teaching
Authors: Wang DongXu , Huai BingCheng , Ma Xing , Jin BaiMing , Wang YuGuang , Chen MengYu , Sang JunZhi , Liu RuiNan
Published: April 2024

Background

In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching.

Methods

Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups.

Results

The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90).

Conclusions

Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities.