bluuebunny/crossref_metadata_2025 huggingface dataset:
Agreement in non-cycloplegic and cycloplegic refraction between a photoscreener and a calibrated autorefractor
Authors: Kanclerz Piotr , Przewłócka Katarzyna , Arnold Robert W.
Published: March 2024

Introduction

Photoscreeners have been shown to provide excellent measurements of the refractive error. However, whether they could be used for assessing cycloplegic refraction has not been examied. This study aimed to evaluate the agreement between cycloplegic and non-cycloplegic measurements obtained using a photoscreener and stationary autorefractor, respectively.

Methods

This study included all patients undergoing routine ophthalmic examination at the Hygeia Clinic (Poland) from June to July 2022. Each patient underwent non-cycloplegic and cycloplegic refraction assessments using the 2WIN photoscreener (Adaptica SRL, Padova, Italy) and an ARK-1 stationary autorefractor ARK-1 (Nidek Co Ltd., Tokyo, Japan), respectively. Each pair of assessments was conducted in random order, and all values were determined at a vertical distance of 12 mm. The agreement between cycloplegic and non-cycloplegic measurements was assessed using paired t-tests, Bland-Altman and ABCD ellipsoids.

Results

This analysis included 82 patients, of which 52 were female. Their mean age was 34.39 ± 13.13 years. The non-cycloplegic spherical equivalent (SE) did not differ significantly between the 2WIN (− 1.22 ± 2.45) and ARK-1 (− 1.19 ± 2.96) devices (p = 0.580). However, the cycloplegic SE values demonstrated more negative values with the 2WIN device (− 1.13 ± 2.19) than with the ARK-1 device (− 0.75 ± 3.03; p = 0.007). The non-cycloplegic and cycloplegic measurements were strongly correlated between the devices (r = 0.9473 and 0.9411, respectively). However, the correlation between their cycloplegic shifts in SE was low (r = 0.2645). Ellipsoid refraction aligned better non-cycloplegic (ARK-1 = 1.00; 2WIN = 1.74) than with cycloplegic refraction (ARK-1 = 1.43; 2WIN = 1.90).

Conclusion

While the cycloplegic measurements obtained with the 2WIN photoscreener were strongly correlated with those obtained with the ARK-1 stationary autorefractor for most of the analyzed parameters, they should not be considered interchangeable.
Association between admission albumin levels and 30-day readmission after hip fracture surgery in geriatric patients: a propensity score-matched study
Authors: Tang Wanyun , Yao Wei , Wang Wei , Ding Wenbo , Ni Xiaomin , He RenJian
Published: March 2024

Purpose

This study aimed to evaluate the correlation admission albumin levels and 30-day readmission after hip fracture surgery in geriatric patients.

Methods

In this retrospective cohort study, 1270 geriatric patients admitted for hip fractures to a level I trauma center were included. Patients were stratified by clinical thresholds and albumin level quartiles. The association between admission albumin levels and 30-day readmission risk was assessed using multivariate logistic regression and propensity score-matched analyses. The predictive accuracy of albumin levels for readmission was evaluated by ROC curves. The dose–response relationship between albumin levels and readmission risk was examined.

Results

The incidence of 30-day readmission was significantly higher among hypoalbuminemia patients than those with normal albumin levels (OR = 2.090, 95%CI:1.296–3.370, p = 0.003). Furthermore, propensity score-matched analyses demonstrated that patients in the Q2(35.0–37.9 g/L) (OR 0.621, 95%CI 0.370–1.041, p = 0.070), Q3(38.0–40.9 g/L) (OR 0.378, 95%CI 0.199–0.717, p < 0.001) and Q4 (≥ 41 g/L) (OR 0.465, 95%CI 0.211–0.859, p = 0.047) quartiles had a significantly lower risk of 30-day readmission compared to those in the Q1(< 35 g/L) quartile. These associations remained significant after propensity score matching (PSM) and subgroup analyses. Dose–response relationships between albumin levels and 30-day readmission were observed.

Conclusions

Lower admission albumin levels were independently associated with higher 30-day readmission rates in elderly hip fracture patients. Our findings indicate that serum albumin may assist perioperative risk assessment, and prompt correction of hypoalbuminemia and malnutrition could reduce short-term readmissions after hip fracture surgery in this high-risk population.
How stable are moral judgements? A longitudinal study of context dependency in attitudes towards patient responsibility
Authors: Bringedal Berit H , Rø Karin Isaksson
Published: March 2024

Background

Whether patients' life-style should involve lower priority for treatment is a controversial question in bioethics. Less is known about clinicians' views.

Aim

To study how clinical doctors' attitudes to questions of patient responsibility and priority vary over time.

Method

Surveys of doctors in Norway in 2008, 2014, 2021. Questionnaires included statements about patients' lifestyle's significance for priority to care, and vignettes of priority cases (only in 2014).

Results

Attitudes were fairly stable between 2008 and 2021. 17%/14% agreed that patients' lifestyle should count, while 19%/22% agreed that it should involve lower priority to scarce organs. 42/44% agreed that smokers should have lower priority. Substantially more agreed in 2014. Regression analyses showed that being male, working in hospital, and younger age increased the likelihood of agreeing.

Conclusion

A substantial minority of doctors agreed that lifestyle should be a priority criterion, possibly contrary to Norwegian legislation and professional ethics. The finding might be explained by the unspecified meaning of priority, increased scarcity-awareness, or socio-cultural trends towards individualism. The 2014 results indicate a framing effect; the vignettes may have primed the respondents towards accepting lifestyle as a criterion. We conclude that attitudes to normative questions are unstable and depend on context. A substantial minority of doctors seems to be positive to deprioritizing patients allegedly responsible for their illness. However, what deprioritization implies in practice is not clear.
Evaluating person-centered care in neurological outpatient care: a mixed-methods content validity study
Authors: Olsson Mia , Bala Sidona-Valentina , Hagell Peter
Published: March 2024

Background

Person-centered care (PCC) is gaining increased attention. PCC concerns the whole person behind the disease and can improve care for people with long-term conditions such as multiple sclerosis (MS) and Parkinson’s disease (PD). However, there is a lack of tools to assess PCC from the patients’ perspective, particularly in outpatient care. The Person-Centered Care instrument for outpatient care (PCCoc) is an instrument under development with the intention to fill this gap. The aim of this study was to test the user-friendliness and content validity of the PCCoc as experienced by persons with MS and PD in neurological outpatient care.

Methods

Twenty persons with MS or PD completed the 35-item PCCoc followed by an interview regarding the instrument’s intelligibility and ease of use to assess its user-friendliness. Participants then rated the relevance of each item. These ratings were used to calculate the content validity index (CVI) for individual items (I-CVI) and for the overall scale (S-CVI).

Results

It took a median of 5 min for participants to complete the PCCoc. Instrument instructions were found clear, items easy to understand, and response categories distinct. No important missing areas were reported. I-CVI values ranged between 0.75 and 1, and S-CVI was 0.96.

Conclusions

We found support for the user-friendliness and content validity of the PCCoc among persons with MS and PD, suggesting that the PCCoc can be useful for evaluating and developing PCC in neurological outpatient care. Further testing in broader contexts, including psychometric testing, is warranted to establish its usefulness.
LncRNA WFDC21P interacts with SEC63 to promote gastric cancer malignant behaviors by regulating calcium homeostasis signaling pathway
Authors: Dong Jinyao , Lv Yongqiang , Meng Debin , Shi Ruyi , Li Feng , Guo Rui , Wang Yi , Guo Jiansheng , Zhang Yanyan
Published: March 2024

Background

Gastric cancer is currently estimated to be the fifth leading common cancer in the world, and responsible for about one million new cases and an estimated 769,000 cancer-related deaths each year. WFDC21P is long non-coding RNA and has been reported to play critical roles in serval types of cancer. Our research aims to investigate the biological effects and molecular mechanism of WFDC21P in gastric cancer.

Methods

Datasets (GSE53137, GSE58828, and GSE109476) in GEO database were used to screen differential expressed lncRNAs in gastric cancer by online GEO2R analysis tool. Quantitative RT-PCR was used to verify the above prediction in ten pairs of gastric cancer and corresponding paracancerous tissues. Pan-cancer analysis was used to analyze the expression of WFDC21P in different types of cancer. Small interfering RNAs were used to WFDC21P knockdown. CCK-8 and colony formation assays were used to measure the proliferation and tumorigenesis abilities. Wound healing and Transwell assay were used to detect the migration and invasion abilities. Proteins that interact with WFDC21P were predicted by catRAPID database. RNA pull down and RNA Immunoprecipitation were used to confirm the interaction. Western blotting was used to detect the key proteins level in calcium homeostasis signaling pathway. Loss-of-function and rescue assays were used to evaluate the biological function of SEC63 at the background of WFDC21P silencing.

Results

WFDC21P was upregulated in gastric cancer tissues and cell lines. WFDC21P downregulation suppressed proliferation, tumorigenesis, migration, invasion, and promoted apoptosis in gastric cancer. SEC63 protein had the capability to bind with WFDC21P and the expression of SEC63 was regulated by WFDC21P. SEC63 was also upregulated in gastric cancer and exerted effects during tumor growth and metastasis.

Conclusions

This study confirmed that lncRNA WFDC21P aggravated gastric cancer malignant behaviors by interacting with SEC63 to regulate the calcium homeostasis signaling pathway.
Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction
Authors: Jia Congzhuo , Wu Wanying , Lu Huan , Liu Jin , Chen Shiqun , Liang Guoxiao , Zhou Yang , Yu Sijia , Qiao Linfang , Chen Jinming , Tan Ning , Liu Yong , Chen Jiyan
Published: March 2024

Background

Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI.

Methods

A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death.

Results

Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99–3.65) and 1.48 (1.26–1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05).

Conclusion

AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients.

Trial registration

The Cardiorenal ImprovemeNt II registry NCT05050877.
Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy
Authors: Yang Haonan , Lei Zheng , He Jiang , Zhang Lu , Lai Tangmin , Zhou Liu , Wang Nuohan , Tang Zheng , Sui Jiangdong , Wu Yongzhong
Published: March 2024

Background

Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated.

Methods

Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining.

Results

Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control.

Conclusions

Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.
Mendelian randomization analysis reveals causal relationship between obstetric-related diseases and COVID-19
Authors: Fang Yan , Fang Dajun
Published: March 2024

Background

Several observational studies demonstrated that pregnant individuals with COVID-19 had a higher risk of preeclampsia and preterm birth. We aimed to determine whether women with COVID-19 diagnosis had adverse pregnancy outcomes.

Methods

A two-sample Mendelian randomization (MR) analysis in this study was used to evaluate the casual relationships between COVID-19 infection and obstetric-related diseases based on genome-wide association studies (GWAS) dataset. Inverse-variance weighted (IVW), MR-Egger and MR-PRESSO were used to infer the connection and estimate the pleiotropy respectively.

Results

The significant connection was observed between COVID-19 and placental disorders with betaIVW of 1.57 and odds ratio (OR) of 4.81 (95% confidence interval [CI]: 1.05–22.05, p = 0.04). However, there were no associations between COVID-19 infection and gestational diabetes mellitus (GDM) (OR = 1.12; 95% CI: 0.85–1.45, p = 0.41), other disorders of amniotic fluid and membranes (OR = 0.90; 95% CI: 0.61–1.32, p = 0.59), Intrahepatic Cholestasis of Pregnancy (ICP) (OR = 1.42; 95% CI: 0.85–2.36, p = 0.18), birth weight (OR = 1.02; 95% CI: 0.99–1.05, p = 0.19), gestational hypertension (OR = 1.00; 95% CI: 1.00–1.00, p = 0.85), spontaneous miscarriages (OR = 1.00; 95% CI: 0.96–1.04, p = 0.90) and stillbirth (OR = 1.00; 95% CI: 0.98–1.01, p = 0.62).

Conclusion

There was no direct causal relationship between COVID-19 infection and maternal and neonatal poor outcomes. Our study could alleviate the anxiety of pregnant women under the COVID-19 pandemic conditions partly.
Gentiopicroside ameliorates the lipopolysaccharide-induced inflammatory response and hypertrophy in chondrocytes
Authors: Li Longfei , Fan Qianqian , Zhao Yixuan , Zhang Qian , Qin Gaofeng , Li Chen , Li Wei
Published: March 2024

Purpose

This study aimed to evaluate the protective effects of gentiopicroside against lipopolysaccharide-induced chondrocyte inflammation.

Methods

SW 1353 chondrosarcoma cells were stimulated with LPS (5 μg/ml) for 24 h and treated with different concentrations of gentiopicroside (GPS) for 24 h. The toxic effects of GPS on chondrocytes were determined using a CCK-8 assay and EdU staining. Western blotting, qPCR, and immunofluorescence analysis were used to examine the protective effect of GPS against the inflammatory response in chondrocytes induced by lipopolysaccharide (LPS). One-way ANOVA was used to compare the differences between the groups (significance level of 0.05).

Results

The CCK-8 results showed that 10, 20 and 40 μM GPS had no significant toxic effects on chondrocytes; GPS effectively reduced the production of IL-1β and PGE2, reversed LPS-induced extracellular matrix degradation in cartilage by inhibiting the Stat3/Runx2 signaling pathway, and suppressed the hypertrophic transformation of SW 1353 chondrosarcoma cells.

Conclusion

Our study demonstrated that GPS significantly inhibited the LPS-induced inflammatory response and hypertrophic cellular degeneration in SW 1353 chondrosarcoma cells and is a valuable traditional Chinese medicine for the treatment of knee osteoarthritis.
The value of machine learning technology and artificial intelligence to enhance patient safety in spine surgery: a review
Authors: Arjmandnia Fatemeh , Alimohammadi Ehsan
Published: March 2024

Machine learning algorithms have the potential to significantly improve patient safety in spine surgeries by providing healthcare professionals with valuable insights and predictive analytics. These algorithms can analyze preoperative data, such as patient demographics, medical history, and imaging studies, to identify potential risk factors and predict postoperative complications. By leveraging machine learning, surgeons can make more informed decisions, personalize treatment plans, and optimize surgical techniques to minimize risks and enhance patient outcomes. Moreover, by harnessing the power of machine learning, healthcare providers can make data-driven decisions, personalize treatment plans, and optimize surgical interventions, ultimately enhancing the quality of care in spine surgery. The findings highlight the potential of integrating artificial intelligence in healthcare settings to mitigate risks and enhance patient safety in surgical practices. The integration of machine learning holds immense potential for enhancing patient safety in spine surgeries. By leveraging advanced algorithms and predictive analytics, healthcare providers can optimize surgical decision-making, mitigate risks, and personalize treatment strategies to improve outcomes and ensure the highest standard of care for patients undergoing spine procedures. As technology continues to evolve, the future of spine surgery lies in harnessing the power of machine learning to transform patient safety and revolutionize surgical practices. The present review article was designed to discuss the available literature in the field of machine learning techniques to enhance patient safety in spine surgery.
PELI1: key players in the oncogenic characteristics of pancreatic Cancer
Authors: Fei Xiaobin , Zhu Changhao , Liu Peng , Liu Songbai , Ren Likun , Lu Rishang , Hou Junyi , Gao Yongjia , Wang Xing , Pan Yaozhen
Published: March 2024

Background

Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant tumors has been demonstrated, its association with PC remains uncertain.

Methods

Bioinformatics, qRT-PCR, Western blot and IHC were used to detect the expression of PELI1 in pancreas or PC tissues and cells at mRNA and protein levels. The effects of PELI1 on the proliferation and metastatic ability of pancreatic cancer in vitro and in vivo were investigated using CCK8, cloning formation, EdU, flow cytometry, IHC, Transwell assay, wound healing, nude mice subcutaneous tumorigenesis and intrasplenic injection to construct a liver metastasis model. The interactions of PELI1 with proteins as well as the main functions and pathways were investigated by protein profiling, Co-IP, GST-pull down, Immunofluorescence techniques, immunohistochemical co-localization and enrichment analysis. The rescue experiment verified the above experimental results.

Results

The mRNA and protein expression levels of PELI1 in PC tissues were upregulated and were associated with poor prognosis of patients, in vitro and in vivo experiments confirmed that PELI1 can affect the proliferation and metastatic ability of PC cells. Co-IP, GST-pull down, and other experiments found that PELI1 interacted with Ribosomal Protein S3 (RPS3) through the FHA structural domain and promoted the polyubiquitination of RPS3 in the K48 chain, thereby activates the PI3K/Akt/GSK3β signaling pathway. Moreover, ubiquitinated degradation of RPS3 further reduces Tumor Protein P53 (p53) protein stability and increases p53 degradation by MDM2 Proto-Oncogene (MDM2).

Conclusion

PELI1 is overexpressed in PC, which increased ubiquitination of RPS3 proteins and activates the PI3K/Akt/GSK3β signaling pathway, as well as reduces the protective effect of RPS3 on p53 and promotes the degradation of the p53 protein, which facilitates the progression of PC and leads to a poor prognosis for patients. Therefore, PELI1 is a potential target for the treatment of PC.
Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer
Authors: Ding Lin , Jiang Hui , Li Qiangwei , Li Qiushuang , Zhang Tian-Tian , Shang Limeng , Xie Bin , Zhu Yaling , Ding Keshuo , Shi Xuanming , Zhu Tao , Zhu Yong
Published: March 2024

Background

Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive.

Methods

The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently.

Results

Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells.

Conclusion

Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.
An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study
Authors: Servadio Michela , Finocchietti Marco , Vassallo Chiara , Cipelli Riccardo , Heiman Franca , Di Lucchio Giulia , Oresta Bianca , Addis Antonio , Belleudi Valeria
Published: March 2024

Background

Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context.

Methods

This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described.

Results

A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use.

Conclusions

The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.
Eukaryotic-driven directed evolution of Cas9 nucleases
Authors: Ruta Giulia Vittoria , Ciciani Matteo , Kheir Eyemen , Gentile Michele Domenico , Amistadi Simone , Casini Antonio , Cereseto Anna
Published: March 2024

Background

Further advancement of genome editing highly depends on the development of tools with higher compatibility with eukaryotes. A multitude of described Cas9s have great potential but require optimization for genome editing purposes. Among these, the Cas9 from Campylobacter jejuni, CjCas9, has a favorable small size, facilitating delivery in mammalian cells. Nonetheless, its full exploitation is limited by its poor editing activity.

Results

Here, we develop a Eukaryotic Platform to Improve Cas Activity (EPICA) to steer weakly active Cas9 nucleases into highly active enzymes by directed evolution. The EPICA platform is obtained by coupling Cas nuclease activity with yeast auxotrophic selection followed by mammalian cell selection through a sensitive reporter system. EPICA is validated with CjCas9, generating an enhanced variant, UltraCjCas9, following directed evolution rounds. UltraCjCas9 is up to 12-fold more active in mammalian endogenous genomic loci, while preserving high genome-wide specificity.

Conclusions

We report a eukaryotic pipeline allowing enhancement of Cas9 systems, setting the ground to unlock the multitude of RNA-guided nucleases existing in nature.
Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters
Authors: Koestler Stefan A. , Ball Madeleine L. , Muresan Leila , Dinakaran Vineet , White Robert
Published: March 2024

Chromatin state is thought to impart regulatory function to the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate to one another to regulate gene expression is unclear. In this study, we have used super-resolution microscopy to image the Y loops of Drosophila melanogaster primary spermatocytes, which are enormous transcriptionally active chromatin fibres, each representing single transcription units that are individually resolvable in the nuclear interior. We previously found that the Y loops consist of regular clusters of nucleosomes, with an estimated median of 54 nucleosomes per cluster with wide variation.

In this study, we report that the histone modifications H3K4me3, H3K27me3, and H3K36me3 are also clustered along the Y loops, with H3K4me3 more associated with diffuse chromatin compared to H3K27me3. These histone modifications form domains that can be stretches of Y loop chromatin micrometres long, or can be in short alternating domains. The different histone modifications are associated with different sizes of chromatin clusters and unique morphologies. Strikingly, a single chromatin cluster almost always only contains only one type of the histone modifications that were labelled, suggesting exclusivity, and therefore regulation at the level of individual chromatin clusters. The active mark H3K36me3 is more associated with actively elongating RNA polymerase II than H3K27me3, with polymerase often appearing on what are assumed to be looping regions on the periphery of chromatin clusters.

These results provide a foundation for understanding the relationship between chromatin state, chromatin organisation, and transcription regulation – with potential implications for pause-release dynamics, splicing complex organisation and chromatin dynamics during polymerase progression along a gene.
Enhancing recurrence risk prediction for bladder cancer using multi-sequence MRI radiomics
Authors: Yang Guoqiang , Bai Jingjing , Hao Min , Zhang Lu , Fan Zhichang , Wang Xiaochun
Published: March 2024

Objective

We aimed to develop a radiomics-clinical nomogram using multi-sequence MRI to predict recurrence-free survival (RFS) in bladder cancer (BCa) patients and assess its superiority over clinical models.

Methods

A retrospective cohort of 229 BCa patients with preoperative multi-sequence MRI was divided into a training set (n = 160) and a validation set (n = 69). Radiomics features were extracted from T2-weighted images, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced images. Effective features were identified using the least absolute shrinkage and selection operator (LASSO) method. Clinical risk factors were determined via univariate and multivariate Cox analysis, leading to the creation of a radiomics-clinical nomogram. Kaplan-Meier analysis and log-rank tests assessed the relationship between radiomics features and RFS. We calculated the net reclassification improvement (NRI) to evaluate the added value of the radiomics signature and used decision curve analysis (DCA) to assess the nomogram’s clinical validity.

Results

Radiomics features significantly correlated with RFS (log-rank p < 0.001) and were independent of clinical factors (p < 0.001). The combined model, incorporating radiomics features and clinical data, demonstrated the best prognostic value, with C-index values of 0.853 in the training set and 0.832 in the validation set. Compared to the clinical model, the radiomics-clinical nomogram exhibited superior calibration and classification (NRI: 0.6768, 95% CI: 0.5549-0.7987, p < 0.001).

Conclusion

The radiomics-clinical nomogram, based on multi-sequence MRI, effectively assesses the BCa recurrence risk. It outperforms both the radiomics model and the clinical model in predicting BCa recurrence risk.

Critical relevance statement

The radiomics-clinical nomogram, utilizing multi-sequence MRI, holds promise for predicting bladder cancer recurrence, enhancing individualized clinical treatment, and performing tumor surveillance.

Key points

• Radiomics plays a vital role in predicting bladder cancer recurrence.

• Precise prediction of tumor recurrence risk is crucial for clinical management.

• MRI-based radiomics models excel in predicting bladder cancer recurrence.

Graphical Abstract
Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study
Authors: Sawada Tomonori , Okawara Hiroki , Nakashima Daisuke , Aoki Kentaro , Namba Mira , Iwabuchi Shuhei , Katsumata Yoshinori , Nakamura Masaya , Nagura Takeo
Published: March 2024

Background

Local alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.

Methods

Twenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.

Results

Alternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from − 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).

Conclusions

Local alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.

Trial registration

UMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710. UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359).
Influencing factors of sleep quality in pregnant: a structural equation model approach
Authors: Bahani Mailiman , Zhang Yuxia , Guo Yufeng , Haretebieke Salawati , Wu Di , Zhang Liping
Published: March 2024

Background

To describe the changes in the level of sleep quality during pregnancy among pregnant women in Urumqi; also to construct a structural equation model of the factors influencing the sleep quality of pregnant women, to analyze the path relationship between the influencing factors, and to take reasonable interventions to prevent and reduce the occurrence of sleep disorders among pregnant women.

Methods

986 pregnant women who gave birth in Urumqi Maternal and Child Health Hospital and Urumqi Youai Hospital between August 2021 and May 2023 were selected. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Edinburgh Postpartum Depression Scale (EPDS) were used to assess the sleep, anxiety, and depression of pregnant women, Building a structural equation model based on AMOS 23.0 Tools.

Results

The results of structural equation modeling showed that: basic characteristics, obstetrical characteristics, tocolysis, lifestyle, psychological had a direct effect on the PSQI, with path coefficients of 0.243, 0.106, 0.140, 0.174, 0.658, the corresponding T-values for each path are 4.585, 2.677, 2.578, 2.297, and 9.036. The indirect effect of basic characteristics, obstetric characteristics and lifestyle on PSQI was 0.123, 0.020, 0.027.

Conclusions

The high incidence of sleep disorders in pregnant women and their close association with psychological symptoms in pregnant women should focus on screening and counseling regarding psychological disorders in pregnant women, thus improving the quality of sleep in pregnant women.
Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner
Authors: Zeng Miao , Zhang Wei , Li Yisheng , Yu Li
Published: March 2024

Recombinant adenovirus (rAd) regimens, including replication-competent oncolytic adenovirus (OAV) and replication-deficient adenovirus, have been identified as potential cancer therapeutics. OAV presents advantages such as selective replication, oncolytic efficacy, and tumor microenvironment (TME) remodeling. In this perspective, the principles and advancements in developing OAV toolkits are reviewed. The burgeoning rAd may dictate efficacy of conventional cancer therapies as well as cancer immunotherapies, including cancer vaccines, synergy with adoptive cell therapy (ACT), and TME reshaping. Concurrently, we explored the potential of rAd hitchhiking to adoptive immune cells or stem cells, highlighting how this approach facilitates synergistic interactions between rAd and cellular therapeutics at tumor sites. Results from preclinical and clinical trials in which immune and stem cells were infected with rAd have been used to address significant oncological challenges, such as postsurgical residual tumor tissue and metastatic tissue. Briefly, rAd can eradicate tumors through various mechanisms, resulting from tumor immunogenicity, reprogramming of the TME, enhancement of cellular immunity, and effective tumor targeting. In this context, we argue that rAd holds immense potential for enhancing cellular immunity and synergistically improving antitumor effects in combination with novel cancer immunotherapies.
The more we search, the more we find: discovering and expanding the biodiversity in the ring nematode genus Xenocriconemella De Grisse and Loof, 1965 (Nematoda: Criconematidae)
Authors: Archidona-Yuste A. , Clavero-Camacho I. , Ruiz-Cuenca A. N. , Cantalapiedra-Navarrete C. , Liebanas G. , Castillo P. , Palomares-Rius J. E.
Published: March 2024

The ring nematode genus Xenocriconemella De Grisse and Loof, 1965 comprises only one nominal species, Xenocriconemella macrodora (Taylor, 1936) De Grisse and Loof, 1965. The initial objective of the present study was to investigate the morphological–morphometric and molecular diversity of 28 X. macrodora populations in the Iberian Peninsula associated with tree forests (mainly Quercus spp.). However, a detailed integrative taxonomic analysis (morphological–morphometric and molecular data) from each population and analysis of this data using principal component analysis (PCA) for morphometric data (including these 28 populations and other 25 X. macrodora populations around the world) and molecular and phylogenetic species delimitation methods revealed that X. macrodora forms a species complex. This species complex is composed by species that are morphometricly and morphologically similar, but clearly different at the molecular level. Three new species are described applying integrative taxonomy, namely as Xenocriconemella iberica sp. nov., Xenocriconemella paraiberica sp. nov. and Xenocriconemella pradense sp. nov. However, the molecular diversity of this species in USA and Italy confirmed that additional species are likely present in this species complex, and the diversity of this group may be higher than expected. The study of X. macrodora topotypes can clarify the position of this species using molecular markers under an integrative approach.
Efficiency analysis and benchmarking of container ports operating in lower-middle-income countries: a DEA approach
Authors: Danladi Caleb , Tuck Sarah , Tziogkidis Panagiotis , Tang Lijun , Okorie Chukwuneke
Published: March 2024

Container ports play a pivotal role in international trade, facilitating the movement of goods and fostering economic development. While much attention has been given to the efficiency of ports in high-income countries, container ports in lower-middle-income (LMI) countries have received less attention. This paper addresses this research gap by assessing container ports' operational efficiency across diverse LMI countries and determining ways for their efficiency enhancement and management optimization. The cross-sectional data for the year 2012 was collected for 53 container ports in LMI countries. This research utilizes data envelopment analysis, which offers the advantage of considering multiple inputs and outputs. The results show that the overall technical inefficiencies of LMI countries' container ports are mainly due to pure technical inefficiency rather than scale inefficiencies, and the most efficient ports have a combination of large and hub ports. They also reveal that larger ports (as measured by throughput) are not necessarily more efficient than ports with a small production scale. The results of this research can provide government authorities, port authorities, terminal operators, and investors with valuable insights into resource allocation, competitive advantage, and optimization of operating performance.
The impact of the belt and road initiative on the Suez Canal cargo trade
Authors: Rakha Anas , El‑Aasar Khadiga
Published: March 2024

The Suez Canal (SC) serves as the shortest maritime transport route from east to west. In the absence of the SC, global trade and transportation costs would increase substantially, impeding the expansion potential of the global economy. The Belt and Road Initiative (BRI) is a key component of China's future international trading network, with significant implications for global seaborne trade. The BRI's two primary pillars are the Maritime Silk Road (MSR) and the Silk Road Economic Belt, both of which have significant infrastructural investments. The MSR connects China to various regions in Asia, Africa, and Europe via the SC, thereby serving as a significant maritime trade route on a global scale, particularly between Europe and China. This is due to the SC's distinctive positioning on the MSR. Consequently, studying the significance of BRI for the SC cargo trade is crucial. This study uses annual data from 1990 to 2022 to examine this dynamic relationship. To account for the interaction effect of the variables, we use the vector autoregressive model and the impulse response function. Model results show that China's seaborne trade will increase SC trade by 23%, and China's BRI investment projects are anticipated to have a 5% significant impact on SC cargo trade and will continue to grow in the medium and long run. According to these findings, the SC has to continue to adopt more flexible pricing and marketing strategies to encourage and attract more customers. As a result, the SC could become a global logistics center and transform from a trade gateway to a global hub if it develops more value-added activities in its adjacent areas and attracts substantial Chinese investments.
In-target production of [11C]CH4 from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature
Authors: Helin Semi , Rajander Johan , Aromaa Jussi , Arponen Eveliina , Helin Jatta S. , Solin Olof
Published: March 2024

Background

Production of [11C]CH4 from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [11C]CO2 to [11C]CH4 is a widely used roundabout method in 11C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [11C]CH4 is superior with respect to molar activity. We studied the in-target production of [11C]CO2 and [11C]CH4 from nitrogen gas targets as a function of beam current, irradiation time, and target temperature.

Results

[11C]CO2 production was practically unchanged across the range of varied parameters, but the [11C]CH4 yield, presented in terms of saturation yield YSAT(11CH4), had a negative correlation with beam current and a positive correlation with target chamber temperature. A formulated model equation indicates behavior where the [11C]CH4 formation follows a parabolic graph as a function of beam current. The negative square term, i.e., the yield loss, is postulated to arise from Haber–Bosch-like NH3 formation: N2 + 3H2 → 2NH3. The studied conditions suggest that the NH3 (liq.) would be condensed on the target chamber walls, thus depleting the hydrogen reserve needed for the conversion of nascent 11C to [11C]CH4.

Conclusions

[11C]CH4 production can be improved by increasing the target chamber temperature, which is presented in a mathematical formula. Our observations have implications for targetry design (geometry, gas volume and composition, pressure) and irradiation conditions, providing specific knowledge to enhance [11C]CH4 production at high beam currents. Increased [11C]CH4 radioactivity is an obvious benefit in radiosynthesis in terms of product yield and molar radioactivity.
Association between thoracic density and area with COVID-19 outcomes
Authors: Ahmadzadeh Nanva Amirhasan , Haghighi-Morad Maryam , Taheri Mahbobeh , Nosrati Maryam
Published: March 2024

Background

The relationship between sarcopenia and the consequences of COVID-19 is not yet fully understood. It is noteworthy that information about muscle status can be easily retrieved by segmenting specific regions of skeletal muscles on CT scans. Our aim in this study was to investigate the relationship between sarcopenia and the consequences of COVID-19.

Methods

In this analytical cross-sectional study, 338 patients with COVID-19 who had a positive PCR test for COVID-19 and underwent chest CT scan in Loghman-e-Hakim Hospital from July to September 2021 were evaluated. Age, sex, background diseases, mechanical ventilation, duration of hospitalization, as well as lab tests, ICU admission and mortality were extracted from patient records. The severity of COVID-19 disease and the area and density of paraspinal muscles at the level of T5 and T12 vertebrae were evaluated through chest CT scans.

Results

Length of stay had significant relationship with T5 density (1.15 (< 0.001)) and T12 density (1.24 (< 0.001). The mean of T12 area (3.35 (P = 0.005) and T12 density 4.59 (P = 0.012) were significantly lower in ICU admitted. There was a significant relationship between mortality and age, cardiovascular disorders, COPD, underlying disease, length of stay, WBC and lymphocyte levels, as well as the severity of the disease.

Conclusions

Based on the results of this study, we can infer that the use of CT scan in patients with COVID-19 and the determination of muscle area and density can predict the consequences of COVID-19, such as a longer duration of hospitalization, the need for admission to the ICU, and mortality.