bluuebunny/crossref_metadata_2025 huggingface dataset:
Virology, epidemiology, transmissions, diagnostic tests, prophylaxis and treatments of human Mpox: Saudi Arabia perspective
Authors: Hershan Almonther Abdullah
Published: February 2025

Mpox (Monkeypox) is a highly contagious viral disease that can be transmitted from animal-to-human or human-to-human through intimate contact, Mpox is caused by the monkeypox virus (MPXV), which is an enveloped double-stranded DNA that belongs to the genus Orthopoxvirus, Poxviridae family, and subfamily Chordopoxvirinae. Mpox cases were previously only reported in West and Central Africa, however in recent times non-endemic countries including Saudi Arabia (SA) also reported confirmed Mpox cases. The first laboratory-confirmed human Mpox case in SA was reported on 14 July 2022, since then a number of confirmed Mpox cases have been reported by WHO in SA. These confirmed Mpox cases in SA were observed among individuals with a history of visiting European Union countries. SA is not only at risk of importation of Mpox cases owing to travel to such countries, but also there are various other risk factors including geographic proximity to the African continent, trade in exotic animals, and massive inflow of tourists. Therefore, government health authorities of SA should continue to collaborate with various international health organizations including WHO to prevent, manage or monitor potential health risks at most of the entry points in SA including highways, seaports, and airports by ensuring adherence to hygiene protocols, vaccinations, and health screenings. There are a range of diagnostic tests are currently available that can be used in SA to confirm Mpox infections, including real-time PCR, loop-mediated isothermal amplification, serological testing, clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas)-based systems, whole-genome sequencing, electron microscopy, and virus isolation and culture. There is no approved treatment specifically for Mpox, however multiple approved antiviral agents for smallpox treatment were found to be useful in Mpox treatment and in the management of Mpox outbreaks, such as- trifluridine, brincidofovir, tecovirimat, and cidofovir. The aim of this review is to provide valuable insights regarding virology, pathogenesis, epidemiology, transmissions, clinical presentation, diagnostic tests, prophylactic measures and therapeutic options of Mpox from SA perspective. Moreover, a side-by-side discussion on the global trend and scenarios of Mpox has been provided for comparison and further improvement in measures against Mpox in SA.
Characteristics of myocardial work during exercise stress echocardiography in healthy adults
Authors: Huang Liwei , Ye Luwei , Zhang Hongmei , Zhang Qingfeng , Ding Geqi , Li Chunmei , Deng Yan , Yin Lixue , Wang Yi
Published: February 2025

Background

Non-invasive myocardial work (MW) is a more precise parameter for evaluating left ventricular (LV) systolic function. However, studies examining sex-based differences in MW during exercise stress echocardiography (SE) in healthy individuals are scarce. Previous research has shown that global work efficiency (GWE) decreases following exercise.

Objectives

To characterize sex-based differences in MW during exercise SE in healthy adults and to explore the factors influencing the decline in GWE post-exercise.

Methods

The study enrolled 200 healthy adults, all of whom underwent echocardiographic assessments both at rest and immediately after completing a symptom-limited treadmill stress test. We measured LV volume, ejection fraction (EF), force, peak positive strain (PPS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and GWE at rest and post-exercise.

Results

GWI, GCW, and GWW increased, while GWE decreased after exercise. There were no significant differences in any of the global MW parameters between sexes at rest (all p > 0.05). The change in △GWE was greater in women (p < 0.05), but no significant differences were found in other MW reserve parameters between sexes. The multivariable linear regression analysis revealed that GWW was independently associated with PPS (β = 0.842, p < 0.0001) and force (β = 0.306, p = 0.023). Furthermore, the multivariable linear regression analysis showed that GWE was independently associated with PPS (β = −0.395, p = 0.018) and EF (β = −0.236, p < 0.001).

Conclusion

Sex had a minimal effect on MW-based LV systolic function in healthy adults. GWE decreased post-exercise, and both PPS and force were independently associated with GWW. These findings suggest that higher contractility is achieved at the cost of increased wasted work, which subsequently leads to a decrease in mechanical efficiency.
bk-5214S2L, an allelic variant of bk-5, as high-quality silage maize genetic resource
Authors: Li Gang , Du Jiyuan , Li Xiaohu , Zhuge Shilin , Ren Shuolin , Wu Min , Ma Haoran , Guo Xinrui , Chen Ziqiang , Ding Haiping
Published: February 2025

Introduction

Stem brittleness significantly affects both yield and quality of maize.

Methods

Using phenotypic identification and sequence analysis, we identified a new brittle stalk maize mutant. Furthermore, we assessed its feeding value by content determination of cellulose, hemicellulose, lignin crude fiber, starch, and protein contents.

Results

Here, we identified a brittle stalk maize mutant, bk-5214S2L, an allelic variant of bk-5. The stem brittleness of bk-5214S2L was similar to that of bk-5, but not identical. Unlike bk-5, bk-5214S2L leaves did not fall off completely and its stems did not break in windy conditions. We identified a missense mutation (C>T) in the fifth exon of the candidate gene Zm00001d043477, resulting in an amino acid change from serine to leucine at position 214. A significant reduction in cell wall thickness in the leaf veins and stems of bk-5214S2L compared with the inbred line RP125. Among the major cell wall components in stems and leaves, total cellulose, hemicellulose, and lignin were lower in bk-5214S2L than in RP125. We also evaluated the application value of bk-5214S2L silage and found that the detergent fiber contents of bk-5214S2L stems were significantly reduced compared with RP125, while the crude fiber, starch, and protein contents remained unchanged. The reduced tannin content improved the palatability of the silage for livestock.

Conclusion

Overall, bk-5214S2L, an allelic variant of bk-5, is a high-quality genetic resource for breeding forage and grain-feed maize.
Unveiling the immunological landscape of disseminated tuberculosis: a single-cell transcriptome perspective
Authors: Gong Zhen , Xu Hongxiang , Zhang Qiao , Wang Guirong , Fan Lin , Wang Zilu , Fan Lichao , Liu Chang , Yu Yanhong , Liu Zhou , Zhou Qiang , Xiao Huasheng , Hou Rui , Zhao Ying , Chen Yu , Xie Jianping
Published: February 2025

Introduction

Hematogenous disseminated tuberculosis (DTB) has an unclear etiology that likely involves multiple factors. Understanding the underlying immunological characteristics of DTB is crucial for elucidating its pathogenesis.

Methods

We conducted single-cell RNA transcriptome and T cell receptor (TCR) sequencing on samples from seven DTB patients. Additionally, we integrated and analyzed data from two published profiles of latent TB infection, three active TB cases, and two healthy controls.

Results

Our analysis revealed a significantly higher proportion of inflammatory immune cells (e.g., monocytes and macrophages) in DTB patients, along with a notably lower abundance of various lymphocytes (including T cells, B cells, and plasma cells), suggesting that lymphopenia is a prominent feature of the disease. T cell pseudotime analysis indicated a decrease in the expression of most hypervariable genes over time, pointing to T cell functional exhaustion. Furthermore, a marked absence of mucosal-associated invariant T (MAIT) cells was observed in the peripheral blood of DTB patients. In the TCR repertoire, specific polymorphisms (TRAV9-2, TRAV13-1, TRBV20-1, and TRBV5-1) and dominant clones (TRAJ49, TRBJ2-7, and TRBJ2-1) were identified. Analysis of the complementarity determining region 3 (CDR3) showed that the most frequent combination was TRAV1-2/TRAJ33, with the motif “CAAMD” being significantly reduced in DTB patients.

Discussion

These findings suggest that lymphopenia and T cell exhaustion, along with unique TCR signatures, may play critical roles in DTB pathogenesis. The reduced “CAAMD” motif and altered TCR clonotypes provide novel insights into the complex cellular dynamics associated with the disease, potentially offering new avenues for targeted immunological interventions.
Berberine hydrochloride enhances innate immunity to protect against pathogen infection via p38 MAPK pathway
Authors: Xiao Yi , Cui Yingwen , Zhang Yan , Fu Wenqiao , Liu Yun , Liu Fang
Published: February 2025

The p38 MAPK pathway, an evolutionarily conserved mechanism, plays a crucial role in defending hosts against bacterial infections in both mammals and nematodes. Activating p38 MAPK signaling has been identified as a promising strategy to strengthen innate immunity and enhance resistance to pathogenic infections across various organisms.Berberine hydrochloride (BH), an isoquinoline alkaloid derived from Coptis, is known for its diverse biological activities, including anticancer, antibacterial, anti-inflammatory, lipid-lowering, and hepatoprotective effects. However, its impact on innate immunity and the associated molecular mechanisms remains unclear. In this study, we discovered that 10 μM Berberine hydrochloride enhanced resistance against both Gram-negative pathogens, such as Pseudomonas aeruginosa, Salmonella enterica and Gram-positive pathogen Listeria monocytogenes. Notably, Berberine hydrochloride improved pathogen resistance by reducing bacterial load in the intestine. Screening of classical innate immune pathways in Caenorhabditis elegans revealed that Berberine hydrochloride conferred protection against infections through the p38 MAPK pathway, specifically by activating p38/PMK-1 signaling in the intestine to bolster innate immunity. Furthermore, Berberine hydrochloride also stimulated innate immunity in mice via the p38 MAPK pathway and significantly reduced bacterial load in the lungs. These findings indicate that Berberine hydrochloride may have therapeutic potential for protecting host from infectious diseases.
T cells in the microenvironment of solid pediatric tumors: the case of neuroblastoma
Authors: Maggi Enrico , Landolina Nadine , Munari Enrico , Mariotti Francesca Romana , Tumino Nicola , Vacca Paola , Azzarone Bruno , Moretta Lorenzo
Published: February 2025

Neuroblastoma (NB) is an immunologically “cold” tumor with poor or no inflamed substrates as most of solid pediatric tumors (SPT). Consistent data indicate that NB tumor microenvironment (TME) is dominated by myeloid cells, with little (but variable) T cell infiltration. The obstacles to lymphocyte infiltration and to their anti-tumor activity are due to different tumor immune evasion strategies, including loss of HLA Class I molecules, high expression of immune checkpoint molecular ligands leading to exhaustion of T effector (and NK) cells, induction of T regulatory, myeloid and stromal cells and secretion of immunosuppressive mediators. In odds with adult solid tumors, NB displays weak immunogenicity caused by intrinsic low mutational burden and scant expression of neoepitopes in the context of MHC-class I antigens which, in turn, are particularly poorly expressed on NB cells, thus inducing low anti-tumor T cell responses. In addition, NB is generated from embryonal cells and is the result of transcriptional abnormalities and not of the accumulation of genetic mutations over time, thus further explaining the low immunogenicity. The poor expression of immunogenic molecules on tumor cells is associated with the high production of immunosuppressive factors which further downregulate lymphocyte infiltration and activity, thus explaining the limited efficacy of new drugs in NB, as immune checkpoint inhibitors. This review is focused on examining the role of T effector and regulatory cells infiltrating TME of NB, taking into account their repertoire, phenotype, function, plasticity and, importantly, predictive value for defining novel targets for therapy.
Tandem CAR-T cell therapy: recent advances and current challenges
Authors: Gómez-Melero Sara , Hassouneh Fakhri , Vallejo-Bermúdez Isabel M. , Agüera-Morales Eduardo , Solana Rafael , Caballero-Villarraso Javier
Published: February 2025

CAR-T cell therapy has revolutionized cancer treatment. However, despite the achievements of this approach, there are still clinical challenges to address, such as antigen loss and the design of an optimal CAR structure. Multi-targeted CAR-T therapies, including tandem CAR-T cells, have emerged as a strategy to overcome some of these limitations and improve outcomes. Tandem CAR-T cells are currently being evaluated in preclinical and clinical studies for the treatment of hematological malignancies and solid tumors, showing promising results. These CARs have demonstrated efficacy, safety, and a relatively low relapse rate in these studies. Research suggests that TanCAR-T cells can enhance the outcomes and benefits of CAR-T cell therapy. However, challenges such as identifying the ideal CAR construct, selecting appropriate targets, and improving transduction efficiency remain unresolved, and further research is essential to address these limitations. This review highlights the potential of tandem CAR-T cells as a cancer treatment, summarizing preclinical and clinical studies with this innovative therapy and emphasizing the importance of continued research to overcome its limitations and improve its effectiveness.
Inhibiting melanoma tumor growth: the role of oxidative stress-associated LINC02132 and COPDA1 long non-coding RNAs
Authors: Xu JingWen , Jin MingZhu , Mu ZhenZhen , Li ZhengXiu , Qi RuiQun , Han XiuPing , Jiang HangHang
Published: February 2025

Background

Cutaneous melanoma is a type of malignant tumor that is challenging to predict and is readily stimulated by various factors. Oxidative stress can induce damage and alterations in melanocytes, subsequently triggering immune responses. Given that oxidative stress is a prevalent tumor stimulus, we aimed to enhance melanoma prediction by identifying lncRNA signatures associated with oxidative stress.

Methods

We screened for oxidative stress-related lncRNAs that could improve melanoma patient prognosis using the TCGA and GTEx databases. Utilizing differentially expressed oxidative stress-related lncRNAs (DE-OSlncRNAs), we constructed a Lasso regression model. The accuracy of the model was validated using univariate and multivariate regression, Kaplan-Meier (K-M) curves, and ROC curves. Subsequently, we conducted immune infiltration analysis, immune checkpoint differential analysis, IC50 pharmaceutical analysis, and gene set enrichment analysis. Investigating the effects of the target gene on melanoma using fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), Edu assay, wound healing assay, transwell assay, flow cytometry, and reactive oxygen species (ROS) detection.

Results

Thirteen lncRNAs were identified as significant prognostic factors. Four oxidative stress-related lncRNAs (COPDA1, LINC02132, LINC02812, and MIR205HG) were further validated by fluorescence in situ hybridization (FISH), with results consistent with our data analysis. LINC02132 and COPDA1 can influence the proliferation, invasion, migration, and apoptosis of melanoma.

Conclusion

Our findings suggest that upregulation of the LINC02132 or COPDA1 genes elevates intracellular reactive oxygen species (ROS) levels in melanoma cells, suppresses tumor cell proliferation, migration, and invasion, and promotes apoptosis. These results suggest a novel therapeutic strategy for melanoma treatment.
Healthcare AI, explainability, and the human-machine relationship: a (not so) novel practical challenge
Authors: Giorgetti Claudia , Contissa Giuseppe , Basile Giuseppe
Published: February 2025

This paper focuses on the lack of explainability that afflicts machine-learning-based AI systems applied in the field of healthcare. After a brief introduction to the topic, from both a technical and legal point of view, this work aims to assess the main consequences that the lack of explainability has on the human-machine relationship in clinical care, through a practical perspective. It then questions whether explainability is truly an objective worth seeking and, if so, to what extent, taking into account the current possible solutions.
Chromatin structure and gene transcription of recombinant p53 adenovirus vector within host
Authors: Ning Duo , Deng Yuqing , Tian Simon Zhongyuan
Published: February 2025

Introduction

The recombinant human p53 adenovirus (Ad-p53) offers a promising approach for cancer therapy, yet its chromatin structure and effects on host chromatin organization and gene expression are not fully understood.

Methods

In this study, we employed in situ ChIA-PET to investigate the colorectal cancer cell line HCT116 with p53 knockout, comparing them to cells infected with the adenovirus-vector expressing p53. We examined alterations in chromatin interactions and gene expression following treatment with the anti-cancer drug 5-fluorouracil (5-FU).

Results

Our results indicate that Ad-p53 forms a specific chromatin architecture within the vector and mainly interacts with repressive or inactive regions of host chromatin, without significantly affecting the expression of associated genes. Additionally, Ad-p53 does not affect topologically associating domains (TADs) or A/B compartments in the host genome.

Discussion

These findings suggest that while Ad-p53 boosts p53 expression, enhancing drug sensitivity without substantially altering host HCT116 chromatin architecture.
Behavior at work: propositions for optimizing the human and organizational challenges of digital materials passports
Authors: Grozev Vladislav Hristov , Axtell Carolyn , Zhang Hui , Nielsen Karina
Published: February 2025

There is growing research on the implementation of Digital Materials Passports (DMPs) in different industries, yet there is lack of guidance for preparing the human and organizational components within this ecosystem of change. To help fill this void, in this position paper, we develop propositions for dealing with the people and organizational challenges of implementing DMP’s within organizations and across supply chains. Applying a socio-technical systems approach, we highlight the interconnectedness between the human, organizational, and technical factors when designing and implementing DMPs. We also use the IGLOO framework which highlights that organizational support needs to occur at the individual, group, leader, organizational, and omnibus (interorganizational) levels. We draw on research from the literature on human behavior at work, covering areas such as social identity, trust, resilience in organizations, leadership, participatory job redesign, and training and learning as mechanisms to reduce socio-technical challenges and to reach important interorganizational goals. Understanding these mechanisms helps us to develop seven propositions that organizations and supply chains can put in place when implementing DMPs. These propositions can offer mutually reinforcing support for organizations when implemented, and can be adapted to consider both the long-term and the immediate implementation context. We also discuss the role of employee involvement in enhancing the benefit of the propositions for organizations and supply chains in moving towards Industry 5.0.
Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
Authors: Ibrahim Yehia , Macerollo Antonella , Sardone Rodolfo , Shen Yaochun , Romano Vito , Zheng Yalin
Published: February 2025

Background

Alzheimer’s disease (AD) is a major healthcare challenge, with existing diagnostics being costly/infeasible. This study explores retinal biomarkers from optical coherence tomography (OCT) and OCT angiography (OCTA) as a cost-effective and non-invasive solution to differentiate AD, mild cognitive impairment (MCI), and healthy controls (HCs).

Methods

Participants from the CALLIOPE Research Program were classified as “Dem” (AD and early AD), “MCI,” and “HCs” using neuropsychological tests and clinical diagnosis by a neurologist. OCT/OCTA examinations were conducted using the RTVue XR 100 Avanti SD-OCT system (VISIONIX), with retinal parameters extracted. Statistical analysis included normality and homogeneity of variance (HOV) tests to select ANOVA methods. Post-hoc analyses utilized Mann–Whitney U, Dunnett, or Tukey-HSD tests based on parameters’ normality and HOV. Correlations with age were assessed via Pearson or Spearman tests. A generalized linear model (GLM) using Tweedie regression modeled the relationship between OCT/OCTA parameters and MMSE scores, correcting for age. Another ordinal logistic GLM (OL-GLM) modeled OCT/OCTA parameters against classes, adjusting for multiple confounders.

Results

We analyzed 357 participants: 44 Dem, 139 MCI, and 174 HCs. Significant microvascular density (VD) reductions around the fovea were linked with MCI and Dem compared to HCs. Age-related analysis associated thickness parameters with HCs’ old age. Our OL-GLM demonstrated significant thickness/volume reductions in Inner_Retina and Full_Retina layers. Foveal avascular zone (FAZ) area and perimeter were initially not correlated with cognitive decline; however, OL-GLM significantly associated FAZ perimeter enlargement with Dem and MCI groups. Significant average and inferior peripapillary RNFL thinning were linked to Dem and MCI groups.

Conclusion

This is the first study to examine VD changes in G grid sections among Dem, MCI, and HCs. We found a significant association between various VD parameters and cognitive decline. Most macular thickness/volume changes did not correlate with cognitive decline initially; however, our OL-GLM succeeded, highlighting the importance of the confounders’ corrections. Our analysis excluded individual retinal layer parameters due to limitations; however, the literature suggests their value. Our study confirmed existing biomarkers’ efficacy and uncovered novel retinal parameters for cognitive decline, requiring further validation.
The combination of Shenhuang plaster and paclitaxel inhibits lung metastasis in breast cancer via modulation of the tumor microenvironment
Authors: Chen Shiqi , Karekad Maryam Mohammed Abbas , Liu Ting , Ding Bin , Wang Rongyun , Sun Qiuhua , Xu Xiaohong , Shi Yanan
Published: February 2025

Background

Paclitaxel (PTX) is a chemotherapeutic agent that is frequently used for breast cancer treatment, but it has been associated with promoting distant metastases, including to the lungs, liver, and bones. Shenhuang plaster (SHP), a traditional Chinese medicine, has shown potential for modulating the tumor microenvironment (TME). This study investigates whether a combination of SHP and PTX can enhance the anti-tumor efficacy of PTX and mitigate its pro-metastatic effects in a 4T1 breast cancer mouse model.

Methods

Female Balb/c mice were injected with 4T1 breast cancer cells and then divided into four treatment groups: control, PTX, SHP, and PTX+SHP. The combination of SHP and PTX was evaluated using bioluminescence imaging (BLI), histological analysis, and hematoxylin and eosin (HE) staining to assess lung metastasis. Flow cytometry was employed to analyze immune cell populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and cytotoxic T cells (CD8+ and CD4+).

Results

SHP alone did not significantly inhibit lung metastasis but the combination of PTX and SHP led to a marked reduction in lung lesions, as confirmed by BLI and histological analysis. SHP improved the overall health of PTX-treated mice, reducing their body weight loss and mortality. Flow cytometry revealed that the combination therapy reduced the infiltration of M2 macrophages, MDSCs, and Tregs, while increasing the proportion of antitumor M1 macrophages, cytotoxic CD8+ T cells, and helper CD4+ T cells.

Conclusions

The combination of PTX and SHP has a synergistic effect, reducing lung metastasis and modulating immune cell populations within the TME. These results suggest that integrating traditional Chinese medicine with standard chemotherapy can enhance therapeutic efficacy and reduce adverse effects.
PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for Asian patients with advanced triple-negative breast cancer: a phase III RCTs based meta-analysis
Authors: Ruan Hua , Zou Yubin , Huang Lifeng , Zha Wenjuan , Ouyang Qingqing , Yang Ling
Published: February 2025

Background

Advanced triple-negative breast cancer (TNBC) presents significant therapeutic challenges, particularly in Asian populations, which exhibit distinct biological and genetic characteristics. Immunotherapy combined with chemotherapy has emerged as a promising approach; however, its efficacy compared to chemotherapy alone remains under investigation. This meta-analysis aims to evaluate the clinical outcomes of PD-1/PD-L1 inhibitors combined with chemotherapy (PIC) versus chemotherapy alone in the treatment of advanced TNBC in Asian patients.

Methods

A systematic literature search was performed across six databases for phase 3 randomized controlled trials (RCTs). Only studies comparing the outcomes of PIC versus chemotherapy alone in patients with advanced TNBC, including subgroup analyses of Asian populations, were included. Data were pooled to assess overall survival (OS), progression-free survival (PFS), responses, and safety profiles.

Results

A total of 1041 patients from five phase 3 RCTs were included in the final analysis. Compared to chemotherapy alone, PIC therapy significantly improved PFS (hazard ratio [HR]: 0.74 [0.62, 0.88], P = 0.0008). No significant difference was observed in OS (HR: 0.78 [0.55, 1.12], P = 0.18), although a slight trend favoring PIC therapy was noted. Among PD-L1-positive patients, both OS (HR: 0.62 [0.44, 0.86], P = 0.005) and PFS (HR: 0.66 [0.50, 0.86], P = 0.003) were significantly improved in the PIC group. The PIC group also exhibited a substantially higher OS rate at 12–36 months and a higher PFS rate at 6–30 months. However, the incidence of immune-related AEs (irAEs) (risk ratio [RR]: 1.69 [1.33, 2.15], P < 0.0001) and grade 3–5 irAEs (RR: 3.11 [1.59, 6.10], P = 0.001) was significantly higher in the PIC group. The most common irAEs in the PIC group were hypothyroidism (14.40%), dermatitis (10.00%), and infusion reactions (8.85%). Both treatment groups exhibited similar response rates and treatment-related AEs (TRAEs).

Conclusions

In Asian patients with advanced TNBC, PIC significantly improved survival compared to chemotherapy alone. Although the combination therapy was associated with a higher incidence of irAEs, its clinical benefits support its use as a viable treatment option for this population.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024622428.
Retrospective analysis of early neurodevelopmental outcomes after esophageal atresia repair at a single institution: short-gap vs. long-gap defect
Authors: Lowdermilk Mary Madelyn , Evanovich Devon Michael , Wang Jue Teresa , Pier Danielle Bennett , Sadhwani Anjali , Zendejas Benjamin , Bajic Dusica
Published: February 2025

Background

With increased survival of infants born with esophageal atresia (EA), there is a knowledge gap regarding neurodevelopmental outcomes. We aimed to quantify the frequency of (1) documented developmental delay, and (2) implementation of early intervention services in the first and the second year of life following repair of short- and long-gap EA.

Method

We retrospectively analyzed term-born (n = 44) and premature infants (n = 26) following EA repair at a single institution (2009–2020). Infants with anomalies associated with known neurological disorders were excluded. Clinical data was obtained from the electronic medical record, and presented as means and percentages. Developmental delay included clinically documented motor, speech/language, and cognitive delays that were stratified according to a surgical group: short- and long-gap EA.

Results

Nearly half of short-gap (24/54; 44%) and most of long-gap EA patients (12/16; 75%) had documented developmental delay in the first year of life that persisted into the second year of life [52% [28/54] short-gap; 69% [11/16] long-gap EA]. Developmental delay was noted irrespective of gestational age at birth, co-existing cardiac anomalies, or presence of cranial/brain findings on imaging. By age 2, 70% (38/54) of short-gap and 69% (11/16) of long-gap EA patients had received early intervention.

Interpretation

Infants born with EA are at high-risk for developmental delay. Early neurodevelopmental assessments and intervention is recommended for EA patients.
Effectiveness of pharmacological treatments for COVID-19 due to SARS-CoV-2: a systematic literature review
Authors: Garcia Vidal Carolina , González Jonathan , Lumbreras Carlos , Salavert Miguel , Castro Antonio , Rubio-Rodríguez Darío , Rubio-Terrés Carlos
Published: February 2025

Aim

Since the first cases of the COVID-19 pandemic, caused by the SARS-CoV-2 virus, described in 2019, numerous drugs have been proposed for the treatment of the disease. However, studies have given contradictory or inconclusive results, making it difficult to determine which treatments are truly effective. The objective was to carry out a systematic review of the literature analyzing the effectiveness (mortality, hospitalization and clinical improvement) of COVID-19 treatments initially proposed and finally authorized in the European Union.

Methods

PubMed and other electronic databases were systematically searched for meta-analyses published between January 2020 and December 2022, as well as two additional searches: one of individual clinical studies published until October 2023 and another of those drugs that were considered at the beginning and that were discarded early because the clinical results were unfavorable.

Results

In the synthesis, 85 meta-analyses and 19 additional clinical studies were included (base case). All medications indicated in the treatment of COVID-19 have favorable efficacy results (mortality, hospitalization rate, clinical improvement) but these results were not confirmed in all studies carried out, being frequently contradictory (confirming or not confirming the impact of treatment on mortality). According to meta-analysis with the largest sample size, the drugs with the greatest evidence of effectiveness in reducing mortality are remdesivir (HR= 0.79; 95% CI 0.73–0.85) and tocilizumab (OR= 0.73; 95% CI 0.56–0.93). Regarding the composite of Covid-19–related hospitalization or death from any cause, the drugs with the greatest evidence of efficacy are remdesivir, nirmatrelvir/ritonavir and sotrovimab (although, currently the effectiveness of monoclonal antibodies against the new variants of the virus has not been demonstrated).

Conclusion

According to this systematic review, the treatments with the greatest evidence of reducing mortality in patients with COVID-19 are remdesivir and tocilizumab.
Inflammation-fibrosis interplay in inflammatory bowel disease: mechanisms, progression, and therapeutic strategies
Authors: Li Yanan , Xu Feng , Fang Yulai , Cui Yuan , Zhu Zhenxing , Wu Yuguang , Tong Yiheng , Hu Jingyi , Zhu Lei , Shen Hong
Published: February 2025

Background

The incidence of intestinal fibrosis in Inflammatory bowel disease has increased in recent years, and the repair process is complex, leading to substantial economic and social burdens. Therefore, understanding the pathogenesis of intestinal fibrosis and exploring potential therapeutic agents is crucial.

Purpose

This article reviews the pathogenesis of IBD-related intestinal fibrosis, potential therapeutic targets, and the progress of research on Traditional Chinese Medicine (TCM) in inhibiting intestinal fibrosis. It also provides foundational data for developing innovative drugs to prevent intestinal fibrosis.

Methods

This article reviews the literature from the past decade on advancements in the cellular and molecular mechanisms underlying intestinal fibrosis. Data for this systematic research were obtained from electronic databases including PubMed, CNKI, SciFinder, and Web of Science. Additionally, a comprehensive analysis was conducted on reports regarding the use of TCM for the treatment of intestinal fibrosis. The study synthesizes and summarizes the research findings, presenting key patterns and trends through relevant charts.

Results

This study reviewed recent advancements in understanding the cellular and molecular mechanisms of intestinal fibrosis, the active ingredients of TCM that inhibit intestinal fibrosis, the efficacy of TCM formulae in preventing intestinal fibrosis, and dietary modification that may contribute to the inhibition of intestinal fibrosis.

Conclusion

This article examines the cellular and molecular mechanisms that promote the development of intestinal fibrosis, as well as potential therapeutic targets for its treatment. It also provides a theoretical basis for exploring and utilizing TCM resources in the management of intestinal fibrosis. Through the analysis of various TCM medicines, this article underscores the clinical significance and therapeutic potential of TCM and dietary modifications in treating intestinal fibrosis.
Dehydrodiisoeugenol targets the PLK1-p53 axis to inhibit breast cancer cell cycle
Authors: Li Lin , Zheng Yifan , Yang Yongxia , Shi Senlin , Liu Shangjie , Huang Keying , Qiu Luonan , Zhang Rongxin , Huang Wenbin , Leng Yin
Published: February 2025

Introduction

There are about 2,300,000 new cases of breast cancer worldwide each year. Breast cancer has become the first most common cancer in the world and the leading cause of death among women. At the same time, chemotherapy resistance in patients with advanced breast cancer is still a serious challenge. Alpinia Katsumadai Hayata (AKH), as a traditional Chinese herbal medicine, has a wide range of pharmacological activities. Related studies have found that many compounds in AKH have anti-breast cancer activity. However, it is still worth exploring which component is the main active component of AKH in inhibiting breast cancer and its mechanism of action.

Methods

In this study, dehydrodiisoeugenol (DHIE) was screened as the main active ingredient of AKH against breast cancer based on LC-MS combined with drug similarity and disease enrichment analysis. WGCNA, network pharmacology, molecular docking, transcriptome sequencing analysis, immune infiltration analysis and single-cell sequencing were used to explore the mechanism of DHIE on breast cancer. CCK-8, flow cytometry and Western blot were used to verify the results in vitro. The efficacy of the drugs was verified in vivo by constructing a subcutaneous tumor-bearing mouse model.

Results

Our research showed that DHIE and breast cancer enriched core gene targets mainly act on epithelial cells in breast cancer tissues and significantly inhibit the growth of breast cancer by affecting the PLK1-p53 signaling axis to arrest the breast cancer cell cycle at G0/G1 phase. Further analysis showed that although DHIE had opposite regulatory effects on different isoforms of p53 in different types of breast cancer cells, they eventually caused cell cycle arrest. In addition, in vivo studies showed that DHIE reduced tumor burden, significantly reduced the infiltration level of tumor proliferation-related marker Ki-67, and inhibited the expression of PLK1 in the mouse model, which was further enhanced when combined with DOX.

Discussion

Collectively, our study suggests that DHIE in AHK may eventually induce cell cycle arrest and inhibit breast cancer growth by regulating the PLK1-p53 signaling axis, which may provide a new therapeutic strategy for breast cancer. However, the specific mechanisms by which DHIE regulates p53 in different subtypes of breast cancer and the advantages of chemotherapeutic combinations compared with other drugs are still worth exploring.
Bonding with nature: a validation of the dispositional empathy with nature scale in Italy
Authors: Lovati Chiara , Manzi Federico , Di Dio Cinzia , Massaro Davide , Gilli Gabriella , Marchetti Antonella
Published: February 2025

This study proposes a psychometric validation of the Italian version of the Dispositional Empathy with Nature (DEN). Scientific research data has found high levels of environmental concern among people around the world, showing that majority of the population is aware of the seriousness of the environmental problems we are witnessing, as well as is conscious of the damage that some of their behaviors cause to the environment. Based on this premise, Empathy with Nature could be an important educational strategy for addressing the environmental crisis. A study was conducted involving 307 Italian adults (CFA = 146; 45.9% women; 54.1% man; Mean age = 34.65; SD = 11.770); (EFA = 161; 50.3% women; 49.7% man; Mean age = 34.30; SD = 10.360) to o assess the psychometric properties of a scale in the Italian context. The study aimed to establish the internal consistency of the DEN scale and evaluate its convergent, discriminant, and predictive validity. Both confirmatory and exploratory factor analyses, using a split sample, supported the one-factor structure consistent with the original version proposed by Tam. These findings strongly suggest that the DEN scale is reliable and valid in the Italian context.
Establishing a peer advisory board in a mental health ethics research group – challenges, benefits, facilitators and lessons learned
Authors: Faissner Mirjam , Braun Esther , Efkemann Simone Agnes , Gaillard Anne-Sophie , Haferkemper Iris , Hempeler Christin , Heuer Imke , Lux Ursula , Potthoff Sarah , Scholten Matthé , Spiegel Sylvia , Stefaniak Christina , Thesing Madeleine , Werning Anna , Gather Jakov
Published: February 2025

While participatory methods are regarded as beneficial in many areas of psychiatric research, they are still rarely considered in the field of mental health ethics. Yet, there are several epistemic and ethical reasons why participatory research is particularly important in this field, such as the high relevance of experiential knowledge for ethical analyses. In this article, we report our experiences with establishing a peer advisory board for an existing mental health ethics research group. We demonstrate how a peer advisory board can provide low-threshold opportunities for various forms of participation, which can occur simultaneously within one research project. We first describe how we established the peer advisory board and explain its structure. We then give an overview of several research projects that involved various forms of participation by members of the peer advisory board, such as the development of a template for a psychiatric advance directive, the co-writing of articles, and the organization of scientific events. We discuss the challenges, benefits, and facilitators of a peer advisory board from our different vantage points as service users, relatives, clinicians, and researchers. Challenges included organizational barriers such as time constraints and rigid bureaucratic structures within academic institutions and funding bodies as well as the persistence of power imbalances between members of the research group and the peer advisory board. Benefits included the opportunity for personal development and capacity building among both peer advisory board members and members of the research group, and the multiplication of research results among the relevant communities. Based on a reflection on our own experiences, we argue that participatory research in mental health ethics is not only ethically and epistemically desirable but also practically feasible. We close by formulating several lessons learned from our experiences.
Emotional labor and its influencing factors of clinical nurses: a cross-sectional study based on latent profile analysis
Authors: Zhou Li , Xiong Wei , Hu Mengmeng , Chang Hongjuan
Published: February 2025

Objective

The present study aimed to investigate latent classes of emotional labor among clinical nurses in China and analyze the influencing factors of emotional labor. With this as a reference, care managers can develop more targeted emotional labor intervention programs.

Methods

This study enrolled 1,320 clinical nurses by using stratified random sampling from August to October 2023. A total of 1,279 nurses completed the following questionnaires: General Information Questionnaire, Emotional Labor Scale, Generalized Anxiety Disorder-7 scale (GAD-7), Patient Health Questionnaire-9 scale (PHQ-9), and Work–Family Conflict Scale. Based on the Emotional Labor Scale, the latent profile analysis (LPA) was used to explore the latent classes of nurses’ emotional labor. Then, univariate analysis and multivariate logistic regression analysis were used to explore the influencing factors of emotional labor.

Results

Three latent classes were identified: generally low-level group (1.5%), high-level deep-acting group (17.2%), and high-level surface-acting group (81.3%). Male nurses were more likely to be in the generally low-level group than female nurses. Nurses with low scores on Work–Family Conflict Scale were more likely to be in the high-level deep-acting group than those with high scores. Compared with the nurses with very poor health, the nurses with very good health were more likely to be in the high-level deep-acting group, and nurses with general health were more likely to be in the high-level surface-acting group.

Conclusion

The emotional labor of clinical nurses can be identified into three latent classes. Nursing managers can predict the latent classes of emotional labor based on characteristics such as demographic information and work–family conflict. Therefore, precise intervention can be implemented to reduce the consumption of internal resources and the occurrence of nursing adverse events caused by excessive emotional labor.
Epidemiology of road traffic accidents and its associated factors among public transportation in Africa: systematic review and meta-analysis
Authors: Atalay Yibeltal Assefa , Alemie Bersufekad Wubie , Gelaw Belete , Gelaw Kelemu Abebe
Published: February 2025

Introduction

Nowadays, Injuries, disabilities, and deaths due to road traffic accidents pose a major threat to public health worldwide. There was no meta-analysis study conducted in this area in Africa, hence the need for the study.

Objectives

This review aimed to assess the pooled prevalence and associated factors of road traffic accidents among public transportation in Africa.

Methods

This systematic review and meta-analysis study was conducted in Africa according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using Boolean logic operators and targeted keywords, we searched for publications on several electronic databases (Web of Science, PubMed, Google Scholar, African Journals Online (AJOL), and Science Direct). The degree of heterogeneity among the included studies, the 95% confidence interval, and the pooled prevalence were estimated using a random effects model.

Results

This review included 45 studies with 15,968 participants. The overall estimated pooled prevalence of road traffic accident among public transportation in Africa was found to be 38.83% (95% CI: 33.54, 44.12). Meta-regression analysis indicated that sample size, publication year, country, study design, and sub-region had no significant impact on RTA prevalence. Based on a sub-group analysis by countries where the studies were conducted, the higher pooled prevalence of road traffic accidents was found in Congo at 67.90% (95% CI: 59.99, 75.81), while the lower pooled prevalence of road traffic accidents was in Libya at 15.80% (95% CI: 10.99, 20.61). Driving experience (AOR: 2.64, 95% CI: 1.70, 3.34), chewing Khat while driving (AOR = 4.69, CI: 2.80, 7.85), alcohol use (AOR = 2.72, CI: 1.49, 4.97), and receiving mobile phone calls while driving (AOR = 2.37, CI: 1.42, 3.95) were factors significantly associated with road traffic accidents.

Conclusion

In conclusion, the pooled prevalence of road traffic accidents in Africa was found to be high. Therefore, we recommend that drivers have to strictly adhere to traffic regulations Moreover, It is recommended that policymakers and administrators ought to gain awareness of road traffic accidents and its risk factors to put existing road traffic accidents preventive and control measures into action.
Systematic review of the epidemiological evidence of associations between quantified occupational exposure to respirable crystalline silica and the risk of silicosis and lung cancer
Authors: Mundt Kenneth A. , Thompson William J. , Dhawan Gaurav , Checkoway Harvey , Boffetta Paolo
Published: February 2025

Introduction

Occupational exposure to respirable crystalline silica (RCS) has been associated with both silicosis and lung cancer, but no systematic review (SR) specifically focused on exposure-response relationships has been published for these diseases.

Methods

We conducted this SR in compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed searches, supplemented with Web of Science and Google Scholar searches, identified 1,007 potentially relevant articles. After applying selection criteria and removing duplicates, 65 publications were reviewed and evaluated, 20 of which presented at least semi-quantitative exposure-response results for lung cancer (n = 12) and/or silicosis (n = 10).

Results

Cumulative RCS exposure was most commonly reported. Increasing silicosis risk with increasing cumulative RCS exposure was reported in all studies, with exposure thresholds indicated, but at different cumulative exposures. For most studies defining silicosis as International Labor Organization (ILO) score ≥ 1/0, substantially increased risks were clear at or above 1 mg-/m3-yr. For lung cancer, exposure-response estimates were mixed with 4 studies reporting no statistically significantly increased relative risk of lung cancer at any cumulative RCS exposure. Three studies reported statistically significant increased risks but only for high cumulative RCS exposures. Residual confounding by smoking was not explicitly discussed in most studies. One case–control study presented an exposure-response analysis for silica and lung cancer limited to never-smokers with substantial silica exposure; risk was increased only among those in the highest RCS exposure category. Studies with more detailed smoking information generally reported risks close to background levels except at the highest cumulative RCS exposure categories.

Conclusion

Silicosis risk clearly and consistently was increased above cumulative exposure thresholds of roughly 1 mg/m3-years across most studies. However, for lung cancer, results were heterogeneous with potential residual confounding by smoking complicating interpretation. Results suggest that lung cancer risk may not be increased at cumulative RCS exposures below the reported exposure thresholds for silicosis risk.