bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology
Authors: Youssef Emile , Fletcher Brandon , Palmer Dannelle
Published: January 2025

Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As the field advances, its transformative potential is now expanding into oncology, where personalized therapies address the genetic and immune-related complexities of cancer. This review highlights innovative therapeutic strategies, including gene replacement, gene silencing, oncolytic virotherapy, CAR-T cell therapy, and CRISPR-Cas9 gene editing, with a focus on their application in both hematologic malignancies and solid tumors. CRISPR-Cas9, a revolutionary tool in precision medicine, enables precise editing of cancer-driving mutations, enhancing immune responses and disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form of cell death—offering new possibilities for selectively inducing tumor cell death in resistant cancers. Despite significant breakthroughs, challenges such as tumor heterogeneity, immune evasion, and the immunosuppressive tumor microenvironment (TME) remain. To overcome these barriers, novel approaches like dual-targeting, armored CAR-T cells, and combination therapies with immune checkpoint inhibitors and ferroptosis inducers are being explored. Additionally, the rise of allogeneic “off-the-shelf” CAR-T therapies offers scalable and more accessible treatment options. The regulatory landscape is evolving to accommodate these advancements, with frameworks like RMAT (Regenerative Medicine Advanced Therapy) in the U.S. and ATMP (Advanced Therapy Medicinal Products) in Europe fast-tracking the approval of gene therapies. However, ethical considerations surrounding CRISPR-based gene editing—such as off-target effects, germline editing, and ensuring equitable access—remain at the forefront, requiring ongoing ethical oversight. Advances in non-viral delivery systems, such as lipid nanoparticles (LNPs) and exosomes, are improving the safety and efficacy of gene therapies. By integrating these innovations with combination therapies and addressing regulatory and ethical concerns, gene therapy is poised to revolutionize cancer treatment, providing durable, effective, and personalized solutions for both hematologic and solid tumors.
Serological, phenotypic and molecular characterization of brucellosis in small ruminants in northern Algeria
Authors: Nabi Ibrahim , Achek Rachid , Karim Abdelkadir , Melzer Falk , Brangsch Hanka , Elschner Mandy C. , Neubauer Heinrich , El-Adawy Hosny
Published: January 2025

Brucellosis is considered a common bacterial zoonotic disease of high prevalence in countries of the Middle East and the Mediterranean region with economic and public health impact. The present study aimed to investigate the current situation of brucellosis in small ruminants reared in Médéa and Sidi Bel-Abbès provinces, north Algeria. To achieve this objective, 96 sera (77 sheep and 19 goat) and 57 milk (42 sheep and 15 goat) samples were collected from suspected infected animals and serologically analyzed by using ELISA. For isolation of Brucella spp., four placentas, two fetuses and forty-four milk samples were subjected to microbiological investigation. Whole genome sequencing (WGS) was used for genomic analysis of isolated Brucella species. The results of this study showed that anti-Brucella antibodies were detected in 46 (83.6%) and 52 (54.2%) milk and serum samples, respectively. However, among 27 cases where blood samples were negative, anti-Brucella antibodies were still detected in 19 of the corresponding milk samples, resulting in an overall discordance rate of 36.5%. Ten Brucella melitensis were isolated and identified from six sheep and four goats. Of these, eight originated from milk samples. The isolated strains were assigned to sequence type ST-11 using Multilocus sequence typing (MLST). Five isolates revealing high similarity (0–2 nucleotide differences) originated from different farms, indicating a close transmission link. However, two identical caprine isolates and three other isolates showed notable genotypic variation, in comparison. The highest base difference (449–462 nucleotides) was observed for an ovine isolate originating from Sidi Bel-Abbès. The phylogenetic analysis and clustering with the West Mediterranean lineage of B. melitensis revealed high genetic similarity of the investigated isolates with B. melitensis of human origin from North Africa and travel-associated ‘European’ cases, especially from Morroco, Tunisia, Sweden and Italy. The results of this study highlight brucellosis in small ruminants as a significant public health risk and will help to develop effective control strategies in Algeria. These findings provide specific evidence of this risk, with Brucella isolation from milk and by linking theses isolates to human cases in Algeria and abroad. The use of WGS-based analysis has revealed effective in tracing patterns of transmission, and can be recommended for tracking outbreaks at a high resolution.
Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study
Authors: Hassanein Mai M. , Hagyousif Yousra A. , Zenati Ruba A. , Al-Hroub Hamza M. , Khan Farman Matloob , Abuhelwa Ahmad Y. , Alzoubi Karem H. , Soares Nelson C. , El-Huneidi Waseem , Abu-Gharbieh Eman , Omar Hany , Zaher Dana M. , Bustanji Yasser , Semreen Mohammad H.
Published: January 2025

Background

Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments.

Methods

We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).

Results

Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis.

Significance

This in vivo study highlights TNBC’s metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.
Enhanced intestinal epithelial co-culture model with orbital mechanical stimulation: a proof-of-concept application in food nanotoxicology
Authors: Santoni Mattia , Piccinini Giovanni , Liguori Giovanni , Randi Maria Roberta , Baroncini Massimo , Milani Liliana , Danesi Francesca
Published: January 2025

Introduction

Current in vitro intestinal models lack the mechanical forces present in the physiological environment, limiting their reliability for nanotoxicology studies. Here, we developed an enhanced Caco-2/HT29-MTX-E12 co-culture model incorporating orbital mechanical stimulation to better replicate intestinal conditions and investigate nanoparticle interactions.

Methods

We established co-cultures under static and dynamic conditions, evaluating their development through multiple approaches including barrier integrity measurements, gene expression analysis, and confocal microscopy. We introduced novel quantitative analysis of dome formation as a differentiation marker and demonstrated the model application by investigating cellular responses to titanium dioxide (TiO₂) nanoparticles in a digested food matrix.

Results

Dynamic conditions accelerated epithelial differentiation, achieving functional barrier properties by day 14 rather than day 21, with enhanced mucin production and more organized three-dimensional structure. Mechanical stimulation selectively promoted goblet cell differentiation without affecting general epithelial markers. The optimized model successfully detected concentration-dependent oxidative stress responses to TiO₂ exposure, revealing cellular dysfunction preceding membrane damage.

Discussion

This improved co-culture system provides a better physiological platform for nanotoxicology studies. By incorporating mechanical forces, each cell type exhibits more representative behavior, creating a more realistic experimental setup. The model bridges the gap between simple monocultures and complex 3D systems, offering a practical approach for investigating nanoparticle-epithelium interactions in a food-relevant context.
A deep learning model for carotid plaques detection based on CTA images: a two stepwise early-stage clinical validation study
Authors: Guo Zhongping , Liu Ying , Xu Jingxu , Huang Chencui , Zhang Fandong , Miao Chongchang , Zhang Yonggang , Li Mengshuang , Shan Hangsheng , Gu Yan
Published: January 2025

Objective

To develop a deep learning (DL) model for carotid plaque detection based on CTA images and evaluate the clinical application feasibility and value of the model.

Methods

We retrospectively collected data from patients with carotid atherosclerotic plaques who underwent continuous CTA examinations of the head and neck at a tertiary hospital from October 2020 to October 2022. The model combined ResUNet with the Pyramid Scene Parsing Network (PSPNet) to enhance plaque segmentation. Patient plaques were divided into training, validation, and testing sets in a ratio of 7:1.5:1.5. We analyzed recall (lesion-level sensitivity), sensitivity (patient-level), and precision to evaluate the model’s diagnostic performance for carotid plaques. The two stepwise early-stage clinical validation study (Comparison study and Model-human study) was used to simulate real clinical plaque diagnostic scenarios.

Results

In total, 647 patients were included in the dataset, including 475 for training, 86 for validation, and 86 for testing. The DL model based on CTA images showed good precision in plaque diagnosis (validation set: precision = 80.49%, sensitivity = 90.70%, recall = 84.62%; test set: precision = 78.37%, sensitivity = 91.86%, recall = 84.58%). In addition, subgroup analysis of the plaque was carried out in the test set. The model had high accuracy in identifying plaques at different locations (Recall: 83.72, 76.32, 89.25, and 83.02%) and with different morphologies (Recall: 86.03, 79.17%). This model also analyzed the results of different types of plaques and showed good to moderate plaque diagnostic accuracy for different plaque types (Recall: 70.00, 86.87, 84.29%). Especially, in the clinical application scenario analysis, the model’s diagnostic results for plaques were found to be higher than those of 4 out of 6 radiologists (p < 0.001). Furthermore, in Model-human Real Clinical Scenarios study, we found that the model improved the radiologists’ sensitivity in diagnosing plaques. Additionally, the model’s diagnostic time for plaques (6 s) was found to be significantly shorter than that all of radiologists (p < 0.001).

Conclusion

This AI model demonstrated strong clinical potential for carotid plaque detection with improved clinician diagnostic performance, shortening time, and practical implementation in real-world clinical cases.
Assessment of upper GI motor activity and GI symptoms in patients with amyotrophic lateral sclerosis: an observational study
Authors: Ribichini Emanuela , Pallotta Nadia , Badiali Danilo , Carlucci Maria , Ceccanti Marco , Cambieri Chiara , Libonati Laura , Corazziari Enrico Stefano , Ruoppolo Giovanni , Inghilleri Maurizio
Published: January 2025

Background/aims

Oro-pharyngeal dysfunction has been reported in Amyotrophic Lateral Sclerosis (ALS). We aimed to assess ALS patients upper gastrointestinal (GI) motor activity and GI symptoms according to bulbar and spinal onset and severity of ALS.

Methods

ALS bulbar (B) and spinal (S) patients with ALS Functional Rating Scale (ALSFRS-r) ≥35, bulbar sub-score ≥10, and Forced Vital Capacity (FVC) >50%, underwent to: Fiberoptic Endoscopic Evaluation of Swallowing (FEES); esophageal manometry; gastric emptying; Rome symptom questionnaire. Medical Research Council Scale for Muscle Strength (MRC) was performed for the upper and lower limbs. Mann-Whitney's U, Fisher's ranks test, Pearson's test was used.

Results

Thirteen ALS patients were included (6 F; mean age 61.2 ± 13.7 years, range: 37-87), 5 with B and 8 with S onset (ALSFRS-R score 39.5 ± 4.9, MRC score 128.6 ± 23.3, disease duration 22.8 ± 17.9 months). FEES detected a high dysphagia score in 5 patients with no difference between S and B phenotype. Lower esophageal sphincter pressure was normal in all patients. Esophageal dysmotility was observed in three S and two B onset patients. Upper esophageal sphincter (UES) pressure was higher in all ALS patients. UES spasms and delayed gastric emptying were detected in two B and one S and in two B and four S patients, respectively. There was no correlation between esophagogastric motor abnormalities and clinical characteristics of ALS, nor GI symptoms.

Conclusions

The presence of UES spasm and the delayed gastric emptying in a subgroup of ALS patients may suggest the role of ANS dysfunction in ALS.
Ketogenic diet treatment for super-refractory status epilepticus in the intensive care unit: feasibility, safety and effectiveness
Authors: Ren Yishu , Zhang Mengyao , Fu Xinxiao , Zhang Yan , Liu Fang , Wu Chenglin , Shi Haiyan , Tian Fei , Liu Gang , Lin Yicong , Su Yingying , Chen Weibi
Published: January 2025

Background and aims

To investigate the feasibility, safety and effectiveness of the ketogenic diet (KD) for super-refractory status epilepticus (SRSE) in the intensive care unit (ICU).

Methods

We conducted a prospective investigation on patients with SRSE treated with the KD. The primary outcome measures were ketosis development as a biomarker of feasibility and resolution of SRSE as effectiveness. KD-related side effects were also investigated.

Results

Twelve patients (9 females and 3 males) with SRSE, with a median age of 34 years [range 16–69, interquartile range (IQR) 18–52], were treated with a KD. The median duration of SRSE prior to KD treatment was 21 days (range 4–46). SRSE resolved in 75% (9/12) of patients at a median of 3 days (range 1–18) after KD initiation. Among the nine KD responders, all were successfully weaned off anesthetic agents at a median of 16 days (range 4–32) after KD initiation, and all were also successfully weaned off ventilator. Side effects varied, and included gastrointestinal intolerances, malnutrition and metabolic abnormalities, electrolyte disturbance, and acute weight loss, although most of them could be corrected. No patient died due to KD, and neurofunctions continued to improve under KD therapy.

Conclusion

The KD may be feasible and effective for the treatment of SRSE in the ICU. Moreover, it is relatively safe. However, there are numerous adverse events that can be corrected under close monitoring.
Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
Authors: Burns Jennifer N. , Jenkins Aaron K. , Xue Xiangning , Petersen Kaitlyn A. , Ketchesin Kyle D. , Perez Megan S. , Vadnie Chelsea A. , Scott Madeline R. , Seney Marianne L. , Tseng George C. , McClung Colleen A.
Published: January 2025

Introduction

Alterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents.

Methods

Here, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC).

Results

We find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes.

Discussion

Together, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models.
The association between controlling nutritional status and postoperative pulmonary complications in patients with colorectal cancer
Authors: Li Yafang , Nie Chuang , Li Na , Liang Jieying , Su Ning , Yang Chunhua
Published: January 2025

Background

Postoperative pulmonary complications (PPCs) significantly impact surgical outcomes, and Controlling Nutritional Status (CONUT) score, a simple and easily available nutritional score, has been demonstrated to be significantly associated with postoperative patient outcomes and complications, including PPCs. However, there are few studies that specifically focus on patients undergoing radical surgery for colorectal cancer (CRC).

Methods

We retrospectively analyzed the clinical data of 2,553 patients who underwent radical surgery for CRC at the Sixth Affiliated Hospital of Sun Yat-sen University. Patients were divided into three groups: normal nutrition group (CONUT≤1), mild malnutrition group (2 ≤ CONUT≤4), and moderate-to-severe malnutrition group (CONUT≥5). Risk factors for PPCs and all-cause mortality were evaluated by multivariate regression. In addition, we assessed surgical outcomes including ICU admission, hospital stay, 1-year mortality and tumor-related mortality.

Results

The incidence of PPCs was 9.0% (n = 230). Multiple regression showed that the higher the CONUT score, the higher the risk of PPCs (mild malnutrition group vs. normal nutrition group, OR: 1.61, 95% CI: 1.18–2.20, p = 0.003; moderate-to-severe malnutrition group vs. normal nutrition group, OR: 2.41, 95% CI: 1.51–3.84, p < 0.001). All-cause mortality was significantly higher in moderate-to-severe malnutrition group than that in normal nutrition group, HR: 1.88, (95% CI: 1.34–2.62, p < 0.001). Older age, male sex, chronic heart disease, open surgery, blood transfusion during surgery, distant metastasis of tumor and colon tumor were all risk factors for PPCs. Furthermore, the malnutrition groups had poor surgical outcomes including postoperative pneumonia (mild vs. normal nutrition, OR: 1.64, 95% CI: 1.07–2.52, p = 0.024; moderate-to-severe vs. normal nutrition, OR: 2.51, 95% CI: 1.36–4.62, p = 0.00), ICU admission (mild vs. normal nutrition, OR: 2.16, 95% CI: 1.31–3.56, p = 0.002; moderate-to-severe vs. normal nutrition, OR: 3.86, 95% CI: 2.07–7.20, p < 0.001), hospital stay ≥14 days (mild vs. normal nutrition, OR: 1.30, 95% CI: 1.08–1.56, p = 0.006) and 1-year mortality (mild vs. normal nutrition, HR: 1.65, 95% CI: 1.11–2.46, p = 0.014; moderate-to-severe vs. normal nutrition, HR: 2.27, 95% CI: 1.28–4.02, p = 0.005).

Conclusion

The preoperative CONUT score is a potential indicator for predicting PPCs and surgical outcomes in CRC patients.
Trends and future predictions of chronic kidney disease due to diabetes mellitus type 2 attributable to dietary risks: insights based on GBD 2021 data
Authors: Xu Ming , Wei Hongxia , Lv Dongqing , Wei Yanhong , Liu Ziang , Zhang Yi , Liu Yunfeng
Published: January 2025

Background

The 2021 Global Burden of Disease (GBD) study shows a continuous increase in the burden of chronic kidney disease due to diabetes mellitus type 2 (CKD-T2DM) from 1990 to 2021. This study examines the influence of dietary risk factors across various populations and socioeconomic groups.

Methods

Utilizing the 2021 GBD data, we analyzed age-standardized CKD-T2DM metrics—including mortality, disability-adjusted life years (DALY), and age-standardized rates (ASR)—stratified by age, gender, and region. The study employs estimated annual percentage changes (EAPC) to monitor temporal trends and project future trends from 2022 to 2035 using bayesian age-period-cohort (BAPC) analysis.

Results

The results indicate that, in 2021, 20.55% of CKD-T2DM mortality and 23.21% of CKD-T2DM DALY were attributed to poor diets, especially those low in fruits and high in red and high processed meat. Throughout this period, both mortality and DALY rates associated with dietary risks increased significantly, with the most rapid increase in diet high in sugar-sweetened beverages, highlighting the considerable impact of dietary factors on the global CKD-T2DM landscape. Geographic disparities in T2DM trends are evident, with the most significant increases in age-standardized mortality rates (ASMR) and age-standardized DALY rates (ASDR) observed in regions such as high-income North America and Central Latin America. Socio-demographic index (SDI) is negatively correlated with the CKD-T2DM burden attributable to dietary risk factors.

Conclusion

Public health interventions that target dietary changes can significantly reduce the global burden of CKD-T2DM.
Case report: Endolymphatic sac tumor with blurred vision
Authors: Yuan Ke , Luo Weijian , Chen Jia , Peng Quanzhou , Tong Xiaoguang , Hu Jiliang
Published: January 2025

Introduction

Endolymphatic sac tumor (ELST) is a rare neoplasm that exhibits aggressive growth primarily in the endolymphatic capsule and can potentially affect nearby neurovascular structures. The diagnosis of ELST poses challenges due to its low prevalence, gradual progression, and nonspecific symptomatology. It is currently believed that prompt surgical intervention is recommended for endolymphatic sac tumors upon diagnosis. In cases where the lesion is complex or in close proximity to vital blood vessels and nerves, making complete resection challenging, adjuvant therapy may be employed postoperatively. This approach aims to enhance treatment outcomes.

Case presentation

A case of a 53-year-old male was admitted to the Department of Neurosurgery of Shenzhen People’s Hospital with the main cause of dizziness and blurred vision, and was found to have an occupation in the pontocerebellar angle for about 20 days. Preoperative cranial CT suggested that the temporal bone mastoid was widely damaged with worm-like bone, and some of them showed honeycomb changes. MRI suggested that shadow was seen in the posterior part of the left internal auditory canal, temporal bone mastoid and jugular foramen, with a size of about 28x21x27mm.The T1-weighted image showed low and equal signals, and the T2-weighted image showed equal and slightly low signals in the center with multicompartmental cystic high signals in the margin. The center of the mass strengthened significantly after enhancement. The patient had no other clinical manifestations and no family history. The clinical diagnosis was left-sided pontocerebellar angle occupation - nature to be determined. The occupation was resected microscopically using the distal lateral combined anterior approach to the sigmoid sinus. Due to the extremely rich blood supply of the tumor, the tumor was embedded in the petrous humerus, which was soft and tough, and the surrounding structures were not clearly displayed, making surgical resection extremely difficult. postoperative pathology and immunohistochemistry confirmed that this lesion was an endolymphatic cystic tumor. After surgery, most of the tumor was successfully resected while preserving neurological function well, and the residual tumor was treated with adjuvant gamma knife with good results.

Conclusion

ELST is a rare, low-grade, locally aggressive tumor that is difficult to diagnose early. During the surgery, it was observed that the tumor had a significant blood supply, which made its removal challenging. Preoperative embolization of the tumor’s blood supply artery would facilitate surgical resection and help avoid massive intraoperative bleeding. Complete surgical resection is the treatment of choice, and any remaining tumor remnants can be managed with adjuvant radiotherapy post-surgery, necessitating long-term follow-up to monitor any developments.
Prognostic and diagnostic value of circRNA expression in cervical cancer: a meta analysis
Authors: Xu Yi , Li Changxia , Cheng Lifang , Wang Shaoheng , Wu Yuqing , Li Shiyang , Liu Mingqiang , Tao Xiaohua
Published: January 2025

Introduction

Cervical cancer (CC) is a highly prevalent malignancy of the reproductive system. This study aimed to methodically assess the function of circular RNAs (circRNAs) as possible indicators of CC, with a specific emphasis on their usefulness in the identification, prediction, and correlation with clinicopathological elements.

Methods

A comprehensive literature search was conducted using databases such as PubMed, Cochrane Library, Web of Science, Embase, and the China National Knowledge Infrastructure (CNKI). The latest data were extracted on May 3rd, 2024. The diagnostic potential of circRNA expression was evaluated using a range of metrics including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The importance of circRNAs was further evaluated in terms of clinical relevance, pathological features, and prognostic value using pooled odds ratios (ORs) and hazard ratios (HRs).

Results

The meta-analysis included 27 studies, which were categorised based on diagnostic applications (n=3), clinicopathological correlations (n=15), and prognostic evaluations (n=23). Elevated expression levels of oncogenic circRNAs were significantly associated with poor clinical indicators, including tumour size (odds ratio [OR] = 0.425, 95% confidence interval [CI]: 0.267–0.676), International Federation of Gynaecology and Obstetrics (FIGO) stage (OR = 0.315, 95% CI: 0.224–0.443), and lymph node metastasis (OR = 2.975, 95% CI: 1.816–4.872). This upregulation of oncogenic circRNA was also identified as a predictor of worse survival outcomes, with a hazard ratio (HR) of 2.13 (95% CI: 1.73–2.62, P < 0.001). The downregulation of circRNAs with tumour-suppressor properties was similarly associated with poor clinical parameters, such as tumour size (OR = 0.310, 95% CI: 0.102–0.941), FIGO stage (OR = 0.231, 95% CI: 0.101–0.527), and lymph node metastasis (OR = 2.430, 95% CI: 1.156–5.110), and was indicative of a worsened prognosis (HR = 2.20, 95% CI: 1.03–4.70, P = 0.042). In terms of diagnostic value, the pooled sensitivity, specificity, and area under the curve (AUC) were calculated to be 0.85, 0.83, and 0.91, respectively.

Conclusion

The results of our meta-analysis indicate that circRNAs have the potential to serve as promising biomarkers for CC diagnosis, prognosis, and clinicopathology.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024544997.
Case report: Innovative approach to esophageal cancer with right aortic arch: neoadjuvant immunotherapy and 3D reconstruction
Authors: Luo Chengwen , Luo Zhilin
Published: January 2025

Background

We report a rare case of locally advanced esophageal cancer with a right aortic arch (RAA), successfully treated with neoadjuvant immunotherapy and minimally invasive esophagectomy, guided by three-dimensional (3D) reconstruction.

Case presentation

A 50-year-old male with stage III esophageal squamous cell carcinoma (cT3N0M0) and RAA underwent four cycles of neoadjuvant immunotherapy with sintilimab, resulting in significant tumor regression. Minimally invasive esophagectomy was performed with the aid of preoperative 3D reconstruction, which was critical in navigating the complex vascular anatomy and ensuring surgical precision.

Conclusion

This case demonstrates the efficacy of neoadjuvant immunotherapy combined with 3D reconstruction in managing esophageal cancer complicated by vascular anomalies. This approach offers a promising alternative for complex cases where conventional treatments pose higher risks.
Biochemical characteristics, genetic variants and treatment outcomes of 55 Chinese cases with neonatal intrahepatic cholestasis caused by citrin deficiency
Authors: Li Juan , Duan Jintao , He Shuli , Li Ying , Wang Meifen , Deng Chengjun
Published: January 2025

Background

The diagnostic criteria of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) have not been established due to non-specific clinical manifestations, and our understanding on the treatment outcome is still limited. We aim to investigate the biochemical characteristics, genetic variants, and treatment outcome of NICCD patients.

Methods

We compared the nutritional status and biochemical characteristics of 55 NICCD infants and 27 idiopathic neonatal cholestasis (INC) infants. SLC25A13 gene variant analysis was performed for definitive diagnosis of NICCD. NICCD infants received 12 months of lactose-free and/or medium-chain triglyceride-enriched (LF/MCT) formula treatment. The treatment efficacy was evaluated by comparing the outcome of NICCD with the 24 healthy infants that were selected as normal controls. All NICCD patients were followed up until death or at least 1 year of age.

Results

Compared to INC group, significant increase was found in levels of total bilirubin, indirect bilirubin, total bile acid, gamma-glutamyl transpeptidase, alkaline phosphatase, prothrombin time, thrombin time, international normalized ratio, alpha-fetoprotein (AFP), Vitamin D, and Vitamin E of NICCD group, while alanine aminotransferase, albumin, fibrinogen, glucose, and Vitamin A levels showed significant decrease in the NICCD group (P < 0.05). There were 7 novel variants among 19 SLC25A13 variant types. No significant differences were found between NICCD patients treated for 12 months and normal controls. In long term follow-up, 2 cases developed FTTDCD, 8 cases had special dietary habits, and 1 case died from cirrhosis.

Conclusions

NICCD showed more severe impairments in liver, coagulation, and metabolic function than INC. Significantly increased AFP levels could provide reference for the differential diagnosis of NICCD. The newly discovered variants may be meaningful for the individualized treatment of NICCD patients. LF/MCT formula was recommended for NICCD patients.
Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
Authors: Zhang Shilei , Gong Fukai , Liu Jiali , You Shuping , Liu Tao , Yang Jianhua , Hu Junping
Published: January 2025

Objective

To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from Cistanche tubulosa alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.

Methods

BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated. Finally, liquid chromatography-mass spectrometry (LC/MS) was employed to investigate alterations in the plasma metabolic profile of tumor-bearing mice with CRF in response to ACT treatment, and the affinity between metabolite-associated proteins and ACT was verified by Surface plasmon resonance (SPR) assay.

Results

Our study demonstrated the presence of CRF in the colon cancer mouse model, with the severity of fatigue increasing alongside tumor growth. Administration of ACT ameliorated both tumor burden and PTX-induced muscle fatigue-like behavior. LC/MS analysis identified a panel of differentially regulated metabolites, including trans-aconitine, citric acid, 3-coumaric acid, ephedrine, thymine, cytosine, indole-3-acetic acid, and pantothenol-9. These metabolites were primarily enriched in pathways associated with valine biosynthesis, tyrosine metabolism, tryptophan metabolism, and biosynthesis of pyridine alkaloids. Furthermore, several key enzymes, including CYP3A4, CYP19A1, CYP2E1, TNF, BCL-2, RYR2, and ATP2A1, were identified as potential targets underlying the anti-CRF effects of ACT.

Conclusion

This study suggests that ACT derived from C. tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.
Clopidogrel combined with rivaroxaban in peripheral artery disease after revascularization
Authors: Lu Min , Li Jiaqi , Ni Huanyu , Qiao Tong , Wang Baoyan
Published: January 2025

Background

To evaluate the efficacy and safety of clopidogrel-rivaroxaban combination compared to aspirin-rivaroxaban combination in patients with symptomatic peripheral artery disease (PAD).

Methods

Consecutive patients with symptomatic PAD patients were analyzed from January, 2018 to June, 2022 at Nanjing Drum Tower Hospital. Patients were divided into two groups based on the antithrombotic therapy. The primary efficacy outcome was a composite of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and the primary safety outcome was major bleeding. Patients were followed until the first occurrence of any outcomes or the study end date (30 June 2024).

Results

A total of 695 patients were enrolled into this study. The clopidogrel-rivaroxaban combination significantly reduced the risk of composite outcome (HR: 0.59, 95%CI: 0.41–0.83) without increasing the risk of major bleeding (HR: 0.68, 95%CI: 0.27–1.69). When analyzed separately, clopidogrel-rivaroxaban combination was associated with a reduced risk of MALE (HR: 0.61, 95%CI: 0.41–0.91), although no significant differences were observed in terms of MACE (HR: 0.64, 95%CI: 0.34–1.20) or all bleeding events (HR: 1.00, 95%CI: 0.52–1.93). In the subgroup analysis, there were no significant interactions between the treatment groups and the subgroups of age, diabetes, lesion sites, Rutherford classifications and renal function for composite outcome, MACE and MALE.

Conclusion

The clopidogrel-rivaroxaban combination in PAD patients may offer enhanced cardiovascular protection without increasing the risk of bleeding complications. These findings suggested that clopidogrel could be a superior alternative to aspirin in dual antithrombotic therapy for PAD management.
On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations
Authors: Pushkin Alexander , Kao Liyo , Zhekova Hristina R. , Azimov Rustam , Abuladze Natalia , Shao Xuesi M. , Tieleman D. Peter , Kurtz Ira
Published: January 2025

A transport protein’s turnover rate (TOR) is the maximum rate of substrate translocation under saturating conditions. This parameter represents the number of transporting events per transporter molecule (assuming a single transport site) per second (s). From this standpoint, a transporter’s TOR is similar to an enzyme’s catalytic constant. Knowledge of a transporter’s TOR allows comparison of the transport capacity of various transporters at the molecular level as well as the total transport per cell and whole organ levels. Despite this, there is currently a very limited number of transporters, for which TOR has been determined experimentally. In the SLC4 transporter family of CO32−/HCO3− transporters, erythrocyte AE1 (eAE1; SLC4A1) is the only member, for which TOR has been determined (∼50,000 s−1). Whether other SLC4 family members have similar TOR values is currently unknown. Here we report TOR measurements of the electrogenic Na+-CO32− cotransporter NBCe1-A (SLC4A4) and the kidney specific AE1 splice variant, kAE1, that play important roles in renal bicarbonate absorption and are mutated in proximal and distal renal tubular acidosis respectively. We have also remeasured the eAE1 TOR value for comparison. NBCe1-A had a TOR value of ∼30,400 s−1 whereas kAE1 and eAE1 had significantly higher values (62,000 s−1 and 60,500 s−1 respectively). We modeled the inward-facing (IF) conformation of NBCe1-A to determine conformational changes during its transport cycle. Comparison of this IF model with our previously determined cryoelectron microscopy (cryoEM) outward-facing (OF) conformation structure, demonstrates that NBCe1-A has an elevator-type transport mechanism with a small vertical ∼5 Å shift of the ion coordination site as we have previously shown for AE1. We speculate that this very small vertical movement plays an important role in contributing to the very high TOR numbers of SLC4 transporters.
Impact of muscle fatigue on anticipatory postural adjustments during gait initiation
Authors: Storniolo Jorge L. , Farinelli Veronica , Esposti Roberto , Cavallari Paolo
Published: January 2025

Introduction

Prolonged or strenuous exercise leads to a temporary decrease in muscle function and performance, which interferes with activity of both prime movers and postural muscles. This effect of fatigue has been reported both for single segment movements and for locomotion. However, little is known regarding the effects of fatigue on anticipatory postural adjustments (APAs) during gait initiation, a task in which the control of focal movement should be strictly coupled to a feedforward control of posture.

Methods

We studied APAs during gait initiation in 16 healthy well-trained adult males, searching for muscle activities that precede the backward shift of the Center of Pressure (CoP). Participants stood on a force plate for about 10 s and then started walking at their natural speed. APAs were evaluated before and after a 1 min exhausting sequence of countermovement jumps. An optoelectronic system captured the heel-off events while a force plate measured the CoP position and vertical ground reaction force. Wireless probes recorded the electromyogram of trunk and leg muscles from both sides.

Results

It was observed that muscle fatigue delayed excitatory and inhibitory APAs, of about 40 and 80 ms, respectively, and a parallel delay was induced on prime movers; moreover, velocity and amplitude of backward CoP shift were reduced. Regarding APAs sign and occurrence, most of the participants showed bilateral inhibition in dorsal muscles and excitation in the ventral ones, displaying a forward “diving” strategy that was almost unaffected by fatigue. However, after fatigue, three of the “diving” participants switched to a “turning” strategy, i.e., they displayed a reciprocal activation/inhibition pattern in the dorsal muscles, compatible with a trunk rotation.

Discussion

The “turning” strategy has been previously described in untrained individuals and in a toes-amputee mountain climber, who showed a “diving” approach to gait initiation when wearing his prosthetic shoes and switched to the “turning” approach when barefoot. Altogether, these results support the idea that one and the same person may develop a repertoire of postural strategies among which the central nervous system will choose, according to the personal fitness and the constraints in which the action is performed.
Achievement emotions in kindergarten: the association of solution accuracy with discrete joy, sadness, and surprise
Authors: Kutaka Traci Shizu , Chernyavskiy Pavel , Hofkens Tara
Published: January 2025

Children experience a variety of emotions in achievement settings. Yet, mathematics-related emotions other than anxiety are understudied, especially for young children entering primary school. The current study reports the prevalence and intensity of six basic, discrete achievement emotions (joy/happiness, sadness, surprise, anger, fear, and disgust) expressed on the faces of 15 kindergarten-aged children as they solved increasingly complex arithmetic story problems in a 3-month teaching experiment. We also examine how the extent to which the expressed emotions influenced arithmetic accuracy at the end of an instructional session at the beginning, middle, and end of the teaching experiment. Through the application of FaceReader9, the three most intensely expressed emotions at the launch of the instructional sessions were happiness/joy, sadness, and surprise. Using functional regressions, these expressed achievement emotions predicted arithmetic accuracy at the end of the instructional session. However, when the effect of session over time was added to the model, the relationship between happiness/joy and accuracy, as well as sadness and accuracy, became non-significant. In contrast, the relationship between surprise and accuracy remained significant. We discuss potential explanations for these patterns of significance and non-significance. This study serves as a critical first step in clarifying how emotions contribute to problem-solving behavior as we grapple with how to respond to the sometimes intense, but always present emotions of young learners in ways that are affirming, as well as mathematically productive and generative.
Electroencephalographic markers in Major Depressive Disorder: insights from absolute, relative power, and asymmetry analyses
Authors: Özçoban Mehmet Akif , Tan Oğuz
Published: January 2025

Introduction

Major Depressive Disorder (MDD) leads to dysfunction and impairment in neurological structures and cognitive functions. Despite extensive research, the pathophysiological mechanisms and effects of MDD on the brain remain unclear. This study aims to assess the impact of MDD on brain activity using EEG power spectral analysis and asymmetry metrics.

Methods

EEG recordings were obtained from 48 patients with MDD and 78 healthy controls. The data were segmented into 2-second windows (1024 data points) and analyzed using the Welch method, an advanced variant of the Fast Fourier Transform (FFT). A Hanning time window with 50% overlap was applied to compute the modified periodogram. Absolute and relative power, along with asymmetry values in the theta, alpha, and beta frequency bands, were calculated.

Results

Patients with MDD exhibited significantly higher absolute and relative power in the theta and beta bands and decreased power in the alpha band compared to healthy controls. Asymmetry analysis revealed significant differences between symmetric channels in the theta band (F7-F8, C3-C4, T3-T4, T5-T6), alpha band (F7-F8, C3-C4, T3-T4, T5-T6, O1-O2), and beta band (C3-C4, T3-T4, T5-T6, P3-P4).

Discussion

The findings suggest that MDD affects brain mechanisms and cognitive functions, as evidenced by altered power values in the theta and alpha bands. Additionally, asymmetry values in theta, alpha, and beta bands may serve as potential biomarkers for MDD. This study highlights that beyond the commonly used alpha asymmetry, theta and beta asymmetry can also provide valuable insights into the neurophysiological effects of MDD, aligning with previous neuroimaging studies that indicate impairments in memory, attention, and neuroanatomical connectivity in MDD.
AI-assisted neurocognitive assessment protocol for older adults with psychiatric disorders
Authors: Díaz-Guerra Diego D. , Hernández-Lugo Marena de la C. , Broche-Pérez Yunier , Ramos-Galarza Carlos , Iglesias-Serrano Ernesto , Fernández-Fleites Zoylen
Published: January 2025

Introduction

Evaluating neurocognitive functions and diagnosing psychiatric disorders in older adults is challenging due to the complexity of symptoms and individual differences. An innovative approach that combines the accuracy of artificial intelligence (AI) with the depth of neuropsychological assessments is needed.

Objectives

This paper presents a novel protocol for AI-assisted neurocognitive assessment aimed at addressing the cognitive, emotional, and functional dimensions of older adults with psychiatric disorders. It also explores potential compensatory mechanisms.

Methodology

The proposed protocol incorporates a comprehensive, personalized approach to neurocognitive evaluation. It integrates a series of standardized and validated psychometric tests with individualized interpretation tailored to the patient’s specific conditions. The protocol utilizes AI to enhance diagnostic accuracy by analyzing data from these tests and supplementing observations made by researchers.

Anticipated results

The AI-assisted protocol offers several advantages, including a thorough and customized evaluation of neurocognitive functions. It employs machine learning algorithms to analyze test results, generating an individualized neurocognitive profile that highlights patterns and trends useful for clinical decision-making. The integration of AI allows for a deeper understanding of the patient’s cognitive and emotional state, as well as potential compensatory strategies.

Conclusions

By integrating AI with neuro-psychological evaluation, this protocol aims to significantly improve the quality of neurocognitive assessments. It provides a more precise and individualized analysis, which has the potential to enhance clinical decision-making and overall patient care for older adults with psychiatric disorders.
A gut instinct for childhood leukemia prevention: microbiome-targeting recommendations aimed at parents and caregivers
Authors: Kameri Ersen , Jepsen Vera Helena , Stachura Pawel , Rüchel Nadine , Bhave Rigveda , Benitez Leticia , Crispi Fatima , Gratacos Eduard , Dragano Nico , Janssen Stefan , Borkhardt Arndt , Pandyra Aleksandra , Kögler Gesine , Fischer Ute
Published: January 2025

Childhood leukemia accounts for 30% of all pediatric cancer cases with acute lymphoblastic leukemia (ALL) being the most common subtype. Involvement of the gut microbiome in ALL development has recently garnered interest due to an increasing recognition of the key contribution the microbiome plays in maintaining the immune system's homeostatic balance. Commensal gut microbiota provide a first line of defense against different pathogens and gut microbiome immaturity has been implicated in ALL pathogenesis. Several environmental factors such as nutrition, mode of delivery, breastfeeding and, early social or livestock contacts are known to alter the composition of the gut microbiota. Variations in these factors influence the risk of childhood leukemia onset. This review aims to elucidate the risk factors influencing microbial composition in the context of childhood ALL. The link between gut microbiome diversity and childhood ALL offers the opportunity to develop risk-reducing strategies that can be communicated to a broad target population of (future) parents and caregivers for childhood leukemia prevention. Here, we summarize evidence on how promoting a diverse gut microbiome in newborns through simple measures such as increasing social contacts early in life may decrease the risk of developing ALL in these children later on.