bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Communicable Diseases Among Forcibly Displaced People: A Systematic Mapping Review
Authors: Nishino Kyohei , Gyeltshen Tshewang , Rahman Mahbubur
Published: January 2025

Background: Non-communicable diseases (NCDs) pose a serious global health challenge, accounting for 74% of all deaths worldwide, with low- and middle-income countries (LMICs) disproportionately affected. These challenges are further exacerbated in humanitarian settings, particularly among forcibly displaced people (FDP). Despite the critical need for NCD management in these populations, their epidemiology remains poorly understood. This highlights an urgent research priority to address knowledge gaps and improve their health outcomes. Methods: In this research, we conducted a systematic mapping review to aggregate and categorize existing publications on NCDs among FDP. Literature searches were performed across five electronic databases, namely PubMed, Cochrane Library, Embase, Global Index Medicus, and Google Scholar, using predefined criteria related to target populations, research domains, and study design. The evidence was systematically coded and analyzed to assess the current research status on NCDs among FDP. Results: A total of 310 publications were included in the review. The findings indicate an increasing trend in publications on NCDs among FDP since 2014. In contrast, most studies revealed low evidence levels. Disease-specific research primarily focused on diabetes mellitus (DM) (26.4%) and hypertension (19.8%), addressing health status (43.1%) and health policy (32.0%). Studies mainly concentrated on Syrian (45.5%) and Palestinian (18.9%) refugees, with limited research on other countries and types of FDP. Funding sources were mostly governmental (23.1%) and philanthropic foundations (17.6%), although many studies were unfunded (26.2%). Conclusions: This is the first systematic mapping review on NCDs among FDP. The findings revealed both current knowledge areas of focus and gaps. Although the research quantity has increased, the evidence quality remains low. The retrieved studies predominantly focused on DM and hypertension among Syrian and Palestinian refugees, causing significant knowledge gaps regarding other geographical areas and types of FDP. Future research should prioritize higher-quality studies, expand the geographical scope, and include diverse types of FDP.
LEAP2 in Physiology—A Narrative Review
Authors: Sosinski Oskar , Pruszynska-Oszmalek Ewa , Leciejewska Natalia , Sassek Maciej , Kolodziejski Pawel Antoni
Published: January 2025

Liver Enriched Antimicrobial Peptide 2 (LEAP2) is a fascinating peptide that has gained significant attention since its discovery in 2003. Initially identified as an antimicrobial peptide, LEAP2 has more recently been found to play a key role in the regulation of energy metabolism. One of the most notable functions of LEAP2 is its interaction with the ghrelin hormone, which is known for stimulating hunger. LEAP2 acts as an inhibitor of ghrelin, thereby reducing food intake and influencing energy balance. The physiological roles of LEAP2 extend beyond appetite suppression. Studies have shown that LEAP2 has an impact on insulin secretion, suggesting its potential involvement in glucose metabolism and possibly insulin sensitivity, which is crucial in managing conditions like type 2 diabetes. Moreover, LEAP2 levels appear to fluctuate based on factors such as gender, developmental stage, and even interventions like bariatric surgery, which is known for its role in managing obesity and diabetes. Given these findings, LEAP2 shows potential as a therapeutic target, particularly for addressing obesity and metabolic diseases such as type 2 diabetes. Its ability to influence food intake and energy balance makes it a promising candidate for further research into therapies aimed at weight regulation and glycemic control. In the future, LEAP2 could become an important agent in the development of treatments aimed at curbing obesity and its associated metabolic disorders.
Phytochemicals Controlling Enterohemorrhagic Escherichia coli (EHEC) Virulence—Current Knowledge of Their Mechanisms of Action
Authors: Strzelecki Patryk , Karczewska Monika , Szalewska-Pałasz Agnieszka , Nowicki Dariusz
Published: January 2025

Enterohemorrhagic Escherichia coli (EHEC) is a common pathotype of E. coli that causes numerous outbreaks of foodborne illnesses. EHEC is a zoonotic pathogen that is transmitted from animals to humans. Ruminants, particularly cattle, are considered important reservoirs for virulent EHEC strains. Humans can become infected with EHEC through the consumption of contaminated food and water or through direct contact with infected animals or humans. E. coli O157:H7 is one of the most commonly reported causes of foodborne illnesses in developed countries. The formation of attaching and effacing (A/E) lesions on the intestinal epithelium, combined with Shiga toxin production, is a hallmark of EHEC infection and can lead to lethal hemolytic–uremic syndrome (HUS). For the phage-dependent regulation of Shiga toxin production, antibiotic treatment is contraindicated, as it may exacerbate toxin production, limiting therapeutic options to supportive care. In response to this challenge and the growing threat of antibiotic resistance, phytochemicals have emerged as promising antivirulence agents. These plant-derived compounds target bacterial virulence mechanisms without promoting resistance. Therefore, the aim of this study is to summarize the recent knowledge on the use of phytochemicals targeting EHEC. We focused on the molecular basis of their action, targeting the principal virulence determinants of EHEC.
Comparative Analysis of Serum BAFF and IL-17 Levels Pre- and Post-Antipsychotic Treatment for Acute Schizophrenia
Authors: Samoud Samar , Mtiraoui Ahlem , Zamali Imen , Galai Yousr , Hannachi Naila , Manoubi Wiem , Nakhli Jaafar , Louzir Hechmi , Kissi Yousri El
Published: January 2025

The interplay between the cytokine network and antipsychotic treatment in schizophrenia remains poorly understood. This study aimed to investigate the impact of psychotropic medications on serum levels of IFN-γ, IL-4, TGF-β1, IL-17, and BAFF, and to explore their relationship with psychopathological features. We recruited 63 patients diagnosed with schizophrenia in the acute phase, all of whom were either drug-naïve or had been drug-free for at least three months. Serum levels of IL-4, IFN-γ, TGF-β1, IL-17, and BAFF were measured at baseline and after six months of antipsychotic treatment. The severity of symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms (SANS). Fifty-two patients completed the six-month follow-up for immunoassay analysis. Antipsychotic treatment led to a significant decrease in serum levels of IFN-γ, TGF-β1, and IL-17, alongside a significant increase in BAFF levels. Changes in IFN-γ were positively correlated with SANS scores and negatively correlated with Global Assessment of Functioning (GAF) scores. Changes in TGF-β1 were negatively correlated with GAF scores. Changes in BAFF were negatively correlated with SAPS scores. Multivariable regression models were used to explore the association between cytokine level changes (IL-17, BAFF, IFN-γ, and TGF-β1) and independent variables, including demographic (gender, age), behavioral (tobacco use), clinical (schizophrenia type, disease course, date of onset, prior treatment), and biological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) factors, as well as standardized assessment scores. No significant associations were found, except for a significant negative correlation between TGF-β1 changes and GAF scores, as well as a positive correlation with age. Interestingly, advanced statistical analyses revealed that only changes in IL-17 and BAFF levels were significantly associated with antipsychotic treatment. Our findings suggest that antipsychotic drugs exert both pro- and anti-inflammatory effects on the cytokine network. The observed modulation of IL-17 and BAFF highlights their potential as future therapeutic targets in schizophrenia.
Oxidative Homeostasis in Follicular Fluid and Embryo Quality—A Pilot Study
Authors: Jeremic Ana , Vasiljevic Mladenko , Mikovic Zeljko , Bukumiric Zoran , Simic Petar , Stanisavljevic Tamara , Simic Tatjana , Djukic Tatjana
Published: January 2025

The objective of this study was to measure the different redox biomarker levels within the follicular fluid (FF) and evaluate correlations with embryo quality using the one follicle–one oocyte/embryo approach. The prospective study included 54 women (average age 34.6 ± 3.0 years). Out of the 235 mature metaphase II cells that underwent intracytoplasmic sperm injection, fertilization was achieved in 177 cells, producing 92 Grade I embryos, 26 Grade II embryos, 39 Grade III embryos, and 20 Grade IV embryos. The activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione transferase were significantly higher in the group consisting of lower-quality (Grades II–IV) embryos in comparison with top-quality (Grade I) embryos (p = 0.011; p = 0.021; p = 0.008, respectively). The concentration of oxidative stress markers, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and thiol groups was significantly increased in the group with lower-quality embryos (Grades II–IV) compared to top-quality embryos (0.027; 0.018; 0.021, respectively). Furthermore, a significant positive correlation between each oxidative marker and the activities of antioxidant enzymes was observed (p < 0.001). According to our findings, the best embryos and, consequently, better in vitro fertilization outcomes are linked to low levels of oxidative stress and low antioxidant enzyme activity.
Chemoresistance in Pancreatic Cancer: The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes
Authors: Parvaneh Shahram , Miklós Vanda , Páhi Zoltán Gábor , Szűcs Diána , Monostori Tamás , Póliska Szilárd , Venglovecz Viktória , Pankotai Tibor , Kemény Lajos , Veréb Zoltán
Published: January 2025

Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses. Transcriptomic analyses revealed OXP-induced transcriptional reprogramming in ASCs, with over 7000 differentially expressed genes, highlighting the pathways related to DNA damage response, cell cycle regulation, and stress-related signaling. In contrast, 5-FU elicited limited transcriptional changes, affecting only 192 genes. Cytokine proteome profiling revealed that OXP-treated ASCs significantly influenced the tumor microenvironment by promoting immune evasion (via IL-4, GM-CSF, IP-10, and GROα) and driving extracellular matrix remodeling (through EMMPRIN and DPPIV). In contrast, 5-FU induced comparatively weaker effects, primarily limited to hypoxia-related pathways. Although OXP reduced angiogenic factors, it paradoxically activated pro-survival pathways, thereby enhancing ASC-mediated tumor support. These findings underscore ASCs as modulators of chemoresistance via secretome alterations and stress adaptation. Therefore, future strategies should prioritize the precise targeting of tumor cells while also focusing on the development of personalized treatments to achieve durable therapeutic responses in PDAC.
Enhancement Strategy for Protocatechuic Acid Production Using Corynebacterium glutamicum with Focus on Continuous Fermentation Scale-Up and Cytotoxicity Management
Authors: Chung Jiwoon , Shin Wooshik , Park Chulhwan , Cho Jaehoon
Published: January 2025

Protocatechuate acid (PCA) is a phenolic acid naturally synthesized by various organisms. Protocatechuic acid is synthesized by plants for physiological, metabolic functions, and self-defense, but extraction from plants is less efficient compared to the microbial culture process. The microbial synthesis of protocatechuic acid is sustainable and, due to its high yield, can save energy consumption when producing the same amount. To enhance PCA production using Corynebacterium glutamicum, a statistical optimization of the production medium was performed using full factorial design, the steepest ascent method, and the response surface method. The optimized production medium enabled a PCA production of over 5 g/L in a 72 h batch culture. However, PCA cytotoxicity affected the strain growth and PCA production rate, with an inhibitory concentration of approximately 5 g/L in the fermentation broth. Finally, continuous fermentation was operated for 150 h in the steady-state mode, maintaining the concentration of PCA below 5 g/L. The optimization method established in this study successfully increased PCA production levels, and the findings presented herein are anticipated to contribute to the industrialization of PCA production using C. glutamicum.
Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies
Authors: Pereira-Silva Raquel , Neto Fani L. , Martins Isabel
Published: January 2025

Diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, is a paradigm wherein the heterotopic application of a noxious stimulus results in the attenuation of another spatially distant noxious input. The pre-clinical and clinical studies show the involvement of several neurochemical systems in DNIC/CPM and point to a major contribution of the noradrenergic, serotonergic, and opioidergic systems. Here, we thoroughly review the latest data on the monoaminergic and opioidergic studies, focusing particularly on pre-clinical models of chronic pain. We also conduct an in-depth analysis of these systems by integrating the available data with the descending pain modulatory circuits and the neurochemical systems therein to bring light to the mechanisms involved in the regulation of DNIC. The most recent data suggest that DNIC may have a dual outcome encompassing not only analgesic effects but also hyperalgesic effects. This duality might be explained by the underlying circuitry and the receptor subtypes involved therein. Acknowledging this duality might contribute to validating the prognostic nature of the paradigm. Additionally, DNIC/CPM may serve as a robust paradigm with predictive value for guiding pain treatment through more effective targeting of descending pain modulation.
Pathophysiology and Management Strategies for Post-Stroke Spasticity: An Update Review
Authors: Chen Bei , Yang Tong , Liao Zi , Sun Feiyue , Mei Zhigang , Zhang Wenli
Published: January 2025

Post-stroke spasticity (PSS), characterized by a velocity-dependent increase in muscle tone and exaggerated reflexes, affects a significant portion of stroke patients and presents a substantial obstacle to post-stroke rehabilitation. Effective management and treatment for PSS remains a significant clinical challenge in the interdisciplinary aspect depending on the understanding of its etiologies and pathophysiology. We systematically review the relevant literature and provide the main pathogenic hypotheses: alterations in the balance of excitatory and inhibitory inputs to the descending pathway or the spinal circuit, which are secondary to cortical and subcortical ischemic or hemorrhagic injury, lead to disinhibition of the stretch reflex and increased muscle tone. Prolongation of motoneuron responses to synaptic excitation by persistent inward currents and secondary changes in muscle contribute to hypertonia. The guidelines for PSS treatment advocate for a variety of therapeutic approaches, yet they are hindered by constraints such as dose-dependent adverse effects, high cost, and limited therapeutic efficacy. Taken together, we highlight key processes of PSS pathophysiology and summarize many interventions, including neuroprotective agents, gene therapy, targeted therapy, physiotherapy, NexTGen therapy and complementary and alternative medicine. We aim to confer additional clinical benefits to patients and lay the foundation for the development of new potential therapies against PSS.
Correction: Abou-ElNaga et al. Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice. Int. J. Mol. Sci. 2017, 18, 813
Authors: Abou-ElNaga Amoura , Mutawa Ghada , El-Sherbiny Ibrahim M. , Abd-ElGhaffar Hassan , Allam Ahmed A. , Ajarem Jamaan , Mousa Shaker A.
Published: January 2025

In the original publication [...]
Study on the Chemical Composition and Multidrug Resistance Reversal Activity of Euphorbia uralensis (Euphorbiaceae)
Authors: Ding Yina , Liu Yuhao , Dang Qianru , Akram Zubair , Arshad Anam , Zhu Haochan , Zhang Jianxiang , Han Bo , Turghun Chimengul
Published: January 2025

Euphorbia uralensis belongs to the family Euphorbiaceae and is widely distributed in northern Xinjiang, making it a characteristic plant of the region in Xinjiang, China. The chemical composition and biological activity of Euphorbia uralensis have not yet been reported, although certain compounds isolated from Euphorbia plants in Xinjiang, China, have demonstrated exceptional multidrug resistance (MDR) reversal. This study aims to investigate the chemical components present in Euphorbia uralensis with the potential to reverse MDR. The aerial parts of Euphorbia uralensis were extracted using organic solvents of varying polarities, resulting in dichloromethane (Fr-E) and petroleum ether (Fr-S) fractions, which exhibited greater MDR reversal activity than the other fractions. The chemical constituents of the Fr-S fraction were analyzed using GC-MS. The chemical components of the Fr-E fraction were isolated and purified using column chromatography. The most effective compounds with MDR reversal activity were screened out, and the mechanism was investigated using molecular docking, molecular dynamics simulations, Western blotting, and rhodamine 123 staining. GC-MS analysis showed that the Fr-S fraction was rich in triterpenes, fatty acids, phenols, and long-chain alkanes, all of which were identified for the first time in Euphorbia uralensis. Among these, palmitic acid was present at a content level of 15.86%. This study notably unveils the discovery of a new compound and 16 previously recorded compounds for the first time in this plant, with the main types identified as steroids, sesquiterpenes, and flavonoids. The isolated compounds were tested for cytotoxicity and MDR reversal activity. The new compounds Euphouralosides A, pubinernoid A, naringenin, and punigratine showed good MDR reversal activity against MCF-7 and MCF-7/ADR cell lines. Punigratine was the most active compound. Moreover, punigratine could stably bind to the ABCB1 protein. Western blot analysis revealed that punigratine did not affect the expression of the ABCB1 protein in cells (p > 0.05). However, following treatment with punigratine (0.16 μM), there was a significant increase the intracellular accumulation of Rh123 in MCF-7/ADR cells (p < 0.05). These findings suggest that punigratine can inhibit the efflux of the ABCB1 protein, thereby overcoming MDR in tumors. This study provides a foundation for further research on the biological activity and medicinal potential of Euphorbia uralensis.
Dual Roles of miR-10a-5p and miR-10b-5p as Tumor Suppressors and Oncogenes in Diverse Cancers
Authors: Singh Rajan , Ha Se Eun , Yu Tae Yang , Ro Seungil
Published: January 2025

Cancer is a complex genetic disorder characterized by abnormalities in both coding and regulatory non-coding RNAs. microRNAs (miRNAs) are key regulatory non-coding RNAs that modulate cancer development, functioning as both tumor suppressors and oncogenes. miRNAs play critical roles in cancer progression, influencing key processes such as initiation, promotion, and metastasis. They exert their effects by targeting tumor suppressor genes, thereby facilitating cancer progression, while also inhibiting oncogenes to prevent further disease advancement. The miR-10 family, particularly miR-10a-5p and miR-10b-5p (miR-10a/b-5p), is notably involved in cancer progression. Intriguingly, their functions can differ across different cancers, sometimes promoting and at other times suppressing tumor growth depending on the cancer type and target genes. This review explores the dual roles of miR-10a/b-5p as tumor-suppressive miRNAs (TSmiRs) or oncogenic miRNAs (oncomiRs) in various cancers by examining their molecular and cellular mechanisms and their impact on the tumor microenvironment. Furthermore, we discuss the potential of miR-10a/b-5p as therapeutic targets, emphasizing miRNA-based strategies for cancer treatment. The insights discussed in this review aim to advance our understanding of miR-10a/b-5p’s roles in tumor biology and their application in developing innovative cancer therapies.
Metal Ion Supplementation to Boost Melanin Production by Streptomyces nashvillensis
Authors: Restaino Odile Francesca , Kordjazi Talayeh , Tancredi Francesco , Manini Paola , Lanzillo Fabiana , Raganati Francesca , Marzocchella Antonio , Porta Raffaele , Mariniello Loredana
Published: January 2025

As Streptomycetes might produce melanin to survive in stressful environmental conditions, like under metal exposure, supplementing metal ions to the growth medium could be a wise strategy for boosting the production of the pigment. The aim of this study was to test, for the first time, the possibility of boosting S. nashvillensis DSM40314 melanin biosynthesis by adding to the growth medium singularly or, at the same time, different concentrations (1.0, 1.5, and 2.0 g∙L−1) of CuSO4 or/and Fe2(SO4)3. A maximum melanin production of 4.0 ± 0.1 g·L−1 was obtained in shake flasks with a 2.0 g∙L−1 coupled addition of the two metals, while the extracellular tyrosinase activities ranged values between 5.4 and 11.6 ± 0.1 U·L−1. The pigments produced in different conditions were precipitated from the broth supernatants under acidic conditions, purified, and characterized by UV-VIS, FT-IR, and NMR analyses that determined structures like eumelanin pigments. Fermentation experiments in stirred tank reactors allowed to scale up the process in more controlled conditions, further boosting the pigment production up to 4.9 ± 0.1 g·L−1, with an increase of about 22.0% compared to the results obtained in shake flasks.
Genome-Wide Identification and Functional Characterization of SKP1-like Gene Family Reveal Its Involvement in Response to Stress in Cotton
Authors: Geng Zhao , Liu Jianguang , Zhao Guiyuan , Geng Xiangli , Liu Xu , Liu Xingyu , Zhang Hanshuang , Wang Yongqiang
Published: January 2025

SKP1 constitutes the Skp1-Cullin-F-box ubiquitin E3 ligase (SCF), which plays a role in plant growth and development and biotic and abiotic stress in ubiquitination. However, the response of the SKP1-like gene family to abiotic and biotic stresses in cotton has not been well characterized. In this study, a total of 72 SKP1-like genes with the conserved domain of SKP1 were identified in four Gossypium species. Synteny and collinearity analyses revealed that segmental duplication played a major role in the expansion of the cotton SKP1-like gene family. All SKP1-like proteins were classified into three different subfamilies via phylogenetic analysis. Furthermore, we focused on a comprehensive analysis of SKP1-like genes in G. hirsutum. The cis-acting elements in the promoter site of the GhSKP1-like genes predict their involvement in multiple hormonal and defense stress responses. The expression patterns results indicated that 16 GhSKP1-like genes were expressed in response to biotic or abiotic stresses. To further validate the role of the GhSKP1-like genes in salt stress, four GhSKP1-like genes were randomly selected for gene silencing via VIGS. The results showed that the silencing of GhSKP1-like_7A resulted in the inhibition of plant growth under salt stress, suggesting that GhSKP1-like_7A was involved in the response to salt stress. In addition, yeast two-hybrid results revealed that GhSKP1-like proteins have different abilities to interact with F-box proteins. These results provide valuable information for elucidating the evolutionary relationships of the SKP1-like gene family and aiding further studies on the function of SKP1-like genes in cotton.
Ligand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin
Authors: Kise Satoko , Morita Shinichi , Sakaki Toshiyuki , Kimura Hiroyuki , Kinuya Seigo , Yasuda Kaori
Published: January 2025

Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (Vdr-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since Vdr-KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among Vdr-KO, Vdr-R270L/H301Q, and wild-type (WT) rats. While Vdr-R270L/H301Q rats exhibited normal skin formation similar to WT rats, Vdr-KO rats showed remarkable hyperkeratosis and trans-epidermal water loss in the skin. RNA sequencing and proteomic analysis revealed that the gene and protein expression patterns in Vdr-KO rats significantly differed from those in WT and Vdr-R270L/H301Q rats, with a marked decrease in the expression of factors involved in Shh, Wnt, and Bmp signaling pathways, a dramatic reduction in the expression of hair keratins, and a substantial increase in the expression of epidermal keratins. This study clearly demonstrated that non-liganded VDR is significantly involved in the differentiation, proliferation, and cell death of keratinocytes in hair follicles and the epidermis.
Whole-Exome Sequencing: Discovering Genetic Causes of Granulomatous Mastitis
Authors: Ozcinar Beyza , Ocak Zeynep , Billur Deryanaz , Ertugrul Baris , Timirci-Kahraman Ozlem
Published: January 2025

Granulomatous mastitis (GM) is a rare, benign, but chronic and recurrent inflammatory breast disease that significantly impacts physical and psychological well-being. It often presents symptoms such as pain, swelling, and discharge, leading to diagnostic confusion with malignancy. The etiology of GM remains unclear, though autoimmune and multifactorial components are suspected. This study aimed to explore the genetic underpinnings of GM using whole-exome sequencing (WES) on 22 GM patients and 52 healthy controls to identify single nucleotide variants (SNVs) and copy number variations (CNVs) potentially linked to the disease. WES analysis revealed novel SNVs in six genes: BRCA2 (rs169547), CFTR (rs4727853), NCF1 (rs10614), PTPN22 (rs2476601), HLA-DRB1 (seven variants), and C3 (rs406514). Notably, most of these variants are associated with immune regulation and inflammatory pathways, supporting the hypothesis that GM is an autoimmune disease. However, all identified variants were classified as benign according to the American College of Medical Genetics and Genomics (ACMG) guidelines, necessitating further investigation into their potential functional effects. Despite conducting CNV analysis, no significant variations were identified. This study represents a foundational step in linking genetic predisposition to GM and highlights the need for integrating genetic, clinical, and functional data to better understand GM’s pathophysiology. Future research should focus on larger cohorts, functional studies, and exploring multifactorial contributors to GM, including hormonal and environmental factors.
Anti-Tumor Effects of Sheep Umbilical Cord Mesenchymal Stem Cells on Melanoma Cells
Authors: Yue Fengjiao , Zhao Yuqing , Lv Yiting , Li Songmei , Wang Weihai , Li Yajun , Wang Shujie , Wang Chunsheng
Published: January 2025

Melanoma is among the most common malignancies and has recently exhibited increased resistance to treatments, resulting in a more aggressive disease course. Mesenchymal stem cells (MSCs) secrete cytokines both in vivo and in vitro, which regulate tumor cell signaling pathways and the tumor microenvironment, thereby influencing tumor progression. This study investigates the anti-melanogenesis effects of sheep umbilical cord mesenchymal stem cells (SUCMSCs) to assess their potential application in melanoma treatment. Our findings indicate that, in vitro, SUCMSCs reduce melanin content and tyrosinase activity, inhibit melanoma cell viability, proliferation, migration, and invasion, and promote melanoma cell apoptosis. Subsequent in vivo experiments confirmed that SUCMSCs effectively suppress tumor growth, and histological analysis via HE staining revealed notable differences. Additionally, transcriptome sequencing analysis indicated that the anti-tumor effects were primarily mediated through autophagy, apoptosis, and the TGF-β and NF-κB signaling pathways. The RT-qPCR validation results aligned with the transcriptome data. In summary, SUCMSCs exert anti-melanogenesis effects through the interaction of multiple signaling pathways and cytokines, demonstrating significant potential for melanoma treatment.
Predictive Value of FDG Uptake on PET for Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series
Authors: Shatila Malek , Takigawa Kei , Lu Yang , Urias Rivera Andres Caleb , Mittal Nitish , Aleem Abdullah Sagar , Ngo Sean , Lu Eric , Wu Deanna , Sperling Gabriel , Naz Sidra , Schneider Bryan , Shirwaikar Thomas Anusha , Wang Yinghong
Published: January 2025

Objectives: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis. Methods: Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time. We included patients who had signs and symptoms of colitis and reviewed their surveillance PET/CT scans obtained 2 to 6 weeks before and up to 3 months after diagnosis. Results: For the 33 included patients, surveillance scans were reviewed in collaboration with a nuclear radiologist. A total of 17 patients (51.5%) received combination therapy, while 14 (42.4%) received anti–PD-1/PD-L1 monotherapy. While ICI therapy has a median duration of 6.5 months, most patients (72.7%) had negative surveillance PET/CT for colitis. Diarrhea and colitis severity were similar among those with positive and negative findings for colitis on surveillance PET/CT. The outcomes of colitis were similar, with an 81.8% resolution in patients with negative PET/CT and 71.4% in patients with positive PET/CT. Conclusions: PET/CT imaging did not appear to assist in predicting IMC. This may be due to the long interval between clinical IMC and surveillance PET/CT imaging. The continued use of clinical criteria combined with laboratory markers, e.g., lactoferrin and calprotectin, and endoscopy/histology will enable more accurate detection and timely treatment of IMC.
Complete Abdominal Evisceration After Open Hysterectomy: A Case Report and Evidence-Based Review
Authors: Varlas Valentin Nicolae , Bălescu Irina , Varlas Roxana Georgiana , Adnan Al-Aloul , Filipescu Alexandru George , Bacalbașa Nicolae , Suciu Nicolae
Published: January 2025

Background/Objectives: Despite its low incidence, complete postoperative abdominal evisceration represents a complication requiring an urgent solution. We aimed to present a rare case of an abdominal evisceration of the omentum and small-bowel loops after a total abdominal hysterectomy and review the literature regarding this condition’s diagnosis and therapeutic management. Case report: On the sixth postoperative day for a uterine fibroid, a 68-year-old patient presented with an abdominal evisceration of the omentum and small bowel that occurred two hours before. An emergency laparotomy was performed to correct the evisceration and restore the integrity of the abdominal wall structure. The literature review was carried out in the PubMed, Embase, and Web of Science databases using the terms “abdominal wall dehiscence”, “abdominal evisceration”, “open abdomen”, “burst abdomen”, “abdominal fascial dehiscence”, “abdominal dehiscence post-hysterectomy”, and “hysterectomy complications” by identifying all-time articles published in English. Results: Seven studies were included in this electronic search. The early diagnosis of abdominal evisceration, the identification of risk factors and comorbidities, followed by the choice of surgical technique, and postoperative follow-up were parts of the standard algorithm for managing this life-threatening case. Conclusions: Abdominal evisceration, as a surgical emergency, requires the diagnosis and treatment of this complication alongside the identification of the risk factors that can lead to its occurrence, as well as careful postoperative monitoring adapted to each case.
Limited Changes in Red Blood Cell Parameters After Probiotic Supplementation in Depressive Individuals: Insights from a Secondary Analysis of the PRO-DEMET Randomized Controlled Trial
Authors: Gajewska Agata , Wysokiński Adam , Strzelecki Dominik , Gawlik-Kotelnicka Oliwia
Published: January 2025

Background: Depression often coexists with anemia, potentially sharing common pathways, highlighting the need for treatments addressing both conditions simultaneously. This study evaluated the effect of probiotics on red blood cell (RBC) parameters in adults with depressive disorder. We hypothesized that probiotics would positively influence RBC parameters, potentially modulated by baseline inflammation or dietary intake, with improved RBC function correlating with better antidepressant outcomes. Methods: This secondary analysis of a two-arm, randomized, double-blind, controlled trial involved 116 adults with depressive disorder. Participants received a probiotic formulation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or a placebo for 60 days. Data from 97 subjects were analyzed for RBC parameters, including hemoglobin (HGB), RBC count, hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW). Results: Probiotic supplementation did not result in significant changes in RBC parameters compared to the placebo. However, probiotics may help stabilize HGB, HCT, MCH, and MCHC levels, potentially preventing fluctuations observed in the placebo group. Conclusions: While probiotics showed potential benefits for depressive symptoms, significant changes in RBC parameters were not observed. Larger studies are needed to clarify the mechanisms and clinical implications.
Risk Factors and Impact of Intra-Articular Scarring After Open Reduction and Internal Fixation in Mandibular Condylar Head Fractures—A Prospective Analysis
Authors: Reichert Clarissa Sophie , Pienkohs Simon Patrik , Skroch Linda , Meisgeier Axel , Neff Andreas
Published: January 2025

Background: During the routine removal of osteosynthesis materials after surgical treatment (ORIF) of condylar head fractures (CHFs), as performed at our clinic, localised and sometimes pronounced intra-articular scarring were observed quite regularly. This prospective study therefore investigates the causes of intra-articular scarring and its impact on functionality after surgical treatment (ORIF) of condylar head fractures (CHFs). Methods: Moreover, 80/98 patients with 96/114 CHFs (ORIF between 2014 and 2024) were evaluated when performing hardware removal. Statistical analysis used logistic regression and sign tests. Results: Postoperative scarring was seen in 72/96 cases (75%), either localised (n = 54; 56%) or pronounced (n = 18; 19%). Scarring correlated with limitations of laterotrusion for pronounced scarring (p = 0.016; OR = 6.806; 95% CI [1.422, 32.570]; large effect size) and with limitations of mediotrusion for localised scarring (p = 0.013; OR = 0.236; 95% CI [0.076, 0.734]; very small effect size). Factors favouring localised scarring were reduced ipsilateral dental support (p = 0.022; OR = 3.36; 95% CI [1.191, 9.459]; medium effect size) and major fragmentation (p = 0.029; OR = 3.182; 95% CI [1.123, 9.013]; medium effect size). However, there was no correlation between scarring and types (screws w/wo microplates) or number of osteosynthesis materials. Pronounced scarring showed a significantly higher risk for osseous degenerative complications (p = 0.041; OR = 4.171; CI [1.058, 16.452]; medium effect size). Conclusions: Intra-articular scarring after ORIF of CHFs poses a risk for functional limitations and osseous degenerative changes. Early adhesiolysis during the removal of hardware seems favourable for functional outcomes after CHFs.
Comparative Analysis of Liposuction and Conservative Treatment in Lipedema Patients: A Modified Body-Q Questionnaire Study
Authors: Aitzetmüller-Klietz Marie-Luise , Ozturk Mahmut , Seefeldt Tobias , Wiebringhaus Philipp , Wellenbrock Sascha Veiz , Tav Baksan , Hirsch Tobias , Harati Kamran , Aitzetmüller-Klietz Matthias
Published: January 2025

Background: Despite its estimated high prevalence among women and increasing awareness, lipedema remains under-investigated. Ignoring its debilitating nature, surgical treatment for this condition is frequently covered by health insurance only in advanced stages and after the exhaustion of conservative therapies. Methods: A total of 1015 patients with lipedema were recruited via social media platforms. Of these, 860 patients provided answers to at least one complete section of the modified Body-Q questionnaire (response rate 85%). The Mann–Whitney U and Kruskal–Wallis tests were utilized to assess the impact of the surgical treatment by means of patient-reported outcomes on the self-perception of various body areas. Results: The satisfaction scores among conservatively treated patients for abdominal appearance, arms, back, body, buttocks, and inner thighs showed a statistically significant decline with increasing stages of lipedema. The comparison of patient evaluation scores in the appearance domain demonstrated better patient self-perception scores in patients who received at least one session of the surgical treatment for the hips and thighs (p < 0.01), inner thighs (p < 0.01), and excess skin (0.01) scales. On the body scale, the patients who underwent liposuction again reported better satisfaction scores; however, this did not reach statistical significance (p < 0.081). In the health-related quality of life domain, the patients who received liposuction treatment reported a better outcome in the body image (p < 0.01), physical function (p = 0.05), physical symptoms (p = 0.04), and psychological function (p < 0.01) scales. Conclusions: The current study underscores the burden of lipedema of affected patients and its negative impact on self-perception. As the disease progresses, conservatively treated patients experience a decline in satisfaction with various aspects of their appearance. However, surgical interventions, particularly liposuction, does not address esthetic concerns but significantly improve health-related quality of life across multiple domains, emphasizing the comprehensive benefits of surgical intervention in the management of lipedema.
Exploring the Relationship Between Continuously Monitored Vital Signs, Clinical Deterioration, and Clinical Actions
Authors: Peelen Roel V. , Eddahchouri Yassin , Spenkelink Ilse M. , van Goor Harry , Bredie Sebastian J. H.
Published: January 2025

Continuous monitoring on the general ward leads to more and earlier interventions to prevent clinical deterioration. These clinical actions influence outcomes and may serve as an indicator of impending deterioration. This study aims to correlate clinical actions with clinical endpoints and deviating vital signs. Methods: This cohort study prospectively charted all patients undergoing continuous vital sign monitoring on a gastro-intestinal and oncological surgery, and an internal ward of an academic hospital in The Netherlands from 1 August 2018 till 31 July 2019 (METC 2018-4330, NCT04189653). Clinical actions recorded in electronic medical records were analyzed to assess correlations with patient outcomes, hospital length of stay, and alarming monitoring minutes. Results: A total of 1529 patients were included, of which 68 patients had a negative clinical endpoint. There were 2749 clinical actions recorded. Clinical actions correlated to negative clinical endpoints (ρ = 0.259; p < 0.001, OR: 3.4 to 79.5) and to the length of stay (ρ = 0.560; p < 0.001). Vital sign deviations correlated with clinical actions (ρ = 0.025–0.056; p < 0.001–p = 0.018). In the last 72 h before a clinical endpoint, for alarming minutes, this correlation with clinical actions was more pronounced (ρ = 0.340, p < 0.001). Conclusions: Predefined clinical actions performed on admitted general ward patients correlated with negative endpoints, an increased length of stay, and with deviating vital signs, especially in the period directly preceding severe deterioration. Clinical actions have potential as an intermediate measurement of deterioration.
Removal of Spontaneously Fractured Leads with Their Proximal Ends in the Heart and Vasculature—Description of Different Approaches and Tools
Authors: Kutarski Andrzej , Jacheć Wojciech , Pietura Radosław , Czajkowski Marek , Stefańczyk Paweł , Kosior Jarosław , Sawonik Sebastian , Nowosielecka Dorota
Published: January 2025

Background: Removal of spontaneously fractured leads with their proximal ends migrated into the vascular space has not been analysed in detail thus far. The study aimed to compare the effectiveness of different approaches and auxiliary tools for removing fractured leads with migrated proximal ends. Methods: Retrospective analysis of 72 cases from a database containing 3847 TLEs (transvenous lead extraction). Results: Most of the leads were passive, especially unipolar. Procedure complexity in such cases was high but with satisfying effectiveness (procedural success rate 93.06%) and independent of the position of the proximal end. The rate of major complications was 2.78%, which may be attributed to long implant duration (152.2 months). Extraction of such leads did not influence long-term survival. The femoral approach was most often used (62.50%). In 79.16% of leads, mechanical dissection was required. In 66.7%, proximal ends were strongly attached to the wall, and a loop had to be applied. In 15.28% of procedures, the lead was wrapped around a pig-tail catheter (“spaghetti twisting technique”). Conclusions: (1) Spontaneous lead fracture with the proximal ends migrated into the vascular space is a rare finding (1.87% of the TLE). (2) Removal of such leads requires the use of different approaches as well as dedicated and non-dedicated tools. (3) Despite a high level of procedure complexity, its effectiveness is high, with an acceptable rate of major complications.
Artificial Intelligence in Sepsis Management: An Overview for Clinicians
Authors: Bignami Elena Giovanna , Berdini Michele , Panizzi Matteo , Domenichetti Tania , Bezzi Francesca , Allai Simone , Damiano Tania , Bellini Valentina
Published: January 2025

Sepsis is one of the leading causes of mortality in hospital settings, and early diagnosis is a crucial challenge to improve clinical outcomes. Artificial intelligence (AI) is emerging as a valuable resource to address this challenge, with numerous investigations exploring its application to predict and diagnose sepsis early, as well as personalizing its treatment. Machine learning (ML) models are able to use clinical data collected from hospital Electronic Health Records or continuous monitoring to predict patients at risk of sepsis hours before the onset of symptoms. Background/Objectives: Over the past few decades, ML and other AI tools have been explored extensively in sepsis, with models developed for the early detection, diagnosis, prognosis, and even real-time management of treatment strategies. Methods: This review was conducted according to the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research Type) framework to define the study methodology. A critical overview of each paper was conducted by three different reviewers, selecting those that provided original and comprehensive data relevant to the specific topic of the review and contributed significantly to the conceptual or practical framework discussed, without dwelling on technical aspects of the models used. Results: A total of 194 articles were found; 28 were selected. Articles were categorized and analyzed based on their focus—early prediction, diagnosis, mortality or improvement in the treatment of sepsis. The scientific literature presents mixed outcomes; while some studies demonstrate improvements in mortality rates and clinical management, others highlight challenges, such as a high incidence of false positives and the lack of external validation. This review is designed for clinicians and healthcare professionals, and aims to provide an overview of the application of AI in sepsis management, reviewing the main studies and methodologies used to assess its effectiveness, limitations, and future potential.
Exploring the Interplay of Handgrip Neuromuscular, Morphological, and Psychological Characteristics in Tactical Athletes and General Population: Gender- and Occupation-Based Specific Patterns
Authors: Milošević Miloš M. , Koropanovski Nenad , Vuković Marko , Božović Branislav , Kukić Filip , Mudrić Miloš R. , Stamatis Andreas , Dopsaj Milivoj
Published: January 2025

Background/Objectives: The correlation of handgrip strength (HGS) and morphological characteristics with Big Five personality traits is well documented. However, it is unclear whether these relationships also exist in highly trained and specialized populations, such as tactical athletes, and whether there are specific differences compared to the general population. This study aimed to explore the interplay of handgrip neuromuscular, morphological, and psychological characteristics in tactical athletes and the general population of both genders. Methods: The research was conducted on a sample of 205 participants. A standardized method, procedure, and equipment (Sports Medical solutions) were used to measure the isometric neuromuscular characteristics of the handgrip. Basic morphological characteristics of body height, body mass, and body mass index were measured with a portable stadiometer and the InBody 720 device. Psychological characteristics were assessed with the Mental Toughness Index and Dark Triad Dirty Dozen questionnaires. Results: Numerous significant correlations were obtained, as well as differences between tactical athletes and the general population of both genders. The most prominent correlations were between the excitation index with Psychopathy and the Dark Triad (ρ = −0.41, −0.39) in female tactical athletes, as well as Neuroticism with body height, maximal force, and the maximum rate of force development in the male general population (ρ = 0.49, 0.43, 0.41). The obtained results also revealed gender and occupational specific patterns of researched relationships. Conclusions: Although the results of this study indicated the possibility of the existence of correlations between handgrip neuromuscular, morphological, and psychological characteristics in tactical athletes of both genders, nevertheless, at the moment, there is not enough solid evidence for that. That is why new research is needed. An analysis of muscle contractile and time parameters as neuromuscular indicators in the HGS task proved to be a possible promising method, which brought numerous new insights about the researched relationships. For practical application in the field, we propose including Mental Toughness and the Dark Triad traits in the selection process for future police officers and national security personnel based on the obtained results.