bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Characterization of Wholly Disordered Proteins in Arabidopsis
Authors: Long Wenfen , Zhao Liang , Yang Huimin , Yang Xinyi , Bai Yulong , Xue Xiuhua , Wang Doudou , Han Shengcheng
Published: January 2025

Intrinsically disordered proteins (IDPs) include two types of proteins: partial disordered regions (IDRs) and wholly disordered proteins (WDPs). Extensive studies focused on the proteins with IDRs, but less is known about WDPs because of their difficult-to-form folded tertiary structure. In this study, we developed a bioinformatics method for screening more than 50 amino acids in the genome level and found a total of 27 categories, including 56 WDPs, in Arabidopsis. After comparing with 56 randomly selected structural proteins, we found that WDPs possessed a more wide range of theoretical isoelectric point (PI), a more negative of Grand Average of Hydropathicity (GRAVY), a higher value of Instability Index (II), and lower values of Aliphatic Index (AI). In addition, by calculating the FCR (fraction of charged residue) and NCPR (net charge per residue) values of each WDP, we found 20 WDPs in R1 (FCR < 0.25 and NCPR < 0.25) group, 15 in R2 (0.25 ≤ FCR ≤ 0.35 and NCPR ≤ 0.35), 19 in R3 (FCR > 0.35 and NCPR ≤ 0.35), and two in R4 (FCR > 0.35 and NCPR > 0.35). Moreover, the gene expression and protein-protein interaction (PPI) network analysis showed that WDPs perform different biological functions. We also showed that two WDPs, SIS (Salt Induced Serine rich) and RAB18 (a dehydrin family protein), undergo the in vitro liquid-liquid phase separation (LLPS). Therefore, our results provide insight into understanding the biochemical characters and biological functions of WDPs in plants.
Evaluation of Serum Supplementation on the Development of Haemonchus contortus Larvae In Vitro and on Compound Screening Results
Authors: Thilakarathne Sandani S. , Taki Aya C. , Wang Tao , Nowell Cameron , Chang Bill C. H. , Gasser Robin B.
Published: January 2025

A high-throughput platform for assessing the activity of synthetic or natural compounds on the motility and development of Haemonchus contortus larvae has been established for identifying new anthelmintic compounds active against strongylid nematodes. This study evaluated the impact of serum supplementation on larval development, motility and survival in vitro and its implications for phenotypic compound screening. Of five blood components assessed, 7.5% sheep serum significantly enhanced larval development, motility and survival compared to the original medium (LB*), leading to the formulation of an improved medium (LBS*). Proteomic analysis revealed marked differences in protein expression in larvae cultured in LBS* versus LB*, including molecules associated with structural integrity and metabolic processes. The phenotypic screening of 240 compounds (“Global Priority Box” from Medicines Malaria Venture) using LBS* yielded results distinct from those in LB*, highlighting the effect of culture conditions on screening assessments. These findings indicate/emphasise the critical need to evaluate and optimise culture media for physiologically relevant conditions in screening platforms, improving the reliability of anthelmintic discovery.
Complete Polar Lipid Profile of Kefir Beverage by Hydrophilic Interaction Liquid Chromatography with HRMS and Tandem Mass Spectrometry
Authors: Ventura Giovanni , Bianco Mariachiara , Losito Ilario , Cataldi Tommaso R. I. , Calvano Cosima D.
Published: January 2025

Kefir, a fermented milk product produced using kefir grains, is a symbiotic consortium of bacteria and yeasts responsible for driving the fermentation process. In this study, an in-depth analysis of kefir’s lipid profile was conducted, with a focus on its phospholipid (PL) content, employing liquid chromatography with high-resolution mass spectrometry (LC-HRMS). Nearly 300 distinct polar lipids were identified through hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization (ESI) and Fourier-transform orbital-trap MS and linear ion-trap tandem MS/MS. The identified lipids included phosphatidylcholines (PCs), lyso-phosphatidylcholines (LPCs), phosphatidylethanolamines (PEs) and lyso-phosphatidylethanolamines (LPEs), phosphatidylserines (PSs), phosphatidylglycerols (PGs), and phosphatidylinositols (PIs). The presence of lysyl-phosphatidylglycerols (LyPGs) was identified as a key finding, marking a lipid class characteristic of Gram-positive bacterial membranes. This discovery highlights the role of viable bacteria in kefir and underscores its probiotic potential. The structural details of minor glycolipids (GLs) and glycosphingolipids (GSLs) were further elucidated, enriching the understanding of kefir’s lipid complexity. Fatty acyl (FA) composition was characterized using reversed-phase LC coupled with tandem MS. A mild epoxidation reaction with meta-chloroperoxybenzoic acid (m-CPBA) was performed to pinpoint double-bond positions in FAs. The dominant fatty acids were identified as C18:3, C18:2, C18:1, C18:0 (stearic acid), C16:0 (palmitic acid), and significant levels of C14:0 (myristic acid). Additionally, two isomers of FA 18:1 were distinguished: ∆9-cis (oleic acid) and ∆11-trans (vaccenic acid). These isomers were identified using diagnostic ion pairs, retention times, and accurate m/z values. This study provides an unprecedented level of detail on the lipid profile of kefir, shedding light on its complex composition and potential nutritional benefits.
The Role of Elacridar, a P-gp Inhibitor, in the Re-Sensitization of PAC-Resistant Ovarian Cancer Cell Lines to Cytotoxic Drugs in 2D and 3D Cell Culture Models
Authors: Stasiak Piotr , Sopel Justyna , Lipowicz Julia Maria , Rawłuszko-Wieczorek Agnieszka Anna , Korbecki Jan , Januchowski Radosław
Published: January 2025

Chemotherapy resistance is a significant barrier to effective cancer treatment. A key mechanism of resistance at the single-cell level is the overexpression of drug transporters in the ABC family, particularly P-glycoprotein (P-gp), which leads to multidrug resistance (MDR). Inhibitors of these transporters can help re-sensitize cancer cells to chemotherapeutics. This study evaluated elacridar (GG918 and GF120918), a potent third-generation P-gp inhibitor, for its ability to reverse MDR in paclitaxel (PAC)-resistant ovarian cancer cell lines. Sensitive and PAC-resistant cells were cultured in two-dimensional (2D) and three-dimensional (3D) models. MDR1 gene expression was analyzed using Q-PCR, and P-gp protein expression was examined via Western blot and immunofluorescence. Drug sensitivity was evaluated with MTT assays, and P-gp activity was analyzed by flow cytometry and fluorescence microscopy. Elacridar effectively inhibited P-gp activity and increased sensitivity to PAC and doxorubicin (DOX) in 2D cultures but not cisplatin (CIS). In 3D spheroids, P-gp activity inhibition was observed via Calcein-AM staining. However, no re-sensitization to PAC occurred and limited improvement was observed for DOX. These findings suggest that elacridar effectively inhibits P-gp in both 2D and 3D conditions. However, its ability to overcome drug resistance in 3D models is limited, highlighting the complexity of tissue-specific resistance mechanisms.
Cytogenomic Characterization of Murine Cell Line Sarcoma 180 = S-180
Authors: Liehr Thomas , Rincic Martina
Published: January 2025

The cell line Sarcoma 180, which is also called S-180 (or S180), was established about 110 years ago from a murine axillary sarcoma. It has been applied in >5000 studies but was never genetically characterized in detail; this study fills that gap. The cell line Sarcoma 180 was analyzed for its chromosomal constitution using molecular cytogenetic approaches, specifically murine multicolor banding (mcb). Additionally, array comparative genomic hybridization was performed to characterize copy number alterations. Sarcoma 180 has a near tetraploid karyotype without Y-chromosome material and only two X-chromosomes. The complex karyotype includes dicentrics and simple and complex rearrangements and shows a relatively high chromosomal instability. An in silico translation of the obtained results to the human genome indicated that Sarcoma 180 is suitable as a model for advanced human mesenchymal chondrosarcoma.
Exploring the Characters of Non-Coding RNAs in Spermatogenesis and Male Infertility
Authors: Yan Qiu , Wang Qi
Published: January 2025

Infertility is a widespread clinical problem that affects human reproduction and species persistence worldwide. Around 40–70% of cases are due to male reproductive defects. Functional spermatogenesis (sperm production through several coordinated events) is at the heart of male fertility. Non-coding RNAs (ncRNAs) are the primary regulators of gene expression, controlling extensive critical cellular processes, for example proliferation, differentiation, apoptosis, and reproduction. Due to advancements in high-throughput sequencing tools, many studies have revealed that ncRNAs are widely expressed in germ cells, meiosis, spermatogenesis, sperm fertility, early post-fertilization development, and male infertility. The present review examines the biology and function of ncRNAs, including microRNAs, circular RNAs, and long ncRNAs, in spermatogenesis, their correlation with infertility, and their potential as biomarkers for sperm quality and fertility. The function of ncRNA in Sertoli cells (SCs) and Leydig cells (LCs) is also outlined throughout this study, because spermatogenesis requires testicular somatic cells to be involved in testicular development and male fertility. Meanwhile, the future development of ncRNAs for the clinical treatment of male infertility is also anticipated and discussed.
CX3CR1–Fractalkine Dysregulation Affects Retinal GFAP Expression, Inflammatory Gene Induction, and LPS Response in a Mouse Model of Hypoxic Retinopathy
Authors: Rorex Colin , Cardona Sandra M. , Church Kaira A. , Rodriguez Derek , Vanegas Difernando , Saldivar Reina A. , El-Sheikh Amira , Wang Yufeng , Gyoneva Stefka , Cotleur Anne C. , Cardona Astrid E.
Published: January 2025

Diabetic retinopathy (DR) causes vision loss due to sustained inflammation and vascular damage. The vascular damage is evident by fibrinogen leakage, angiogenesis, and hypoxia. Neuronal regulation of microglia via the CX3CL1 (Fractalkine or FKN)-CX3CR1 pathway plays a significant role in retinal pathology. Defects in FKN or CX3CR1 exacerbate inflammation, vascular damage, and vision impairment. However, the contribution of hypoxic astrocytes to the pathological process of DR is unclear. A hypoxic model (7 days of systemic 7.5% O2) was utilized to induce retinal damage in adult mice in the absence of systemic inflammatory signals. This model induced vascular and microglial responses similar to 10 weeks of STZ-induced hyperglycemia. The goal of this study is to characterize retinal damage in WT and mice with defects in the FKN-CX3CR1 signaling axis and hence assess the impact of the microglial inflammatory responses to hypoxic retinopathy. Tissues were analyzed by immunostaining, RNA sequencing, and cytokine quantification. We found that CX3CR1 deficiency in hypoxic animals induced reactive astrogliosis and that Müller glial responses to hypoxia and systemic inflammation were dependent on FKN signaling. Exacerbated microglial reactivity to hypoxic conditions significantly altered the expression of HIF transcripts. Microglial dysregulation was found to reduce the anti-inflammatory response to hypoxic conditions, downregulate hypoxia-responsive gene expression, and restrained LPS-induced inflammatory responses. We found that microglia dysregulation alters the hypoxic response by inhibiting the upregulation of HIF2α/3α, increasing CD31 immunoreactivity, and altering the expression of ECM-associated transcripts such as type I, III, and XVIII collagens to hypoxic conditions.
Advancements in Surface Modification of NiTi Alloys for Orthopedic Implants: Focus on Low-Temperature Glow Discharge Plasma Oxidation Techniques
Authors: Witkowska Justyna , Sobiecki Jerzy , Wierzchoń Tadeusz
Published: January 2025

Nickel–titanium (NiTi) shape memory alloys are promising materials for orthopedic implants due to their unique mechanical properties, including superelasticity and shape memory effect. However, the high nickel content in NiTi alloys raises concerns about biocompatibility and potential cytotoxic effects. This review focuses on the recent advancements in surface modification techniques aimed at enhancing the properties of NiTi alloys for biomedical applications, with particular emphasis on low-temperature glow discharge plasma oxidation methods. The review explores various surface engineering strategies, including oxidation, nitriding, ion implantation, laser treatments, and the deposition of protective coatings. Among these, low-temperature plasma oxidation stands out for its ability to produce uniform, nanocrystalline layers of titanium dioxide (TiO2), titanium nitride (TiN), and nitrogen-doped TiO2 layers, significantly enhancing corrosion resistance, reducing nickel ion release, and promoting osseointegration. Plasma-assisted oxynitriding processes enable the creation of multifunctional coatings with improved mechanical and biological properties. The applications of modified NiTi alloys in orthopedic implants, including spinal fixation devices, joint prostheses, and fracture fixation systems, are also discussed. Despite these promising advancements, challenges remain in achieving large-scale reproducibility, controlling process parameters, and reducing production costs. Future research directions include integrating bioactive and antibacterial coatings, enhancing surface structuring for controlled biological responses, and expanding clinical validation. Addressing these challenges can unlock the full potential of surface-modified NiTi alloys in advanced orthopedic applications for safer, longer-lasting, and more effective medical implants.
Identification of Leaf Stripe Resistance Genes in Hulless Barley Landrace Teliteqingke from Qinghai-Tibet Plateau
Authors: Tan Zemin , Zhang Sai , Qu Yunfeng , Kang Shenghua , Fang Shiyu , Hou Lu
Published: January 2025

Leaf stripe disease, caused by Pyrenophora graminea, is a seed-borne fungal disease that significantly impacts hulless barley (Hordeum vulgare var. nudum) production on the Qinghai-Tibet Plateau. This study aimed to identify genetic factors conferring resistance to the leaf stripe by analyzing an F3 population derived from a cross between the resistant landrace Teliteqingke and the susceptible landrace Dulihuang. Genetic analysis revealed that resistance in Teliteqingke was governed by two dominant genes. Using bulked segregant analysis combined with an SNP array (BSA-SNP) and RNA-seq, we identified two candidate regions on chromosomes 3H and 7H. Further analysis focused on chromosome 3H, which revealed a candidate genomic region containing seven potential disease-resistance genes. Among these, RT-qPCR experiments demonstrated significant expression induction of HORVU.MOREX.r3.3HG0232110.1 (encoding a RING/U-box superfamily protein) and HORVU.MOREX.r3.3HG0232410.1 (encoding a bZIP transcription factor) showed significant expression induction following inoculation with P. graminea. These genes are strong candidates for the resistance mechanism against leaf stripes in Teliteqingke. These results provide a foundation for functional validation of these genes and offer valuable insights for breeding disease-resistant hulless barley.
Unraveling the Role of RSPRY1 in TGF-β Pathway Dysregulation: Insights into the Pathogenesis of Spondyloepimetaphyseal Dysplasia
Authors: Imren Gozde , Karaosmanoglu Beren , Muratoglu Bihter , Ozdemir Cansu , Utine Gulen Eda , Simsek-Kiper Pelin Ozlem , Taskiran Ekim Z.
Published: January 2025

Skeletal dysplasias, characterized by bone, cartilage, and connective tissue abnormalities, often arise due to disruptions in extracellular matrix (ECM) dynamics and growth factor-dependent signaling pathways. RSPRY1, a secreted protein with RING and SPRY domains, has been implicated in bone development, yet its exact role remains to be determined. RSPRY1 gene mutations are associated with spondyloepimetaphyseal dysplasia (SEMD), a rare skeletal disorder characterized by severe epiphyseal and metaphyseal deformities. This study aimed to determine the molecular and cellular mechanisms by which RSPRY1 deficiency affects skeletal homeostasis. Transcriptome analysis of fibroblasts from patients with homozygous RSPRY1 mutations showed there was significant enrichment of transforming growth factor beta (TGF-β) signaling and ECM-related pathways. Functional wound healing assays showed that RSPRY1 knockout fibroblasts exhibited enhanced motility, a phenotype that was abrogated in RSPRY1 + SMAD3 double knockout fibroblasts, highlighting the SMAD3-dependence of RSPRY1′s effects. The observed limited response to exogenous TGF-β in RSPRY1-deficient cells indicated that there was constitutive pathway activation. These findings show that RSPRY1 is a critical regulator of TGF-β signaling in ECM dynamics and cell motility, contributing to the pathophysiology of SEMD. An improvement in our understanding of the molecular roles of RSPRY1 might yield novel therapeutic strategies that target TGF-β signaling in patients with SEMD and other skeletal dysplasias.
Promyelocytic Leukemia Protein (PML) Regulates Stem Cell Pluripotency Through Novel Sumoylation Targets
Authors: Spanou Syrago , Makatounakis Takis , Filippopoulou Chrysa , Dougalis Georgios , Stamatakis George , Nikolaou Christoforos , Samiotaki Martina , Chachami Georgia , Papamatheakis Joseph , Kretsovali Androniki
Published: January 2025

The promyelocytic leukemia protein (PML) and its associated nuclear bodies have recently emerged as critical regulators of embryonic stem (ES) cell identity. Despite their recognized importance, the complete spectrum of PML-mediated molecular events in ES cells remains unclear. In this report, we study how PML is shaping the proteomic and SUMO proteomic landscape in ES cells. Proteomic profiling of PML-depleted ES cells uncovered a downregulation of self-renewal factors and an upregulation of proteins associated with translation and proteasomal activity, reflecting a cellular transition from pluripotency to differentiation. Importantly, PML promotes the sumoylation of pluripotency-related factors, chromatin organizers, and cell cycle regulators. We identified SALL1 and CDCA8 as novel PML-directed sumoylation targets, both critical for ES cell maintenance. SALL1 sumoylation increases the activation of the Wnt pathway, contributing to its ability to inhibit ES cell differentiation. Similarly, CDCA8 sumoylation enhances its capacity to promote cell proliferation. Collectively, our findings demonstrate that PML regulates ES cell identity by modulating the abundance or sumoylation of key regulators involved in pluripotency and cell cycle progression.
The Current Status of Virtual Autopsy Using Combined Imaging Modalities: A Scoping Review
Authors: Cergan Romica , Taciuc Iulian Alexandru , Dumitru Mihai , Vrinceanu Daniela , Manole Felicia , Sanda Nicoleta , Marinescu Andreea Nicoleta
Published: January 2025

Background/Objectives: Virtual autopsy (virtopsy) is a new domain of research for interdisciplinary teams of radiologists and forensic specialists. This scoping review aims to underline the current state-of-the-art research using combined imaging modalities. Methods: We searched the PubMed database using the term virtopsy for articles that are available in free full text, indexed in the Medline Database, and published in English. The query returned 49 articles on this subject that have been published since 2002. Results: The main imaging modalities used for postmortem imaging were computed tomography (PMCT), angiography (PMCTA), magnetic resonance imaging (PMMRI), and ultrasonography (PMUS). PMCT is highly effective for detecting complex osseous injuries, tracing bullet trajectories, or identifying characteristic findings in drowning cases. PMCTA is valuable for evaluating vascular lesions, particularly in natural death cases. PMMRI is superior in analyzing soft tissues, including brain and spinal structures, cerebrospinal fluid, microbleeds, and laryngohyoid lesions, and identifying cardiomyopathies in young individuals. PMUS serves as an alternative, and its portability also allows for use in forensic settings. One specific situation observed was the increased number of studies published about virtopsy during the COVID-19 pandemic. Another aspect is the increased focus on this alternative to conventional autopsy in the regions where maneuvering of the deceased is limited according to cultural and social customs. Conclusions: We underline the advantages and limitations of each imaging modality used for virtopsy. Further studies need to be developed in order to gather supplementary data regarding the use of these imaging modalities in the new era of artificial intelligence in medicine.
Clustering and Machine Learning Models of Skeletal Class I and II Parameters of Arab Orthodontic Patients
Authors: Midlej Kareem , Zohud Osayd , Lone Iqbal M. , Awadi Obaida , Masarwa Samir , Paddenberg-Schubert Eva , Krohn Sebastian , Kirschneck Christian , Proff Peter , Watted Nezar , Iraqi Fuad A.
Published: January 2025

Background: Orthodontic problems can affect vital quality of life functions, such as swallowing, speech sound production, and the aesthetic effect. Therefore, it is important to diagnose and treat these patients precisely. The main aim of this study is to introduce new classification methods for skeletal class I occlusion (SCIO) and skeletal class II malocclusion (SCIIMO) among Arab patients in Israel. We conducted hierarchical clustering to detect critical trends within malocclusion classes and applied machine learning (ML) models to predict classification outcomes. Methods: This study is based on assessing the lateral cephalometric parameters from the Center for Dentistry Research and Aesthetics based in Jatt, Israel. The study involved the encoded records of 394 Arab patients with diagnoses of SCIO/SCIIMO, according to the individualized ANB of Panagiotidis and Witt. After clustering analysis, an ML model was established by evaluating the performance of different models. Results: The clustering analysis identified three distinct clusters for each skeletal class (SCIO and SCIIMO). Among SCIO clusters, the results showed that in the second cluster, retrognathism of the mandible was less severe, as represented by a lower ANB angle. In addition, the third cluster had a lower NL-ML angle, gonial angle, SN-Ba angle, and lower ML-NSL angle compared to clusters 1 and 2. Among SCIIMO clusters, the results also showed that the second cluster has less severe retrognathism of the mandible, which is represented by a lower ANB angle and Calculated_ANB and a higher SNB angle (p < 0.05). The general ML model that included all measurements for patient classification showed a classification accuracy of 0.87 in the Random Forest and the Classification and Regression Tree models. Using ANB angle and Wits appraisal only in the ML, an accuracy of 0.78 (sensitivity = 0.80, specificity = 0.76) was achieved to classify patients as SCIO or SCIIMO. Conclusions: The clustering analysis revealed distinguished patterns that can be present within SCIO and SCIIMO patients, which can affect the diagnosis and treatment plan. In addition, the ML model can accurately diagnose SCIO/SCIIMO patients, which should improve precise diagnostics.
Medium-Term Effect of Inhaled Nitric Oxide in Mechanically Ventilated COVID-19 Patients
Authors: Freidkin Lev , Garsiel Katz Tamar , Peles Ido , Ben Shitrit Itamar , Abayev Marya , Almog Yaniv , Galante Ori , Fuchs Lior
Published: January 2025

Background: Nitric oxide (NO) plays a key role in various physiological processes. Inhaled NO (iNO) has been studied for treating acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, interest grew in its potential role for patients with COVID-19 ARDS, with studies showing improved oxygenation over 48 h. Methods: This is a retrospective study of adult patients with severe COVID-19 ARDS and refractory hypoxemia admitted to the medical ICU requiring mechanical ventilation and treated with iNO. The effect on oxygenation, respiratory, and ventilation parameters is measured. Significant improvement is defined as an increase in PaO2/FiO2 ≥ 20% from a baseline. Results: This study includes 87 patients (55 men, mean age 58.7 ± 15.2) with 164 iNO connections (mean 1.9 per patient). iNO is independently associated with a significant PaO2/FiO2 ratio improvement, with an OR of 1.26 (95% CI 1.09–1.46), even after accounting for these potential confounders. The time to maximal PaO2/FiO2 improvement is 14.5 ± 5.0 h for men and 78.5 ± 5.5 h for women, with respective ratio increases of 42.5 ± 8.1 and 52.5 ± 13.6 mmHg. Conclusions: Our study demonstrates that severe ARDS COVID-19 patients may benefit from inhaled nitric oxide, with delayed oxygenation improvements lasting up to 96 h and slower responses observed in women, raising the possibility that current guidelines against its use could be reconsidered.
Factors Associated with Potentially Inappropriate Prescribing in Patients with Prostate Cancer
Authors: Peulic Marija , Zivkovic Zaric Radica , Stojadinovic Milorad , Peulic Miodrag , Gavrilovic Jagoda , Zivkovic Radojevic Marija , Grujic Milos , Petronijevic Marina , Mutavdzic Vladan , Zivkovic Ognjen , Randjelovic Nevena , Milosavljevic Neda
Published: January 2025

Background/Objectives: Drug prescribing in elderly people with chronic diseases carries certain risks. The desire to treat several different diseases at the same time increases the risk of inadequate drug prescribing. Prostate cancer is a disease of older men and occurs in most men over the age of 65. With age, the risk of prostate cancer increases, but so does the risk of the inadequate prescription of drugs. Our research aimed to highlight the potential inadequate prescription of drugs in patients with prostate cancer, considering that it is mostly a population of older men in whom a greater number of comorbidities is expected, followed by the use of a greater number of drugs. Methods: Our investigation was designed as an observational, cross-sectional study of 334 male patients who presented at the Multidisciplinary Tumor Board (MDT) for urological cancers at the University Clinical Center Kragujevac, Kragujevac, Serbia, from 1 September to 15 December 2023. Our primary outcome was obtaining the MAI score. Results: Our study showed that a significant number of drugs per patient with a prostate cancer diagnosis were prescribed potentially inadequately. The factors associated with greater risk for PIP were the initial level of PSA, ADT meta (intermittent), and several prescribed drugs; on the other hand, secondary hormonal therapy was the reason for less frequent PIP. Conclusions: In conclusion, patients with prostate cancer are under increased risk of inappropriate prescribing when they are prescribed more medication, have high PSA, and have ADT meta (intermittent). To stop the incidence of inappropriate prescribing and its serious economic and health consequences, clinicians should take special care when prescribing new drugs to such patients.
Evaluation of LVEDP Change During High-Risk PCI With and Without Impella Support (ELVIS)—A Pilot Trial
Authors: Leick Juergen , Gjata Anida , Pulz Jan , Weisbarth Tobias , Richter Kristof , Krause Tobias , Saad Louai , Zayat Rashad , Kolat Philipp , Haneya Assad , Sinning Jan-Malte , Werner Nikos
Published: January 2025

Background: The decision-making process to use percutaneous mechanical circulatory support in the context of elective high-risk percutaneous coronary intervention (HRPCI) is complex and evolving. The aim of this study is to evaluate the left ventricular end-diastolic pressure (LVEDP) as a parameter to identify patients that may benefit from a protected HRCPI (pHRPCI) procedure. Methods: Overall, 62 patients (pHRPCI n = 31 vs. non-pHRPCI n = 31) with a complex coronary artery disease and a left ventricular ejection fraction (LVEF) ≤35% were included. The primary endpoint was defined as a change in LVEDP and its correlation with laboratory measurements. The secondary safety endpoint was a composite of the incidence of major in-hospital adverse cardiac and cerebrovascular events (MACCE). Results: Baseline characteristics were similar, including age (pHRPCI 72.8 ± 8.8 vs. non-pHRPCI 75.0 ± 10.4; p = 0.408), male (pHRPCI 83.9% vs. non-pHRPCI 96.8; p = 0.195), pre-PCI Syntax Score (pHRPCI 33.9 ± 13.1 vs. non-pHRPCI 35.4 ± 12; p = 0.643), post-PCI Syntax Score (pHRPCI 7.4 ± 6.2 vs. non-pHRPCI 9.6 ± 8.4; p = 0.239) and baseline LVEDP between the groups (pHRPCI 18.5 ± 10.5 mmHg vs. non-pHRPCI 15.7 ± 8.1 mmHg; p = 0.237). There was a trend to a lower LVEF in the pHRPCI group (26.4 ± 6.7% vs. 29.4 ± 5%; p = 0.051). The primary endpoint analysis revealed a significant change in LVEDP (pHRPCI −4.7 ± 9 mmHg vs. non-pHRPCI +3.1 ± 7.5 mmHg; p < 0.001) that did not correlate with changes in creatinine (p = 0.285), NT-proBNP (p = 0.383) or troponin (p = 0.639) concentrations within 24 h. Overall, low rates of in-hospital (pHRPCI 6.5% vs. non-pHRPCI 3.2%; p = 0.999) and 90-days (pHRPCI 12.9% vs. non-pHRPCI 12.9%; p = 0.999) MACCE were observed in both groups. Conclusions: Protected HRPCI leads to a significant reduction in LVEDP without influencing biomarkers of myocardial damage. There was no difference in MACCE rates between the groups.
Ectropion Repair Techniques and the Role of Adjunctive Superotemporal Skin Transposition for Tarsal Ectropion
Authors: Tao Brendan K. , Dhivagaran Thanansayan , Butt Fahad R. , Balas Michael , Hussain Ahsen , Nijhawan Navdeep , Nassrallah Georges , Ing Edsel
Published: January 2025

Background: Ectropion is a common eyelid problem and is defined as eversion of the eyelid margin and typically involves the lower eyelid. The main acquired causes of ectropion include involutional, cicatricial, paralytic, and mechanical. A severe manifestation of ectropion is tarsal ectropion, where much of the tarsal conjunctiva is visible, often with keratinization of the conjunctiva. causes. Common techniques for ectropion repair include horizontal tightening of the lid with lateral tarsal strip or Bick procedure, lateral tarsorraphy, inverting sutures and the sub-orbicularis oculi fat lift. However, all surgical techniques are prone to ectropion recurrence. We review the techniques for ectropion repair and describe a novel adjunctive technique called the superotemporal skin transposition (STS), which is well suited for patients with recurrent or tarsal ectropion. Methods: The STS is combined with a lateral tarsal strip or Bick procedure. For the STS, all of the anterior lamellae of the lateral lower lid is retained. The posterior lamellae is sutured to the lateral orbital tubercle. A triangular bed of skin is excised superotemporally, and the lower lid anterior lamellae is transposed and secured with multiple sutures. The STS can be combined with inverting sutures, or skin graft for cicatricial cases. Results: We used the STS with Bick procedure and optional inverting sutures on 23 patients, 4 of whom required bilateral ectropion repair. At 1–6 month followup all patients achieved satisfactory outcomes with a well-positioned eyelid and improved symptoms. The STS had more lateral cutaneous scarring than with a Bick procedure alone, but patients did not find this objectionable. No reoperations were required. Conclusion: The STS is a straightforward and useful adjunct for patients with severe, recurrent or tarsal ectropion. Further studies are needed to determine the long-term efficacy of this technique.
Evolution of Coronary Microvascular Dysfunction Prevalence over Time and Across Diagnostic Modalities in Patients with ANOCA: A Systematic Review
Authors: Zimmerli Aurelia , Salihu Adil , Antiochos Panagiotis , Lu Henri , Pitta Gros Barbara , Berger Alexandre , Muller Olivier , Meier David , Fournier Stephane
Published: January 2025

Background: A considerable number of patients with angina undergo invasive coronary angiography, which might reveal non-obstructive coronary arteries (ANOCA). In this setting, they might have coronary microvascular disease (CMD). Its prevalence significantly varies in the literature. This systematic review aims to document the prevalence of CMD over time according to the diagnostic modalities. Methods: A systematic literature review was conducted using PubMed, the Cochrane Library, and Embase, covering publications from inception to 1 May 2024. Among 1471 identified articles, 297 full-text articles were assessed for eligibility. All studies reporting the prevalence of CMD in ANOCA patients based on invasive coronary artery (ICA), positron emission tomography–computed tomography (PET-CT), transthoracic echocardiography (TTE), or cardiac magnetic resonance (CMR) were included. Results: The review included 53 studies (published between 1998 and 2024), encompassing a total of 16,602 patients. Of these studies, 23 used ICA, 15 used PET-CT, 8 used TTE, and 7 used CMR. A statistically significant increase in CMD prevalence over time was observed across all diagnostic modalities (p < 0.05), except for PET-CT, which showed a consistent and stable prevalence over time. Notably, the prevalence rates from all of the diagnostic methods converged towards the 50% prevalence detected by PET-CT. Conclusions: The prevalence of CMD in patients with ANOCA is subject to debate. However, the current data suggest that regardless of the diagnostic method used, the most recent studies tend to converge towards a prevalence value of 50%, which has been consistently reported by PET-CT from the beginning.
Comparative Analysis of Ixekizumab Effectiveness with and Without Induction Therapy in Moderate-to-Severe Psoriasis: A Real-World Study
Authors: Ruiz-Villaverde Ricardo , Ezomo-Gervilla Pedro José , Molina-Espinosa Jose , Galán-Gutierrez Manuel , Herrera-Acosta Enrique , Suarez-Perez Jorge Alonso
Published: January 2025

Background: Ixekizumab, an IL-17A inhibitor, is an effective treatment for moderate-to-severe plaque psoriasis. Although clinical trials support the use of an induction phase for optimal results, real-world evidence comparing induction versus maintenance-only regimens is limited. Objectives: This study assessed the real-world effectiveness, safety, and drug survival of ixekizumab with and without an induction phase in patients with moderate-to-severe plaque psoriasis. Methods: A multicenter, observational study was conducted with 183 patients treated with ixekizumab over five years at tertiary hospitals in Andalucía, Spain. Patients were divided into two groups: an induction group (160 mg at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then every 4 weeks) and a non-induction group (80 mg every 4 weeks from initiation). Baseline characteristics, clinical outcomes (PASI [Psoriasis Activity Skin Index] and PGA [Physician Global Assessment] scores), and drug survival were analyzed. Results: The majority of patients were male (64.48% in the induction group, 58.74% in the non-induction group). No significant differences were found in age or BMI [body mass index] between groups. Baseline PASI and PGA scores were higher in the induction group, reflecting greater initial disease severity. Both regimens achieved significant clinical improvements, though the induction group demonstrated faster initial responses. Drug survival was lower in the induction group (p = 0.0033), potentially due to the higher baseline disease burden and severity in these patients. Comorbidities, including metabolic syndrome, cardiovascular risks, and psychiatric conditions, were prevalent, particularly in the induction group. Conclusions: Ixekizumab is effective for moderate-to-severe plaque psoriasis, with induction therapy yielding faster responses. However, lower drug survival in the induction group highlights the influence of initial disease severity on long-term outcomes. Real-world findings support the flexibility of ixekizumab across diverse patient populations, though further research is warranted.
Alterations in Implantation Genes and Dendritic Cells in Endometrial Samples After Antibiotic Treatment
Authors: Darawshe Baraa , Hantisteanu Shay , Meisel Sharon Shilhav , Groisman Gabriel , Haimovich Sergio , Shalom-Paz Einat
Published: January 2025

Background/Objectives: This retrospective study assessed the impact of chronic endometritis (CE) on the expression of implantation genes HOXA10 (Homeobox A10) and IGF-1 (insulin-like growth factor 1), and on dendritic cells before and after antibiotic treatment, as well as on clinical reproductive outcomes. Methods: The study was conducted from 2021 to 2022. Ten assisted reproductive technology patients who underwent an endometrial biopsy before antibiotic treatment, confirming the diagnosis of CE, and a second biopsy after completing a course of 100 mg doxycycline twice daily for 14 days were included. Paraffin-embedded endometrial samples from these patients were obtained from the pathology department. The samples were evaluated for quantifying implantation genes HOXA10 and IGF-1 using RT-PCR, and for identification of dendritic cells using immunohistochemical staining of CD141. Conceptions and live births were also evaluated. Results: Endometrial expression of HOXA10 and IGF-1 genes was significantly elevated after antibiotic treatment and expression of dendritic cells CD141 was decreased. Eight of the ten patients required second-line antibiotic treatment due to persistent CE. Six patients conceived and delivered. Conclusions: CE is reversible with antibiotic treatment that resulted in improvements in implantation genes and clinical results. A high proportion of patients required broader spectrum antibiotic treatment.
A 6-Year Single Center Experience in Neonatal Aortic Arch Surgery with Whole-Body Perfusion: Showing the Perks by Strict Propensity Score Matching
Authors: Doll Isabelle , Sandoval Boburg Rodrigo , Berger Rafal , Rustenbach Christian Jörg , Jost Walter , Michel Jörg , Magunia Harry , Schlensak Christian
Published: January 2025

Objectives: Perfusion strategy is crucial for the outcome of neonatal aortic arch surgery. This study investigates Whole-Body Perfusion to potentially improve postoperative outcomes for neonates, addressing a significant gap in current research. Methods: Retrospective analysis was conducted for neonates receiving aortic arch reconstruction in our institution: 33 patients were treated with Antegrade Cerebral Perfusion (ACP, 2014–2017) and 61 patients with Whole-Body Perfusion (WBP, 2017–2022). After strict Propensity Score Matching, 20 patients were analyzed in each group. WBP consists of ACP and Lower Body Perfusion (LBP), achieved through a femoral arterial sheath. Results: Patients with WBP had a shorter time on Cardiopulmonary Bypass (86.65 ± 25.47 vs. 172.95 ± 60.12 min) and Cross-Clamp time (46.70 ± 18.48 vs. 91.30 ± 40.10 min) (p ≤ 0.001). Lactate at the time of reperfusion and after 24 h was lower in the WBP group (1.73 ± 0.63 vs. 4.29 ± 1.61, p < 0.001; 1.45 ± 0.57 vs. 2.09 ± 0.96 mmol/L, p = 0.026). Patients with WBP needed significantly fewer intraoperative transfusions of Red Blood Cells, Fresh Frozen Plasma and Platelets (p ≤ 0.001). WBP patients had a shorter time on ventilator (5.15 ± 4.05 vs. 10.00 ± 8.72 days, p = 0.01) and a higher urine output after 24 h (200.85 ± 100.87 vs. 118.10 ± 82.33 mL, p = 0.002). Conclusions: Patients treated with WBP received significantly fewer intraoperative transfusions and had a shorter time on extracorporeal circulation and ventilator. Furthermore, there was a trend for reduced multiorgan dysfunction.
A Dimensional Diagnostic Strategy for Depressive Disorders
Authors: Patten Scott B.
Published: January 2025

Background/Objectives: Depressive disorders are diagnosed using categorical definitions provided by DSM-5 and ICD-11. However, categorization for diagnostic purposes fails to account for the inherently dimensional nature of depression. Artificial categorization may impede research and obstruct the achievement of optimal treatment outcomes. Methods: The current study utilized a Canadian historical dataset called the National Population Health Survey (NPHS) to explore a simple alternative approach that does not depend on categorization. The NPHS collected complete data from 5029 participants through biannual interviews conducted in 1994–2010. Data collection included the K6 Distress Scale as well as the Composite International Diagnostic Interview Short Form for Major Depression. Data from the National Population Health Survey (NPHS) were used to quantify vulnerability to depressive symptoms through longitudinal K6 Distress Scale assessments. Variability of symptoms across this dimension of apparent vulnerability was quantified using ordinal regression, adjusting for age and sex. Results: Predicted probabilities from these models were used in simulations to produce a visualization of the epidemiology and to explore clinical implications. Conclusions: Consideration of these two dimensional factors (estimated overall level of vulnerability to depression and variability over time) is already a component of clinical assessment and is also accessible to repeated measurement in settings adopting measurement-based care. More formal consideration of these elements may provide a complementary approach to categorical diagnostic assessment and an opportunity for greater personalization of care and improved clinical outcomes. Future studies should validate these findings in diverse clinical settings to ensure their applicability in real-world contexts.
The Use of Nerve Conduction Study to Evaluate the Effects of Frozen Sock Treatment on Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Prospective Clinical Trial
Authors: Kim Eun-Young , Lee Mi-Yeon , Suh Bum-Chun
Published: January 2025

Background/Objectives: Docetaxel is a cytotoxic agent for the treatment of breast cancer, and its toxicities include peripheral neuropathy (PN). This study evaluated the ability of frozen sock (FS) treatment to prevent docetaxel-induced PN by performing nerve conduction study (NCS). Methods: From October 2017 to October 2018, 48 patients who had invasive carcinoma and were planned for docetaxel treatment every three weeks were evaluated. Patients wore a FS on the right foot, and the left foot was not protected by the FS during docetaxel infusion. Motor and sensory NCS as well as nail and skin toxicities were assessed. Results: The amplitude and velocity of the motor and sensory nerves significantly decreased after three months in both feet. Before and after three months of chemotherapy, the compound motor action potentials (CMAPs) for the right peroneal nerve were 7.64 ± 2.42 and 6.81 ± 2.21 mV, respectively (p < 0.001), and 7.13 ± 2.41 and 5.90 ± 2.24 mV, respectively (p < 0.001), for the left peroneal nerve. Reductions in the CMAP amplitude of the peroneal nerve were significantly lower in the right foot compared to the left foot (−9.58 vs. −16.8, p = 0.043). Application of the FS did not significantly decrease the overall incidence of skin and nail toxicity compared with the left foot during the study period (all p > 0.05). Conclusions: Docetaxel induced motor and sensory PN, but the use of a FS resulted in a smaller reduction in peroneal nerve amplification three months after the end of chemotherapy.
DXA-Measured Total and Regional Body Composition in Female Athletes with a Physical Impairment
Authors: Cavedon Valentina , Peluso Ilaria , Toti Elisabetta , Sandri Marco , Pedrinolla Anna , Zancanaro Carlo , Milanese Chiara
Published: January 2025

Background/Objectives: In recent years, awareness has been growing regarding the needs of female athletes with physical impairments. Despite the importance from both health and performance perspectives of assessing body composition in this athletic population, there is limited literature focusing on this topic. This study explored whole-body and regional three-compartment body composition in female athletes with a physical impairment to assess the impact of impairment and sex on body composition parameters in this population. Methods: Twenty female athletes with a physical impairment were pair-matched by age with an able-bodied female athlete and a male athlete with a comparable physical impairment. All athletes underwent whole-body scanning with dual-energy X-ray absorptiometry. Results: Female athletes with physical impairments showed body composition changes including higher amounts of fat mass, particularly in the lower body regions. Among athletes with a physical impairment, sex showed an independent effect on whole-body composition, with females showing higher fat mass and lower lean mass and bone mineral content compared with males, especially in the legs. Conclusions: Female athletes with physical impairments had a distinct body composition profile, characterized by sex-specific distribution of body tissue at the regional level. Nutritional and training strategies aimed at optimizing body composition in female athletes with physical impairments should be specifically tailored to meet the needs of this athletic population.
Visualizing Oral Infection Dynamics of Beauveria bassiana in the Gut of Tribolium castaneum
Authors: Preisegger Lautaro , Flecha Juan Cruz , Ghilini Fiorella , Espin-Sánchez Daysi , Prieto Eduardo , Oberti Héctor , Abreo Eduardo , Huarte-Bonnet Carla , Pedrini Nicolás , Mannino Maria Constanza
Published: January 2025

The ability of entomopathogenic fungi, such as Beauveria bassiana, to infect insects by penetrating their cuticle is well documented. However, some insects have evolved mechanisms to combat fungal infections. The red flour beetle (Tribolium castaneum), a major pest causing significant economic losses in stored product environments globally, embeds antifungal compounds within its cuticle as a protective barrier. Previous reports have addressed the contributions of non-cuticular infection routes, noting an increase in mortality in beetles fed with conidia. In this study, we further explore the progression and dynamics of oral exposure in the gut of T. castaneum after feeding with an encapsulated B. bassiana conidia formulation. First, we characterized the formulation surface using atomic force microscopy, observing no significant topological differences between capsules containing and not containing conidia. Confocal microscopy confirmed uniform conidia distribution within the hydrogel matrix. Then, larvae and adult insects fed with the conidia-encapsulated formulation exhibited B. bassiana distributed throughout the alimentary canal, with a higher presence of conidia before the pyloric chamber. More conidia were found in the larval midgut and hindgut compared to adults, but no germinated conidia were observed in the epithelium. These results suggest that the presence of conidia obstructs the gut, impairing the insect’s ability to ingest, process, and absorb nutrients. This disruption may weaken the host, increasing its susceptibility to infections and, ultimately, leading to death. By providing the first direct observation of fungal conidia within the alimentary canal of T. castaneum, this study highlights a novel aspect of fungal–host interaction and opens new avenues for advancing fungal-based pest control strategies by exploiting stage-specific vulnerabilities.