bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Pigment Epithelium Pigment Granules: Norms, Age Relations and Pathology
Authors: Dontsov Alexander , Ostrovsky Mikhail
Published: March 2024

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch’s membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent “age pigment” lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing both types of pigments simultaneously—melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of the oxidative degradation of pigment granules are considered. A mechanism is proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy the melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.
Influence of Molecular Design on the Tumor Targeting and Biodistribution of PSMA-Binding Tracers Labeled with Technetium-99m
Authors: Bezverkhniaia Ekaterina , Kanellopoulos Panagiotis , Rosenström Ulrika , Tolmachev Vladimir , Orlova Anna
Published: March 2024

Previously, we designed the EuK-based PSMA ligand BQ0413 with an maE3 chelator for labeling with technetium-99m. It showed efficient tumor targeting, but our preclinical data and preliminary clinical results indicated that the renal excretion levels need to be decreased. We hypothesized that this could be achieved by a decrease in the ligand’s total negative charge, achieved by substituting negatively charged glutamate residues in the chelator with glycine. The purpose of this study was to evaluate the tumor targeting and biodistribution of two new PSMA inhibitors, BQ0411 and BQ0412, compared to BQ0413. Conjugates were radiolabeled with Tc-99m and characterized in vitro, using PC3-pip cells, and in vivo, using NMRI and PC3-pip tumor-bearing mice. [99mTc]Tc-BQ0411 and [99mTc]Tc-BQ0412 demonstrated PSMA-specific binding to PC3-pip cells with picomolar affinity. The biodistribution pattern for the new conjugates was characterized by rapid excretion. The tumor uptake for [99mTc]Tc-BQ0411 was 1.6-fold higher compared to [99mTc]Tc-BQ0412 and [99mTc]Tc-BQ0413. [99mTc]Tc-BQ0413 has demonstrated predominantly renal excretion, while the new conjugates underwent both renal and hepatobiliary excretion. In this study, we have demonstrated that in such small targeting ligands as PSMA-binding EuK-based pseudopeptides, the structural blocks that do not participate in binding could have a crucial role in tumor targeting and biodistribution. The presence of a glycine-based coupling linker in BQ0411 and BQ0413 seems to optimize biodistribution. In conclusion, the substitution of amino acids in the chelating sequence is a promising method to alter the biodistribution of [99mTc]Tc-labeled small-molecule PSMA inhibitors. Further improvement of the biodistribution properties of BQ0413 is needed.
Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach
Authors: Blanot Morgane , Casaroli-Marano Ricardo Pedro , Mondéjar-Medrano Jordi , Sallén Thaïs , Ramírez Esther , Segú-Vergés Cristina , Artigas Laura
Published: March 2024

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI’s MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors’ predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI’s MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood–retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.
Analysis of the Gene Networks and Pathways Correlated with Tissue Differentiation in Prostate Cancer
Authors: Filippi Alexandru , Aurelian Justin , Mocanu Maria-Magdalena
Published: March 2024

Prostate cancer (PCa) is the most prevalent non-cutaneous cancer in men. Early PCa detection has been made possible by the adoption of screening methods based on the serum prostate-specific antigen and Gleason score (GS). The aim of this study was to correlate gene expression with the differentiation level of prostate adenocarcinomas, as indicated by GS. We used data from The Cancer Genome Atlas (TCGA) and included 497 prostate cancer patients, 52 of which also had normal tissue sample sequencing data. Gene ontology analysis revealed that higher GSs were associated with greater responses to DNA damage, telomere lengthening, and cell division. Positive correlation was found with transcription factor activator of the adenovirus gene E2 (E2F) and avian myelocytomatosis viral homolog (MYC) targets, G2M checkpoints, DNA repair, and mitotic spindles. Immune cell deconvolution revealed high M0 macrophage counts and an increase in M2 macrophages dependent on the GS. The molecular pathways most correlated with GSs were cell cycle, RNA transport, and calcium signaling (depleted). A combinatorial approach identified a set of eight genes able to differentiate by k-Nearest Neighbors (kNN) between normal tissues, low-Gleason tissues, and high-Gleason tissues with high accuracy. In conclusion, our study could be a step forward to better understanding the link between gene expression and PCa progression and aggressiveness.
Selection of Catechin Biosynthesis-Related Genes and Functional Analysis from Chromosome-Level Genome Assembly in C. sinensis L. Variety ‘Sangmok’
Authors: Lee Dong-Jun , Kim Jin-Hyun , Lee Tae-Ho , Park Myung-Eun , Ahn Byung-Ohg , Lee So-Jin , Cho Jeong-Yong , Kim Chang-Kug
Published: March 2024

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar ‘Sangmok’, one of Korea’s standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar ‘Sangmok’ was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that ‘Sangmok’ is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in ‘Sangmok’ were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 ‘Sangmok’-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The ‘Sangmok’ genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of ‘Sangmok’ and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.
Identification of the Efficient Enhancer Elements in FVIII-Padua for Gene Therapy Study of Hemophilia A
Authors: Xiao Rou , Chen Yan , Hu Zhiqing , Tang Qiyu , Wang Peiyun , Zhou Miaojin , Wu Lingqian , Liang Desheng
Published: March 2024

Hemophilia A (HA) is a common X-linked recessive hereditary bleeding disorder. Coagulation factor VIII (FVIII) is insufficient in patients with HA due to the mutations in the F8 gene. The restoration of plasma levels of FVIII via both recombinant B-domain-deleted FVIII (BDD-FVIII) and B-domain-deleted F8 (BDDF8) transgenes was proven to be helpful. FVIII-Padua is a 23.4 kb tandem repeat mutation in the F8 associated with a high F8 gene expression and thrombogenesis. Here we screened a core enhancer element in FVIII-Padua for improving the F8 expression. In detail, we identified a 400 bp efficient enhancer element, C400, in FVIII-Padua for the first time. The core enhancer C400 extensively improved the transcription of BDDF8 driven by human elongation factor-1 alpha in HepG2, HeLa, HEK-293T and induced pluripotent stem cells (iPSCs) with different genetic backgrounds, as well as iPSCs-derived endothelial progenitor cells (iEPCs) and iPSCs-derived mesenchymal stem cells (iMSCs). The expression of FVIII protein was increased by C400, especially in iEPCs. Our research provides a novel molecular target to enhance expression of FVIII protein, which has scientific value and application prospects in both viral and nonviral HA gene therapy strategies.
Unveiling Anti-Diabetic Potential of Baicalin and Baicalein from Baikal Skullcap: LC–MS, In Silico, and In Vitro Studies
Authors: Zhao Wencheng , Cui Huizi , Liu Kaifeng , Yang Xiaotang , Xing Shu , Li Wannan
Published: March 2024

Type 2 diabetes mellitus (T2DM) is marked by persistent hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction, imposing substantial health burdens and elevating the risk of systemic complications and cardiovascular diseases. While the pathogenesis of diabetes remains elusive, a cyclical relationship between insulin resistance and inflammation is acknowledged, wherein inflammation exacerbates insulin resistance, perpetuating a deleterious cycle. Consequently, anti-inflammatory interventions offer a therapeutic avenue for T2DM management. In this study, a herb called Baikal skullcap, renowned for its repertoire of bioactive compounds with anti-inflammatory potential, is posited as a promising source for novel T2DM therapeutic strategies. Our study probed the anti-diabetic properties of compounds from Baikal skullcap via network pharmacology, molecular docking, and cellular assays, concentrating on their dual modulatory effects on diabetes through Protein Tyrosine Phosphatase 1B (PTP1B) enzyme inhibition and anti-inflammatory actions. We identified the major compounds in Baikal skullcap using liquid chromatography–mass spectrometry (LC–MS), highlighting six flavonoids, including the well-studied baicalein, as potent inhibitors of PTP1B. Furthermore, cellular experiments revealed that baicalin and baicalein exhibited enhanced anti-inflammatory responses compared to the active constituents of licorice, a known anti-inflammatory agent in TCM. Our findings confirmed that baicalin and baicalein mitigate diabetes via two distinct pathways: PTP1B inhibition and anti-inflammatory effects. Additionally, we have identified six flavonoid molecules with substantial potential for drug development, thereby augmenting the T2DM pharmacotherapeutic arsenal and promoting the integration of herb-derived treatments into modern pharmacology.
StMAPKK5 Positively Regulates Response to Drought and Salt Stress in Potato
Authors: Luo Yu , Wang Kaitong , Zhu Liping , Zhang Ning , Si Huaijun
Published: March 2024

MAPKKs, as one of the main members of the mitogen-activated protein kinase (MAPK) cascade pathway, are located in the middle of the cascade and are involved in many physiological processes of plant growth and development, as well as stress tolerance. Previous studies have found that StMAPKK5 is responsive to drought and salt stress. To further investigate the function and regulatory mechanism of StMAPKK5 in potato stress response, potato variety ‘Atlantic’ was subjected to drought and NaCl treatments, and the expression of the StMAPKK5 gene was detected by qRT-PCR. StMAPKK5 overexpression and RNA interference-mediated StMAPKK5 knockdown potato plants were constructed. The relative water content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as proline (Pro) and malondialdehyde (MDA) contents of plant leaves, were also assayed under drought and NaCl stress. The StMAPKK5 interacting proteins were identified and validated by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC). The results showed that the expression of StMAPKK5 was significantly up-regulated under drought and NaCl stress conditions. The StMAPKK5 protein was localized in the nucleus, cytoplasm, and cell membrane. The expression of StMAPKK5 affected the relative water content, the enzymatic activities of SOD, CAT, and POD, and the proline and MDA contents of potatoes under drought and salt stress conditions. These results suggest that StMAPKK5 plays a significant role in regulating drought and salt tolerance in potato crop. Yeast two-hybrid (Y2H) screening identified four interacting proteins: StMYB19, StZFP8, StPUB-like, and StSKIP19. BiFC confirmed the authenticity of the interactions. These findings suggest that StMAPKK5 is crucial for potato growth, development, and response to adversity.
Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function
Authors: Xie Su , Liu Quan , Fu Chong , Chen Yansen , Li Mengxun , Tian Cheng , Li Jiaxuan , Han Min , Li Changchun
Published: March 2024

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein–protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.
Genomics of Brain Disorders 4.0
Authors: Cacabelos Ramón
Published: March 2024

Several historic, scientific events have occurred in the decade 2013–2023, in particular the COVID-19 pandemic. This massive pathogenic threat, which has affected the world’s population, has had a devastating effect on scientific production worldwide. [...]
Synthetic Displays and Their Potential for Driver Assistance Systems
Authors: Wögerbauer Elisabeth Maria , Bernhard Christoph , Hecht Heiko
Published: March 2024

Advanced visual display technologies typically supplement the out-of-window view with separate displays (e.g., analog speedometer or artificial horizon) or with overlays (e.g., projected speedometer or map). Studies on head-up displays suggest that altering the out-of-window view itself is superior to supplemental displays, as sensor-based information not normally visible to the driver can be included. Such novel synthetic displays have been researched for cockpit implementation but less so for driving. We discuss such view-altering synthetic displays in general, and camera–monitor systems (CMS) designed to replace rear-view mirrors as a special instance of a novel synthetic display in the automotive domain. In a standard CMS, a camera feed is presented on a monitor, but could also be integrated into the windshield of the car. More importantly, the camera feed can undergo alterations, augmentations, or condensations before being displayed. The implications of these technologies are discussed, along with findings from an experiment examining the impact of information reduction on a time-to-contact (TTC) estimation task. In this experiment, observers judged the TTC of approaching cars based on the synthetic display of a futuristic CMS. Promisingly, TTC estimations were unaffected by information reduction. The study also emphasizes the significance of the visual reference frame.
Production of Sm2Fe17N3 Bulk Magnets
Authors: Saito Tetsuji
Published: March 2024

Sm2Fe17N3 powder exhibits excellent magnetic properties but is unstable and decomposes into α-Fe and SmN phases at high temperatures. Therefore, the key to producing Sm2Fe17N3 bulk magnets is to reduce the deterioration of Sm2Fe17N3 powder during sintering. Herein, Sm2Fe17N3 bulk magnets were made using the spark plasma sintering (SPS) method with the addition of zinc stearate powder and zinc powder. Adding small amounts of zinc stearate powder and zinc powder improved the magnetic anisotropy and the coercivity of the magnets, respectively. The magnets produced by the SPS method using zinc stearate powder and zinc powder exhibited enhanced magnetic properties almost comparable to those of Sm2Fe17N3 powder.
An Integrated Pest Management Strategy Approach for the Management of the Stable Fly Stomoxys calcitrans (Diptera: Muscidae)
Authors: González Mikel A. , Duvallet Gérard , Morel Damien , de Blas Ignacio , Barrio Elena , Ruiz-Arrondo Ignacio
Published: March 2024

Stable flies, Stomoxys calcitrans, stand as formidable pests with a global impact, inflicting significant economic losses on the livestock sector. Larval development occurs in diverse substrates, including decomposing plant material and manure, while emerged adults pose a threat through blood-feeding on both animals and humans. Conventional chemical control methods, predominantly reliant on insecticides, not only pose environmental risks but also face challenges of resistance among stable fly populations. To address this pressing issue, we propose an integrated pest management (IPM) strategy for stable fly control. This approach involved a combination of sanitary-cultural practices, animal protection, the release of natural enemies targeting immature stages, and a specialized trapping system for adults. The Stomoxycc® trap, designed for mass trapping of adult Stomoxys, was employed alongside the release of the predatory mite Macrocheles robustulus and two wasp parasitoids, Spalangia cameroni and Muscidifurax raptor (under the commercial brands Biomite® and Biowasp®) on animal bedding as a key component of this IPM strategy. The implementation of this initiative has been undertaken at a significant sanctuary for donkeys and mules in western Spain. In this publication, we present the application and results of the IPM strategy utilized and provide insights into its use as a sustainable and environmentally friendly option for controlling stable fly populations.
Chromosomal-Level Reference Genome for the Chinese Endemic Pygmy Grasshopper, Zhengitettix transpicula, Sheds Light on Tetrigidae Evolution and Advancing Conservation Efforts
Authors: Guan De-Long , Chen Ya-Zhen , Qin Ying-Can , Li Xiao-Dong , Deng Wei-An
Published: March 2024

The pygmy grasshopper, Zhengitettix transpicula, is a Chinese endemic species with an exceedingly limited distribution and fragile population structure, rendering it vulnerable to extinction. We present a high-continuity, chromosome-scale reference genome assembly to elucidate this species’ distinctive biology and inform conservation. Employing an integrated sequencing approach, we achieved a 970.40 Mb assembly with 96.32% coverage across seven pseudo-chromosomes and impressive continuity (N50 > 220 Mb). Genome annotation achieves identification with 99.2% BUSCO completeness, supporting quality. Comparative analyses with 14 genomes from Orthoptera-facilitated phylogenomics and revealed 549 significantly expanded gene families in Z. transpicula associated with metabolism, stress response, and development. However, genomic analysis exposed remarkably low heterozygosity (0.02%), implying a severe genetic bottleneck from small, fragmented populations, characteristic of species vulnerable to extinction from environmental disruptions. Elucidating the genetic basis of population dynamics and specialization provides an imperative guideline for habitat conservation and restoration of this rare organism. Moreover, divergent evolution analysis of the CYP305m2 gene regulating locust aggregation highlighted potential structural and hence functional variations between Acrididae and Tetrigidae. Our chromosomal genomic characterization of Z. transpicula advances Orthopteran resources, establishing a framework for evolutionary developmental explorations and applied conservation genomics, reversing the trajectory of this unique grasshopper lineage towards oblivion.
The Effectivity of a School-Based Early Intervention Targeting Psychological Complaints and Non-Suicidal Self-Injury in Adolescents
Authors: Baetens Imke , Van Hove Lisa , Azadfar Zahra , Van Heel Martijn , Soyez Veerle
Published: March 2024

Background: Recent research suggests a concerning trend of non-suicidal self-injury (NSSI) and suicidal behaviors emerging at younger ages (as early as age 12). Early onset of NSSI is linked to more severe outcomes. While universal school-based prevention programs have shown promise in addressing suicidal behaviors, there is limited research on their effectiveness in preventing NSSI onset among adolescents. This study aims to evaluate the efficacy of a universal prevention program in schools for NSSI and mental complaints while enhancing resilience and mental health in 11–14-year-old adolescents. Methods: In total, 329 Flemish secondary school students (55.6% female), aged 11 to 14 years, participated in a 4 h classroom universal prevention, with a focus on emotion regulation, mental health, and specific strategies to prevent NSSI and reduce stigma. For both the intervention and control group (N = 124), a pre-, post-, and one-month follow-up questionnaire was administered, containing reliable and valid measures for NSSI and suicidality, emotion regulation, help-seeking behaviors, well-being, and psychological distress. Results: The prevention program effectively reduced NSSI and psychological distress, particularly for adolescents with a history of NSSI. Conclusions: These findings support previous research on the effectiveness of school-based programs in reducing mental complaints and suggest promising outcomes for NSSI prevention.
Transplant Candidates of 70+ Years Have Superior Survival If Receiving Pre-Emptively a Living Donor Kidney
Authors: Betjes Michiel G. H. , Kho Marcia M. L. , Roodnat Joke , de Weerd Annelies E.
Published: March 2024

Background: The number of kidney transplant recipients over 70 years of age is increasing but detailed data on patient and graft survival in the modern era of immune suppression are few. Methods: A single-center cohort of patients of 70 years and older (n = 349) at time of kidney transplantation from 2010–2020 were followed until January 2023. Results: The median age was 73 years with a median follow-up of 4.3 years. Fifty percent of recipients of a living donor kidney (LDK, n = 143) received their graft pre-emptively. Cumulative death-censored graft survival was excellent in the LDK group and reached 98% at 5 years vs. 85% in the deceased donor kidney (DDK) group. Primary non-function (38%) and rejection (43%) were the major causes of graft loss in the first year after DDK transplantation. Rejection-related graft loss was 4.6% during follow-up. Median recipient survival was superior in the subgroup of pre-emptively transplanted LDK patients compared to non-pre-emptively LDK transplanted patients (11.1 versus 6.2 years). Non-pre-emptively transplanted patients had a significantly increased incidence of infection (HR 3.81, 1.46–9.96) and cardiovascular-related causes of death (HR 3.35, 1.16–9.71). Pre-emptive transplantation was also associated with a significantly improved graft survival in the DDK recipients but this result was confounded by significantly better HLA matching and younger donor age in this group. Conclusions: Pre-emptive LDK transplantation in patients of 70 years or older confers superior graft and recipient survival.
Changes in Body Weight in Severely Obese Patients Treated with the Anorexiant Mazindol
Authors: Tanaka Yoshimitsu , Maeda Norikazu , Koseki Masahiro , Maeda Kazuhisa
Published: March 2024

(1) Background: The number of severely obese patients worldwide is rapidly increasing. Recently, novel therapeutic approaches, such as bariatric surgery or GLP-1 receptor agonists, have emerged, bringing about a paradigm shift in this field. However, these therapies sometimes face challenges, such as peri-surgical complications or supply shortages. Mazindol, which is an appetite suppressant approved decades ago in Japan, remains a valuable option. In this study, we investigated the effectiveness of mazindol in reducing body weight in 147 patients, and we examined the factors influencing said effectiveness. (2) Methods: The patients were divided into four groups based on the treatment cycles they underwent: 1 cycle, 2 cycles, 3–5 cycles, and over 6 cycles. We compared the changes in body weight before and after the treatment among these four groups. Additionally, we sought to identify the factors correlated to the effectiveness of mazindol. (3) Results: The change in body weight was more pronounced in the group which underwent 3–5 cycles compared to the groups which underwent 1 cycle and 2 cycles; this change was also more pronounced in the group which underwent over 6 cycles compared to those which underwent 1 cycle. Furthermore, we observed a significant correlation between the initial body weight and the extent of body weight change. (4) Conclusions: Mazindol demonstrated effectiveness in reducing the body weight of patients in a cycle-dependent manner.
Impact of Albumin Leakage on the Mortality of Patients Receiving Hemodialysis or Online Hemodiafiltration
Authors: Tashiro Manabu , Okada Kazuyoshi , Tanaka Yusaku , Michiwaki Hiroyuki , Shima Hisato , Inoue Tomoko , Doi Toshio , Minakuchi Jun
Published: March 2024

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275–0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588–0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival.
Botulinum Toxin A as an Adjunct for the Repair Giant Inguinal Hernias: Case Reports and a Review of the Literature
Authors: Huerta Sergio , Raj Roma , Chang Jonathan
Published: March 2024

The management of giant inguinoscrotal hernias remains a challenge as a result of the loss of the intra-abdominal domain from long-standing hernia contents within the scrotum. Multiple techniques have been described for abdominal wall relaxation and augmentation to allow the safe return of viscera from the scrotum to the intraperitoneal cavity without adversely affecting cardiorespiratory physiology. Preoperative progressive pneumoperitoneum, phrenectomy, and component separation are but a few common techniques previously described as adjuncts to the management of these massively large hernias. However, these strategies require an additional invasive stage, and reproducibility remains challenging. Botulinum toxin A (BTA) has been successfully used for the management of complex ventral hernias. Its use for these hernias has shown reproducibility and a low side effect profile. In the present report, we describe our institutional experience with BTA for giant inguinal hernias in two patients and present a review of the literature. In one case, a 77-year-old man with a substantial cardiac history presented with a giant left inguinal hernia that was interfering with his activities of daily living. He had BTA six weeks prior to inguinal hernia repair. Repair was performed via an inguinal incision with a favorable return of the viscera into the peritoneum. He was discharged on the same day of the operation. A second patient, 78 years of age, had a giant right inguinoscrotal hernia. He had a significant cardiac history and was treated with BTA six weeks prior to inguinal hernia repair via a groin incision. Neither patient had complaints nor recurrence at 7- and 3-month follow-ups. While the literature on this topic is scarce, we found 13 cases of inguinal hernias treated with BTA as an adjunct. BTA might be a promising adjunct for the management of giant inguinoscrotal hernias in addition to or in place of current strategies.
Hypertensive Emergency with Thrombotic Microangiopathy or TTP? A Case Series and Literature Review
Authors: Song Yang , Lee Shi Yan , Chee Yen-Lin , Jen Wei-Ying
Published: March 2024

Thrombotic microangiopathy (TMA) is associated with both hypertensive emergency and primary thrombocytopenia purpura (TTP). However, their clinical management is vastly different, with the latter necessitating urgent plasma exchange (PEX). We report two cases of hypertension-associated TMA (HTN-TMA) and a literature review of the clinical management of malignant hypertension. We suggest that in patients presenting with hypertensive emergency associated with TMA, a clinical diagnosis of HTN-TMA should be made, with emergent treatment to lower blood pressure started immediately. Although TTP is a differential diagnosis for TMA, PEX should not be started concurrently in the absence of other supporting evidence for TTP.
Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy
Authors: Sucato Vincenzo , Ortello Antonella , Comparato Francesco , Novo Giuseppina , Galassi Alfredo Ruggero
Published: March 2024

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes.
Primary Radial Nerve Lesions in Humerus Shaft Fractures—Revision or Wait and See
Authors: Böhringer Alexander , Cintean Raffael , Schütze Konrad , Gebhard Florian
Published: March 2024

Background: This study investigates the surgical state-of-the-art procedure for humeral shaft fractures with primary radial nerve palsy based on its own case series in relation to the current and established literature. Methods: Retrospective review of treated cases between January 2018 and December 2022 describing radial nerve palsy after humerus shaft fractures, radiological fracture classification, intraoperative findings, surgical procedure, patient follow-up and functional outcome. Results: A total of 804 patients (463 women and 341 men) with humerus shaft fractures were identified. A total of 33 patients showed symptomatic lesions of the radial nerve (4.1%). The primary lesion was identified in 17 patients (2.1%). A broad and inhomogeneous distribution of fractures according to the AO classification was found. According to the operative reports, the distraction of the radial nerve was found eleven times, bony interposed three times and soft tissue constricted/compressed three times. In every case the radial nerve was surgically explored, there was no case of complete traumatic nerve transection. Four intramedullary nails and thirteen locking plates were used for osteosynthesis. Complete recovery of nerve function was seen in 12 cases within 1 to 36 months. Three patients still showed mild hypesthesia in the thumb area after 18 months. Two patients were lost during follow-up. Conclusions: With this study, we support the strategy of early nerve exploration and plate osteosynthesis in humeral fractures with primary radial nerve palsy when there is a clear indication for surgical fracture stabilisation. In addition, early exploration appears sensible in the case of palsies in open fractures and secondary palsy following surgery without nerve exposure as well as in the case of diagnostically recognisable nerve damage. Late nerve exploration is recommended if there are no definite signs of recovery after 6 months. An initial wait-and-see strategy with clinical observation seems reasonable for primary radial nerve palsies without indication for surgical fracture stabilisation.
A Qualitative Exploration of the Perceptions of Women Living with Pelvic Floor Disorders and Factors Related to Quality of Life
Authors: Rodríguez-Almagro Julián , Hernández Martínez Antonio , Martínez-Vázquez Sergio , Peinado Molina Rocío Adriana , Bermejo-Cantarero Alberto , Martínez-Galiano Juan Miguel
Published: March 2024

Background: Pelvic floor dysfunction encompasses conditions like urinary and fecal incontinence, pelvic organ prolapse, and pelvic pain, significantly affecting women’s quality of life. Despite its prevalence, few studies have adopted a qualitative approach to understanding women’s perceptions and emotions regarding these issues. This study aims to delve into how women with pelvic floor disorders perceive their condition and its impact on their daily lives. Methods: We analyzed qualitative data from interviews with 160 women suffering from pelvic floor dysfunctions. Using inductive qualitative content analysis, we systematically examined the data to identify variations, differences, and similarities. Results: The analysis revealed four primary themes in the women’s narratives: “Physical Impacts”, “Emotional and Psychological Impacts”, “Social and Relational Impacts”, and “Sexual Health Impacts”, along with 12 subthemes. The findings predominantly highlight how pelvic floor dysfunctions detrimentally affect women’s quality of life and emotional well-being, instilling fear and insecurity in daily activities, compounded by sleep disturbances and sexual dysfunction. Conclusions: Women living with pelvic floor dysfunction face multifaceted challenges that adversely affect various aspects of their lives, diminishing their overall quality of life. This includes notable impacts on sleep, physical, and sexual activities. However, not all affected women report these issues, often due to fear of stigma, choosing instead to conceal their struggles in an effort to maintain an appearance of normalcy.
Abdominal Arterial Translation in Lower Lumbar Spine Level Due to Positional Change: A Clinical Survey Using Intraoperative Computed Tomography
Authors: Asari Toru , Wada Kanichiro , Sasaki Eiji , Kumagai Gentaro , Tanaka Sunao , Ishibashi Yasuyuki
Published: March 2024

Background: Abdominal vascular injury, a fatal complication of lumbar disc surgery, should concern spine surgeons. This study aimed to compare the position of the abdominal arteries in the supine and prone positions and the factors involved. Thirty patients who underwent lumbar surgery by posterior approach were included. Methods: All patients underwent computed tomography (CT) preoperatively in the supine position and intraoperatively in the prone position. In the CT axial image, at the L4, L4/5 disc, L5, and L5/S1 disc level, we measured the shortest distance between the abdominal arteries and the vertebral body (SDA: shortest distance to the aorta), and the amount of abdominal arterial translation, defined as “SDA on intraoperative CT” minus “SDA on preoperative CT”. Additionally, the preoperative CT axial images were evaluated for the presence of aortic calcification. Results: No significant difference in SDA values based on patients’ positions was observed at each level. In males, the supine position brought the abdominal artery significantly closer to the spine at the left side of the L5/S level (p = 0.037), and, in cases of calcification of the abdominal artery, the abdominal artery was found to be closer to the spine at the left side of the L4/5 level (p = 0.026). Conclusions: It is important to confirm preoperative images correctly to prevent great vessel injuries in lumbar spine surgery using a posterior approach.
Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation
Authors: Polak Mateusz , Wieczorek Joanna , Botor Malwina , Auguścik-Duma Aleksandra , Hoffmann Andrzej , Wnuk-Wojnar Anna , Gawron Katarzyna , Mizia-Stec Katarzyna
Published: March 2024

Background: MicroRNA (miRNA) have the potential to be non-invasive and attractive biomarkers for a vast number of diseases and clinical conditions; however, a reliable analysis of miRNA expression in blood samples meets a number of methodological challenges. In this report, we presented and discussed, specifically, the principles and limitations of miRNA purification and analysis in blood plasma samples collected from the left atrium during an ablation procedure on patients with atrial fibrillation (AF). Materials and Methods: Consecutive patients hospitalized in the First Department of Cardiology for pulmonary vein ablation were included in this study (11 with diagnosed paroxysmal AF, 14 with persistent AF, and 5 without AF hospitalized for left-sided WPW ablation—control group). Whole blood samples were collected from the left atrium after transseptal puncture during the ablation procedure of AF patients. Analysis of the set of miRNA molecules was performed in blood plasma samples using the MIHS-113ZF-12 kit and miScript microRNA PCR Array Human Cardiovascular Disease. Results: The miRNS concentrations were in the following ranges: paroxysmal AF: 7–23.1 ng/µL; persistent AF: 4.9–66.8 ng/µL; controls: 6.3–10.6 ng/µL. The low A260/280 ratio indicated the protein contamination and the low A260/A230 absorbance ratio suggested the contamination by hydrocarbons. Spectrophotometric measurements also indicated low concentration of nucleic acids (<10 ng/µL). Further steps of analysis revealed that the concentration of cDNA after the Real-Time PCR (using the PAXgene RNA Blood kit) reaction was higher (148.8 ng/µL vs. 68.4 ng/µL) and the obtained absorbance ratios (A260/A280 = 2.24 and A260/A230 = 2.23) indicated adequate RNA purity. Conclusions: Although developments in miRNA sequencing and isolation technology have improved, detection of plasma-based miRNA, low RNA content, and sequencing bias introduced during library preparation remain challenging in patients with AF. The measurement of the quantity and quality of the RNA obtained is crucial for the interpretation of an efficient RNA isolation.
Landmark Evolutions in Time and Indication for Cardiac Resynchronization Therapy: Results from a Multicenter Retrospective Registry
Authors: Bijnens Jeroen , Trenson Sander , Voros Gabor , Martens Pieter , Ingelaere Sebastian , Betschart Pascal , Voigt Jens-Uwe , Dupont Matthias , Breitenstein Alexander , Steffel Jan , Willems Rik , Ruschitzka Frank , Mullens Wilfried , Winnik Stephan , Vandenberk Bert
Published: March 2024

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12–2.03; atrial fibrillation: HR 2.08, 95% CI 1.30–3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29–2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.
Morphological Aspects of the Aberrant Right Subclavian Artery—A Systematic Review of the Literature
Authors: Nedelcu Alin Horatiu , Lupu Ancuta , Moraru Marius Constantin , Tarniceriu Cristina Claudia , Stan Cristinel Ionel , Partene Vicoleanu Simona Alice , Haliciu Ana Maria , Statescu Gabriel , Ursaru Manuela , Danielescu Ciprian , Ioniuc Ileana , Tepordei Razvan Tudor , Lupu Vasile Valeriu
Published: March 2024

Background: The aberrant origin of the right subclavian artery (ARSA), also known as the lusoria artery, is a congenital malformation with an incidence of 0.5–4.4%. Most cases are incidental due to minimal clinical manifestations. Computer tomography (CT) is important in diagnosing and evaluating these patients. Materials and Methods: We conduct a computerized search in two databases, PubMed and EMBASE, for articles published between 1 January 2022 and 31 December 2023, PROSPERO code: CRD42024511791. Eligible for inclusion were case reports and case series that presented the aberrant origin of the right subclavian artery. The main outcome was the highlighting of the morphological types of ARSA. In this context, we proposed a new classification system of this anomaly. The secondary outcome was the evaluation of the demographic distribution of the lusoria artery. Results: Our search identified 47 articles describing 51 patients with ARSA. The typical course for ARSA is retroesophageal, being registered in 49 out of 51 patients. This malformation is frequently associated with Kommerell diverticulum (15 out of 51), troncus bicaroticus (7 out of 51), and aberrant origins of the right vertebral artery (7 out of 51). We observed a higher incidence of the condition among women (32 out of 51) compared to men (19 out of 51). From a demographic point of view, ARSA is more frequent in the “44 to 57 years” and “58 to 71 years” age ranges. Conclusions: ARSA is a congenital malformation resulting from a defect in the development of the aortic arches. The imaging studies such as computer tomography play a defined diagnostic role.
The Impact of Laparoscopic Myomectomy on Pregnancy Outcomes: A Systematic Review
Authors: Balulescu Ligia , Brasoveanu Simona , Pirtea Marilena , Grigoras Dorin , Secoșan Cristina , Olaru Flavius , Erdelean Dragos , Margan Mădălin-Marius , Alexandru Alexandru , Ivan Cristiana-Smaranda , Pirtea Laurențiu
Published: March 2024

Study objective: The objective of this systematic review is to investigate the impact of laparoscopic myomectomy techniques on pregnancy outcomes, with a specific focus on the correlation between the type of suture used during the procedure and the incidence of uterine rupture. Additionally, the study aims to examine how the localization and size of myomas, key factors in laparoscopic myomectomy, may influence fertility outcomes. Data Sources: extensive searches were conducted using MDPI, PubMed, Web of Science, and Cochrane Library databases from 2008 to November 2023. Methods of Study Selection: The study involved women of reproductive age diagnosed with fibroids who underwent surgical removal of fibroids using either laparotomy or laparoscopy. The evaluation of pregnancy outcomes focused on indicators such as live birth rates, miscarriage rates, stillbirth rates, premature delivery rates, and cases of uterine rupture. Quality assessment was systematically performed by employing the National Institutes of Health Study Quality Assessment Tools, with the subsequent formulation of clinical recommendations that were meticulously graded in accordance with the robustness of the underlying evidence. Results: The pregnancy outcomes post-myoma treatment, as reflected in one of the presented tables, show a promising number of pregnancies and live births, but also indicate the potential risks of miscarriages and preterm births. The diversity in outcomes observed among various studies underscores the imperative for tailored patient care, as well as the necessity for additional research aimed at optimizing fertility and pregnancy outcomes following myoma treatment. Conclusion: This study offers insights into the criteria for patient selection and intraoperative methodologies specifically related to laparoscopic myomectomy. To enhance our understanding of the associations between fibroid characteristics (location, size) and reproductive outcomes, additional research is warranted, particularly through well-designed clinical trials.