bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel DNA Variant in SMARCA4 Gene Found in a Patient Affected by Early Onset Colon Cancer
Authors: Di Maggio Federica , Boccia Giuseppe , Nunziato Marcella , Filotico Marcello , Montesarchio Vincenzo , D’Armiento Maria , Corcione Francesco , Salvatore Francesco
Published: February 2024

Colorectal cancer is the third leading cause of death from neoplasia worldwide. Thanks to new screening programs, we are now seeing an increase in Early Onset of ColoRectal Cancer (EOCRC) in patients below the age of 50. Herein, we report a clinical case of a woman affected by EOCRC. This case illustrates the importance of genetic predisposition testing also in tumor patients. Indeed, for our patient, we used a combined approach of multiple molecular and cellular biology technologies that revealed the presence of an interesting novel variant in the SMARCA4 gene. The latter gene is implicated in damage repair processes and related, if mutated, to the onset of various tumor types. In addition, we stabilized Patient-Derived Organoids from the tumor tissue of the same patient and the result confirmed the presence of this novel pathogenic variant that has never been found before even in early onset cancer. In conclusion, with this clinical case, we want to underscore the importance of including patients even those below the age of 50 years in appropriate screening programs which should also include genetic tests for predisposition to early onset cancers.
TRP Ion Channels in Immune Cells and Their Implications for Inflammation
Authors: Yan Qiyue , Gao Chuanzhou , Li Mei , Lan Rui , Wei Shaohan , Fan Runsong , Cheng Wei
Published: February 2024

The transient receptor potential (TRP) ion channels act as cellular sensors and mediate a plethora of physiological processes, including somatosensation, proliferation, apoptosis, and metabolism. Under specific conditions, certain TRP channels are involved in inflammation and immune responses. Thus, focusing on the role of TRPs in immune system cells may contribute to resolving inflammation. In this review, we discuss the distribution of five subfamilies of mammalian TRP ion channels in immune system cells and how these ion channels function in inflammatory mechanisms. This review provides an overview of the current understanding of TRP ion channels in mediating inflammation and may offer potential avenues for therapeutic intervention.
Discovering New Substrates of a UDP-Glycosyltransferase with a High-Throughput Method
Authors: Lethe Mary C. L. , Bui Dinh , Hu Ming , Wang Xiaoqiang , Singh Rashim , Chan Clement T. Y.
Published: February 2024

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC–MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.
Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease
Authors: Amin Sohil , Massoumi Hamed , Tewari Deepshikha , Roy Arnab , Chaudhuri Madhurima , Jazayerli Cedra , Krishan Abhi , Singh Mannat , Soleimani Mohammad , Karaca Emine E. , Mirzaei Arash , Guaiquil Victor H. , Rosenblatt Mark I. , Djalilian Ali R. , Jalilian Elmira
Published: February 2024

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.
Drought Stress Induced Different Response Mechanisms in Three Dendrobium Species under Different Photosynthetic Pathways
Authors: Xia Ke , Wu Qiaofen , Yang Yanni , Liu Qiao , Wang Zaihua , Zhao Zhiguo , Li Jie , He Jinxiang , Chai Shengfeng , Qiu Shuo
Published: February 2024

Many Dendrobium species, which hold a high status and value in traditional Chinese medicine, grow on barks and rocks in the wild, often encountering harsh environments and facing droughts. However, the molecular mechanisms underlying the shift in the photosynthetic pathway induced by drought remain unclear. To address this issue, three Dendrobium species with different photosynthetic pathways were selected for sequencing and transcriptome data analysis after drought treatment. The findings included 134.43 GB of sequencing data, with numerous Differentially Expressed Genes (DEGs) exhibiting different response mechanisms under drought stress. Gene Ontology (GO)–KEGG-based enrichment analysis of DEGs revealed that metabolic pathways contributed to drought tolerance and alterations in photosynthetic pathways. Phosphoenolpyruvate Carboxylase (PEPC) was subjected to phylogenetic tree construction, sequence alignment, and domain analysis. Under drought stress, variations were observed in the PEPC gene structure and expression among different Dendrobium species; the upregulation of Dc_gene2609 expression may be caused by dof-miR-384, which resulted in the shift from C3 photosynthesis to CAM, thereby improving drought tolerance in Dendrobium. This study revealed the expression patterns and roles of PEPC genes in enhancing plant drought tolerance and will provide an important basis for in-depth research on Dendrobium’s adaptation mechanisms in arid environments.
Skin Anti-Aging Potential through Whitening and Wrinkle Improvement Using Fermented Oil Derived from Hermetia illucens Larvae
Authors: Hwang Dooseon , Goo Tae-Won , Lee Seung Hun , Yun Eun-Young
Published: February 2024

As the aging population increases, so has interest among emerging seniors in anti-aging ingredients that enhance functionality by incorporating fermentation with natural materials. In this study, fermentation conditions for enhancing the functionality of Hermetia illucens larvae oil (HIO) were established, and its anti-aging potential was evaluated. First, the lipase activity and amount of lipid degradation products of the fermentation strains were measured in order to select Lactobacillus gasseri and Lactiplantibacillus plantarum as the strains with high fermentation ability. A fermentation period of 28 d and a fermentation method that uses only the strain culture medium were established by evaluating the fermentation degree after fermenting HIO with the selected strains. The whitening functionality test results of fermented HIO (FHIO) showed an increase of approximately 20% in extracellular tyrosinase inhibition activity compared with HIO. Additionally, within melanocytes, there was a 12% increase in tyrosinase inhibition activity and a 26% enhancement in melanin production inhibition ability. For wrinkle-improving functionality, it was observed that, for fibroblasts, there was a 10% increase in collagen production, a 9% increase in collagenase inhibition ability, and an 8% increase in elastase inhibition ability. Therefore, FHIO was confirmed to be an effective cosmetic raw material, with high functionality for anti-aging within the senior generation. This is achieved through increased whitening and wrinkle-improving functionality.
Age-Related Pathology in Corticobasal Degeneration
Authors: Mimuro Maya , Iwasaki Yasushi
Published: February 2024

Elderly human brains are vulnerable to multiple proteinopathies, although each protein has a different transmission pathway. Tau-immunoreactive astrocytes are well-known in elderly brains. In contrast, astrocytic plaques, a hallmark in corticobasal degeneration (CBD), rarely occur in aging and neurodegenerative disease other than CBD. To elucidate the clinicopathological correlation of aging-related pathology in CBD, we examined 21 pathologically proven CBD cases in our institute (12 males and 9 females, with a mean age of death 70.6 years). All CBD cases showed grains and neurofibrillary tangles (NFTs). Fifteen cases (71.4%) showed beta-amyloid deposition such as senile plaques or cerebral amyloid angiopathy. Three cases (14.3%) had Lewy body pathology. One case was classified as amygdala-predominant Lewy body disease, although no cases met the pathological criteria for Alzheimer’s disease. Five cases (23.8%) displayed Limbic-predominant and age-related TDP-43 encephalopathy (LATE). NFTs, grains, and TDP-43-positive neuronal inclusions were widely distributed throughout the limbic system of CBD patients, but their densities were low. CBD might a have similar cell vulnerability and transmission pathway to that of multiple proteinopathy in aging brains.
Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging
Authors: Guglielmi Valeria , Cheli Marta , Tonin Paola , Vattemi Gaetano
Published: February 2024

Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting the quadriceps, deep finger flexors, and foot extensors. At present, there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathological phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and the accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis, including environmental factors, autoimmunity, abnormalities of protein transcription and processing, the accumulation of several toxic proteins, the impairment of autophagy and the ubiquitin–proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has also been proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.
Inhibitory Effects of Eicosapentaenoic Acid on Vascular Endothelial Growth Factor-Induced Monocyte Chemoattractant Protein-1, Interleukin-6, and Interleukin-8 in Human Vascular Endothelial Cells
Authors: Takenoshita Yoko , Tokito Akinori , Jougasaki Michihisa
Published: February 2024

Vascular endothelial growth factor (VEGF) induces monocyte chemoattractant protein-1 (MCP-1) and plays an important role in vascular inflammation and atherosclerosis. We investigated the mechanisms of VEGF-induced MCP-1 expression and the effects of eicosapentaenoic acid (EPA) in human umbilical vein endothelial cells (HUVECs). Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that VEGF enhanced MCP-1 gene expression and protein secretion in HUVECs. Western immunoblot analysis revealed that VEGF induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and inhibitor of nuclear factor (NF)-κB (IκB). Treatment with pharmacological inhibitors of p38 MAPK (SB203580) or NF-κB (BAY11-7085) significantly suppressed VEGF-induced MCP-1 in HUVECs. EPA inhibited VEGF-induced MCP-1 mRNA, protein secretion, phosphorylation of p38 MAPK, and the translocation of phospho-p65 to the nucleus. Additionally, VEGF also stimulated gene expressions of interleukin (IL)-6 and IL-8, which were suppressed by SB203580, BAY11-7085, and EPA. The present study has demonstrated that VEGF-induced activation of MCP-1, IL-6, and IL-8 involves the p38 MAPK and NF-κB signaling pathways and that EPA inhibits VEGF-induced MCP-1, IL-6, and IL-8 via suppressing these signaling pathways. This study supports EPA as a beneficial anti-inflammatory and anti-atherogenic drug to reduce the VEGF-induced activation of proinflammatory cytokine and chemokines.
Simultaneous Purification of Human Interferon Alpha-2b and Serum Albumin Using Bioprivileged Fluorinated Ionic Liquid-Based Aqueous Biphasic Systems
Authors: Carvalho Sara F. , Pereiro Ana B. , Araújo João M. M.
Published: February 2024

Interferon alpha-2b (IFN-α2b) is an essential cytokine widely used in the treatment of chronic hepatitis C and hairy cell leukemia, and serum albumin is the most abundant plasma protein with numerous physiological functions. Effective single-step aqueous biphasic system (ABS) extraction for the simultaneous purification of IFN-α2b and BSA (serum albumin protein) was developed in this work. Effects of the ionic liquid (IL)-based ABS functionalization, fluorinated ILs (FILs; [C​2C​1Im][C​4F​9SO​3] and [N​1112(OH)][C​4F​9SO​3]) vs. mere fluoro-containing IL ([C​4C​1Im][CF​3SO​3]), in combination with sucrose or [N​1112(OH)][H​2PO​4] (well-known globular protein stabilizers), or high-charge-density salt K​3PO​4 were investigated. The effects of phase pH, phase water content (%wt), phase composition (%wt), and phase volume ratio were investigated. The phase pH was found to have a significant effect on IFN-α2b and BSA partition. Experimental results show that simultaneous single-step purification was achieved with a high yield (extraction efficiency up to 100%) for both proteins and a purification factor of IFN-α2b high in the enriched IFN-α2b phase (up to 23.22) and low in the BSA-enriched phase (down to 0.00). SDS-PAGE analysis confirmed the purity of both recovered proteins. The stability and structure of IFN-α2b and BSA were preserved or even improved (FIL-rich phase) during the purification step, as evaluated by CD spectroscopy and DSC. Binding studies of IFN-α2b and BSA with the ABS phase-forming components were assessed by MST, showing the strong interaction between FILs aggregates and both proteins. In view of their biocompatibility, customizable properties, and selectivity, FIL-based ABSs are suggested as an improved purification step that could facilitate the development of biologics.
Radiotherapy Metastatic Prostate Cancer Cell Lines Treated with Gold Nanorods Modulate miRNA Signatures
Authors: Soares Sílvia , Aires Fátima , Monteiro Armanda , Pinto Gabriela , Faria Isabel , Sales Goreti , Correa-Duarte Miguel A. , Guerreiro Susana , Fernandes Rúben
Published: February 2024

MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.
The Relevance of Reperfusion Stroke Therapy for miR-9-3p and miR-9-5p Expression in Acute Stroke—A Preliminary Study
Authors: Gendosz de Carrillo Daria , Kocikowska Olga , Rak Małgorzata , Krzan Aleksandra , Student Sebastian , Jędrzejowska-Szypułka Halina , Pawletko Katarzyna , Lasek-Bal Anetta
Published: February 2024

Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients.
Critical Facets of European Corn Borer Adult Movement Ecology Relevant to Mitigating Field Resistance to Bt-Corn
Authors: Sappington Thomas W.
Published: February 2024

The European corn borer (Ostrinia nubilalis, Hübner) has been managed successfully in North America since 1996 with transgenic Bt-corn. However, field-evolved resistance to all four available insecticidal Bt proteins has been detected in four provinces of Canada since 2018. Evidence suggests resistance may be spreading and evolving independently in scattered hotspots. Evolution and spread of resistance are functions of gene flow, and therefore dispersal, so design of effective resistance management and mitigation plans must take insect movement into account. Recent advances in characterizing European corn borer movement ecology have revealed a number of surprises, chief among them that a large percentage of adults disperse from the natal field via true migratory behavior, most before mating. This undermines a number of common key assumptions about adult behavior, patterns of movement, and gene flow, and stresses the need to reassess how ecological data are interpreted and how movement in models should be parameterized. While many questions remain concerning adult European corn borer movement ecology, the information currently available is coherent enough to construct a generalized framework useful for estimating the spatial scale required to implement possible Bt-resistance prevention, remediation, and mitigation strategies, and to assess their realistic chances of success.
Prophylactic Pulmonary Artery Banding in Pediatric Dilated Cardiomyopathy: An Additional Therapeutic Option
Authors: Panaioli Elena , Khraiche Diala , Pontailler Margaux , Ader Flavie , Raisky Olivier , Gaudin Regis , Bonnet Damien
Published: February 2024

Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with considerable early mortality. Heart transplantation is often the only viable life-saving option. Pulmonary artery banding (PAB) has been recently proposed as a bridge or alternative to transplantation for DCM. In our cohort, PAB was selectively addressed to heritable DCM or DCM with congenital left ventricle aneurysm (CLVA). This study aimed to describe the clinical evolution and left ventricle reverse remodeling (LVRR) over time (6 months and 1 year after surgery). Ten patients with severe DCM received PAB between 2016 and 2021 and underwent clinical and postoperative echocardiography follow-ups. The median age at PAB was <1 year. The in-hospital mortality was zero. Two patients died two months after PAB of end-stage heart failure. The modified Ross class was improved in the eight survivors with DCM and remained stable in the two patients with CLVA. We observed a positive LVRR (LV end-diastolic diameter Z-score: 8.4 ± 3.7 vs. 2.8 ± 3; p < 0.05; LV ejection fraction: 23.8 ± 5.8 to 44.5 ± 13.1 (p < 0.05)). PAB might be useful as part of the armamentarium available in infants and toddlers with severe DCM not sufficiently responding to medical treatment with limited probability of spontaneous recovery.
Advances in Therapeutic Strategies for the Management of Clostridioides difficile Infection
Authors: Vitiello Antonio , Sabbatucci Michela , Zovi Andrea , Salzano Antonio , Ponzo Annarita , Boccellino Mariarosaria
Published: February 2024

The infection caused by Clostridioides difficile represents one of the bacterial infections with the greatest increase in incidence among nosocomial infections in recent years. C. difficile is a Gram-positive bacterium able to produce toxins and spores. In some cases, infection results in severe diarrhoea and fulminant colitis, which cause prolonged hospitalisation and can be fatal, with repercussions also in terms of health economics. C. difficile is the most common cause of antibiotic-associated diarrhoea in the healthcare setting. The problem of bacterial forms that are increasingly resistant to common antibiotic treatments is also reflected in C. difficile infection (CDI). One of the causes of CDI is intestinal dysmicrobialism induced by prolonged antibiotic therapy. Moreover, in recent years, the emergence of increasingly virulent strains resistant to antibiotic treatment has made the picture even more complex. Evidence on preventive treatments to avoid recurrence is unclear. Current guidelines indicate the following antibiotics for the treatment of CDI: metronidazole, vancomycin, and fidaxomycin. This short narrative review provides an overview of CDI, antibiotic resistance, and emerging treatments.
Reply to Wostyn, P. Targeting the Cerebrospinal Fluid Compartment in Glaucoma: Still the Dark Side of the Moon? Comment on “Passaro et al. Glaucoma as a Tauopathy—Is It the Missing Piece in the Glaucoma Puzzle? J. Clin. Med. 2023, 12, 6900”
Authors: Passaro Maria Laura , Matarazzo Francesco , Abbadessa Gianmarco , Pezone Antonio , Porcellini Antonio , Tranfa Fausto , Rinaldi Michele , Costagliola Ciro
Published: February 2024

We are grateful to the author of the comment [...]
The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome
Authors: Granholm Ann-Charlotte , Hamlett Eric D.
Published: February 2024

Background: Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer’s disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread. This review is focused on current findings regarding p-Tau and its potential to seed pathology as a “prion-like” spreader. It also considers the consequences of p-Tau pathology leading to AD, particularly in individuals with Down syndrome. Methods: Scopus (SC) and PubMed (PM) were searched in English using keywords “tau AND seeding AND brain AND down syndrome”. A total of 558 SC or 529 PM potentially relevant articles were identified, of which only six SC or three PM articles mentioned Down syndrome. This review was built upon the literature and the recent findings of our group and others. Results: Misfolded p-Tau isoforms are seeding competent and may be responsible for spreading AD pathology. Conclusions: This review demonstrates recent work focused on understanding the role of neurofibrillary tangles and monomeric/oligomeric Tau in the prion-like spreading of Tau pathology in the human brain.
Real-World Data Analysis of Patients Affected by Immune-Mediated Thrombotic Thrombocytopenic Purpura in Italy
Authors: Angelucci Emanuele , Artoni Andrea , Fianchi Luana , Dovizio Melania , Iacolare Biagio , Saragoni Stefania , Esposti Luca Degli
Published: February 2024

Background: The therapeutic management of immune-mediated thrombotic thrombocytopenic purpura (iTTP) has recently benefited from the introduction of caplacizumab, an agent directed at the inhibition of platelet aggregation. This real-world analysis investigated the epidemiology and the demographic and clinical characteristics of iTTP patients in Italy before and after caplacizumab introduction in 2020. Methods: Hospitalized adults with iTTP were included using the administrative databases of healthcare entities covering 17 million residents. Epidemiological estimates of iTTP considered the 3-year period before and after caplacizumab introduction. After stratification by treatment with or without caplacizumab, iTTP patients were characterized for their baseline features. Results: The annual incidence before and after 2020 was estimated in the range of 4.3–5.8 cases/million and 3.6–4.6 cases/million, respectively. From 2018 to 2022, 393 patients with iTTP were included, and 42 of them were treated with caplacizumab. Caplacizumab-treated patients showed better clinical outcomes, with tendentially shorter hospital stays and lower mortality rates (no treated patients died at either 1 month or 3 months after caplacizumab treatment initiation, compared to 10.5% and 11.1% mortality rates at 1 and 3 months, respectively, of the untreated ones). Conclusions: These findings may suggest that caplacizumab advent provided clinical and survival benefits for patients with iTTP.
Long-Term Outcomes in Two-Year Follow-Up after Primary Treatment in Patients with a Prior Venous Thromboembolic Event: A Prospective, Observational, Real-Life Study
Authors: Palareti Gualtiero , Antonucci Emilia , Bucherini Eugenio , Caronna Antonella , Chistolini Antonio , Di Giorgio Angela , Di Giulio Rosella , Falanga Anna , Fregoni Vittorio , Garzia Mariagrazia , Mastroiacovo Daniela , Marzolo Marco , Pancani Roberta , Pastori Daniele , Podda Gian Marco , Rigoni Anna Maria , Ria Luigi , Sivera Piera , Testa Sophie , Visonà Adriana , Parisi Roberto , Poli Daniela ,   on behalf of the START POST VTE Investigators
Published: February 2024

Background: Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy. Methods: This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study. Results: A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue (n = 281, 39%; 76.1% with a DOAC) or discontinue (n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC). Conclusion: Physicians’ decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed.
Use of Rotational Atherectomy-Assisted Balloon Angioplasty in the Treatment of Isolated Below-the-Knee Atherosclerotic Lesions in Patients with Chronic Limb-Threatening Ischemia
Authors: Pitoulias Apostolos G. , Taneva Gergana T. , Avranas Konstantinos , Abu Bakr Nizar , Pitoulias Georgios A. , Donas Konstantinos P.
Published: February 2024

The aim of the study is to evaluate the safety and effectiveness of rotational atherectomy-assisted balloon angioplasty (BTK-RA) for the treatment of isolated below the knee (BTK) atherosclerotic lesions and to compare the outcomes to plain old balloon angioplasty (POBA). Between January 2020 and September 2023, 96 consecutive patients with chronic limb threatening ischemia (CTLI) and isolated BTK-lesions underwent POBA (group A) or BTK-RA (group B). The primary outcome measures were: periprocedural technical success, primary patency, postoperative increase of the ankle branchial index (ABI), target lesion revascularization (TLR), limb salvage, minor amputation and death. Both techniques had similar technical success, operative time, intraprocedural complications and bailout stent implantations, independently of the operator’s experience. Group B had significantly higher primary patency rates (93.5% vs. 72.0%, respectively, p = 0.006), TLR (2.1% vs. 24%, p = 0.057), lower in-hospital stay (2.0–3.0 vs. 4.0–6.0 days, respectively, p < 0.001) and higher postoperative ABI (0.8–0.2 vs. 0.7–0.1, respectively, p = 0.008), compared to group A. Significant differences (POBA n: 20, 40%, BTK-RA n = 3, 6.5%) were found in minor amputation rates between the two groups (p < 0.001), while the respective limb salvage rates were similar in both groups (94.0% vs. 97.8%, p = 0.35). The use of BTK-RA for the treatment of BTK-lesions in patients with CTLI showed significant clinical advantages in comparison to POBA.
A Randomized Clinical Trial Comparing Dubuisson Laparoscopic Lateral Suspension with Laparoscopic Sacropexy for Pelvic Organ Prolapse: Short-Term Results
Authors: Malanowska-Jarema Ewelina , Starczewski Andrzej , Melnyk Mariia , Oliveira Dulce , Balzarro Matteo , Rubillota Emanuel
Published: February 2024

Background: Laparoscopic sacrocolpopexy (LSC) is the gold standard for the treatment of apical prolapse, although dissection of the promontory may be challenging. Laparoscopic lateral suspension (LLS) with mesh is an alternative technique for apical repair with similar anatomical and functional outcomes, according to recent studies. The purpose of this study was to compare these operative techniques. Methods: Women with uterine Pelvic Organ Prolapse Quantification (POP-Q) stage 2 were enrolled in this prospective study and were randomly allocated to the LLS or LSC group. At the 12-month follow-up, primary measures included both anatomical and functional outcomes. Perioperative parameters and complications were recorded. Results: A total of 93 women were randomized, 48 in the LLS group and 45 in the LSC group, with 2 women lost to follow-up in both groups. LSC anatomic success rates were 81.82% for the apical compartment and 95.22% for the anterior compartment. LLS anatomic success rates for the apical and anterior compartments were 90% and 92.30%, respectively. The mean operative time for LLS was 160.3 min, while for LSC it was 168.3 min. The mean blood loss was 100 mL in both procedures. Conversion to laparotomy was necessary in three women. Mesh erosion was not observed in any of the cases. In terms of the complication, Clavien–Dindo grade 1 was observed in two patients in the LLS group and a complication rated grade 3b was observed in one patient in LSC group. Conclusions: LLS is a good alternative to LSC, with promising anatomical and quality-of-life results.
Arrhythmic Mitral Valve Prolapse and Sports Activity: Pathophysiology, Risk Stratification, and Sports Eligibility Assessment
Authors: Compagnucci Paolo , Selimi Adelina , Cipolletta Laura , Volpato Giovanni , Gasperetti Alessio , Valeri Yari , Parisi Quintino , Curcio Antonio , Natale Andrea , Dello Russo Antonio , Casella Michela
Published: February 2024

Although mitral valve prolapse (MVP) is the most prevalent valvular abnormality in Western countries and generally carries a good prognosis, a small subset of patients is exposed to a significant risk of malignant ventricular arrhythmias (VAs) and sudden cardiac death (SCD), the so-called arrhythmic MVP (AMVP) syndrome. Recent work has emphasized phenotypical risk features of severe AMVP and clarified its pathophysiology. However, the appropriate assessment and risk stratification of patients with suspected AMVP remains a clinical conundrum, with the possibility of both overestimating and underestimating the risk of malignant VAs, with the inappropriate use of advanced imaging and invasive electrophysiology study on one hand, and the catastrophic occurrence of SCD on the other. Furthermore, the sports eligibility assessment of athletes with AMVP remains ill defined, especially in the grey zone of intermediate arrhythmic risk. The definition, epidemiology, pathophysiology, risk stratification, and treatment of AMVP are covered in the present review. Considering recent guidelines and expert consensus statements, we propose a comprehensive pathway to facilitate appropriate counseling concerning the practice of competitive/leisure-time sports, envisioning shared decision making and the multidisciplinary “sports heart team” evaluation of borderline cases. Our final aim is to encourage an active lifestyle without compromising patients’ safety.
The Uricosuric Effect of SGLT2 Inhibitors Is Maintained in the Long Term in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus
Authors: Sánchez-Briales Paula , Marques Vidas María , López-Sánchez Paula , López-Illázquez María , Martín-Testillano Lucía , Vedat-Ali Aylin , Portolés Jose
Published: February 2024

(1) Background: Sodium–glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up.
The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients
Authors: Belei Oana , Basaca Diana-Georgiana , Olariu Laura , Pantea Manuela , Bozgan Daiana , Nanu Anda , Sîrbu Iuliana , Mărginean Otilia , Enătescu Ileana
Published: February 2024

Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut–brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.
A Clinician’s Perspective on the Accuracy of the Shade Determination of Dental Ceramics—A Systematic Review
Authors: Dudkiewicz Katarzyna , Łacinik Szymon , Jedliński Maciej , Janiszewska-Olszowska Joanna , Grocholewicz Katarzyna
Published: February 2024

Background: No systematic review or meta-analysis has been identified that provides a clinician’s perspective on the shade selection process for ceramic restorations. The aim of the present systematic review is to find and systematize the available knowledge by referring to the methods to assess the color of dental ceramics. Methods: The final search was performed on 10 December 2023 in six search engines. The keywords used in the search strategy were as follows: (“color matching” OR “shade matching” OR “color measurement” AND “porcelain” OR “dental ceramics”) AND “dentistry” AND “accuracy”. Results: The search strategy identified 139 potential articles. After the screening process, sixteen articles were included in the review. Conclusions: In conclusion, the most common method, the visual method, has lower accuracy and repeatability. Devices like spectrophotometers and colorimeters provide precise, repeatable, and objective measurements, but fail to be widely applied in everyday clinical practice. Clinicians should not rely solely on their senses for shade determination, but should turn to quantitative methods. Colorimetric devices connected to mobile applications are an interesting and useful tool. Software and apps based on artificial intelligence are emerging as promising tools, but they require further research.
Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion
Authors: Tan Hu , Yu Li , Chen Jingsi , Wang Xiaoyi , He Fang , Yu Lin , Du Lili , Chen Dunjin
Published: February 2024

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.
Comparison of Electromagnetic Induction and Electrical Resistivity Tomography in Assessing Soil Salinity: Insights from Four Plots with Distinct Soil Salinity Levels
Authors: Paz Maria Catarina , Castanheira Nádia Luísa , Paz Ana Marta , Gonçalves Maria Conceição , Monteiro Santos Fernando , Farzamian Mohammad
Published: February 2024

Electromagnetic induction (EMI) and electrical resistivity tomography (ERT) are geophysical techniques measuring soil electrical conductivity and providing insights into properties correlated with it to depths of several meters. EMI measures the apparent electrical conductivity (ECa, dS m−1) without physical contact, while ERT acquires apparent electrical resistivity (ERa, ohm m) using electrodes. Both involve mathematical inversion to obtain models of spatial distribution for soil electrical conductivity (σ, mS m−1) and electrical resistivity (ρ, ohm m), respectively, where ρ is the reciprocal of σ. Soil salinity can be assessed from σ over large areas using a calibration process consisting of a regression between σ and the electrical conductivity of the saturated soil paste extract (ECe, dS m−1), used as a proxy for soil salinity. This research aims to compare the prediction abilities of the faster EMI to the more reliable ERT for estimating σ and predicting soil salinity. The study conducted surveys and sampling at four locations with distinct salinity levels in Portugal, analysing the agreement between the techniques, and obtained 2D vertical soil salinity maps. In our case study, the agreement between EMI and ERT models was fairly good in three locations, with σ varying between 50 and 500 mS m−1. However, this was not the case at location 4, where σ exceeded 1000 mS m−1 and EMI significantly underestimated σ when compared to ERT. As for soil salinity prediction, both techniques generally provided satisfactory and comparable regional-level predictions of ECe, and the observed underestimation in EMI models did not significantly affect the overall estimation of soil salinity. Consequently, EMI demonstrated an acceptable level of accuracy in comparison to ERT in our case studies, supporting confidence in utilizing this faster and more practical technique for measuring soil salinity over large areas.
Spatial-Temporal Dynamics of Carbon Budgets and Carbon Balance Zoning: A Case Study of the Middle Reaches of the Yangtze River Urban Agglomerations, China
Authors: Fan Yiqi , Wang Ying , Han Rumei , Li Xiaoqin
Published: February 2024

Analysis of the spatial variation characteristics of regional carbon sources/sinks is a prerequisite for clarifying the position of carbon balance zones and formulating measures to reduce emissions and increase sinks. Studies of carbon sinks have often used the coefficient method, which is limited by sample size, measurement error, and low spatial resolution. In this study, 31 cities in the middle reaches of the Yangtze River urban agglomerations (MRYRUA) were studied with the improved CASA (Carnegie Ames Stanford Approach) model to estimate the grid-scale net ecosystem productivity (NEP) and explore the spatial-temporal evolution of carbon budgets from 2005 to 2020. By calculating the carbon balance index (CBI), economic contribution coefficient (ECC), and ecological support coefficient (ESC), carbon balance zoning was conducted. Corresponding suggestions are based on the carbon balance zoning results. From 2005 to 2020, carbon budgets increased and were high in the north-central region and low in the south. In addition, carbon sink functional zones were distributed in cities with rich ecological resources. Low-carbon economic zones shifted from the Poyang Lake Urban Agglomeration to the Wuhan City Circle; low-carbon optimization zones occurred from the Wuhan City Circle to the Poyang Lake Urban Agglomeration. Carbon intensity control and high-carbon optimization zones were distributed in cities with rapid economic development. Our results support the MRYRUA in achieving “double carbon” targets and formulating regional collaborative emissions reduction policies.