bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Gender Expression, Protective Coping Strategies, Alcohol Saliency, and High-Risk Alcohol Use in Post-Secondary Students at Two Canadian Universities
Authors: Bahji Anees , Boonmak Paul , Koller Michelle , Milani Christina , Sutherland Cate , Horgan Salinda , Chen Shu-Ping , Patten Scott , Stuart Heather
Published: January 2024

Background: This study, conducted in October 2017 at two Canadian universities, aimed to explore the relationships between gender expression, protective coping strategies, alcohol saliency, and high-risk alcohol use. Methods: Validated scales were employed to assess these variables using survey data. Multivariate analyses were conducted to investigate the associations between these factors and high-risk drinking. Results: This study revealed significant associations between high-risk drinking and androgynous gender roles (OR = 1.58, 95% CI: 1.19–2.10) as well as among self-reported males (OR = 2.21; 95% CI: 1.77–2.75). Additionally, protective behavioural strategies were inversely related to high-risk drinking (OR = 0.95; 95% CI: 0.94–0.96), while higher alcohol saliency exhibited a positive correlation with high-risk drinking (OR = 1.12; 95% CI: 1.11–1.14). Conclusions: These findings underscore the importance of considering gender, alcohol saliency beliefs, and protective behavioural strategies in the development and refinement of interventions aimed at reducing high-risk alcohol use on Canadian campuses.
Bioactive-Glass-Based Materials with Possible Application in Diabetic Wound Healing: A Systematic Review
Authors: Vargas Guerrero Marian , Aendekerk Floor M. A. , de Boer Candice , Geurts Jan , Lucchesi Jimmy , Arts Jacobus J. C.
Published: January 2024

Diabetes affected 537 million adults in 2021, costing a total of USD 966 billion dollars in healthcare. One of the most common complications associated with diabetes corresponds to the development of diabetic foot ulcers (DFUs). DFUs affect around 15% of diabetic patients; these ulcers have impaired healing due to neuropathy, arterial disease, infection, and aberrant extracellular matrix (ECM) degradation, among other factors. The bioactive-glass-based materials discussed in this systematic review show promising results in accelerating diabetic wound healing. It can be concluded that the addition of BG is extremely valuable with regard to the wound healing rate and wound healing quality, since BG activates fibroblasts, enhances M1-to-M2 phenotype switching, induces angiogenesis, and initiates the formation of granulation tissue and re-epithelization of the wound. In addition, a higher density and deposition and better organization of collagen type III are seen. This systematic review was made using the PRISMA guideline and intends to contribute to the advancement of diabetic wound healing therapeutic strategies development by providing an overview of the materials currently being developed and their effect in diabetic wound healing in vitro and in vivo.
microRNAs: Key Regulators in Plant Responses to Abiotic and Biotic Stresses via Endogenous and Cross-Kingdom Mechanisms
Authors: Ding Tianze , Li Wenkang , Li Fuguang , Ren Maozhi , Wang Wenjing
Published: January 2024

Dramatic shifts in global climate have intensified abiotic and biotic stress faced by plants. Plant microRNAs (miRNAs)—20–24 nucleotide non-coding RNA molecules—form a key regulatory system of plant gene expression; playing crucial roles in plant growth; development; and defense against abiotic and biotic stress. Moreover, they participate in cross-kingdom communication. This communication encompasses interactions with other plants, microorganisms, and insect species, collectively exerting a profound influence on the agronomic traits of crops. This article comprehensively reviews the biosynthesis of plant miRNAs and explores their impact on plant growth, development, and stress resistance through endogenous, non-transboundary mechanisms. Furthermore, this review delves into the cross-kingdom regulatory effects of plant miRNAs on plants, microorganisms, and pests. It proceeds to specifically discuss the design and modification strategies for artificial miRNAs (amiRNAs), as well as the protection and transport of miRNAs by exosome-like nanovesicles (ELNVs), expanding the potential applications of plant miRNAs in crop breeding. Finally, the current limitations associated with harnessing plant miRNAs are addressed, and the utilization of synthetic biology is proposed to facilitate the heterologous expression and large-scale production of miRNAs. This novel approach suggests a plant-based solution to address future biosafety concerns in agriculture.
Knockout of the Tnfa Gene Decreases Influenza Virus-Induced Histological Reactions in Laboratory Mice
Authors: Savenkova Darya A. , Gudymo Andrey S. , Korablev Alexey N. , Taranov Oleg S. , Bazovkina Darya V. , Danilchenko Nataliya V. , Perfilyeva Olga N. , Ivleva Elena K. , Moiseeva Anastasiya A. , Bulanovich Yulia A. , Roshchina Elena V. , Serova Irina A. , Battulin Nariman R. , Kulikova Elizabeth A. , Yudkin Dmitry V.
Published: January 2024

Tumor necrosis factor alpha (TNF-α) is a cytokine that is responsible for many processes associated with immune response and inflammation. It is involved in the development of an antiviral response to many virus infections. This factor was shown to be activated in influenza A virus infection, which enhances production of other cytokines. The overexpression of these cytokines can lead to a cytokine storm. To study the role of TNF-α in the development of pathologies associated with viral infection, we generated a Tnfa knockout mouse strain. We demonstrated that these mice were characterized by a significant increase in the number of viral genomes compared to that in the parental strain, but the amount of live virus did not differ. A histopathology of the lungs in the genetically modified animals was significantly lower in terms of interalveolar septal infiltration. The generated model may be used to further study pathological processes in viral infections.
A Cross-Sectional Study of Alzheimer-Related Proteins in Women with Polycystic Ovary Syndrome
Authors: Butler Alexandra E. , Moin Abu Saleh Md , Sathyapalan Thozhukat , Atkin Stephen L.
Published: January 2024

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer’s disease (AD). Proteins increased in AD have been reported to include fibronectin (FN) fragments 3 and 4 (FN1.3 and FN1.4, respectively) and ApoE. We hypothesized that Alzheimer-related proteins would be dysregulated in PCOS because of associated insulin resistance and obesity. In this comparative cross-sectional analysis, aptamer-based SomaScan proteomic analysis for the detection of plasma Alzheimer-related proteins was undertaken in a PCOS biobank of 143 women with PCOS and 97 control women. Amyloid precursor protein (APP) (p < 0.05) and amyloid P-component (APCS) (p < 0.001) were elevated in PCOS, while alpha-synuclein (SNCA) (p < 0.05) was reduced in PCOS. Associations with protective heat shock proteins (HSPs) showed that SNCA positively correlated with HSP90 (p < 0.0001) and HSP60 (p < 0.0001) in both the PCOS and control women. Correlations with markers of inflammation showed that APCS correlated with interleukin 6 (IL6) (p = 0.04), while Apolipoprotein (Apo) E3 correlated with TNF-alpha (p = 0.02). FN, FN1.3, FN1.4 and ApoE were all elevated significantly (p < 0.05). An AD-associated protein pattern with elevated FN, FN1.3, FN1.4 and ApoE was found in PCOS, in addition to elevated APP and reduced SNCA, which was the same as reported for type 2 diabetes (T2D) with, additionally, an elevation in APCS. With the AD biomarker pattern in PCOS being very similar to that in T2D, where there is an association between AD and T2D, this suggests that larger prospective cohort studies are needed in women with PCOS to determine if there is a causal association with AD.
Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance
Authors: Conte Maddalena , Poggio Paolo , Monti Maria , Petraglia Laura , Cabaro Serena , Bruzzese Dario , Comentale Giuseppe , Caruso Aurelio , Grimaldi Mariagabriella , Zampella Emilia , Gencarelli Annarita , Cervasio Maria Rosaria , Cozzolino Flora , Monaco Vittoria , Myasoedova Veronika , Valerio Vincenza , Ferro Adele , Insabato Luigi , Bellino Michele , Galasso Gennaro , Graziani Francesca , Pucci Pietro , Formisano Pietro , Pilato Emanuele , Cuocolo Alberto , Perrone Filardi Pasquale , Leosco Dario , Parisi Valentina
Published: January 2024

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.
Molecular Mechanisms and Regulatory Pathways Underlying Drought Stress Response in Rice
Authors: Geng Anjing , Lian Wenli , Wang Yihan , Liu Minghao , Zhang Yue , Wang Xu , Chen Guang
Published: January 2024

Rice is a staple food for 350 million people globally. Its yield thus affects global food security. Drought is a serious environmental factor affecting rice growth. Alleviating the inhibition of drought stress is thus an urgent challenge that should be solved to enhance rice growth and yield. This review details the effects of drought on rice morphology, physiology, biochemistry, and the genes associated with drought stress response, their biological functions, and molecular regulatory pathways. The review further highlights the main future research directions to collectively provide theoretical support and reference for improving drought stress adaptation mechanisms and breeding new drought-resistant rice varieties.
TR-57 Treatment of SUM159 Cells Induces Mitochondrial Dysfunction without Affecting Membrane Potential
Authors: Mishukov Artem , Mndlyan Ekaterina , Berezhnov Alexey V. , Kobyakova Margarita , Lomovskaya Yana , Holmuhamedov Ekhson , Odinokova Irina
Published: January 2024

Recent works identified ClpXP, mitochondrial caseinolytic protease, as the only target of imipridones, a new class of antitumor agents. Our study of the mechanism of imipridone derivative TR-57 action in SUM159 human breast cancer cells demonstrated mitochondrial fragmentation, degradation of mitochondrial mtDNA and mitochondrial dysfunction due to inhibition of Complex I and Complex II activity. Complete inhibition of oxidative phosphorylation accompanied 90, 94, 88 and 87% decreases in the content of Complex I, II, III and IV proteins, respectively. The content of the FOF1-ATPase subunits decreased sharply by approximately 35% after 24 h and remained unchanged up to 72 h of incubation with TR-57. At the same time, a disappearance of the ATPIF1, the natural inhibitor of mitochondrial FOF1-ATPase, was observed after 24 h exposure to TR-57. ATPase inhibitor oligomycin did not affect the mitochondrial membrane potential in intact SUM159, whereas it caused a 65% decrease in TR-57-treated cells. SUM159 cells incubated with TR57 up to 72 h retained the level of proteins facilitating the ATP transfer across the mitochondrial membranes: VDAC1 expression was not affected, while expression of ANT-1/2 and APC2 increased by 20% and 40%, respectively. Thus, our results suggest that although TR-57 treatment leads to complete inhibition of respiratory chain activity of SUM159 cells, hydrolysis of cytoplasmic ATP by reversal activity of FOF1-ATPase supports mitochondrial polarization.
Rising Lysophosphatidylcholine Levels Post-Hepatitis C Clearance
Authors: Peschel Georg , Krautbauer Sabrina , Weigand Kilian , Grimm Jonathan , Höring Marcus , Liebisch Gerhard , Müller Martina , Buechler Christa
Published: January 2024

Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis.
Long-Term Atrioventricular Block Following Valve Surgery: Electrocardiographic and Surgical Predictors
Authors: Farina Jacopo , Biffi Mauro , Folesani Gianluca , Di Marco Luca , Martin Sofia , Zenesini Corrado , Savini Carlo , Ziacchi Matteo , Diemberger Igor , Martignani Cristian , Pacini Davide
Published: January 2024

Background: Bradyarrhythmia requiring pacemaker implantation among patients undergoing valve surgery may occur even after several years, with unclear predictors. Our aim was to investigate the incidence of pacemaker implantation at different follow-up times and identify associated predictors. Methods: We conducted a retrospective study evaluating 1046 consecutive patients who underwent valve surgery at the Cardiac Surgery Division of Bologna University Hospital from 2005 to 2010. Results: During 10 ± 4 years of follow-up, 11.4% of these patients required pacemaker implantation. Interventions on both atrioventricular valves independently predicted long-term pacemaker implantation (SHR 2.1, 95% CI 1.2–3.8, p = 0.014). Preoperative atrioventricular conduction disease strongly predicted long-term atrioventricular block, with right bundle branch block as the major predictor (SHR 7.0, 95% CI 3.9–12.4, p < 0.001), followed by left bundle branch block (SHR 4.9, 95% CI 2.4–10.1, p < 0.001), and left anterior fascicular block (SHR 3.9, 95% CI 1.8–8.3, p < 0.001). Conclusion: Patients undergoing valvular surgery have a continuing risk of atrioventricular block late after surgery until the 12-month follow-up, which was clearly superior to the rate of atrioventricular block observed at long-term. Pre-operative atrioventricular conduction disease and combined surgery on both atrioventricular valves are strong predictors of atrioventricular block requiring pacemaker implantation.
Relationship between Anemia and Readmission among Older Patients in Rural Community Hospitals: A Retrospective Cohort Study
Authors: Amano Shiho , Ohta Ryuichi , Sano Chiaki
Published: January 2024

Readmission rates among older adults are a growing concern, and the association of readmission with anemia and the potential benefits of a systematic assessment and intervention remain unclear. This study investigated the association between anemia and readmission within 28 and 90 days in an older population. Data from 1280 patients admitted to the Department of General Medicine of Unnan City Hospital between April 2020 and December 2021 were retrospectively analyzed. Variables such as anemia status, Charlson comorbidity index (CCI) score, Functional Independence Measure (FIM) score, and dependent status were evaluated. Multivariate logistic regression was used to determine the associations between 28-day and 90-day readmissions. The average age was 84.9 years, and the prevalence of anemia was 36.4%. The readmission rates within 28 and 90 days were 10.4% and 19.1%, respectively. Anemia was significantly associated with readmission in both periods (28-day adjusted odds ratio, 2.28; 90-day adjusted odds ratio, 1.65). CCI score, FIM score, and dependent status were also identified as significant factors. Anemia is significantly associated with short- and medium-term readmissions in older patients. Addressing anemia, along with other identified factors, may help reduce readmission rates.
Association between Resistant Arterial Hypertension, Type 2 Diabetes, and Selected microRNAs
Authors: Błaszczyk Robert , Petniak Alicja , Bogucki Jacek , Kocki Janusz , Wysokiński Andrzej , Głowniak Andrzej
Published: January 2024

Introduction: In recent years, a very close relationship between miRNA and cardiovascular diseases has been found. RAH and T2DM are accompanied by a change in the microRNA expression spectrum. Objectives: This study aimed to evaluate the clinical characteristics and expression of selected microRNAs in patients with idiopathic RAH and T2DM. Patients and methods: A total of 115 patients with RAH were included in this study. Among them were 53 patients (46.09%) with T2DM. miRNA levels were determined using quantitative real-time polymerase chain reaction. The expression of the examined genes was calculated from the formula RQ = 2−ΔΔCT. Results: Analysis using the Mann–Whitney U test showed a statistically significant (p < 0.05) difference in the expression of MIR1-1 (p = 0.031) and MIR195 (p = 0.042) associated with the occurrence of T2DM in the subjects. The value of MIR1-1 gene expression was statistically significantly higher in patients with T2DM (median: 0.352; mean: 0.386; standard deviation: 0.923) compared to patients without T2DM (median: 0.147; mean: −0.02; standard deviation: 0.824). The value of MIR195 gene expression was statistically significantly higher in patients with T2DM (median: 0.389, mean: 0.442; standard deviation: 0.819) compared to patients without T2DM (median: −0.027; mean: 0.08; standard deviation: 0.942). Conclusions: The values of MIR1-1 and MIR195 gene expression were statistically significantly higher in patients with RAH and T2DM compared to patients with RAH and without T2DM. Further studies are necessary to precisely clarify the roles of miRNAs in patients with RAH and T2DM. They should demonstrate the utility of these genetic markers in clinical practice.
Exploring the Choice of Graft Materials in Tympanoplasty: A Perspective on the Use of Temporalis Fascia and Cartilage Grafts. Comment on Ferlito et al. Type 1 Tympanoplasty Outcomes between Cartilage and Temporal Fascia Grafts: A Long-Term Retrospective Study. J. Clin. Med. 2022, 11, 7000
Authors: Ronsivalle Salvatore , Di Luca Milena
Published: January 2024

I am writing this letter to discuss and share my thoughts on the recently published research comparing the outcomes of using temporalis fascia and cartilage grafts in type I tympanoplasty [...]
The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis
Authors: Ceccherini Elisa , Michelucci Elena , Signore Giovanni , Coco Barbara , Zari Michela , Bellini Massimo , Brunetto Maurizia Rossana , Cecchettini Antonella , Rocchiccioli Silvia
Published: January 2024

Background: Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. Methods: Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography–tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. Results: We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. Conclusion: We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.
Scientific Status Quo of Small Renal Lesions: Diagnostic Assessment and Radiomics
Authors: Trovato Piero , Simonetti Igino , Morrone Alessio , Fusco Roberta , Setola Sergio Venanzio , Giacobbe Giuliana , Brunese Maria Chiara , Pecchi Annarita , Triggiani Sonia , Pellegrino Giuseppe , Petralia Giuseppe , Sica Giacomo , Petrillo Antonella , Granata Vincenza
Published: January 2024

Background: Small renal masses (SRMs) are defined as contrast-enhanced renal lesions less than or equal to 4 cm in maximal diameter, which can be compatible with stage T1a renal cell carcinomas (RCCs). Currently, 50–61% of all renal tumors are found incidentally. Methods: The characteristics of the lesion influence the choice of the type of management, which include several methods SRM of management, including nephrectomy, partial nephrectomy, ablation, observation, and also stereotactic body radiotherapy. Typical imaging methods available for differentiating benign from malignant renal lesions include ultrasound (US), contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI). Results: Although ultrasound is the first imaging technique used to detect small renal lesions, it has several limitations. CT is the main and most widely used imaging technique for SRM characterization. The main advantages of MRI compared to CT are the better contrast resolution and tissue characterization, the use of functional imaging sequences, the possibility of performing the examination in patients allergic to iodine-containing contrast medium, and the absence of exposure to ionizing radiation. For a correct evaluation during imaging follow-up, it is necessary to use a reliable method for the assessment of renal lesions, represented by the Bosniak classification system. This classification was initially developed based on contrast-enhanced CT imaging findings, and the 2019 revision proposed the inclusion of MRI features; however, the latest classification has not yet received widespread validation. Conclusions: The use of radiomics in the evaluation of renal masses is an emerging and increasingly central field with several applications such as characterizing renal masses, distinguishing RCC subtypes, monitoring response to targeted therapeutic agents, and prognosis in a metastatic context.
Correction: Schuderer et al. Risk Factors for Flap Loss: Analysis of Donor and Recipient Vessel Morphology in Patients Undergoing Microvascular Head and Neck Reconstructions. J. Clin. Med. 2023, 12, 5206
Authors: Schuderer Johannes G. , Dinh Huong T. , Spoerl Steffen , Taxis Jürgen , Fiedler Mathias , Gottsauner Josef M. , Maurer Michael , Reichert Torsten E. , Meier Johannes K. , Weber Florian , Ettl Tobias
Published: January 2024

In the original publication by Schuderer et al., there was a mistake in Table 1 as published [...]
Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis
Authors: Pezzolo Elena , Ortoncelli Michela , Ferrucci Silvia Mariel , Guanti Mario Bruno , Schena Donatella , Napolitano Maddalena , Rossi Mariateresa , Foti Caterina , D’Amico Domenico , Amoruso Giuseppe Fabrizio , Morrone Pietro , Ribero Simone , Barei Francesca , Biagi Matteo , Pascucci Enrico , Patruno Cataldo , Calzavara Pinton Piergiacomo , Romita Paolo , Gargiulo Luigi , Narcisi Alessandra , Naldi Luigi
Published: January 2024

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18–75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020–August 2023. Upadacitinib survival was investigated through Kaplan–Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.
Lower Lip Reconstruction after Skin Cancer Excision: A Tailored Algorithm for Elderly Patients
Authors: Russo Raffaele , Pentangelo Paola , Ceccaroni Alessandra , Losco Luigi , Alfano Carmine
Published: January 2024

Background: Lower lip reconstruction is crucial to restore oral integrity post-cancer excision. A perfect balance between form and function should be achieved. With an aging demographic, adapting surgical methods to meet the unique needs of the elderly becomes imperative. Our study aims to introduce a specialized algorithm for lower lip reconstruction; it was tailored to geriatric patients and emphasized the use of “simpler flaps”. Additionally, “Pearls and Pitfalls” were provided for surgeons approaching lower lip reconstruction. Methods: Between January 2018 and June 2021, a retrospective study was carried out. Data collection included patient demographics, defect attributes, reconstructive approaches, flap viability assessment, wound healing, and complications. The follow-up was carried out for a period of a minimum of 6 months. Results: Among 78 patients, squamous cell carcinoma predominated with a mean defect area of 3308 cm2. Postoperative complications were recorded in two patients. All patients reported sensory restoration and overall satisfaction at the 6-month follow-up; secondary procedures were not necessary. Conclusion: Our reconstructive algorithm, focused on elderly patients, prioritizes less invasive reconstructive techniques and introduces innovative modifications to the established methods to achieve both aesthetic and functional outcomes with a low complication rate. In patients undergoing lower lip reconstruction, the subjective microstomia was found to be less relevant than the objective microstomia.
Prevention of Breast Cancer-Related Lymphedema: An Up-to-Date Systematic Review of Different Surgical Approaches
Authors: Pagliara Domenico , Grieco Federica , Rampazzo Silvia , Pili Nicola , Serra Pietro Luciano , Cuomo Roberto , Rubino Corrado
Published: January 2024

Breast cancer-related lymphedema (BCRL) affects approximately 20% of women after breast cancer therapy. Advances in treatment have increased the life expectancy; thus, the prevalence of BCRL will continue to rise with the number of cancer survivors, hence the need to develop strategies to prevent this condition. We provide a systematic review of the literature on the primary prevention of BCRL by prophylactic lymphatic surgery (PLS). Between June and August 2022, we conducted a search of PubMed, Google Scholar and Cochrane. In the end, a total of eighteen papers were selected. The eleven studies without a control group reported only 15 of 342 patients who developed lymphedema at least six months after PLS (4.59%). The seven studies with a control group included 569 patients, 328 cases and 241 controls. Among the cases, 36 (10%) developed lymphedema. In contrast, the incidence of lymphedema in the controls was 40% (98 of 241 patients). The formulation of definite recommendations in favor of PLS is hindered by low-quality studies. There is no consensus on which technique should be preferred, nor on whether adjuvant radiotherapy might affect the efficacy of PLS. Randomized controlled trials are mandatory to conceive evidence-based recommendations.
Adalimumab Persistence and Its Biosimilar in Inflammatory Bowel Disease: A Real-World Study
Authors: Fernández-Cano María Carmen , Fernández-Cano Antonio Jesús , Martín-Rodríguez María Mar , Sánchez-Capilla Antonio Damián , Cabello-Tapia María José , Redondo-Cerezo Eduardo
Published: January 2024

Adalimumab biosimilar experience is still recent. Interchangeability differences could reduce persistence times. Our goal was to compare biosimilar persistence differences with a reference. A retrospective observational study was performed in three groups divided according to the adalimumab received. The primary outcome measure was persistence, represented with Kaplan–Meier analysis, and we secondarily evaluated security, efficacy, and biomarkers. We obtained approval from the regional ethical committee, and the study was conducted following the Helsinki Declaration as revised in 2013. Data from 104 patients were collected: 50 received the biosimilar, 29 received the reference, and 25 switched from the original to the biosimilar. After a follow-up of 12 months, the biosimilar’s persistence was higher, without differences in mild adverse events per group. In contrast, there were differences in severe events, with the switched group’s frequency being higher. Biomarkers were reduced at similar proportions in all groups, and 43% had a clinical response at week 20 without differences. Adalimumab biosimilars are a valuable option for IBD based on clinical equivalence that are less expensive than the original drug. Their use does not have a detrimental influence on disease, although there are a few nuances in terms of interchangeability. These results support increasing confidence in using biosimilars, thus promoting the better sustainability of health systems.
Heart Transplantation
Authors: Chrysakis Nikolaos , Magouliotis Dimitrios E. , Spiliopoulos Kyriakos , Athanasiou Thanos , Briasoulis Alexandros , Triposkiadis Filippos , Skoularigis John , Xanthopoulos Andrew
Published: January 2024

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list. Advanced heart failure and resistant angina are among the main indications of HTx, whereas active infection, peripheral vascular disease, malignancies, and increased body mass index (BMI) are important contraindications. The main complications of HTx include graft rejection, graft angiopathy, primary graft failure, infection, neoplasms, and retransplantation. Recent advances in the field of HTx include the first two porcine-to-human xenotransplantations, the inclusion of hepatitis C donors, donation after circulatory death, novel monitoring for acute cellular rejection and antibody-mediated rejection, and advances in donor heart preservation and transportation. Lastly, novel immunosuppression therapies such as daratumumab, belatacept, IL 6 directed therapy, and IgG endopeptidase have shown promising results.
Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes
Authors: Wagener Nele , Hardt Sebastian , Pumberger Matthias , Schömig Friederike
Published: January 2024

(1) Background: Around 50% of hemophilia patients develop severe arthropathy, with even subclinical hemorrhage in childhood potentially leading to intra-articular iron deposition, synovia proliferation, neoangiogenesis, and eventual damage to articular cartilage and subchondral bone. Treatments typically include coagulation factor substitution, radiosynoviorthesis, and joint replacement for advanced cases. This study aims to elucidate programmed cell death mechanisms in hemophilic arthropathy (HA) to identify novel treatments. (2) Methods: Human chondrocytes were exposed to lysed/non-lysed erythrocytes, ferroptosis inducer ML-162, cytokines (IL-1ß, TNFα), and ferric citrate, then assessed for metabolic activity, DNA content, and cell death using Alamar Blue, cyQUANT, and Sytox assays. Three-dimensional spheroids served as a cartilage model to study the effects of erythrocytes and ML-162. (3) Results: Erythrocytes caused significant cell death in 2D cultures (p < 0.001) and damaged 3D chondrocyte spheroids. Iron citrate and erythrocytes reduced chondrocyte DNA content (p < 0.001). The ferroptosis pathway was implicated in cell death, with no effects from apoptosis and necroptosis inhibitors. (4) Conclusions: This study offers insights into HA’s cell death pathway, suggesting ferroptosis inhibitors as potential therapies. Further studies are needed to evaluate their efficacy against the chronic effects of HA.
Prevalence of Hyperuricemia and Associated Cardiovascular Risk Factors in Elite Athletes Practicing Different Sporting Disciplines: A Cross-Sectional Study
Authors: Di Gioia Giuseppe , Crispino Simone Pasquale , Maestrini Viviana , Monosilio Sara , Squeo Maria Rosaria , Lemme Erika , Segreti Andrea , Serdoz Andrea , Fiore Roberto , Zampaglione Domenico , Pelliccia Antonio
Published: January 2024

Uricemia has been identified as an independent risk factor for cardiovascular disease. In the general population, hyperuricemia is associated with hypertension, endothelial dysfunction, and other cardiovascular risk (CVR) factors. Our aim was to explore the prevalence of hyperuricemia among Olympic athletes, evaluating the influence of sporting discipline and its correlation with CVR factors. We enrolled 1173 Olympic athletes classified into four disciplines: power, skill, endurance, and mixed. Clinical, anthropometric data, and complete blood test results were collected. Hyperuricemia was present in 4.4% of athletes, 0.3% were hypertensive, 11.7% had high-normal blood pressure values, 0.2% were diabetic, 1.2%. glucose intolerance, 8.2% active smokers, and 3% were obese. Males had a higher prevalence of hyperuricemia (5.3%) than females (3.4%) with no significant differences between different sporting disciplines (male, p = 0.412; female p = 0.561). Males with fat mass >22% presented higher uricemia (5.8 ± 1 vs. 5.3 ± 1 mg/dL, p = 0.010) like hypertensive athletes (6.5 ± 0.3 vs. 5.3 ± 1 mg/dL, p = 0.031), those with high-normal blood pressure (5.13 ± 1 vs. 4.76 ± 1.1 mg/dL, p = 0.0004) and those with glucose intolerance (6 ± 0.8 vs. 5.3 ± 1 mg/dL, p = 0.066). The study provides a comprehensive evaluation of hyperuricemia among Olympic athletes, revealing a modest prevalence, lower than in the general population. However, aggregation of multiple CVR factors could synergistically elevate the risk profile, even in a population assumed to be at low risk. Therefore, uric acid levels should be monitored as part of the CVR assessment in athletes.
Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study
Authors: Mai Aaron Shengting , Tan Brendan Jen-Wei , Sun Qiao-Yang , Tan Eng-King
Published: January 2024

While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson’s disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW—OR 0.93, 95% CI 0.91–0.96, p = 3.12 × 10−5; MR-Egger—OR 0.93, 95% CI 0.88–0.98, p = 1.45 × 10−2; weighted median—OR 0.93, 95% CI 0.89–0.98, p = 2.76 × 10−3; and weighted mode—OR 0.94, 95% CI 0.9–0.98, p = 1.58 × 10−2). The findings were then replicated with another independent GWAS dataset on T1DM (IVW—OR 0.97, 95% CI 0.95–0.99, p = 3.10 × 10−3; MR-Egger—OR 0.96, 95% CI 0.93–0.99, p = 1.08 × 10−2; weighted median—OR 0.97, 95% CI 0.94–0.99, p = 1.88 × 10−2; weighted mode—OR 0.97, 95% CI 0.94–0.99, p = 1.43 × 10−2). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.
Optic Nerve Head and Retinal Changes in Idiopathic Intracranial Hypertension: Correlation with Short-Term Cerebrospinal Fluid Pressure Monitoring
Authors: Toro Mario Damiano , Castellino Niccolò , Russo Andrea , Scollo Davide , Avitabile Teresio , Rejdak Robert , Rejdak Magdalena , Cimino Vincenzo , Costagliola Ciro , Carnevali Adriano , Chisari Clara Grazia
Published: January 2024

Background: We aimed to assess the status of the optic nerve and retina by optical coherence tomography (OCT) in a group of patients with idiopathic intracranial hypertension (IIH) on the basis of dynamic changes in intracranial pressure. Methods: This observational and cross-sectional study included patients affected by idiopathic intracranial hypertension with papilledema (IIHWP) and patients with idiopathic intracranial hypertension without papilledema (IIHWOP). All participants underwent an OCT examination of the macula and optic nerve head. Parameters related to intracranial pressure, including cerebrospinal fluid (CSF) opening pressure (oCSFp), CSF mean pressure (mCSFp), and pulse wave amplitude (PWA), were included in the analysis. Results: Out of the 22 subjects enlisted for the study, a total of 16 patients suggestive of IIH were finally enrolled. Papilledema was detected in nine subjects (56.2%) and seven patients were affected by IIHWOP (43.7%). The OCT examination showed a higher mean RNFL thickness in IIHWP patients in comparison to IIHWOP in both eyes (p < 0.05 and p < 0.01, respectively). Intracranial pressure (ICP) measurements showed that IIHWP had higher values of oCSFp, mCSFp, and PWA compared to IIHWOP (p = 0.0001, p = 0.0001, and p = 0.0001, respectively). In addition, ICP parameters significantly correlated with RNFL. Conclusions: Clinical parameters suggestive of idiopathic intracranial hypertension are associated with retina and optic nerve OCT parameters. OCT is a useful tool to detect these alterations in a non-invasive fashion.
Inhaled Pulmonary Vasodilators for the Treatment of Right Ventricular Failure in Cardio-Thoracic Surgery: Is One Better than the Others?
Authors: Benedetto Maria , Piccone Giulia , Gottin Leonardo , Castelli Andrea , Baiocchi Massimo
Published: January 2024

Right ventricular failure (RFV) is a potential complication following cardio-thoracic surgery, with an incidence ranging from 0.1% to 30%. The increase in pulmonary vascular resistance (PVR) is one of the main triggers of perioperative RVF. Inhaled pulmonary vasodilators (IPVs) can reduce PVR and improve right ventricular function with minimal systemic effects. This narrative review aims to assess the efficacy of inhaled nitric oxide and inhaled prostacyclins for the treatment of perioperative RVF. The literature, although statistically limited, supports the clinical similarity between them. However, it failed to demonstrate a clear benefit from the pre-emptive use of inhaled nitric oxide in patients undergoing left ventricular assist device implantation or early administration during heart-lung transplants. Additional concerns are related to cost safety and IPV use in pathologies associated with pulmonary venous congestion. The largest ongoing randomized controlled trial on adults (INSPIRE-FLO) is addressing whether inhaled Epoprostenol and inhaled nitric oxide are similar in preventing RVF after heart transplants and left ventricular assist device placement, and whether they are similar in preventing primary graft dysfunction after lung transplants. The preliminary analysis supports their equivalence. Several key points may be achieved by the present narrative review. When RVF occurs in the setting of elevated PVR, IPV should be the preferred initial treatment and they should be preventively used in patients at high risk of postoperative RVF. If severe refractory postoperative RVF occurs, IPVs should be combined with complementary pharmacology (inotropes and inodilators). If unsuccessful, right ventricular mechanical support should be established.
Does Systemic Hematological Therapy Influence the Course of Paraproteinemic Keratopathy?
Authors: Al Hariri Mohammad , Munder Markus , Pfeiffer Norbert , Wasielica-Poslednik Joanna
Published: January 2024

The purpose of this article is to evaluate the course of paraproteinemic keratopathy (PPK) in patients undergoing systemic therapy for the underlying hematological disease. Baseline and follow-up examinations included hematological work-up, best-corrected visual acuity, slit-lamp biomicroscopy, and in vivo confocal laser scanning microscopy (IVCM). We included 22 patients with bilateral PPK (aged 68 ± 10.4 years, 11 males). Ten patients with multiple myeloma (MM) underwent on-label systemic therapy. During follow-up, we observed a regression of corneal opacities in three patients under slit-lamp examination and under IVCM, while PPK remained unchanged in seven patients. In three patients with monoclonal gammopathy of ocular significance (MGOS), systemic therapy was initiated off-label to reduce the serum paraprotein load before penetrating keratoplasty (PKP). These patients showed no signs of PPK recurrence for up to 24 months after PKP. In one patient without systemic therapy, a recurrence in corneal grafts occurred within 12 months of PKP. In eight patients without systemic therapy, PPK remained stable. In conclusion, systemic therapy for MM patients reduced corneal opacity in 30% of treated patients. Furthermore, systemic therapy performed before PKP in patients without conventional systemic therapy indication (MGOS) likely postpones PPK recurrence in the corneal graft.
Predictive Model for Hydrostatic Curves of Chine-Type Small Ships Based on Deep Learning
Authors: Lee Dongkeun , Lim Chaeog , Oh Sang-jin , Kim Minjoon , Park Jun Soo , Shin Sung-chul
Published: January 2024

Capsizing accidents are regarded as marine accidents with a high rate of casualties per accident. Approximately 89% of all such accidents involve small ships (vessels with gross tonnage of less than 10 tons). Stability calculations are critical for assessing the risk of capsizing incidents and evaluating a ship’s seaworthiness. Despite the high frequency of capsizing accidents involving them, small ships are generally exempt from adhering to stability regulations, thus remaining systemically exposed to the risk of capsizing. Moreover, the absence of essential design documents complicates direct ship stability calculations. This study utilizes hull form feature data—obtained from the general arrangement of small ships—as input for a deep learning model. The model is structured as a multilayer neural network and aims to infer hydrostatic curves, which are required data for stability calculations.
Personalized Medicine in Urolithiasis: AI Chatbot-Assisted Dietary Management of Oxalate for Kidney Stone Prevention
Authors: Aiumtrakul Noppawit , Thongprayoon Charat , Arayangkool Chinnawat , Vo Kristine B. , Wannaphut Chalothorn , Suppadungsuk Supawadee , Krisanapan Pajaree , Garcia Valencia Oscar A. , Qureshi Fawad , Miao Jing , Cheungpasitporn Wisit
Published: January 2024

Accurate information regarding oxalate levels in foods is essential for managing patients with hyperoxaluria, oxalate nephropathy, or those susceptible to calcium oxalate stones. This study aimed to assess the reliability of chatbots in categorizing foods based on their oxalate content. We assessed the accuracy of ChatGPT-3.5, ChatGPT-4, Bard AI, and Bing Chat to classify dietary oxalate content per serving into low (<5 mg), moderate (5–8 mg), and high (>8 mg) oxalate content categories. A total of 539 food items were processed through each chatbot. The accuracy was compared between chatbots and stratified by dietary oxalate content categories. Bard AI had the highest accuracy of 84%, followed by Bing (60%), GPT-4 (52%), and GPT-3.5 (49%) (p < 0.001). There was a significant pairwise difference between chatbots, except between GPT-4 and GPT-3.5 (p = 0.30). The accuracy of all the chatbots decreased with a higher degree of dietary oxalate content categories but Bard remained having the highest accuracy, regardless of dietary oxalate content categories. There was considerable variation in the accuracy of AI chatbots for classifying dietary oxalate content. Bard AI consistently showed the highest accuracy, followed by Bing Chat, GPT-4, and GPT-3.5. These results underline the potential of AI in dietary management for at-risk patient groups and the need for enhancements in chatbot algorithms for clinical accuracy.