bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Approach to Metabolomic Data Predicts Type 2 Diabetes Mellitus Incidence
Authors: Leiherer Andreas , Muendlein Axel , Mink Sylvia , Mader Arthur , Saely Christoph H. , Festa Andreas , Fraunberger Peter , Drexel Heinz
Published: May 2024

Metabolomics, with its wealth of data, offers a valuable avenue for enhancing predictions and decision-making in diabetes. This observational study aimed to leverage machine learning (ML) algorithms to predict the 4-year risk of developing type 2 diabetes mellitus (T2DM) using targeted quantitative metabolomics data. A cohort of 279 cardiovascular risk patients who underwent coronary angiography and who were initially free of T2DM according to American Diabetes Association (ADA) criteria was analyzed at baseline, including anthropometric data and targeted metabolomics, using liquid chromatography (LC)–mass spectroscopy (MS) and flow injection analysis (FIA)–MS, respectively. All patients were followed for four years. During this time, 11.5% of the patients developed T2DM. After data preprocessing, 362 variables were used for ML, employing the Caret package in R. The dataset was divided into training and test sets (75:25 ratio) and we used an oversampling approach to address the classifier imbalance of T2DM incidence. After an additional recursive feature elimination step, identifying a set of 77 variables that were the most valuable for model generation, a Support Vector Machine (SVM) model with a linear kernel demonstrated the most promising predictive capabilities, exhibiting an F1 score of 50%, a specificity of 93%, and balanced and unbalanced accuracies of 72% and 88%, respectively. The top-ranked features were bile acids, ceramides, amino acids, and hexoses, whereas anthropometric features such as age, sex, waist circumference, or body mass index had no contribution. In conclusion, ML analysis of metabolomics data is a promising tool for identifying individuals at risk of developing T2DM and opens avenues for personalized and early intervention strategies.
Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans
Authors: Zhang La-Mei , Zhou Sheng-Wen , Huang Xiao-Shan , Chen Yi-Fan , Mwangi James , Fang Ya-Qun , Du Ting , Zhao Min , Shi Lei , Lu Qiu-Min
Published: May 2024

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.
Role of Phosphodiesterases in Biology and Pathology 2.0
Authors: Giorgi Mauro , Pellegrini Manuela , Massimi Mara
Published: May 2024

Phosphodiesterases (PDEs) are ubiquitous enzymes that hydrolyse cAMP and cGMP second messengers temporally, spatially, and integratedly according to their expression and compartmentalization inside the cell [...]
Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy
Authors: Prasse Nele , Wessolowski Charlotte , Müller Ingo , Cornils Kerstin , Franke Anna-Katharina
Published: May 2024

Osteosarcoma is a type of bone cancer that primarily affects children and young adults. The overall 5-year survival rate for localized osteosarcoma is 70–75%, but it is only 20–30% for patients with relapsed or metastatic tumors. To investigate potential glycan-targeting structures for immunotherapy, we stained primary osteosarcomas with recombinant C-type lectin CD301 (MGL, CLEC10A) and observed moderate to strong staining on 26% of the tumors. NK92 cells expressing a CD301-CAR recognized and eliminated osteosarcoma cells in vitro. Cytotoxic activity assays correlated with degranulation and cytokine release assays. Combination with an inhibitory antibody against the immune checkpoint TIGIT (T-cell immunoreceptor with lg and ITIM domains) showed promising additional effects. Overall, this study showed, for the first time, the expression of CD301 ligands in osteosarcoma tissue and demonstrated their use as potential target structures for lectin-based immunotherapy.
Clinical and Immunologic Characteristics of Colorectal Cancer Tumors Expressing LY6G6D
Authors: Sanvicente García Adrián , Pedregal Manuel , Paniagua-Herranz Lucía , Díaz-Tejeiro Cristina , Nieto-Jiménez Cristina , Pérez Segura Pedro , Munkácsy Gyöngyi , Győrffy Balázs , Calvo Emiliano , Moreno Víctor , Ocaña Alberto
Published: May 2024

The identification of targets that are expressed on the cell membrane is a main goal in cancer research. The Lymphocyte Antigen 6 Family Member G6D (LY6G6D) gene codes for a protein that is mainly present on the surface of colorectal cancer (CRC) cells. Therapeutic strategies against this protein like the development of T cell engagers (TCE) are currently in the early clinical stage. In the present work, we interrogated public genomic datasets including TCGA to evaluate the genomic and immunologic cell profile present in tumors with high expression of LY6G6D. We used data from TCGA, among others, and the Tumor Immune Estimation Resource (TIMER2.0) platform for immune cell estimations and Spearman correlation tests. LY6G6D expression was exclusively present in CRC, particularly in the microsatellite stable (MSS) subtype, and was associated with left-side tumors and the canonical genomic subgroup. Tumors with mutations of APC and p53 expressed elevated levels of LY6G6D. This protein was expressed in tumors with an inert immune microenvironment with an absence of immune cells and co-inhibitory molecules. In conclusion, we described clinical, genomic and immune-pathologic characteristics that can be used to optimize the clinical development of agents against this target. Future studies should be performed to confirm these findings and potentially explore the suggested clinical development options.
Clinical and Immunological Impact of Ocrelizumab Extended Interval Dosing in Multiple Sclerosis: A Single-Center, Real-World Experience
Authors: Nasello Martina , Zancan Valeria , Rinaldi Virginia , Marrone Antonio , Reniè Roberta , Diamant Selene , Marconi Martina , Le Mura Lorenzo , Salvetti Marco , Buscarinu Maria Chiara , Bellucci Gianmarco
Published: May 2024

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.
FOSL1’s Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review
Authors: Khedri Azam , Guo Shanchun , Ramar Vanajothi , Hudson BreAnna , Liu Mingli
Published: May 2024

This review specifically examines the important function of the oncoprotein FOSL1 in the dimeric AP-1 transcription factor, which consists of FOS-related components. FOSL1 is identified as a crucial controller of invasion and metastatic dissemination, making it a potential target for therapeutic treatment in cancer patients. The review offers a thorough examination of the regulatory systems that govern the influence exerted on FOSL1. These include a range of changes that occur throughout the process of transcription and after the translation of proteins. We have discovered that several non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a significant role in regulating FOSL1 expression by directly interacting with its mRNA transcripts. Moreover, an investigation into the functional aspects of FOSL1 reveals its involvement in apoptosis, proliferation, and migration. This work involves a comprehensive analysis of the complex signaling pathways that support these diverse activities. Furthermore, particular importance is given to the function of FOSL1 in coordinating the activation of several cytokines, such as TGF-beta, and the commencement of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that migrate into the tumor microenvironment. There is a specific emphasis on evaluating the predictive consequences linked to FOSL1. Insights are now emerging on the developing roles of FOSL1 in relation to the processes that drive resistance and reliance on specific treatment methods. Targeting FOSL1 has a strong inhibitory effect on the formation and spread of specific types of cancers. Despite extensive endeavors, no drugs targeting AP-1 or FOSL1 for cancer treatment have been approved for clinical use. Hence, it is imperative to implement innovative approaches and conduct additional verifications.
Transcriptional Control of Seed Life: New Insights into the Role of the NAC Family
Authors: Fuertes-Aguilar Javier , Matilla Angel J.
Published: May 2024

Transcription factors (TFs) regulate gene expression by binding to specific sequences on DNA through their DNA-binding domain (DBD), a universal process. This update conveys information about the diverse roles of TFs, focusing on the NACs (NAM-ATAF-CUC), in regulating target-gene expression and influencing various aspects of plant biology. NAC TFs appeared before the emergence of land plants. The NAC family constitutes a diverse group of plant-specific TFs found in mosses, conifers, monocots, and eudicots. This update discusses the evolutionary origins of plant NAC genes/proteins from green algae to their crucial roles in plant development and stress response across various plant species. From mosses and lycophytes to various angiosperms, the number of NAC proteins increases significantly, suggesting a gradual evolution from basal streptophytic green algae. NAC TFs play a critical role in enhancing abiotic stress tolerance, with their function conserved in angiosperms. Furthermore, the modular organization of NACs, their dimeric function, and their localization within cellular compartments contribute to their functional versatility and complexity. While most NAC TFs are nuclear-localized and active, a subset is found in other cellular compartments, indicating inactive forms until specific cues trigger their translocation to the nucleus. Additionally, it highlights their involvement in endoplasmic reticulum (ER) stress-induced programmed cell death (PCD) by activating the vacuolar processing enzyme (VPE) gene. Moreover, this update provides a comprehensive overview of the diverse roles of NAC TFs in plants, including their participation in ER stress responses, leaf senescence (LS), and growth and development. Notably, NACs exhibit correlations with various phytohormones (i.e., ABA, GAs, CK, IAA, JA, and SA), and several NAC genes are inducible by them, influencing a broad spectrum of biological processes. The study of the spatiotemporal expression patterns provides insights into when and where specific NAC genes are active, shedding light on their metabolic contributions. Likewise, this review emphasizes the significance of NAC TFs in transcriptional modules, seed reserve accumulation, and regulation of seed dormancy and germination. Overall, it effectively communicates the intricate and essential functions of NAC TFs in plant biology. Finally, from an evolutionary standpoint, a phylogenetic analysis suggests that it is highly probable that the WRKY family is evolutionarily older than the NAC family.
Locally Centralized Execution for Less Redundant Computation in Multi-Agent Cooperation
Authors: Bai Yidong , Sugawara Toshiharu
Published: May 2024

Decentralized execution is a widely used framework in multi-agent reinforcement learning. However, it has a well-known but neglected shortcoming, redundant computation, that is, the same/similar computation is performed redundantly in different agents owing to their overlapping observations. This study proposes a novel method, the locally centralized team transformer (LCTT), to address this problem. This method first proposes a locally centralized execution framework that autonomously determines some agents as leaders that generate instructions and other agents as workers to act according to the received instructions without running their policy networks. For the LCTT, we subsequently propose the team-transformer (T-Trans) structure, which enables leaders to generate targeted instructions for each worker, and the leadership shift, which enables agents to determine those that should instruct or be instructed by others. The experimental results demonstrated that the proposed method significantly reduces redundant computations without decreasing rewards and achieves faster learning convergence.
Numerical Simulation of Effective Heat Recapture Ammonia Pyrolysis System for Hydrogen Energy
Authors: Lim Jian Tiong , Ng Eddie Yin-Kwee , Saeedipour Hamid , Lee Hiang Kwee
Published: May 2024

This paper proposes a solution to address the challenges of high storage and transport costs associated with using hydrogen (H2) as an energy source. It suggests utilizing ammonia (NH3) as a hydrogen carrier to produce H2 onsite for hydrogen gas turbines. NH3 offers higher volumetric hydrogen density compared to liquid H2, potentially reducing shipping costs by 40%. The process involves NH3 pyrolysis, which utilizes the heat waste from exhaust gas generated by gas turbines to produce H2 and nitrogen (N2). Numerical simulations were conducted to design and understand the behaviour of the heat recapture NH3 decomposition system. The design considerations included the concept of the number of transfer units and heat exchanger efficiency, achieving a heat recapture system efficiency of up to 91%. The simulation of NH3 decomposition was performed using ANSYS, a commercial simulation software, considering wall surface reactions, turbulent flow, and chemical reaction. Parameters such as activation energy and pre-exponential factor were provided by a study utilizing a nickel wire for NH3 decomposition experiments. The conversion of NH3 reached up to 94% via a nickel-based catalyst within a temperature range of 823 K to 923 K which is the exhaust gas temperature range. Various factors were considered to compare the efficiency of the system, including the mass flow of NH3, operating gauge pressure, mass flow of exhaust gas, among others. Result showed that pressure would not affect the conversion of NH3 at temperatures above 800 K, thus a lower amount of energy is required for a compression purpose in this approach. The conversion is maintained at 94% to 97% when lower activation energy is applied via a ruthenium-based catalyst. Overall, this study showed the feasibility of utilizing convective heat transfer from exhaust gas in hydrogen production by NH3 pyrolysis, and this will further enhance the development of NH3 as the potential H2 carrier for onsite production in hydrogen power generation.
The Impact of Acute Heart Failure on Frailty Degree and Outcomes in Elderly Patients with Severe Aortic Stenosis and Chronic Heart Failure with Preserved Ejection Fraction
Authors: Esposito Augusto , Foffa Ilenia , Vecoli Cecilia , Bastiani Luca , Berti Sergio , Mazzone Annamaria
Published: May 2024

Frailty degree plays a critical role in the decision-making and outcomes of elderly patients with severe aortic stenosis (AS). Acute heart failure (AHF) results in a severely worse clinical hemodynamic status in this population. This study aimed to evaluate the impact of AHF on frailty degree and outcomes in older patients referred for tailored interventional treatment due to AS. A total of 109 patients (68% female; mean age 83.3 ± 5.4), evaluated by a multidisciplinary path for “frailty-based management” of valve disease, were divided into two groups, one with (AHF+) and one without AHF (AHF-) and preserved ejection fraction (mean value EF: 57.4 ± 8.6). AHF occurred a mean value of 55 days before geriatric, clinical, and surgical assessment. A follow-up for all-cause mortality and readmission was conducted at 20 months. AHF+ patients showed a higher frequency of advanced frailty (53.3% vs. 46.7%, respectively), rehospitalization (35.5% vs. 12.8; p = 0.007), and death (41.9% vs. 12.8%; p < 0.001). In stepwise logistic regression analysis, AHF emerged as an independent risk factor for advanced frailty (OR: 3.8 CI 1.3–10.7; p = 0.01) and hospital readmission (OR: 3.6 CI 1.1–11.6; p = 0.03). In addition, preceding AHF was an independent determinant associated with a higher risk of mortality (HR 2.65; CI 95% 1.04–6.74; p-value 0.04). AHF is independently associated with advanced frailty and poor outcomes in elderly patients with severe AS. So, this population needs careful clinical and geriatric monitoring and the implementation of interventional therapy for AS in the early stages of frailty to avoid the occurrence of AHF and poor outcomes.
Sarcopenia Prevalence among Hospitalized Patients with Severe Obesity: An Observational Study
Authors: Cancello Raffaella , Brenna Ettore , Soranna Davide , Zambon Antonella , Villa Valentina , Castelnuovo Gianluca , Donini Lorenzo Maria , Busetto Luca , Capodaglio Paolo , Brunani Amelia
Published: May 2024

Background: Sarcopenic obesity (SO) is the combination of excess fat, skeletal muscle and muscular strength/function deficit. The ESPEN/EASO have proposed new diagnostic criteria, but the SO prevalence in patients with severe obesity remains to be established. The aim of this study was to establish the SO prevalence in a large cohort of inpatients with obesity, considering sex, age, BMI, type, and number of concomitant diseases. Methods: Patient data of both genders aged between 18 and 90 years with a body mass index (BMI) of ≥30 kg/m2 underwent hospital evaluation including bioelectrical impedance analysis (BIA) and handgrip strength (HS). QoL scores were obtained by the Psychological General Well-Being Index questionnaire. The study was approved by the institutional Ethic Committee. Results: Among the 3858 patients, 444 (11.51%) exhibited a strength deficit, while 3847 (99.71%) had skeletal muscle mass deficit. The prevalence of SO was then 11.48%, with higher rates in women (12.39%), in individuals aged >70 years (27%), and in those reporting a ‘poor’ QoL (12.6%). No significant difference in SO prevalence was found when stratifying by BMI (30–40 kg/m2 vs. >40 kg/m2, p = 0.1710). In SO patients, osteoarticular diseases (57%), hypertension/heart failure (38%), type 2 diabetes mellitus (34%), and obstructive sleep apnea (32%) were the more frequent comorbidities. Conclusions: The application of ESPEN/EASO-SO criteria in a cohort of inpatients with severe obesity revealed 11.48% SO prevalence, which was associated with age (particularly > 70 years), gender (women), but not BMI, as determinants. Disease staging and QoL screening may improve the identification of SO high-risk patients.
Surgical Risk in Elderly Patients with Meningiomas in Japan
Authors: Ikawa Fusao , Michihata Nobuaki , Oya Soichi , Yasunaga Hideo , Horie Nobutaka
Published: May 2024

Background/Objective: No guidelines indicate surgical risk factors for the elderly because of the lack of data from general neurosurgeons. To better understand the management of surgical risk in elderly patients with meningiomas based on a national database in Japan. Methods: Results of surgically treated meningiomas were explored in 8138 patients registered in the Diagnosis Procedure Combination database in Japan during 2010–2015. Age (<65, 65–74, and ≥75 years), sex, Barthel index (BI), medical history, tumor location, oral medication prescriptions on admission, and stroke complications were evaluated. Multivariate logistic regression analysis identified risk factors for stroke complications, BI deterioration between admission and discharge, and in-hospital mortality. Results: Advanced age was the prominent risk factor for BI deterioration (odds ratio: 3.26; 95% confidence interval: 2.69–3.95) but not for in-hospital mortality. Lower BI (60–80) on admission increased the risk of BI deterioration in all age groups; however, BI < 60 demonstrated a significant inverse risk (0.47; 0.32–0.69) in the elderly (≥75 years). Location (falx, parasagittal, and deep) and anticoagulants were not significant risk factors for BI deterioration in patients aged ≥ 75 years, despite being significant risk factors in patients aged <65 and/or 65–74 years. Conclusions: Although advanced age could lead to postoperative functional decline at discharge, it was not sufficiently significant enough to be associated with in-hospital mortality. Because of the possibility of recovery even in elderly patients with severe disabilities, appropriate surgical selection and optimal management may lead to favorable functional outcomes in elderly patients with meningiomas.
Novel Techniques, Biomarkers and Molecular Targets to Address Cardiometabolic Diseases
Authors: Di Fiore Valerio , Cappelli Federica , Del Punta Lavinia , De Biase Nicolò , Armenia Silvia , Maremmani Davide , Lomonaco Tommaso , Biagini Denise , Lenzi Alessio , Mazzola Matteo , Tricò Domenico , Masi Stefano , Mengozzi Alessandro , Pugliese Nicola Riccardo
Published: May 2024

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs’ increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular–arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs. Similarly, epigenetic changes involving noncoding RNAs, chromatin modulation, and cellular senescence could represent both novel biomarkers and targets for CMDs. Despite the promising data available, significant challenges remain in translating basic research findings into clinical practice, highlighting the need for further investigation into the complex pathophysiology underlying CMDs.
High Prevalence of the Lung Ultrasound Interstitial Syndrome in Systemic Sclerosis Patients with Normal HRCT and Lung Function—A Pilot Study
Authors: Mercier Camille , Thoreau Benjamin , Flament Thomas , Legué Sylvie , Pearson Arthur , Jobard Stephanie , Marchand-Adam Sylvain , Plantier Laurent , Diot Elisabeth
Published: May 2024

Objective: High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT). Methods: Thirty SSc patients with normal HRCT, FVC > 80% predicted and DLCO > 70% predicted were included. Echocardiography and PFT including impulse oscillometry and cardiopulmonary exercise testing were performed. Lung ultrasound was analyzed by two blinded operators. Patients were classified into two groups, according to the presence or absence of ultrasound interstitial syndrome, defined as the sum of B-lines in all thoracic areas ≥10 and/or pleural line thickness >3 mm on at least one thoracic area and/or a pleural line irregularity score >16%. Results: Ultrasound interstitial syndrome was present in 12 patients (40%). Inter-reader agreement for the diagnosis of ultrasound interstitial syndrome defined by the Kappa coefficient was 0.93 (95%CI 0.79–1.00). Patients with ultrasound interstitial syndrome were younger (37 years vs. 53 years, p = 0.009), more often had pitting scars (n = 7/12 vs. 3/18, p = 0.045) and had lower FVC (102 vs. 110% pred, p = 0.009), TLC (114 vs. 122% pred, p = 0.042) and low-frequency respiratory system reactance (Xrs5 Z-score 0.16 vs. 1.02, p = 0.018), while pulmonary gas exchange was similar. Conclusions: Ultrasound interstitial syndrome was detected in 12/30 SSc patients with normal HRCT and PFT. Patients with ultrasound interstitial syndrome had differences in lung function consistent with reduced respiratory compliance, suggesting minimal and/or early suspected SSc-ILD.
Expandable Cages for Lumbar Interbody Fusion: A Narrative Review
Authors: Lee Soo-Bin , Yoon Jonghun , Park Sung-Jun , Chae Dong-Sik
Published: May 2024

Lumbar fusion surgery for treating degenerative spinal diseases has undergone significant advancements in recent years. In addition to posterior instrumentation, anterior interbody fusion techniques have been developed along with various cages for interbody fusion. Recently, expandable cages capable of altering height, lordotic angle, and footprint within the disc space have garnered significant attention. In this manuscript, we review the current status, clinical outcomes, and future prospects of expandable cages for lumbar interbody fusion based on the existing literature. Expandable cages are suitable for minimally invasive spinal surgeries. Small-sized cages can be inserted and subsequently expanded to a larger size within the disc space. While expandable cages generally demonstrate superior clinical outcomes compared to static cages, some studies have suggested comparable or even poorer outcomes with expandable cages than static cages. Careful interpretation through additional long-term follow-ups is required to assess the utility of expandable cages. If these shortcomings are addressed and the advantages are further developed, expandable cages could become suitable surgical instruments for minimally invasive spinal surgeries.
Transcervical Fibroid Ablation (TFA): Update on Pregnancy Outcomes
Authors: Hansen-Lindner Leslie , Schmid-Lossberg Juliette , Toub David
Published: May 2024

Background/Objectives: Transcervical fibroid ablation (TFA) is an incisionless method to treat symptomatic uterine fibroids. While safety regarding future pregnancy remains to be established, TFA does not preclude the possibility of pregnancy, and a previous 36-patient case series of post-TFA pregnancies reported normal outcomes. That prior series did not include postmarket cases in the United States, as the Sonata® System was initially cleared and used in Europe. This is a substantive update of known pregnancies with the Sonata System since June 2011, and includes pregnancies in Europe, Mexico, and the US. Methods: TFA was carried out under both clinical trial and postmarket use to treat symptomatic uterine fibroids. All post-TFA pregnancies reported by physicians with their patient’s consent were included. Results: 89 pregnancies and 55 deliveries have occurred among 72 women treated with the Sonata System. This includes 8 women who conceived more than once after TFA. Completed pregnancies (n = 62 women) include 19 vaginal deliveries, 35 Cesarean sections, 5 therapeutic abortions, 1 ectopic pregnancy, and 1 delivery by an unknown route. Ten pregnancies are ongoing. Mean birthweight was 3276.7 ± 587.3 g. Ten women experienced 18 first-trimester spontaneous abortions (SAbs), with 10 of the 18 SAbs (55.6%) occurring between two patients with a history of recurrent abortion. The SAb rate was 22.8%, inclusive of these two patients, and 10.1% if they were excluded as outliers. There were no instances of uterine rupture, placenta accreta spectrum, or stillbirth. Conclusions: This case series, the largest to date for any hyperthermic ablation modality, suggests that TFA with the Sonata System could be a feasible, safe treatment option regarding eventual pregnancy in women with symptomatic uterine fibroids.
Correction: Colombatti et al. Systematic Literature Review Shows Gaps in Data on Global Prevalence and Birth Prevalence of Sickle Cell Disease and Sickle Cell Trait: Call for Action to Scale Up and Harmonize Data Collection. J. Clin. Med. 2023, 12, 5538
Authors: Colombatti Raffaella , Hegemann Inga , Medici Morten , Birkegård Camilla
Published: May 2024

In the original publication [...]
Association between Obesity and Atrial Function in Patients with Non-Valvular Atrial Fibrillation: An Echocardiographic Study
Authors: Pucci Martina , Gammaldi Vittoria , Capece Luca Maria , Paoletta Daniele , Iervolino Adelaide , Pontoriero Mariateresa , Iacono Marina , Megaro Pasquale , Esposito Roberta
Published: May 2024

Background: Obesity is a public health problem which prevalence has increased worldwide and is associated with different degrees of hemodynamic alterations and structural cardiac changes. The aim of the study is to investigate the impact of body mass index (BMI) on left atrial function using standard and advanced echocardiography in a population of patients with non-valvular atrial fibrillation (AF). Methods: 395 adult patients suffering from non-valvular AF, divided into three tertiles based on BMI value, carry out a cardiological examination with standard and advanced echocardiography. Results: Peak atrial longitudinal strain (PALS), a measure of left atrial function, is lower in the tertile with highest BMI (14.3 ± 8.2%) compared to both the first (19 ± 11.5%) and the second tertile (17.7 ± 10.6%) in a statistically significant manner (p < 0.002). Furthermore, BMI is significantly associated independent with the PALS by multilinear regression analysis, even after correction of the data for CHA2DS2-VASc score, left ventricular mass index, left ventricular ejection fraction, E/E’ ratio and systolic pulmonary arterial pressure (coefficient standardized β = −0.127, p < 0.02; Cumulative R2 = 0.41, SEE = 0.8%, p < 0.0001). Conclusions: BMI could be considered an additional factor in assessing cardiovascular risk in patients with non-valvular atrial fibrillation, in addition to the well-known CHA2DS2-VASc score.
Advances in Microvascular Reconstruction of the Orbit and Beyond: Considerations and a Checklist for Decision-Making
Authors: Bottini Gian Battista , Joos Veronika , Steiner Christoph , Zeman-Kuhnert Katharina , Gaggl Alexander
Published: May 2024

This paper aims to discuss the microvascular reconstruction of the orbit and adjacent regions and to propose a checklist to aid the reconstructive surgeon in this challenging undertaking. The discussion is based on a literature review that includes 32 retrospective case series, 5 case reports published in the last 34 years in PubMed, and 3 textbook chapters. Additionally, it relies on the senior author’s expertise, described in a case series, and two case reports published elsewhere. Classifications and treatment algorithms on microvascular orbit reconstruction generally disregard patient-related factors. A more holistic approach can be advantageous: patient-related factors, such as age, comorbidities, prognosis, previous interventions, radiotherapy, and the wish for maximal dental rehabilitation and a prosthetic eye, have the same importance as defect-related considerations and can inform the choice of a reconstructive option. In this manuscript, we examine defect- and patient-related factors and new technologies, provide a checklist, and examine future directions. The checklist is intended as a tool to aid in the decision-making process when reconstructing the orbital region with microvascular flaps.
Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients
Authors: Esze Regina , Balkay László , Barna Sándor , Egeresi Lilla Szatmáriné , Emri Miklós , Páll Dénes , Paragh György , Rajnai Liliána , Somodi Sándor , Képes Zita , Garai Ildikó , Káplár Miklós
Published: May 2024

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = −0.27 and −0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.
The Impact of Early Rehabilitation and the Acceptance of the Disease on the Quality of Life of Patients after Hip Arthroplasty: An Observational Study
Authors: Chojnowska Joanna , Lewko Jolanta , Chilińska Joanna , Cybulski Mateusz , Pogroszewska Wioletta , Krajewska-Kułak Elżbieta , Sierżantowicz Regina
Published: May 2024

Background: The early introduction of physiotherapy significantly shortens the time required for a patient to regain full mobility after hip arthroplasty. Obtaining the expected result is determined by cooperation with a physiotherapist and the patient’s involvement in the rehabilitation process. The aim of this study was to assess the quality of life, life satisfaction, and motor ability of patients after hip arthroplasty. Methods: This study included 147 patients who underwent hip arthroplasty at the Orthopedic and Trauma Department. The research material was collected using questionnaires, and the study used the Barthel Index (BI), Harris Hip Score (HHS), Visual Analogue Scale (VAS), Acceptance of Illness Scale (AIS), and Quality of Life Assessment Questionnaire (WHOQOL-BREF). In the studied group of patients, the Excia cementless endoprosthesis was primarily used (69.39%), as well as the Metha Short Hip prosthesis (15.65%), AM hip prosthesis (10.20%), and bipolar hip prosthesis (4.76%). Results: The analyzed group of patients included 95 women (64.63%) and 52 men (35.37%); the average age was 67 years. Six weeks after hip arthroplasty, mild disability occurred in 53.74% of the patients, while the remaining 46.26% had no disability, and 95.24% of the patients achieved a high level of acceptance of the disease and quality of life. Conclusions: Early improvement after hip replacement surgery contributes to eliminating the disability of the hip joint in the following areas: pain sensation, functionality, lack of deformation, and range of motion. Each subsequent stage of treatment increased the level of acceptance of the disease in the study group. The applied surgical treatment increased satisfaction with overall health and quality of life.
The Enhanced Recovery after Surgery Approach in Heart Valve Surgery: A Systematic Review of Clinical Studies
Authors: Malvindi Pietro Giorgio , Bifulco Olimpia , Berretta Paolo , Galeazzi Michele , Alfonsi Jacopo , Cefarelli Mariano , Zingaro Carlo , Zahedi Hossein M. , Munch Christopher , Di Eusanio Marco
Published: May 2024

Background: Enhanced recovery after surgery (ERAS) protocols aim to reduce postoperative complications and promote earlier recovery. Although it is well established in noncardiac surgery fields, the ERAS approach has only recently been adopted in cardiac surgery. The aim of this review is to evaluate the status and implementation of ERAS protocols in patients undergoing heart valve surgery and to summarise associated clinical results. Methods: A literature search for the period January 2015 and January 2024 was performed through online databases. Clinical studies (randomised controlled trials and cohort studies) on patients undergoing heart valve surgical procedures and comparing ERAS and conventional approaches were included. The data extracted covered studies and populations characteristics, early outcomes and the features of each ERAS protocol. Results: There were 14 studies that fulfilled the final search criteria and were ultimately included in the review. Overall, 5142 patients were identified in the 14 studies, with 2501 in ERAS groups and 2641 patients who were representative of control groups. Seven experiences exclusively included patients who underwent heart valve surgery. Twelve out of fourteen protocols involved multiple interventions from the preoperative to postoperative phase, while two studies reported actions limited to intraoperative and postoperative care. We found high heterogeneity among the included protocols regarding key actions targeted for improvement and measured outcomes. All the studies showed that ERAS pathways can be safely adopted in cardiac surgery and in most of the experiences were associated with shorter mechanical ventilation time, reduced postoperative opioid use and reduced ICU and hospital stays. Conclusions: As demonstrated in noncardiac surgery, the adoption of structured ERAS protocols has the potential to improve results in patients undergoing heart valve surgery. Further evidence based on larger populations is needed, including more homogenous pathways and reporting further outcomes in terms of patient satisfaction, recovery and quality of life after surgery.
Comprehensive Review of the Imaging Recommendations for Diagnosis, Staging, and Management of Thyroid Carcinoma
Authors: Chakrabarty Nivedita , Mahajan Abhishek , Basu Sandip , D’Cruz Anil K.
Published: May 2024

Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma.
Advances in Dynamization of Plate Fixation to Promote Natural Bone Healing
Authors: Bottlang Michael , Shetty Sunil S. , Blankenau Connor , Wilk Jennifer , Tsai Stanley , Fitzpatrick Daniel C. , Marsh Lawrence J. , Madey Steven M.
Published: May 2024

The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating.
Effectiveness, Safety and Patients’ Satisfaction of Nabiximols (Sativex®) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study
Authors: Sacco Rosaria , Riccitelli Gianna Carla , Disanto Giulio , Bogousslavsky Julien , Cavelti Ariane , Czell David , Kamm Christian Philipp , Kliesch Uta , Ramseier Simon Peter , Gobbi Claudio , Zecca Chiara
Published: May 2024

Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients’ satisfaction in MS patients treated with nabiximols as monotherapy. Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient. Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45–62); female 70%; median EDSS 6 (IQR 4–6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6–9) and 9/10 (IQR: 7–10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status. Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait).
High-Speed Fluorescence Imaging Corroborates Biological Data on the Influence of Different Nozzle Types on Cell Spray Viability and Formation
Authors: Heuer Miriam , Stiti Mehdi , Eras Volker , Scholz Julia , Ahmed Norus , Berrocal Edouard , Brune Jan C.
Published: May 2024

Treating severe dermal disruptions often presents significant challenges. Recent advancements have explored biological cell sprays as a promising treatment, but their success hinges on efficient cell delivery and complete wound coverage. This requires a good spray distribution with a small droplet size, high particle number, and ample surface coverage. The type of nozzle used with the spray device can impact these parameters. To evaluate the influence of different nozzles on spray characteristics, we compared air-assisted and unassisted nozzles. The unassisted nozzle displayed small particle size, high particle number, good overall coverage, high cell viability, preserved cell metabolic activity, and low cytotoxicity. Air-assisted nozzles did not perform well regarding cell viability and metabolic activity. Flow visualization analysis comparing two different unassisted nozzles using high-speed imaging (100 kHz frame rate) revealed a tulip-shaped spray pattern, indicating optimal spray distribution. High-speed imaging showed differences between the unassisted nozzles. One unassisted nozzle displayed a bi-modal distribution of the droplet diameter while the other unassisted nozzle displayed a mono-modal distribution. These findings demonstrate the critical role of nozzle selection in successful cell delivery. A high-quality, certified nozzle manufactured for human application omits the need for an air-assisted nozzle and provides a simple system to use with similar or better performance characteristics than those of an air-assisted system.