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Malignant gliomas belong to the most threatening tumor entities and are hallmarked by rapid proliferation, hypervascularization and an invasive growth pattern. The primary obstacle in surgical treatment lies in differentiation between healthy and pathological tissue at the tumor margins, where current visualization methods reach their limits. Here, we report on a novel technique (vascular dual intraoperative visualization approach - vDIVA) enabling visualization of different tumor zones (TZ I-III) on the basis of angiogenic hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence-guided surgery with simultaneous intraoperative ICG fluorescence angiography. This vDIVA technique revealed hypervascularized areas which were further histologically investigated. Neuropathological assessments revealed tissue areas at the resection margins corresponding to TZ II, and postoperative CD34- and Map2 immunostaining confirmed these angiogenic hotspots to be occupied by glioma cells. Hence, the vascular architecture in this transitional zone could be well differentiated from both primary tumor bulk and healthy brain parenchyma. These data demonstrate that ICG fluorescence angiography improves state-of-the-art glioma surgery techniques and facilitates the future characterization of polyclonal attributes of malignant gliomas. [ABSTRACT FROM AUTHOR]

Atomistic molecular dynamics (MD) simulations are a much-used tool for investigating the structure and dynamics of biomembranes with atomic resolution. The validity of the representations obtained is determined by the accuracy and realism of the MD model (force field). Here, we evaluated the proprietary OPLS4 force field of Schrödinger, Inc. against atomic-resolution experimental data, and compared its performance to CHARMM36, one of the best-performing openly available force fields. As a benchmark, we used high-resolution nuclear magnetic resonance (NMR) order parameters for C-H bonds─directly and reliably calculable from MD simulations─measured in phosphatidylcholine (PC) lipid bilayers under varying hydration conditions. Comparisons were made with two dehydration data sets: for saturated (1,2-dimyristoylphosphatidylcholine, DMPC) lipid bilayers from the literature and for unsaturated (1-palmitoyl-2-oleoylphosphatidylcholine, POPC) lipid bilayers measured here. Our findings indicate that OPLS4 reproduces the structure and dehydration response of PC-lipid bilayers fairly well, even slightly outperforming CHARMM36. Both models' main inaccuracies appear in (1) the order parameter magnitudes in the glycerol backbone and unsaturated carbon segments and (2) the qualitatively differing structural response of the PC headgroup to dehydration compared to experiments. In summary, this work underscores the importance of independent validation for (proprietary) force fields and highlights the striking similarities and nuanced differences between OPLS4 and CHARMM36 in describing biomembranes.

Blood-based biomarkers are minimally invasive tools to detect the pathological changes of Alzheimer's Disease (AD). This meta-analysis aims to investigate the use of blood-derived p-tau isoforms (181, 217, 231) to predict conversion from mild cognitive impairment (MCI) to AD dementia (ADD). Studies involving MCI patients with data on blood p-tau isoforms at baseline and clinical diagnosis at follow-up (≥1 year) were included. Twelve studies on p-tau 181 (4340 MCI, conversion rate 20.6%), four on p-tau 217 (913 MCI, conversion rate 33.4%), and one on p-tau 231 (135 MCI, conversion rate 33%) were included. For p-tau 181, the pooled area under the receiver operating characteristic curve (AUC) was 0.73 (95% CI = 0.68-0.78), and for p-tau 217 was 0.85 (95% CI = 0.75-0.91). Plasma levels of p-tau 181 had good discriminatory power to identify MCI patients who will convert to ADD. Although only four studies on p-tau 217 have been included in the meta-analysis, in the last year the predictive power of p-tau 217 is emerging as superior to that of other isoforms. However, given the high heterogeneity detected in the p-tau 217 studies included in this meta-analysis, additional supportive evidence is needed. Insufficient results were available for p-tau 231. These findings support the prognostic utility of p-tau 181 and p-tau 217 measured in blood to predict progression to ADD in MCI and encourage its future implementation in clinical practice.

The erythrocyte sedimentation rate (ESR) is a widely used diagnostic test, influenced by all physiological and pathological conditions that can bias blood rheology by interfering factors. This study aimed to evaluate the performance of the CUBE 30 touch ESR analyzer in samples with preanalytical variables, as lipemia, hemolysis, and icterus or in presence of fibrinogen., Moreover we focused to define the maximum time limits to ensure a reliable ESR measure. Accuracy, intra-run and inter-run precision, and stability studies were performed. Moreover, hemolytic, jaundiced, lipemic samples and fibrinogen sensitivity were analyzed for interference study. Statistical analyses were performed. CUBE 30 touch and Westergren method comparison showed no statistical differences (Spearman Coefficient, R 2 =0,95). In the intra-run precision, the CV% mean obtained on samples with normal ESR level was 8,9%; with middle ESR level was 5,9% and with high ESR level the CV% was 4,3%. Inter-run precision test showed CV% of for single samples and overall samples in the range (12,3% for normal level and 4,8% for abnormal level). The samples stored at 4 °C showed good stability up to 3 h from collecting time. ESR samples showing lipemia, hemolysis or jaundice showed good correlations with the gold standard method (R 2 0,901, 0,940, 0,911; p  < 0,0001), however, Westergren tests were more sensitive than CUBE 30 touch to fibrinogen additions. The high comparability with the Westergren method, both in normal and interfering samples, and the good precision, support the usefulness of CUBE 30 touch in the clinical routine laboratory.

Introduction: Mild traumatic brain injury (mTBI) represents a major public health concern and affects millions of people worldwide every year. Diagnosis mainly relies on clinical criteria and computed tomography (CT) scans. GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin carboxyl-terminal hydrolase-L1) have been recently studied as potential biomarkers of mTBI. This study retrospectively evaluated the possible use of these combined biomarkers as negative predictors for excluding brain injuries in patients with suspected mTBI in the emergency department., Methods: Adult patients (n = 130) enrolled at Tor Vergata University Hospital (Rome, Italy), consecutively registered at the triage of the emergency department between October 2022 and January 2023, with non-penetrating TBI and Glasgow Coma Scale (GCS) score of 13-15, were considered. All eligible patients underwent intracranial CT scans and blood tests, within 12 h after trauma, for GFAP and UCH-L1 serum concentrations., Results: Intracranial CT detected injuries in only seven patients (5%); GFAP and UCH-L1 tested positive in 96 patients and negative in 34 patients (74% vs. 26%). Combined biomarkers had a sensitivity equal to 1.00 (95% CI 0.64-1.00) and a negative predictive value (NPV) of 1.00 (0.99-1.00) in mTBI diagnosis with a negative CT., Conclusions: Combined laboratory tests for GFAP and UCH-L1 biomarkers might play a potential clinical role in avoiding unnecessary head CT scans after mTBI in emergency departments., (© 2024. The Author(s).)

Background: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored., Aim: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens., Method: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels., Results: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05)., Conclusion: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We would like to declare that all Mindray kits used in this paper were provided as in-kind support for GKN lab., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives:  This in vitro study aimed to investigate the impact of bicarbonate air-abrasive powders and ultrasonic scaling with stainless steel tips on the micro- and nanotopography and roughness of three different implant-abutment junction titanium surfaces., Materials and Methods:  Three types of sterile and decontaminated titanium surfaces (RS, UTM, XA) were used for analysis. Nine disks per surface type were subjected to micro- and nanotopography analysis, scanning electron microscopy (SEM), roughness analysis, and fibroblast cultivation. Ultrasonic debridement and air polishing were performed on the surfaces. Human dermal fibroblasts were cultured on the surfaces for 5 days., Statistical Analysis:  Data analysis adhered to ISO 25178 standards for surface texture assessment. SEM micrographs were used to reconstruct areas for extracting roughness parameters. Excel and Mex 6.0 software were utilized for quantitative and stereoscopic analysis., Results:  The study found varying effects on surface roughness posttreatment. RS Disco samples exhibited higher surface roughness compared with UTM and XA samples, both in average and nanoscale roughness. Decontamination led to increased surface roughness for all samples, particularly RS Disco. Fibroblast growth tests revealed enhanced cell network formation on decontaminated discs, possibly due to increased nanoscale roughness or the presence of bicarbonate salts., Conclusion:  The study underscores the complex interplay between surface topography, microbial biofilm, and treatment efficacy in peri-implant disease management. While smoother surfaces may resist biofilm accumulation, increased nanoscale roughness postdecontamination can enhance fibroblast attachment and soft tissue integration. This dichotomy highlights the need for tailored treatment protocols that consider material-specific factors, emphasizing that successful implant therapy should balance microbial control with conducive surface characteristics for long-term osseointegration and soft tissue stability., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Erythrocyte Sedimentation Rate (ESR) is an easy test used to diagnose and monitor inflammatory and infectious diseases. The aim of this study was the evaluation of the performance of three ESR automated analyzers, VES-MATIC 5, CUBE 30 TOUCH, and MINI-CUBE, involving four Italian polyclinics in Rome, Siena, Como, and Arezzo, as well as inter-site variability assessment to detect possible device-dependent and operator-dependent influences., Methods: Accuracy analysis was carried out by analyzing the same samples with all three instruments and comparing them with the Westergren method. Precision was assessed with quality control material through intra-run and inter-run precision. Repeatability was estimated by reanalyzing fresh blood samples belonging to three ESR ranges (low, intermediate, and high) six times., Results: The results showed a strong correlation (Spearman coefficients R 2 ) between the manual method and VES-MATIC 5 (0.978), CUBE 30 TOUCH (0.981), and MINI-CUBE (0.974). The accuracy of all clinics was excellent, with coefficients of variation (CVs) of less than 10% for all instruments. Repeatability confirmed an excellent level for all ESR ranges, with CVs below 10%., Conclusions: The study proved that all three automated instruments offer optimal performance for accuracy and precision and are suitable for both large and small facilities without influences of the laboratory environment.

Introduction: Prostate cancer (PCa) is one of the prevailing forms of cancer among men. At present, multiparametric MRI is the imaging method for localizing tumors and staging cancer. Radiomics plays a key role and hold potential for PCa detection, reducing the need for unnecessary biopsies, characterizing tumor aggression, and overseeing PCa recurrence post-treatment., Methods: Furthermore, the integration of radiomics data with clinical and histopathological data can further enhance the understanding and management of PCa and decrease unnecessary transfers to specialized care for expensive and intrusive biopsies. Therefore, the aim of this study is to develop a risk model score to automatically detect PCa patients by integrating non-invasive diagnostic parameters (radiomics and Prostate-Specific Antigen levels) along with patient's age., Results: The proposed approach was evaluated using a dataset of 189 PCa patients who underwent bi-parametric MRI from two centers. Elastic-Net Regularized Generalized Linear Model achieved 91% AUC to automatically detect PCa patients. The model risk score was also used to assess doubt cases of PCa at biopsy and then compared to bi-parametric PI-RADS v2., Discussion: This study explored the relative utility of a well-developed risk model by combining radiomics, Prostate-Specific Antigen levels and age for objective and accurate PCa risk stratification and supporting the process of making clinical decisions during follow up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Castaldo, Brancato, Cavaliere, Pecchia, Illiano, Costantini, Ragozzino, Salvatore, Nicolai and Franzese.)

Background: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273., Methods: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers., Results: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization., Conclusion: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

TNF receptor-associated factor 2 (TRAF2) is involved in different cellular processes including signal transduction and transcription regulation. We here provide evidence of a direct interaction between the TRAF domain of TRAF2 and the monosialotetrahexosylganglioside (GM1). Previously, we showed that the TRAF domain occurs mainly in a trimeric form in solution, but it can also exist as a stable monomer when in the nanomolar concentration range. Here, we report that the quaternary structure of the TRAF domain is also affected by pH changes, since a weakly acidic pH (5.5) favors the dissociation of the trimeric TRAF domain into stable monomers, as previously observed at neutral pH (7.6) with the diluted protein. The TRAF domain-GM1 binding was similar at pH 5.5 and 7.6, suggesting that GM1 interacts with both the trimeric and monomeric forms of the protein. However, only the monomeric protein appeared to cause membrane deformation and inward vesiculation in GM1-containing giant unilamellar vesicles (GUVs). The formation of complexes between GM1 and TRAF2, or its TRAF domain, was also observed in cultured human leukemic HAP1 cells expressing either the truncated TRAF domain or the endogenous full length TRAF2. The GM1-protein complexes were observed after treatment with tunicamycin and were more concentrated in cells undergoing apoptosis, a condition which is known to cause cytoplasm acidification. These findings open the avenue for future studies aimed at deciphering the physiopathological relevance of the TRAF domain-GM1 interaction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131 I (RAI) therapy and post-therapy 131 I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18 F-fluoro-D-glucose (FDG) or 18 F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18 F-NaF PET/CT and 18 F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS., Methods: Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18 F-NaF PET/CT and 18 F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance., Results: At post-therapy 131 I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18 F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18 F-NaF PET/CT, the 19 bone lesions detected at 18 F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding., Conclusions: In patients with DTC, 18 F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131 I WBS and 18 F-FDG PET/CT.

Background: In solid organ transplant (SOT) recipients, the humoral response following COVID-19 vaccination is reduced, as a result of their immunosuppressed treatment. In this study, we investigated antibody concentrations after booster vaccinations until the fifth dose, the latter by monovalent or bivalent BA1 or BA4/5 vaccines. In addition, we evaluated the efficacy of vaccination by recording breakthrough infections, hospitalizations, and deaths., Method: This prospective cohort study included 438 SOT recipients (>18 years) vaccinated with mRNA vaccines against COVID-19 from January 2021 until March 2023. Blood samples were drawn before and after each vaccination and tested for SARS-CoV-2 spike RBD IgG antibodies with the lowest and highest cut-off at 7.1 and 5,680 BAU/mL, respectively. Vaccine information, breakthrough infections, and hospitalizations were collected from the medical records., Results: Most participants received BNT162b2 and 61.4% received five vaccine doses. The response proportion in SOT recipients increased from 86.7% after the fourth dose to 93.0% following the fifth dose. Antibody concentration decreased with 142.7 BAU/mL between the third and fourth dose (median 132 days, Quartile 1: 123, Quartile 3: 148) and 234.3 BAU/mL between the fourth and fifth (median 250 days, Quartile 1: 241, Quartile 3: 262) dose among those without breakthrough infection (p=0.34). When comparing the Omicron BA.1 or Omicron BA.4/BA.5 adapted vaccines, no significant differences in antibody concentration were found, but 20.0% of SOT recipients receiving a monovalent fifth vaccine dose had a breakthrough infection compared to 4.0% and 7.9% among those who received BA.1 and BA.4/BA.5 adapted vaccines, respectively (p=0.04). Since January 2021, 240 (54.8%) participants had a breakthrough infection, and 22 were hospitalized, but no deaths were observed., Conclusions: The fifth COVID-19 vaccine dose raised antibody response to 93.0% of the study population. Additional booster doses, as well as bivalent vaccines, led to higher levels of antibody concentration in SOT recipients. We found a lower incidence of breakthrough infections among SOT recipients after receiving a bivalent vaccine as a fifth dose compared to those receiving a monovalent dose. Antibody concentrations did not wane when the time between doses was prolonged from four to eight months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Christophorou, Nilsson, Petersen, Lindvig, Davidsen, Abazi, Poulsen, Pedersen, Justesen, Johansen, Bistrup, Madsen and Johansen.)

(1) Background: The erythrocyte sedimentation rate (ESR) is widely diffused in hematology laboratories to monitor inflammatory statuses, response to therapies (such as antibiotics), and oncologic diseases. However, ESR is not a specific diagnostic marker but needs to be contextualized and compared with clinical and other laboratory findings. This study aimed to investigate the performance of two automated instruments, namely the DIESSE CUBE 30 TOUCH (DIESSE, Siena, Italy) and the Alifax Test 1 (Alifax Srl, Polverara, Italy), in comparison with the gold standard, the Westergren method, in lymphoproliferative and myeloproliferative patients. (2) Methods: 97 EDTA samples were selected from the hematology department of Roma Tor Vergata Hospital and analyzed. Statistical analysis was applied. (3) A good correlation between CUBE 30 TOUCH and the gold standard was observed in the overall sample (R 2 = 0.90), as well as in patients with lymphoproliferative diseases (R 2 = 0.90) and myeloproliferative diseases (R 2 = 0.90). The correlation between Test 1 and the gold standard was observed in the overall sample (R 2 = 0.68), as well as in patients with lymphoproliferative diseases (R 2 = 0.79) and myeloproliferative diseases (R 2 = 0.53). (4) Conclusions: The CUBE 30 TOUCH appears to be a more trustworthy tool for evaluating ESR in these pathologies.

Background: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations., Aim: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months., Method: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis., Results: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups., Conclusion: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19., Competing Interests: Declaration of Competing Interest There are no known conflicts of interest associated with this publication., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Erythrocyte sedimentation rate (ESR) indirectly measures blood fibrinogen, and it is altered by all those pathological conditions that modify the aggregation of red blood cells. The international guidelines by the International Council for Standardization in Hematology (ICSH) define the Westergren method as the gold standard for ESR, although it is completely operator-dependent, time-consuming, and requires a patient's blood consumption. Therefore, the validation of new ESR analyzers is needed. The aim of this study is the validation of a new automated ESR analyzer, MINI-CUBE (DIESSE, Diagnostica Senese, Italy)., Methods: The samples (n = 270) were collected at the University Hospital of the University of Rome Tor Vergata. A comparison between the automated instrument and the gold standard was performed. Statistical analyses were processed by MedCalc software., Results: The comparison analysis performed on the overall samples reported a good agreement, showing a Spearman rank correlation coefficient of 0.94 (P < 0.001), compared to the Westergren test. The Bland-Altman analysis showed a mean bias of 1.5 (maximum (max.):19.6; minimum (min.): -16.6). Inter-run (level 1 coefficient of variation (CV): 4.9%; level 2 CV: 0.8%), intra-run (level 1 CV: 21.1%; level 2 CV: 3.2%), and inter-instrument (level 1 CV: 27.1%; level 2 CV: 5.6%) precision were also assessed. The hematocrit value did not interfere with the analysis: Spearman rank correlation coefficient of 0.929 (P < 0.001); mean bias of 1.3 (max.:18.3; min.: -15.6)., Conclusions: Overall results from MINI-CUBE asserted a good correlation rate with the gold standard, and it could be considered an accurate, and objective alternative for the Westergren test., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as a potential competing interest: DIESSE Diagnostica Senese S.p.A. Societa Benefit provided the MINI-PET® ESR instrument. Dr. Daniela Diamanti is a DIESSE Diagnostica Senese S.p.A. Societa Benefit member. None of the other authors has any other financial or personal relationship that could inappropriately influence or bias the content of the paper., (Copyright 2023, Tomassetti et al.)

The use of vaccines has allowed the containment of coronavirus disease 2019 (COVID-19) at a global level. The present work aims to add data on vaccination by evaluating the level of neutralizing antibodies in individuals who have received a three-vaccination series. For this purpose, we ran a surveillance program directed at measuring the level of IgG Abs against the Receptor Binding Domain (RBD) and surrogate virus neutralizing Ab (sVNT) anti-SARS-CoV-2 in the serum of individuals undergoing vaccination. This study was performed on employees from the University of Rome Tor Vergata and healthcare workers from the University Hospital who received the Vaxzevria vaccine (n = 56) and Comirnaty vaccine (n = 113), respectively. After the second dose, an increase in both RBD and sVNT Ab values was registered. In individuals who received the Comirnaty vaccine, the antibody titer was about one order of magnitude higher after 6 months from the first dose. All participants in this study received the Comirnaty vaccine as the third dose, which boosted the antibody response. Five months after the third dose, nearly one year from the first injection, the antibody level was >1000 BAU/mL (binding antibody units/mL). According to the values reported in the literature conferring protection against SARS-CoV-2 infection, our data indicate that individuals undergoing three vaccine doses present a low risk of infection., Competing Interests: The authors declare no conflict of interest.

Saliva is a very complex fluid and it is essential to maintain several physiological processes and functions, including oral health, taste, digestion and immunological defenses. Saliva composition and the oral microbiome can be influenced by several factors, like diet and smoking habits, and their alteration can represent an important access point for pathogens and, thus, for systemic illness onset. In this review, we explore the potentiality of saliva as a new tool for the early detection of some pathological conditions, such as oral diseases, chronic degenerative non-communicable diseases, among these chronic kidney disease (CKD). We also examined the possible correlation between oral and systemic diseases and oral and gut microbiota dysbiosis. In particular, we deeply analyzed the relationship between oral diseases and CKD. In this context, some salivary parameters can represent a new device to detect either oral or systemic pathologies. Moreover, the positive modulation of oral and gut microbiota induced by prebiotics, postbiotics, or symbiotics could represent a new possible adjuvant therapy in the clinical management of oral diseases and CKD.

Infectious diseases such as HIV and HBV are a global concern for their impact in terms of public health and costs for national health services. A central role in contrasting the spread of the infections is represented by timely diagnosis. The speed of detection depends on several factors including the type of test used. Antibody response to hepatitis B surface antigens (anti-HBs) is an important serological marker used for HBV-infection detection. The aim of this study was to compare the performance of the Abbott system and of the new analyser Mindray 1200i in the detection of HBV- and HIV-infections. Clinical serum samples were collected from patients randomly selected from PTV University Hospital of University of Rome "Tor Vergata" and tested for HBV and HIV antibodies. Samples were evaluated by Mindray Cl 1200i CLIA screening tests for HBV and HIV and the results were compared with the Abbott Architect analytical system, the routine instrument of the hospital clinical biochemistry laboratory. Precision study, linearity, and carryover were performed on the results obtained. The agreement between the results of the Abbott and Mindray CLIA ranged from 99% to 100% and the discrepancy rate from 0% to 1%. The measurements demonstrated that the Mindray CL-1200i platform offers high-level performance with accurate and consistent test results and could represent a valuable tool if implemented in routine analysis.

The World Health Organization has recently identified three categories of pathogens, namely: critical, high, and medium priority, according to the need for new antibiotics. Critical priority pathogens include carbapenem-resistant microorganism (CPO) such as A. baumannii and P. aeruginosa , K. pneumoniae , and Enterobacter spp., whereas vancomycin-resistant E. faecium (VRE) , methicillin and vancomycin-resistant S. aureus (MRSA) are in the high priority list. We compared the trend of antimicrobial resistants (AMRs) in clinical isolates, divided by year and bacteria spp. , of samples obtained from nosocomial and community patients. Patient records were collected, including age, sex, site of infection, isolated organisms, and drug susceptibility patterns. From 2019 to 2022, a total of 113,635 bacterial isolates were tested, of which 11,901 resulted in antimicrobial resistants. An increase in the prevalence of several antibiotics resistant bacteria was observed. Specifically, the percentage of CPO cases increased from 2.62% to 4.56%, the percentage of MRSA increased from 1.84% to 2.81%, and the percentage of VRE increased from 0.58% to 2.21%. AMRs trend resulted in increases in CPO and MRSA for both community and nosocomial. Our work aims to highlight the necessity of preventive and control measures to be adopted in order to reduce the spread of multidrug-resistant pathogens.

Pooling radiomic features coming from different centers in a statistical framework is challenging due to the variability in scanner models, acquisition protocols, and reconstruction settings. To remove technical variability, commonly called batch effects, different statistical harmonization strategies have been widely used in genomics but less considered in radiomics. The aim of this work was to develop a framework of analysis to facilitate the harmonization of multicenter radiomic features extracted from prostate T2-weighted magnetic resonance imaging (MRI) and to improve the power of radiomics for prostate cancer (PCa) management in order to develop robust non-invasive biomarkers translating into clinical practice. To remove technical variability and correct for batch effects, we investigated four different statistical methods (ComBat, SVA, Arsynseq, and mixed effect). The proposed approaches were evaluated using a dataset of 210 prostate cancer (PCa) patients from two centers. The impacts of the different statistical approaches were evaluated by principal component analysis and classification methods (LogitBoost, random forest, K-nearest neighbors, and decision tree). The ComBat method outperformed all other methods by achieving 70% accuracy and 78% AUC with the random forest method to automatically classify patients affected by PCa. The proposed statistical framework enabled us to define and develop a standardized pipeline of analysis to harmonize multicenter T2W radiomic features, yielding great promise to support PCa clinical practice.

Background: Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI)., Aim: Finding significant features associated with PD-MCI through a machine learning approach., Patients and Methods: Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model., Results: Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2., Conclusions: This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI., Competing Interests: Unrelated to this study, PB received consultancies as a member of the advisory board for Zambon, Lundbeck, UCB, Chiesi, Abbvie, and Acorda; RE received consultancies from Zambon and honoraria from TEVA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amboni, Ricciardi, Adamo, Nicolai, Volzone, Erro, Cuoco, Cesarelli, Basso, D'Addio, Salvatore, Pace and Barone.)