Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

alexandrossfakianakis shared this article with you from Inoreader Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades via Journal of Medical Virology Abstract COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

alexandrossfakianakis shared this article with you from Inoreader Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol via Pediatric Blood & Cancer Abstract The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Automated Creak Differentiates Adductor Laryngeal Dystonia and Muscle Tension Dysphonia

alexandrossfakianakis shared this article with you from Inoreader Automated Creak Differentiates Adductor Laryngeal Dystonia and Muscle Tension Dysphonia via The Laryngoscope Objective The purpose of this study was to determine whether automated estimates of vocal creak would differentiate speakers with adductor laryngeal dystonia (AdLD) from speakers with muscle tension dysphonia (MTD) and speakers without voice disorders. Methods Sixteen speakers with AdLD, sixteen speakers with MTD, and sixteen speakers without voice disorders were recorded in a quiet environment reading aloud a standard paragraph. An open-source creak detector was used to calculate the percentage of creak (% creak) in each of the speaker's six recorded sentences. Results A Kruskal-Wallis one-way analysis of variance revealed a statistically significant effect of group on the % creak with a large effect size. Pairwise Wilcoxon tests revealed a statistically significant difference in % creak between speakers with AdLD and controls as well as between speakers with AdLD and MTD. Receiver operating characteristic curve analyses indicated that % creak differentiated AdLD from both controls and speakers with MTD with high sensitivity and specificity (area under the curve statistics of 0.94 and 0.86, respectively). Conclusion Percentage of creak as calculated by an automated creak detector may be useful as a quantitative indicator of AdLD, demonstrating the potential for use as a screening tool or to aid in a differential diagnosis. Level of Evidence 3 Laryngoscope, 2023 View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices

alexandrossfakianakis shared this article with you from Inoreader Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices via American Journal of Epidemiology - Advance Access Abstract Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation patterns (DNAm)), we report on three different approaches – 1 incorrect and 2 correct – in the epidemiologic literature on treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used the correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%), or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introdu ced by the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias to the null, and we discuss implications for extant research and recommendations for best practices. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups

alexandrossfakianakis shared this article with you from Inoreader Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups via Neuro-Oncology Advance Access Abstract Background The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse. Methods Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated. Results Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering de lineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations. Conclusion These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of r elapse. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Accuracy of implant placement using CAD‐CAM tooth‐supported surgical guides for an auricular prosthesis in vitro

alexandrossfakianakis shared this article with you from Inoreader Accuracy of implant placement using CAD‐CAM tooth‐supported surgical guides for an auricular prosthesis in vitro via Journal of Prosthodontics Abstract Purpose To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal was compared. Materials and methods This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into two groups according to the surgical guide, with 10 bone blocks in each group (with or without the external auditory canal plug (Guide 1 and Guide 2)). Three implant positions (Implants 1, 2, and 3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation which was analyzed by Student's t-test. Results Each group of 10 bone blocks with 30 implant positions were successfully prepared and digitally reproduced as implants. The accuracy of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p<0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p<0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p<0.001), and depth (p<0.001) deviation of Implant 1; apical (p = 0.036) and angular (p<0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the external auditory canal plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid. Conclusion Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an external auditory canal plug was considered to be more precise. This article is protected by copyright. All rights reserved View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study via Clinical Infectious Diseases Advance Access ABSTRACT Background Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron). Methods This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status. Results The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. Conclusions Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Novel Murine Glioblastoma Models That Reflect the Immunotherapy Resistance Profile of Human Disease

alexandrossfakianakis shared this article with you from Inoreader Novel Murine Glioblastoma Models That Reflect the Immunotherapy Resistance Profile of Human Disease via Neuro-Oncology Advance Access Abstract Background The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We therefore developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and underlying mechanisms. Methods The differential responsiveness of QPP lines was assessed in the brain and flank in untreat ed, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on responsiveness of each tumor was measured through whole exome sequencing. The immune microenvironments of sensitive (QPP7) versus resistant (QPP8) lines were compared in the brain using flow cytometry. Drivers of flank sensitivity versus brain resistance were also measured for QPP8. Results QPP lines are syngeneic to C57BL/6J mice and demonstrate varied sensitivities to T cell immune checkpoint blockade ranging from curative responses to complete resistance. Infiltrating tumor immune analysis of QPP8 reveals improved T cell fitness and augmented effector to suppressor ratios when implanted subcutaneously (sensitive), which are absent upon implantation in the brain (resistant). Upregulation of PD-L1 across the myeloid stroma acts to establish this state of immune privilege in the brain. In contrast, QPP7 responds to checkpoint immunotherapy even in the brain likely resulting from its elevated neoa ntigen burden. Conclusions These syngeneic QPP models of glioblastoma demonstrate clinically-relevant profiles of immunotherapeutic sensitivity and potential utility for both mechanistic discovery and evaluation of immune therapies. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

68Ga-PSMA–Avid Intranasal Solitary Fibrous Tumor

alexandrossfakianakis shared this article with you from Inoreader 68Ga-PSMA–Avid Intranasal Solitary Fibrous Tumor via Clinical Nuclear Medicine - Published Ahead-of-Print The utility of molecular imaging in solitary fibrous tumors has not been fully established. We present a rare case of recurrent intranasal solitary fibrous tumor incidentally localized on 68Ga-PSMA PET/CT scan, which turned out to be metabolically inactive on 18F-FDG PET/CT. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme

alexandrossfakianakis shared this article with you from Inoreader Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme via Clinical Nuclear Medicine - Published Ahead-of-Print A 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fi broblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.