Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis ‐ an umbrella review

alexandrossfakianakis shared this article with you from Inoreader Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis ‐ an umbrella review Via International Endodontic Journal Abstract Background The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. Objectives This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area, and (iii) present recommendations to conduct future clinical studies and systematic reviews. Methods A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) - 2 tool. Two independent reviewers were involved in study selection, data extraction, and appraising the included reviews; disagreements were resolved by a third reviewer. Results The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor – alpha (TNF-α) -308 G>A and interleukin 1-beta (IL-1β) +3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed. Discussion The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G>A and IL-1β +3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution. Conclusions No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prognostic and therapeutic significance of XPO1 in T-cell lymphoma

alexandrossfakianakis shared this article with you from Inoreader Prognostic and therapeutic significance of XPO1 in T-cell lymphoma Via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 27 April 2022 Source: Experimental Cell Research Author(s): Danian Nie, Xiaohui Xiao, Jiaoting Chen, Shuangfeng Xie, Jie Xiao, Wenjuan Yang, Hongyun Liu, Jieyu Wang, Liping Ma, Yumo Du, Kezhi Huang, Yiqing Li View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

KDR genetic predictor of toxicities induced by sorafenib and regorafenib

alexandrossfakianakis shared this article with you from Inoreader <i>KDR</i> genetic predictor of toxicities induced by sorafenib and regorafenib Via The Pharmacogenomics Journal - Issue - nature.com science feeds The Pharmacogenomics Journal, Published online: 28 April 2022; doi:10.1038/s41397-022-00279-3 KDR genetic predictor of toxicities induced by sorafenib and regorafenib View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evidence for Loss of Activity in Low-Spontaneous-Rate Auditory Nerve Fibers of Older Adults

alexandrossfakianakis shared this article with you from Inoreader Evidence for Loss of Activity in Low-Spontaneous-Rate Auditory Nerve Fibers of Older Adults Via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com This study is the first to successfully assess forward-masked recovery functions in both younger and older adults and provides important insights into the structural and functional changes occurring in the AN with increasing age. (Source: JARO - Journal of the Association for Research in Otolaryngology) View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of Selective Carboplatin-Induced Inner Hair Cell Loss on Temporal Integration

alexandrossfakianakis shared this article with you from Inoreader Effect of Selective Carboplatin-Induced Inner Hair Cell Loss on Temporal Integration in Chinchillas Via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractIntegration of acoustic information over time is essential for processing complex stimuli, such as speech, due to its continuous variability along the time domain. In both humans and animals, perception of acoustic stimuli is a function of both stimulus intensity and duration. For brief acoustic stimuli, as duration increases, thresholds decrease by approximately 3  dB for every doubling in duration until stimulus duration reaches 500 ms, a phenomenon known as temporal integration. Although hearing loss and damage to outer hair cells (OHC) have been shown to alter temporal integration in some studies, the role of cochlear inner hair cells (IHC) on temporal i ntegration is unknown. Because IHC transmit nearly all acoustic information to the central auditory system and are believed... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high‐risk first relapse B‐cell precursor acute lymphoblastic leukemia

alexandrossfakianakis shared this article with you from Inoreader Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high‐risk first relapse B‐cell precursor acute lymphoblastic leukemia Via Pediatric Blood & Cancer Abstract Background Blinatumomab, a CD3/CD19 BiTE® (bispecific T cell engager) molecule, was superior to high-risk third course consolidation chemotherapy (HC3) in prolonging event-free survival (EFS) in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (B-ALL). Here, we report results from a post hoc measurable residual disease (MRD) analysis of this phase 3 study (NCT02393859). Procedure Children >28 days and <18 years with high-risk first-relapse B-ALL in cytomorphological complete remission (M1 marrow, <5% blasts) or with M2 marrow (≥5% and <25% blasts) after induction and two cycles of high-risk consolidation chemotherapy (baseline) were enrolled in this trial. Patients received one cycle of blinatumomab (15 μg/m2/day, 4 weeks, continuous intravenous infusion) or HC3. The primary endpoint was EFS. In this post hoc analysis, patients with MRD <10–4 by PCR were grouped as having positive but not quantifiable (pbnq) or undetectable disease. Results A higher proportion of patients with MRD <10–4 had undetectable versus pbnq disease after blinatumomab (day 29) than after HC3 (p = 0.0367). Of the 22 patients with MRD ≥10–4 at baseline who achieved MRD remission after blinatumomab, 20 (91%) achieved MRD <10–4 remission by day 15. Patients treated with blinatumomab had improved EFS and overall survival compared with those treated with HC3 independent of end-of-induction or baseline (end-of-second consolidation) MRD levels. Conclusions Blinatumomab was more efficacious than HC3 regardless of MRD status before treatment. These data support the role of blinatumomab in inducing deep MRD remission, negating the poor prognostic value of MRD. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of SARS‐CoV‐2 Mu variant on vaccine effectiveness: a comparative genomics study at the peak of the third wave

alexandrossfakianakis shared this article with you from Inoreader Impact of SARS‐CoV‐2 Mu variant on vaccine effectiveness: a comparative genomics study at the peak of the third wave in Bogota, Colombia Via Journal of Medical Virology Abstract We assessed the circulation of SARS-CoV-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above possibly associated with specific mutations that confers it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g. Omicron) and their impact on vaccination efforts worldwide. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation of A NEW “All in One” SARS‐CoV‐2 antigen‐detecting rapid diagnostic test AND self‐test: diagnostic performance and usability in child and adult populationS

alexandrossfakianakis shared this article with you from Inoreader Evaluation of A NEW "All in One" SARS‐CoV‐2 antigen‐detecting rapid diagnostic test AND self‐test: diagnostic performance and usability in child and adult populationS Via Journal of Medical Virology Abstract The control of the COVID-19 epidemics has been one global health priorities for the last two years. To that end, more reliable and easy-to-use, regardless of age, diagnostic tests are necessary. Considering that, we evaluated an innovative two-step self-test, the AAZ COVID-VIRO ALL IN®, switching from the classic nasal swab to a nasal sponge. We performed a multicentre study, on 124 adults and children, in a point-of-care setting. Sensitivity, specificity and overall acceptance of the COVID-VIRO ALL IN® self-test compared to RT-PCR on nasopharyngeal samples were of 93.0%, 100% and 97.5%, respectively. We then performed a multicentre, usability study to evaluate the ease of use of COVID-VIRO ALL IN® on 68 laypersons adults. A vast majority of participants correctly executed and interpreted the test. The usability was then specifically investigated on 40 children and teenagers, comparing COVID-VIRO® first generation to the new COVID-VIRO ALL IN®. They all found COVID-VIRO ALL IN® more comfortable and easier to use. For young children, the new self-test seems safer (less risk of trauma, no liquid exposure), and faster than saliva-based RT-PCR. Moreover, the COVID-VIRO ALL IN® can easily be adapted as a multiplex self-test for other respiratory viruses, opening new perspectives of simultaneous, rapid and massive detection of respiratory infections, especially among vulnerable populations like children and elderly people. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials.

alexandrossfakianakis shared this article with you from Inoreader Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials. Via Clinical Infectious Diseases Advance Access Abstract Background Daily dosing of tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), has high efficacy in preventing HIV infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Methods Participant data from TFV-based daily oral and topical active arms of phase III trials (iPrEx, VOICE and Partners PrEP) were pooled (n = 2,950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models (NONMEM). Results Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherenc e (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high risk females (45.8 ng/mL) compared to high risk males (16.1 ng/mL) and to low risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high risk women require full adherence to maintain protective levels. Conclusions Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high risk females need higher levels of plasma TFV to achieve HIV protection compared to males. HIV protection exceeds 90% in all populations if daily adherence is achieved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors Correlating with Survival Following Adjuvant or Definitive Radiosurgery for Large Brain Metastases

alexandrossfakianakis shared this article with you from Inoreader Factors Correlating with Survival Following Adjuvant or Definitive Radiosurgery for Large Brain Metastases Via Neuro-Oncology Advance Access Abstract Background We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4cc) brain metastases (BrM). Methods We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. Results We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P<0.001), BrM quantity [HR 1.13 (1.06-1.22) (P<0.001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P<0.001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P<0.001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P<0.001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P<0.0054)], SRS target volume [HR 1.03 (1.01,1.06) (P<0.0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P<0.015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P=0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P =0.091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. Conclusion SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies

alexandrossfakianakis shared this article with you from Inoreader The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies Via Neuro-Oncology Advance Access Abstract Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically 'cold' tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1 and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG's intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide in the development of immunotherapies that we hope will improve outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

alexandrossfakianakis shared this article with you from Inoreader Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis Via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 27 April 2022; doi:10.1038/s41368-022-00171-7 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.