The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess ...the immunogenicity of a third-dose vaccine in HTx recipients.
This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14-28 days after the third dose. Titres above 50 U/ml were interpreted positive.
We Included 42 HTx recipients at a median age of 65 years interquartile range (IQR) 58-70. At baseline, the median of 27 days (IQR 13-42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4-130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7-6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre.
Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.
The rate of skip metastasis to neck level IV in patients with clinically node-negative neck (cN0) oral cavity squamous cell carcinoma (OCSCC) remains controversial.
To provide a high level of ...evidence using a meta-analysis on the rate of skip metastasis to level IV in this subset of patients.
The Embase, PubMed, and Google Scholar databases were searched for articles published during the period of January 1, 1970, through December 31, 2017, using the following key terms: neck dissection, N0 neck, squamous cell carcinoma, skip metastasis, radical neck dissection, lymph node management, neck metastasis, oral cavity cancer, and tongue cancer. Some terms were also used in combination, and the reference section of each article was searched for additional potentially relevant publications. Data were analyzed from January 8 through 11, 2018.
Inclusion criteria were all cohorts, including from any randomized clinical trial, case-control study, case study, and case report; studies of patients with the histopathologic diagnosis of OCSCC; and studies that differentiated data between skip metastasis and sequential metastasis to neck level IV. Of the 115 articles retrieved from the literature, 11 retrospective studies and 2 prospective randomized clinical trials (n = 1359 patients) were included.
Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Fixed-effects model and 95% CIs were estimated, and data of included studies were pooled using a fixed-effects model.
Overall proportion of neck involvement and the rate of level IV skip metastasis. Subgroup analysis for primary site and tumor staging.
The rate of level IV involvement in patients with cN0 ranged between 0% and 11.40% with a fixed-effects model of 2.53% (95% CI, 1.64%-3.55%). The rate of skip metastasis ranged from 0% to 5.50% with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%). The rate of level IV skip metastasis did not increase significantly in cases that involved neck levels I through III. Tumor staging and primary site tumor did not significantly affect the rate of skip metastasis.
This meta-analysis showed very low rates of skip metastasis to neck level IV in patients diagnosed with cN0 OCSCC. Encountering an allegedly positive lymph node during neck dissection does not portend high rates of level IV involvement. Supraomohyoid neck dissection is therefore adequate for this subset of patients.
This is the fourth part of a study presenting a miniature, combustion-type gas sensor (dubbed GMOS) based on a novel thermal sensor (dubbed TMOS). The TMOS is a micromachined CMOS-SOI transistor, ...which acts as the sensing element and is integrated with a catalytic reaction plate, where ignition of the gas takes place. The GMOS measures the temperature change due to a combustion exothermic reaction. The controlling parameters of the sensor are the ignition temperature applied to the catalytic layer and the increased temperature of the hotplate due to the released power of the combustion reaction. The solid-state device applies electrical parameters, which are related to the thermal parameters. The heating is applied by Joule heating with a resistor underneath the catalytic layer while the signal is monitored by the change in voltage of the TMOS sensor. Voltage, like temperature, is an intensive parameter, and one always measures changes in such parameters relative to a reference point. The reference point for both parameters (temperature and voltage) is the blind sensor, without any catalytic layer and hence where no reaction takes place. The present paper focuses on the study of the effect of humidity upon performance. In real life, the sensors are exposed to environmental parameters, where humidity plays a significant role. Humidity is high in storage rooms of fruits and vegetables, in refrigerators, in silos, in fields as well as in homes and cars. This study is significant and innovative since it extends our understanding of the performance of the GMOS, as well as pellistor sensors in general, in the presence of humidity. The three main challenges in simulating the performance are (i) how to define the operating temperature based on the input parameters of the heater voltage in the presence of humidity; (ii) how to measure the dynamics of the temperature increase during cyclic operation at a given duty cycle; and (iii) how to model the correlation between the operating temperature and the sensing response in the presence of humidity. Due to the complexity of the 3D analysis of packaged GMOS, and the many aspects of humidity simultanoesuly affecting performane, advanced simulation software is applied, incorporating computational fluid dynamics (CFD). The simulation and experimental data of this study show that the GMOS sensor can operate in the presence of high humidity.
Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at ...over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through local genotype and, quite surprisingly, found that genetic factors explained an overwhelming majority of the variation in DNAm levels at other, previously identified, environmentally-associated CpGs. These results indicate that race-associated blood DNAm patterns in particular, and blood DNAm levels in general, are primarily driven by genetic factors, and are not as sensitive to environmental exposures as previously suggested, at least during the first 7 years of life.
Exclusive enteral nutrition EEN and corticosteroids CS induce similar rates of remission in mild to moderate paediatric Crohn's disease CD, but differ with regard to mucosal healing. Our goal was to ...evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes.
We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications fibrostenotic disease, penetrating disease, and active perianal disease and growth were recorded throughout the study. A propensity score analysis was performed.
A total of 147 children mean age 12.9 ± 3.2 years, treated by EEN n = 60 or CS n = 87 were included. New complications developed in 13.7% of CS 12/87 versus 11.6% of EEN 7/60, p = 0.29. Remission was achieved in 41/87 47% in CS and 38/60 63% EEN, p = 0.036. Median time to relapse did not differ 14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28. Mean height Z scores decreased from Week 0 to Week 78 with CS -0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01, but not with EEN -0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56. In a propensity score analysis, EEN was superior to CS for inducing remission p = 0.05 and trended to superiority for height Z score p = 0.055.
Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD.
Purpose
The endoscopic endonasal approach is increasingly being used for resection and reconstruction of anterior skull base lesions. The vascularized nasoseptal flap (NSF) has become the workhorse ...for reconstruction of anterior skull base defects, resulting in a significant decrease in the incidence of cerebrospinal fluid (CSF) leak. This study presents a single center’s experience with NSFs and reports associated complications.
Methods
Patients who underwent endoscopic skull base defect repair with a NSF between 2008 and 2014 were retrospectively evaluated. Complications reviewed were divided into major and minor. Major complications included new-onset and continuing CSF leak and meningitis. Minor complications included long-standing crust formation, synechia, epistaxis, septal perforation, sinusitis and anosmia.
Results
Of the 77 patients included in the study, 47 (61%) underwent trans-sphenoidal surgery for pituitary lesions during which CSF leak was observed. The other 30 patients underwent reconstructive surgeries for post-traumatic CSF leaks or extirpation of lesions involving the anterior skull base. A high-flow intra-operative CSF leak was observed in 25 patients (25/77, 32%). The median follow-up was 16 months (range 3–81 months). 9 patients had major complications and 27 patients had minor complications. Only high-flow intra-operative CSF leak correlated with major complications (
p
= 0.012).
Conclusion
NSF is an extremely effective tool for skull base reconstruction. While it is associated with a low rate of major complications, minor complications are frequent and require local treatment, although they tend to resolve in the late postoperative period.
Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat ...on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI).
In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory.
Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms.
Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.
We have isolated a cDNA encoding a novel human intracytoplasmic tyrosine kinase, termed RAFTK (for a related adhesion focal
tyrosine kinase). In addition, we have cloned and characterized the murine ...homolog of the human RAFTK cDNA. Comparison of the deduced amino acid sequences of human RAFTK and murine Raftk cDNAs revealed 95% homology, indicating that RAFTK is highly conserved between these species. The RAFTK cDNA clone, encoding a polypeptide of 1009 amino acids, has closest homology (48% identity, 65% similarity) to the focal
adhesion kinase (pp125 ). Comparison of the deduced amino acid sequences also indicates that RAFTK, like pp125 , lacks a transmembrane region, myristylation sites, and SH2 and SH3 domains. In addition, like pp125 , RAFTK contains a kinase domain flanked by large N-terminal (426 residues) and C-terminal (331 residues) domains, and the
C-terminal region contains a predicted proline-rich stretch of residues. In fetal tissues, RAFTK expression was abundant in
brain, and low levels were observed in lung and liver. In adult tissues, it was less restricted, indicating that RAFTK expression
is developmentally up-regulated. Expression of RAFTK was also observed in human CD34 marrow cells, primary bone marrow megakaryocytes, platelets, and various areas of brain. The human RAFTK gene was assigned to human chromosome 8 using genomic DNAs from human/rodent somatic cell hybrid lines. The mouse Raftk gene was mapped to chromosome 14, closely linked to gonadotropin-releasing hormone. Using specific antibodies for RAFTK,
a 123-kDa protein from the human megakaryocytic CMK cell line was immunoprecipitated. Treatment of the megakaryocytic CMK cells
with thrombin caused a rapid induction of tyrosine phosphorylation of RAFTK protein. The structural features of RAFTK suggest
that it is a member of the focal adhesion kinase gene family and may participate in signal transduction in human megakaryocytes
and brain as well as in other cell types.
This work presents an innovative ultrasonic-assisted process for the fast infiltration of solventless epoxy into carbon nanotube (CNT) nanopaper (NP) (50 μm thick thin film) to fabricate prepregs and ...composites. The effect of process parameters including: ultrasonic time (infiltration time), ultrasonic amplitude, pressure, and mold temperature on the resin impregnation quality and composite mechanical properties were evaluated. Nanopapers made of multi wall carbon nanotube (MWNT) or single wall carbon nanotube (SWNT) were used in this work. Homogeneous resin impregnation was achieved in the MWNT NP/epoxy composite with 30.5 wt. % MWNT loading. For coating applications, the MWNT NP/epoxy composite showed 167% improvement in sand erosion resistance compared to glass fiber/epoxy composite. NPs with different MWNT wt. % and SWNT wt. % were fabricated. Although non-uniform resin impregnation was observed in SWNT NP/epoxy composites, there was still 142% improvement in tensile strength compared to pure epoxy due to the rigid SWNT NP structure. The EMI shielding of SWNT NP reached 57 dB, which was higher than commercial carbon fiber preform (51 dB). The CNT NP/epoxy composites offer multi-functional properties, and demonstrate promising coating applications in wind energy, automotive and sporting goods industries.
Real-world healthcare data sharing is instrumental in constructing broader-based and larger clinical datasets that may improve clinical decision-making research and outcomes. Stakeholders are ...frequently reluctant to share their data without guaranteed patient privacy, proper protection of their datasets, and control over the usage of their data. Fully homomorphic encryption (FHE) is a cryptographic capability that can address these issues by enabling computation on encrypted data without intermediate decryptions, so the analytics results are obtained without revealing the raw data. This work presents a toolset for collaborative privacy-preserving analysis of oncological data using multiparty FHE. Our toolset supports survival analysis, logistic regression training, and several common descriptive statistics. We demonstrate using oncological datasets that the toolset achieves high accuracy and practical performance, which scales well to larger datasets. As part of this work, we propose a cryptographic protocol for interactive bootstrapping in multiparty FHE, which is of independent interest. The toolset we develop is general-purpose and can be applied to other collaborative medical and healthcare application domains.
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