Serum Neurofilament Light Protein as a Marker for Diffuse Axonal Injury: Results from a Case Series Study

Diffuse axonal injury (DAI) is an important cause of morbidity in patients with traumatic brain injury (TBI). There is currently no simple and reliable technique for early identification of patients with DAI, or to prognosticate long-term outcome in this patient group. In the present study, we examined acute serum concentrations of neurofilament light (NFL) in nine patients with severe TBI and DAI using a novel ultrasensitive single molecule array (Simoa) assay. The relationships between the NFL concentrations and MRI in the acute stage as well as clinical outcome and magnetic resonance diffusion tensor imaging (MR-DTI) parameters at 12 months were analyzed. We found that the mean NFL concentrations among the patients displayed a 30-fold increase compared with controls, and that NFL completely discriminated between the patients and controls. We also found a relationship between serum NFL and MR-DTI parameters, with higher NFL concentrations in patients with higher trace (R2 = 0.79) and lower fractional anisotropy (FA) (R 2 = 0.83). These results suggest that serum NFL may be a valuable blood biomarker for TBI, reflecting the severity of DAI

Stable isotope records for the last 10 000 years from Okshola cave (Fauske, northern Norway) and regional comparisons

The sensitivity of terrestrial environments to past changes in heat transport is expected to be manifested in Holocene climate proxy records on millennial to seasonal timescales. Stalagmite formation in the Okshola cave near Fauske (northern Norway) began at about 10.4 ka, soon after the valley was deglaciated. Past monitoring of the cave and surface has revealed stable modern conditions with uniform drip rates, relative humidity and temperature. Stable isotope records from two stalagmites provide time-series spanning from c. 10 380 yr to AD 1997; a banded, multi-coloured stalagmite (Oks82) was formed between 10 380 yr and 5050 yr, whereas a pristine, white stalagmite (FM3) covers the period from ~7500 yr to the present. The stable oxygen isotope (δ<sup>18</sup>O<sub>c</sub>), stable carbon isotope (δ<sup>13</sup>C<sub>c</sub>), and growth rate records are interpreted as showing i) a negative correlation between cave/surface temperature and δ<sup>18</sup>O<sub>c</sub>, ii) a positive correlation between wetness and δ<sup>13</sup>C<sub>c</sub>, and iii) a positive correlation between temperature and growth rate. Following this, the data from Okshola show that the Holocene was characterised by high-variability climate in the early part, low-variability climate in the middle part, and high-variability climate and shifts between two distinct modes in the late part. <br><br> A total of nine Scandinavian stalagmite δ<sup>18</sup>O<sub>c</sub> records of comparable dating precision are now available for parts or most of the Holocene. None of them show a clear Holocene thermal optimum, suggesting that they are influenced by annual mean temperature (cave temperature) rather than seasonal temperature. For the last 1000 years, δ<sup>18</sup>O<sub>c</sub> values display a depletion-enrichment-depletion pattern commonly interpreted as reflecting the conventional view on climate development for the last millennium. Although the δ<sup>18</sup>O<sub>c</sub> records show similar patterns and amplitudes of change, the main challenges for utilising high-latitude stalagmites as palaeoclimate archives are i) the accuracy of the age models, ii) the ambiguity of the proxy signals, and iii) calibration with monitoring data

A Comparison of Deep Learning MOS Predictors for Speech Synthesis Quality

This paper introduces a comparison of deep learning-based techniques for the MOS prediction task of synthesised speech in the Interspeech VoiceMOS challenge. Using the data from the main track of the VoiceMOS challenge we explore both existing predictors and propose new ones. We evaluate two groups of models: NISQA-based models and techniques based on fine-tuning the self-supervised learning (SSL) model wav2vec2_base. Our findings show that a simplified version of NISQA with 40% fewer parameters achieves results close to the original NISQA architecture on both utterance-level and system-level performances. Pre-training NISQA with the NISQA corpus improves utterance-level performance but shows no benefit on the system-level performance. Also, the NISQA-based models perform close to LDNet and MOSANet, 2 out of 3 baselines of the challenge. Fine-tuning wav2vec2_base shows superior performance than the NISQA-based models. We explore the mismatch between natural and synthetic speech and discovered that the performance of the SSL model drops consistently when fine-tuned on natural speech samples. We show that adding CNN features with the SSL model does not improve the baseline performance. Finally, we show that the system type has an impact on the predictions of the non-SSL models.Comment: Submitted to INTERSPEECH 202

Circulating Brain-Injury Markers After Surgery for Craniosynostosis

Objective: Historically, there have been few quantitative methods for effectively evaluating outcomes after surgery for craniosynostosis. In this prospective study, we assessed a novel approach for detecting possible postsurgery brain injury in patients with craniosynostosis. Methods: We included consecutive patients operated on for sagittal (pi-plasty or craniotomy combined with springs) or metopic (frontal remodeling) synostosis at the Craniofacial Unit at Sahlgrenska University Hospital, Gothenburg, Sweden, from January 2019 to September 2020. Plasma concentrations of the brain-injury biomarkers neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau were measured immediately before induction of anesthesia, immediately before and after surgery, and on the first and the third postoperative days using single-molecule array assays. Results: Of the 74 patients included, 44 underwent craniotomy combined with springs for sagittal synostosis, 10 underwent pi-plasty for sagittal synostosis, and 20 underwent frontal remodeling for metopic synostosis. Compared with baseline, GFAP level showed a maximal significant increase at day 1 after frontal remodeling for metopic synostosis and pi-plasty (P = 0.0004 and P = 0.003, respectively). By contrast, craniotomy combined with springs for sagittal synostosis showed no increase in GFAP. For neurofilament light, we found a maximal significant increase at day 3 after surgery for all procedures, with significantly higher levels observed after frontal remodeling and pi-plasty compared with craniotomy combined with springs (P < 0.001). Conclusions: These represent the first results showing significantly increased plasma levels of brain-injury biomarkers after surgery for craniosynostosis. Furthermore, we found that more extensive cranial vault procedures resulted in higher levels of these biomarkers relative to less extensive procedures

Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS

No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations

Background: germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9. Considering the potential implications of the finding, we undertook the task of validating the initial results in this study. Methods: allele-specific expression was measured using the highly quantitative and robust technique of pyrosequencing. Individuals from two different populations were studied, one Caucasian-dominated and the other of Ashkenazi Jewish descent, with different sources of non-tumoral genetic material in each. Results: our results showed no statistically significant differences in the degree of ASE between CRC patients and controls, considering ASE as either a quantitative or a binary trait. Using defined cutoff values to categorise ASE, 1.0% of blood lymphocytes from informative Israeli cases (total n=96) were ASE positive (median 1.00; range 0.76-1.31) and 2.2% of informative matched controls (total n=90) were ASE positive (median 1.00; range 0.76-1.87). Likewise, normal mucosae from Spanish patients (median 1.03; range: 0.68-1.43; n=75) did not show significant differences in the degree of ASE when compared with the Israeli patients or controls. Conclusions: taken together, these results suggest that ASE of TGFBR1 does not confer an increased risk of CRC

Fluid Antenna Array Enhanced Over-the-Air Computation

Over-the-air computation (AirComp) has emerged as a promising technology for fast wireless data aggregation by harnessing the superposition property of wireless multiple-access channels. This paper investigates a fluid antenna (FA) array-enhanced AirComp system, employing the new degrees of freedom introduced by antenna movements. Specifically, we jointly optimize the transceiver design and antenna position vector (APV) to minimize the mean squared error (MSE) between target and estimated function values. To tackle the resulting highly non-convex problem, we adopt an alternating optimization technique to decompose it into three subproblems. These subproblems are then iteratively solved until convergence, leading to a locally optimal solution. Numerical results show that FA arrays with the proposed transceiver and APV design significantly outperform the traditional fixed-position antenna arrays in terms of MSE.Horizon Europe COVER project under grant number 101086228; UKRI grant EP/Y028031/1. The work of M. Di Renzo is supported in part by the Horizon Europe projects COVER-101086228, UNITE-101129618, and INSTINCT- 101139161, and the ANR projects NF-PERSEUS 22-PEFT-004 and PASSIONATE CHIST-ERA-22-WAI-04 (ANR-23-CHR4-0003-01)

A histological and micro-CT investigation in to the effect of NGF and EGF on the periodontal, alveolar bone, root and pulpal healing of replanted molars in a rat model - a pilot study

Background: This study aims to investigate, utilising micro-computed tomography (micro-CT) and histology, whether the topical application of nerve growth factor (NGF) and/or epidermal growth factor (EGF) can enhance periodontal, alveolar bone, root and pulpal tissue regeneration while minimising the risk of pulpal necrosis, root resorption and ankylosis of replanted molars in a rat model. Methods: Twelve four-week-old male Sprague-Dawley rats were divided into four groups: sham, collagen, EGF and NGF. The maxillary right first molar was elevated and replanted with or without a collagen membrane impregnated with either the growth factors EGF or NGF, or a saline solution. Four weeks after replantation, the animals were sacrificed and the posterior maxilla was assessed using histological and micro-CT analysis. The maxillary left first molar served as the control for the corresponding right first molar. Results: Micro-CT analysis revealed a tendency for all replanted molars to have reduced root length, root volume, alveolar bone height and inter-radicular alveolar bone volume. It appears that the use of the collagen membrane had a negative effect while no positive effect was noted with the incorporation of EGF or NGF. Histologically, the incorporation of the collagen membrane was found to negatively affect pulpal, root, periodontal and alveolar bone healing with pulpal inflammation and hard tissue formation, extensive root resorption and alveolar bone fragmentation. The incorporation of EGF and NGF did not improve root, periodontal or alveolar bone healing. However, EGF was found to improve pulp vascularisation while NGF improved pulpal architecture and cell organisation, although not to the level of the control group.Conclusions: Results indicate a possible benefit on pulpal vascularisation and pulpal cell organisation following the incorporation of EGF and NGF, respectively, into the alveolar socket of replanted molars in the rat model. No potential benefit of EGF and NGF was detected in periodontal or root healing, while the use of a collagen membrane carrier was found to have a negative effect on the healing response