SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease.

Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aß deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aß deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.

Fe and Cu Double-Doped Co3O4 Nanorod with Abundant Oxygen Vacancies: A High-Rate Electrocatalyst for Tandem Electroreduction of Nitrate to Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is an attractive green alternative to the conventional Haber-Bosch method for the synthesis of NH3. However, this reaction is a tandem process that involves multiple steps of electrons and protons, posing a significant challenge to the efficient synthesis of NH3. Herein, we report a high-rate NO3RR electrocatalyst of Fe and Cu double-doped Co3O4 nanorod (Fe1/Cu2-Co3O4) with abundant oxygen vacancies, where the Cu preferentially catalyzes the rapid conversion of NO3- to NO2- and the oxygen vacancy in the Co3O4 substrate can accelerate NO2- reduction to NH3. In addition, the introduction of Fe can efficiently capture atomic H* that promotes the dynamics of NO2- to NH3, improving Faradaic efficiency of the produced NH3. Controlled experimental results show that the optimal electrocatalyst of Fe1/Cu2-Co3O4 exhibits good performance with high conversion (93.39%), Faradaic efficiency (98.15%), and ammonia selectivity (98.19%), which is significantly better than other Co-based materials. This work provides guidance for the rational design of high-performance NO3RR catalysts.

A hybrid approach of random forest and random parameters logit model of injury severity modeling of vulnerable road users involved crashes.

Vulnerable road users (VRUs) involved crashes are a major road safety concern due to the high likelihood of fatal and severe injury. The use of data-driven methods and heterogeneity models separately have limitations in crash data analysis. This study develops a hybrid approach of Random Forest based SHAP algorithm (RF-SHAP) and random parameters logit modeling framework to explore significant factors and identify the underlying interaction effects on injury severity of VRUs-involved crashes in Shenyang (China) from 2015 to 2017. The results show that the hybrid approach can uncover more underlying causality, which not only quantifies the impact of individual factors on injury severity, but also finds the interaction effects between the factors with random parameters and fixed parameters. Seven factors are found to have significant effect on crash injury severity. Two factors, including primary roads and rural areas produce random parameters. The interaction effects reveal interesting combination features. For example, even though rural areas and primary roads increase the likelihood of fatal crash occurrence individually, the interaction effect of the two factors decreases the likelihood of being fatal. The findings form the foundation for developing safety countermeasures targeted at specific crash groups for reducing fatalities in future crashes.

A hybrid clustering and random forest model to analyse vulnerable road user to motor vehicle (VRU-MV) crashes.

The main goal of this study is to investigate the unobserved heterogeneity in VRU-MV crash data and to determine the relatively important contributing factors of injury severity. For this end, a latent class analysis (LCA) coupled with random parameters logit model (LCA-RPL) is developed to segment the VRU-MV crashes into relatively homogeneous clusters and to explore the differences among clusters. The random-forest-based SHapley Additive exPlanation (RF-SHAP) approach is used to explore the relative importance of the contributing factors for injury severity in each cluster. The results show that, vulnerable group (VG), intersection or not (ION) and road type (RT) clearly distinguish the crash clusters. Moto-vehicle type and functional zone have significant impact on the injury severity among all clusters. Several variables (e.g. ION, crash type [CT], season and RT) demonstrate a significant effect in a specific sub-cluster model. Results of this study provide specific and insightful countermeasures that target the contributing factors in each cluster for mitigating VRU-MV crash injury severity.

Characteristics of large vestibular aqueduct syndrome in wideband acoustic immittance.

Objective: To describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results. Methods: Subjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups. Results: The LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p < 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p < 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343-1,124 Hz was significantly different between the two groups (p < 0.001), and 343-1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group. Conclusion: Large vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.

Surgical treatment of pulsatile tinnitus related to the sigmoid sinus.

Objective: Tinnitus-a common clinical symptom-can be categorized into pulsatile tinnitus (PT) and non-PT. Among these, PT is usually associated with sigmoid sinus symptoms, such as sigmoid sinus wall defect or diverticulum, for which various surgical treatments are available. We have discussed the clinical efficacy of surgery for sigmoid sinus-associated PT via the transmastoid approach in this study. Methods: We conducted a retrospective review of 4 patients who underwent surgery for sigmoid sinus-associated PT via the transmastoid approach at Nanjing Drum Tower Hospital from January to December 2020. Of these, 2 patients had sigmoid sinus wall defect and 2 had sigmoid sinus diverticulum. Post-operative tinnitus grading and surgical efficacy were determined. Results: After surgery, PT dissolved in 3 patients, while tinnitus significantly decreased in 1 patient. During the follow-up period of 12-18 months, none of the 4 patients showed complications related to increased intracranial pressure or venous sinus thrombosis, and tinnitus symptoms disappeared in 3 patients without recurrence, although 1 patient occasionally developed tinnitus. Postoperative thin-slice CTA of the temporal bone indicated that the sigmoid sinus bone wall defect or diverticulum was completely repaired with a thick soft tissue coverage. Conclusion: Surgical repair of sigmoid sinus-associated PT via the transmastoid approach deserves clinical promotion as it exhibited better efficiency while being relatively less invasive.

Can mental imagery boost the effect of the positive cognitive bias modification of interpretation (CBM-I) on interpretation bias and memory bias?

BACKGROUND AND OBJECTIVES: Cognitive bias modification of interpretation (CBM-I) has been widely used and yielded mixed results. This experiment explored the unique role of mental imagery in positive CBM-I. METHODS: 60 participants (M = 23.13, SD = 1.04) were randomly assigned to a imagery-based positive CBM-I group (imagery group) and a conventional verbal-based positive CBM-I group (control group). The imagery group received additional practice in generating mental imagery and were instructed to fully focus on the imagery during the formal training. The dependent variables included interpretation bias (probe latencies and similarity ratings for recognition task), memory bias, and intrusive memory. RESULTS: (1) For the positive probe scenario, the reaction time of the two groups was shorter in the posterior five blocks than the anterior five blocks. However, the difference in latency between pre- and post- training for the imagery group was larger than that of the control group; (2) For the recognition task, the positive target statement score was significantly higher, while the negative one was significantly lower for the imagery group than that of the control group (3) The imagery group (vs. control); showed more beneficial effects on memory bias. LIMITATIONS: The limitations consisted of the difference in time of the manipulation between the two groups, the richness of the imagery operationalization, generalizability, and the lack of pre-manipulation of interpretation bias assessments. CONCLUSIONS: The imagery-based CBM-I led to more positive interpretation biases, less negative interpretations, and more positive memory biases, indicating that mental imagery can boost the effect of the positive CBM-I.

Mechanical Thrombectomy for M2 Segment Occlusion in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The safety and benefit of mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) patients with M2 segment middle cerebral artery occlusions remain uncertain. OBJECTIVE: To investigate the benefit of mechanical thrombectomy for M2 occlusion compared with M1 occlusion in patients with AIS. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from inception to April 2021 to identify relevant articles. The main results comprised 90-day functional independence (modified Rankin Score from 0-2), successful recanalization (thrombectomy in cerebral infarction [TICI] 2b/3), mortality, and rates of symptomatic intracerebral hemorrhage after using modern thrombectomy devices. Odds ratios (ORs) were generated for binary variants. ReviewManager 5.3 software was used. RESULTS: Ultimately, a total of 14 trials were included, with 3454 participants enrolled. MT for M2 occlusion had a higher rate of 3-month functional independence than M1 occlusion, but the difference was nonsignificant (OR: 1.19, 95% confidence interval [CI]: 0.98 to 1.46). The TICI2b/3 scores (OR: 0.71, 95% CI: 0.58-0.88) in M2 occlusion were remarkably lower than those in M1. The mortality and symptomatic intracerebral hemorrhage rates were comparable between the 2 groups. When comparing M2 and M1 occlusions, we found that there was no significant difference between stent retriever and aspiration in the modified Rankin Score (0-2) after AIS, but aspiration exerted an eminently higher recanalization rate with regard to TICI2b/3 (OR: 0.77, 95% CI: 0.61-0.96). CONCLUSIONS: Compared with M1 occlusion, patients with M2 occlusion treated by MT demonstrated similar clinical outcomes in this study. Moreover, there was no difference between stent retriever and aspiration in treating M2 occlusion in terms of functional independence at 90 days. However, aspiration exerted a conspicuously higher recanalization rate in M2 occlusion than in M1 occlusion.

Influence factors on injury severity of bicycle-motor vehicle crashes: A two-stage comparative analysis of urban and suburban areas in Beijing.

OBJECTIVE: More attention should be given to bicycle-motor vehicle (BMV) crashes, as cyclists are at a higher risk of suffering injuries than motor vehicle users in a crash. This study aims to explore the factors influencing the injury severity of bicycle-motor vehicle (BMV) crashes in Beijing (China) and discusses the commonalities and differences between the urban and suburban areas. METHODS: Information regarding 1,136 crashes between bicycles and motor vehicles were collected using police reported data from 2014 to 2015. A two-stage approach integrating random parameters logit (RP-logit) model and two-step clustering (TSC) algorithm was proposed to investigate the significant influence factors and their combination characteristics. Specifically, the RP-logit model was first used to identify the significant influence factors of urban and suburban areas, and then the TSC algorithm was applied to reveal the combination characteristics of significant influence factors for the fatal crashes. RESULTS: Five factors were found to be statistically significant and had random effects on the injury severity in urban areas, i.e., type of motor vehicle, motor vehicle license ownership, type of bicycle, signal control mode and lighting condition; and seven factors were found to be statistically significant on the injury severity in suburban areas, i.e., type of motor vehicle, motor vehicle license ownership, physical isolation facility, signal control mode, weather, visibility and lighting condition. Based on TSC, the combination of significant factors showed different characteristics for fatal crashes in urban and suburban areas, in which two types of the scene including five factors should be concerned in urban areas while one type of scene containing four factors in suburban areas. CONCLUSIONS: The results suggest that different influence factors and individual heterogeneity exist in the RP-logit model for injury severity analysis of BMV crashes in urban and suburban areas. It shows that in urban areas, heavy truck, light truck and bus significantly increase the likelihood of fatal injury than that of suburban areas. These findings can provide valuable reference information for BMV crashes response, such as heavy truck restriction, to facilitate regional safety measures for urban and suburban areas.

Snow albedo reductions induced by the internal/external mixing of black carbon and mineral dust, and different snow grain shapes across northern China.

Previous studies have indicated that black carbon (BC) potentially induces snow albedo reductions across northern China. However, the effects of other light-absorbing particles (LAPs, e.g., mineral dust, MD), snow grain shape, or BC-snow mixing state on snow albedo have been largely ignored. Here we evaluate the BC- and MD-induced snow albedo reductions and radiative forcings (RFs) using an updated Snow, Ice, and Aerosol Radiation radiative transfer model, considering all of the potential factors that can be derived from the field observations across northern China. The results highlight that the LAP-induced albedo reductions for nonspherical snow grains are 2%-30% less than those for spherical grains. Furthermore, BC-snow internal mixing can significantly enhance albedo reduction by a factor of 1.42-1.48 relative to external mixing, with snow grain radius ranging from 100 to 1000 µm. The mean regional BC + MD-induced snow albedo reductions are amplified by the increase of snow grain radius, ranging from 0.012 to 0.123 for fresh snow to 0.016-0.227 for old snow. Finally, we discuss the relative contributions of BC and MD to the albedo reductions and RFs, highlighting the dominant role of BC in reducing snow albedo across northern China.