A Robust α-l-Fucosidase from Prevotella nigrescens for Glycoengineering Therapeutic Antibodies.

Eliminating the core fucose from the N-glycans of the Fc antibody segment by pathway engineering or enzymatic methods has been shown to enhance the potency of therapeutic antibodies, especially in the context of antibody-dependent cytotoxicity (ADCC). However, there is a significant challenge due to the limited defucosylation efficiency of commercially available α-l-fucosidases. In this study, we report a unique α-l-fucosidase (PnfucA) from the bacterium Prevotella nigrescens that has a low sequence identity compared with all other known α-l-fucosidases and is highly reactive toward a core disaccharide substrate with fucose α(1,3)-, α (1,4)-and α(1,6)-linked to GlcNAc, and is less reactive toward the Fuc-α(1,2)-Gal on the terminal trisaccharide of the oligosaccharide Globo H (Bb3). The kinetic properties of the enzyme, such as its Km and kcat, were determined and the optimized expression of PnfucA gave a yield exceeding 30 mg/L. The recombinant enzyme retained its full activity even after being incubated for 6 h at 37 °C. Moreover, it retained 92 and 87% of its activity after freezing and freeze-drying treatments, respectively, for over 28 days. In a representative glycoengineering of adalimumab (Humira), PnfucA showed remarkable hydrolytic efficiency in cleaving the α(1,6)-linked core fucose from FucGlcNAc on the antibody with a quantitative yield. This enabled the seamless incorporation of biantennary sialylglycans by Endo-S2 D184 M in a one-pot fashion to yield adalimumab in a homogeneous afucosylated glycoform with an improved binding affinity toward Fcγ receptor IIIa.

Chemical Synthesis of Truncated Capsular Oligosaccharide of Serotypes 6C and 6D of Streptococcus pneumoniae with Their Immunological Studies.

Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.

Design and Characterization of a New Formulation for the Delivery of COVID-19-mRNA Vaccine to the Nasal Mucosa.

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies.

Increasing Risk of Dementia Among Patients with Subsequent Epilepsy Within 2 Years Post-Traumatic Brain Injury: A Population-Based Case-Control Study.

Background: Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial. Aim: This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period. Methods: This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression. Results: Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a >3.03 times risk of dementia after correcting for age, sex, and comorbidities. Conclusion: These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.

Visual field asymmetries in visual word form identification.

Visual performance across the visual fields interacts with visual tasks and visual stimuli, and visual resolution decreases as a function of eccentricity, varying at isoeccentric locations. In this study, we investigated the extent of asymmetry and the rate of change in visual acuity threshold for visual word form (VWF) identification at horizontal and vertical azimuths across the fovea, and at eccentricities of 1°, 2°, 4°, 6° and 8° for 10%, 20%, 40%, and 80% contrast levels, to determine whether and how the eccentricities, meridians, and contrasts modulated the VWF identification acuity threshold. The stimuli were 16 traditional Chinese characters of similar legibility. Participants pressed a key to indicate the character presented, either monocularly or binocularly, at one of 21 randomly selected locations. A staircase procedure was used to determine the threshold, and a multiple linear regression model was used to fit the linear cortical magnification factor (CMF). We found that (1) the asymmetry was most pronounced on the vertical and superior azimuths, (2) the asymmetry between the right and left azimuths was not significant, (3) the CMF was significantly smaller on the vertical azimuth than on the horizontal azimuth, (4) the CMF was smaller on the superior vertical azimuth than on the inferior azimuth, and (5) monocular viewing and low contrast enhanced the CMF difference between azimuths. In conclusion, vertical and horizontal azimuths, location of eccentricity, contrast levels of word symbols, and monocular/binocular viewing have different effects on visual field asymmetry and cortical magnification factors.

Body constitutions of traditional Chinese medicine caused a significant effect on irritable bowel syndrome.

BACKGROUND: According to the theory of traditional Chinese medicine (TCM), all types of body constitutions, except for the Gentleness (ie, the control group in our study), have disease susceptibility and affect the disease development process. This study attempted to investigate the relationship between TCM body constitutions and irritable bowel syndrome (IBS). METHODS: This cross-sectional study was based on Taiwan Biobank (TWB) and collected clinical data from 13 941 subjects aged 30 to 70. The results of the study showed that subjects with Yang-deficiency (N = 3161 subjects, odds ratio [OR] = 2.654, 95% CI = 1.740-3.910), Ying-deficiency (N = 3331 subjects, OR = 1.096, 95% CI = 0.627-1.782) or Stasis (N = 2335 subjects, OR = 1.680, 95% CI = 0.654-3.520) were more likely to have IBS. RESULTS: If the subjects with two or more TCM body constitutions: Yang-deficiency + Ying-deficiency (OR = 3.948, 95% CI = 2.742-5.560), Yang-deficiency + Stasis (OR = 2.312, 95% CI = 1.170-4.112), Ying-deficiency + Stasis (OR = 1.851, 95% CI = 0.828-3.567), or Yang-deficiency + Ying-deficiency + Stasis (OR = 3.826, 95% CI = 2.954-4.932) were also prone to IBS. CONCLUSION: These results confirmed the high correlation between TCM body constitutions and IBS. Because the current treatment for IBS is not entirely satisfactory, integrated traditional Chinese and Western medicine might provide patients with an alternative treatment option to alleviate IBS.

Spatial and single-nucleus transcriptomics decoding the molecular landscape and cellular organization of avian optic tectum.

The avian optic tectum (OT) has been studied for its diverse functions, yet a comprehensive molecular landscape at the cellular level has been lacking. In this study, we applied spatial transcriptome sequencing and single-nucleus RNA sequencing (snRNA-seq) to explore the cellular organization and molecular characteristics of the avian OT from two species: Columba livia and Taeniopygia guttata. We identified precise layer structures and provided comprehensive layer-specific signatures of avian OT. Furthermore, we elucidated diverse functions in different layers, with the stratum griseum periventriculare (SGP) potentially playing a key role in advanced functions of OT, like fear response and associative learning. We characterized detailed neuronal subtypes and identified a population of FOXG1+ excitatory neurons, resembling those found in the mouse neocortex, potentially involved in neocortex-related functions and expansion of avian OT. These findings could contribute to our understanding of the architecture of OT, shedding light on visual perception and multifunctional association.

Oral rhabdomyosarcoma, a rare malignant tumor mimicking an endodontic-periodontal lesion in an adult patient: a case report.

BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.

Evolving from Didactic to Dialogic: How to Improve Faculty Development and Support Faculty Developers by Using Action Research.

Problem: Since competency-based medical education has gained widespread acceptance to guide curricular reforms, faculty development has been regarded as an indispensable element to make these programs successful. Faculty developers have striven to design and deliver myriad of programs or workshops to better prepare faculty members for fulfilling their teaching roles. However, how faculty developers can improve workshop delivery by researching their teaching practices remains underexplored. Intervention: Action research aims to understand real world practices and advocates for formulation of doable plans through cycles of investigations, and ultimately contributes to claims of knowledge and a progression toward the goal of practice improvement. This methodology aligns with the aim of this study to understand how I could improve a faculty development workshop by researching my teaching practices. Context: In 2016, we conducted four cycles of action research in the context of mini-Clinical Evaluation Exercise (mini-CEX) workshops within a faculty development program aiming for developing teaching and assessment competence in faculty members. We collected multiple sources of qualitative data for thematic analysis, including my reflective journal, field notes taken by a researcher-observer, and post-workshop written reflection and feedback in portfolio from fourteen workshop attendees aiming to develop faculty teaching and assessment competence. Impact: By doing action research, I scrutinized each step as an opportunity for change, enacted adaptive practice and reflection on my teaching practices, and formulated action plans to transform a workshop design through each cycle. In so doing, my workshop evolved from didactic to dialogic with continuous improvement on enhanced engagement, focused discussion and participant empowerment through a collaborative inquiry into feedback practice. Moreover, these processes of action research also supported my growth as a faculty developer. Lessons Learned: The systematic approach of action research serves as a vehicle to enable faculty developers to investigate individual teaching practices as a self-reflective inquiry, to examine, rectify, and transform processes of program delivery, and ultimately introduce themselves as agents for change and improvement.

The impact of visual function on staircase use performance in glaucoma.

OBJECTIVES: This cross-sectional study aimed to investigate the relationship between visual function and staircase use in glaucoma. METHODS: Overall, 181 patients with glaucoma with a best-corrected visual acuity ≥20/400 were classified into mild to moderate (mean deviation [MD] ≥ -12 dB) and advanced (MD < -12 dB) groups, according to 24-2 VF of the worse eye. Staircase use evaluation included stair descent and ascent time (SDT/SAT) and self-reported stair difficulty. Correlations between staircase use and visual function were analysed, including binocular visual acuity, integrated visual field (IVF), and binocular contrast sensitivity (CS). Linear and logistic regression adjusted by age, sex, and comorbidities inspected the effect of visual parameters on SDT/ SAT and stair difficulty. RESULTS: Visual function best correlated with SDT among staircase use. In mild to moderate glaucoma, area under the log CS function (AULCSF) (ß = -1.648, P = 0.031) was the only visual factor significant for SDT (adjusted R2 = 0.106), whereas AULCSF (ß = -1.641, P = 0.048) and MD of IVFINF0-24 (ß = -0.089, P = 0.013) were associated with SDT in advanced glaucoma (adjusted R2 = 0.589). The AULCSF was the only significant visual parameter related to SAT (ß = -1.125, P = 0.019) and stair difficulty (adjusted odds ratio = 0.003; 95% confidence interval, 0-0.302; P = 0.013). CONCLUSIONS: SDT provides a higher correlation with visual function than self-reported stair difficulty. Patients with impaired CS or inferior IVF defects should be advised on stair safety and referred to low-vision services.

Fluvial flood adaptation using nature-based solutions: A comprehensive and effective assessment of hydro-meteorological risks.

The growing prominence of Nature-based Solutions (NbS) for disaster risk reduction (DRR) has sparked increased interest. This study is motivated by the need to establish a quantifiable and standardized method for assessing the risks mitigated by NbS in engineering applications. The goal is to establish a comprehensive and effective system framework for assessing hydro-meteorological risks related to NbS in engineering applications. The proposed framework considers flood disaster mechanisms, uncertain factors, and ecosystem services, integrating them to comprehensively assess the benefits of NbS. Specifically, 2-D hydraulic analysis and an in-house adaptive Kriging-based reliability analysis are developed and applied to establish flood prevention standards for NbS. Additionally, the InVEST toolkit is utilized to evaluate ecosystem services. To demonstrate the applicability of the framework, the Baoli River Watershed located in Pingtung County of Taiwan is selected as a case study. It is found that NbS can effectively withstand a 25-year return period flood and reduce flooding on agricultural land by 46.03 %. Furthermore, the probability of flooding decreased from 100 % to 27 % for a 20-year return period flood. NbS was found to provide approximately NT$1.20-4.65 million more in total benefit value compared to the engineering governance strategy. The supporting source codes are available at https://github.com/johnthedy/Adaptive-Kriging-Using-PSO-HHs-in-HECRAS3D.git.

Multiple Imputation of Missing Race/Ethnicity Information in the National Assisted Reproductive Technology Surveillance System.

Background: Missing race/ethnicity data are common in many surveillance systems and registries, which may limit complete and accurate assessments of racial and ethnic disparities. Centers for Disease Control and Prevention's National Assisted Reproductive Technology (ART) Surveillance System (NASS) has a congressional mandate to collect data on all ART cycles performed by fertility clinics in the United States and provides valuable information on ART utilization and treatment outcomes. However, race/ethnicity data are missing for many ART cycles in NASS. Materials and Methods: We multiply imputed missing race/ethnicity data using variables from NASS and additional zip code-level race/ethnicity information in U.S. Census data. To evaluate imputed data quality, we generated training data by imposing missing values on known race/ethnicity under missing at random assumption, imputed, and examined the relationship between race/ethnicity and the rate of stillbirth per pregnancy. Results: The distribution of imputed race/ethnicity was comparable to the reported one with the largest difference of 0.53% for non-Hispanic Asian. Our imputation procedure was well calibrated and correctly identified that 89.91% (standard error = 0.18) of known race/ethnicity values on average in training data. Compared to complete-case analysis, using multiply imputed data reduced bias of parameter estimates (the range of bias for stillbirth per pregnancy across race/ethnicity groups is 0.02%-0.18% for imputed data analysis, versus 0.04%-0.66% for complete-case analysis) and yielded narrower confidence intervals. Conclusions: Our results underscore the importance of collecting complete race/ethnicity information for ART surveillance. However, when the missingness exists, multiply imputed race/ethnicity can improve the accuracy and precision of health outcomes estimated across racial/ethnic groups.

Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells.

BACKGROUND: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. RESULTS: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. CONCLUSIONS: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.

The development of cancers research based on mitochondrial heat shock protein 90.

Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.

Low-sugar universal mRNA vaccine against coronavirus variants with deletion of glycosites in the S2 or stem of SARS-CoV-2 spike messenger RNA (mRNA).

Since the outbreak of Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2) in 2019, more than 15 million spike protein sequences have been identified, raising a new challenge for the development of a broadly protective vaccine against the various emerging variants. We found that the virus, like most other human viruses, depends on host-made glycans to shield the conserved epitopes on spike protein from immune response and demonstrated that deletion of the glycan shields exposed highly conserved epitopes and elicited broadly protective immune responses. In this study, we identified 17 conserved epitopes from 14 million spike protein sequences and 11 of the conserved epitopes are in the S2 domain, including the six most conserved epitopes in the stem region. We also demonstrated that deletion of the glycosites in the spike messenger RNA (mRNA) S2 domain or the stem region exposed the highly conserved epitopes and elicited broadly protective immune responses, particularly CD-8+ T cell response against various SARS-CoV-2 variants, and other human coronaviruses including MERS, SARS viruses, and those causing common cold.

The Development of Immunotherapy for the Treatment of Recurrent Glioblastoma.

Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neuro-oncology, and the survival status of patients after relapse usually means rapid deterioration, thus becoming the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulating the body's immune system to recognize and attack cancer cells, which could be used in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma. This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and especially focus on rGBM.

Striving to thrive or striving to survive: Professional identity constructions of medical trainees in clinical assessment activities.

CONTEXT: Assessment plays a key role in competence development and the shaping of future professionals. Despite its presumed positive impacts on learning, unintended consequences of assessment have drawn increasing attention in the literature. Considering professional identities and how these can be dynamically constructed through social interactions, as in assessment contexts, our study sought to understand how assessment influences the construction of professional identities in medical trainees. METHODS: Within social constructionism, we adopted a discursive, narrative approach to investigate the different positions trainees narrate for themselves and their assessors in clinical assessment contexts and the impact of these positions on their constructed identities. We purposively recruited 28 medical trainees (23 students and five postgraduate trainees), who took part in entry, follow-up and exit interviews of this study and submitted longitudinal audio/written diaries across nine-months of their training programs. Thematic framework and positioning analyses (focusing on how characters are linguistically positioned in narratives) were applied using an interdisciplinary teamwork approach. RESULTS: We identified two key narrative plotlines, striving to thrive and striving to survive, across trainees' assessment narratives from 60 interviews and 133 diaries. Elements of growth, development, and improvement were identified as trainees narrated striving to thrive in assessment. Neglect, oppression and perfunctory narratives were elaborated as trainees narrated striving to survive from assessment. Nine main character tropes adopted by trainees with six key assessor character tropes were identified. Bringing these together we present our analysis of two exemplary narratives with elaboration of their wider social implications. CONCLUSION: Adopting a discursive approach enabled us to better understand not only what identities are constructed by trainees in assessment contexts but also how they are constructed in relation to broader medical education discourses. The findings are informative for educators to reflect on, rectify and reconstruct assessment practices for better facilitating trainee identity construction.

Association between short-term air pollution exposure and traumatic intracranial hemorrhage: pilot evidence from Taiwan.

Introduction: The detrimental effects of air pollution on the brain are well established. However, few studies have examined the effect of air pollution on traumatic brain injury (TBI). This pilot study evaluated the association between short-term air pollution exposure and traumatic intracranial hemorrhage (TIH). Methods: Hospital data of patients with TBI following road traffic accidents were retrospectively collected from the electronic medical records at five trauma centers in Taiwan between 1 January and 31 December 2017. TIH was employed as an outcome measure. All road accident locations were geocoded, and air quality data were collected from the nearest monitoring stations. Air pollutants were entered into five multivariable models. A sensitivity analysis was performed on patients who are vulnerable to suffering TBI after road accidents, including motorcyclists, bicyclists, and pedestrians. Results: Among 730 patients with TBI, 327 had TIH. The ages of ≥65 [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.85-5.70], 45-64 (OR, 2.61; 95% CI, 1.64-4.15), and 25-44 (OR, 1.79; 95% CI, 1.13-2.84) years were identified as significant risk factors in the multivariable analysis. In the best-fit multivariable model, exposure to higher concentrations of particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) was associated with an elevated TIH risk (OR, 1.50; 95% CI, 1.17-1.94). The concentration of nitrogen oxides (NOX) did not increase the risk of TIH (OR, 0.45; 95% CI, 0.32-0.61). After categorizing the air pollution concentration according to quartile, the trend tests in the multivariate model showed that the concentrations of PM2.5 and NOX were significant (p = 0.017 and p < 0.001, respectively). There was a negative borderline significant association between temperature and TIH risk (OR, 0.75; 95% CI, 0.56-1.00, p = 0.05). Notably, the single-vehicle crash was a significant risk factor (OR, 2.11; 95% CI, 1.30-3.42) for TIH. Discussion: High PM2.5 concentrations and low temperatures are risk factors for TIH in patients with TBI. High NOX concentrations are associated with a lower TIH risk.