Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species.

Optimization of an autaptic culture system for studying cholinergic synapses in sympathetic ganglia.

An autaptic synapse (or 'autapse') is a functional connection between a neuron and itself, commonly used in studying the molecular mechanisms underlying synaptic transmission and plasticity in central neurons. Most previous studies on autonomic synaptic functions have relied on spontaneous connections among neurons in mass cultures. However, growing evidence supports the utility of microcultures cultivating autaptic neurons for examining cholinergic transmission within sympathetic ganglia. Despite these advancements, standardized protocols for culturing autaptic sympathetic neurons have yet to be established. Drawing on historical literature, this study delineates optimal experimental conditions to efficiently and reliably produce cholinergic synapses in sympathetic neurons within a short time frame. Our research emphasizes five key factors: (i) the generation of uniformly sized microislands of growth permissive substrates; (ii) the addition of nerve growth factor, ciliary neurotrophic factor (CNTF), and serum to the culture medium; (iii) independence from specific serum and neuronal medium types; (iv) the reciprocal roles of CNTF and glial cells; and (v) the promotion of cholinergic synaptogenesis in SCG neurons through indirect glia co-cultures, rather than direct glial feeder layer cultures. In conclusion, glia-free monocultures of SCG neurons are relatively simple to prepare and yield robust and reliable synaptic currents. This makes them an effective model system for straightforwardly addressing fundamental questions about neurogenic mechanisms involved in cholinergic synaptic transmission in autonomic ganglia. Furthermore, autaptic culture experiments could eventually be implemented to investigate the roles of functional neuron-satellite glia units in regulating cholinergic functions under physiological and pathological conditions.

Reliability of brain volume measures of accelerated 3D T1-weighted images with deep learning-based reconstruction.

PURPOSE: The time-intensive nature of acquiring 3D T1-weighted MRI and analyzing brain volumetry limits quantitative evaluation of brain atrophy. We explore the feasibility and reliability of deep learning-based accelerated MRI scans for brain volumetry. METHODS: This retrospective study collected 3D T1-weighted data using 3T from 42 participants for the simulated acceleration dataset and 48 for the validation dataset. The simulated acceleration dataset consists of three sets at different simulated acceleration levels (Simul-Accel) corresponding to level 1 (65% undersampling), 2 (70%), and 3 (75%). These images were then subjected to deep learning-based reconstruction (Simul-Accel-DL). Conventional images (Conv) without acceleration and DL were set as the reference. In the validation dataset, DICOM images were collected from Conv and accelerated scan with DL-based reconstruction (Accel-DL). The image quality of Simul-Accel-DL was evaluated using quantitative error metrics. Volumetric measurements were evaluated using intraclass correlation coefficients (ICCs) and linear regression analysis in both datasets. The volumes were estimated by two software, NeuroQuant and DeepBrain. RESULTS: Simul-Accel-DL across all acceleration levels revealed comparable or better error metrics than Simul-Accel. In the simulated acceleration dataset, ICCs between Conv and Simul-Accel-DL in all ROIs exceeded 0.90 for volumes and 0.77 for normative percentiles at all acceleration levels. In the validation dataset, ICCs for volumes > 0.96, ICCs for normative percentiles > 0.89, and R2 > 0.93 at all ROIs except pallidum demonstrated good agreement in both software. CONCLUSION: DL-based reconstruction achieves clinical feasibility of 3D T1 brain volumetric MRI by up to 75% acceleration relative to full-sampled acquisition.

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Effect of Illite Treatment on Quality Characteristics and Antioxidant Activity of Broccoli (Brassica oleracea L. var. italica) Sprouts.

Microgreens have recently gained popularity owing to their reliable economic and nutritional value. This study aimed to increase the quality of microgreen broccoli via treatment with different concentrations (1%, IPB-1; 3%, IPB-3; 5%, IPB-5; or 7%, IPB-7 w/v) of illite-a natural mineral powder. The results showed that the illite treatments considerably increased the content of mineral elements, such as Ca, P, and K; of vitamin C; and of free amino acids; and also increased the total weight of the broccoli sprouts. The content of sulforaphane, a bioactive compound, also increased by up to 47% with illite treatment, with the highest increase being in the IPB-5 group. However, several of the parameters were lower in the IPB-7 group. Aromatic compounds were categorized by functional groups such as hydrocarbons which numbered 36, 30, 34, 28, and 30 in the control, IPB-1, IPB-3, IPB-5, and IPB-7 groups, respectively. We found 16, 15, 15, 13, and 14 sulfides, including dimethyl sulfide, in the control, IPB-1, IPB-3, IPB-5, and IPB-7 groups, respectively. Additionally, aldehydes, comprising seven compounds, were detected in the IPB-1, IPB-3, IPB-5, and IPB-7 groups. Illite treatment significantly increased the activities of antioxidants such as DPPH and the polyphenol content of the microgreens. These results indicate a potential role for appropriate illite doses in microgreen treatment to address multinutrient deficiencies and to increase the quality of microgreen vegetables.

Assessing eating ability and mealtime behaviors of persons living with dementia: A systematic review of instruments.

This systematic review aimed to describe the characteristics of instruments that assess eating ability and/or mealtime behaviors in persons living with dementia, and evaluate their psychometric properties. Five databases were searched for relevant records between 1/1/1980 and 5/25/2023. Records included instruments assessing eating ability and/or mealtime behaviors of people with dementia. The psychometric quality of the instruments was evaluated using the Psychometric Assessment for Self-report and Observational Tools (PAT). 45 eligible instruments were identified from 115 records. While 38 instruments were scored as having low psychometric quality, 7 had moderate quality. Edinburgh Feeding Evaluation in Dementia (EdFED), Mealtime Difficulty Scale for older adults with Dementia (MDSD), and Dementia Hyperphagic Behavior Scale (DHBS) were scored as having the highest quality (total PAT score = 9). Further refinement of existing instruments and additional psychometric testing in larger, diverse samples will improve pragmatic use in dementia mealtime care research and practice.

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia.

Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca2+ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca2+ entry (SOCE) which is critical for cellular Ca2+ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca2+ stores were depleted in the absence of extracellular Ca2+, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca2+ entry channels. Intracellular Ca2+ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca2+ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.

Classification of white matter lesions and characteristics of small vessel disease markers.

OBJECTIVES: Radiological markers for cerebral small vessel disease (SVD) may have different biological underpinnings in their development. We attempted to categorize SVD burden by integrating white matter signal abnormalities (WMSA) features and secondary presence of lacunes, microbleeds, and enlarged perivascular spaces. METHODS: Data were acquired from 610 older adults (aged > 40 years) who underwent brain magnetic resonance imaging exam as part of a health checkup. The WMSA were classified individually by the number and size of non-contiguous lesions, distribution, and contrast. Age-detrended lacunes, microbleeds, and enlarged perivascular space were quantified to further categorize individuals. Clinical and laboratory values were compared across the individual classes. RESULTS: Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds; class II had large periventricular WMSA and a high burden of lacunes and microbleeds; and class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. Class II was associated with older age, diabetes, and a relatively higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I. CONCLUSION: The heterogeneity of SVD was categorized into three classes with distinct clinical correlates. This categorization will improve our understanding of SVD pathophysiology, risk stratification, and outcome prediction. KEY POINTS: • Classification of white matter signal abnormality (WMSA) features was associated with different characteristic of lacunes, microbleeds, and enlarged perivascular space and clinical variability. • Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds. Class II had large periventricular WMSA and a high burden of lacunes and microbleeds. Class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. • Class II was associated with older age, diabetes, and higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I.

Development and psychometric testing of the dyadic communication observational coding scheme in DEmentia care (DCODE): family dyadic communication in dementia.

OBJECTIVES: Understanding family dyadic communication in dementia is essential to promote the well-being of family caregivers and persons living with dementia. The Dyadic Communication Observational coding scheme in DEmentia care (DCODE) was developed and tested to assess family dyadic communication in dementia. METHODS: The DCODE was developed from a review of literature, expert review, and pretesting. A secondary analysis of the 75 in-home care video observations from 19 family caregiver-care recipient dyads was conducted to test psychometric properties. RESULTS: The DCODE consists of 43 caregiver items and 41 care recipient items. We observed internal consistency, intra-rater reliability, and inter-rater reliability as adequate. Content validity and convergent validity were moderate. Predictive validity was moderate in predicting caregiver burden. The overall psychometric properties demonstrated a moderate quality of the DCODE. CONCLUSIONS: Findings provided the preliminary psychometric evidence of the DCODE as a promising instrument to assess family dyadic communication in dementia. Future testing for concurrent, divergent, and structural validity of the DCODE is needed.

Pathophysiological insight into transient global amnesia from quantitative electroencephalography.

Transient global amnesia (TGA) is recognized as a benign memory disorder, with characteristic clinical and imaging features. However, the pathophysiology of TGA remains elusive. This study aims to elucidate the pathophysiological changes underlying TGA by exploring the brain activities. In total, 215 patients with TGA (age: 61.8 ± 7.8 years; women: 146) with MRI (within 7 days) and EEG studies (within 90 days) were recruited. Quantitative EEG (QEEG) power spectra and network analysis were performed by the artificial intelligence EEG analysis platform (iSyncBrain®). Subgroup analyses were conducted for different clinical groups, based on symptom duration, EEG timing after onset, and cytotoxic lesions on the MRI. Compared with 252 age- and sex-matched subjects (age: 64.5 ± 8.3 years, women: 182), TGA patients showed a global decrease in absolute power in all band waves, a relative decrease in alpha waves, a relative increase in theta waves, and atypical compensation activity. These QEEG changes were observed regardless of having cytotoxic lesions in MRI and they were significant up to 1 week after symptom onset. Network analysis showed that TGA was more activated than normal controls in alpha1 band-waves, exhibiting a compensatory process. TGA results in prolonged and widespread alterations of brain activity and connectivity. QEEG provide insight into pathophysiology of TGA.

Two-year follow-up results of the use of a fecal diverting device as a substitute for a defunctioning stoma.

PURPOSE: Our previously published clinical studies described the short-term outcomes of a newly developed intraluminal fecal diverting device (FDD). FDD was a safe and effective substitute for a defunctioning stoma. However, the long-term efficacy and safety of this device remain unknown. We investigated the long-term outcomes of the use of the FDD as a substitute for a defunctioning stoma. METHODS: We examined the medical records of patients who participated in our two previous FDD clinical studies. The main outcome was the number of patients with bowel continuity for 2 years after undergoing the FDD procedure or defunctioning stoma creation. RESULTS: Between May 2015 and July 2018, 85 patients were screened for inclusion in this study. Of those, 27 patients underwent a defunctioning ileostomy after proctectomy. The remaining 58 underwent the FDD procedure after proctectomy. Seventy-two patients (ileostomy group, n = 22; FDD group, n = 50) with a follow-up duration > 24 months were included in this analysis. The mean duration of fecal diversion was significantly shorter (p < 0.001) in the FDD group (3.1 [1.6-6.1] weeks) than in the ileostomy group (16.7 [10.0-31.6] weeks). However, the rate of permanent stoma creation was not statistically different between the two groups (ileostomy and FDD groups, 13.6% [3/22] and 10.0% [5/50], respectively; p = 0.693). CONCLUSIONS: The FDD procedure is a feasible substitute for a defunctioning stoma after proctectomy. Multicenter large-scaled clinical studies are required to validate our results.

Near-infrared autofluorescence-based parathyroid glands identification in the thyroidectomy or parathyroidectomy: a systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic accuracy of near-infrared autofluorescence-based identification in the identification of parathyroid glands during thyroidectomy or parathyroidectomy. METHODS: The clinical studies were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar. The study protocol was registered on Open Science Framework ( https://osf.io/um8rj/ ). The search period ranged from the date of each database's inception to May 2021. Cohort studies dealing with patients of whom parathyroid glands were detected by near-infrared autofluorescence and confirmed clinically or pathologically during thyroidectomy or parathyroidectomy were included. Editorials, letters, "how-I-do-it" descriptions, other site head and neck tumors, and articles with lack of diagnostic identification data were excluded. True positive, true negative, false positive, and false negative were extracted. The QUDAS ver. 2 was used to evaluate the methodological quality. RESULTS: Seventeen studies with 1198 participants were evaluated in this analysis. Near-infrared autofluorescence-based identification of parathyroid glands showed a diagnostic odds ratio of 228.8759 (95% confidence interval, 134.1099; 390.6063). The area under the summary receiver operating characteristic curve was 0.967. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9693 (0.9491; 0.9816), 0.9248 (0.8885; 0.9499), 0.9517 (0.8981; 0.9778), and 0.9488 (0.9167; 0.9689), respectively. Subgroup analyses were performed to compare two autofluorescence detection methods, because there was high heterogeneity in the outcomes. The diagnostic accuracy was higher in probe-based detection than in image-based detection. CONCLUSIONS: Near-infrared autofluorescence-based identification is valuable for identifying the parathyroid glands of patients during thyroidectomy or parathyroidectomy.

Comparison of treatment effects after total mandibular arch distalization with miniscrews vs ramal plates in patients with Class III malocclusion.

INTRODUCTION: This study aimed to compare treatment effects after total mandibular arch distalization with buccal interradicular miniscrews vs ramal plates in patients with Class III malocclusion. METHODS: The sample consisted of 40 patients with Class III malocclusion; 20 were treated with distalization via buccal miniscrews (age, 25.8 ± 7.9 years), whereas 20 were treated with ramal plates (age, 26.4 ± 6.1 years). Twenty-three linear and angular measurements were analyzed on pretreatment and posttreatment lateral cephalograms. The changes in each group and differences in treatment effects between the 2 groups were evaluated. RESULTS: The mean amount of distalization at the crown and root levels of the mandibular first molars and the amount of distal tipping was 1.8 mm, 0.6 mm, and 5.4° in the buccal miniscrew group vs 3.6 mm, 2.0 mm, and 6.8° in the ramal plate group, respectively. In addition, 2.2° of counterclockwise rotation of the occlusal plane was observed in the buccal miniscrew group after 1.3 mm of molar intrusion (P <0.001). The distal movement of the lower lip was 0.6 mm in the buccal miniscrew group vs 2.3 mm in the ramal plate group. CONCLUSIONS: The buccal miniscrew group showed more molar intrusion and counterclockwise rotation of the occlusal plane than in the ramal plate group. The ramal plate produced more distalization of the mandibular dentition with clockwise rotation of the mandible. Therefore, these results can be useful when selecting the type of temporary skeletal anchorage devices to treat patients with Class III malocclusion, depending on their vertical pattern.

Benefits of Virtual Reality Program and Motor Imagery Training on Balance and Fall Efficacy in Isolated Older Adults: A Randomized Controlled Trial.

Background and Objectives: for isolated older adults, alternative training indoors to maintain balance is essential; however, related studies are lacking. To improve the balance of isolated older adults and reduce their fear of falling, we aimed to examine the balance−keeping effect of a virtual reality (VR) program and motor imagery training (MIT) and propose training that could improve physical activity among older adults. Methods: a total of 34 older adults admitted to a convalescent hospital were assessed. VR (n = 12) and MIT (n = 10) groups completed their assigned intervention in six weeks, whereas the control group (CG) (n = 12) did not. The follow−up was performed after two weeks. Results: in group × time interactions, body center movement area, open and closed eyes balance scores, and fall efficacy were significantly different (p < 0.05). In contrast with the VR group, the MIT group did not show a significant difference in the open or closed eyes balance scores depending on the period. However, there was a significant difference between the MIT group and CG in the open eyes balance score post-test (d = 1.13, 95% confidence interval, 0.40−12.33). Conclusions: we propose VR and MIT as training methods to prevent physical weakness in isolated older adults.

Effect of 9% Hydrofluoric Acid Gel Hot-Etching Surface Treatment on Shear Bond Strength of Resin Cements to Zirconia Ceramics.

Background and Objectives: There is no consensus regarding the surface treatment method for achieving optimal bonding strength between zirconia and resin cements. We evaluated the effect of hot-etching with 9% hydrofluoric acid (HF) gel using the Zirconia Etchant Cloud System on zirconia surfaces and the consequent shear bond strength (SBS) of different resin cements to such surface-treated zirconia ceramics. Materials and Methods: Forty-five zirconia specimens were randomly assigned to surface-treatment groups (n = 15/group): no treatment (control, CT); sandblasting with 110-µm Al2O3 at an air pressure of 1 bar for 10 s (SB); hot-etching with 9% HF gel (HE). Post-treatment, specimens were examined using scanning electron microscopy (SEM) and surface roughness (SR) analysis. After treatment, self-adhesive resin cements (Maxcem Elite, MAZIC Cem, RelyX U200, 3M ESPE: Maplewood, MN, USA) were bonded to zirconia specimens, which were stored in distilled water at 37 °C for 24 h. All specimens were then subjected to SBS testing, using a universal testing machine, until failure. Data were analyzed using one-way analysis of variance and Tukey's post hoc test (α = 0.05). Results: In the SEM images, roughness was greater in SB than in HE specimens. Ra and Rt values were highest in SB, followed by HE, and CT specimens. HE specimens showed significantly higher SBS values than CT or SB specimens (p < 0.05). MAZIC Cem cement, with 10-methacryloyloxydcyl dihydrogen phosphate yielded the highest SBS values. Conclusions: Hot-etching with 9% HF gel in a safe shell formed uniformly small, defined holes on the zirconia surface and achieved significantly higher SBS values than sandblasting (p < 0.05). Zirconia prostheses can be bonded micromechanically with resin cement, without the deterioration of properties due to t-m transformation, using chemical acid etching with the Zirconia Etchant Cloud System.

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer.

BACKGROUND: Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. MATERIALS AND METHODS: We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. RESULTS: Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P = 0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P = 0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. CONCLUSIONS: Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

Therapeutic efficacy of cancer vaccine adjuvanted with nanoemulsion loaded with TLR7/8 agonist in lung cancer model.

Although immune checkpoint inhibitors have significantly improved clinical outcomes in various malignant cancers, only a small proportion of patients reap benefits, likely due to the low number of T cells and high number of immunosuppressive cells in the tumor microenvironment (TME) of patients with advanced disease. We developed a cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) and analyzed its therapeutic effect alone or in combination with immune checkpoint inhibitors, on antitumor immune responses and the reprogramming of suppressive immune cells in the TME. NE (R848) demonstrated robust local and systemic antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, inducing tumor-specific T cell activation and mitigating T cell exhaustion. Combination with anti-PD-1 antibodies showed synergistic effects with respect to therapeutic efficacy and survival rate. Thus, NE (R848)-based cancer vaccines could prevent tumor recurrence and prolong survival by activating antitumor immunity and reprogramming immunosuppression.

Accuracy of intraoral scan images in full arch with orthodontic brackets: a retrospective in vivo study.

OBJECTIVES: The purpose of this retrospective study was to evaluate the accuracy of intraoral scan (IOS) images in the maxillary and mandibular arches with orthodontic brackets. MATERIAL AND METHODS: From digital impressions of 140 patients who underwent orthodontic treatment, consecutive IOS images were selected based on standardized inclusion criteria: Two pre-orthodontic IOS images (IOS1 and IOS2) of permanent dentition with fully erupted second molars and IOS images obtained immediately after orthodontic bracket bonding (IOSb). Superimpositions were performed to evaluate the reproducibility of repeated IOS images. Accuracy of IOSb images was analyzed by comparing the average surface errors between IOS1c and IOS2c images, which were IOS images cut based on the same region of the interest as between IOS1 and IOSb images. RESULTS: A total of 84 IOS images was analyzed. The average surface errors between IOS1 and IOS2 images were 57 ± 8 µm and 59 ± 14 µm in the maxillary and mandibular arch, respectively, and their reliability was almost perfect. The average errors between IOSb and IOS1c images exhibited an increase, which measured 97 ± 28 µm in the maxillary arch and 95 ± 29 µm in the mandibular arch. These surface deviations between IOSb and IOS1c images were significantly larger in each region as well as entire dentition (P < 0.001) compared to those between IOS1c and IOS2c images. CONCLUSIONS: The average surface errors of the scans with brackets showed increased values compared with those without brackets. This suggests that orthodontic brackets could affect the trueness of intraoral scan images. CLINICAL RELEVANCE: It is necessary for clinicians to consider the effect of brackets on digital impression when using IOS images in orthodontic patients.

Soft Tissue Changes After Clockwise Rotation of Maxillo-Mandibular Complex in Class III Patients: Three-Dimensional Stereophotogrammetric Evaluation.

OBJECTIVES: To evaluate the linear, angular, and volumetric changes of soft tissue after clockwise repositioning of the maxillo-mandibular complex in skeletal class III patients using three-dimensional (3D) stereophotogrammetry and to determine the correlation between changes in the skeletal and soft tissue variables. METHODS: This study included 18 skeletal class III patients who underwent two-jaw surgery; superior impaction and clockwise rotational movement of the maxilla with the rotation center at upper incisors, and setback of the mandible. Lateral cephalograms and 3D photographs taken before and 6 months after surgery were compared. RESULTS: After maxillary impaction of anteriorly 1.7 mm and posteriorly 3.1 mm, and mandibular setback of 8.7 mm, the volume of lower lip and chin region decreased significantly by 33.6 cm3 (13% net change, P < 0.001), while paranasal and upper lip region volume increased by 3.2 cm3 (2%) and 7.2 cm3 (4%), respectively. CONCLUSION: The clockwise rotation of maxillo-mandibular complex in class III patients significantly reduced lower lip and chin volume with minimal increase in paranasal and upper lip volumes. 3D stereophotogrammetry can provide quantitative evaluation of facial soft tissue volumetric changes.

Neck Stabilization Exercises Enhance Respiratory Function after Stroke: Respiratory Function Index Change Trajectory Analyzed Using a Hierarchical Linear Model.

Background and Objectives: This study aimed to assess the effect of neck stabilization exercise on respiratory function in stroke patients through longitudinal observation and determine whether there is a difference in its effect based on the side of paralysis in the patients. It is difficult to observe the amount of change observed in individuals and groups as most intergroup comparison studies only use mean values. To address these shortcomings, this study adopted a hierarchical linear model (HLM) in our trajectory analysis. Materials and Methods: We conducted neck stabilization training three times a week for four weeks in a single group of 21 stroke patients. To evaluate respiratory function, their forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), forced expiration ratio (FEV1/FVC), and peak cough flow (PCF) were measured. Data analysis was performed using HLM 8.0. Results: A significant increase was found in the respiratory function after neck stabilization training (p < 0.05). While neck stabilization training overall was longitudinally effective, the growth rate of respiratory function in left-sided paralytic patients was less than the whole group value. Conversely, the growth rate of respiratory function in right-sided paralytic patients was greater than the whole group value. Conclusions: This study demonstrated that neck stabilization training is longitudinally effective in improving respiratory function in stroke patients. Additionally, the growth rate of respiratory function was greater in patients with right side paralysis than in patients with left side paralysis.