[Constructing a predictive model for the death risk of patients with septic shock based on supervised machine learning algorithms].

OBJECTIVE: To construct and validate the best predictive model for 28-day death risk in patients with septic shock based on different supervised machine learning algorithms. METHODS: The patients with septic shock meeting the Sepsis-3 criteria were selected from Medical Information Mart for Intensive Care-IV v2.0 (MIMIC-IV v2.0). According to the principle of random allocation, 70% of these patients were used as the training set, and 30% as the validation set. Relevant predictive variables were extracted from three aspects: demographic characteristics and basic vital signs, serum indicators within 24 hours of intensive care unit (ICU) admission and complications possibly affecting indicators, functional scoring and advanced life support. The predictive efficacy of models constructed using five mainstream machine learning algorithms including decision tree classification and regression tree (CART), random forest (RF), support vector machine (SVM), linear regression (LR), and super learner [SL; combined CART, RF and extreme gradient boosting (XGBoost)] for 28-day death in patients with septic shock was compared, and the best algorithm model was selected. The optimal predictive variables were determined by intersecting the results from LASSO regression, RF, and XGBoost algorithms, and a predictive model was constructed. The predictive efficacy of the model was validated by drawing receiver operator characteristic curve (ROC curve), the accuracy of the model was assessed using calibration curves, and the practicality of the model was verified through decision curve analysis (DCA). RESULTS: A total of 3 295 patients with septic shock were included, with 2 164 surviving and 1 131 dying within 28 days, resulting in a mortality of 34.32%. Of these, 2 307 were in the training set (with 792 deaths within 28 days, a mortality of 34.33%), and 988 in the validation set (with 339 deaths within 28 days, a mortality of 34.31%). Five machine learning models were established based on the training set data. After including variables at three aspects, the area under the ROC curve (AUC) of RF, SVM, and LR machine learning algorithm models for predicting 28-day death in septic shock patients in the validation set was 0.823 [95% confidence interval (95%CI) was 0.795-0.849], 0.823 (95%CI was 0.796-0.849), and 0.810 (95%CI was 0.782-0.838), respectively, which were higher than that of the CART algorithm model (AUC = 0.750, 95%CI was 0.717-0.782) and SL algorithm model (AUC = 0.756, 95%CI was 0.724-0.789). Thus above three algorithm models were determined to be the best algorithm models. After integrating variables from three aspects, 16 optimal predictive variables were identified through intersection by LASSO regression, RF, and XGBoost algorithms, including the highest pH value, the highest albumin (Alb), the highest body temperature, the lowest lactic acid (Lac), the highest Lac, the highest serum creatinine (SCr), the highest Ca2+, the lowest hemoglobin (Hb), the lowest white blood cell count (WBC), age, simplified acute physiology score III (SAPS III), the highest WBC, acute physiology score III (APS III), the lowest Na+, body mass index (BMI), and the shortest activated partial thromboplastin time (APTT) within 24 hours of ICU admission. ROC curve analysis showed that the Logistic regression model constructed with above 16 optimal predictive variables was the best predictive model, with an AUC of 0.806 (95%CI was 0.778-0.835) in the validation set. The calibration curve and DCA curve showed that this model had high accuracy and the highest net benefit could reach 0.3, which was significantly outperforming traditional models based on single functional score [APS III score, SAPS III score, and sequential organ failure assessment (SOFA) score] with AUC (95%CI) of 0.746 (0.715-0.778), 0.765 (0.734-0.796), and 0.625 (0.589-0.661), respectively. CONCLUSIONS: The Logistic regression model, constructed using 16 optimal predictive variables including pH value, Alb, body temperature, Lac, SCr, Ca2+, Hb, WBC, SAPS III score, APS III score, Na+, BMI, and APTT, is identified as the best predictive model for the 28-day death risk in patients with septic shock. Its performance is stable, with high discriminative ability and accuracy.

Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis.

RNA molecules with the expanded CAG repeat (eCAGr) may undergo sol-gel phase transitions, but the functional impact of RNA gelation is completely unknown. Here, we demonstrate that the eCAGr RNA may form cytoplasmic gel-like foci that are rapidly degraded by lysosomes. These RNA foci may significantly reduce the global protein synthesis rate, possibly by sequestering the translation elongation factor eEF2. Disrupting the eCAGr RNA gelation restored the global protein synthesis rate, whereas enhanced gelation exacerbated this phenotype. eEF2 puncta were significantly enhanced in brain slices from a knock-in mouse model and from patients with Huntington's disease, which is a CAG expansion disorder expressing eCAGr RNA. Finally, neuronal expression of the eCAGr RNA by adeno-associated virus injection caused significant behavioral deficits in mice. Our study demonstrates the existence of RNA gelation inside the cells and reveals its functional impact, providing insights into repeat expansion diseases and functional impacts of RNA phase transition.

Optogenetic control of GGGGCC repeat-containing RNA phase transition.

The GGGGCC (G4C2) hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia. Recent studies have shown that G4C2 hexanucleotide repeat-containing RNA transcripts ((G4C2)n RNA) could go through liquid-liquid phase separation to form RNA foci, which may elicit neurodegeneration. However, the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated. Here we introduce an optogenetic control system that can induce the assembly and phase separation of (G4C2)n RNA foci with blue light illumination in human cells, by fusing a specific (G4C2)n RNA binding protein as the linker domain to Cry2, a protein that oligomerizes in response to blue light. Our results demonstrate that a higher number of G4C2 repeats have the potential to be induced into more RNA foci in the cells. Both spontaneous and induced RNA foci display liquid-like properties according to FRAP measurements. Computational simulation shows strong consistency with the experimental results and supports the effect of our system to promote the propensity of (G4C2)n RNA towards phase separation. This system can thus be used to investigate whether (G4C2)n RNA foci would disrupt normal cellular processes and lead to pathological phenotypes relevant to repeat expansion disorders.

Effect of predictive trauma care on fracture healing and complications of traumatic fracture patients in emergency department.

OBJECTIVE: To explore the advantages of predictive trauma care in fracture healing and prevention of complications in patients with traumatic fracture. METHODS: Through prospective research methods, 80 patients with traumatic fractures were divided into a research group and a control group, each with 40 cases. The control group was given regular emergency care, while the research group was given predictive trauma care. The related clinical indicators, complications and scores on changes in joint range of motion (ROM), mental status and quality of life before and after intervention were compared between the two groups. RESULTS: Compared with the control group, the time of pain relief, fracture recovery and hospital stay of the research group was significantly shortened (all P<0.01). The overall incidence of complications in the research group was lower than that in the control group (5.00% vs 20.00%, P<0.05). For patients with limb fractures, the ROM scores of the two groups after intervention were significantly higher than those before intervention, and the scores of the research group were higher than those of the control group (all P<0.05). Compared with the condition before intervention, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores of the two groups of patients were significantly reduced after intervention, and the scores of research group were lower than those of the control group (all P<0.05). Compared with the condition before intervention, the scores of physical function, social function, psychological function and daily life condition of the two groups of patients were significantly increased 3 months after discharge from hospital, and the scores of the research group were significantly higher than those of the control group (all P<0.05). CONCLUSION: Predictive trauma care can effectively reduce the risk of postoperative complications in patients with traumatic fractures, promote the fracture healing, relieve the patients' anxiety and depression, and improve their quality of life.

Alteration of occlusal vertical dimension induces signs of neuroplastic changes in corticomotor control of masseter muscles: Preliminary findings.

PURPOSE: To investigate the effect of altering occlusal vertical dimension (OVD) in patients with severe attrition on corticomotor control of the masseter muscles as assessed by navigated transcranial magnetic stimulation (nTMS). METHODS: Seven patients (58.6 ± 8.4 years) with decreased OVD due to severe attrition were given mandibular occlusal splints to alter the OVD with the instruction to wear during the whole awake time for a period of four weeks. Motor-evoked potentials (MEPs) and the motor cortex maps of the masseter muscles and first dorsal interosseous (FDI) muscles as control were recorded by nTMS at baseline and at least 4 weeks after the alteration of OVD. The stimulus-response curves of MEPs were analysed with two-way repeated-measures ANOVA, and the numerical rating scale scores, motor thresholds, onset latencies, motor cortex maps and centre of gravity (COG) were analysed with paired t tests. RESULTS: There was a significant increase in the amplitude of the masseter muscle MEPs (P = 0.036), but no change in the motor cortex map areas (P = 0.111) four weeks after the alteration of OVD. Furthermore, there was no significant difference in either the amplitude of the FDI muscle MEPs (P = 0.466) or the motor cortex map areas (P = 0.230) before and after OVD alteration. CONCLUSION: The results suggest that alteration of OVD in patients with severe attrition was associated with signs of neuroplastic changes in the corticomotor control of the masseter muscles. The results of the study may add to our understanding of the putative mechanisms related to cortical changes in response to OVD alterations.

Effect of Experimental Periodontal Ligament Pain on Gingival Somatosensory Sensitivity.

AIMS: To use a randomized, blinded, crossover design to evaluate the possible heterotopic effects of experimental periodontal ligament pain on adjacent gingival somatosensory sensitivity. METHODS: A total of 12 healthy volunteers (8 female, 4 male; mean age ± standard error in means (SEM): 28 ± 1 years) participated in two randomized experimental quantitative sensory testing (QST) sessions, one in which capsaicin (experimental) was injected into the periodontal ligament and one in which isotonic saline (control) was injected. A total of 13 standardized QST measures were obtained on the buccal attached gingiva of a maxillary central incisor before, immediately after, and 30 minutes after injection of 30 µL of 5% capsaicin or isotonic saline into the periodontal ligament of the same incisor. The injection-evoked pain was evaluated on a 0-10 numeric rating scale (NRS). QST data were analyzed with two-way repeated measurement analysis of variance. RESULTS: Capsaicin injected into the periodontal ligament evoked moderate levels of pain (mean peak NRS ± SEM: capsaicin: 5.5 ± .7; control: 0.6 ± 0.5 [P < .001]). Capsaicin injected into the periodontal ligament significantly modulated gingival somatosensory sensitivity: increased sensitivity to warmth and painful heat stimuli occurred immediately and 30 minutes after the injection (P < .025), whereas decreased sensitivity to both tactile and painful mechanical stimuli (P < .011) occurred immediately after the injection and to painful mechanical stimuli only after 30 minutes (P = .016). No somatosensory changes were detected following the injection of isotonic saline (P > .050). CONCLUSION: Capsaicin injected into the periodontal ligament caused gain of heterotopic somatosensory sensitivity toward warmth and painful heat stimuli as well as reduction in mechanical sensitivity of the gingiva adjacent to the injected tooth. These findings may have implications for interpretation of somatosensory functions in patients with chronic intraoral pain, where gingival somatosensory profiles similar to those detected after capsaicin injection in the present study may be interpreted as signs of nerve damage.

Spatial and Temporal Effects of Capsaicin and Menthol on Intraoral Somatosensory Sensitivity.

AIMS: To assess the spatial and temporal sensory effects of the topical application of capsaicin and menthol on the gingiva of healthy volunteers. METHODS: Capsaicin, menthol, and saline (control) were applied topically on the gingiva in the maxillary premolar area of healthy volunteers for 15 minutes. Pain intensity was rated on a 0 to 10 visual analog scale (VAS). Before, immediately after, and 30 minutes after application, three mechanical stimuli were applied at 15 gingival sites: fixed-intensity stimuli were applied by 32 mN and 512 mN von Frey filaments, and stimuli of increasing intensity were applied by an electronic von Frey (EVF, 10 g/s). The EVF was used to test the pinprick pain threshold (PiPT). The perceived pain from filament stimulation was rated on a 0-50-100 numeric rating scale (NRS). Analysis of variance for repeated measures was used to analyze the NRS scores, PiPT values, the number of hypersensitive or hyposensitive test sites, and the coordinates of the center of gravity (COG) of somatosensory sensitivity. RESULTS: The mean ± SEM VAS score of pain intensity produced by the application of capsaicin (4.6 ± 0.5) was significantly higher than that produced by menthol (0.3 ± 0.2) and saline (0.1 ± 0.1) (P < .001). Capsaicin induced local desensitization to all stimuli (P < .047) , and at the application site, capsaicin induced significant desensitization to 512 mN stimuli (P = .003). Menthol did not induce significant somatosensory changes (P > .147), and saline induced slight desensitization in two sites surrounding the application site (P < .023). The COG coordinates did not shift significantly over time during any condition (P > .125). CONCLUSION: Capsaicin but not menthol induced mechanical desensitization in the application area but not in the surrounding areas.

Differential changes in gingival somatosensory sensitivity after painful electrical tooth stimulation.

We aimed to evaluate the effect of painful tooth stimulation on gingival somatosensory sensitivity of healthy volunteers in a randomized, controlled design. Thirteen healthy volunteers (six women, seven men; 28.4 ± 5.0 years) were included for two experimental sessions of electrical tooth stimulation: painful tooth stimulation and tooth stimulation below the sensory threshold (control). Eight of the human subjects participated in a third session without tooth stimulation. In all sessions, the somatosensory sensitivity of the gingiva adjacent to the stimulated tooth was evaluated with a standardized battery of quantitative sensory tests (QST) before, immediately after and 30 min after tooth stimulation. Painful tooth stimulation evoked significant decreases in warmth and heat pain thresholds (P < 0.001) as well as pressure pain thresholds (increased sensitivity) (P = 0.024) and increases in mechanical detection thresholds (decreased sensitivity) (P < 0.050). Similar thermal threshold changes (P < 0.019) but no mechanical changes were found after tooth stimulation below the sensory threshold (P > 0.086). No QST changes were detected in the session without tooth stimulation (P > 0.060). In conclusion, modest increased gingival sensitivity to warmth, painful heat and pressure stimuli as well as desensitization to non-painful mechanical stimulation were demonstrated after tooth stimulation. This suggests involvement of competing heterotopic facilitatory and inhibitory mechanisms. Furthermore, stimulation below the sensory threshold induced similar thermal sensitization suggesting the possibility of activation of axon-reflex-like mechanisms even at intensities below the perception threshold. These findings may have implications for interpretation of somatosensory results in patients with chronic intraoral pain.

One hour jaw muscle training does not evoke plasticity in the corticomotor control of the masseter muscle.

UNLABELLED: Transcranial magnetic stimulation (TMS) has been used to assess corticomotor control of jaw muscles, but few studies have examined cortical plasticity of the masticatory system and potential modification by jaw muscle training. OBJECTIVES: To determine if a 1-h jaw muscle training task would be sufficient to induce signs of neuroplastic changes in the corticomotor excitability of the masseter muscle. MATERIALS AND METHODS: Corticomotor excitability was assessed by changes in electromyographic activity evoked by TMS in 15 healthy participants. Motor evoked potentials (MEPs) recorded in the masseter and the first dorsal interosseos (FDI - as a control) muscle were assessed at four time points: at baseline, immediately after the 1-h training, 1h after training and 1 day follow-up (n=7). MEPs were assessed by stimulus-response curves and corticomotor mapping. RESULTS: All participants successfully performed the task (mean success rate: 47.0±4.1%) which increased significantly during the 1-h training. However, no significant effect of jaw muscle training on masseter and FDI MEPs or corticomotor maps were observed. CONCLUSION: The present finding showed that 1-h jaw muscle training is insufficient to evoke neuroplastic changes in corticomotor excitability. The potential for training-induced neuroplasticity may vary among different cranial muscles which may have therapeutic consequences.

Somatosensory profiling of intra-oral capsaicin and menthol in healthy subjects.

This study was designed to investigate the effect of surrogate orofacial pain models on the quantitative sensory testing (QST) profile in healthy participants. Capsaicin, menthol, or saline (control) were applied topically onto the gingiva of 15 healthy subjects for 15 min. During application, the subjects rated pain intensity on a score of 0-10, on an electronic visual analog scale (VAS). A standardized intra-oral QST protocol was performed before and immediately after application. Data obtained before and after application were compared using rank-sum tests, and QST profiles were made after Z-transformation. Application of capsaicin caused moderate levels of pain (VAS(peak)  = 6.0 ± 0.7), and application of menthol produced mild levels of pain (VAS(peak)  = 1.8 ± 0.6). Capsaicin induced hypersensitivity to warmth, heat pain and cold pain and hyposensitivity to mechanical stimuli. Menthol induced hypersensitivity to cold and warmth. Saline caused hypersensitivity to heat pain and hyposensitivity to mechanical stimuli. However, somatosensory profiles from Z-scores demonstrated sensory gains regarding warmth detection and heat pain only after application of capsaicin. In conclusion, a standardized battery of QST showed somatosensory changes after application of capsaicin, menthol and saline to the gingiva. However, the Z-score-based profiles may only reflect the most prominent somatosensory changes and thus represent a conservative approach for evaluation of data.

Reliability of a new technique for intraoral mapping of somatosensory sensitivity.

Diagnosis of intraoral pain conditions may be facilitated by assessment of somatosensory sensitivity not only at a single test site but also at multiple test sites, that is, intraoral somatosensory mapping. No standardized mapping techniques are currently available. The aim of this study was to evaluate: (1) spatial variations in somatosensory sensitivity; (2) the reliability of a new technique for mapping of intraoral somatosensory sensitivity. Fifteen healthy volunteers participated in two experimental sessions. In each session, three mechanical stimuli (32 mN and 512 mN von Frey and electronic von Frey (EVF)) were each applied to 15 test sites in a 5 × 3 matrix located at the gingivomucosal area adjacent to the upper premolar region on both sides. A custom-made silicone-based template secured standardization of the test sites. The subjects rated the perceived intensity on a 0-50-100 numerical rating scale (NRS) for tactile (32 mN) and pinprick (512 mN) stimuli and determined the pinprick threshold (PiPT) by EVF by pushing a stop button. Analyses of variance for NRS scores and PiPT for all three stimulus modalities showed no significant differences between sessions or sides (p = 0.077), whereas there were significant site-to-site differences (p < 0.001). Generally, the anterior and apical regions were more sensitive than posterior and cervical regions. Intraclass correlation coefficients for between session reliability ranged between 0.76 and 0.87 for NRS scores and PiPT measures. In conclusion, good test-retest reliability of intraoral somatosensory mapping was found with the help of a new template, which can be used for further studies of intraoral pain mechanisms.

Supersensitive, ultrafast, and broad-band light-harvesting scheme employing carbon nanotube/TiO2 core-shell nanowire geometry.

We demonstrate a novel, feasible strategy for practical application of one-dimensional photodetectors by integrating a carbon nanotube and TiO(2) in a core-shell fashion for breaking the compromise between the photogain and the response/recovery speed. Radial Schottky barriers between carbon nanotube cores and TiO(2) shells and surface states at TiO(2) shell surface regulate electron transport and also facilitate the separation of photogenerated electrons and holes, leading to ultrahigh photogain (G = 1.4 × 10(4)) and the ultrashort response/recovery times (4.3/10.2 ms). Additionally, radial Schottky junction and defect band absorption broaden the detection range (UV-visible). The concept using metallic core oxide-shell geometry with radial Schottky barriers holds potential to pave a new way to realize nanostructured photodetectors for practical use.

Microcirculation volumetric flow assessment using high-resolution, contrast-assisted images.

To improve the resolution of contrast-assisted imaging systems, we previously developed a 25-MHz microbubbles-destruction/replenishment imaging system with a spatial resolution of 160 X 160 microm. The goal of the present study was to propose a new approach for functionally evaluating the microvascular volumetric blood flow based on this high-frequency, ultrasound imaging system. The approach includes locating the perfusion area and estimating the blood flow velocity therein. Because the correlation changes between before and after microbubble destruction in two adjacent images, a correlated-based approach was introduced to detect the blood perfusion area. We also have derived a new sigmoid-based model for characterizing the microbubbles replenishment process. Two parameters derived from the sigmoid-based model - the rate constant and inflection time - were adopted to evaluate the blood flow velocity. This model was validated using both simulations and in vitro experiments for mean flow velocities ranging from 1 to 10 mm/s, which showed that the model was in good agreement with simulated and measured microbubble-replenishment time-intensity curves. The results indicate that the actual flow velocity is highly correlated with the estimates of the rate constant and the reciprocal of the inflection time. B-mode imaging experiments for mean flow velocities ranging from 0.4 to 2.1 mm/s were used to assess the volumetric flow in the microcirculation. The results indicated the high correlation between the actual volumetric flow rate and the product of the estimated perfusion area and rate constant, and the reciprocal of the inflection time. We also found that the boundary of the microbubble destruction volume significantly affected estimations of the flow velocity. The perfusion area can be located, and the corresponding flow velocity can be estimated simultaneously in a one-stage, microbubble-destruction/replenishment process, which makes the assessment of the volumetric bloo- d flow in the microcirculation feasible using a real-time, high-frequency ultrasound system.

[Bacteriological analysis of subgingival plaque in adolescents].

OBJECTIVE: To investigate the changes in characteristics of periodontal pathogens in subgingival plaque of patients with puberty gingivitis and its relevance with clinical symptoms. METHODS: A total of 108 subgingival plaque samples were collected from 30 patients with puberty gingivitis (Group G), 9 cases of chronic periodontitis (Group P) and 15 healthy controls (Group H). The age of the 54 participants was from 11 to 17. The black-pigmented bacteria (BPB), Fusobacterium nucleatum (Fn), Actinobacillus actinomycetemcomitans (Aa), Actinomyces were detected using bacterial culture. The probing depth (PD), gingival index (GI), bleeding index (BI) and attachment loss (AL) were also recorded. RESULTS: In all these three groups, the detection rates of black-pigmented bacteria were: 3%, 30% and 100%; Fn were: 30%, 68% and 94%, statistically significantly different (P < 0.01). The lgCFU/ml of black-pigmented bacteria and Actinomyces was higher in mild-moderate group [(3.8 +/- 0.7) and (5.3 +/- 0.9)] than in Group H (P < 0.001). The lgCFU/ml of black-pigmented bacteria and Fn significantly was higher in severe inflammation group [(4.7 +/- 1.2) and (4.4 +/- 0.8)] than in the mild-moderate group (P < 0.01). The lgCFU/ml of black-pigmented bacteria, Fn and Aa was higher in severe gingivitis group [(6.6 +/- 1.0), (5.5 +/- 1.0) and (4.2 +/- 1.7)] than in mild gingivitis group (P < 0.01). The detection rate and lgCFU/ml of black-pigmented bacteria, Fn and Aa were both positively correlated with BI, PD and AL. CONCLUSIONS: In the stage of severe gingivitis, the periodontal pathogens increased markedly, suggesting that risk of further destruction of periodontal tissue may exist.

The correlation-based algorithm to perfusion assessment in ultrasound image.

A high frequency contrast-assisted destruction/reperfusion imaging system has been developed to improve image resolution in previous study. Our goal in this work is to build a fast and robust algorithm to evaluate volumetric microcirculation blood flow. The microcirculation flow rate is determined by the multiplication of perfusion area and corresponding blood flow velocity mapping. The blood flow velocity can be estimated from B-mode time-intensity curves (TICs). Two new methods, correlation-based approach (CBA) and sum-absolute-difference approach (SADA), are proposed to locate and assess perfusion area. In vitro experiments were introduced to test the performance of two approaches. The results indicate a good correlation between the actual flow rate and the estimated volumetric flow rate. Potential applications of this blood flow estimation method include high-resolution flow assessment in small animal tumor and glaucoma models and the evaluation of superficial vasculature in clinical studies.