Individual Parameters Research Articles

Prognostic Significance of Histopathological Parameters for Salivary Gland Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.

The triglyceride-glucose index might be a better indicator for predicting poor cardiovascular outcomes in chronic coronary syndrome

Abstract Background Abnormal glucose, and lipid metabolism all play major roles in the process of atherogenesis and are thus substantial risk factors for the development of coronary artery disease. Purpose We sought to investigate whether the triglyceride-glucose index (TyG) and the Atherogenic Index of Plasma (AIP), surrogates for atherosclerosis, are linked to major adverse cardiovascular events (MACE) in patients with Chronic Coronary Syndrome (CCS). Methods and Results Seven hundred ten-five consecutive patients with intermediate risk for CCS who presented to the outpatient clinic between June 2020 and August 2022 were included retrospectively. MACE included non-fatal myocardial infarction, heart failure, cerebrovascular events, non-cardiac mortality, and cardiac mortality. The composite of MACE was determined to be the primary outcome at follow-up after discharge. Secondary outcomes were defined as each individual parameter of MACE. For the primary outcome's time-to-event analysis, the Kaplan-Meier plots, and Cox proportional hazard models were done.The overall population’s median age was 55 years, with males accounting for 58%. The median follow-up time was 17 months. On multivariate cox regression analysis, age, hypertension, Coronary Artery Disease-Reporting and Data System score, and TyG index were found to be independent predictors of the primary outcome. The primary outcome rate was higher in individuals with high TyG than in those with low TyG (18.7% vs 3.8%, p<0.001). Likewise, patients with high TyG had statistically higher rates of cerebrovascular events, heart failure, non-fatal MI, non-cardiac mortality, and cardiac mortality than the latter. Conclusion We found that the TyG might predict poor cardiovascular outcomes in CCS patients.Table 1Figure 1

Exploring the spatial interplay between built-up environments and surface urban heat island phenomena in the main urban area of Shanghai

The urban built-up environment, consisting of buildings, roads, and various facilities, plays a crucial role in forming surface urban heat islands (SUHI). This study aims to address this issue by creating a comprehensive indicator system for the urban built-up environment, drawing from previous research. By employing multi-source data and diverse geospatial processing methods, this article examine the influence of 20 environmental factors on the spatial and temporal variability of SUHI in Shanghai during the summer and winter seasons from 2016 to 2020. This article findings reveal four key observations. (1) The average SUHI intensity in Shanghai's main urban area during the summers of 2016–2020 showed an increasing trend, with the heat island's shape and location differing between seasons. (2) The correlation values (R-values) between the built and road environment indicators and SUHI changed with season and year, reflecting the dynamic interplay among urban morphology, weather conditions, and human activities that affect heat generation and dissipation. (3) This article found that the increasing SUHI trend was not solely dependent on changes in individual built-up environment parameters. (4) This article analysis demonstrated that the built environment factor significantly influenced heat island intensity in summer, while the green space environment factor had a substantial impact during winter. In conclusion, the results emphasize the complex relationship between the urban built-up environment and SUHI, highlighting the need to consider various environmental factors when assessing their impact on SUHI formation. This study offers valuable insights to inform the development of effective strategies for mitigating the negative effects of SUHI on urban environments and promoting sustainable urban development.

Pharmacokinetic Consideration of Venetoclax in Acute Myeloid Leukemia Patients: A Potential Candidate for TDM? A Short Communication.

Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected. Even if VNX PKs have been well characterized and described in the literature, only 1 clinical trial-based PK study has been conducted in patients with AML. This study aimed to evaluate the PK of VNX in AML patients. We retrospectively analyzed all patients treated with a combination of VNX-azacitidine between January and July 2022 at our center, using at least 1 available VNX blood sample. Based on a previously published population PK model, individual PK parameters were estimated to evaluate the exposure and IIV. and Discussion. Twenty patients received VNX in combination with azacitidine, according to the PK data. A total of 93 plasma concentrations were collected. The dose of VNX was 400 mg, except in 7 patients who received concomitant posaconazole (VNX 70 mg). The patients' weight ranged from 49 kg to 108 kg (mean = 78 kg). Mean individual clearance was 13.5 ± 9.4 L/h with mean individual daily area under the concentration-time curves of 35.8 mg.h/L with significant IIV (coefficient of variation = 41.1%). Ten patients were still alive (8 in complete response), but all experienced at least 1 hematological toxicity of grade ≥ 3. Based on the observed large PK variability in the data from our real-world AML patients, the risk of drug interactions and the recommended fixed-dosage regimen of VNX therapeutic drug monitoring may be useful.

Whole-body vibration may not affect bone mineral density and bone turnover in persons with chronic spinal cord injury: A preliminary study

Context Spinal-cord injury (SCI) induces bone loss and dramatically increases the risk of fracture. Objectives Determine the effects of whole-body vibration (WBV) on areal bone mineral density (aBMD), whole body composition and bone biological parameters in individuals with chronic-state SCI. Design Randomized study. Setting Centre Neurologique PROPARA. Participants Fourteen subjects were randomly assigned to a WBV or a control group. Interventions WBV (20–45 min, 30–45 Hz, 0.5 g) was performed in verticalized persons twice weekly for 6 months. Outcome Measures aBMD was measured by DXA at baseline and 6 months and bone biological parameters at baseline, 1, 3 and 6 months. Results No significant aBMD change was found in either the WBV or control group after 6 months of follow-up. Similarly, periostin, sclerostin and bone turnover markers remained relatively stable throughout follow-up and no difference in variation was observed within-group and between groups. Except for whole-body fat mass, which showed a significant decrease in the WBV group compared to controls, no difference in changes was observed, whatever the localization for fat and lean body mass. Conclusions During the chronic phase, aBMD and bone remodeling reach a new steady state. However, the DXA technique and the bone markers, including sclerostin and periostin, both of which reflect bone cell activity influenced by mechanical strain, showed that the bone tissue of individuals with SCI was insensitive to 6 months of WBV training at the study dose. Nevertheless, results of this preliminary study that was underpowered need to be confirmed and other modalities of WBV may be more effective in improving aBMD of this population. Trials registration N°IDRCB:2011-A00224–37

Abstract 18621: Platelet Aggregation is Heightened in Those With Metabolic Syndrome and Less Effectively Mediated by Aspirin Therapy

Background: Patients with metabolic syndrome (MetS) are at a higher risk of developing cardiovascular disease (CVD); however, interventions to mitigate this risk are not fully known. Platelets play a significant role in atherothrombosis, and aspirin is an important, yet controversial therapy used for the primary prevention of CVD. In this study, we examined platelet phenotype in MetS and degree of inhibition from ex vivo aspirin administration. Methods: In a study examining the mechanisms of atherothrombosis in pro-inflammatory conditions, patients without clinical CVD were enrolled and underwent phenotyping. Patients with MetS (n = 34, age 53.3 ± 13 years, 59% male) were compared to patients with no MetS (n = 63, age 41.1 ± 16 years, 52% male). Platelet aggregation of freshly isolated platelets was measured via light transmission aggregometry (LTA) in resting and stimulated conditions, in response to agonists adenosine diphosphate (ADP), high and low dose of arachidonic acid (AA), and after ex vivo aspirin (ASA) administration. Results: MetS patients were older and similar in sex and race (Figure 1A). As expected, patients with MetS had higher individual components of MetS, yet similar LDL-C (Figure 1A). Platelet aggregation to low dose ADP (p=0.09) and AA (p=0.04) was significantly increased in MetS (Figure 1B). Platelet aggregation in response to AA and coincubation with ASA was significantly lower in the no MetS cohort (Figure 1C). The efficacy of aspirin therapy was significantly lower in MetS (Figure 1D). In response to high dose AA after ASA treatment, platelet aggregation increased as number of MetS parameters also increased (Figure 1E). However, no individual metabolic syndrome parameter appeared to be driving these findings (Figure 1E). Conclusion: Among MetS patients, platelet aggregation is heightened and less inhibited by aspirin than those with no MetS. Additional research is warranted to explore possible anti-platelet strategies in patients with MetS.

Abstract 13937: Socioeconomic Status in Pediatric Patients With Anomalous Aortic Origins of Coronary Arteries: An Individual- and Zip Code-Level Analysis

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden cardiac death in the young. Limited data is available on potential disparities on access to care and whether socioeconomic status is associated with AAOCA. Hypothesis: AAOCA occurrence, severity, and treatment relate to socioeconomic status and may unfold inequities to care. Methods: Single-center retrospective study of 553 pediatric patients with AAOCA residing in Texas. Zip code socioeconomic characteristics were extracted from American Community Survey 2021 5-year estimates. All Texas zip codes were ordered into quartiles by characteristic. Age at diagnosis, signs of ischemia, and surgery status were compared by race and zip code parameters. Mann-Whitney U test was for non-parametric variables and χ 2 test, Fisher’s test, or one-way ANOVA for categorical variables. Results: Table 1 depicts patients’ demographics. AAOCA patients tended to reside in zip codes at the 4 th quartile of income (39%, p=<0.001), education (29%, p=0.003), and employment (42%, p=<0.001) (Table 2). There was no difference in age at diagnosis, signs of ischemia, or occurrence of coronary surgery by individual race or zip code socioeconomic parameters. Conclusions: AAOCA pediatric patients tend to live in zip codes with higher socioeconomic status (SES). These differences may reflect disparities in access to diagnosis and care. Further studies are needed to determine the burden of AAOCA in low SES populations.

Assessment of the angle of articular inclination in patients with different skeletal classes according to axiography

The morphology of the articular tubercle of the temporal bone varies in the population and is being formed during the growth and development of the patient. When planning and implementing comprehensive dental treatment, it is necessary to take into account the individual parameters of the articular tubercle inclination in order to achieve a predictable result.The aim of the research was to study the values of the articular inclination angle depending on the subjects’ skeletal class.Materials and methods  A clinical cross-sectional retrospective simple centric study in which 265 patients participated: 80 men and 185 women.Clinical studies included filling in the dental formula, intraoral photographs of dentition, palpation of the masticatory muscles and the TMJ area, analysis of the jaws plaster models. Each subject underwent electronic axiography with registration of the lower jaw hinge axis movements. The assessment of the angle of articular inclination (SCI) during translational movements was carried out: protrusion-retrusion, right media intrusion, left media intrusion. The skeletal class was evaluated on the basis of cephalometry data by analyzing teleroentgenograms (TRG) in a lateral projection with markers of the hinge-suborbital axis.Result. In the course of the study, the average values of the articular inclination angle were obtained for protrusion-retrusion, right-hand media intrusion, left-hand media intrusion according to the «Skeletal class» criterion. Differences were found between skeletal classes in terms of SCI.During protrusion – retrusion, the SCI values were significantly higher in the subjects with skeletal class II than in the subjects with skeletal class III. It should be noted that the subjects with II skeletal class with protrusion – retrusion had the highest values of SCI than the subjects with I and III skeletal classes, but no significant differences were found.ConclusionsThe values of the sagittal condular inclination depend on the skeletal class of jaw relationship.A decrease in the values of sagittal condular inclination is a risk factor for the maxillofacial dysfunction development.The lowest values of sagittal condular inclination were observed in subjects with the III skeletal class which requires special attention when diagnosing and treating this risk group.The value of the sagittal condular inclination should be taken into account when modeling the anatomy of orthopedic structures during prosthetic treatment.

Assessment of urinary podocalyxin as a biomarker of early diagnosis of hypertensive nephropathy

Chronically high blood pressure-related kidney injury is known as hypertensive nephropathy (HN). Podocyte damage in the pathogenesis of this disease can result in the release of the sialoglycoprotein podocalyxin into the urine, so podocalyxin may be useful in the early diagnosis of HN. The purpose of the study was to examine the relationships between urine podocalyxin level and clinical and biochemical parameters in individuals with HN and to assess the diagnostic utility of urinary podocalyxin as an early marker of HN. Participants (114 individuals) were enrolled in this cross-sectional study, including 30 healthy controls and 84 patients with clinically proven chronic hypertension (CH). Biochemical tests were performed on the blood samples. Urinary microalbumin and creatinine levels were measured using immunoturbidimetric and spectrophotometric methods, respectively; urinary podocalyxin level was estimated with ELISA. All CH patients were classified into subgroups according to urine microalbumin/creatinine ratio (UM/CR) and the stage of chronic kidney disease (CKD). The results obtained showed that urinary podocalyxin level was significantly increased in both UM/CR and CKD staging subgroups compared with the healthy control group. A gradual increase in urinary podocalyxin level with CKD stage, especially in IV and V stages, and the higher sensitivi­ty of urinary podocalyxin as compared to UM/CR ratio in early detection of HN was demonstrated. It was concluded that urinary podocalyxin may be an important and highly sensitive marker for early diagnosis of hypertensive nephropathy in patients with chronic hypertension. Keywords: creatinine, diagnostic marker, hypertensive nephropathy, microalbumin, podocalyxin, urine

Impacts of different triathlon races on systemic cytokine profile and metabolic parameters in healthy individuals: a systematic review

The present systematic review aimed to discuss the impacts of different triathlon protocols on the level of pro and anti-inflammatory cytokines, as well as biomarkers related to the performance of healthy individuals. Four databases [PubMed (28 articles), Scopus (24 articles), Science Direct (200 articles), and SPORT Discus (1101 articles) were assessed. The eligibility criteria were applied, and the selected articles were used in the peer review, independently, as they were identified by March 2022. Of the 1359 articles found, 10 were included in this systematic review. Despite the difference in triathlon protocols, it was observed an increase in pro and anti-inflammatory cytokines including IL-4 and IL-10, and chemokines, such as IL-8 and MCP-1. Moreover, the anti-inflammatory serum levels increase after triathlon. Overall, the studies also reported enhancement in the serum levels of cortisol, creatine kinase, C reactive protein, Endothelial Growth Factor, Vascular Endothelial Growth Factor, Myostatin, Lactate dehydrogenase, free fatty acids, and lactate dehydrogenase in triathlon athletes. This systematic review indicates that different triathlon race promotes an acute elevation of circulating cytokines and chemokines levels which return to standard levels after triathlon races. The findings of this systematic review demonstrate that the modulation of inflammatory parameters may be associated with an increase in metabolic indicators (CK, Cortisol, and LDH) after the end of different types of triathlon races.

PSXIV-16 Evaluation of Water Intake Equations with an Emphasis on Physiological Status and Evaluation of Current Relevance Behind Environmental Parameters

Abstract Water requirements for beef cattle are often computed according to body weight (BW) and environmental variables. Inherent variation in environmental conditions within geographical locations, in addition to a cascade of physiological changes triggered as consequence of such variability are somewhat fomented by multicollinearity amongst these variables. This conundrum generates instability of current predictive models in reaching optimization equilibrium inflating its overall predictability and robustness. The goals herein involved the identification of physiologically relevant parameters and the generation of robust, data-driven, individualistic models through high frequency data loggers. Further, we evaluate re-parametrized and current proposed equations (e.g.: Hicks et al., 1988 and Arias and Mader, 2011) for the prediction of water intake for beef cattle at different life stages and physiological conditions. The dataset utilized consisted of more than 30,000 observations, including longitudinal data on lactating animals (n = 23), grass finished steers (n = 12), grain finished steers (n = 21), and grain finished implanted steers (n = 9), steers backgrounded on a low (n = 20) or moderate (n = 20) plane of nutrition bulls under negative (n = 13), maintenance (n = 13) and positive energy balance (n = 13). Individual monitoring systems allowed for the daily collection of BW, water and feed intake, and ingestive behavior. Additionally, an on-site data-logging weather station (1-min intervals) collected relative humidity, temperature, wind speed, wind direction, solar radiation, and precipitation. All reported statistics were generated on out-of-bag randomly split portions of the dataset. For identification of relevant predictive parameters of water intake, several feature selection and penalization techniques were examined. When comparing our equations to current, the errors generated for water intake predictions using physiological classification and on-site environmental variables, explained 50% more of the variation in predicting water intake (r2 = 0.38 vs r2 = 0.22-0.27). When evaluating the errors of prediction (root mean squared error, RMSE and mean absolute error, MAE), significant decreases of up to three-fold were observed on the equations generated herein (RMSE = 9.05 vs 28.8 to 35.31, MAE = 7.04 vs 26.9 to 33.9). Accurate monitoring of individual parameters such as feed intake were better predictors of water intake than environmental parameters when evaluating re-parametrization of models. Further, inclusion of a physiological stage (categorical variable) was more significant than any of the other environmental predictors. Overall, the results discussed highlight the importance of appropriately accounting for the water requirements of beef cattle and how far-off current assumptions are. Further, it raises concern on current equations that use environmental monitoring equations and techniques that attempt to describe nutrient requirements of the animals, and potentially brings the approach to requirements rather than environment.

Adaptive optimization technology of segmented reconstruction signal based on genetic algorithm for enhancing radar jamming effect

Given the improved capabilities of radar systems, addressing unfamiliar signals presents a challenge for radar jamming technology. To tackle this issue, this study proposes an adaptive technique for optimizing jamming waveforms to suppress multiple false targets in escort jamming scenarios. The objective is to minimize the detectability of false targets by fine-tuning phase modulation and individual waveform parameters. The optimization model adjusts the energy and delay of jamming waveform segments using intercepted radar signal phase modulation and direct forwarding. Real-time adaptation is achieved through the utilization of a genetic algorithm and radar constant false alarm rate detection based on received emissions. The key findings highlight the advantages of adaptivity in effectively suppressing false targets under diverse conditions. The technique successfully learns efficient waveforms through feedback, even without specific knowledge of the radar system. The optimized waveforms maintain consistent jamming impact across different constant false alarm rate settings, surpassing the limitations associated with fixed assumptions. The introduction of phase modulation enhances the resilience of false targets by creating noise-like characteristics. Remarkably, robust jamming is achieved with only 12 false targets, reducing complexity. The unified waveform design is particularly suitable for single platform jamming, eliminating the need for multiple jammers. Furthermore, the optimized waveforms demonstrate improved coverage of real targets under position errors. As a result, the approach exhibits versatility across various signals, processing methods, and scenarios. This study suggests that increased adaptability and the incorporation of machine learning techniques contribute to the advancement of radar jamming capabilities. By optimizing jamming waveforms, the adaptive approach presented in this study may enhance the effectiveness of countering advanced radar systems.

Evaluation of the pleth variability index, perfusion index, and other physiological parameters after COVID-19.

The aim of this study was to observe the changes in pleth variability index (PVI), perfusion index (PI) and other hemodynamic parameters in adult individuals who had had Coronavirus disease 2019 (COVID-19) and were currently living a normal life. A further aim was to draw attention to the fact that some hemodynamic changes after COVID-19 may cause long-term health problems. A total of 174 adult individuals who had had COVID-19 and were currently living a normal life and 56 healthy individuals with similar demographic characteristics who had not had COVID-19 were included in the study. The PI, PVI, oxygen saturation (SpO2), pulse rate (PR), total hemoglobin (Hgb), oxygen reserve index (ORI), and blood pressure values were measured by Masimo Radical 7. The data of individuals who had and did not have COVID-19 before were compared. The mean PVI (p = 0.008) and PI (p < 0.001) were significantly lower in people who had been exposed to COVID-19. Likewise, the mean of ORI, SpO2, and SpOC values was observed to be significantly lower in participants exposed to COVID-19 disease (p < 0.001, p < 0.001, and p = 0.006, respectively). The PVI had a positive correlation with body mass index (BMI) (r = 0.263, p < 0.001) and a negative correlation with SpO2 (r = -0.194, p = 0.003) and PR (r = 0.190, p = 0.004). The PVI, PI, and other physiological parameters could potentially be useful for monitoring COVID-19 patients and evaluating their response to therapy. We believe that people who have been exposed to COVID-19 may be more susceptible to other diseases; therefore, they should be subjected to regular clinical checks.

34 Neurocomputational Mechanisms of Social Reward Processing in Combat-Exposed Veterans

Objective:Combat exposure is associated with higher rates of depressive symptoms, including anhedonia (i.e., a reduced ability to seek and experience rewards) and feelings of social disconnectedness. While these symptoms are commonly documented in combat-exposed Veterans following deployment, the cognitive mechanisms underlying this pathology is less well understood. Computational modeling can provides detailed mechanistic insights into complex cognition, which may be particularly useful to understand how social reward processing is altered following combat exposure. Here, we use a Bayesian learning model framework to address this question.Participants and Methods:Thirty-three Operation Enduring Freedom (OEF)/ Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) Veterans (25 Male, 8 Female) between the ages of 18-65 years old (M = 41.61, SD = 10.49) participated in this study. In both classic/monetary and social reward conditions, participants completed a 2-arm bandit task, in which they must choose on each trial between two options (i.e., slot machine vs social partner) with unknown reward rates. While they received monetary outcomes in the classic condition, participants received compliments from different fictitious partners in the social condition. We first compared a learning-independent Win-stay/Lose-shift (WSLS) heuristic and either a Rescorla-Wagner Q-learning or a Bayesian learning model (Dynamic Belief Model/DBM) paired with a Softmax reward maximization policy. DBM+Softmax provided the best fit of the data for most participants (31/33). Individual DBM parameters of prior reward expectation, reward learning (i.e., perceived stability of reward rates), and Softmax reward maximization were estimated and compared across conditions.Results:Participants did not differ in their reward learning parameters across monetary and social conditions (t(30)= -0.70, p = 0.490), suggesting similar perception of reward stability in both modalities. However, higher Bayesian prior mean (i.e., initial belief of reward rate; t(30)= -2.31, p = 0.028, d=0.42) and greater reward maximization (i.e., Softmax parameter; t(30)= -2.26, p = 0.031, d=0.41) were observed in response to social vs monetary rewards. In the social reward condition, higher self-reported social connectedness was associated with greater model fit of our DBM model (i.e., smaller Bayesian Information Criterion/BIC; r = -0.38, p = 0.041). In this condition, those expecting higher reward rates when initiating reward exploration (those with higher DBM prior mean) endorsed lower self-esteem (Spearman's ρ = -0.43, p = 0.078) and lower positive affect (ρ = -0.32, p = 0.078).Conclusions:A Bayesian learning modeling framework can characterize mechanistic differences in the processing of social vs non-social reward among combat-exposed Veterans. Individuals with higher social connectedness were more model-based in their performance, consistent with the notion that they are more likely to estimate and anticipate how much social peers have to offer. Combat-exposed individuals with lower self-esteem and positive affect appear to have higher initial expectations of reward from unknown partners, which could reflect greater need for mood and/or self-esteem repair in those individuals. Overall, Bayesian modeling of social reward behavior provides a useful quantitative framework to predict clinically relevant construct of functional outcomes in military populations.

Transcutaneous Spinal Cord Stimulation to Stabilize Seated Systolic Blood Pressure in Persons With Chronic Spinal Cord Injury: Protocol Development.

Transcutaneous spinal cord stimulation (tSCS) is an emerging therapeutic strategy to target spinal autonomic circuitry to normalize and stabilize blood pressure (BP) in hypotensive persons living with chronic spinal cord injury (SCI). Our aim is to describe our current methodological approach to identify individual tSCS parameters that result in the maintenance of seated systolic blood pressure (SBP) within a pre-defined target range. The parent study is a prospective, randomized clinical trial in which eligible participants will undergo multiple mapping sessions to optimize tSCS parameter settings to promote stable SBP within a target range of 110-120 mm Hg for males and 100-120 mm Hg for females. Parameter mapping includes cathode electrode placement site (T7/8, T9/10, T11/12, and L1/2), stimulation frequency (30, 60 Hz), current amplitudes (0-120 mA), waveform (mono- and biphasic), pulse width (1000 μs), and use of carrier frequency (0, 10 kHz). Each participant will undergo up to 10 mapping sessions involving different electrode placement sites and parameter settings. BP will be continuously monitored throughout each mapping session. Stimulation amplitude (mA) will be increased at intervals of between 2 and 10 mA until one of the following occurs: 1) seated SBP reaches the target range; 2) tSCS intensity reaches 120 mA; or 3) the participant requests to stop. Secondary outcomes recorded include 1) symptoms related to autonomic dysreflexia and orthostatic hypotension, 2) Likert pain scale, and 3) skin appearance after removal of the tSCS electrode. Clinical Trials Registration: NCT05180227.

The Role of Thoracic Vertebral Body Dosimetry in Minimizing Acute Hematologic Toxicities of Patients With Non-Small Cell Lung Cancer Receiving Lung Radiation Therapy and Immunotherapy

IntroductionHematologic toxicities (HTs) are among the most common toxicities of combined immunotherapy and radiotherapy (RT). It remains essential to prevent RT-induced HTs because they can cause treatment discontinuation (influencing antitumoral effects), and because lymphopenia might dampen the effects of immunotherapy. To date, there are no studies examining the impact of thoracic vertebral body (TVB) RT dose on HTs in non-small cell lung cancer (NSCLC) patients receiving combined lung RT and PD(L)-1 immunotherapy. MethodsFor standardization, all doses were reported as 2-Gy equivalents (EQD2). Mirroring publications prior to the immunotherapy era, TVB volumes referred to T1-T10 and specific dosimetric parameters (DmeanEQD2, V5EQD2‒V60EQD2) were analyzed. Logistic regression estimated associations between grade ≥3 HTs (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability (NTCP) models were constructed by logistic regression analysis modeling for HT3+. Receiver operating characteristic (ROC) analysis delineated TVB dosimetric thresholds, stratification of which was able to evaluate post-RT absolute lymphocyte count (ALC) and immunotherapy responses. Areas under the curve (AUCs) for NTCP models were corroborated by bootstrapping (optimism-corrected) methodology. ResultsIn 132 patients, there were 26 (19.7%) instances of HT3+. On multivariate analysis, DmeanEQD2 and V5EQD2‒V20EQD2 associated with HT3+ (P<0.05 for all). The NTCP models illustrated a 50% probability of HT3+ at a DmeanEQD2=39.8 Gy, V5EQD2=87.4%, V10EQD2=77.0%, and V20EQD2=68.4%. ROC analysis delineated optimal thresholds of HT3+ with DmeanEQD2 ±30.2 Gy, V5EQD2 ±69.1%, V10EQD2 ±64.6%, and V20EQD2 ±53.5%. Patients treated with values above those cutoffs had over double the risk of HT3+, with significant differences in post-RT ALC and immunotherapy responses (P<0.05 for all). AUCs for each individual parameter ranged from 0.743 to 0.798, and combining all four aforementioned cutoffs into a ROC curve resulted in a qualitatively higher AUC (0.836). ConclusionsThis hypothesis-generating work suggests that TVB dosimetry may equate with HT3+ in NSCLC patients undergoing combined lung RT/immunotherapy. Applying TVB dose constraints in this population could reduce HT3+ and avoid dampening of immunotherapy responses, but prospective validation is required.

Hydrocarbon gas huff-n-puff optimization of multiple horizontal wells with complex fracture networks in the M unconventional reservoir

The oil production of the multi-fractured horizontal wells (MFHWs) declines quickly in unconventional oil reservoirs due to the fast depletion of natural energy. Gas injection has been acknowledged as an effective method to improve oil recovery factor from unconventional oil reservoirs. Hydrocarbon gas huff-n-puff becomes preferable when the CO2 source is limited. However, the impact of complex fracture networks and well interference on the EOR performance of multiple MFHWs is still unclear. The optimal gas huff-n-puff parameters are significant for enhancing oil recovery. This work aims to optimize the hydrocarbon gas injection and production parameters for multiple MFHWs with complex fracture networks in unconventional oil reservoirs. Firstly, the numerical model based on unstructured grids is developed to characterize the complex fracture networks and capture the dynamic fracture features. Secondly, the PVT phase behavior simulation was carried out to provide the fluid model for numerical simulation. Thirdly, the optimal parameters for hydrocarbon gas huff-n-puff were obtained. Finally, the dominant factors of hydrocarbon gas huff-n-puff under complex fracture networks are obtained by fuzzy mathematical method. Results reveal that the current pressure of hydrocarbon gas injection can achieve miscible displacement. The optimal injection and production parameters are obtained by single-factor analysis to analyze the effect of individual parameter. Gas injection time is the dominant factor of hydrocarbon gas huff-n-puff in unconventional oil reservoirs with complex fracture networks. This work can offer engineers guidance for hydrocarbon gas huff-n-puff of multiple MFHWs considering the complex fracture networks.

Respiratory function rehabilitation in individuals with Covid-19: swimming exercise

Background and Study Aim. Understanding the impact of swimming exercises on post-Covid-19 respiratory function is crucial for optimizing recovery strategies in affected individuals. The aim of this study is to determine the effect of 8-week swimming exercises on respiratory function parameters in adult individuals who have had Covid-19 disease. Material and Methods. Sixteen male students, aged 19-21, voluntarily participated in the study. Eight participants were assigned to the experimental group (EG), and eight to the control group (CG), all of whom were students of the Faculty of Sports Sciences at the University. The EG underwent an 8-week swimming exercise program conducted at the Bingöl Youth and Sports swimming pool (25 meters), three days a week. The CG was not involved in any exercise regimen. Pulmonary function tests (FVC, FEV1, FEV1/FVC, PEF) were conducted using a Cosmed Pony FXdel 2016 spirometer, one day before and one day after the exercise program for both EG and CG. Data analysis was performed using Independent Samples and Paired Samples T tests in SPSS 25, with a significance level set at p &lt; 0.05. Results. A statistically significant increase in respiratory FVC, FEV1, FEV1/FVC, and PEF function values was observed in the experimental group (EG) after the exercise intervention (p &lt; 0.05). This increase was observed when comparing these values to their pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function results before and after exercise in the control group (CG) (p &gt; 0.05). Conclusions. The findings of this study highlight the therapeutic potential of an 8-week swimming exercise program in significantly enhancing respiratory function among adult individuals who have previously contracted Covid-19. These results offer valuable insights for the development of post-Covid-19 rehabilitation protocols, emphasizing the importance of regular exercise, such as swimming, in the recovery process.

Probing the physics in the core boundary layers of the double-lined B-type binary KIC 4930889 from its gravito-inertial modes

Context. Stellar evolution models of B-type stars are still uncertain in terms of internal mixing properties, notably in the area between the convective core and the radiative envelope. This impacts age determination of such stars in addition to the computation of chemical yields produced at the end of their life. Aims. We investigated the thermal and chemical structure and rotation rate in the near-core boundary layer of the double-lined B-type binary KIC 4930889 from its four-year Kepler light curve, ground-based spectroscopy, and Gaia astrometry. Methods. We computed grids of 1D stellar structure and evolution models for different mixing profiles and prescriptions of the temperature gradient in the near-core region. We examined the preferred prescription and the near-core rotation rate using 22 prograde dipole modes detected by Kepler photometry of KIC 4930889. We employed a Mahalanobis distance merit function and considered various nested stellar model grids, rewarding goodness of fit but penalising model complexity. Results. We were able to constrain the near-core rotation rate of the pulsator to Ωrot = 0.73−0.06+0.02 d−1. Furthermore, we found a preference for either an exponentially decaying mixing profile in the near-core region or absence of additional near-core mixing, but found no preference among the various options for the temperature gradient in this region. The frequency (co)variances of our theoretical predictions are much larger than the errors on the observed frequencies. This forms the main limitation on further constraining the individual parameters of our models. A combination of spectroscopic, astrometric, binary, and asteroseismic information was used to achieve these constraints. Additionally, non-adiabatic pulsation computations of our best models indicate a need for opacity enhancements to accurately reproduce the observed mode excitation. Conclusions. The eccentric close binary system KIC 4930889 proves to be a promising target to investigate additional physics in close binaries by developing new modelling methods with the capacity to include the effect of tidal interactions for full exploitation of all detected oscillation modes.

Impact of Surgical Resection Without Spinal Fusion for Thoracic Dumbbell Tumors on Postoperative Global Spinal Sagittal Alignment and Clinical Outcomes.

A retrospective comparative study. This study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes after tumor resection without spinal fusion in patients with thoracic dumbbell tumors. Thirty patients with thoracic dumbbell tumors who were followed up for at least 3 years were included in this study. Variations in the outcome variables were analyzed using individual GSSA parameters measured on radiography. Clinical outcomes were assessed using the modified McCormick scale (MMCS), Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS). To assess the impact of the affected levels on these outcomes, we divided the patients into three groups according to the location of the tumor (upper [T1-4], middle [T5-8], or lower [T9-12] thoracic spine). The GSSA parameters (cervical lordosis, T1 slope, thoracic kyphosis [global, upper, middle, and lower], thoracolumbar kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt) of all the patients did not change significantly after surgery. Eleven of thirty patients had preoperative gait disturbances but they could walk without support (MMCS grade I or II) at the final follow-up. The JOA score and VAS showed significant postoperative improvements. No statistically significant differences were observed in each postoperative sagittal profile or clinical outcome between the upper, middle, and lower groups. Tumor resection without spinal fusion did not affect the various GSSA parameters and resulted in satisfactory clinical outcomes, indicating that spinal fusion may not always be necessary when resecting thoracic dumbbell tumors.