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This is a radiobiological modelling study aimed at comparing stereotactic ablative body radiotherapy (SABR) with conventional palliative radiotherapy (CPRT) and curative-dose volumetric-modulated arc therapy (CD-VMAT) in the palliation of patients with previously untreated head and neck cancer.
Methods:
Three radiotherapy plans were generated for 8 patients with head and neck cancer: SABR, prescribed to 45 Gy in 5 fractions; CPRT, prescribed to 30 Gy in 5 fractions and CD-VMAT, prescribed to 70 Gy in 35 fractions. The tumour control probability (TCP) and normal tissue complication probability for salivary and swallowing function (NTCPsaliva and NTCPswallow, respectively) were determined. From those values, the therapeutic ratio, as measured by the uncomplicated tumour control probability (UTCP), was determined.
Results:
Dosimetric objectives were achieved in all treatment plans. SABR had a higher mean TCP compared to CPRT and CD-VMAT (100% vs 81% vs 93%, p = 0·003). There were no statistically significant differences in the mean NTCPs for salivary or swallowing function (mean NTCPsaliva 27% vs 41% vs 36%, p = 0·093 and mean NTCPswallow 9% vs 12% vs 23%, p = 0·093). This resulted in the mean UTCP being statistically significantly higher for SABR plans compared to CPRT and CD-VMAT (66% vs 42% vs 49%, p = 0·004).
Conclusion:
It is feasible to create SABR plans that satisfy the dosimetric objectives in this study. Based on radiobiological modelling, SABR has superior TCP and similar NTCP, leading to a better therapeutic ratio than CPRT and CD-VMAT.
Objectives/Goals: Sexual minority populations (SMPs), including lesbian, gay, and bisexual groups, disproportionately encounter discriminatory experiences due to bi/homonegativity and systemic inequities across various social domains. We aim to understand how the neighborhood-level stressors and resilience sources differed across specific groups in SMPs. Methods/Study Population: Utilizing the NIH All of Us’ cloud-based platform, we selected cohorts self-identifying as gay (n = 9,454), bisexual (n = 15,284), lesbian (n = 5267), or straight (n = 349,748). We explored multiple key measures of neighborhood-level stressors (e.g., neighborhood disorder, neighborhood cohesion, and environment index) and resilience sources (e.g., neighbor cohesion, social support), and other factors (e.g., food insecurity, housing insecurity, and housing instability) by their sexual orientations using analysis of variance or Chi-square analyses. Results/Anticipated Results: Our sample comprised 60.8% females and 37.5% males identifying as non-binary or transgender, with an average age of 55.6 years (SD = 17.1). The racial composition was 56.0% White, 19.4% Black, 18.7% Hispanic, and 5.9% others (e.g., Asian, multiracial). Compared to straight individuals, SMPs reported high neighborhood stressors (e.g., disorder, worse environment) but lower neighborhood-level resilience sources (e.g., social support, cohesion). In addition, bisexual groups reported highest prevalence of housing insecurity (6.7% vs. 2.3%), housing instability (36.0% vs. 19.6%), and food insecurity (26.57% vs. 12.21%). Discussion/Significance of Impact: SMPs, particularly bisexual individuals, face greater neighborhood stressors and fewer resilience sources than their straight counterparts. These findings call for targeted interventions to address these disparities and promote health equity, using large-scale datasets to inform community-based solutions.
Objectives/Goals: Discriminatory experiences within healthcare settings significantly hinder equitable health access for sexual minority groups (SMPs) in the USA. These discriminatory experiences can manifest in various forms (e.g., refusal of care). We aimed to explore different types of discrimination encountered by SMPs in the healthcare settings. Methods/Study Population: This study utilized secondary data from the NIH All of Us Research Program. For this analysis, we selected cohorts self-identifying as gay (n = 9,454), bisexual (n = 15,284), lesbian (n = 5,267), and straight (n = 349,748), enabling robust comparisons across SMPs and straight individuals. We employed analysis of variance and Chi-square analyses to assess group differences in healthcare discrimination, using key indicators from the Discrimination in Medical Settings Scale. These indicators captured experiences such as being treated with less respect or courtesy and feeling ignored by healthcare providers, providing a comprehensive view of discriminatory encounters in healthcare settings for SMPs. Results/Anticipated Results: Our analyses revealed that bisexual individuals reported the highest levels of healthcare discrimination (mean = 3.64, SD = 2.45), followed by lesbians (mean = 3.37, SD = 2.47), other SMPs (mean = 3.36, SD = 2.53), gay (mean = 2.69, SD = 2.47), and straight participants (mean = 2.60, SD = 2.42). Among the seven discrimination indicators, the most reported experience was feeling like a doctor or nurse was not listening, with 76.8% of bisexual participants, 72.3% of lesbians, 68.8% of other SMPs, and 56.9% of gay participants reporting this experience. This was followed by reports of being treated with less respect and being treated with less courtesy in healthcare settings. These findings highlight the pervasive nature of healthcare discrimination among SMPs, particularly bisexual individuals. Discussion/Significance of Impact: SMPs experience higher levels of discrimination in healthcare settings compared to their straight counterparts. Our results underscore the urgent need to foster respectful, inclusive healthcare environments and ensure that healthcare providers are adequately trained to address the unique health needs and experiences of SMPs.
Cathepsin B (CTSB) is a cysteine protease that is widely found in eukaryotes and plays a role in insect growth, development, digestion, metamorphosis, and immunity. In the present study, we examined the role of CTSB in response to environmental stresses in Myzus persicae Sulzer (Hemiptera: Aphididae). Six MpCTSB genes, namely MpCTSB-N, MpCTSB-16D1, MpCTSB-3098, MpCTSB-10270, MpCTSB-mp2, and MpCTSB-16, were identified and cloned from M. persicae. The putative proteins encoded by these genes contained three conserved active site residues, i.e. Cys, His, and Asn. A phylogenetic tree analysis revealed that the six MpCTSB proteins of M. persicae were highly homologous to other Hemipteran insects. Real-time polymerase chain reaction revealed that the MpCTSB genes were expressed at different stages of M. persicae and highly expressed in winged adults or first-instar nymphs. The expression of nearly all MpCTSB genes was significantly upregulated under different environmental stresses (38°C, 4°C, and ultraviolet-B). This study shows that MpCTSB plays an important role in the growth and development of M. persicae and its resistance to environmental stress.
The study aimed to determine the patterns of the vestibular and ocular motor findings in cerebellar infarction (CI).
Methods:
We retrospectively analyzed vestibular and ocular motor test results in 23 CI patients and 32 acute unilateral vestibulopathy (AUVP) patients.
Results:
Among CI cases, the posterior inferior cerebellar artery (PICA) was the most commonly affected territory. Vertigo is predominantly observed in patients with infarctions affecting PICA or anterior inferior cerebellar artery (AICA). Lesions involving the superior cerebellar artery (SCA) mainly result in dizziness. Saccadic intrusion and oscillation, abnormal bilateral smooth pursuit (SP) and abnormal saccades were more prevalent in the CI group than in the AUVP group (all p < 0.05). Horizontal saccades were abnormal in 11 patients (47.8%) with CI. All AUVP patients had normal horizontal saccades. Horizontal SP was impaired in 13 patients (56.5%) with CI, with decreased gain toward both sides in 10 and toward 1 side in 3. Impaired horizontal SP was noted in nine patients (28.1%) with AUVP, with decreased gain toward the contralesional side in all cases. A total of 26.3% (5/19) of patients with CI exhibited subjective visual vertical (SVV) deviation toward the affected side and 31.6% (6/19) toward the unaffected side. In patients with AUVP, 70.0% (21/30) showed SVV deviation toward the affected side.
Conclusions:
Vertigo is mainly seen in PICA or AICA infarctions. SCA lesions mostly cause dizziness. Saccadic intrusion and oscillation, abnormal bilateral SP and abnormal saccades contribute to the diagnosis of CI. Moreover, SVV deviation varies depending on the cerebellar structures involved.
Recent neuroimaging studies have demonstrated that the heterogeneous antidepressant responsiveness in patients with major depressive disorder (MDD) is associated with diverse resting-state functional brain network (rsFBN) topology; however, only limited studies have explored the rsFBN using electroencephalography (EEG). In this study, we aimed to identify EEG-derived rsFBN-based biomarkers to predict pharmacotherapeutic responsiveness.
Methods
The resting-state EEG signals were acquired for demography-matched three groups: 98 patients with treatment-refractory MDD (trMDD), 269 those with good-responding MDD (grMDD), and 131 healthy controls (HCs). The source-level rsFBN was constructed using 31 sources as nodes and beta-band power envelope correlation (PEC) as edges. The degree centrality (DC) and clustering coefficients (CCs) were calculated for various sparsity levels. Network-based statistic and one-way analysis of variance models were employed for comparing PECs and network indices, respectively. The multiple comparisons were controlled by the false discovery rate.
Results
Patients with trMDD were characterized by the altered dorsal attention network and salience network. Specifically, they exhibited hypoconnection between eye fields and right parietal regions (p = 0.0088), decreased DC in the right supramarginal gyrus (q = 0.0057), and decreased CC in the reward circuit (qs < 0.05). On the other hand, both MDD groups shared increased DC but decreased CC in the posterior cingulate cortex.
Conclusions
We confirmed that network topology was more severely deteriorated in patients with trMDD, particularly for the attention-regulatory networks. Our findings suggested that the altered rsFBN topologies could serve as potential pathologically interpretable biomarkers for predicting antidepressant responsiveness.
In this paper, on–off switching digitization of a W-band variable gain power amplifier (VGPA) with above 60 dB dynamic range is introduced for large-scale phased array. Digitization techniques of on–off switching modified stacking transistors with partition are proposed to optimize configuration of control sub-cells. By the proposed techniques, gain control of a radio frequency variable gain amplifier (VGA) could be highly customized for both coarse and fine switching requirements instead of using additional digital-to-analog converters to tune the overall amplifier bias. The designed VGA in 130 nm SiGe has achieved switchable gain range from −46.4 to 20.6 dB and power range from −25.0 to 15.7 dBm at W band. The chip size of the fabricated VGPA is about 0.31 mm × 0.1 mm.
Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD).
Method
Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test.
Results
euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068).
Conclusions
Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.
Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19.
Objective:
To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED.
Material and methods:
Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25).
Results:
Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data.
Conclusion:
Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.
Motivated by practical applications of inspection and maintenance, we have developed a wall-climbing robot with passive compliant mechanisms that can autonomously adapt to curved surfaces. At first, this paper presents two failure modes of the traditional wall-climbing robot on the variable curvature wall surface and further introduces the designed passive compliant wall-climbing robot in detail. Then, the motion mechanism of the passive compliant wall-climbing robot on the curved surface is analyzed from stable adsorption conditions, parameter design process, and force analysis. At last, a series of experiments have been carried out on load capability and curved surface adaptability based on a developed principle prototype. The experimental results indicated that the wall-climbing robot with passive compliant mechanisms can effectively promote both adsorption stability and adaptability to variable curvatures.
Chinmen Island is located in the west of the Taiwan Strait, 15 km from the coast of mainland China. Mesozoic granitic gneiss forms the basement rocks of the island. High-defect kaolin deposits, both major sedimentary and minor residual types of clays, have been mined for ceramic uses for many years. The objectives of this study were to characterize the kaolin deposits and to discuss the genesis of kaolin minerals on the island. The kaolin samples were characterized by X-ray diffraction and transmission and scanning electron microscopy. In general, the particle-size distribution of the sedimentary kaolin was 0.5–5.0% sand, 15–55% silt and 30–85% clay. In the clay fraction, the ratio of kaolinite to illite ranged from 9:1 to 3:1. The sedimentary kaolin materials were originally transported by river from mainland China. Kaolinite occurred generally as pseudo-hexagonal platelets of ∼1 µm in diameter. The residual kaolin minerals resulted from the argillization of granitoid rocks by in situ weathering which possibly occurred during the Pleistocene. The residual kaolin contained more tubular halloysite.
Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10−3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.
To identify the optimal weight gain at the end of the second trimester.
Design:
This was a population-based cohort study from the antenatal care system in Tianjin, China. We calculated gestational weight gain (GWG) based on the weight measured in the first trimester and the end of the second trimester. Restricted cubic spline analysis was performed to model the possible non-linear relationships between GWG and adverse outcomes. The optimal GWG was defined as the value of the lowest risk. Non-inferiority margins and the shape of the spline curves identified the recommended ranges in Chinese-specific BMI categories.
Setting:
Tianjin Maternal and Child Health Cohort.
Participants:
Singleton pregnant women aged 18–45 years.
Results:
In total, 69 859 pregnant women were included. Adverse outcome (including stillbirth, preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, small and large for gestational age) was significantly associated with GWG at the end of the second trimester. The risk score was non-linearly correlated with GWG in the underweight, normal weight and overweight groups. GWG at the end of the second trimester should not be < 7 kg in underweight group. For most normal-weight women, a GWG of about 8 kg is optimal. Pregnant women who are overweight should not have a GWG of more than 9 kg. We advised women with overweight and obesity to keep positive growth of GWG (> 0 kg) in the first and second trimesters.
Conclusions:
According to the comprehensive adverse maternal and infant outcomes, we recommend the optimal GWG at the end of the second trimester. This study may provide a considerable reference for weight management.
The predictive methods of tool wear are usually based on different algorithm predictors, different source data, and different sensing devices for remaining useful life (RUL). In general, it has challenges to model and ensure all of the cutting conditions that are suitable in the actual cutting process for sustainable manufacturing. In order to overcome the doing large amount of experimental data and predict different tool RULs, this study combines the analytical force modeling, the back-propagation neural network (BPNN) machine learning, and the current sensor which all are integrated in smart machine box (SMB) to realize the practical RUL prediction for on-line and real-time applications. The analytical model of the cutting force coefficients of shear and ploughing was established from average cutting forces, it could reduce the experimental number and predict the different cutting conditions. In general, the loading current of the cutting tool from a spindle motor is relatively easier acquired than the resultant forces. Thus, the loading currents of the spindle are used to train and predict the cutting forces using the BPNN model during intelligent manufacturing. The SMB architecture mainly performed the autonomous actions based on the edge layer, the fog layer, and the cloud layer via the TCP/IP, the MQTT protocol, and the unified communication library. Results showed that a predictive error for the ends of the tool life is about 3–10% that are based on the calculating of the cumulative current ratio.
A novel couple-constrained parallel wrist with three measuring force flexible fingers is designed for grabbing heavy objects and measuring grabbed forces. Its prototype is developed, its dynamics model is established, and its grabbing forces are measured. First, using the extended formulas of the skew-symmetric matrix, the kinematic formulas are derived for solving the Jacobian/Hessian matrices and the general velocity/acceleration of the moving links in the couple-constrained parallel wrist. Second, a dynamics model is established for solving the dynamic actuation forces, the couple-constrained forces, and the torque in the couple-constrained parallel wrist. Third, the theoretical solutions of the kinematics/dynamics of the couple-constrained parallel wrist are verified using a simulation mechanism. Finally, the grabbing forces of the three flexible fingers are measured and analyzed.
This study aimed to determine the impact of current hepatitis B virus (HBV) infection on patients hospitalised with sepsis. This was a retrospective cohort study. Patients from three medical centres in Suzhou from 10 January 2016 to 23 July 2022 participated in this study. Demographic characteristics and clinical characteristics were collected. A total of 945 adult patients with sepsis were included. The median age was 66.0 years, 68.6% were male, 13.1% presented with current HBV infection, and 34.9% of all patients died. In the multivariable-adjusted Cox model, patients with current HBV infection had significantly higher mortality than those without (hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.11–2.02). A subgroup analysis showed that being infected with HBV significantly increased in-hospital mortality in patients younger than 65 years old (HR 1.74, 95% CI 1.16–2.63), whereas no significant impact was observed in patients ≥65 years. The propensity score-matched case–control analysis showed that the rate of septic shock (91.4% vs. 62.1%, P < 0.001) and in-hospital mortality (48.3% vs. 35.3%, P = 0.045) were much higher in the propensity score-matched HBV infection group compared with the control group. In conclusion, current HBV infection was associated with mortality in adults with sepsis.
OBJECTIVES/GOALS: Clinical tissue specimens are primarily destined for formalin fixed, paraffin embedded processing to create a basis for diagnosis by microscopic examination. Innovations in specimen processing are required to expand its availability for inclusion as the substrate in assays that can contribute to the further development of Precision Medicine. METHODS/STUDY POPULATION: Transurethral resection of bladder tumors were selected for testing based on availability and tissue composition. A wash step was used to generate daughter aliquots composed of dislodged cells and a solution with prior contact to the parent tissue. This wash step served two purposes: 1) reduce the amount of contaminating material from spreading to other cases, a problem known to be associated with this type of specimen; and 2) create aliquots from which additional informative data could be generated. These daughter aliquots were then examined to determine their value as a source for exosome profiling, metabolomic studies, molecular characterization and organoid development. The parent tissue was not compromised, was able to undergo conventional processing and yielded results equivalent to unwashed specimens. RESULTS/ANTICIPATED RESULTS: Exosomes secreted by the tumor cells were identified to be present in the daughter aliquots by a combination of their isolation using CD31 and detection of miR-21 expression. These exosomes were confirmed to be not related to fragmented cells from testing for beta-tubulin. A global/discovery-based approach using mass spectrometry provided insights into early characterization of metabolomic profiles present in these tumor cells. Ample amounts of high quality DNA (226 ng/ul concentrations; 11.3 ug total) were recovered from the dislodged, excess cells in the wash for molecular studies. Finally, from viable cells recovered in one of the daughter wash aliquots, the ability to grow organoids was proven to be possible and reproducible. DISCUSSION/SIGNIFICANCE: Based on these results, the value of the clinical specimen can be markedly expanded for utilization in research and possible clinical use without detracting from the parent tissue. This non-destructive, easy to adopt wash procedure can potentially lead to an influx of data that may ultimately prove useful in improving patient care.
In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.