CT-guided online adaptive stereotactic body radiotherapy for pancreas ductal adenocarcinoma: Dosimetric and initial clinical experience.

Purpose/Objectives: Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. Materials/Methods: This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Results: 21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36-49:40) and average active physician time was 19:41 min (9:25-39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. Conclusions: Daily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Comprehensive stereotactic radiosurgery platform characterization: A novel end-to-end approach with anthropomorphic 3D dosimetry.

BACKGROUND: Stereotactic radiosurgery (SRS) is a widely employed strategy for intracranial metastases, utilizing linear accelerators and volumetric modulated arc therapy (VMAT). Ensuring precise linear accelerator performance is crucial, given the small planning target volume (PTV) margins. Rapid dose falloff is vital to minimize brain radiation necrosis. Despite advances in SRS planning, tools for end-to-end testing of SRS treatments are lacking, hindering confidence in the procedure. PURPOSE: This study introduces a novel end-to-end three-dimensional (3D) anthropomorphic dosimetry system for characterization of a radiosurgery platform, aiming to measure planning metrics, dose gradient index (DGI), brain volumes receiving at least 10 and 12 Gy (V10, V12), as well as assess delivery uncertainties in multitarget treatments. The study also compares metrics from benchmark plans to enhance understanding and confidence in SRS treatments. METHODS: The developed anthropomorphic 3D dosimetry system includes a modified Stereotactic End-to-End Verification (STEEV) phantom with a customized insert integrating 3D dosimeters and a fiber optic CT scanner. Labview and MATLAB programs handle optical scanning, image preprocessing, and dosimetric analysis. SlicerRT is used for 3D dose visualization and analysis. A film stack insert was used to validate the 3D dosimeter measurements at specific slices. Benchmark plans were developed and measured to investigate off-axis errors, dose spillage, small field dosimetry, and multi-target delivery. RESULTS: The accuracy of the developed 3D dosimetry system was rigorously assessed using radiochromic films. Two two-dimensional (2D) dose planes, extracted from the 3D dose distribution, were compared with film measurements, resulting in high passing rates of 99.9% and 99.6% in gamma tests. The mean relative dose difference between film and 3D dosimeter measurements was -1%, with a standard deviation of 2.2%, well within dosimeter uncertainties. In the first module, evaluating single-isocenter multitarget treatments, a 1.5 mm dose distribution shift was observed when targets were 7 cm off-axis. This shift was attributed to machine mechanical errors and image-guided system uncertainties, indicating potential limitations in conventional gamma tests. The second module investigated discrepancies in intermediate-to-low dose spillage, revealing higher measured doses in the connecting region between closely positioned targets. This discrepancy was linked to uncertainties in treatment planning system (TPS) modeling of out-of-field dose and multileaf collimator (MLC) characteristics, resulting in lower DGI values and higher V10 and V12 values compared to TPS calculations. In the third module, irradiating multiple targets showed consistent V10 and V12 values within 1 cm3 agreement with dose calculations. However, lower DGI values from measurements compared to calculations suggested intricacies in the treatment process. Conducting vital end-to-end testing demonstrated the anthropomorphic 3D dosimetry system's capacity to assess overall treatment uncertainty, offering a valuable tool for enhancing treatment accuracy in radiosurgery platforms. CONCLUSIONS: The study introduces a novel anthropomorphic 3D dosimetry system for end-to-end testing of a radiosurgery platform. The system effectively measures plan quality metrics, captures mechanical errors, and visualizes dose discrepancies in 3D space. The comprehensive evaluation capability enhances confidence in the commissioning and verification process, ensuring patient safety. The system is recommended for commissioning new radiosurgery platforms and remote auditing of existing programs.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

Unilateral severe gynecomastia in a 14 year-old adolescent with neurofibromatosis type 1 undergoing endoscopic mastectomy: a case report.

Gynecomastia can be caused by neurofibromas but has rarely been reported. The present case report describes the clinical appearance, diagnosis, and therapy of a rare combination of a 14 year-old adolescent male unilateral severe gynecomastia with NF-1 neurofibromatosis. In this particular case, we successfully performed minimally invasive surgery using endoscopic mastectomy, which not only resulted in a satisfactory appearance but also confirmed the presence of neurofibroma type 1 by detecting typical immunohistochemical indicators associated with the disease. Additionally, we analyzed the gene responsible for the disease, c.1431del: p. F477Lfs*21, based on the patient's family history.

Sleep Deprivation Triggers Mitochondrial DNA Release in Microglia to Induce Neural Inflammation: Preventative Effect of Hydroxytyrosol Butyrate.

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.

Study on full-scale pores characterization and heterogeneity of coal based on low-temperature nitrogen adsorption and low-field nuclear magnetic resonance experiments.

The characteristics and heterogeneity of coal pores are crucial for understanding the production mechanism of coalbed methane (CBM). In this study, coal samples with varying degrees of metamorphism (0.58% ≤ RO, max ≤ 3.44%) were collected. The characteristics of pore development and the heterogeneous properties of pores were revealed through low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR) experiments. The results indicate that pores with varying diameters exhibit favorable development in low-rank coals, along with favorable pores connectivity. The micropores composition of middle-rank coals was found to be 73.56%, however, the connectivity among transitional, meso, and macropores was observed to be poor. In high-rank coals, the proportion of micropores was 92.74%, with numerous micropores being closed or semi-closed. This resulted in inferior connectivity between micropores and transitional pores. As coal metamorphism progressed, the DL1 (characterizing the roughness of adsorption pores (AP) surface, ranging from 2.13 to 2.45) and DL2 (characterizing the complexity of AP structure, ranging from 2.56 to 2.77) initially decreased and then increased, whereas the DN (characterizing the heterogeneity of seepage pores (SP), ranging from 2.92 to 2.95) consistently improved. Furthermore, the roughness of pore surface and the complexity of pore structure in AP increased as the specific surface area and volume of pores increased. On the contrary, as the SP content increased, the uniformity of the pore structure improved. When the volume of SP remained constant, the complexity of the pore structure decreased due to increased pore connectivity.

Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the vlPAG and the Analgesic and Anxiolytic Effects of EA.

Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.Significance Statement Neuropathic pain is clinically accompanied by anxiety. Both glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) and electroacupuncture (EA) have demonstrated analgesic properties. However, the efficacy of these interventions in addressing neuropathic pain and its concomitant anxiety has yet to be fully elucidated. In a mice model of spared nerve injury (SNI), we observed a decreased excitability of vlPAG CamkIIα neurons. Remarkably, EA treatment significantly enhanced the excitability of these neurons. Further, chemogenetic activation of vlPAGCamkIIα+ neurons not only resulted in analgesia but also mitigated anxiety-like behaviors in SNI mice, mirroring the effects observed with EA treatment. Conversely, inhibition of vlPAGCamkIIα+ neurons activity in naive mice reduced pain thresholds and induced anxiety-like behavior, while also negating the beneficial effects of EA. These findings provide novel insights into the mechanistic interplay between chronic neuropathic pain and anxiety, highlighting the therapeutic potential of targeting vlPAG glutamatergic neurons in these conditions.

Metabolomic and transcriptomic analysis of flavonoids biosynthesis mechanisms in mulberry fruit (Hongguo 2) under exogenous hormone treatments.

The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.

Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke.

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX3CR1Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.

The TRPV6 Calcium Channel and Its Relationship with Cancer.

Transient receptor potential vanilloid-6 (TRPV6) is a cation channel belonging to the TRP superfamily, specifically the vanilloid subfamily, and is the sixth member of this subfamily. Its presence in the body is primarily limited to the skin, ovaries, kidney, testes, and digestive tract epithelium. The body maintains calcium homeostasis using the TRPV6 channel, which has a greater calcium selectivity than the other TRP channels. Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers. The function of TRPV6 in regulating calcium signaling in cancer will be covered in this review, along with its potential applications as a cancer treatment target.

Golden bile powder prevents drunkenness and alcohol-induced liver injury in mice via the gut microbiota and metabolic modulation.

BACKGROUND: Drunkenness and alcoholic liver disease (ALD) are critical public health issues associated with significant morbidity and mortality due to chronic overconsumption of alcohol. Traditional remedies, such as bear bile powder, have been historically acclaimed for their hepatoprotective properties. This study assessed the efficacy of a biotransformed bear bile powder known as golden bile powder (GBP) in alleviating alcohol-induced drunkenness and ALD. METHODS: A murine model was engineered to simulate alcohol drunkenness and acute hepatic injury through the administration of a 50% ethanol solution. Intervention with GBP and its effects on alcohol-related symptoms were scrutinized, by employing an integrative approach that encompasses serum metabolomics, network medicine, and gut microbiota profiling to elucidate the protective mechanisms of GBP. RESULTS: GBP administration significantly delayed the onset of drunkenness and decreased the duration of ethanol-induced inebriation in mice. Enhanced liver cell recovery was indicated by increased hepatic aldehyde dehydrogenase levels and superoxide dismutase activity, along with significant decreases in the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triglyceride, and total cholesterol levels (P < 0.05). These biochemical alterations suggest diminished hepatic damage and enhanced lipid homeostasis. Microbiota analysis via 16S rDNA sequencing revealed significant changes in gut microbial diversity and composition following alcohol exposure, and these changes were effectively reversed by GBP treatment. Metabolomic analyses demonstrated that GBP normalized the alcohol-induced perturbations in phospholipids, fatty acids, and bile acids. Correlation assessments linked distinct microbial genera to serum bile acid profiles, indicating that the protective efficacy of GBP may be attributable to modulatory effects on metabolism and the gut microbiota composition. Network medicine insights suggest the prominence of two active agents in GBP as critical for addressing drunkenness and ALD. CONCLUSION: GBP is a potent intervention for alcohol-induced pathology and offers hepatoprotective benefits, at least in part, through the modulation of the gut microbiota and related metabolic cascades.

Electroacupuncture Alleviates Hyperalgesia and Anxiety-Like Behaviors in Pain Memory Model Rats Through Activation of GABAergic Neurons and GABA Receptor in the Rostral Anterior Cingulate Cortex.

Recent studies have confirmed that pain memory is often accompanied by negative emotions. Electroacupuncture (EA) can block the retrieval of painful memories, thereby alleviating the associated negative behaviors. However, the underlying mechanism is poorly understood. This study revealed that the effect of EA on pain memory-induced negative behaviors is related to the mediation of GABAergic neuron activity and GABA receptor expression in the rostral anterior cingulate cortex (rACC). Previous studies have shown that the rACC is a crucial area for regulating nociceptive behaviors and negative emotions in pain memory models. The GABAergic neurons and receptors in the rACC are largely involved in pain sensation and related effects. However, the relationships among pain memory, GABAergic neurons and receptors in the rACC have not been investigated. In this study, we established a pain memory model via secondary plantar cross-injection of carrageenan and EA treatment. Using chemogenetic methods and behavioral assessments of pain and negative emotion, we found that early excitation of GABAergic neurons in the rACC blocked the recall of pain memories and reduced anxiety-like behaviors in pain memory model rats. Furthermore, pharmacological methods revealed that excitation of GABAA and GABAB receptors in the rACC blocks hyperpathia associated with pain memory and pain-induced anxiety-like behaviors, while inhibition of GABAA and GABAB receptors reverses these effects. These results suggest that EA may alleviate pain and associated anxiety-like behaviors related to pain memories through the activation of GABAergic neurons and excitation of GABAA and GABAB receptors in the rACC.

Determining the potency of primordial germ cells by injection into early mouse embryos.

Primordial germ cells (PGCs) are the earliest precursors of the gametes. During normal development, PGCs only give rise to oocytes or spermatozoa. However, PGCs can acquire pluripotency in vitro by forming embryonic germ (EG) cells and in vivo during teratocarcinogenesis. Classic embryological experiments directly assessed the potency of PGCs by injection into the pre-implantation embryo. As no contribution to embryos or adult mice was observed, PGCs have been described as unipotent. Here, we demonstrate that PGCs injected into 8-cell embryos can initially survive, divide, and contribute to the developing inner cell mass. Apoptosis-deficient PGCs exhibit improved survival in isolated epiblasts and can form naive pluripotent embryonic stem cell lines. However, contribution to the post-implantation embryo is limited, with no functional incorporation observed. In contrast, PGC-like cells show an extensive contribution to mid-gestation chimeras. We thus propose that PGC formation in vivo establishes a latent form of pluripotency that restricts chimera contribution.

ELK1/MTOR/S6K1 Pathway Contributes to Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer.

The development of acquired resistance to small molecule tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) signaling has hindered their efficacy in treating non-small cell lung cancer (NSCLC) patients. Our previous study showed that constitutive activation of the 70 kDa ribosomal protein S6 kinase 1 (S6K1) contributes to the acquired resistance to EGFR-TKIs in NSCLC cell lines and xenograft tumors in nude mice. However, the regulatory mechanisms underlying S6K1 constitutive activation in TKI-resistant cancer cells have not yet been explored. In this study, we recapitulated this finding by taking advantage of a gefitinib-resistant patient-derived xenograft (PDX) model established through a number of passages in mice treated with increasing doses of gefitinib. The dissociated primary cells from the resistant PDX tumors (PDX-R) displayed higher levels of phosphor-S6K1 expression and were resistant to gefitinib compared to cells from passage-matched parental PDX tumors (PDX-P). Both genetic and pharmacological inhibition of S6K1 increased sensitivity to gefitinib in PDX-R cells. In addition, both total and phosphorylated mechanistic target of rapamycin kinase (MTOR) levels were upregulated in PDX-R and gefitinib-resistant PC9G cells. Knockdown of MTOR by siRNA decreased the expression levels of total and phosphor-S6K1 and increased sensitivity to gefitinib in PDX-R and PC9G cells. Moreover, a transcription factor ELK1, which has multiple predicted binding sites on the MTOR promoter, was also upregulated in PDX-R and PC9G cells, while the knockdown of ELK1 led to decreased expression of MTOR and S6K1. The chromatin immunoprecipitation (ChIP)-PCR assay showed the direct binding between ELK1 and the MTOR promoter, and the luciferase reporter assay further indicated that ELK1 could upregulate MTOR expression through tuning up its transcription. Silencing ELK1 via siRNA transfection improved the efficacy of gefitinib in PDX-R and PC9G cells. These results support the notion that activation of ELK1/MTOR/S6K1 signaling contributes to acquired resistance to gefitinib in NSCLC. The findings in this study shed new light on the mechanism for acquired EGFR-TKI resistance and provide potential novel strategies by targeting the ELK1/MTOR/S6K1 pathway.

Association between dietary zinc intake and olfactory dysfunction: a study based on the NHANES database.

OBJECTIVE: The primary objective of this study was to find the association between dietary zinc intake and the prevalence of olfactory disorders using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: A cross-sectional study was conducted using the 2013-2014 NHANES data. A linear regression model was constructed with dietary zinc intake as the independent variable and olfactory dysfunction as the dependent variable. Initially, in the unadjusted model, weighted logistic regression analysis was carried out for continuous variables, and stratified analysis was conducted for categorical variables. Subsequently, three models were created to perform subgroup analysis by adjusting for different confounding factors, further investigating the relationship between dietary zinc intake and olfactory dysfunction. Finally, restricted cubic spline (RCS) models adjusting for all confounding factors were utilized to study the nonlinear associations of age and dietary zinc intake with olfactory dysfunction and their relevant thresholds. RESULTS: A total of 2958 samples were analyzed in this study. Weighted logistic regression analysis displayed a negative relationship between dietary zinc intake and the prevalence of olfactory dysfunction in the population of non-Hispanic whites and other Hispanics, as well as in individuals with body mass index (BMI) ≥ 25 kg/m2 (OR < 1, P < 0.05). The P values for the multiplicative interaction terms adjusting for all confounding factors were not significant (P for interaction > 0.05). In the three regression models adjusting for different confounding factors, dietary zinc intake was significantly negatively related to olfactory dysfunction in all populations (Crude: OR 0.63, 95% CI 0.44-0.91; Model I: OR 0.58, 95% CI 0.38-0.90; Model II: OR 0.59, 95% CI 0.35-1.00). Subgroup analysis based on BMI showed a remarkable negative relationship between dietary zinc intake and olfactory dysfunction in the group with BMI of 25-30 kg/m2 (Crude: OR 0.50, 95% CI 0.28-0.90, P = 0.012; Model I: OR 0.49, 95% CI 0.24-1.00, P = 0.021) and the group with BMI ≥ 30 kg/m2 (Crude: OR 0.55, 95% CI 0.33-0.92, P = 0.013; Model I: OR 0.51, 95% CI 0.29-0.88, P = 0.005; Model II: OR 0.51, 95% CI 0.29-0.91, P = 0.004). RCS analysis revealed a remarkable nonlinear association of age and dietary zinc intake with olfactory dysfunction (P-non-linear < 0.05). The prevalence of olfactory dysfunction was considerably higher in individuals aged 60 and above compared to those under 60 years old. Daily dietary zinc intake within the range of 9.60-17.45 mg was a protective factor for olfactory dysfunction, while intake outside this range increased the prevalence of olfactory dysfunction. CONCLUSION: Daily dietary zinc intake within the range of 9.60-17.45 mg has a protective effect against olfactory dysfunction. Intake outside this range increases the prevalence of olfactory dysfunction. The prevalence of olfactory dysfunction is significantly higher in individuals aged 60 and above compared to those under 60 years old. For individuals with a BMI of 25-30 kg/m2 and a BMI ≥ 30 kg/m2, dietary zinc intake is negatively correlated with olfactory dysfunction. Therefore, it is recommended that these populations increase their dietary zinc intake to develop healthier lifestyles and maintain olfactory health.

Enhancing Safety in AI-Driven Cone Beam CT-based Online Adaptive Radiation Therapy: Development and Implementation of an Interdisciplinary Workflow.

Purpose: The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the "black box" adaptation process. This study identifies high-risk failure modes (FMs) associated with AI-driven OART and proposes an interdisciplinary workflow to mitigate potential medical errors from highly automated processes, enhance treatment efficiency, and reduce the burden on clinicians. Methods and Materials: An interdisciplinary working group was formed to identify safety concerns in each process step using failure mode and effects analysis (FMEA). Based on the FMEA results, the team designed standardized procedures and safety checklists to prevent errors and ensure successful task completion. The Risk Priority Numbers (RPNs) for the top twenty FMs were calculated before and after implementing the proposed workflow to evaluate its effectiveness. Three hundred seventy-four adaptive sessions across 5 treatment sites were performed, and each session was evaluated for treatment safety and FMEA assessment. Results: The OART workflow has 4 components, each with 4, 8, 13, and 4 sequentially executed tasks and safety checklists. Site-specific template preparation, which includes disease-specific physician directives and Intelligent Optimization Engine template testing, is one of the new procedures introduced. The interdisciplinary workflow significantly reduced the RPNs of the high-risk FMs, with an average decrease of 110 (maximum reduction of 305.5 and minimum reduction of 27.4). Conclusions: This study underscores the importance of addressing high-risk FMs associated with AI-driven OART and emphasizes the significance of safety measures in its implementation. By proposing a structured interdisciplinary workflow and integrated checklists, the study provides valuable insights into ensuring the safe and efficient delivery of OART while facilitating its effective integration into clinical practice.

A Comparative Study on Fixed-order Event Sequence Visualizations: Gantt, Extended Gantt, and Stringline Charts.

We conduct two in-lab experiments (N=93) to evaluate the effectiveness of Gantt charts, extended Gantt charts, and stringline charts for visualizing fixed-order event sequence data. We first formulate five types of event sequences and define three types of sequence elements: point events, interval events, and the temporal gaps between them. Our two experiments focus on event sequences with a pre-defined, fixed order, and measure task error rates and completion time. The first experiment shows single sequences and assesses the three charts' performance in comparing event duration or gap. The second experiment shows multiple sequences and evaluates how well the charts reveal temporal patterns. The results suggest that when visualizing single fixed-order event sequences, 1) Gantt and extended Gantt charts lead to comparable error rates in the duration-comparing task; 2) Gantt charts exhibit either shorter or equal completion time than extended Gantt charts; 3) both Gantt and extended Gantt charts demonstrate shorter completion times than stringline charts; 4) however, stringline charts outperform the other two charts with fewer errors in the comparing task when event type counts are high. Additionally, when visualizing multiple point-based fixed-order event sequences, stringline charts require less time than Gantt charts for people to find temporal patterns. Based on these findings, we discuss design opportunities for visualizing fixed-order event sequences and discuss future avenues for optimizing these charts.

Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN.

Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.

InnovationInsights: A Visual Analytics Approach for Understanding the Dual Frontiers of Science and Technology.

Science has long been viewed as a key driver of economic growth and rising standards of living. Knowledge about how scientific advances support marketplace inventions is therefore essential for understanding the role of science in propelling real-world applications and technological progress. The increasing availability of large-scale datasets tracing scientific publications and patented inventions and the complex interactions among them offers us new opportunities to explore the evolving dual frontiers of science and technology at an unprecedented level of scale and detail. However, we lack suitable visual analytics approaches to analyze such complex interactions effectively. Here we introduce InnovationInsights, an interactive visual analysis system for researchers, research institutions, and policymakers to explore the complex linkages between science and technology, and to identify critical innovations, inventors, and potential partners. The system first identifies important associations between scientific papers and patented inventions through a set of statistical measures introduced by our experts from the field of the Science of Science. A series of visualization views are then used to present these associations in the data context. In particular, we introduce the Interplay Graph to visualize patterns and insights derived from the data, helping users effectively navigate citation relationships between papers and patents. This visualization thereby helps them identify the origins of technical inventions and the impact of scientific research. We evaluate the system through two case studies with experts followed by expert interviews. We further engage a premier research institution to test-run the system, helping its institution leaders to extract new insights for innovation. Through both the case studies and the engagement project, we find that our system not only meets our original goals of design, allowing users to better identify the sources of technical inventions and to understand the broad impact of scientific research; it also goes beyond these purposes to enable an array of new applications for researchers and research institutions, ranging from identifying untapped innovation potential within an institution to forging new collaboration opportunities between science and industry.

HealthPrism: A Visual Analytics System for Exploring Children's Physical and Mental Health Profiles with Multimodal Data.

The correlation between children's personal and family characteristics (e.g., demographics and socioeconomic status) and their physical and mental health status has been extensively studied across various research domains, such as public health, medicine, and data science. Such studies can provide insights into the underlying factors affecting children's health and aid in the development of targeted interventions to improve their health outcomes. However, with the availability of multiple data sources, including context data (i.e., the background information of children) and motion data (i.e., sensor data measuring activities of children), new challenges have arisen due to the large-scale, heterogeneous, and multimodal nature of the data. Existing statistical hypothesis-based and learning model-based approaches have been inadequate for comprehensively analyzing the complex correlation between multimodal features and multi-dimensional health outcomes due to the limited information revealed. In this work, we first distill a set of design requirements from multiple levels through conducting a literature review and iteratively interviewing 11 experts from multiple domains (e.g., public health and medicine). Then, we propose HealthPrism, an interactive visual and analytics system for assisting researchers in exploring the importance and influence of various context and motion features on children's health status from multi-levelperspectives. Within HealthPrism, a multimodal learning model with a gate mechanism is proposed for health profiling and cross-modality feature importance comparison. A set of visualization components is designed for experts to explore and understand multimodal data freely. We demonstrate the effectiveness and usability of HealthPrism through quantitative evaluation of the model performance, case studies, and expert interviews in associated domains.