Metabolic reprogramming: a new option for the treatment of spinal cord injury.

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

Prefrontal cortex neurons encode ambient light intensity differentially across regions and layers.

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions' contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.

A leak K+ channel TWK-40 sustains the rhythmic motor program.

Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to the rhythmic defecation motor program (DMP) in Caenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function (gf) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.

A wearable non-enzymatic sensor for continuous monitoring of glucose in human sweat.

To enhance personalized diabetes management, there is a critical need for non-invasive wearable electrochemical sensors made from flexible materials to enable continuous monitoring of sweat glucose levels. The main challenge lies in developing glucose sensors with superior electrochemical characteristics and high adaptability. Herein, we present a wearable sensor for non-enzymatic electrochemical glucose analysis. The sensor was synthesized using hydrothermal and one-pot preparation methods, incorporating gold nanoparticles (AuNPs) functionalized onto aminated multi-walled carbon nanotubes (AMWCNTs) as an efficient catalyst, and crosslinked with carboxylated styrene butadiene rubber (XSBR) and PEDOT:PSS. The sensors were then integrated onto screen-printed electrodes (SPEs) to create flexible glucose sensors (XSBR-PEDOT:PSS-AMWCNTs/AuNPs/SPE). Operating under neutral conditions, the sensor exhibits a linear range of 50 µmol/L to 600 µmol/L, with a limit of detection limit of 3.2 µmol/L (S/N = 3), enabling the detection of minute glucose concentrations. The flexible glucose sensor maintains functionality after 500 repetitions of bending at a 180° angle, without significant degradation in performance. Furthermore, the sensor exhibits exceptional stability, repeatability, and resistance to interference. Importantly, we successfully monitored changes in sweat glucose levels by applying screen-printed electrodes to human skin, with results consistent with normal physiological blood glucose fluctuations. This study details the fabrication of a wearable sensor characterized by ease of manufacture, remarkable flexibility, high sensitivity, and adaptability for non-invasive blood glucose monitoring through non-enzymatic electrochemical analysis. Thus, this streamlined fabrication process presents a novel approach for non-invasive, real-time blood glucose level monitoring.

Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.

The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-ß, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfß, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.

Liver injury in paraquat poisoning: A retrospective cohort study.

BACKGROUND AND AIMS: Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. METHODS: We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. RESULTS: A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. CONCLUSIONS: The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.

An innovative triple interface reinforced photocatalytic system based on BiOCl/BaTiO3@Co-BDC-MOF composite for the simultaneous detoxification of Cr(VI) and sulfamethoxazole.

The development of effective photocatalysts for the reduction of Cr(VI) and the degradation of antibiotics remains a challenge. The present work reports the development of a novel heterojunction composite material, BiOCl/BaTiO3@Co-BDC-MOF (BOC/BTO@Co-MOF), based on solvothermal techniques. To characterize the surface and bulk features of the material, techniques such as FE-SEM, HR-TEM, BET/BJH, XPS, FT-IR, p-XRD, and UV-Vis-DRS were used. Based on the results, the BiOCl/BaTiO3 nanocomposites are uniformly dispersed on the rod-shaped Co-BDC MOF, resulting in a layered texture on the surface. A further advantage of the composite structure is the strong interfacial enhancement facilitating the separation of photoexcited electron-hole pairs. Also, compared to its pristine counterparts, the heterostructure material exhibited excellent surface area and pore properties. The photocatalytic efficiency towards reduction and degradation of Cr(VI)/SMX pollutants were evaluated by optimizing various analytical parameters, such as pH, catalytic loading concentrations, analyte concentration, and scavenger role. The specially designed BOC/BTO@Co-MOF composite achieved a 96.5% Cr(VI) reduction and 98.2% SMX degradation under 60.0-90.0 min of visible light illumination at pH 3.0. This material is highly reusable and has a six-time recycling potential. The findings of this study contribute to a better understanding of the efficient decontamination of inorganic and organic pollutants in water purification systems.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

Integrating experiments with modeling to understand key bacterial taxa dynamics after episodic mixing of a stratified water column.

Hydraulic mixing of stratified reservoirs homogenizes physicochemical gradients and microbial communities. This has potential repercussions for microbial metabolism and water quality, not least in dams and hydraulically controlled waters. A better understanding of how key taxa respond to mixing of such stratified water bodies is needed to understand and predict the impact of hydraulic operations on microbial communities and nutrient dynamics in reservoirs. We studied taxa transitions between cyanobacteria and sulfur-transforming bacteria following mixing of stratified water columns in bioreactors and complemented the experimental approach with a biogeochemical model. Model predictions were consistent with experimental observations, suggesting that stable stratification of DO is restored within 24 h after episodic and complete mixing, at least in the absence of other more continuous disturbances. Subsequently, the concentration of S2- gradually return to pre-mixing states, with higher concentration at the surface and lower in the bottom waters, while the opposite pattern was seen for SO42-. The total abundance of sulfate-reducing bacteria and phototrophic sulfur bacteria increased markedly after 24h of mixing. The model further predicted that the rapid re-oxygenation of the entire water column by aeration will effectively suppress the water stratification and the growth of sulfur-transforming bacteria. Based on these results, we suggest that a reduction of thermocline depth by optimal flow regulation in reservoirs may also depress sulfur transforming bacteria and thereby constrain sulfur transformation processes and pollutant accumulation. The simulation of microbial nutrient transformation processes in vertically stratified waters can provide new insights about effective environmental management measures for reservoirs.

Potential mediation effect of insulin resistance on the association between iron metabolism indicators and non-alcoholic fatty liver disease.

OBJECTIVES: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. METHODS: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. RESULTS: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. CONCLUSION: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.

Hysteretic and asynchronous regime shifts of bacterial and micro-eukaryotic communities driven by nutrient loading.

Nutrient pollution is pervasive in many urban rivers, while restoration measures that reduce nutrient loading but fail to improve biological communities often lack effectiveness due to the indispensable role of biota, especially multi-taxa, in enhancing ecosystem stability and function. The investigation of the response patterns of multi-taxa to the nutrient loading in urban rivers is important for the recovery of biota structure and thus ecosystem function. However, little is known about the response patterns of multi-taxa and their impact on ecosystem structure and function in urban rivers. Here, the study, from the perspective of alternative stable states theory, showed the hysteretic response of both bacterial and micro-eukaryotic communities to nutrient loading based on the field investigation and environmental DNA metabarcoding. Bistability was shown to exist in both bacterial and micro-eukaryotic communities, demonstrating that the response of microbiota to nutrient loading was a regime shifts with hysteresis. Potential analysis then indicated that the increased nutrient loading drove regime shifts in the bacterial community and the micro-eukaryotic community towards a state dominated by anaerobic bacteria and benthic Bacillariophyta, respectively. High nutrient loading was found to reduce the relative abundance of metazoan, but increase that of eukaryotic algae, which made the trophic pyramid top-lighter and bottom-heavier, probably exacerbating the degradation of ecosystem function. It should be noted that, in response to the reduced nutrient loading, the recovery threshold of micro-eukaryotic communities (nutrient loading = ∼0.5) was lower than that of bacterial communities (nutrient loading = ∼1.2), demonstrating longer hysteresis of micro-eukaryotic communities. In addition, the markedly positive correlation between the status of microbial communities and N-related enzyme activities suggested the recovery of microbial communities probably will benefit the improvement of N-cycling functionality. The obtained results provide a deep insight into the collapse and recovery trajectories of multi-trophic microbiota to the nutrient loading gradient and their impact on the N transformation potential, therefore benefiting the restoration and management of urban rivers.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

Predictions of Colloidal Molecular Aggregation Using AI/ML Models.

To facilitate the triage of hits from small molecule screens, we have used various AI/ML techniques and experimentally observed data sets to build models aimed at predicting colloidal aggregation of small organic molecules in aqueous solution. We have found that Naïve Bayesian and deep neural networks outperform logistic regression, recursive partitioning tree, support vector machine, and random forest techniques by having the lowest balanced error rate (BER) for the test set. Derived predictive classification models consistently and successfully discriminated aggregator molecules from nonaggregator hits. An analysis of molecular descriptors in favor of colloidal aggregation confirms previous observations (hydrophobicity, molecular weight, and solubility) in addition to undescribed molecular descriptors such as the fraction of sp3 carbon atoms (Fsp3), and electrotopological state of hydroxyl groups (ES_Sum_sOH). Naïve Bayesian modeling and scaffold tree analysis have revealed chemical features/scaffolds contributing the most to colloidal aggregation and nonaggregation, respectively. These results highlight the importance of scaffolds with high Fsp3 values in promoting nonaggregation. Matched molecular pair analysis (MMPA) has also deciphered context-dependent substitutions, which can be used to design nonaggregator molecules. We found that most matched molecular pairs have a neutral effect on aggregation propensity. We have prospectively applied our predictive models to assist in chemical library triage for optimal plate selection diversity and purchase for high throughput screening (HTS) in drug discovery projects.

Narrative review of stereotactic body radiation therapy combined with tyrosine kinase inhibitors for oligometastatic EGFR-mutated non-small cell lung cancer: present and future developments.

Background and Objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC. Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC. Key Content and Findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness. Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.

Assessing the prognostic utility of clinical and radiomic features for COVID-19 patients admitted to ICU: challenges and lessons learned.

Severe cases of COVID-19 often necessitate escalation to the Intensive Care Unit (ICU), where patients may face grave outcomes, including mortality. Chest X-rays play a crucial role in the diagnostic process for evaluating COVID-19 patients. Our collaborative efforts with Michigan Medicine in monitoring patient outcomes within the ICU have motivated us to investigate the potential advantages of incorporating clinical information and chest X-ray images for predicting patient outcomes. We propose an analytical workflow to address challenges such as the absence of standardized approaches for image pre-processing and data utilization. We then propose an ensemble learning approach designed to maximize the information derived from multiple prediction algorithms. This entails optimizing the weights within the ensemble and considering the common variability present in individual risk scores. Our simulations demonstrate the superior performance of this weighted ensemble averaging approach across various scenarios. We apply this refined ensemble methodology to analyze post-ICU COVID-19 mortality, an occurrence observed in 21% of COVID-19 patients admitted to the ICU at Michigan Medicine. Our findings reveal substantial performance improvement when incorporating imaging data compared to models trained solely on clinical risk factors. Furthermore, the addition of radiomic features yields even larger enhancements, particularly among older and more medically compromised patients. These results may carry implications for enhancing patient outcomes in similar clinical contexts.

A comparative study of sampling methods in the detection of esophageal cancer-related microbiota.

Esophageal cancer (EC) is a multifaceted disease. Our understanding of the involvement of esophageal microbiota in its pathogenesis and progression is limited, which is due to the lack of proper endoscopic sampling methods. Hereby, we conducted a comparative analysis of paired samples obtained through endoscopic brushing and cytosponge, aiming at assessing the feasibility of using cytosponge as a minimally invasive sampling way for studying esophageal microbiota. Our findings suggest that cytosponge sampling yielded significantly superior community richness and diversity compared to endoscopic brushing in both controls (non-cancerous) and EC individuals. The analysis of beta-diversity revealed distinct microbial community pattern in the genus diversity between the two sampling methods, underscoring the importance of selecting appropriate sampling methods to effectively characterize the esophageal microbiota. Specifically, Lactococcus and Serratia showed higher abundance in the samples collected by endoscopic brushing, while Alloprevotella and Leptotrichia were more enriched in the samples collected by cytosponge. These differences in dominant microbes were associated with metabolic pathways that particularly were related to host inflammation, such as pyruvate and glucose metabolisms. Notably, the phylogenetic levels of the microbiota indicated varied explanatory power for different detection purposes. This study underscores the substantial impact of sampling method selection on the acquisition of esophageal microbiota associated with the EC development, encompassing considerations of both abundance and diversity. This highlights the significance of selecting an appropriate sampling method for investigating the esophageal microbial status and studying the micro-environment in EC-related individuals. IMPORTANCE: This study addresses a critical issue in esophageal cancer study by comparing two different sampling methods, endoscopic brushing and cytosponge, for investigating the esophageal microbiota. Our work highlights the suitability of the cytosponge technique as a minimally invasive sampling method for studying the esophageal microbiota and emphasizes the importance of selecting an appropriate sampling method to characterize the microbial community. Our findings have significant implications for advancing the understanding of the role of the esophageal microbiota in cancer development and will inform future research and clinical approaches in this field.

Incidence and patterns of lymph node metastases in head and neck rhabdomyosarcoma: One-institution study.

INTRODUCTION: Head and neck rhabdomyosarcoma (HNRMS) is an aggressive malignant soft tissue tumor that easily develops lymph node metastasis (LNM) and distant metastasis. No literature investigates the pattern of LNM in HNRMS. METHODS: Ninety-five consecutive patients with HNRMS newly diagnosed at one institution between November 2011 and July 2023 were retrospectively reviewed. All the patients underwent head and neck contrast-enhanced MRI and/or CT, PET-CT if necessary. The associations between LNMs and clinical characteristics and histopathological parameters were discovered. RESULTS: 44.2% of patients had evidence of LNM at diagnosis, and the most common LNM occurred in the ipsilateral retropharyngeal space. The primary tumor metastasizes to the retropharyngeal space, and then next to level II is the most common LN drainage basin. In multivariate analysis, only distant metastasis determines the prognosis, other than LN status. CONCLUSIONS: LNM has a high incidence in HNRMS and rarely causes contralateral metastasis for localized lesions or skip metastasis.