Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer.

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.

Lactate and Lactylation: Clinical Applications of Routine Carbon Source and Novel Modification in Human Diseases.

Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for posttranslational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play a pleiotropic role in shaping cell identities through metabolic rewiring and epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among glycolysis, lactate, and lactylation. Furthermore, the multiple metabolic fates of lactate make it an ideal substrate for metabolic imaging in clinical application. Several studies have identified the crucial role of protein lactylation in human diseases associated with cell fate determination, embryonic development, inflammation, neoplasm, and neuropsychiatric disorders. Herein, this review will focus on the metabolic fate of lactate-derived carbon to provide useful information for further research and therapeutic approaches in human diseases. We comprehensively discuss its role in reprogramming and modification during the regulation of glycolysis, the clinical translation prospects of the hyperpolarized lactate signal, lactyl modification in human diseases, and its application with other techniques and omics.

Controllable non-uniformly distributed spiking cluster generation in broadband optoelectronic oscillator.

An approach to achieve controllable non-uniformly distributed spiking cluster generation is proposed and demonstrated based on an externally-triggered broadband optoelectronic oscillator (OEO). The theory of controlling the distribution of the spiking pulses in a spiking cluster is established. Based on the theory, the dynamic and the distribution characteristics are analyzed and revealed in the stable spiking oscillation state under different externally-injected trigger signal voltages. The peak-voltage envelop of the cluster and the interval of the spiking pulses are demonstrated to have an approximate negative linearity relationship with the externally-injected trigger signal voltage in both the numerical simulation and the experiment, where a square waveform, a trapezoidal waveform, a parabola waveform, and a half-sinusoidal waveform are used as the externally-injected trigger signals. The results indicate that the spiking pulse distribution in the generated spiking cluster can be well controlled through tuning the externally-injected trigger signal voltage. The proposed scheme can be utilized in spiking encoding and reservoir computing.

Phase-locked dual-frequency microwave signal generation in an optoelectronic oscillator based on frequency mixing mutual injection.

An approach to generating stable phase-locked dual-frequency microwave signals is proposed and demonstrated based on a dual-passband optoelectronic oscillator (OEO). Mode gain competition is broken by employing frequency mixing mutual injection effect to realize phase locking between the two oscillation signals, which is achieved by applying a single-tone signal to a microwave mixer in the OEO cavity. In addition, a dual-loop configuration with balanced detection is utilized to ensure a high side mode suppression ratio (SMSR) and ultra-low phase noise, which also enhances the stability of the generated signal. In the experiment, a phase-locked dual-frequency microwave signal at 9.9982 GHz and 10.1155 GHz is generated by using the proposed OEO scheme. The SMSR and the phase noise are 75 dB and -141 dBc/Hz@10 kHz, respectively. Additionally, the Allan deviation of the generated signal is in the order of 10-11@1 s. These parameters are superior to those based on the same OEO but with a single-loop configuration, which are also compared in detail.

Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.

BACKGROUND: Protein kinase C delta (PRKCD) and caspase recruitment domain family member 9 (CARD9) are genes involved in B and T cell activation, and cytokine production, which are vital mechanisms underlying autoimmune disease development. This study aimed to explore the association of the PRKCD and CARD9 genes with Vogt-Koyanagi-Harada disease (VKH) disease. The case-control study was performed to in 912 patients with VKH and 878 normal controls. MassARRAY system, SHEsis online platform, real-time PCR, and enzyme-linked immunosorbent assay were used to detect genotyping, haplotyping, mRNA expression, and cytokine levels, respectively. RESULTS: We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10-5, OR = 1.810; Pc = 2.76 × 10-5, OR = 1.698, respectively). However, the rs74437127 T allele, and rs3812555 TC genotype and T allele were linked with decreased susceptibility to VKH (Pc = 0.020, OR = 0.616; Pc = 7.85 × 10-5, OR = 0.559; Pc = 2.76 × 10-5, OR = 0.589, respectively). PRKCD ATG and CARD9 GCTTA haplotypes decreased susceptibility to VKH (Pc = 3.11 × 10-3, OR = 0.594; Pc = 5.00 × 10-3, OR = 0.639, respectively). Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10-4; P = 2.00 × 10-3, respectively). CONCLUSIONS: We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α.

Application of sourdough in gluten-free bakery products.

ABSTRACTSIn recent years, the demand for gluten-free (GF) bakery products has grown rapidly due to the remarkable rising number of celiac patients and the increasing health awareness of GF products. However, GF products generally suffer from defects such as poor sensorial level, low nutritional value, high prices and short shelf life. Sourdough is the important starter culture applied in bakery field, and it has been proven to be ideal for enhancing the overall quality of bakery products. This review aims to systematically reviewed the application of sourdough in GF bakery products and its improvement to GF bakery products in terms of texture, shelf life, nutrition and flavor. Its positive effects derive from the complex metabolic activities of sourdough microorganisms, such as acidification, proteolysis, production of exopolysaccharides (EPS), activation of endogenous enzymes, and production of antibacterial substances. Finally, researchers are encouraged to expand the use of sourdough in GF bakery products to increase the variety of GF products. And the technical and nutritional potential of sourdough should be developed more widely.

Silicon induces ROS scavengers, hormone signalling, antifungal metabolites, and silicon deposition against brown stripe disease in sugarcane.

Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.

Ionomer structure and component transport in the cathode catalyst layer of PEM fuel cells: A molecular dynamics study.

The transport of water and protons in the cathode catalyst layer (CCL) of proton exchange membrane (PEM) fuel cells is critical for cell performance, but the underlying mechanism is still unclear. Herein, the ionomer structure and the distribution/transport characteristics of water and protons in CCLs are investigated via all-atom molecular dynamics simulations. The results show that at low water contents, isolated water clusters form in ionomer pores, while proton transport is mainly via the charged sites of the ionomer side chains and the Grotthuss mechanism. Moreover, with increasing water content, water clusters are interconnected to form continuous water channels, which provide effective paths for proton transfer via the vehicular and Grotthuss mechanisms. Increasing the ionomer mass content can enhance the dense arrangement of the ionomer, which, in turn, increases the density of charge sites and improves the proton transport efficiency. When the ionomer mass content is high, the clustering effect reduces the space for water diffusion, increases the proton transport path, and finally decreases the proton transport efficiency. By providing physics insights into the proton transport mechanism, this study is helpful for the structural design and performance improvement of CCLs of PEM fuel cells.

Expression and functional analysis of Fushi Tarazu transcription factor 1 (FTZ-F1) in the regulation of steroid hormones during the gonad development of Fujian Oyster, Crassostrea angulata.

Crassostrea angulata, a major shellfish cultivated in Southern China, has experienced a notable surge in commercial value in recent years. Understanding the molecular mechanisms governing their reproductive processes holds significant implications for advancing aquaculture practices. In this study, we cloned the orphan nuclear receptor gene, Fushi Tarazu transcription factor 1 (FTZ-F1), of C. angulata and investigated its functional role in the gonadal development. The full-length cDNA of FTZ-F1 spans 2357 bp and encodes a protein sequence of 530 amino acids. Notably, the amino acid sequence of FTZ-F1 in C. angulata shares remarkable similarity with its homologues in other species, particularly in the DNA-binding region (>90%) and ligand-binding region (>44%). In C. angulata, the highest expression level of FTZ-F1 was observed in the ovary, exhibiting more than a 200-fold increase during the maturation stage compared to the initiation stage (P < 0.001). Specifically, FTZ-F1 was mainly expressed in the follicular cells surrounding the oocytes of C. angulata. Upon inhibiting FTZ-F1 gene expression in C. angulata through RNA interference (RNAi), a substantial reduction in the expression of genes involved in the synthesis of sex steroids in the gonads, including 3ß-HSD, Cyp17, and follistatin, was observed. In addition, estradiol (E2) and testosterone (T) levels also showed a decrease upon FTZ-F1 silencing, resulting in a delayed gonadal development. These results indicate that FTZ-F1 acts as a steroidogenic factor, participating in the synthesis and regulation of steroid hormones and thus playing an important role in the reproductive and endocrine systems within oysters.

Application Effect of 6S Management Mode in Operating Room Nursing.

Background: The nursing work in the operating room is heavy, intensive, and irregular, and the quality of nursing work can directly affect the surgical effect and patient prognosis. Therefore, nursing management in the operating room should be strengthened to protect patients' life safety effectively. Objective: To assess the effectiveness of applying the 6S management model in operating room nursing. Design: This was a retrospective study. Setting: This study was conducted at the Department of Anesthesia Surgery, Nanfang Hospital, Southern Medical University. Participants: The research included 100 operating room nurses on duty between January 2020 and December 2022. Intervention: From January 2020 to June 2021, the hospital conducted routine training programs for nurses in the operating room. From July 2021 to December 2022, the hospital adopted the 6S management model for overseeing nursing work in the operating room. Primary Outcome Measures: (1) nursing quality score (2) nursing staff safety awareness (3) nursing disputes and complaints (4) incidence of adverse reactions (5) patient satisfaction with the quality of nursing care. Results: Following the adoption of the 6S management model, there was a noticeable improvement in the nursing quality scores, the nursing staff's awareness of safety, and the satisfaction levels of patients with the quality of care provided by operation nurses (P < .05). Additionally, the incidence of nursing disputes, complaints, and adverse events among patients decreased significantly compared to before the implementation of 6S (P = .01). Conclusion: Implementing 6S management with a focus on the work of operation room nurses enhanced the competence of the nursing staff and improved management effectiveness, ultimately leading to increased patient satisfaction.

Genomic and Comparative Transcriptomic Analyses Reveal Key Genes Associated with the Biosynthesis Regulation of Okaramine B in Penicillium daleae NBP-49626.

Restricted production of fungal secondary metabolites hinders the ability to conduct comprehensive research and development of novel biopesticides. Okaramine B from Penicillium demonstrates remarkable insecticidal efficacy; however, its biosynthetic yield is low, and its regulatory mechanism remains unknown. The present study found that the yield difference was influenced by fermentation modes in okaramine-producing strains and performed genomic and comparative transcriptome analysis of P. daleae strain NBP-49626, which exhibits significant features. The NBP-49626 genome is 37.4 Mb, and it encodes 10,131 protein-encoding genes. Up to 5097 differentially expressed genes (DEGs) were identified during the submerged and semi-solid fermentation processes. The oka gene cluster, lacking regulatory and transport genes, displayed distinct transcriptional patterns in response to the fermentation modes and yield of Okaramine B. Although transcription trends of most known global regulatory genes are inconsistent with those of oka, this study identified five potential regulatory genes, including two novel Zn(II)2Cys6 transcription factors, Reg2 and Reg19. A significant correlation was also observed between tryptophan metabolism and Okaramine B yields. In addition, several transporter genes were identified as DEGs. These results were confirmed using real-time quantitative PCR. This study provides comprehensive information regarding the regulatory mechanism of Okaramine B biosynthesis in Penicillium and is critical to the further yield improvement for the development of insecticides.

Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.

Cancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs.

aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients.

BACKGROUND & AIMS: The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS: A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS: The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

Nano Silicon Anode without Electrolyte Adding for Sulfide-Based All-Solid-State Lithium-Ion Batteries.

All-solid-state lithium-ion batteries (ASSLBs) employing silicon (Si) anode and sulfide electrolyte attract much attention, since they can achieve both high energy density and safety. For large-scale application, sheet-type Si anode matching sulfide based ASSLBs is preferred. Here, a LiAlO2 layer coated Si (Si@LiAlO2 ) is reported for sheet-type electrode. This electrode employs conventional slurry coating methods without adding any sulfide electrolyte. The effect of LiAlO2 coating on the electrochemical performance and morphology evolution of Si electrode is investigated. Since the high mechanical strength and ionic conductivity of LiAlO2 layer can sufficiently relieve the huge expansion of Si and promote the Li+ diffusion, the electrochemical performance is significantly enhanced. The Si@LiAlO2 electrodes deliver high coulombic efficiency exceeding 80% and hold considerable specific capacity of 1205 mAh g-1 (150 cycles, 0.33 C). The Si@LiAlO2 | LiNi0.83 Co0.11 Mn0.06 O2 full-cells exhibit a high reversible capacity of 147 mAh g-1 (0.28 mA cm-2 ) and a considerable capacity retention of 80.2% (62 cycles, 2.8 mA cm-2 ). This work demonstrates promising practicability and provides a new route for the scalable preparation of Si electrode sheets for ASSLBs with extended lifespan.

High-resolution real-time Fourier transform based on optical frequency comb injected frequency shifting loop.

A high-resolution real-time Fourier transform scheme is proposed and demonstrated based on injecting an optical frequency comb (OFC) into a frequency shifting loop (FSL). Through setting the frequency interval between neighboring teeth in the coherent OFC to be equal to an integer multiple of the frequency shift and also the free spectral range of the FSL, the number of the effective signal replicas from the FSL is increased by M times, where M is the tooth number of the OFC. Hence, it breaks the limitation on the number of round trips due to the gain saturation effect and the cumulative amplified spontaneous emission noise in the FSL under a single optical carrier injection, which greatly enhances the frequency resolution. In the experiment, a coherent three-tone optical carrier is injected into an FSL to realize real-time spectrum analysis, where the frequency resolution is enhanced by three times compared with that by using a single-tone optical carrier injection, i.e., from 60 kHz to 20 kHz.

Neuromorphic regenerative memory optoelectronic oscillator.

Neuromorphic spiking information processing based on neuron-like excitable effect has achieved rapid development in recent years due to its advantages such as ultra-high operation speed, programming-free implementation and low power consumption. However, the current physical platforms lack building blocks like compilers, logic gates, and more importantly, data memory. These factors become the shackles to construct a full-physical layer neural network. In this paper, a neuromorphic regenerative memory scheme is proposed based on a time-delayed broadband nonlinear optoelectronic oscillator (OEO), which enables reshaping and regenerating on-off keying encoding sequences. Through biasing the dual-drive Mach-Zehnder electro-optic modulator in the OEO cavity near its minimum transmission point, the OEO can work in excitable regime, where localized states are maintained for robust nonlinear spiking response. Both simulation and experiment are carried out to demonstrate the proposed scheme, where the simulation results and the experimental results fit in with each other. The proposed OEO-based neuromorphic regenerative memory scheme exhibits long-term response ability for short-term excitation, which shows an enormous application potential for high-speed neuromorphic information buffering, optoelectronic interconnection and computing.

Time-delay signature suppression of the chaotic signal in a semiconductor laser based on optoelectronic hybrid feedback.

An approach to generating chaotic signals with low time-delay signatures (TDSs) from a semiconductor laser (SCL) is proposed and demonstrated based on optoelectronic hybrid feedback. Through using a chirped fiber Bragg grating (CFBG) to provide distributed feedback, a chaotic signal with a low TDS is generated from the SCL. With the assistance of the nonlinear optoelectronic feedback provided by a microwave photonic link, the relaxation oscillation effect in the SCL is effectively suppressed, and the periodicity of the oscillation is greatly weakened. Hence, the TDS of the generated chaotic signal from the SCL is further suppressed, and the effective bandwidth is enlarged. Both simulation and experiment are carried out to verify the feasibility of the proposed scheme to suppress the TDS. In the experiment, a chaotic signal with a large effective bandwidth of 12.93 GHz, an extremely high permutation entropy (PE) of 0.9983, and a low TDS of 0.04, is generated by using a CFBG with a dispersion coefficient of 22.33 ps/nm. This TDS value is at the same level as that obtained by using the SCL-based scheme relying solely on distributed feedback in a CFBG with a dispersion coefficient of 2000 ps/nm.

Pulse generation with programmable positions based on a phase-modulated optical frequency-shifting loop.

An approach to generating pulses with programmable positions is proposed and demonstrated based on a phase-modulated optical frequency-shifting loop (OFSL). By setting the OFSL to operate in the integer Talbot state, pulses are generated in the phase-locked positions, since the additional phase introduced by the electro-optic phase modulator (PM) in the OFSL is equal to an integer multiple of 2π in each round trip. Therefore, the pulse positions can be controlled and encoded by designing the driving waveform of the PM in a round-trip time. In the experiment, linear, round-trip, quadratic, and sinusoidal variations of pulse intervals are achieved by applying the corresponding driving waveforms to the PM. Pulse trains with coded pulse positions are also realized. In addition, the OFSL driven by waveforms with repetition rates equal to double and triple the free spectral range of the loop is also demonstrated. The proposed scheme paves a way to generate optical pulse trains with user-defined pulse positions, which can be used for such applications as compressed sensing and lidar.

Management of metastatic melanoma in Texas: disparities in the utilization of immunotherapy following the regulatory approval of immune checkpoint inhibitors.

BACKGROUND: The utilization of modern-immunotherapies, notably immune checkpoint inhibitors (ICIs), has increased markedly in patients with metastatic melanoma over the past decade and are recommended as standard treatment. Given their increasing adoption in routine care for melanoma, understanding patient access to immunotherapy and patterns of its use in Texas is crucial as it remains one of the few states without Medicaid expansion and with high rates of the uninsured population. The objectives of this study were to examine the trend in the utilization of immunotherapy and to determine factors associated with immunotherapy utilization among patients with metastatic melanoma in the era of ICIs in Texas. METHODS: A retrospective cohort study was conducted using the Texas Cancer Registry (TCR) database. The cohort comprised of adult (≥ 18 years) patients with metastatic melanoma diagnosed between June 2011 and December 2018. The trend in immunotherapy utilization was assessed by determining the proportion of patients receiving immunotherapy each year. The Average Annual Percent Change (AAPC) in immunotherapy utilization was assessed using joinpoint regression, while multivariable logistic regression was used to determine the association between patient characteristics and immunotherapy receipt. RESULTS: A total of 1,795 adult patients with metastatic melanoma were identified from the TCR. Immunotherapy utilization was higher among younger patients, those with no comorbidities, and patients with private insurance. Multivariable analysis showed that the likelihood of receipt of immunotherapy decreased with older age [(adjusted Odds Ratio (aOR), 0.92; 95% CI, 0.89- 0.93, p = 0.001], living in high poverty neighborhood (aOR, 0.52; 95% CI, 0.44 - 0.66, p < 0.0001), having Medicaid (aOR, 0.58; 95% CI, 0.44 - 0.73, p = 0.02), being uninsured (aOR, 0.49; 95% CI, 0.31 - 0.64, p = 0.01), and having comorbidities (CCI score 1: aOR, 0.48; 95% CI, 0.34 - 0.71, p = 0.003; CCI score ≥ 2: aOR, 0.32; 95% CI, 0.16 - 0.56, p < 0.0001). CONCLUSIONS AND RELEVANCE: This cohort study identified sociodemographic and socioeconomic disparities in access to immunotherapy in Texas, highlighting the need for policies such as Medicaid expansion that would increase equitable access to this innovative therapy.

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

BACKGROUND: Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. PURPOSE: To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional. SUBJECTS: Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). FIELD STRENGTH/SEQUENCE: 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). ASSESSMENT: GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. RESULTS: In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). DATA CONCLUSION: GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.