RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Orientation and stretching of supracolloidal chains of diblock copolymer micelles by spin-coating process.

Supracolloidal chains consisting of nano- or micro-scale particles exhibit anisotropic properties not observed in individual particles. The orientation of the chains is necessary to manifest such characteristics on a macroscopic scale. In this study, we demonstrate the orientation of supracolloidal chains composed of nano-scale micelles of a diblock copolymer through spin-coating. We observed separate chains coated on a substrate with electron microscopy, and analyzed the orientation and stretching of the chains quantitatively with image analysis software. In drop-casting, the chains were coated randomly with no preferred orientation, and the degree of stretching exhibited an intrinsic semi-flexible nature. In contrast, spin-coated chains were aligned in the radial direction, and the apparent persistence length of the chain increased, confirming the stretching of the chain quantitatively. Furthermore, by incorporating fluorophores into supracolloidal chains and confirming the oriented chains with confocal fluorescence microscopy, it is demonstrated that oriented chains can be utilized as a template to align functional materials.

Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.

Objectives: This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries. Methods: Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group. Results: Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up. Conclusion: Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.

Understanding the Fluctuations in Korea's Suicide Rates: A Change-Point Analysis and Interrupted Time Series Analysis.

BACKGROUND: Korea has witnessed significant fluctuations in its suicide rates in recent decades, which may be related to modifications in its death registration system. This study aimed to explore the structural shifts in suicide trends, as well as accidental and ill-defined deaths in Korea, and to analyze the patterns of these changes. METHODS: We analyzed age-adjusted death rates for suicides, deaths due to transport accidents, falls, drowning, fire-related incidents, poisonings, other external causes, and ill-defined deaths in Korea from 1997 to 2021. We identified change-points using the 'breakpoints' function from the 'strucchange' package and conducted interrupted time series analyses to assess trends before and after these change-points. RESULTS: Korea's suicide rates had three change-points in February 2003, September 2008, and June 2012, characterized by stair-step changes, with level jumps at the 2003 and 2008 change-points and a sharp decline at the 2012 change-point. Notably, the 2003 and 2008 spikes roughly coincided with modifications to the death ascertainment process. The trend in suicide rates showed a downward slope within the 2003-2008 and 2008-2012 periods. Furthermore, ill-defined deaths and most accidental deaths decreased rapidly through several change-points in the early and mid-2000s. CONCLUSION: The marked fluctuations in Korea's suicide rate during the 2000s may be largely attributed to improvements in suicide classification, with potential implications beyond socio-economic factors. These findings suggest that the actual prevalence of suicides in Korea in the 2000s might have been considerably higher than officially reported.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation.

Objective: This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. Methods: A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery-Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8-14-year period after the initial stroke as long-term stroke outcome. We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. Results: Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8-14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. Conclusion: The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

Study on Compressibility According to Mixing Ratio and Milling Time of Fe-6.5wt.%Si.

Recently, researchers have focused on improving motor performance and efficiency. To manufacture motors with performance and efficiency higher than those of motors manufactured through the additive process, compressibility verification through the parameter control of soft magnetic composites (SMCs) is essential. To this end, this study aims to select suitable powders for manufacturing high-performance, high-efficiency motors by exploring powder mixing ratios and milling times. Through physical property tests, the optimal mixing ratio is predicted using the Multi-Particle Finite Element Method (MPFEM) and powder compression molding analysis, and compressibility is predicted in view of the influence of a change in particle size as a function of the powder mixing ratio and milling time. In addition, based on the result of a comparative analysis of density through experiments and an analysis of internal defects through SEM, a 50:50 mixing ratio of hybrid atomizing and gas atomizing powders milled for 3 h provided the best compressibility. Therefore, the use of SMC cores fabricated using powder compression molding is expected to improve motor performance and efficiency.

Deep Learning Prediction of Triplet-Triplet Annihilation Parameters in Blue Fluorescent Organic Light-Emitting Diodes.

The triplet-triplet annihilation (TTA) ratio and the rate coefficient (kTT) of TTA are key factors in estimating the contribution of triplet excitons to radiative singlet excitons in fluorescent TTA organic light-emitting diodes. In this study, deep learning models are implemented to predict key factors from transient electroluminescence (trEL) data using new numerical equations. A new TTA model is developed that considers both polaron and exciton dynamics, enabling the distinction between prompt and delayed singlet decays with a fundamental understanding of the mechanism. In addition, deep learning models for predicting the kinetic coefficients and TTA ratio are established. After comprehensive optimization inspired by photophysics, determination coefficient values of 0.992 and 0.999 are achieved in the prediction of kTT and TTA ratio, respectively, indicating a nearly perfect prediction. The contribution of each kinetic parameter of polaron and exciton dynamics to the trEL curve is discussed using various deep-learning models.

Optimizing Binding Site Spacing in Fluidic Self-Assembly for Enhanced Microchip Integration Density.

This manuscript presents a comprehensive study on the assembly of microchips using fluidic self-assembly (FSA) technology, with a focus on optimizing the spacing between binding sites to improve yield and assembly. Through a series of experiments, we explored the assembly of microchips on substrates with varying binding site spacings, revealing the impact of spacing on the rate of undesired chip assembly across multiple sites. Our findings indicate a significant reduction in incorrect assembly rates as the spacing increases beyond a critical threshold of 140 µm. This study delves into the mechanics of chip alignment within the fluid medium, hypothesizing that the extent of the alloy's grip on the chips at different spacings influences assembly outcomes. By analyzing cases of undesired assembly, we identified the relationship between binding site spacing and the area of chip contact, demonstrating a decrease in the combined left and right areas of chips as the spacing increases. The results highlight a critical spacing threshold, which, when optimized, could significantly enhance the efficiency and precision of microchip assembly processes using FSA technology. This research contributes to the field of microcomponent assembly, offering insights into achieving higher integration densities and precision in applications, such as microLED displays and augmented reality (AR) devices.

Impact of suicidality on delayed-onset post-traumatic stress disorder is modified by age: A two-year longitudinal study.

OBJECTIVES: This study aimed to investigate the relationship between early suicidality and post-traumatic stress disorder (PTSD) onset in patients with physical injuries, focusing on age as a modifying factor. METHODS: At baseline, 1014 patients were evaluated for suicidality, age divided into younger (<60 years) vs. older (≥60 years) groups, and potential covariates. PTSD was diagnosed at follow-up at 3, 6, 12, and 24 months, and then were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models were used after adjusting for covariates. RESULTS: Presence of suicidality at baseline was significantly associated with delayed-onset PTSD in older but not younger patients with significant interaction terms, whereas it was significantly associated with early-onset PTSD across all age groups. CONCLUSION: Age-specific associations were found between suicidality and PTSD onset. The findings highlight the importance of early suicidality assessment, especially in older patients for ongoing monitoring and support, and underscore the critical need for early PTSD identification and intervention for all ages.

Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers.

BACKGROUND: Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. METHODS: This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. RESULTS: Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001). CONCLUSIONS: The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.

A novel ultrasensitive RNase H assay based on phosphorothioated-terminal hairpin formation and self-priming extension reaction.

We herein present a novel ultrasensitive RNase H assay based on phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP) reaction. The detection probe employed as a key component in this technique serves as a substrate for RNase H and triggers the PS-THSP reaction upon the RNase H-mediated degradation of the probe. As a consequence, a large number of long concatemeric amplification products could be produced and used to identify the RNase H activity through the fluorescence signals produced by the nucleic acid-specific fluorescent dye, SYTO 9. Importantly, the use of the gp32 protein allowed the PS-THSP reaction to be performed at 37 °C, ultimately enabling an isothermal one-step RNase H assay. Based on this sophisticated design principle, the RNase H activity was very sensitively detected, down to 0.000237 U mL-1 with high specificity. We further verified its practical applicability through its successful application to the screening of RNase H inhibitors. With its operational convenience and excellent analytical performance, this technique could serve as a new platform for RNase H assay in a wide range of biological applications.

Cellular Modeling of CLN6 with IPSC-derived Neurons and Glia.

Neuronal ceroid lipofuscinosis (NCL), type 6 (CLN6) is a neurodegenerative disorder associated with progressive neurodegeneration leading to dementia, seizures, and retinopathy. CLN6 encodes a resident-ER protein involved in trafficking lysosomal proteins to the Golgi. CLN6p deficiency results in lysosomal dysfunction and deposition of storage material comprised of Nile Red + lipids/proteolipids that include subunit C of the mitochondrial ATP synthase (SUBC). White matter involvement has been recently noted in several CLN6 animal models and several CLN6 subjects had neuroimaging was consistent with leukodystrophy. CLN6 patient-derived induced pluripotent stem cells (IPSCs) were generated from several of these subjects. IPSCs were differentiated into oligodendroglia or neurons using well-established small-molecule protocols. A doxycycline-inducible transgenic system expressing neurogenin-2 (the I3N-system) was also used to generate clonal IPSC-lines (I3N-IPSCs) that could be rapidly differentiated into neurons (I3N-neurons). All CLN6 IPSC-derived neural cell lines developed significant storage material, CLN6-I3N-neuron lines revealed significant Nile Red + and SUBC + storage within three and seven days of neuronal induction, respectively. CLN6-I3N-neurons had decreased tripeptidyl peptidase-1 activity, increased Golgi area, along with increased LAMP1 + in cell bodies and neurites. SUBC + signal co-localized with LAMP1 + signal. Bulk-transcriptomic evaluation of control- and CLN6-I3N-neurons identified >1300 differentially-expressed genes (DEGs) with Gene Ontogeny (GO) Enrichment and Canonical Pathway Analyses having significant changes in lysosomal, axonal, synaptic, and neuronal-apoptotic gene pathways. These findings indicate that CLN6-IPSCs and CLN6-I3N-IPSCs are appropriate cellular models for this disorder. These I3N-neuron models may be particularly valuable for developing therapeutic interventions with high-throughput drug screening assays and/or gene therapy.

Predicting suicidal ideation using multiple serum biomarkers in patients with acute coronary syndrome.

BACKGROUND: Biomarkers for suicidal behavior in patients with acute coronary syndrome (ACS) have yet to be elucidated. This study aimed to identify a panel of serum biomarkers associated with suicidal ideation (SI) in patients with ACS. METHODS: The study evaluated 969 patients within 2 weeks of ACS (acute phase) and 711 patients 12 months later (chronic phase). The evaluation included 14 serum biomarkers covering 7 functional systems, socio-demographic/clinical characteristics, and SI assessed by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. Logistic regression models were used to analyze the data. The results showed that 195 patients (20.1 %) had SI in the acute phase, and 87 patients (12.2 %) had SI in the chronic phase. RESULTS: A combination of five serum biomarkers (tumor necrosis factor-α, interleukin-1ß, folate, troponin I, and creatine kinase-MB) was significantly associated with SI in the acute phase, and a combination of three serum biomarkers (tumor necrosis factor-α, interleukin-1ß, and folate) was significantly associated with SI in the chronic phase in a clear dose-dependent manner (all P-values < 0.001) after adjustment for relevant covariates. DISCUSSION: These findings suggest that the application of a combination of multiple serum biomarkers could improve the predictability of SI in patients with ACS at both acute and chronic phases.

Identifying unique subgroups in suicide risks among psychiatric outpatients.

BACKGROUND: The presence of psychiatric disorders is widely recognized as one of the primary risk factors for suicide. A significant proportion of individuals receiving outpatient psychiatric treatment exhibit varying degrees of suicidal behaviors, which may range from mild suicidal ideations to overt suicide attempts. This study aims to elucidate the transdiagnostic symptom dimensions and associated suicidal features among psychiatric outpatients. METHODS: The study enrolled patients who attended the psychiatry outpatient clinic at a tertiary hospital in South Korea (n = 1, 849, age range = 18-81; 61% women). A data-driven classification methodology was employed, incorporating a broad spectrum of clinical symptoms, to delineate distinctive subgroups among psychiatric outpatients exhibiting suicidality (n = 1189). A reference group of patients without suicidality (n = 660) was included for comparative purposes to ascertain cluster-specific sociodemographic, suicide-related, and psychiatric characteristics. RESULTS: Psychiatric outpatients with suicidality (n = 1189) were subdivided into three distinctive clusters: the low-suicide risk cluster (Cluster 1), the high-suicide risk externalizing cluster (Cluster 2), and the high-suicide risk internalizing cluster (Cluster 3). Relative to the reference group (n = 660), each cluster exhibited distinct attributes pertaining to suicide-related characteristics and clinical symptoms, covering domains such as anxiety, externalizing and internalizing behaviors, and feelings of hopelessness. Cluster 1, identified as the low-suicide risk group, exhibited less frequent suicidal ideation, planning, and multiple attempts. In the high-suicide risk groups, Cluster 2 displayed pronounced externalizing symptoms, whereas Cluster 3 was primarily defined by internalizing and hopelessness symptoms. Bipolar disorders were most common in Cluster 2, while depressive disorders were predominant in Cluster 3. DISCUSSION: Our findings suggest the possibility of differentiating psychiatric outpatients into distinct, clinically relevant subgroups predicated on their suicide risk. This research potentially paves the way for personalizing interventions and preventive strategies that address cluster-specific characteristics, thereby mitigating suicide-related mortality among psychiatric outpatients.

Case report: Periventricular heterotopia and early-onset bipolar disorder in adolescent patient with history of childhood attention deficit hyperactivity disorder.

Periventricular heterotopia (PH) is a developmental malformation in the brain. Because the clinical symptoms are heterogeneous, few studies have investigated the psychiatric symptoms associated with PH. We describe the case of a 17-year-old male with bipolar disorder (BD), who had been treated for attention deficit-hyperactivity disorder (ADHD) and developmental delay in childhood. He had experienced depression for 1 year and was admitted to the emergency room following a suicide attempt. He was admitted to the psychiatric ward for further evaluation and treatment for elated mood, decreased need for sleep, increased sexuality, and delusion. The patient was diagnosed with BP-I disorder and PH via brain magnetic resonance imaging. After combined treatment with valproic acid and aripiprazole, his manic symptoms stabilized. To our knowledge, this is the first report of an adolescent PH case with a history of early onset BD and ADHD in childhood.

Use of Serum Biomarkers to Aid Antidepressant Selection in Depressive Patients.

Objective: : This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. Methods: : This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3-12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. Results: : Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1ß and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. Conclusion: : Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.

Two Cases of Posttraumatic Stress Disorder Caused by a Motor Vehicle Accident Treated with Virtual Reality Exposure Therapy.

Exposure-response prevention is an effective approach to treat anxiety disorders. Virtual reality exposure therapy (VRET) is a promising treatment for patients with posttraumatic stress disorder (PTSD). New research has helped refine and update VRET. In this study, we introduce a form of VRET developed for patients suffering from PTSD after a traffic accident, and present two cases treated using this protocol. After 6 weeks of VRET treatment, the two participants not only improved their PTSD symptoms, but also improved their depressed mood, anxiety, and insomnia symptoms. Future studies of VRET for car accident-related PTSD should utilize a controlled design with randomization in order to account for numerous possible confounds.

The moderating role of circadian gene polymorphisms in the relationship between sleep disturbance and circulating lymphocyte subsets in colorectal cancer patients.

AIM: We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms. METHODS: A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate. RESULTS: Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage. CONCLUSION: Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.

Mobocertinib and Bevacizumab for Amivantamab-Refractory Lung Cancer With EGFR Exon 20 Insertion Mutation: A Case Report.

Amivantamab is the first drug approved in EGFR exon 20 insertion-mutated NSCLC. Nevertheless, primary or secondary resistance to amivantamab is a frequent problem in clinical practice. We report a case of a patient with EGFR exon 20-mutated NSCLC who had primary resistance to amivantamab but was successfully treated by combining therapy of another EGFR exon 20 insertion-specific targeted drug mobocertinib and bevacizumab.