Modulation Response Research Articles

Comparative Analysis of Patient-reported Outcomes After Cranial Vault Remodeling and Strip Craniectomy With the FACE-Q Craniofacial Module.

The debate continues among craniofacial surgeons regarding the effectiveness of strip craniectomy (SC) compared with cranial vault remodeling (CVR) in achieving optimal functional and aesthetic outcomes in patients with single-suture craniosynostosis. This study aimed to compare long-term patient-reported outcomes (PROs) between SC and CVR procedures at a single institution using the validated FACE-Q Craniofacial module. Patients older than or equal to 8 years of age and parents of patients younger than 8 years of age who underwent SC or CVR for single-suture craniosynostosis were eligible. Patients with <2 years of follow-up, lambdoid synostosis, and syndromes were excluded. Primary endpoints were PROs as measured by the FACE-Q, with higher scores indicating increased health-related quality of life. Linear regression was used to control for covariates. Sixty-two participants completed the module (response rate 33.3%). SC was performed in 29 patients (46.8%), and CVR in 33 patients (53.2%). On unadjusted bivariate analysis, SC patients had higher eye (P=0.03) and forehead (P=0.05) scores. On regression analysis, controlling for sex, race, craniosynostosis type, and follow-up, there were no significant differences between operation types in any domain. Metopic and sagittal synostosis were associated with higher Eye (metopic: 17.61, P=0.049; sagittal: 41.44, P<0.001) and Head scores (metopic: 48.12, P=0.001; sagittal: 49.35, P<0.001), and sagittal synostosis was associated with higher Face (38.16, P<0.001), Forehead (55.93, P<0.001), and Nose scores (19.28, P=0.003). From patients' and parents' perspectives at a single institution, SC and CVR were equivalent regarding aesthetics and health-related quality of life.

Non-invasive laser bio-speckle technique for the study of optical irradiation on plant leaf lamina: Application to monitor salicylic acid modulated response in Zamioculcas zamiifolia

Non-invasive laser bio-speckle technique for the study of optical irradiation on plant leaf lamina: Application to monitor salicylic acid modulated response in Zamioculcas zamiifolia

Effects of Apnea-Induced Hypoxia on Hypoalgesia in Healthy Subjects

Introduction: Exercise-induced hypoalgesia is a phenomenon in which exercise bouts induce a reduction in pain sensitivity. Apnea training involves similar characteristics that could potentially induce hypoalgesia. Objectives: The objectives of this study are to explore the effect of apnea training on hypoalgesia; assess the correlation between conditioned pain modulation (CPM) response and apnea-induced hypoalgesia; and examine the association between hypoalgesia with hypoxemia, and heart rate (HR) during apnea. Methods: A randomized controlled trial was conducted comparing a walking protocol employing intermittent apnea compared with normal breathing in healthy volunteers. Hypoalgesia was tested with pressure pain thresholds (PPTs) and CPM. Oxygen saturation (SpO2) and HR were also tested. Results: Relevant but not significant changes were detected in the thumb (MD = 0.678 kg/cm2), and tibialis (MD = 0.718 kg/cm2) in favor of the apnea group. No significant differences were detected in CPM. The apnea group presented lower SpO2, but HR values similar to those of the control group during the intervention. Basal CPM and intrasession hypoxemia significantly correlated with the PPT response. However, HR did not correlate with the PPT response. Conclusions: The current results suggest a trend, though not statistically significant, toward an improvement in the PPT in favor of apnea training compared to normal breathing. Nevertheless, subjects who presented greater basal CPM and lower oxygen saturation during the session presented a greater PPT response, suggesting the possibility of mediators of response. Future investigations should clarify this phenomenon.

Numerical characterizations of the thermomechanical response of power modules with ceramic substrates and lead-free bonds

PurposeThe present paper aims to study the influence of the substrate system on the thermomechanical response of various lead-free die attach materials used in power electronics using nonlinear finite element simulations.Design/methodology/approachParticularly, three ceramic substrate systems, including direct copper bonded (DCB) and aluminum nitride (AlN) – as well as silicon nitride (Si3N4) –based insulated metal substrate (IMS) configurations are examined in this study. Additionally, three die attach systems, namely, silver-tin transient liquid phase (TLP), sintered silver (Ag) and sintered copper (Cu) are included in the analysis. ANSYS software is employed to build the finite element models of the power modules and to conduct the nonlinear thermomechanical investigations.FindingsThe simulation results revealed that the IMS, Si3N4 and DCB-based power modules end up with significantly lower interconnect inelastic strains and inelastic strain energies suggesting better fatigue life performance. Additionally, the bonding layer stresses and expected failure mechanism are not influenced by the substrate configuration rather than the bond material. For instance, the silver-tin TLP joints develop high stresses and hence brittle failures are expected. Nonetheless, the sintered Ag and sintered Cu have significantly lower stresses which could lead to fatigue-induced failures.Originality/valuePower electronics use various ceramic-based substrate systems because of their improved thermal conductivity, electrical insulation and heat resistance properties. The proper selection of the substrate structure could highly enhance the thermal fatigue of the power modules. Markedly, the findings of this research are useful for designing highly reliable and effective power modules continuously subjected to thermomechanical loadings.

Research on energy transfer and vibration suppression of nonlinear energy sink with nonlinear damping

The nonlinear energy sink is a nonlinear shock absorber that provides targeted energy transfer and plays a crucial role in structural vibration suppression. In this paper, the energy transfer and dynamic characteristics of nonlinear damping nonlinear energy sink systems are analyzed. Firstly, the theoretical model of the nonlinear damping NES system is described, and secondly, the equations of the system in the free state are derived by using the complex variable average method and the multi-scale method to obtain the energy transfer efficiency equation of the system. Through the study of the slow invariant manifold and energy transfer efficiency of the system, the influence of each system parameter on the energy transfer efficiency is analyzed. Then the equations of the system under harmonic excitation are processed in the same method to obtain the boundary equations of the system, through which the saddle-node bifurcation diagram of the system is plotted to study the influence of each system parameter on the saddle-node bifurcation characteristics of the system. Finally, the slow-varying equation of the system under harmonic excitation is derived, and the influence of each system parameter on the frequency detuning parameter interval of the strongly modulated response is obtained using the phase trajectory and a one-dimensional mapping diagram of the system, and the time-mileage diagram and Poincare section are used to prove the damping effect of the strongly modulated response.

Synthesis and optical properties of fluorinated polyurethaneimide electro-optic waveguide polymer

Fluorinated polyurethaneimide (PUI) electro-optic waveguide polymer with polyurethane and polyimide chain segment structures was synthesized by stepwise polymerization using the synthesized amino ester oligomer pu and imide oligomer pi as monomers. Since the main chain structure of the synthesized PUI had the functionality of both polyurethane and polyimide chain segment structures, it combines the excellent thermal and film-forming properties of polyurethanes and polyimides, as well as lower optical transmission loss in the near-infrared wavelength band. The glass transition temperature (Tg) of PUI was 182 °C, and the 5% heat loss decomposition temperature was 325 °C. The PUI had good optical properties with an optical propagation loss of 1.10 dB/cm and an electro-optic (EO) coefficient (γ33) of 86 pm/V at a wavelength of 1550 nm. A Mach-Zehnder interferometric polymer waveguide EO modulator had been designed and fabricated by using the PUI as a waveguide electro-optic core layer. The prepared polymer waveguide EO modulator showed a good electro-optic modulation response at a wavelength of 1550 nm under an applied 1 kHz sinusoidal modulation signal. The results showed that the synthesized PUI met the performance requirements for the preparation of polymer optical waveguide devices and was a polymer electro-optic waveguide material with good overall performance.

Rapid assessment of cardiac autonomic modulation and adaptive stress responses: Automatic calculation of time-varying parasympathetic, sympathetic, and Baevsky stress indexes

Cardiac autonomic modulation (CAM), which is regulated by the balance between the sympathetic and parasympathetic nervous systems, is involved in various physiological and pathological conditions. Heart rate variability (HRV) analysis has been used to explore the complex relationship between the brain and heart, as described by Porges&amp;rsquo; polyvagal theory and Thayer&amp;rsquo;s neurovisceral integration model. Recently, an automated calculation of new parasympathetic, sympathetic, and Baevsky stress indexes based on HRV parameters has been introduced for faster and more comprehensive CAM assessment, though their normal ranges remain undefined. This study aimed to determine the average values of these indexes in a healthy population of different ages during rest, daily activities, non-rapid eye movement sleep, graded physical effort, and acute psychophysiological stress. At rest, the parasympathetic and sympathetic indexes were consistently within the proposed normal range and inversely related. However, Baevsky stress index values from Kubios were higher than expected, conflicting with the assumption that they are simply the square root of those calculated using the original formula. Despite this, time-varying assessment of all indexes can provide valuable insights into CAM adaptation during physical effort and acute psychophysiological stress in real-world critical situations. Notably, our novel finding shows that the inverse correlation between parasympathetic and sympathetic/stress indexes under stress is better explained by non-linear functions, offering a potential new measure of brain&amp;ndash;heart interaction during real-life critical events.

7141 Disruption of Transient Receptor Potential Channel 5 Causes Obesity and Maladaptive Behavior

Abstract Disclosure: Y. Li: None. T. Cacciottolo: None. I.S. Farooqi: None. Y. Xu: None. The global surge in obesity over recent decades poses formidable challenges to public health and economic well-being. Transient Receptor Potential Channel 5 (TRPC5) emerges as a pivotal membrane-spanning cation channel implicated in energy homeostasis, pain modulation, and fear responses. Here, we identified microdeletions on chromosome Xq23 disrupting TRPC5 in boys with food-seeking, obesity, anxiety and autism. Significantly, these microdeletions were inherited from mothers grappling with a constellation of health issues, including obesity and anxiety, suggesting a potential intergenerational aspect to TRPC5-related conditions. We examined approximately 450,000 individuals with exome sequence data from the UK Biobank and found that the TRPC5 gene is the most strongly associated X-linked gene for human body mass index. Moreover, we identified 7 rare TRPC5 variants in patients with severe obesity underscores the potential role of TRPC5 in shaping the obesity phenotype. Functional experiments with HEK293 cells demonstrated that these variants led to a loss of Trpc5 function. Knock-in male mice harboring a human loss-of-function (LOF) TRPC5 variant developed obesity, anxiety, reduced social exploratory behavior and increased aggression; female mice homozygous for the same variant showed similar deficits with reduced severity. We found approximately 91% proopiomelanocortin (Pomc) neurons in arcuate nucleus of the hypothalamus (ARH) express Trpc5 in wild-type male mice. Utilizing the TRPC5 agonist benzothiadiazide derivative (BTD), we found that BTD (i.p., 10 mg/kg) reduced food intake and increased c-Fos expression in Pomc neurons in wild-type mice compared to the vehicle injection group. Importantly, the activation of Trpc5 using BTD did not induce toxicity or aversive effects. Importantly, chemogenetic inactivation using designer receptor exclusively activated by designer drugs (DREADD) of hM4Di-expressing Pomc neurons with clozapine N-oxide (CNO; i.p., 1 mg/kg) effectively blocked BTD-induced anorexia and c-Fos expression in Pomc neurons. Furthermore, we found that BTD-induced anorexia and c-Fos expression in Pomc neurons were blocked in mice with a LOF TRPC5 variant. This suggesting that the effects of BTD on food intake are mediated through Trpc5 in Pomc neurons. In conclusion, our study provides compelling evidence for the involvement of TRPC5 in the intricate regulation of human appetite, body weight, and maladaptive behaviors. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying TRPC5 variants. We suggest that TRPC5 should be included in diagnostic gene panels for severe childhood-onset obesity. Presentation: 6/1/2024

Regulation of corticosteroid-binding globulin release in murine leydig tumor cell line mLTC-1 by luteinizing hormone and interleukin-6

Exogenous assaults interfere with homeostatic processes in the body by inducing stress responses. Corticosteroid-binding globulin (CBG) binds to stress hormone glucocorticoids to transport and dynamically control their availability to target tissues. In our previous study, we confirmed that CBG is locally produced by Leydig cells in the testes. Here, we explored the potential regulators of CBG using a murine Leydig tumor cell line (mLTC-1). Results indicated that luteinizing hormone (LH) and interleukin-6 (IL-6) were important factors stimulating the release of CBG from mLTC-1 cells. In addition, IL-6 stimulated mLTC-1 cells to release alpha-1 antitrypsin (AAT), a serine proteinase inhibitor (serpin) that affects CBG conformation. The results implied that any challenge that altered LH or IL-6 levels also changed the release and binding status of CBG with steroid hormones in the testicular microenvironment and modulated cellular responses to these stress hormones. In addition, secretory proteomic analysis indicated that the extracellular matrix (ECM), cytoskeleton, and proteasomes were essentially produced by the mLTC-1 cells, and LH evoked the secretion of proteins involved in binding and metabolism. These results emphasize that Leydig cells may undertake more functions than just steroidogenesis, and the regulation of Leydig cells by LH is versatile.

Long-term effects of siponimod on cardiovascular and autonomic nervous system in secondary progressive multiple sclerosis.

Siponimod, a second-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, represents an important therapeutic choice for active secondary progressive multiple sclerosis (SPMS). Besides the beneficial immunomodulatory effects, siponimod impacts cardiovascular function through S1PR1 modulation. Short-term vagomimetic effects on cardiac activity have proved to be mitigated by dose titration. However, long-term consequences are less known. This study aimed to investigate the long-term impact of siponimod on cardiac autonomic modulation in people with SPMS (pwSPMS). Heart rate variability (HRV) and vascular hemodynamic parameters were evaluated using Multiple Trigonometric Regressive Spectral analysis in 47 pwSPMS before siponimod therapy and after one, three, six and 12months of treatment. Autonomic activation tests (tilt test for the sympathetic and deep breathing test for the parasympathetic cardiac modulation) were performed at each examination. pwSPMS preserved regular cardiovascular modulation responses during the autonomic tests reflected in the variation of several HRV parameters, such as RMSSD, pNN50, total power of HRV, high-frequency and low-frequency bands of the spectral domain or hemodynamic vascular parameters (Cwk, Zao, TPR, MAP) and baroreflex sensitivity (BRS). In the long-term follow-up, RMSSD, pNN50, total power, BRS and CwK presented a significant decrease, underlining a reduction of the parasympathetic and a shift towards sympathetic predominance in cardiac autonomic modulation that tends to stabilise after 1year of treatment. Due to dose titration, the short-term effects of siponimod on cardiac autonomic modulation are mitigated. The long-term impact on cardiac autonomic modulation is similar to fingolimod. The autonomic activation tests showed normal cardiovascular responses during 1-year follow-up in pwSPMS, confirming the safety profile of siponimod. Further research on autonomic function could reveal whether the observed sympathetic activation is a compensatory response to S1P signaling intervention or a feature of the disease, while also shedding light on the role of S1PR modulation in MS.

Manipulation of lasing modes in a deformed octagonal microcavity laser

We have demonstrated a deformed octagonal microcavity semiconductor laser with manipulated lasing modes for bistable operation and direct modulation. There are two sets of degenerated four-bounced modes, S01 and S02, in the octagonal microcavity, and the degeneracy between them is broken by introducing a square hole into the center of the cavity. In the deformed octagonal microcavity laser, mode S01 dominates the lasing process during the current rising process. However, mode S02 also lases when the current decreases and interacts nonlinearly with S01, which is caused by the non-uniform distribution of the refractive index induced by the square-ring-shaped current injection. We observe a counterclockwise bistable hysteresis loop with continuous injection current ranging from 31 to 13 mA at 288 K. We also study the small-signal modulation response of the laser at high and low states with different injection currents. By utilizing the photon-photon resonance effect between modes S01 and S02, we effectively increased the 3-dB bandwidth of the laser from 12 GHz to 16.2 GHz.

483 DMI, gastrointestinal tract fermentation and permeability, and white blood cell responses in beef heifers provided post-ruminal yeast cell wall extract following feed restriction

Abstract The objectives of this study were to 1) evaluate gastrointestinal fermentation characteristics and permeability, and white blood cell concentrations as beef heifers recovered from a feed restriction (FR) challenge, and 2) determine whether post-ruminal provision of a yeast cell wall extract (YCW) modulated responses. Ruminally cannulated beef heifers (n = 8) were used in a 2 × 2 crossover design. Treatments (TRT) included an abomasal infusion of a placebo (PLC; maltodextrin) or YCW derived from Saccharomyces cerevisiae (2 g/dose) infused at 0600 and 1800 h. Heifers were subject to 5-d of FR (offering 30% of ad libitum DMI) followed by five 5-d recovery phases (REC1, REC2, REC3, REC4, and REC5). Daily DMI, and rumen, fecal, and blood samples were collected on d 5 of FR, REC1, REC3, and REC5 with an additional collection on d 2 of REC1. Total gastrointestinal and post-ruminal permeability were measured using a ruminal dose of Cr-EDTA and an abomasal dose of Co-EDTA, respectively, during FR, REC1, REC3, and REC5 with concurrent urine collection. Data were analyzed to determine the effects of YCW provision, day, and the 2-way interaction. There were no TRT or TRT×day effects for any variables except DMI (interaction, P = 0.04), where DMI did not differ during the FR challenge; however, heifers provided YCW had a greater increase by REC1 compared with PLC heifers without any means differing. DMI progressively increased from FR, to REC1, REC2, and REC5. Ruminal acetate concentration increased (P &amp;lt; 0.01) from FR (45.4 mmol/L) to REC1 d5 (60.1 mmol/L) and increased further to REC3 (67.3 mmol/L) with no change thereafter (68.3 mmol/L in REC5). Ruminal propionate concentration increased (P &amp;lt; 0.01) from FR (14.5 mmol/L) to REC1 d2 (27.7 mmol/L) and was not different thereafter. Similarly, butyrate concentration increased (P &amp;lt; 0.01) from FR (7.9 mmol/L) to REC1 (d 5; 15.0 mmol/L) and was not different thereafter. Fecal acetate, propionate, and butyrate concentrations were not affected by day (P ≥ 0.12). Total gastrointestinal and post-ruminal permeability were greatest during FR (P &amp;lt; 0.01; 2.6% and 2.2% of the infused marker was excreted in urine, respectively) and decreased to 1.6% and 1.1%, respectively, in REC3 followed by an increase in REC5 for total (2.0% of infused) but not post-ruminal (1.0% of infused) permeability. The concentration of neutrophils (P &amp;lt; 0.01) was greatest on REC1 d2 (4.84 ×106 μmol/mL) and eosinophil concentration (P &amp;lt; 0.01) was greatest during FR (0.53 ×106 μmol/mL), least on d 2 of REC1 and increased on d 5 of REC1 but was not different thereafter. WBC (P &amp;lt; 0.01) gradually decreased (P = 0.02) from FR and REC1 d2 to REC3 and REC5. Post-ruminal provision of YCW may accelerate increases in DMI early in the recovery from FR, yet treatment did not modulate ruminal or fecal SCFA, blood concentrations, or gastrointestinal permeability.

Role of CRISPR-Cas systems in periodontal disease pathogenesis and potential for periodontal therapy: A review.

Clustered regularly interspaced short palindromic repeats (CRISPRs) are DNA sequences capable of editing a host genome sequence. CRISPR and its specific CRISPR-associated (Cas) protein complexes have been adapted for various applications. These include activating or inhibiting specific genetic sequences or acting as molecular scissors to cut and modify the host DNA precisely. CRISPR-Cas systems are also naturally present in many oral bacteria, where they aid in nutrition, biofilm formation, inter- and intraspecies communication (quorum sensing), horizontal gene transfer, virulence, inflammation modulation, coinfection, and immune response evasion. It even functions as an adaptive immune system, defending microbes against invading viruses and foreign genetic elements from other bacteria by targeting and degrading their DNA. Recently, CRISPR-Cas systems have been tested as molecular editing tools to manipulate specific genes linked with periodontal disease (such as periodontitis) and as novel methods of delivering antimicrobial agents to overcome antimicrobial resistance. With the rapidly increasing role of CRISPR in treating inflammatory diseases, its application in periodontal disease is also becoming popular. Therefore, this review aims to discuss the different types of CRISPR-Cas in oral microbes and their role in periodontal disease pathogenesis and precision periodontal therapy.

The web of intrigue: unraveling the role of NETosis within the gut-microbiome-immune-heart axis in acute myocardial infarction and heart failure.

This review summarizes the role of NETosis, or the release of neutrophil extracellular traps (NETs), and its interplay with the gut microbiome in acute myocardial infarction (AMI) and heart failure. NETosis contributes to inflammation, thrombosis, and atherothrombosis, all central to the pathophysiology of AMI and heart failure. NETosis can be activated by inflammation and dietary factors, indicating association with metabolic conditions. In cases of heart failure, NETosis is regulated by inflammatory molecules such as C-reactive protein (CRP), and Krüppel-like factor 2 (KLF2) - a protein that plays a role in controlling inflammation, and angiotensin II. Changes in the gut microbiome are linked to the severity and recovery of cardiac injury post-AMI and heart failure progression. The microbiome's influence extends to immune modulation and inflammatory responses, potentially affecting NETosis.

Thermo-Responsive Hydrogel Containing Microfluidic Chitosan Nanoparticles Loaded with Opuntia ficus-indica Extract for Periodontitis Treatment.

Periodontitis is a chronic inflammatory disease resulting from the dysbiosis of periodontal bacteria and the host's immune response, leading to tissue degradation and sustained inflammation. Traditional treatments, such as mechanical debridement and antimicrobial agents, often fail to fully eradicate pathogenic bacteria, especially in deep periodontal pockets. Consequently, the need for novel therapeutic approaches has increased the interest in bioactive natural extracts, such as that of Opuntia ficus-indica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. This study investigates the encapsulation of Opuntia ficus-indica extract in OFI-loaded chitosan nanoparticles (OFI-NPs) via ionotropic gelation using a microfluidic system, allowing precise control over nanoparticle characteristics and enhancing protection against enzymatic degradation. To achieve localized and sustained release in periodontal pockets, a thermo-responsive hydrogel comprising hyaluronic acid and Pluronic F127 (OFI@tgels) was developed. The transition of OFI@tgels from a solution at low temperatures to a solid at body temperature enables prolonged drug release at inflammation sites. The in vitro application of the optimized formulation eradicated biofilms of S. mutans, P. aeruginosa (PAO1), and P. gingivalis over 36 h and disrupted extracellular polymeric substance formation. Additionally, OFI@tgel modulated immune responses by inhibiting M1 macrophage polarization and promoting a shift to the M2 phenotype. These findings suggest that OFI@tgel is a promising alternative treatment for periodontitis, effectively reducing biofilm formation and modulating the immune response.

Vibration control of FG-pipe conveying fluid using a nonlinear absorber with nonlinear damping in longitudinal direction

This study investigates the use of a nonlinear absorber with nonlinear damping to mitigate the transverse vibrations of a fluid-conveying pipe made of functionally graded materials (FGM). The nonlinear effects arising from the pipe’s curvature and inertia are precisely accounted for in the equation of motion. The governing equations of the FGM pipe-nonlinear absorber system are derived using extended Hamilton’s principle and solved using the method of multiple scales. 1:1 internal resonance condition between the first natural frequency of the pipe and absorber is explored for transferring energy from the pipe to the absorber based on the modal interaction. The frequency-amplitude curves reveal that as the power-law index (n) increases, the nonlinear hardening behavior of the pipe decreases, while that of the absorber increases. Incorporating nonlinear damping in the absorber is found to further improve vibration suppression, leading to a strongly modulated response that reduces the pipe vibrations by over 84.57% and the absorber vibrations by over 94.57%. The impact of the absorber’s nonlinear stiffness on the strongly modulated response is also investigated, indicating that excessively high stiffness can cause the disappearance of this beneficial behavior. The findings of this study provide valuable insights into the optimal design of FGM pipes conveying fluid and the integration of nonlinear absorbers with nonlinear damping for enhanced vibration mitigation.

A quasi-matching scheme for arbitrary group velocity match in electro-optic modulation

Group velocity and impedance matches are prerequisites for high-speed Mach–Zehnder electro-optic (EO) modulators. However, not all platforms can realize matching conditions, restricting high-speed modulation in many practical conditions. Here, we propose and demonstrate a quasi-matching scheme to satisfy the group velocity and characteristic impedance matches by cascading fast-wave and slow-wave traveling wave electrodes. The effective group velocity can be flexibly adjusted by changing the ratio of fast-wave and slow-wave traveling wave electrodes. Moreover, the quasi-matching scheme is experimentally verified by demonstrating a 6 mm long EO modulator on a thin-film lithium-niobate-on-insulator platform with a silica cladding. The radio frequency signal insertion loss at the boundary of the slow-wave and fast-wave electrodes is less than 0.12 dB. The measured small signal EO response of the quasi-matched EO modulator drops less than 2 dB at 67 GHz, while the measured small-signal EO responses of conventional slow and fast traveling wave EO modulators drop 4 dB at 67 GHz. The measured 100 Gb/s on–off key signal eye-diagrams of the quasi-matched EO modulator also exhibit an overwhelming advantage over conventional schemes. Therefore, our results will open many opportunities for high-speed EO modulators in various platforms.

Interleukine-10 in ovarian cancer.

Interleukins serve as communicating molecules between cells, mediating key interactions in the tumor microenvironment (TME) between immune cells and non-immune cells. Interleukin-10 (IL-10), a multifunctional cytokine with multiple properties, has been extensively studied in various aspects of immunology and cancer biology. IL-10 is pleiotropic, promotes cytotoxicity, yet inhibits antitumor-responses. In recent years, the role of IL-10 in ovarian cancer (OC) progression and treatment has gained significant scientific attention, elucidating the signaling pathways triggered by IL-10 action. OC, the leading cause of gynecologic cancer-related deaths, is characterized by ascites, which hosts an intricate TME that is not responsive to treatment by immune checkpoint inhibition. IL-10, known for its immunosuppressive and anti-inflammatory properties, plays a complex role in OC progression, immune modulation, and therapeutic response and has a potential therapeutic property as a target and as an effector. As the literature of basic science research studying the role of IL-10 in the TME of OC scopes a few decades and some data is contrasting, it is important to review the literature and provide concise input derived from it. This review aims to provide a comprehensive overview of the current understanding of IL-10 in OC, highlighting its influence on tumor growth, immune evasion, and potential as a therapeutic target.

THE ROLE OF VITAMIN D IN IMMUNE MODULATION: A REVIEW OF CLINICAL IMPLICATIONS

Vitamin D, often celebrated for its crucial role in maintaining bone health, has garnered significant attention in recent years for its multifaceted contributions to immune modulation. The study aims to find Vitamin D's role in immune modulation. The innate immune system is the first line of defense against invading pathogens, and its leading roles are rapid responses, identification of the pathogen, and neutralization to avoid the aggravation of the disease. The role of Vitamin D in immune modulation extends across a spectrum of immune-related disorders, underscoring its significance in maintaining immune homeostasis and preventing disease. The immune modularity of vitamin D is mainly through the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]; this hormone binds to the Vitamin D receptor (VDR) inherent in several immune cells. This binding triggers the process of gene expression alterations that impact the abilities and duplication of these cells. For instance, in multiple sclerosis (MS), Vitamin D inhibits the production of Th1 and Th17, which are pro-inflammatory T-cells, while enhancing Tregs, which results in the curbing of inflammation and autoimmunity. Vitamin D is pivotal in immune modulation, influencing innate and adaptive immune responses. Its deficiency is linked to an increased risk and severity of various immune-related disorders, highlighting the importance of maintaining adequate Vitamin D levels.

Investigation of CFTR Function in Human Nasal Epithelial Cells Informs Personalized Medicine.

We broaden the clinical versatility of human nasal epithelial (HNE) cells. HNEs were isolated from 10 participants harboring CFTR variants: nine with rare variants (Q359R [n=2], G480S, R334W [n=5], and R560T) and one person harboring R117H;7T;TG10/5T;TG12. Cultures were differentiated at air-liquid interface. CFTR function was measured in Ussing chambers at three conditions - baseline, ivacaftor, and elexacaftor+tezacaftor+ivacaftor (ETI). Four participants initiated modulators. Q359R HNEs had 5.4% (%WT) baseline CFTR function and 25.5% with ivacaftor. With therapy, sweat [Cl-] decreased and symptoms resolved. G480S HNEs had 4.1% baseline and 32.1% CFTR function with ETI. Clinically, FEV1 increased and sweat [Cl-] decreased (119 to 46mmol/L) with ETI. In vitro cultures derived from five individuals harboring R334W showed a moderate increase in CFTR function with exposure to modulators. For one of these participants, ETI was begun in vivo; symptoms and FEV1 improved. c.1679G>C (R560T) HNEs had <4% baseline CFTR function and no modulator response. RNA analysis confirmed that c.1679G>C completely mis-splices. A symptomatic patient harboring R117H;7T;TG10/5T;TG12 exhibited reduced CFTR function (17.5%) in HNEs, facilitating mild CF diagnosis. HNEs responded to modulators (ivacaftor: 32.8%, ETI: 55.5%) and, since beginning therapy, lung function improved. While reaffirming HNE use for guiding therapeutic approaches, we inform predictions on modulator response (e.g. R334W) and closely assess variants affecting splicing (e.g. c.1679G>C). Notably, functional studies in HNEs harboring R117H;7T;TG10/5T;TG12 facilitated mild CF diagnosis, suggesting use for HNE functional studies as a clinical diagnostic test.