Evaluation of the suitability of using ArtiSential in various renal surgery: IDEAL stage 1 study.

BACKGROUND: ArtiSential, a new articulating laparoscopic instruments, addresses the limited movement associated with conventional laparoscopic instruments. This study was conducted to assess the clinical effectiveness of ArtiSential in detailed steps of various renal surgery. METHODS: This study was approved by the Institutional Review Board of our institution and registered on the Clinical Research Information Service site of the Korea Disease Control and Prevention Agency. Participants meeting all inclusion and exclusion criteria were included in the clinical trial and underwent renal surgery. The clinical effectiveness of ArtiSential was assessed in terms of the feasibility and objective and subjective parameters across 9 detailed steps. RESULTS: Of the 15 potential candidates enrolled from October 2021 to November 2021, 1 patient dropped out due to anaphylaxis from an anesthetic agent, and 14 patients underwent laparoscopic surgery using ArtiSential. Of the 14 patients, 2 patients were converted to laparoscopic surgery using straight-shaped instruments due to the ischemia time exceeding 30 min, and 1 patient due to excessive bleeding. The feasibility for most steps was more than 90%, except the renorrhaphy step. The median total operation time and ischemia time were 161 and 23 min, respectively. The median estimated blood loss was 58.5 mL. Two cases of venous injury occurred during renal pedicle dissection step. The accuracy of the procedure judged by reviewers and usability judged by the operator were acceptable in all steps. The surgeon's quantitatively measured stress score was the highest during renorrhaphy step. CONCLUSIONS: Laparoscopic surgery using ArtiSential is feasible for most steps except the renorrhaphy step. The difficulty of performing renorrhaphy is attributed to prolonged ischemia time, which could be addressed by overcoming the learning curve. TRIAL REGISTRATION: Clinical Research Information Service site of the Korea Disease Control and Prevention Agency, KCT0006532. Registered 03/09/2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24071 .

Reflectivity measurement of a silicon carbide mirror sample for ITER divertor vacuum ultraviolet spectrometer.

The first mirror is the front-end optic component that reflects light emitted from the plasma to the diagnostic system in fusion plasmas. Silicon carbide (SiC), known for its relatively high mechanical strength and radiation tolerance, has been selected as the substrate material for the first mirror in the ITER divertor vacuum ultraviolet (VUV) spectrometer. To measure the reflectivity of the ellipse cylindrical SiC mirror to be manufactured, a device for reflectivity measurement in the VUV wavelength range was developed. First, the reflectivity of a sample SiC mirror (15 mm diameter × 10 mm thick) was measured across the ITER-required incidence angles, and the results are reported in this study. A hollow cathode lamp with helium gas was used as the VUV light source in the wavelength range of 23-60 nm, and a dedicated VUV spectrometer to select specific wavelengths was developed. The spectrometer utilized laminar-type replica diffraction gratings (Shimadzu 30-006) and two back-illuminated charge-coupled devices (BI-CCD, Andor DO 940P-BEN) for the grating and detector, respectively. A cropping technique with aperture was employed to precisely localize the VUV light's reflection onto the SiC mirror surface. The experimentally measured reflectivity values of SiC at the required incidence angles of VUV light were compared with theoretically calculated reflectivity curves. The oxidation layer (SiO2) formed on the SiC surface and the incidence angle of VUV light to the BI-CCD chip (E2V) would be the factors affecting the accuracy of the reflectivity.

Validation of analytical methods for newly regulated veterinary drug residues in livestock and fishery products with maximum residue limits in Republic of Korea.

Veterinary drugs play a crucial role in the treatment of various animal diseases. However, their residues, stemming from issues, such as withdrawal period lapses, overuse, or abuse, can jeopardize food safety and human health. This study addresses recent regulations in Korea concerning specific veterinary drugs (anacolin, ephedrine, menichlopholan, piperonyl butoxide, and etisazole HCl) and their ongoing discussions. This study aimed to validate two pre-developed methods for quantifying residues in livestock and fishery products using QuEChERS and liquid chromatography-tandem mass spectrometry. Both methods exhibited excellent linearity, recoveries (70.3-119%), and coefficient of variations (1.3-28%), along with low limits of detection and quantification (0.3-4 ng/g and 1-12 ng/g). This study is significant for its contribution to the detection of veterinary drugs in livestock and fishery products, given the limited research available on the methods for analyzing these substances.

Comparing underwater endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large laterally spreading tumor: a randomized controlled trial.

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is challenging despite its usefulness. Underwater ESD (UESD) provides better traction and a clearer view of the submucosal layer than conventional ESD (CESD). This study compared the efficiency of UESD and CESD for large (20-50 mm) laterally spreading tumor (LST). METHODS: Preplanned sample size was calculated from our previous experience. As a results, 28 patients were required to UESD group or CESD group, respectively. The primary outcome was total procedure time while the secondary outcome was dissection speed. RESULTS: Fifty-six patients were enrolled and a total of 28 patients were assigned to each group. The mean size of LST was 31.6 mm and 31.3 mm in the UESD and CESD group, respectively. Fibrosis was observed in 67.9% and 60.7% patients in the UESD and CESD group. Total procedure time (mean [SD]) for the UESD group was significantly shorter than that for the CESD group, respectively (49.5 minutes [20.3] vs 75.7 minutes [36.1]; mean difference, -26.2 minutes; 95% CI, -42.0 to -10.5). Dissection speed of the UESD group was significantly faster than that of the CESD group (21.9 mm2/min [6.9] vs 15.2 mm2/min [7.3]; mean difference, 6.7 mm2/minutes; 95% CI, 2.8-10.4). There was no difference between groups in the R0 resection rate or en bloc resection rate. No perforations were observed in either group. CONCLUSIONS: UESD was superior to CESD in total procedure time and dissection speed. UESD can be recommended as the preferred method for the resection of large LST.

A study on the formative usability testing for modular powered wheelchair.

The increasing prevalence of mobility impairments underscores the urgent need for accessible and affordable mobility aids. To overcome the mobility limitations of people with disabilities, there is an increasing need for the development of lightweight and portable powered wheelchairs that can be easily loaded. This study aimed to perform an early health technology assessment and a formative usability evaluation on a modular (detachable) powered wheelchair. It aimed to gauge device satisfaction among users, pinpoint areas for improvement, and detect any unforeseen errors to inform future development. Engaging 16 participants, including powered wheelchair users, healthcare professionals, and caregivers, the research evaluated the wheelchair's functionality in various scenarios, emphasizing safety, effectiveness, and convenience. Statistical analyses of task performance and satisfaction surveys highlighted that, while powered wheelchair users successfully completed tasks focusing on driving and power control, healthcare professionals and caregivers encountered difficulties with the wheelchair's assembly and disassembly. Despite general positivity, the surveys indicated mixed satisfaction levels regarding safety, validity, and convenience, with specific issues related to frame durability, seat comfort, and control mechanisms. These findings suggest that refining the wheelchair's design and addressing user concerns could significantly enhance satisfaction and mobility services. Future efforts will include a thorough review of an advanced prototype and further satisfaction assessments.

We believe that our study makes a significant contribution to the literature by addressing a critical gap in the understanding of user-centric design and usability testing for powered wheelchairs.By emphasizing the importance of early assessments and incorporating user feedback into the development process, our research offers practical insights for creating more accessible and user-friendly mobility solutions.This contribution is particularly relevant in the context of advancing assistive technology and improving the quality of life for individuals with disabilities.

Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of Ca2+/Calpain/Cdk5-mediated mitochondrial fragmentation.

Oxidative stress plays an essential role in the progression of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer's disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca2+-mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca2+ accumulation and Ca2+-mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca2+/Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca2+/Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress.

Cholesin and GPR146 in Modulating Cholesterol Biosynthesis.

BACKGROUND: Cholesterol homeostasis in the human body is a crucial process that involves a delicate balance between dietary cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver. Both pathways contribute significantly to the overall pool of cholesterol in the body, influencing plasma cholesterol levels and impacting cardiovascular health. Elevated absorption of cholesterol in the intestines has a suppressive impact on the synthesis of cholesterol in the liver, serving to preserve cholesterol balance. Nonetheless, the precise mechanisms driving this phenomenon remain largely unclear. SUMMARY: This review aimed to discuss the previously unrecognized role of cholesin and GPR146 in the regulation of cholesterol biosynthesis, providing a novel conceptual framework for understanding cholesterol homeostasis. KEY MESSAGES: The discovery of cholesin, a novel protein implicated in the regulation of cholesterol homeostasis, represents a significant advancement in our understanding of cholesterol biosynthesis and its associated pathways. The cholesin-GPR146 axis could have profound implications across various therapeutic areas concerning abnormal cholesterol metabolism, offering new hope for patients and improving overall healthcare outcomes.

Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.

Conventional gene therapy approaches for drug delivery generally rely on constitutive expression of the transgene and thus lack precise control over the timing and magnitude of delivery. Synthetic gene circuits with promoters that are responsive to user-defined stimuli can provide a molecular switch that can be utilized by cells to control drug production. Our laboratory has previously developed a mechanogenetic gene circuit that can deliver biological drugs, such as interleukin-1 receptor antagonist (IL-1Ra), on-demand through the activation of Transient receptor potential family, vanilloid 4 (TRPV4), a mechanosensory ion channel that has been shown to be activated transiently in response to physical stimuli such as physiological mechanical loading or hypo-osmotic stimuli. The goal of this study was to use mutations in TRPV4 to further tune the response of this mechanogenetic gene circuit. Human iPSC-derived chondrocytes harboring targeted gain-of-function mutations of TRPV4 were chondrogenically differentiated. Both mutants-V620I and T89I-showed greater total IL-1Ra production compared with wild type following TRPV4 agonist treatment, as well as mechanical or osmotic loading, but with altered temporal dynamics. Gene circuit output was dependent on the degree of TRPV4 activation secondary to GSK101 concentration or strain magnitude during loading. V620I constructs secreted more IL-1Ra compared with T89I across all experimental conditions, indicating that two mutations that cause similar functional changes to TRPV4 can result in distinct circuit activation profiles that differ from wild-type cells. In summary, we successfully demonstrate proof-of-concept that point mutations in TRPV4 that alter channel function can be used to tune the therapeutic output of mechanogenetic gene circuits.

Peripheral macrophages contribute to nociceptor priming in mice with chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased incidence of chronic musculoskeletal pain. We investigated the mechanism of this association in a mouse model of chronic intermittent hypoxia (CIH) that mimics the repetitive hypoxemias of OSA. After 14 days of CIH, both male and female mice exhibited behaviors indicative of persistent pain, with biochemical markers in the spinal cord dorsal horn and sensory neurons of the dorsal root ganglia consistent with hyperalgesic priming. CIH, but not sleep fragmentation alone, induced an increase in macrophage recruitment to peripheral sensory tissues (sciatic nerve and dorsal root ganglia), an increase in inflammatory cytokines in the circulation, and nociceptor sensitization. Peripheral macrophage ablation blocked CIH-induced hyperalgesic priming. The findings suggest that correcting the hypoxia or targeting macrophage signaling might suppress persistent pain in patients with OSA.

Effect of Using Mouthwash Containing Cibotium barometz J. Smith on Cariogenic Bacteria and Acid-producing Ability of Saliva: A Randomised Blinded Clinical Trial.

PURPOSE: To examine the anti-caries effect of mouthwashes containing Cibotium barometz J. Smith (CB), a natural substance, and compare it with chlorhexidine and saline solution. MATERIALS AND METHODS: A randomised, blinded clinical trial was conducted on 76 study participants. The differences between the 3 gargle groups (saline gargle: SAL; chlorhexidine gargle: CHX; CB gargle group: CB) and the differences over time (baseline, after 1 week, after 2 weeks) were compared. To this end, ANOVA was performed on caries-related clinical indicators (e.g. O'Leary plaque index, caries activity, and satisfaction). RESULTS: The O'Leary index, caries activity, and saliva tests, gradually improved in group CB at one and two weeks. In the case of bacterial tests, unlike SAL and CHX, only in group CB did the decrease occur one and two weeks later. The caries-related indicators decreased significantly over time in group CB compared to SAL and CHX groups, and there was also a statistically significant difference in interaction between groups and time (p<0.05). CONCLUSIONS: The mouthwash containing CB extract showed statistically significant improvement in biofilm adhesion as well as the saliva and bacterial tests compared to SAL and CHX. However, since there were differences in the initial oral conditions of the three groups, additional long-term research is needed through crossover clinical trials to supplement these.

Fostering tissue engineering and regenerative medicine to treat musculoskeletal disorders in bone and muscle.

The musculoskeletal system, which is vital for movement, support, and protection, can be impaired by disorders such as osteoporosis, osteoarthritis, and muscular dystrophy. This review focuses on the advances in tissue engineering and regenerative medicine, specifically aimed at alleviating these disorders. It explores the roles of cell therapy, particularly Mesenchymal Stem Cells (MSCs) and Adipose-Derived Stem Cells (ADSCs), biomaterials, and biomolecules/external stimulations in fostering bone and muscle regeneration. The current research underscores the potential of MSCs and ADSCs despite the persistent challenges of cell scarcity, inconsistent outcomes, and safety concerns. Moreover, integrating exogenous materials such as scaffolds and external stimuli like electrical stimulation and growth factors shows promise in enhancing musculoskeletal regeneration. This review emphasizes the need for comprehensive studies and adopting innovative techniques together to refine and advance these multi-therapeutic strategies, ultimately benefiting patients with musculoskeletal disorders.

Prediction of the bone volume for sinus augmentation through 3-dimensional analysis.

Background/purpose: No consensus has been established regarding the exact amount of bone grafting in maxillary sinus augmentation. The aim of this study was to estimate the minimum bone volume for sinus augmentation and to investigate the factors that influence the augmentation volume (AV). Materials and methods: This study included patients with cone-beam computed tomography scanning. Dome-shaped sinus augmentation was performed virtually at vertical heights (VH) of 3, 5, 7, and 9 mm in Group A (without implantation) and Group B (with implantation). The augmentation angle (AA) and the sinus width (SW) were measured. The AV was measured using the three-dimensional image processing program 3D Slicer. Univariable and multivariable analyses were conducted. Results: This study included 30 patients (120 subjects). In Group A, the mean AVs were 0.062, 0.271, 0.642, and 1.287 cc at VHs of 3, 5, 7, and 9 mm, respectively, in Group B, the mean AVs were 0.037, 0.230, 0.594, and 1.230 cc. Univariable analysis indicated that factors significantly associated with the AV in both groups included SW, AA, and VH (P < 0.001). Multivariable analysis indicated that factors significantly associated with the AV in both groups included AA and VH (P < 0.01). Conclusion: Clinicians can predict the bone volume for sinus augmentation by measuring the augmentation height and angle.

Validation of self-reported morbidities of the Korean Atomic Bomb Survivor Cohort.

Objectives: This study aimed to evaluate the agreement of disease status collected through a survey of the Korean Atomic Bomb Survivor Cohort (K-ABC), compared with medical claim records from the Korean National Health Insurance Service (NHIS) database and the Korean Central Cancer Registry (KCCR). Methods: Data on the lifetime physician-diagnosed morbidities of 1,215 K-ABC participants were collected through an interviewer-administered questionnaire between 2020 and 2022. Survey data were linked to the NHIS and KCCR databases. Eleven diseases were included for validation. We evaluated the following indicators: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, the area under the curve (AUC), and the kappa coefficient. Results: The mean (standard deviation) age was 62.1 (18.7) years, and 42.6% of the participants were aged ≥70 years. Hypertension and cataracts showed the highest prevalence rates (33.8% and 28.8%, respectively). Hypertension, diabetes, and cancer demonstrated high sensitivity (>0.8) and specificity (>0.9), whereas diabetes, cancer, myocardial infarction, angina pectoris, and asthma exhibited high accuracy (>0.9). In contrast, arthritis, allergic rhinitis, and asthma showed low sensitivity (<0.4) and kappa values (<0.3). In the participants aged ≥70 years, the kappa value was ≥0.4 for all diseases except arthritis, allergic rhinitis, and asthma. Conclusion: The results from this initial analysis showed relatively high agreement between the survey and NHIS/KCCR databases, especially for hypertension, diabetes, and cancer. Our findings suggest that the information on morbidities collected through the questionnaires in this cohort was valid for both younger and older individuals.

Dual-Layer Nanoengineered Urinary Catheters for Enhanced Antimicrobial Efficacy and Reduced Cytotoxicity.

Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection; however, current therapeutic strategies remain insufficient for standard clinical application. A novel urinary catheter featuring a dual-layer nanoengineering approach using zinc (Zn) and silver nanoparticles (AgNPs) is successfully fabricated. This design targets microbial resistance, minimizes cytotoxicity, and maintains long-term efficacy. The inner AgNPs layer provides immediate antibacterial effects against the UTI pathogens, while the outer porous Zn layer controls zero-order Ag release and generates reactive oxygen species, thus enhancing long-term bactericidal performance. Enhanced antibacterial properties of Zn/AgNPs-coated catheters are observed, resulting in 99.9% of E. coli and 99.7% of S. aureus reduction, respectively. The Zn/AgNPs-coated catheter significantly suppresses biofilm with sludge formation compared to AgNP-coated and uncoated catheters (all, p < 0.05). The Zn/AgNP-coated catheter in a rabbit model demonstrated a durable, effective barrier against bacterial colonization, maintaining antimicrobial properties during the catheter indwelling period with significantly reduced inflammation and epithelial disruption compared with AgNP and uncoated groups. This innovation has the potential to revolutionize the design of antimicrobial medical devices, particularly for applications requiring long-term implantation. Although further preclinical studies are required to verify its efficacy and safety, this strategy seems to be a promising approach to preventing CAUTI-related complications.

Comparative analysis of child injuries in passenger vehicles and school buses: a multicentre cross-sectional study.

OBJECTIVE: This study investigated the differences in injury profiles and safety device effectiveness among children with road traffic injuries (RTIs) involving passenger vehicles and school buses. METHODS: Using data from the Emergency Department-based Injury In-depth Surveillance database, this multicentre cross-sectional study investigated the injury profiles of 14 669 children aged 12 years old and younger who experienced RTIs from 2011-2021. Demographic factors, injury distribution, severity and effect of safety device use between RITs involving passenger vehicles and school buses were compared. RESULTS: RTIs in children most frequently occurred between 12:00 and 18:00 hours (46.9%). School bus-related RTIs peaked during school commute hours, that is, from 06:00 to 12:00 hours, and were associated with a higher prevalence of head (63.1% vs 58.9%, p<0.05) and extremity injuries (upper extremity: 8.0% vs 6.4% and lower extremity: 11.1% vs 7.6 %, p<0.05) compared with those involving passenger vehicles. However, passenger vehicle crashes showed higher proportions of neck and chest injuries, along with injuries requiring hospitalisation and intensive care. Safety devices exhibited preventive effects against head and lower extremity injuries in both vehicle types. While safety devices showed effective in reducing hospital admissions and severe injuries in passenger vehicles, their effectiveness in school buses was not observed. CONCLUSION: This study highlights the different epidemiology and injury profiles of RTIs among children involving passenger vehicles and school buses. Improved safety devices, particularly in school buses, are necessary to ensure the comprehensive protection of child passengers and reduce the risk of severe injuries during road traffic incidents.

Biomedical Device Surface Treatment by Laser-Driven Hydroxyapatite Penetration-Synthesis Technique for Gapless PEEK-to-Bone Integration.

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration.  Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.

Moderation of thyroid hormones for the relationship between amyloid and tau pathology.

BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

A phase II study of osimertinib in patients with NSCLC harboring EGFR exon 20 insertion: A multicenter trial of the Korean Cancer Study Group (LU17-19).

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion-specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion. METHODS: In this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. RESULTS: Among 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7-5.5) months and 6.5 (95 % CI = 3.9-not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib. CONCLUSION: Osimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions. CLINICALTRIALS: govIdentifier: NCT03414814.