Prognostic implication of extra-pancreatic organ invasion in resectable pancreas ductal adenocarcinoma in the pancreas tail.

OBJECTIVES: To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail. MATERIALS & METHODS: This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic). RESULTS: The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model. CONCLUSION: Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor.

Characteristics of Malassezia furfur at various pH and effects of Malassezia lipids on skin cells.

Malassezia species are commensal and opportunistic fungi found in human skin. All Malassezia species lack fatty acid synthesis genes and survive by utilizing several lipases to degrade and absorb fatty acids from external lipid sources, but little research has been done on their optimal active pH and temperature. Our skin protects itself from external stimuli and maintains homeostasis, involving bacteria and fungi such as Malassezia species that inhabit our skin. Hence, dysbiosis in the skin microbiome can lead to various skin diseases. The skin's pH is slightly acidic compared to neutral, and changes in pH can affect the metabolism of Malassezia species. We used keratinocyte cell lines to determine the effect of lipids bio-converted by Malassezia furfur, Malassezia japonica, and Malassezia yamatoensis under pH conditions similar to those of healthy skin. Lipids bio-converted from Malassezia species were associated with the regulation of transcripts related to inflammation, moisturizing, and promoting elasticity. Therefore, to determine the effect of pH on lipid metabolism in M. furfur, which is associated with seborrheic dermatitis, changes in biomass, lipid content, and fatty acid composition were determined. The results showed that pH 7 resulted in low growth and reduced lipid content, which had a negative impact on skin health. Given that bio-converted Malassezia-derived lipids show positive effects at the slightly acidic pH typical of healthy skin, it is important to study their effects on skin cells under various pH conditions. KEY POINTS: • pH 6, Malassezia spp. bio-converted lipid have a positive effect on skin cells • Malassezia spp. have different lipid, fatty acid, and growth depending on pH • Malassezia spp. can play a beneficial role by secreting lipids to the outside.

A sensorineural hearing loss harboring novel compound heterozygous variant in the TRIOBP gene: A case report.

Background: Autosomal recessive non-syndromic deafness-28 (DFNB28; OMIM #609823) specifically refers to prelingual sensorineural hearing loss (SNHL) resulting from homozygous or compound heterozygous mutations in the TRIO- and F-actin-binding protein, TRIOBP gene. In this report, we present a pediatric patient exhibiting novel compound heterozygous deleterious variants in the TRIOBP gene. Methods: The auditory brainstem response result revealed both left- and right-sided deafness with a threshold of 20 dB normal hearing level in the proband. A comprehensive trio whole exome sequencing (WES) using the Celemics G-Mendeliome Whole Exome Sequencing Panel was employed. Results: The WES analysis revealed compound heterozygous TRIOBP variants in the proband, namely c.1192_1195delCAACinsT/p.Gln398* classified as pathogenic and c.3661C > T/p.Arg1221Trp categorized as a variant of uncertain significance according to American College of Medical Genetics and Genomics guidelines. These variants are considered the most probable cause of the proband's SNHL. Conclusion: TRIOBP isoforms are predominantly expressed in the inner ear, contributing to the formation of stereocilia rootlets. Further investigations are required to fully understand the phenotypic variability and establish the pathogenicity of the identified variant in relation to the TRIOBP gene and SNHL.

Postural and spinal stability analysis for different floor sitting styles.

In contrast to Western countries, traditional floor-seating cultures are prevalent in Korea, Japan, the Middle East, and Africa, where sitting on the floor in static positions such as squatting, kneeling, or sitting cross-legged is common. Most studies on sitting posture have predominantly focused on chair sitting in Western cultures, resulting in a cultural bias. This study aimed to investigate the effects of different cushion types (floor and traditional cushions of 3-cm, 5-cm, and 8-cm thickness) and seating postures (cross-legged, mother's leg, and kneeling) on measures of postural stability, trunk muscle activity, rotational spinal stability, and subjective postural stability in an Asian population. Forty right-hand and right-foot-dominant volunteers who did not experience activity-limiting back pain in the past 12 months were recruited. Multivariate analyses of variance (MANOVA) and ANOVA with a repeated-measures design were employed to assess the within-subject effects of the cushion type and seating posture. An alpha value of 0.05 was set for statistical significance. The results of this study suggest that preventing lordosis posture, seating on the floor, and maintaining a kneeling posture may reduce the loss of balance and trunk muscle fatigue. These results emphasize the need for additional ergonomic studies that focus on the seating traditions of Asian cultures.

Efficacy of RCI001 as a Therapeutic Candidate in a Primary Sjögren Syndrome Mouse Model.

PURPOSE: The aim of this study was to investigate the efficacy of RCI001 (RCI) in a mouse model of primary Sjögren syndrome. METHODS: Eight 12-week-old NOD.B10-H2b mice were used in this study. All experimental animals were randomly divided into phosphate-buffered saline (PBS) and RCI groups in NOD.B10-H2b mice. The eyes of mice were topically treated with PBS or RCI twice a day for a week. Ocular surface staining (OSS) and tear secretion were compared between before and after treatment. The transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in the conjunctiva and cornea (CC) and lacrimal gland were assayed. In addition, immunofluorescence staining of the conjunctiva was assessed. RESULTS: The RCI group showed significant clinical improvement in OSS and tear secretion after 1 week of treatment compared with the baseline (both P < 0.001) and showed better improvement in OSS and tear secretion than the PBS group after 1 week of treatment (both P < 0.05). The levels of IL-1ß and IL-17 in CC and IL-6 in the lacrimal gland were also significantly reduced in the RCI group compared with the PBS group (each P < 0.05). Transcript levels of NOX2 and NOX4 were also significantly reduced in CC of the RCI group compared with those of the PBS group (P < 0.05). The RCI group also resulted in lower conjunctival expression of oxidative stress markers (4-hydroxy-2-nonenal, hexanoyl-lysine, and NOX4) than the PBS group. CONCLUSIONS: Topical RCI001 demonstrated excellent therapeutic efficacy in a mouse model of primary Sjögren syndrome by inhibiting inflammation and oxidative stress.

Acellular Dermal Matrix without Basement Membrane in Immediate Prepectoral Breast Reconstruction: A Randomized Controlled Trial.

BACKGROUND: Acellular dermal matrix (ADM) has become popular in various reconstructive procedures of different anatomic regions. There are different needs depending on the clinical application, including breast, abdominal wall, and any other soft-tissue reconstruction. Removal of the basement membrane, which consists of collagen fibers, may help achieve natural and soft breast reconstruction, which requires highly elastic ADMs. Given the lack of knowledge of the effectiveness of ADM without the basement membrane, the authors compared the clinical outcomes of ADMs with and without basement membrane in breast reconstruction. METHODS: The authors conducted a single-blind randomized controlled trial to evaluate differences in clinical outcomes. The patients were randomized into 2 groups: ADM with or without basement membrane. Both groups underwent immediate prepectoral direct-to-implant breast reconstruction. Demographic characteristics, surgical outcomes, and breast shape change using nipple position were compared between the 2 groups. RESULTS: A total of 56 patients were divided into 2 groups: ADM with basement membrane (n = 30 [53.6%]) or ADM without basement membrane (n = 26 [46.4%]). Clinical and surgical characteristics were similar between the 2 groups. The authors detected no statistically significant differences in the overall rate of complications or breast shape change between the 2 groups. However, the rate of seromas was higher in the ADM with basement membrane group than in the ADM without basement membrane group (10% versus 0%; P = 0.09). CONCLUSIONS: The 2 groups showed similar surgical outcomes. ADM without basement membrane in implant-based breast reconstruction was safe, and had mechanical properties of lower tensile strength and higher elasticity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment.

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1ß, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1ß and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1ß and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Factors associated with generalized anxiety disorder in adolescents with cultural diversity: secondary data analysis.

BACKGROUND: The number of culturally diverse adolescents in South Korea has reached 290,000 and is increasing every year; however, they still represent only 2.5% of the total adolescent population in middle and high schools, making them a minority. Adolescents experiencing cultural diversity are psychologically vulnerable because they grow up in bicultural environments and experience prejudice. Given the nature of generalized anxiety disorder, which can be exacerbated by stress, these adolescents may face an increased risk of developing the disorder not only because of developmental stress but also because of the stress of cultural adaptation. To identify the prevalence of generalized anxiety disorder among adolescents with cultural diversity, we analyzed related factors. Based on the results, strategies have been proposed to reduce anxiety in adolescents with cultural diversity and generalized anxiety disorders. METHODS: This study used data from the 16th - 18th Korea Youth Risk Behavior Survey. Factors associated with generalized anxiety disorders were identified based on the social determinants of the health framework. Statistical analyses were conducted using IBM SPSS 25.0, and statistical methods were used for complex samples. RESULTS: Among adolescents with cultural diversity, 12.8% exhibited generalized anxiety disorders. Among the structural factors, economic status, mother's education level, and gender were significantly associated with the disorder, whereas among the psychosocial factors, suicidal ideation, depressive mood, loneliness, perceived stress level, and subjective health status were significant factors influencing it. CONCLUSION: The factors identified in our research can be used as a resource for the early identification of culturally diverse adolescents who are vulnerable to generalized anxiety disorders. To prevent generalized anxiety disorder among adolescents with cultural diversity, school or community nurses can implement interventions to reduce loneliness or stress management programs.

Concise and Efficient Synthesis of Sequentially Isomeric Hetero[3]rotaxanes.

Stereoisomerism, stemming from the spatial orientation of components in molecular structures, plays a decisive role in nature. While the unconventional bonding found in mechanically interlocked molecules gives rise to unique expressions of stereochemistry, the exploration of their stereoisomers is still in its infancy. Sequence isomerism, characterized by variations in the ordering of mechanically interlocked components in catenanes and rotaxanes, mirrors the sequence variations found in biological macromolecules. Herein, we report the use of artificial molecular pumps for the precise and simple production of sequentially isomeric hetero[3]rotaxanes. Utilizing redox-driven pumping cassettes with different rings, we have synthesized two hetero[3]rotaxane isomers in high isolated yields from two [2]rotaxanes. This research represents a significant advance in sequential molecular assembly, paving the way for the development of sophisticated, functionalized, mechanically interlocked materials.

1-Hour Post-Load Glucose: Early Screening for High Risk of Type 2 Diabetes in Koreans with Normal Fasting Glucose.

CONTEXT: With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. OBJECTIVE: This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. METHODS: 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. RESULTS: At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. CONCLUSION: Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Microwave-assisted solvothermal synthesis of nanostructured Ga-Doped Li7La3Zr2O12 solid electrolyte with enhanced densification and Li-ion conductivity.

Garnet-type Li7La3Zr2O12 (LLZO) Li-ion solid electrolytes are promising candidates for safe, next-generation solid-state batteries. In this study, we synthesize Ga-doped LLZO (Ga-LLZO) electrolytes using a microwave-assisted solvothermal method followed by low-temperature heat treatment. The nanostructured precursor (<50 nm) produced by the microwave-assisted solvothermal process has a high surface energy, facilitating the reaction for preparing garnet-type Ga-LLZO powders (<800 nm) within a short time (<5 h) at a low calcination temperature (<700 °C). Additionally, the calcined nanostructured Ga-LLZO powder can be sintered to produce a high-density pellet with minimized grain boundaries under moderate sintering conditions (temperature: 1150 °C, duration: 10 h). The optimal doping concentration was determined to be 0.4 mol% Ga, which resulted significantly increased the ionic conductivity (1.04 × 10-3 S cm-1 at 25 °C) and stabilized the cycling performance over 1700 h at 0.4 mA cm-2. This approach demonstrates the potential to synthesize oxide-type solid electrolyte materials with improved properties for solid-state batteries.

Bioimpedance-Guided Fluid Removal in Continuous Kidney Replacement Therapy: The VENUS Randomized Clinical Trial.

BACKGROUND: Ultrafiltration with continuous kidney replacement therapy (CKRT) can be used to manage fluid balance in critically ill patients with acute kidney injury (AKI). We aimed to assess whether bioimpedance analysis (BIA)-guided volume management was more efficacious than conventional management for achieving estimated euvolemia (e-euvolemia) in CKRT-treated patients. METHODS: In a multi-center randomized controlled trial from July 2017 to July 2020, the patients with AKI requiring CKRT were eligible if the weight at the start of CKRT had increased by ≥5% compared to the weight at the time of admission, or total body water (TBW)/ height (H)2 ≥13 L/m2. We randomly assigned 208 patients to the control (conventional fluid management; N=103) and intervention groups (BIA-guided fluid management; N=105). Primary outcome was the proportion of attaining e-euvolemia seven days post-randomization. E-euvolemia was defined as the difference between TBW/H2 D7 and D0 was <-2.1 L/m2, or when TBW/H2 measured on D7 was <13 L/m2. The 28-, 60-, and 90-day mortality rate were secondary outcomes. RESULTS: The primary outcome occurred in 34 patients in the intervention group and 27 in the control group (47% versus 41%; P=0.50). The mean value of TBW/H2 measured on D7 was the same at 13.9 L/m2 in both groups. The differences between TBW/H2 D7 and D0 were -1.13 L/m2 in the intervention group and -1.08 L/m2 in the control group (P=0.84). Patients in the intervention group had a significantly higher proportion of reaching e-euvolemia on D1 than those in the control group (13% versus 4%, P=0.02). Adverse events did not differ significantly between the groups. CONCLUSIONS: BIA-guided volume management did not affect the proportion of reaching the estimated euvolemia at seven days of the start of CKRT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03330626 (Registered on 6 November 2017; Seven study participants were retrospectively registered; nonetheless, IRB approval of each institution was completed before study participant registration).

Incidence and Risk Factors of Sacral Fracture following Lumbosacral Fusion for Degenerative Spinal Stenosis with a Minimum Follow-up of 2 years: A Case-Control Study.

BACKGROUND: This study aimed to investigate the incidence and risk factors for sacral fractures following lumbosacral fusion. METHODS: We conducted a retrospective review of patients who underwent lumbosacral fusion for degenerative spinal stenosis with a minimum follow-up of 2 years. Patients who developed and those who did not develop a sacral fracture were categorized into the "sacral fracture" and "non-fracture" groups. The demographic and radiological data were compared between the two groups. RESULTS: A total of 65 patients were included in this study. Among them, seven patients were categorized into the sacral fracture and 58 patients into the non-fracture groups, respectively. The incidence of sacral fracture was 10.8%. In the sacral fracture group, age and fusion levels were significantly higher (P < 0.05), while bone mineral density (BMD) T-score was significantly lower (P < 0.05) than non-fracture group. PI, preoperative PT, postoperative SS, and postoperative LL were significantly higher (P < 0.05) in the sacral fracture than the non-fracture group. Multivariable logistic regression analysis showed that BMD T-score (Odds ratio [OR] 0.25, 95% confidence interval [CI] 0.08-0.79, P = 0.019), postoperative SS (OR 1.14, 95% CI 1.00-1.29, P = 0.047), and changes in L4-S1 lordosis (OR 1.11, 95% CI 1.00-1.23, P = 0.049) were significant factors. CONCLUSIONS: The overall incidence of sacral fracture was 10.8%. In our study, advanced age, low BMD, long fusion levels, and preoperative compensatory pelvic retroversion and excessive correction of it were risk factors for sacral fractures.

Phosphorylated Tau in the Taste Buds of Alzheimer's Disease Mouse Models.

Numerous systemic diseases manifest with oral symptoms and signs. The molecular diagnosis of Alzheimer's disease (AD), the most prevalent neurodegenerative disease worldwide, currently relies on invasive or expensive methods, emphasizing the imperative for easily accessible biomarkers. In this study, we explored the expression patterns of key proteins implicated in AD pathophysiology within the taste buds of mice. We detected the expression of amyloid precursor protein (APP) and tau protein in the taste buds of normal C57BL/6 mice. Phosphorylated tau was predominantly found in type II and III taste cells, while APP was located in type I taste cells. Remarkably, we observed significantly stronger immunoreactivity to phosphorylated tau in the taste buds of aged AD mouse models compared to age-matched controls. These findings underscore the oral expression of biomarkers associated with AD, highlighting the diagnostic potential of the oral cavity for neurodegenerative diseases.

Decoding Arc transcription: a live-cell study of stimulation patterns and transcriptional output.

Activity-regulated cytoskeleton-associated protein (Arc) plays a crucial role in synaptic plasticity, a process integral to learning and memory. Arc transcription is induced within a few minutes of stimulation, making it a useful marker for neuronal activity. However, the specific neuronal activity patterns that initiate Arc transcription have remained elusive due to the inability to observe mRNA transcription in live cells in real time. Using a genetically encoded RNA indicator (GERI) mouse model that expresses endogenous Arc mRNA tagged with multiple GFPs, we investigated Arc transcriptional activity in response to various electrical field stimulation patterns. The GERI mouse model was generated by crossing the Arc-PBS knock-in mouse, engineered with binding sites in the 3' untranslated region (UTR) of Arc mRNA, and the transgenic mouse expressing the cognate binding protein fused to GFP. In dissociated hippocampal neurons, we found that the pattern of stimulation significantly affects Arc transcription. Specifically, theta-burst stimulation consisting of high-frequency (100 Hz) bursts delivered at 10 Hz frequency induced the highest rate of Arc transcription. Concurrently, the amplitudes of nuclear calcium transients also reached their peak with 10 Hz burst stimulation, indicating a correlation between calcium concentration and transcription. However, our dual-color single-cell imaging revealed that there were no significant differences in calcium amplitudes between Arc-positive and Arc-negative neurons upon 10 Hz burst stimulation, suggesting the involvement of other factors in the induction of Arc transcription. Our live-cell RNA imaging provides a deeper insight into the complex regulation of transcription by activity patterns and calcium signaling pathways.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc- in liver cancer: A non-ferroptotic approach.

Erastin, a ferroptosis-inducing system xc- inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.

Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNA (miRNA) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNA, the roles of other micro RNA-binding proteins (miRBPs) remain unclear in regulation of miRNA loading, dissociation from RISC, and extracellular release. In this study, we perform protein arrays to profile miRBPs and identify 118 RNA-binding proteins directly binding with miRNAs. Among those proteins, RBP quaking (QKI) inhibits extracellular release of mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as hnRNPD/AUF1 and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates the Toll-like Receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in mouse cortex. Thus, this study reveals contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.

Characterization of Male Flower Induction by Silver Thiosulfate Foliar Spray in Female Cannabis at the Middle Reproductive Stage for Breeding.

Cannabis (Cannabis sativa) is a versatile crop belonging to the Cannabaceae family, and is dioecious, typically with separate male and female plants. The flowers of female plants, especially the trichomes, accumulate relatively higher contents of cannabinoids compared with those of male plants. For this reason, to obtain seeds that are genetically female, it is desirable to induce the development of male flowers on a female plant that produces genetically female haploid gametes. Silver thiosulfate (STS) is a highly effective chemical for male flower induction. We investigated male flower induction in three commercial cultivars of female cannabis (Spectrum303, SuperwomanS1, and CBGambit) regarding the treatment frequency, stage of application, and concentration of STS applied as a foliar spray. All three cultivars showed adequate induction of male flowers in response to 1.5 mM STS applied at the early reproductive stage. In particular, SuperwomanS1 was most highly responsive to induction of male flowers, even when treated with 0.3 mM STS at the early reproductive stage. Treatment with three applications of STS was more effective compared with a single application, but a single application of 1.5 mM STS at the early reproductive stage was sufficient for male flower induction. A single STS application during the middle stage of reproductive growth was inadequate for induction of male flowers. However, 6 weeks after three applications of STS, CBGambit exhibited approximately 54% male flower induction at 0.3 mM STS, Spectrum303 showed approximately 56% induction at 3 mM STS, and SuperwomanS1 yielded approximately 26% induction at 1.5 mM (expressed as percentage of total number of individuals with the induced male flowers). Pollen stainability tests using KI-I2 solution and Alexander's staining showed high pollen viability with over 65% at different single STS concentrations, indicating that pollen grains induced by STS have sufficient viability for the self-pollination. This study demonstrated that different cultivars of cannabis respond diversely to different STS concentrations and highlighted the potential benefits of three STS applications during the middle reproductive stage for cannabis breeding.

A Preliminary Study of a Prototype Cryoablation Needle on Porcine Livers for Pancreatic Cancer Treatment.

Background and Aims: Despite its relatively low incidence rate compared to others, pancreatic cancer has a poor prognosis owing to its late detection and poor response to systemic chemotherapy. Because the effectiveness of chemotherapy is still restricted, the need for locoregional treatment is increasing. Cryoablation is an effective and minimally invasive treatment for some cancers, but its efficiency in pancreatic cancer is limited. Despite recent reports about promising outcomes, the optimal method and conditions of treatment are not known. In this preliminary study, we aimed to develop a cryoablation needle which can control the ablated area considering application through endoscopic ultrasonography. Methods: Here, we used a novel cryoneedle cooling system which can adjust the ablation range based on a liquid carbon dioxide refrigerant. Applied to the livers of swine, the cryoablation needle rapidly reached -60 °C within 30 s and cryoablation was performed for approximately 240 s. Based on the distance and depth, we collected real-time temperature data during the procedure. To compare the extent of cell death over time, tissue samples were collected hourly from 3 to 6 h after the procedure. Results: Approximately 4-5 mm of tissue was ablated via cryoablation, and cell death progressed over time after cryoablation. Moreover, the ablated lesions could be regulated using an insulating agent on the needle. Conclusions: This preliminary study on a novel surgical cooling needle system compatible with endoscopic ultrasound for cryoablation-based pancreatic cancer treatment confirmed the efficacy of cryoablation and identified the conditions necessary to induce necrosis. Additionally, this study evaluated the effectiveness of the insulation component of the system in protecting normal cells and assessed the extent of necrosis over time after the procedure.

Optimal Positioning of Load-Distributing Band CPR Device by Body Mass Index.

Background: Research investigating the optimal compression position for load-distributing bands (LDBs) in treating cardiac arrest is limited This study aimed to determine the optimal LDB position based on body mass index (BMI). Methods: A simulation study was conducted using chest and abdominal computed tomography imaging data collected with patients in the arms-down position. Participants were categorized into three BMI groups: low (<18.5 kg/m2), normal (18.5-25 kg/m2), and high (≥25 kg/m2). The assumed compression area was 20 cm below the axilla. The optimal compression position was identified by adjusting the axilla to maximize the thorax-to-abdomen volume ratio (TAR) and the covered heart volume ratio (CHR), defined as the ratio of heart volume compressed by the LDB to total heart volume. Optimal compression positions were compared across BMI groups. Results: Among 117 patients, TAR was significantly lower in the low BMI group compared to the normal and high BMI groups (p < 0.001), while CHR differences were not significant (p = 0.011). The distance between the optimal position and axilla height was significantly greater in the normal and high BMI groups than in the low BMI group (46.5 cm vs. 66.0 cm vs. 72 cm, respectively; p < 0.001). For each unit increase in BMI, the optimal position shifted significantly cephalad relative to axilla height (ß coefficient 2.39, adjusted p < 0.001). Conclusions: Significant differences in TAR were observed among BMI groups. As BMI increased, the optimal LDB position shifted progressively cephalad.