Metastable hexagonal close-packed palladium hydride in liquid cell TEM.

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

Entosis implicates a new role for P53 in microcephaly pathogenesis, beyond apoptosis.

Entosis, a form of cell cannibalism, is a newly discovered pathogenic mechanism leading to the development of small brains, termed microcephaly, in which P53 activation was found to play a major role. Microcephaly with entosis, found in Pals1 mutant mice, displays P53 activation that promotes entosis and apoptotic cell death. This previously unappreciated pathogenic mechanism represents a novel cellular dynamic in dividing cortical progenitors which is responsible for cell loss. To date, various recent models of microcephaly have bolstered the importance of P53 activation in cell death leading to microcephaly. P53 activation caused by mitotic delay or DNA damage manifests apoptotic cell death which can be suppressed by P53 removal in these animal models. Such genetic studies attest P53 activation as quality control meant to eliminate genomically unfit cells with minimal involvement in the actual function of microcephaly associated genes. In this review, we summarize the known role of P53 activation in a variety of microcephaly models and introduce a novel mechanism wherein entotic cell cannibalism in neural progenitors is triggered by P53 activation.

Abnormal activation of Yap/Taz contributes to the pathogenesis of tuberous sclerosis complex.

The multi-systemic genetic disorder tuberous sclerosis complex (TSC) impacts multiple neurodevelopmental processes including neuronal morphogenesis, neuronal migration, myelination and gliogenesis. These alterations contribute to the development of cerebral cortex abnormalities and malformations. Although TSC is caused by mTORC1 hyperactivation, cognitive and behavioral impairments are not improved through mTORC1 targeting, making the study of the downstream effectors of this complex important for understanding the mechanisms underlying TSC. As mTORC1 has been shown to promote the activity of the transcriptional co-activator Yap, we hypothesized that altered Yap/Taz signaling contributes to the pathogenesis of TSC. We first observed that the levels of Yap/Taz are increased in human cortical tuber samples and in embryonic cortices of Tsc2 conditional knockout (cKO) mice. Next, to determine how abnormal upregulation of Yap/Taz impacts the neuropathology of TSC, we deleted Yap/Taz in Tsc2 cKO mice. Importantly, Yap/Taz/Tsc2 triple conditional knockout (tcKO) animals show reduced cortical thickness and cortical neuron cell size, despite the persistence of high mTORC1 activity, suggesting that Yap/Taz play a downstream role in cytomegaly. Furthermore, Yap/Taz/Tsc2 tcKO significantly restored cortical and hippocampal lamination defects and reduced hippocampal heterotopia formation. Finally, the loss of Yap/Taz increased the distribution of myelin basic protein in Tsc2 cKO animals, consistent with an improvement in myelination. Overall, our results indicate that targeting Yap/Taz lessens the severity of neuropathology in a TSC animal model. This study is the first to implicate Yap/Taz as contributors to cortical pathogenesis in TSC and therefore as potential novel targets in the treatment of this disorder.

Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study.

BACKGROUND & AIMS: Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC. METHODS: We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR. RESULTS: Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores. CONCLUSIONS: SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL. IMPACT AND IMPLICATIONS: Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes. CLINICAL TRIAL NUMBER: NCT05173610.

Diabetes Mellitus and Acute Facial Palsy: A Nationwide Population-Based Study.

INTRODUCTION: Acute facial palsy, characterized by sudden hemifacial weakness, significantly impacts an individual's quality of life. Despite several predisposing factors identified for acute facial palsy, the specific relationship between diabetes mellitus (DM) and acute facial palsy has not been comprehensively explored in recent studies. The aim of the study was to assess the risk of acute facial palsy in patients with DM using a nationwide population sample cohort. METHODS: DM cohort and non-DM cohort were built using the Korean National Health Insurance Service-Sample Cohort which represents the entire population of the Republic of Korea from January 2002 to December 2019. The DM cohort comprised 92,872 patients with a record of medication and a diagnosis of DM. Individuals who had facial palsy before the diagnosis of DM were excluded. A comparison cohort comprised 1,012,021 individuals without DM matched sociodemographically in a 1:4 ratio. The incidence of Bell's palsy (BP) and Ramsay Hunt syndrome (RHS) were evaluated in both cohorts. The risk factors for acute facial palsy were also assessed. RESULTS: Among the 92,868 patients in the DM cohort, the incidence rate (IR) of BP and RHS were 31.42 (confidence interval [CI], 30.24-32.63) and 4.58 per 10,000 person-years (CI, 4.14-5.05), respectively. Among the 371,392 individuals in the non-DM cohort, the IR of BP was 22.11 per 10,000 person-years (CI, 21.62-22.59) and the IR of RHS was 2.85 per 10,000 person-years (CI, 2.68-3.02). IR ratios for BP and RHS were 1.42 (CI, 1.36-1.48) and 1.61 (CI, 1.43-1.80). In multivariate analysis, DM (hazard ratio [HR] 1.428), age (HR 1.008), and high comorbidity score (HR 1.051) were associated with increased risk of BP, and male (HR 0.803) and living in metropolis (HR 0.966) decreased the risk of BP. And DM (HR 1.615), high comorbidity score (HR 1.078), and living in metropolis (HR 1.201) were associated with increased risk for RHS. CONCLUSION: This study suggests that patients with DM had an increased risk of acute facial palsy including BP and RHS.

Mortality after cardiac arrest in children less than 2 years: relevant factors.

BACKGROUND: There are only scant studies of predicting outcomes of pediatric resuscitation due to lack of population-based data. This study aimed to determine variable factors that may impact the survival of resuscitated children aged under 24 months. METHODS: This is a retrospective study of 66 children under 24 months. Cardiopulmonary resuscitation (CPR) with pediatric advanced life support guideline was performed uniformly for all children. Linear regression analysis with variable factors was conducted to determine impacts on mortality. RESULT: Factors with statistically significant increases in mortality were the number of administered epinephrine (p value < 0.001), total CPR duration (p value < 0.001), in-hospital CPR duration of out-hospital cardiac arrest (p value < 0.001), and changes in cardiac rhythm (p value < 0.040). However, there is no statistically significant association between patient outcomes and remaining factors such as age, sex, underlying disease, etiology, time between last normal to CPR, initial CPR location, initial cardiac rhythm, venous access time, or inotropic usage. CONCLUSION: More than 10 times of epinephrine administration and CPR duration longer than 30 minutes were associated with a higher mortality rate, while each epinephrine administration and prolonged CPR time increased mortality. IMPACT STATEMENT: This study analyzed various factors influencing mortality after cardiac arrest in patients under 24 months. Increased number of administered epinephrine and prolonged cardiopulmonary resuscitation duration do not increase survival rate in patients under 24 months. In patients with electrocardiogram rhythm changes during CPR, mortality increased when the rhythm changed into asystole in comparison to no changes occurring in the rhythm.

Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Facile and cost-effective fabrication of wearable alpha-naphtholphthalein-based halochromic sensor for wound pH monitoring.

The sensor, designed to be worn directly on the skin, is suitable for real-time monitoring of the recovery level of not only general wounds, but also difficult-to-heal wounds, such as those with chronic inflammation. Notably, healthy skin has a pH range of 4-6. When a wound occurs, the pH is known to be approximately 7.4. In this study, alpha-naphtholphthalein (Naph) was immersed in a cotton-blended textile to produce a wearable halochromic sensor that clearly changed color depending on the pH of the skin in the range 6-9, including pH 7.4, which is the skin infection state. The coating was performed without using an organic solvent by dissolving it in micelle form using cetyltrimethylammonium bromide, a surfactant, in water. Naph-based halochromic sensor shows light yellow, which is the dye's own color, at pH 6, which is a healthy skin condition, and gradually showed a clear color change to light green-green-blue as pH increased. Even after washing and drying by rubbing with regular tap water, the color change due to pH was maintained more than 10 times. Naph-based halochromic sensors use a simple solution production and coating method and are not only reusable sensors that can be washed with water but also use environmentally friendly water, making them very suitable for developing commercial products for wound pH monitoring. In addition, it can be easily applied to medical supplies, such as medical gauze, patient clothes, and compression bandages, as well as everyday wear, such as clothing, gloves, and socks. Therefore, it is expected to be widely used as a wound pH sensor, allowing real-time monitoring of the skin condition of individuals with chronic skin inflammation, including patients requiring wound recovery.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Inhaled iloprost in off-pump coronary artery bypass surgery: a randomized controlled trial.

PURPOSE: Mechanical cardiac constraint during off-pump coronary artery bypass surgery (OPCAB) causes right ventricle (RV) compression and increased pulmonary artery pressure (PAP), which may further compromise RV dysfunction. We aimed to assess the effect of inhaled iloprost, a potent selective pulmonary vasodilator, on the cardiac index (CI) during mechanical constraint. The secondary aim was to determine the resultant changes in the hemodynamic and respiratory parameters. METHODS: A total of 100 adult patients with three-vessel coronary artery disease who had known risk factors for hemodynamic instability (congestive heart failure, mean PAP ≥ 25 mm Hg, RV systolic pressure ≥ 50 mm Hg on preoperative echocardiography, left ventricular ejection fraction < 50%, myocardial infarction within one month of surgery, redo surgery, and left main disease) were enrolled in a randomized controlled trial. The patients were randomly allocated to the control or iloprost groups at a 1:1 ratio, in which saline and iloprost (20 µg) were inhaled for 15 min after internal mammary artery harvesting, respectively. Cardiac index was measured by pulmonary artery catheterization. RESULTS: There were no significant intergroup differences in CI during grafting (P = 0.36). The mean PAP had a significant group-time interaction (P = 0.04) and was significantly lower in the iloprost group at circumflex grafting (mean [standard deviation], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0.01). The remaining hemodynamic parameters were similar between the groups. CONCLUSION: Inhaled iloprost showed a neutral effect on hemodynamic parameters, including the CI and pulmonary vascular resistance index, during OPCAB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04598191); first submitted 12 October 2020.

RéSUMé: OBJECTIF: La contrainte cardiaque mécanique lors d'un pontage aortocoronarien à cœur battant (OPCAB) provoque une compression du ventricule droit (VD) et une augmentation de la pression artérielle pulmonaire (PAP), ce qui peut compromettre davantage le dysfonctionnement du VD. Notre objectif était d'évaluer l'effet de l'iloprost inhalé, un puissant vasodilatateur pulmonaire sélectif, sur l'index cardiaque (IC) au cours de la contrainte mécanique. L'objectif secondaire était de déterminer les modifications résultantes des paramètres hémodynamiques et respiratoires. MéTHODE: Au total, 100 patient·es adultes atteint·es d'une coronaropathie à trois vaisseaux qui présentaient des facteurs de risque connus d'instabilité hémodynamique (insuffisance cardiaque congestive, PAP moyenne ≥ 25 mm  Hg, pression systolique du VD ≥ 50 mm Hg à l'échocardiographie préopératoire, fraction d'éjection ventriculaire gauche < 50 %, infarctus du myocarde dans le mois précédant la chirurgie, chirurgie de reprise et maladie principale gauche) ont été inclus·es dans une étude randomisée contrôlée. Les patient·es ont été réparti·es au hasard dans les groupes témoin ou iloprost dans un rapport de 1:1, dans lequel la solution saline et l'iloprost (20 µg) ont été inhalés pendant 15 minutes après le prélèvement de l'artère mammaire interne, respectivement. L'indice cardiaque a été mesuré par cathétérisme de l'artère pulmonaire. RéSULTATS: Il n'y a eu aucune différence significative entre les groupes en matière d'IC pendant le pontage (P = 0,36). La PAP moyenne présentait une interaction significative groupe-temps (P = 0,04) et était significativement plus faible dans le groupe iloprost au pontage de l'artère circonflexe (moyenne [écart type], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0,01). Les autres paramètres hémodynamiques étaient similaires entre les groupes. CONCLUSION: L'iloprost inhalé a montré un effet neutre sur les paramètres hémodynamiques, y compris sur l'IC et l'indice de résistance vasculaire pulmonaire, pendant un pontage aortocoronarien à cœur battant. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04598191); soumis pour la première fois le 12 octobre 2020.

Effect of Retrograde Autologous Priming on Coagulation Assessed by Rotation Thromboelastometry in Patients Undergoing Valvular Cardiac Surgery.

OBJECTIVES: To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery. DESIGN: A prospective, randomized, patient- and outcome assessor-blinded study. SETTING: At a single-center university hospital. PARTICIPANTS: Patients aged 20 years or older undergoing valvular cardiac surgery. INTERVENTIONS: A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms. MEASUREMENTS AND MAIN RESULTS: An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups. CONCLUSIONS: Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery.

Infiltrative fibrous lesion of the facial nerve mimicking a facial nerve tumor.

PURPOSE: To report three cases of facial nerve lesions that were clinically expected to be facial nerve tumors but showed fibrotic infiltration without any apparent signs of a specific tumor on histopathological findings. We also aimed to investigate the clinical characteristics of these cases. METHODS: Medical records of patients who underwent surgery for facial nerve lesions were reviewed. RESULTS: All three cases initially had House-Brackmann (HB) grade IV-V facial nerve palsy. On radiological imaging, schwannoma or glomus tumor originating from the facial nerve was suspected. All patients underwent complete surgical removal of the neoplasm followed by facial nerve reconstruction using the sural nerve. The lesions were histologically confirmed as infiltrative fibrous lesions without tumor cells. In two cases, facial nerve palsy improved to HB grade III by nine months post-surgery, and there were no signs of recurrence on follow-up MRI. The other case, after 1 year of follow-up, showed persistence of HB grade V facial nerve palsy without any evidence of recurrence. CONCLUSION: Fibrotic lesions of the facial nerve could mimic primary facial nerve tumors. Clinicians should consider this condition even when a facial nerve tumor is suspected.

A prognostic value of estimated pulse wave velocity in idiopathic sudden sensorineural hearing loss.

PURPOSE: Arterial stiffness, represented by estimated pulse wave velocity (ePWV), is the independent surrogate marker for cardiovascular event. The aim of the study was to investigate the significance of ePWV in the treatment outcome of idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: One hundred and ten patients with idiopathic SSNHL who hospitalized between April 2019 and March 2022 were evaluated. Arterial stiffness was calculated with formula for ePWV and other cardiovascular parameters of body mass index (BMI), and serum lipid level was determined. All patients received systemic high-dose steroid therapy and intratympanic steroid injections as a salvage management. Treatment outcome was assessed at 6 months after treatment, and classified as recovery and nonrecovery groups according to hearing recovery. RESULTS: The initial pure-tone hearing threshold was 72.6 ± 23.8 dB and final hearing threshold was 52.63 ± 31.10 dB. After treatment, 60 (54.5%) patients included in recovery group and other 50 (45.5%) were classified as nonrecovery group. Age, days of onset to treatment, BMI, waist circumference, and ePWV were higher in the nonrecovery group compared to recovery group in univariate analysis (p = 0.039, p = 0.049, p = 0.003, p = 0.004, p = 0.007, respectively). In multivariate analysis, days of onset to treatment, BMI, and ePWV were associated with recovery (p = 0.030, p = 0.007, p = 0.022). CONCLUSION: Higher ePWV, a measure of arterial stiffness, was associated with a poor hearing recovery of SSNHL.

Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

The effect of apigenin, an aryl hydrocarbon receptor antagonist, in Phthalate-Exacerbated eosinophilic asthma model.

Endocrine disrupting chemicals have been known to contribute to the aggravation of inflammatory diseases including asthma. We aimed to investigate the effects of mono-n-butyl phthalate (MnBP) which is one of the representing phthalates, and its antagonist in an eosinophilic asthma mouse model. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum and followed by three nebulized OVA challenges. MnBP was administered through drinking water administration throughout the study period, and its antagonist, apigenin, was orally treated for 14 days before OVA challenges. Mice were assessed for airway hyperresponsiveness (AHR), differential cell count and type 2 cytokines in bronchoalveolar lavage fluid were measured in vivo. The expression of the aryl hydrocarbon receptor was markedly increased when MnBP was administered. MnBP treatment increased AHR, airway inflammatory cells (including eosinophils), and type 2 cytokines following OVA challenge compared to vehicle-treated mice. However, apigenin treatment reduced all asthma features, such as AHR, airway inflammation, type 2 cytokines, and the expression of the aryl hydrocarbon receptor in MnBP-augmented eosinophilic asthma. Our study suggests that MnBP exposure may increase the risk of eosinophilic inflammation, and apigenin treatment may be a potential therapy for asthma exacerbated by endocrine-disrupting chemicals.

Uniform Gold Nanostructure Formation via Weakly Adsorbed Gold Films and Thermal Annealing for Reliable Localized Surface Plasmon Resonance-Based Detection of DNase-I.

Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.

Biofunctional Inorganic Layered Double Hydroxide Nanohybrid Enhances Immunotherapeutic Effect on Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a widespread, recurrent, and chronic inflammatory skin condition that imposes a major burden on patients. Conventional treatments, such as corticosteroids, are associated with various side effects, underscoring the need for innovative therapeutic approaches. In this study, the possibility of using indole-3-acetic acid-loaded layered double hydroxides (IAA-LDHs) is evaluated as a novel treatment for AD. IAA is an auxin-class plant hormone with antioxidant and anti-inflammatory effects. Following the synthesis of IAA-LDH nanohybrids, their ability to induce M2-like macrophage polarization in macrophages obtained from mouse bone marrow is assessed. The antioxidant activity of IAA-LDH is quantified by assessing the decrease in intracellular reactive oxygen species levels. The anti-inflammatory and anti-atopic characteristics of IAA-LDH are evaluated in a mouse model of AD by examining the cutaneous tissues, immunological organs, and cells. The findings suggest that IAA-LDH has great therapeutic potential as a candidate for AD treatment based on its in vitro and in vivo modulation of AD immunology, enhancement of macrophage polarization, and antioxidant activity. This inorganic drug delivery technology represents a promising new avenue for the development of safe and effective AD treatments.

MRI radiomics may predict early tumor recurrence in patients with sinonasal squamous cell carcinoma.

OBJECTIVES: Sinonasal squamous cell carcinoma (SCC) follows a poor prognosis with high tendency for local recurrence. We aimed to evaluate whether MRI radiomics can predict early local failure in sinonasal SCC. METHODS: Sixty-eight consecutive patients with node-negative sinonasal SCC (January 2005-December 2020) were enrolled, allocated to the training (n = 47) and test sets (n = 21). Early local failure, which occurred within 12 months of completion of initial treatment, was the primary endpoint. For clinical features (age, location, treatment modality, and clinical T stage), binary logistic regression analysis was performed. For 186 extracted radiomic features, different feature selections and classifiers were combined to create two prediction models: (1) a pure radiomics model; and (2) a combined model with clinical features and radiomics. The areas under the receiver operating characteristic curves (AUCs) were calculated and compared using DeLong's method. RESULTS: Early local failure occurred in 38.3% (18/47) and 23.8% (5/21) in the training and test sets, respectively. We identified several radiomic features which were strongly associated with early local failure. In the test set, both the best-performing radiomics model and the combined model (clinical + radiomic features) yielded higher AUCs compared to the clinical model (AUC, 0.838 vs. 0.438, p = 0.020; 0.850 vs. 0.438, p = 0.016, respectively). The performances of the best-performing radiomics model and the combined model did not differ significantly (AUC, 0.838 vs. 0.850, p = 0.904). CONCLUSION: MRI radiomics integrated with a machine learning classifier may predict early local failure in patients with sinonasal SCC. CLINICAL RELEVANCE STATEMENT: MRI radiomics intergrated with machine learning classifiers may predict early local failure in sinonasal squamous cell carcinomas more accurately than the clinical model. KEY POINTS: • A subset of radiomic features which showed significant association with early local failure in patients with sinonasal squamous cell carcinomas was identified. • MRI radiomics integrated with machine learning classifiers can predict early local failure with high accuracy, which was validated in the test set (area under the curve = 0.838). • The combined clinical and radiomics model yielded superior performance for early local failure prediction compared to that of the radiomics (area under the curve 0.850 vs. 0.838 in the test set), without a statistically significant difference.

Anti-obesity effects of Lactiplantibacillus plantarum SKO-001 in high-fat diet-induced obese mice.

PURPOSE: Previous reports showed that some probiotics provide beneficial effects on various diseases including metabolic disorders. This study aimed to investigate the anti-obesity effects of Lactiplantibacillus (L.) plantarum SKO-001 (SKO-001), a probiotic strain newly isolated from Angelica gigas. METHODS: C57BL/6J mice were fed with high-fat diet (HFD, 60% fat) for four weeks, and then different doses of SKO-001 (n = 10 each group) were orally given for 12 weeks. Following treatment, body weight, fat weight, serum parameters and adipose and liver tissues were analyzed. RESULTS: SKO-001 (2 × 1010 CFU/day, per os) reduced body weight gain after 10th week of administration, accompanied by a reduction in body fat mass of mice. In the SKO-001-fed group, increased serum adiponectin, decreased leptin, insulin, total cholesterol, low-density lipoprotein cholesterol, free fatty acids, and triglyceride levels were observed. Hematoxylin and eosin staining of various fat depots showed that increased adipocyte size caused by HFD intake was markedly reduced and correlated with reduced mRNA levels of lipogenesis genes, including sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma, and CCAAT/enhancer binding protein alpha, and increased uncoupling protein 1 levels. Similarly, SKO-001 reduced lipid accumulation, decreased the mRNA levels of lipogenic genes, and reduced α-smooth muscle actin and collagen type 1 alpha 1 levels in the liver. CONCLUSIONS: SKO-001 ameliorates obesity and related metabolic abnormalities in adipose and liver tissues, possibly via the regulation of lipid metabolism. Based on the results of the present study, SKO-001 may be applicable as an anti-obesity therapeutic or functional food.

Morphologic and molecular biologic analyses of the skin rejuvenation effect of the fractional 1064-nm picosecond laser: An animal study.

OBJECTIVES: Application of the picosecond laser in the field of dermatology has expanded from tattoo removal to skin rejuvenation on a clinical basis. Although various mechanisms of pigment removal have been elucidated, the molecular changes associated with skin rejuvenation have yet to be identified. The aim of this study was to explore the theoretical basis and to evaluate the efficacy of skin rejuvenation using a 1064-nm fractional picosecond laser in a mouse model. METHODS: We conducted an in vivo study using a fractional picosecond laser on the skin of old and young female hairless mice and performed topographical, histological, micro-, and electron microscopic assessments. RESULTS: The topography of the skin surface was enhanced and showed increased dermal thickness on histological examination. Electron microscopy revealed disarranged collagen bundles with microspaces and vascular leakage in the upper dermis. Levels of collagen synthesis markers and various inflammatory cytokines, such as procollagens, interleukin-1ß, tumor necrosis factor-α, and heat shock proteins, were elevated in the laser-treated skin. CONCLUSIONS: This study provides a possible mechanism for the skin rejuvenation effect of fractional picosecond laser that has been reported previously in clinical observations. Based on our findings, the fractional picosecond laser could be widely applied in clinical settings where dermal regeneration and promotion of skin rejuvenation is required.