Review of MR spectroscopy analysis and artificial intelligence applications for the detection of cerebral inflammation and neurotoxicity in Alzheimer's disease.

INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders. MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD. RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing. CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.

Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Synergistic role of hydrogen treatment and heterojunction in H-WO3-x/TiO2-x NT/Ti foil-based photoanodes for photoelectrochemical wastewater detoxification and antibacterial activity.

The process of photoelectrochemical wastewater detoxification is limited by significant charge recombination, which is difficult to suppress with efficient single-material photoanodes. We demonstrated the effectiveness of hydrogen treatment in evaluating charge separation properties in WO3-x/TiO2-x NT/Ti foil heterojunction photoanodes. The influence of varying hydrogen annealing (200-400 °C) on the structural and photoelectrochemical properties of WO3/TiO2 NS/NT heterojunction is studied systematically. Additionally, after hydrogen treatment of pristine WO3/TiO2 NT/Ti foil photoanodes, substoichiometric H-WO3-x/TiO2-x NT-300 achieved the 1.21 mA/cm2 photocurrent density, which is 8.06 and 3.27 times than TiO2 NT and WO3/TiO2 NT. The hydrogen-treated H-WO3-x/TiO2-x NT-300 electrode exhibits 3 times greater bulk efficiencies than the WO3/TiO2 NT electrode due to the production of oxygen vacancies at the interface. Additionally, optimum H-WO3-x/TiO2-x NS/NT-300 photoanode exhibited 93.8% E. coli and 99.8% BPA decomposition efficiencies. The present work shows the effectiveness of microwave-assisted H-WO3-x/TiO2-x NT heterojunction photoanodes for organic decomposition and antibacterial activity in a neutral environment without surface-loaded co-catalysts.

A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Volumetric Measurement of Relative CBV Using T1-Perfusion-Weighted MRI with High Temporal Resolution Compared with Traditional T2*-Perfusion-Weighted MRI in Postoperative Patients with High-Grade Gliomas.

BACKGROUND AND PURPOSE: T1-PWI with high temporal resolution may provide a reliable relative CBV value as a valid alternative to T2*-PWI under increased susceptibility. The purpose of this study was to assess the technical and clinical performance of T1-relative CBV in patients with postoperative high-grade gliomas. MATERIALS AND METHODS: Forty-five MRIs of 34 patients with proved high-grade gliomas were included. In all MRIs, T1- and T2*-PWIs were both acquired and processed semiautomatically to generate relative CBV maps using a released commercial software. Lesion masks were overlaid on the relative CBV maps, followed by a histogram of the whole VOI. The intraclass correlation coefficient and Bland-Altman plots were used for quantitative and qualitative comparisons. Signal loss from both methods was compared using the Wilcoxon signed-rank test of zero voxel percentage. The MRIs were divided into a progression group (n = 20) and a nonprogression group (n = 14) for receiver operating characteristic curve analysis. RESULTS: Fair intertechnique consistency was observed between the 90th percentiles of the T1- and T2*-relative CBV values (intraclass correlation coefficient = 0.558, P < .001). T2*-PWI revealed a significantly higher percentage of near-zero voxels than T1-PWI (17.7% versus 3.1%, P < .001). There was no statistically significant difference between the area under the curve of T1- and T2*-relative CBV (0.811 versus 0.793, P = .835). T1-relative CBV showed 100% sensitivity and 57.1% specificity for the detection of progressive lesions. CONCLUSIONS: T1-relative CBV demonstrated exquisite diagnostic performance for detecting progressive lesions in postoperative patients with high-grade gliomas, suggesting the potential role of T1-PWI as a valid alternative to the traditional T2*-PWI.

Attenuation of intrinsic ageing of the skin via elimination of senescent dermal fibroblasts with senolytic drugs.

BACKGROUND: Skin ageing is caused by numerous factors that result in structural and functional changes in cutaneous components. Research has shown that senescent cells are known to accumulate in skin ageing, however, the role of senescent cells in skin ageing has not been defined. OBJECTIVES: To elucidate the role of the senescent cell in skin ageing, we evaluated the effect of known senolytic drugs on senescent dermal fibroblasts. METHODS: Primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, UV irradiation, and H2 O2 treatment. Cell viability was measured after treatment of ABT-263 and ABT-737 on HDFs. Young and aged hairless mice were intradermally injected with drugs or vehicle on the dorsal skin for 10 days. Skin specimens were obtained and reverse-transcription quantitative PCR, western blotting, and histological analysis were performed. RESULTS: We found that ABT-263 and ABT-737 induced selective clearance of senescent dermal fibroblasts, regardless of the method of senescence induction. Aged mouse skin treated with ABT-263 or ABT-737 showed increased collagen density, epidermal thickness, and proliferation of keratinocytes, as well as decreased senescence-associated secretory phenotypes, such as MMP-1 and IL-6. CONCLUSIONS: Taken together, our results indicate that selective clearance of senescent skin cells can attenuate and improve skin ageing phenotypes and that senolytic drugs may be of potential use as new therapeutic agents for treating ageing of the skin.

Increased salivary syndecan-1 level is associated with salivary gland function and inflammation in patients with Sjögren's syndrome.

OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.

Intraindividual Comparison between the Contrast-Enhanced Golden-Angle Radial Sparse Parallel Sequence and the Conventional Fat-Suppressed Contrast-Enhanced T1-Weighted Spin-Echo Sequence for Head and Neck MRI.

BACKGROUND AND PURPOSE: The golden-angle radial sparse parallel-volumetric interpolated breath-hold (GRASP-VIBE) sequence is a recently introduced imaging technique with high resolution. This study compared the image quality between conventional fat-suppressed T1-weighted TSE and GRASP-VIBE after gadolinium enhancement in the head and neck region. MATERIALS AND METHODS: Data from 65 patients with clinical indications for head and neck MR imaging between September 2020 and January 2021 were retrospectively reviewed. Two radiologists assessed the overall image quality, overall artifacts, and image conspicuities in the oropharynx, hypopharynx, and cervical lymph nodes according to 5-point scores (best score: 5). Interobserver agreement was assessed using weighted κ statistics. The SNR and contrast-to-noise ratio were calculated and compared between the 2 sequences using a paired Wilcoxon signed rank test. RESULTS: The analysis included 52 patients (mean age, 60 [SD, 14 ] years; male, 71.2% [37/52]) who were mostly diagnosed with head and neck malignancies (94.3% [50/52]). κ statistics ranged from slight agreement in cervical lymph node conspicuity (κ = 0.18) to substantial agreement in oropharyngeal mucosal conspicuity (κ = 0.80) (κ range, 0.18-0.80). Moreover, GRASP-VIBE demonstrated significantly higher mean scores in overall image quality (4.68 [SD, 0.41] versus 3.66 [SD, 0.73]), artifacts (4.47 [SD, 0.48] versus 3.58 [SD, 0.71]), oropharyngeal mucosal conspicuity (4.85 [SD, 0.41] versus 4.11 [SD, 0.79]), hypopharyngeal mucosal conspicuity (4.84 [SD, 0.34] versus 3.58 [SD, 0.81]), and cervical lymph node conspicuity (4.79 [SD, 0.32] versus 4.08 [SD, 0.64]) than fat-suppressed T1-weighted TSE (all, P < .001). Furthermore, GRASP-VIBE demonstrated a higher SNR (22.8 [SD, 11.5] versus 11.3 [SD, 5.6], P < .001) and contrast-to-noise ratio (4.7 [SD, 5.4] versus 2.3 [SD, 2.7], P = .059) than fat-suppressed T1-weighted TSE. CONCLUSIONS: GRASP-VIBE provided better image quality with fewer artifacts than conventional fat-suppressed T1-weighted TSE for the head and neck regions.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Airway Epithelial Cells Drive Airway Smooth Muscle Cell Phenotype Switching to the Proliferative and Pro-inflammatory Phenotype.

The increased mass of airway smooth muscle (ASM) in the airways of asthmatic patients may contribute to the pathology of this disease by increasing the capacity for airway narrowing. Evidence for the airway epithelium as a participant in ASM remodeling is accruing. To investigate mechanisms by which airway epithelial cells induce ASM cell (ASMC) proliferation, we have employed a co-culture model to explore markers of ASMC proliferative phenotype. Co-culture with epithelial cells led to incorporation of bromodeoxyuridine into ASMCs, indicating augmented proliferation and an associated increase in mRNA of the pro-proliferative co-transcription factor Elk1. Although the mitogen heparin-binding epidermal growth factor (HB-EGF) was augmented in the co-culture supernatant, the ASMC epidermal growth factor receptor (EGFR), an effector of HB-EGF induced proliferation, did not mediate epithelial-induced proliferation. The co-culture increased the expression of ASMC mRNA for the pro-inflammatory cytokines IL-6 and IL-8 as well as the pro-proliferative microRNA miR-210. The transcriptional repressor Max-binding protein (Mnt), a putative target of miR-210, was transcriptionally repressed in co-cultured ASMCs. Together, these data indicate that the airway epithelium-induced proliferative phenotype of ASMCs is not driven by EGFR signaling, but rather may be dependent on miR210 targeting of tumor suppressor Mnt.

Determination of in vitro dry matter, protein, and fiber digestibility and fermentability of novel corn coproducts for swine and ruminants.

New processes are being used in some dry-grind ethanol plants in the United States and Brazil to improve ethanol yield and efficiency of production while also providing nutritionally enhanced corn coproducts compared with conventional corn distillers dried grains with solubles (DDGS). The objectives of this study were to determine the chemical composition and in vitro digestibility of 5 conventional corn DDGS sources and 10 emerging novel corn coproducts for swine and ruminants, and compare coproducts produced using similar processes in the United States and Brazil. Chemical composition, on a dry matter (DM) basis, among the 15 coproducts ranged from 18.5% to 54.7% for crude protein (CP), 12.3% to 51.4% for neutral detergent fiber (NDF), 1.6% to 8.6% for acid detergent fiber, 4.7% to 12.3% for ether extract, and 1.6% to 8.6% for ash. For swine, in vitro hydrolysis of DM and CP were greater (P < 0.01) for the three U.S. corn DDGS sources compared with the two Brazilian corn DDGS sources, but in vitro fermentability of DM was comparable (P > 0.05) among all sources except one U.S. DDGS source that had less fermentable DM. High-protein and yeast dried distillers grains (Ultramax, UM; StillPro, SP) coproducts also had comparable (P > 0.05) DM fermentability for swine, but UM coproducts had greater (P < 0.01) DM and CP hydrolysis compared with SP. High-protein distillers dried grains (HP-DDG) from Brazil had greater (P < 0.01) DM and CP hydrolysis, but less (P < 0.01) DM fermentability for swine than HP-DDG produced in the United States, using the same process. For ruminants, total DM digestibility was greater (P < 0.01) in conventional DDGS sources from the United States compared with the two DDGS sources from Brazil. Total protein digestibility for ruminants was comparable and above 81% for all coproducts except for a DDGS source from Brazil, a HP-DDG source from the United States, and a UM sample. Interestingly, the corn fiber + solubles coproduct had not only relatively high digestibility of NDF (67.9%), DM (91.6%), and total CP (81.9%) for ruminants, but it also had relatively high total tract digestibility of DM (86.2%) and CP (69.9%) for swine. These results suggest that nutrient digestibility of conventional DDGS sources produced in the United States appear to be greater than corn Brazilian DDGS sources, but new process technologies being implemented in ethanol and coproduct production in both countries can enhance the nutritional value of corn coproducts for both swine and ruminants.

Guideline No. 408: management of gestational trophoblastic diseases

This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. Women of reproductive age with gestational trophoblastic diseases. Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care.

Irisin promotes odontogenic differentiation and angiogenic potential in human dental pulp cells.

AIM: To determine whether irisin, a newly discovered myokine that links exercise-induced and metabolic homeostasis, is able to promote odontogenic differentiation and angiogenesis in human dental pulp cells (HDPCs). METHODOLOGY: Cell viability in the presence of irisin was measured. Real-time PCR and Western blot analysis were performed to evaluate the expression levels of irisin, odontogenic and angiogenic markers. The involvement of mitogen-activated protein kinase (MAPK) and the protein kinase B (Akt) signalling pathway was evaluated by Western blot. To evaluate mineralization nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. Scratch wound assays were performed to evaluate the effects of irisin on cell migration. The data were analysed using one-way analysis of variance (anova) followed by Tukey post hoc test and Student's t-test. Statistical significance was considered at P < 0.05. RESULTS: Irisin significantly promoted odontogenic differentiation as evidenced by formation of mineralized nodules, induction of ALP activity and upregulation of odontogenic and angiogenic markers (P < 0.05). Scratch wound assays revealed that irisin significantly increased migration of HDPCs (P < 0.05). Phosphorylation of both MAPK and Akt was increased by irisin. MAPK and Akt inhibitors inhibited mineralization, cell migration and the increased expression of odontogenic and angiogenic markers. CONCLUSIONS: Irisin promoted odontogenic differentiation and mineralization and has the potential for angiogenesis through activation of the MAPK and Akt signalling pathways in HDPCs.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Relationship between dominant frequency, organization index, and left atrial size in patients with atrial fibrillation.

INTRODUCTION: Frequency domain analysis is a methodology for quantifying the organization of atrial fibrillation (AF) pattern to understand the pathophysiology of the electrical mechanism. We aimed to investigate whether the dominant frequency (DF) and organization index (OI) can indicate left atrial (LA) dilatation in patients with AF. METHODS AND RESULTS: This observational, retrospective, single-center cohort study assessed 100 patients with persistent AF. The study population was divided into two groups based on an anterior-posterior LA dimension (LAD of 50 mm) measured by transthoracic echocardiography. The groups were one-to-one propensity score-matched. Frequency domain analysis was performed using signals at leads II and V1 on surface electrocardiogram to calculate the DF and OI. In all patients, the DF was shown to have an inverse relationship with LAD (R = -.369, p < .001 in lead II; R = -.330, p = .001 in lead V1), while the OI was directly associated with LAD (R = .234, p = .190 in lead II; R = .283, p = .004 in lead V1). However, no significant relationship between the signal amplitude and LAD was observed. Compared to patients with LAD ≤ 50 mm, those with LAD > 50 mm had a lower DF (5.057 ± 0.740 vs. 4.542 ± 0.898, p = .002) and higher OI (0.261 ± 0.104 vs. 0.322 ± 0.116, p = .007) in lead V1. These findings were consistent with those found in lead II. CONCLUSION: Patients with persistent AF and a larger LA size had a significantly higher OI and lower DF than those with a smaller LA size. Atrial electrical properties of structural remodeling are associated with increased organization of atrial signals.

Prediction of Human Papillomavirus Status and Overall Survival in Patients with Untreated Oropharyngeal Squamous Cell Carcinoma: Development and Validation of CT-Based Radiomics.

BACKGROUND AND PURPOSE: Human papillomavirus is a prognostic marker for oropharyngeal squamous cell carcinoma. We aimed to determine the value of CT-based radiomics for predicting the human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Eighty-six patients with oropharyngeal squamous cell carcinoma were retrospectively collected and grouped into training (n = 61) and test (n = 25) sets. For human papillomavirus status and overall survival prediction, radiomics features were selected via a random forest-based algorithm and Cox regression analysis, respectively. Relevant features were used to build multivariate Cox regression models and calculate the radiomics score. Human papillomavirus status and overall survival prediction were assessed via the area under the curve and concordance index, respectively. The models were validated in the test and The Cancer Imaging Archive cohorts (n = 78). RESULTS: For prediction of human papillomavirus status, radiomics features yielded areas under the curve of 0.865, 0.747, and 0.834 in the training, test, and validation sets, respectively. In the univariate Cox regression, the human papillomavirus status (positive: hazard ratio, 0.257; 95% CI, 0.09-0.7; P = .008), T-stage (≥III: hazard ratio, 3.66; 95% CI, 1.34-9.99; P = .011), and radiomics score (high-risk: hazard ratio, 3.72; 95% CI, 1.21-11.46; P = .022) were associated with overall survival. The addition of the radiomics score to the clinical Cox model increased the concordance index from 0.702 to 0.733 (P = .01). Validation yielded concordance indices of 0.866 and 0.720. CONCLUSIONS: CT-based radiomics may be useful in predicting human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma.