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The Music, Arts, Physical Education, and Health Education (MAPEH) is one of the K-12 educational field curricula that aims to improve learning competencies through age-appropriate developmental tasks. The Developmental Tasks Theory emphasizes that each stage of life requires certain tasks to be mastered for healthy development and adjustment. Failing to achieve these tasks can negatively impact future stages of development. For intermediate pupils to progress to the next academic level, they must acquire increasing competence and also a sense of responsibility, a realistic perspective, and the potential to self-direct but in order to fulfill these the level of achievement and factors that influence their performances must be determined. The objective of this study was to develop an Instructional Design Model that would serve as an instructional intervention for intermediate pupils. The level of achievement in the MAPEH developmental tasks and the challenges encountered by the pupils were analyzed to develop an instructional design model for MAPEH. Integrating R-2I-2C Pedagogical Approaches based on the theory and findings was created to enhance the teaching of Music, Arts, Physical Education, and Health Education. This compendium of MAPEH lesson plans has been created to seamlessly incorporate R-2I-2C pedagogical approaches.

International science assessments consistently show the Philippines scoring low, highlighting a critical gap in the effectiveness of current learning materials. This study aimed to address this gap by assessing a Strategic Intervention Material (SIM) designed to improve student learning in science. The researchers developed a pocket SIM titled "Transformation City" to target the least mastered competency in the topic 'Transformation of Energy' for Grade 6 students. A mixed-methods research design was employed to analyze the impact of the SIM on 30 students at DMMMSU-MLUC Laboratory Elementary School. The study utilized pre-tests, post-tests, student perception surveys, and student feedback to assess knowledge gained and gather insights for improvement. The findings revealed a significant increase in student learning outcomes after using the "Transformation City" SIM, demonstrating its potential to bridge the gap in science education.

Virtual instructional materials are in high demand amidst the pandemic. Many Filipino teachers were caught off guard and lacked adequate distance education tools. Though there were, the majority were dilapidated and obsolete. A logical approach, such as the ADDIE Model, is essential for developing instructional materials. Its process sequence is crucial since the design's effectiveness is measured by the results of evaluations and how the intended objectives are realized. This study aimed to develop virtual Science interactive learning materials for distance learning in accordance with the five steps of the ADDIE Model. A formal assessment was carried out on the developed materials to examine their validity in terms of Content Quality, Instructional Quality, Technical Quality, and Technical Error, and to evaluate their usability and interoperability.

We introduce a stochastic model in which adjacent planar regions A, B merge stochastically at some rate λ(A, B) and observe analogies with the well-studied topics of mean-field coagulation and of bond percolation. Do infinite regions appear in finite time? We give a simple condition on λ for this hegemony property to hold, and another simple condition for it to not hold, but there is a large gap between these conditions, which includes the case λ(A, B) ≡ 1. For this case, a non-rigorous analytic argument and simulations suggest hegemony. © 2010 IOP Publishing Ltd.

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Background: Social innovations in health are inclusive solutions to address the healthcare delivery gap that meet the needs of end users through a multi-stakeholder, community-engaged process. While social innovations for health have shown promise in closing the healthcare delivery gap, more research is needed to evaluate, scale up, and sustain social innovation. Research checklists can standardize and improve reporting of research findings, promote transparency, and increase replicability of study results and findings.Methods and Findings: The research checklist was developed through a 3-step community-engaged process, including a global open call for ideas, a scoping review, and a 3-round modified Delphi process. The call for entries solicited checklists and related items and was open between November 27, 2019 and February 1, 2020. In addition to the open call submissions and scoping review findings, a 17-item Social Innovation For Health Research (SIFHR) Checklist was developed based on the Template for Intervention Description and Replication (TIDieR) Checklist. The checklist was then refined during 3 rounds of Delphi surveys conducted between May and June 2020. The resulting checklist will facilitate more complete and transparent reporting, increase end-user engagement, and help assess social innovation projects. A limitation of the open call was requiring internet access, which likely discouraged participation of some subgroups.Conclusions: The SIFHR Checklist will strengthen the reporting of social innovation for health research studies. More research is needed on social innovation for health. [ABSTRACT FROM AUTHOR]

Background: Along with obesity, physical inactivity, and family history of metabolic disorders, African American ethnicity is a risk factor for type 2 diabetes (T2D) in the United States. However, little is known about the differences in gene expression and transcriptomic profiles of blood in T2D between African Americans (AA) and Caucasians (CAU), and microarray analysis of peripheral white blood cells (WBCs) from these two ethnic groups will facilitate our understanding of the underlying molecular mechanism in T2D and identify genetic biomarkers responsible for the disparities. Results: A whole human genome oligomicroarray of peripheral WBCs was performed on 144 samples obtained from 84 patients with T2D (44 AA and 40 CAU) and 60 healthy controls (28 AA and 32 CAU). The results showed that 30 genes had significant difference in expression between patients and controls (a fold change of <-1.4 or >1.4 with a P value <0.05). These known genes were mainly clustered in three functional categories: immune responses, lipid metabolism, and organismal injury/abnormaly. Transcriptomic analysis also showed that 574 genes were differentially expressed in AA diseased versus AA control, compared to 200 genes in CAU subjects. Pathway study revealed that "Communication between innate and adaptive immune cells"/"Primary immunodeficiency signaling" are significantly down-regulated in AA patients and "Interferon signaling"/"Complement System" are significantly down-regulated in CAU patients. Conclusions: These newly identified genetic markers in WBCs provide valuable information about the pathophysiology of T2D and can be used for diagnosis and pharmaceutical drug design. Our results also found that AA and CAU patients with T2D express genes and pathways differently. [ABSTRACT FROM AUTHOR]

Background: Postoperative gastrointestinal dysfunction (POGD) remains a common morbidity after gastrointestinal surgery. POGD is associated with delayed hospital recovery, increased length of stay, poor patient satisfaction and experience, and increased economic hardship. The I-FEED scoring system was created by a group of experts to address the lack of a consistent objective definition of POGD. However, the I-FEED tool needs clinical validation before it can be adopted into clinical practice. The scope of this phase 1 Quality Improvement initiative involves the feasibility of implementing percussion into the nursing workflow without additional burden. Methods: All gastrointestinal/colorectal surgical unit registered nurses underwent comprehensive training in abdominal percussion. This involved understanding the technique, its application in postoperative gastrointestinal dysfunction assessment, and its integration into the existing nursing documentation in the Electronic Health Record (EHR). After six months of education and practice, a six-question survey was sent to all inpatient GI surgical unit nurses about incorporating the percussion assessment into their routine workflow and documentation. Results: Responses were received from 91% of day-shift nurses and 76% of night-shift registered nurses. Overall, 95% of the nurses were confident in completing the abdominal percussion during their daily assessment. Conclusion: Nurses' effective use of the I-FEED tool may help improve patient outcomes after surgery. The tool could also be an effective instrument for the early identification of postoperative gastrointestinal dysfunction (POGD) in surgical patients.

Background: Glioblastoma (GBM) is notorious for the aggressive behaviors and easily results in chemo-resistance. Studies have shown that the use of herbal medicines as treatments for GBM as limited by the blood-brain barrier (BBB) and glioma stem cells., Purpose: The aim of this study was to investigate the relationship between GBM suppression and α-terpineol, the monoterpenoid alcohol derived from Eucalyptus glubulus and Pinus merkusii., Study Design: Using serial in-vitro and in-vivo studies to confirm the mechanism of α-terpineol on down-regulating GBM development., Methods: The 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate IC50 of α-terpineol to inhibit GBM cell survival. In order to evaluate the impact of GBM aggressive behaviors by α-terpineol, the analysis of cell migration, invasion and colony formation were implemented. In addition, the ability of tumor spheres and WB of CD44 and OCT3/4 were evaluated under the impression of α-terpineol decreased GBM stemness. The regulation of neoangiogenesis by α-terpineol via the WB of angiogenic factors and human umbilical vein endothelial cells (HUVEC) tube assay. To survey the decided factors of α-terpineol downregulating GBM chemoresistance depended on the impact of O6-methylguanine-DNA methyltransferase (MGMT) expression and autophagy-related factors activation. Additionally, WB and quantitative real-time polymerase chain reaction (qRT/PCR) of KDEL (Lys-Asp-Glu-Leu) containing 2 (KDELC2), endoplasmic reticulum (ER) stress, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) cascade signaling factors were examined to explore the mechanism of α-terpineol inhibiting GBM viability. Finally, the orthotopic GBM mouse model was applied to prove the efficacy and toxicity of α-terpineol on regulating GBM survival., Results: α-terpineol significantly suppressed GBM growth, migration, invasion, angiogenesis and temozolomide (TMZ) resistance. Furthermore, α-terpineol specifically targeted KDELC2 to downregulate Notch and PI3k/mTOR/MAPK signaling pathway. Finally, we also demonstrated that α-terpineol could penetrate the BBB to inhibit GBM proliferation, which resulted in reduced cytotoxicity to vital organs., Conclusion: Compared to published literatures, we firstly proved α-terpineol possessed the capability to inhibit GBM through various mechanisms and potentially decreased the occurrence of chemoresistance, making it a promising alternative therapeutic option for GBM in the future., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. The study design was approved by the appropriate ethics review board. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. All authors declare that there is no conflict of interest in this study., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Intubation is an essential procedure in cardiopulmonary resuscitation (CPR). We conducted a systematic review and meta-analysis of trials and studies comparing the performance of video laryngoscope (VL) and direct laryngoscope (DL) in endotracheal intubation (ETI) during CPR in cardiac arrest (OHCA) patients., Methods: We searched the PUBMED, EMBASE, and Cochrane library databases. We analyzed the first-pass success rate, total intubation time, Cormack-Lehane grade (CL grade), esophageal intubation rate, and dental injury rate among the in-hospital cardiac arrest (IHCA) patients or out-of-hospital cardiac arrest (OHCA) patients. We demonstrated the pooled results of continuous outcomes by mean difference (MD) and dichotomous outcomes by odds ratio (OR), with a 95% confidence interval (CI) using a random-effects model., Results: We obtained six observational studies and one randomized control trial. The pooled results showed a significant increase in first-pass success rate (OR: 1.86, 95% CI: 1.41, 2.47), Cormack-Lehane (CL) grade (OR: 2.01, 95% CI: 1.59,2.53), and a decrease of esophageal intubation rate (OR: 0.25, 95% CI: 0.08, 0.85) in the VL group compared with DL group. Also, a non-significant decrease in dental injury rate [OR: 0.23, 95% CI: 0.05, 1.08) was observed in the VL group compared with the DL group. There was no statistical difference between the VL and DL groups, although the VL group seemed to have a shorter total intubation time (MD: -15.43, 95% CI: -34.67, 3.81). Types of laryngoscopes were not associated with the rate of ROSC [OR 1.01 (0.95,1.07); P = 0.83]. No differences in survival outcomes were observed between the two approaches., Conclusions: Compared to DL, VL was found to be associated with first-pass success and CL grade. We recommend prioritizing VL over DL when performing ETIs for patients with cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess patient and provider perspectives on the acceptability of reproductive goals assessment in public mental health clinics and inform potential tailoring for these settings., Data Sources and Study Setting: Primary qualitative data from patients and providers at four clinics in an urban public mental health system serving individuals with chronic mental illness (collected November 2020-October 2021)., Study Design: This was an exploratory qualitative study with patients (English-speaking women of reproductive age, primarily Black or Latina) and mental health providers (psychiatrists, psychotherapists, case managers, nurses). We examined the acceptability of reproductive goals assessment within mental health care and obtained feedback on two reproductive goals assessment conversation guides: PATH (Pregnancy Attitudes, Timing, and How Important is Pregnancy Prevention) and OKQ (One Key Question)., Data Collection: We conducted semi-structured telephone interviews with 22 patients and 36 providers. We used rapid qualitative analysis to summarize interview transcripts and identified themes using matrix analysis., Principal Findings: Perceptions of reproductive goals assessment were generally positive. Providers said the conversation guides would "open the door" to important discussions, support a better understanding of patients' goals, and facilitate medication counseling and planning. A minority of patients expressed discomfort or ambivalence; several suggested providers ask permission or allow patients to raise the topic. Additional themes included the need for framing to provide context for these personal questions, the need to build rapport before asking them, and the challenge of balancing competing priorities. Many participants found both PATH and OKQ prompts acceptable; some preferred the "conversational" and "open-ended" PATH phrasing., Conclusions: Participants perceived reproductive goals assessment as a promising practice in mental health care with unique functions in this setting. Areas of discomfort highlight the sensitivity of these topics for some women with chronic mental illness and suggest opportunities to tailor language, framing, and provider training to support effective and appropriate implementation., (© 2022 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC., Competing Interests: Declaration of Competing Interest The authors stated they have no potential financial competing interests that could in any way to gain or losing financially in publication of this manuscript now or the future. Furthermore, no nonfinancial competing interests are involved in the manuscript., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Tracheal intubation is an important clinical skill for medical students and junior residents (novice intubators). They are usually trained to use a direct laryngoscope (DL) with straight-to-cuff styletted tracheal tubes first. Only later are they exposed to the bougie as an airway adjunct and videolaryngoscope (VL) with either a standard blade or a hyperangulated blade. The purpose of this study was to investigate the performance of novice intubators in using DL with 3 common stylets., Methods: We conducted a prospective study to compare the performance of DL with 3 common stylets, namely the straight-to-cuff stylet (S), hyperangulated VL stylet (G), and bougie (B), on a manikin model., Results: Among 72 participants, no significant difference was observed between the success rates of S, G, and B at the first attempt (84.72%, 81.94%, and 86.11%, respectively [P = .78]) or within 2 minutes (91.67%, 93.06%, and 91.67%, respectively [P = .94]). For participants with successful intubation within 2 minutes, the average total intubation times for S, G, and B were 25.05, 24.39, and 37.45 seconds, respectively. Among the 3 stylets, B had the longest intubation time, which differed significantly from S and G (P < .01)., Conclusions: The performances of novice intubators with 3 different stylets were similar. The success rates for DL with either hyperangulated VL stylet or bougie were not inferior compared with the straight-to-cuff stylet on manikin airway training model. If we properly trained novice intubators to use corresponding maneuvers, they can learn to use the 3 stylets early in their airway learning course., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Preoxygenation is crucial for providing sufficient oxygen reservoir to a patient before intubation and enables the extension of the period between breathing termination and critical desaturation (safe apnoea time). Conventionally, face mask ventilation is used for preoxygenation. Non-invasive ventilation is a new preoxygenation method. The study objective was to compare the outcomes of non-invasive ventilation and face mask ventilation for preoxygenation., Method: PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry were searched for eligible studies published from database inception to September 2021. Individual effect sizes were standardized, and a meta-analysis was conducted using random effects models to calculate the pooled effect size. Inclusion criteria were randomised controlled trials of comparing the outcomes of non-invasive ventilation or face mask ventilation for preoxygenation in patients scheduled for surgeries. The primary outcome was safe apnea time, and the secondary outcomes were post-operative complications, number of patients who achieved the expired O 2 fraction (FeO 2 ) after 3 min of preoxygenation, minimal SpO 2 during tracheal intubation, partial pressure of oxygen in the arterial blood (PaO 2 ) and partial pressure of carbon dioxide (PaCO 2 ) after preoxygenation, and PaO 2 and PaCO 2 after tracheal intubation., Results: 13 trials were eligible for inclusion in this study. Significant differences were observed in safe apnoea time, number of patients who achieved FeO 2 90% after preoxygenation for 3 min, and PaO 2 and PaCO 2 after preoxygenation and tracheal intubation. Only in the non-obese subgroup, no significant difference was observed in safe apnoea time (mean difference: 125.38, 95% confidence interval: - 12.26 to 263.03)., Conclusion: Non-invasive ventilation appeared to be more effective than conventional methods for preoxygenation. We recommend non-invasive ventilation based on our results., (© 2022. The Author(s).)

Background: Despite therapeutic advancements, metastasis remains a major cause in breast cancer-specific mortality. Breast cancer cells are susceptible to oxidative damage and exhibit high levels of oxidative stress, including protein damage, DNA damage, and lipid peroxidation. Some breast cancer risk factors may change the level of endogenous oxidative stress. Circulating exosomes play critical roles in tumorigenesis, distant metastasis, and poor prognosis in patients with breast cancer., Methods: We used an online database to analyze the expression and prognostic value of core binding factor subunit β (CBFB) and oxidative stress-related targets in patients with breast cancer. Serum from healthy controls and patients with primary breast cancer or bone metastatic breast cancer in the bone was collected. Exosomes were isolated from the sera or cell culture media. We used an MDA-MB-436-innoculated tumor xenograft mouse model for silencing CBFB., Results: Circulating exosomes from patients with breast cancer metastasis to the bone were rich in CBFB. The human mammary fibroblast cells HMF3A and fibroblasts derived from patient samples cocultured with exosomes had increased α -SMA and vimentin expression and IL-6 and OPN secretion. Similarly, nonmetastatic breast cancer cells cocultured with exosomes exhibited increased levels of certain markers, including vimentin, snail1, CXCR4, and Runx2, and the exosomes had high CBFB expression. Silencing CBFB in metastatic MDA-MB-436 and MDA-MB-157 cells resulted in suppressed migration and invasion and downregulation of vimentin, CXCR4, snail1, Runx2, CD44, and OPN. Conversely, CBFB overexpression resulted in upregulation of Runx2, vimentin, snail1, CD44, and OPN in nonmetastatic T47D and MCF12A cells. The CBFB-rich exosomes derived from MDA-MB-436 cells induced enhanced metastatic phenotypes in the low-metastatic T47D and MCF12A cell lines., Conclusion: Our results revealed that CBFB may promote bone metastasis in patients with breast cancer. Of therapeutic relevance, targeting CBFB resulted in decreased tumor burden and bone metastasis, downregulation of bone metastasis markers, and impaired regulation of oxidative stress-related proteins NAE1 and NOS1., Competing Interests: The authors declare that they have no potential financial competing interests related to the publication of this manuscript. The authors also declare no nonfinancial competing interests., (Copyright © 2022 Chia-Hung Hsu et al.)

Background: Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 -) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2- breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells., Methods: We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment., Results: High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4., Conclusion: The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells., (Copyright © 2021. Published by Elsevier Inc.)

Sorafenib is used for treating advanced hepatocellular carcinoma (HCC), but some patients acquire sorafenib resistance. We investigated the mechanisms underlying acquired sorafenib resistance in HCC cells and targeted them to re-sensitize them to sorafenib. In silico analysis indicated that toll-like receptor (TLR)-9 was significantly overexpressed, and that miRNA (hsa-miR-30a-5p) was downregulated in sorafenib-resistant HCC cells, which modulated HCC cell proliferation, oxidative stress, and apoptosis. TLR9 overexpression increased HCC cell proliferation, whereas TLR9 inhibition from hydroxychloroquine (HCQ) decreased HCC cell proliferation, tumor growth, oxidative stress marker (SOD1), and the formation of autophagosome bodies (reduced ATG5 and Beclin-1 expression). Moreover, HCQ treatment reduced epithelial-mesenchymal transition, leading to decreased clonogenicity, migratory ability, and invasiveness. HCQ targeted and reduced the self-renewal capacity phenotype by inhibiting tumorsphere generation. Both in vitro and in vivo results demonstrated the synergistic effect of the HCQ-sorafenib combination on sorafenib-resistant HCC (Huh7-SR) cells, increasing their sensitivity to treatment by modulating TLR9, autophagy (ATG5 and Beclin-1), oxidative stress (SOD1), and apoptosis (c-caspase3) expression and thus overcoming the drug resistance. This study's findings indicate that TLR9 overexpression occurs in sorafenib-resistant HCC cells and that its downregulation aids HCC suppression. Moreover, HCQ treatment significantly increases sorafenib's effect on sorafenib-resistant HCC cells.

Background: Hepatitis virus is a major risk factor for liver cancer. The mitochondrial dysfunction IFN gamma-related pathways are activated after virus infection. Jak family-related protein is involved in the downstream of IFN gamma-related pathways. However, the effect of the IFNGR-JAK-STAT pathway acting as functional regulators of their related protein expression on virus infection and hepatocellular carcinoma (HCC) remains unclear. Interestingly, the role of the DNA repair gene (PARP1) in therapy resistant cancers also has not been studied and explored well. In this study, we hypothesized that momelotinib could suppress the progression of HCC by targeting Jak family related and PARP1 DNA repair protein. Based on this observation, we link the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors., Methods: We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation assay, cell invasion, migration, and tumorsphere-formation assay were used for drug cytotoxicity, cell viability, and possible molecular mechanism., Result: We first demonstrated that the expression of Jak1 and 2 is significantly upregulated in vHCC than in nvHCC/normal liver tissues. In addition, the gene expression of IFN gamma-related pathways is activated after virus infection. Additionally, we found that momelotinib significantly inhibited the growth of HCC cells and reduces the expression of Jak2, which showed the importance of momelotinib in targeting Jak2 and reducing tumorigenesis in HCC. Meanwhile, momelotinib effectively inhibited the IFNGR-JAK-STAT pathway and reduced the migratory/invasive ability of vHCC cells through down-regulating EMT biomarkers (E-cadherin and vimentin), transcription factor (Slug), and significantly inhibits the DNA damage repair enzyme PARP1. It also induced cell apoptosis of vHCC cells. Furthermore, the combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden., Conclusions: Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

Traumatic brain injury (TBI) causes major socioeconomic problems worldwide. In the United States, nearly three-quarters of patients with TBI have mild TBI (mTBI). 32% of these patients may develop dizziness. In this study, we analyzed the factor structure of the traditional Chinese version of the DHI and evaluate the differences in DHI factors between dizziness and nondizziness groups. In total, 315 patients with mTBI, comprising 158 with self-reported dizziness and 157 without dizziness, were recruited from three hospitals. The responses for Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) demonstrated between-group differences. The Chinese DHI had internal validity and had four factors that differed from the English version (3 aspects). The group effects for the physical subscale remained significantly different even after adjustments in the propensity score model. For the Chinese version, two of four factors remained significantly different in the effects between self-reported dizziness and nondizziness groups. The factors of our Chinese DHI differed from those of the original English version of DHI. After adjustments using the propensity score model, the physical subscale demonstrated significant differences between the self-reported dizziness and nondizziness groups. Only two factors from our Chinese DHI were significantly different; moreover, it contained only three physical, five functional, and three emotional items., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Hon-Ping Ma et al.)

Purpose: To report the rate of fetal anomalies detected on anatomy ultrasound in pregnant patients who underwent IVF with preimplantation genetic testing for aneuploidy (PGT-A) compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions., Methods: Retrospective cohort study at a single maternal-fetal medicine practice. Patients with singleton pregnancies who had a mid-trimester anatomy ultrasound between January 2017 and December 2018 were screened for inclusion. A total of 712 patients who conceived after IVF with or without PGT-A were age-matched with natural conception controls. The primary outcome was the rate of fetal and placental anomalies detected on mid-trimester anatomical survey. Secondary outcomes included the rates of abnormal nuchal translucency (NT), second trimester serum analytes, non-invasive prenatal testing (NIPT), and invasive diagnostic testing., Result(s): There were no differences in the rate of fetal anomalies in patients who underwent IVF with PGT-A compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions. Rate of abnormal NT, high-risk NIPT, and abnormal invasive diagnostic testing were also similar. Patients who conceived after IVF with or without PGT-A had higher rates of abnormal placental ultrasound findings and abnormal second trimester serum analytes compared to natural conception controls., Conclusion: The use of PGT-A was not associated with a difference in risk of fetal anomaly detection on a mid-trimester anatomical survey. The results of this study highlight the importance of improved patient counseling regarding the limitations of PGT-A, and of providing standard prenatal care for pregnancies conceived through ART, regardless of whether PGT-A was performed.

Integrated photodetectors are essential components of scalable photonics platforms for quantum and classical applications. However, most efforts in the development of such devices to date have been focused on infrared telecommunications wavelengths. Here, we report the first monolithically integrated avalanche photodetector (APD) for visible light. Our devices are based on a doped silicon rib waveguide with a novel end-fire input coupling to a silicon nitride waveguide. We demonstrate a high gain-bandwidth product of 234 ± 25 GHz at 20 V reverse bias measured for 685 nm input light, with a low dark current of 0.12 μA. We also observe open eye diagrams at up to 56 Gbps. This performance is very competitive when benchmarked against other integrated APDs operating in the infrared range. With CMOS-compatible fabrication and integrability with silicon photonic platforms, our devices are attractive for sensing, imaging, communications, and quantum applications at visible wavelengths.

Rationale: Postpartum ovarian vein thrombophlebitis (POVT) is a rare condition, and it can lead to severe complications and mortality. Here we report a patient who presented with vaginal bleeding and the diagnosis of POVT was confirmed by imaging., Patient Concerns: A 38-year-old postpartum woman without remarkable medical history presented with vaginal bleeding and lower abdominal pain., Diagnoses: The diagnosis was confirmed by computed tomography scan marked by a thrombus mass involving the right ovarian vein and inferior vena cava., Interventions: The patient was treated with intravenous antibiotics and low-molecular-weight heparin., Outcomes: The patient recovered smoothly without complications., Lessons: We should pay high attention to the recognition and management of POVT to prevent morbidity and mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA-LIHC patients ( n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1 , CCNB1 , CDK4 and CDK1 , while simultaneously inhibiting tumor suppressors including PDK4 , KLF9 , FOXO1 and ALDH2 . Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort ( n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with 'normal' paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Optical frequency conversion in semiconductor nanophotonic devices usually imposes stringent requirements on fabrication accuracy and etch surface roughness. Here, we adopt the concept of bound-state-in-continuum (BIC) for waveguide frequency converter design, which obviates the limitations in nonlinear material nano-fabrication and requires to pattern only a low-refractive-index strip on the nonlinear slab. Taking gallium phosphide (GaP) as an example, we study second-harmonic generation using horizontally polarized pump light at 1.55 µm phase matching to vertically polarized BIC modes. A theoretical normalized frequency conversion efficiency of 1.1×10 4 % W -1 c m -2 is obtained using the fundamental BIC mode, which is comparable to that of conventional GaP waveguides.

Introduction: Emergency decompression is needed in patients with tension pneumothorax, a life-threatening condition. The catheter-based needle thoracostomy was suggested using a 5 cm catheter inserted into the 2nd intercostal space (ICS) and 5th ICS according to the ninth and tenth editions of Advanced Trauma Life Support, respectively. A catheter of suitable length may not be available immediately or the muscle structure of the chest wall may be modified in pneumothorax. Furthermore, alternative sites for needle thoracostomy and reference values of chest wall thickness (CWT) should be explored and warranted., Method: CT scan data and medical data of 650 eligible patients from October 2016 to December 2016 were reviewed. CWT values at four ICSs as well as four variables, namely, age, weight, height, and body mass index (BMI) for both men and women were compared using a nonparametric method, namely, the Wilcoxon signed-rank test. The associations between CWT and the four variables were assessed using the Pearson correlation coefficient. The overall performance of BMI, weight, and height in predicting CWT > 5 cm was evaluated using the receiver-operating characteristic (ROC) curve. Finally, the prediction models were built by using the bootstrap method., Results: Four variables, namely, age, height, weight, and BMI, were compared between the men and women groups. All four variables differed significantly between the two groups, and CWTs at all ICSs, except for the 3rd ICS, differed significantly between the two groups. Among the women, the area under the ROC curve (AUROC) of BMI for predicting CWT > 5 cm at 2nd ICS was larger than the AUROC of weight and height. Among the men, the AUROC of weight for predicting CWT > 5 cm at 2nd ICS was larger than that of BMI and height. The reference value tables were provided for five proposed models for women and men, respectively. Under emergencies, the variable, BMI, or even weight itself, could be used for predicting a failure performance of the needle decompression. For women, CWT at 5th ICS was predicted over 5 cm at BMI over 25.9 kg/m 2 or weight over 103.1 kg. For men, CWT at 5th ICS was predicted over 5 cm at BMI over 25.5 kg/m 2 or weight over 157.4 kg., Conclusion: Needle thoracostomy is the preferred first technique for many emergency providers for decompression. Therefore, a reference table for safe needle thoracostomy decompression at four usual sites, namely, 2nd ICS, 3rd CIS, 4th ICS, and 5th ICS, was recommended, which will enable paramedics and emergency specialists to rapidly determine CWT at the appropriate ICSs during emergencies., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Chia-Hung Hsu et al.)

Introduction: Unintentional injury remains the leading cause of death in children worldwide. Adequate parental supervision is a crucial strategy for preventing injury. Many factors, such as a large family size, poor socioeconomic status, and the caregiver being a single mother, contribute to unintentional injury in children. In addition, sleep deprivation in caregivers might be associated with injury in children because sleep deprivation causes impaired daytime cognitive function, wake-state instability, and negative moods, thereby impairing caregiver supervision. Therefore, this study determines the association between injury in children and the sleep quality of their primary caregivers., Method: This is a retrospective case-control study on unintentional injury in children aged 0 to 4 years who visited the emergency department (case group) and an age- and sex-matched control group. Sleep quality in caregivers was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to evaluate the association between aspects of the PSQI and injury. A propensity score model was used to generate a quasirandomized design., Results: This case-control study recruiting 277 injured and 274 noninjured children was conducted in Taiwan. There was no statistically significant difference in child's age and primary caregiver's age between the injured and noninjured groups. The primary outcome, Pittsburgh sleep quality index, was not significantly different between the two groups. The average scores of sleep duration and habitual sleep efficiency in the control group were higher than those in the case group. However, there was no difference between the two groups after adjusting via a propensity score model, including the following potential confounders, child's age, child's sex, number of previous injury, caregiver mental status, caregiver's sex and caregiver's age, and the number of children living together., Conclusion: Our study was the first to examine the association between injury in children and the sleep quality of their primary caregivers. We observed that no PSQI component significantly affected the risk of injury among children., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 I-Tsung Chiu et al.)

Background: With recorded under-performance of current standard therapeutic strategies as highlighted by high rates of post-treatment (resection or local ablation) recurrence, resistance to chemotherapy, poor overall survival, and an increasing global incidence, hepatocellular carcinoma (HCC) constitutes a medical challenge. Accumulating evidence implicates the presence of HCC stem cells (HCC-SCs) in HCC development, drug-resistance, recurrence, and progression. Therefore, treatment strategies targeting both HCC-SCs and non-CSCs are essential., Methods: Recently, there has been an increasing suggestion of MALAT1 oncogenic activity in HCC; however, its role in HCC stemness remains unexplored. Herein, we investigated the probable role of MALAT1 in the SCs-like phenotype of HCC and explored likely molecular mechanisms by which MALAT1 modulates HCC-SCs-like and metastatic phenotypes., Results: We showed that relative to normal, cirrhotic, or dysplastic liver conditions, MALAT1 was aberrantly expressed in HCC, similar to its overexpression in Huh7, Mahlavu, and SK-Hep1 HCC cells lines, compared to the normal liver cell line THLE-2. We also demonstrated a positive correlation between MALAT1 expression and poor cell differentiation status in HCC using RNAscope. Interestingly, we demonstrated that shRNA-mediated silencing of MALAT1 concomitantly downregulated the expression levels of β-catenin, Stat3, c-Myc, CK19, vimentin, and Twist1 proteins, inhibited HCC oncogenicity, and significantly suppressed the HCC-SCs-related dye-effluxing potential of HCC cells and reduced their ALDH-1 activity, partially due to inhibited MALAT1-β-catenin interaction. Additionally, using TOP/FOP (TCL/LEF-Firefly luciferase) Flash, RT-PCR, and western blot assays, we showed that silencing MALAT1 downregulates β-catenin expression, dysregulates the canonical Wnt signaling pathway, and consequently attenuates HCC tumorsphere formation efficiency, with concurrent reduction in CD133+ and CD90+ HCC cell population, and inhibits tumor growth in SK-Hep1-bearing mice. Conclusions: Taken together, our data indicate that MALAT1/Wnt is a targetable molecular candidate, and the therapeutic targeting of MALAT1/Wnt may constitute a novel promising anticancer strategy for HCC treatment.

Resistance to radiotherapy (IR), with consequent disease recurrence, continues to limit the efficacy of contemporary anticancer treatment for patients with hepatocellular carcinoma (HCC), especially in late stage. Despite accruing evidence implicating the PI3K/AKT signaling pathway in cancer-promoting hypoxia, cancerous cell proliferation and radiotherapy-resistance, it remains unclear which molecular constituent of the pathway facilitates adaptation of aggressive HCC cells to tumoral stress signals and drives their evasion of repeated IR-toxicity. This present study investigated the role of PDK1 signaling in IR-resistance, enhanced DNA damage repair and post-IR relapse, characteristic of aggressive HCC cells, while exploring potential PDK1-targetability to improve radiosensitivity. The study employed bioinformatics analyses of gene expression profile and functional protein-protein interaction, generation of IR-resistant clones, flow cytometry-based ALDH activity and side-population (SP) characterization, siRNA-mediated loss-of-PDK1function, western-blotting, immunohistochemistry and functional assays including cell viability, migration, invasion, clonogenicity and tumorsphere formation assays. We showed that the aberrantly expressed PDK1 characterizes poorly differentiated HCC CVCL&#95;7955, Mahlavu, SK-HEP1 and Hep3B cells, compared to the well-differentiated Huh7 or normal adult liver epithelial THLE-2 cells, and independently activates the PI3K/AKT/mTOR signaling. Molecular ablation of PDK1 function enhanced susceptibility of HCC cells to IR and was associated with deactivated PI3K/AKT/mTOR signaling. Additionally, PDK1-driven IR-resistance positively correlated with activated PI3K signaling, enhanced HCC cell motility and invasiveness, augmented EMT, upregulated stemness markers ALDH1A1, PROM1, SOX2, KLF4 and POU5F1, increased tumorsphere-formation efficiency and suppressed biomarkers of DNA damage-RAD50, MSH3, MLH3 and ERCC2. Furthermore, the acquired IR-resistant phenotype of Huh7 cells was strongly associated with significantly increased ALDH activity, SP-enrichment, and direct ALDH1-PDK1 interaction. Moreover, BX795-mediated pharmacological inhibition of PDK1 synergistically enhances the radiosensitivity of erstwhile resistant cells, increased Bax/Bcl-2 apoptotic ratio, while suppressing oncogenicity and clonogenicity. We provide preclinical evidence implicating PDK1 as an active driver of IR-resistance by activation of the PI3K/AKT/mTOR signaling, up-modulation of cancer stemness signaling and suppression of DNA damage, thus, projecting PDK1-targeting as a putative enhancer of radiosensitivity and a potential new therapeutic approach for patients with IR-resistant HCC.

Background: Falls represent a global health issue among older adults and cause a considerable burden on medical systems. In this study, a fall-risk assessment profile was developed for community-dwelling older adults., Method: The data of survey participants aged > 65 years were obtained from three rounds (2005, 2009, and 2013) of the National Health Interview Survey in Taiwan. In total, 8356 older participants were included in this study. Logistic regression analyses were used to determine potential predictors associated with falls. The regression coefficients of the predictors in the final model were translated into scores (by multiplying by 5) and then summed to obtain a total risk-score for falls. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative performance of the risk assessment profile., Result: Self-reported falls within 1 year accounted for 19.1% of the total falls. The predictors that were included in the risk profile according to the logistic regression analysis results were as follows: female sex (adjusted odds ratio = 1.57; risk-score = 2), living alone (adjusted odds ratio = 1.56; risk-score = 2), urinary incontinence (adjusted odds ratio = 1.36; risk-score = 2), perceived unhealthiness (adjusted odds ratio = 1.32; risk-score = 1), perceived pain (adjusted odds ratio = 1.51; risk-score = 2), hospital admission in the past year (adjusted odds ratio = 2.42; risk-score = 4), low activity of daily living (ADL) scores (adjusted odds ratio = 1.29; risk-score = 1), and low mobility function scores (adjusted odds ratio = 1.68; risk-score = 3). At a total risk-score cutoff point of 6 (range 0-17), the model predicted falls with a sensitivity and specificity of 75.16 and 52.75%, respectively (area under the ROC curve = 0.70)., Conclusion: The fall-risk assessment profile comprising eight predictors-female sex, living alone, incontinence, perceived unhealthiness, perceived pain, hospital admission in the past year, low ADL scores, and low mobility function scores-may serve as an assessment tool for identification of older adults with a high risk of falling, and assessment results can be used to facilitate community-based intervention.

Background: Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue., Methods: We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO)., Results: Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively., Conclusion: Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO)., (© 2019 American Headache Society.)

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The G AL4 T echnique for R eal-time a nd C lonal E xpression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide., (Copyright © 2019 Olson et al.)

This study demonstrated a training program of the suction-assisted laryngoscopy assisted decontamination (S.A.L.A.D.) technique for emergency medical technician paramedic (EMT-P). The effectiveness of the training program on the improvements of skills and confidence in managing soiled airway was evaluated.In this pilot before-after study, 41 EMT-P participated in a training program which consisted of 1 training course and 3 evaluation scenarios. The training course included lectures, demonstration, and practice and focused on how to perform endotracheal intubation in soiled airway with the S.A.L.A.D technique. The first scenario was performed on standard airway mannequin head with clean airway (control scenario). The second scenario (pre-training scenario) and the third scenario (post-training scenario) were performed in airway with simulated massive vomiting. The post-training scenario was applied immediately after the training course. All trainees were requested to perform endotracheal intubation for 3 times in each scenario. The "pass" of a scenario was defined as more than twice successful intubation in a scenario. The intubation time, count of successful intubation, pass rate, and the confidence in endotracheal intubation were evaluated.The intubation time in the post-training scenario was significantly shorter than that in the pre-training scenario (P = .031). The pass rate of the control, pre-training, and post-training scenario was 100%, 82.9%, and 92.7%, respectively. The proportion of trainees reporting confident or very confident in endotracheal intubation in soiled airway increased from 22.0% to 97.6% after the training program. Kaplan-Meier analysis revealed that the adjusted hazard ratio of successful intubation for post-training versus pre-training scenario was 2.13 (95% confidence interval of 1.57-2.91).The S.A.L.A.D. technique training could efficiently help EMT-P performing endotracheal intubation during massive vomiting simulation.

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown. Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t -test and Mann-Whitney U -test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test. Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01). Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance.

Deep learning and computer vision algorithms can deliver highly accurate and automated interpretation of medical imaging to augment and assist clinicians. However, medical imaging presents uniquely pertinent obstacles such as a lack of accessible data or a high-cost of annotation. To address this, we developed data-efficient deep learning classifiers for prediction tasks in cardiology. Using pipeline supervised models to focus relevant structures, we achieve an accuracy of 94.4% for 15-view still-image echocardiographic view classification and 91.2% accuracy for binary left ventricular hypertrophy classification. We then develop semi-supervised generative adversarial network models that can learn from both labeled and unlabeled data in a generalizable fashion. We achieve greater than 80% accuracy in view classification with only 4% of labeled data used in solely supervised techniques and achieve 92.3% accuracy for left ventricular hypertrophy classification. In exploring trade-offs between model type, resolution, data resources, and performance, we present a comprehensive analysis and improvements of efficient deep learning solutions for medical imaging assessment especially in cardiology., Competing Interests: Competing interestsThe Authors declare no Competing Interests.

Background: Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning., Methods: We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning., Results: Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session., Conclusions: The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.

Integrated photonics platforms are crucial to the development and implementation of scalable quantum information and networking schemes, but many such devices still rely on external bulk photodetectors. We report the design and simulation of a waveguide-based single-photon avalanche diode (SPAD) for visible wavelengths. The SPAD consists of a p-n junction implemented in a doped silicon waveguide, which is end-fire coupled to an input silicon nitride waveguide. We developed a 2D Monte Carlo model to simulate the avalanche multiplication process of charge carriers following the absorption of an input photon, and calculated the photon detection efficiency (PDE) and timing jitter of the SPAD. We investigated the SPAD performance at a wavelength of 640 nm and temperature of 243K for different device dimensions and device doping configurations. For our simulated parameters, we obtained a maximum PDE of 0.45 at a reverse bias voltage of ~20 V, and full-width-half-max (FWHM) timing jitter values <8 ps.

Background: Emergency intubation in a patient with advanced ankylosing spondylitis (AS) who presents with severe thoracic kyphosis deformity, rigid cervical flexion deformity of the neck, and an inability to achieve the supine position is particularly challenging to emergency physicians., Case Report: This study reports on an AS patient presenting with these difficult airway characteristics and acute respiratory failure who was successfully intubated using video laryngoscope-assisted inverse intubation (II) and blind digital intubation (BDI). By using Pentax AirwayScope-assisted inverse intubation, the tracheal tube tip was passed through the glottic opening, but an unexpected resistance occurred during tube advancement, which was overcome by subsequent BDI. By using laryngoscope-assisted II complemented by the BDI technique, the patient was successfully intubated without complications. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case demonstrated that these two emergency airway management techniques are valuable backup methods and complement each other when applied to certain unstable airways, especially when the traditional patient position is not easily accomplished. Unexpected difficulty is not rare during airway management; emergency physicians should always be well prepared both mentally and practically., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Diet1 modulates intestinal production of the hormone, fibroblast growth factor (FGF)15, which signals in liver to regulate bile acid synthesis. C57BL/6ByJ mice with a spontaneous Diet1 -null mutation are resistant to hypercholesterolemia compared with wild-type C57BL/6J mice through enhanced cholesterol conversion to bile acids. To further characterize the role of Diet1 in metabolism, we generated Diet1 -/- mice on the C57BL/6J genetic background. C57BL/6J Diet1 -/- mice had elevated bile acid levels, reduced Fgf15 expression, and increased gastrointestinal motility and intestinal luminal water content, which are symptoms of bile acid diarrhea (BAD) in humans. Natural genetic variation in Diet1 mRNA expression levels across 76 inbred mouse strains correlated positively with Ffg15 mRNA and negatively with serum bile acid levels. This led us to investigate the role of DIET1 genetic variation in primary BAD patients. We identified a DIET1 coding variant ( rs12256835 ) that had skewed prevalence between BAD cases and controls. This variant causes an H1721Q amino acid substitution that increases the levels of FGF19 protein secreted from cultured cells. We propose that genetic variation in DIET1 may be a determinant of FGF19 secretion levels, and may affect bile acid metabolism in both physiological and pathological conditions., (Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.)

We report on the design and experimental demonstration of a broadband silicon polarization beam splitter (PBS) with a high extinction ratio (ER)≥30  dB. This was achieved using triple-bent-waveguide directional coupling in a single PBS, and cascaded PBS topology. For the single PBS, the bandwidths for an ER≥30  dB are 20 nm for the quasi-TE mode, and 70 nm for the quasi-TM mode when a broadband light source (1520-1610 nm) was employed. The insertion loss (IL) varies from 0.2 to 1 dB for the quasi-TE mode and 0.2-2 dB for the quasi-TM mode. The cascaded PBS improved the bandwidth of the quasi-TE mode for an ER≥30  dB to 90 nm, with a low IL of 0.2-2 dB. To the best of our knowledge, our PBS system is one of the best broadband PBSs with an ER as high as ∼42  dB and a low IL below 1 dB around the central wavelength, and experimentally demonstrated using edge-coupling.