Extensive reading in a second language : literature review and pedagogical implications

textThis Report explores the importance of including extensive reading (ER) program in English as a second language (ESL) or English as a foreign language (EFL) context. To find benefits and implications of L2 extensive reading, the Report reviews comprehensive literature on L2 extensive reading. Research has found that extensive reading enables L2 learners to achieve both cognitive and affective gains. Based on these findings, the report provides some pedagogical implications for an L2 program in ESL/EFL contexts. The suggestions include practical tips such as materials, useful ER activities, and a discussion of teacher roles in an extensive reading program.Foreign Language Educatio

False Memory and Alzheimer’s Disease Pathology in Patients with Amnestic Mild Cognitive Impairment: A Study with Amyloid PET

Introduction: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer’s disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer’s disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. Methods: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into “with” and “without ADP” groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. Results: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated “low” to “moderate” in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. Conclusion: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted

Effective treatment of ductal carcinoma in situ with a HER-2-targeted alpha-particle emitting radionuclide in a preclinical model of human breast cancer

The standard treatment for ductal carcinoma in situ (DCIS) of the breast is surgical resection, followed by radiation. Here, we tested localized therapy of DCIS in mice using the immunoconjugate 225Ac linked-trastuzumab delivered through the intraductal (i.duc) route. Trastuzumab targets HER-2/neu, while the alpha-emitter 225Ac (half-life, 10 days) delivers highly cytotoxic, focused doses of radiation to tumors. Systemic 225Ac, however, elicits hematologic toxicity and at high doses free 213Bi, generated by its decay, causes renal toxicity. I.duc delivery of the radioimmunoconjugate could bypass its systemic toxicity. Bioluminescent imaging showed that the therapeutic efficacy of intraductal 225Ac-trastuzumab (10-40 nCi per mammary gland; 30-120 nCi per mouse) in a DCIS model of human SUM225 cancer cells in NSG mice was significantly higher (p<0.0003) than intravenous (120 nCi per mouse) administration, with no kidney toxicity or loss of body weight. Our findings suggest that i.duc radioimmunotherapy using 225Ac-trastuzumab deserves greater attention for future clinical development as a treatment modality for early breast cancer

Opposing Regulation of PROX1 by Interleukin-3 Receptor and NOTCH Directs Differential Host Cell Fate Reprogramming by Kaposi Sarcoma Herpes Virus

Lymphatic endothelial cells (LECs) are differentiated from blood vascular endothelial cells (BECs) during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV) infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming), but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming). Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα) and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV

Kaposin-B Enhances the PROX1 mRNA Stability during Lymphatic Reprogramming of Vascular Endothelial Cells by Kaposi's Sarcoma Herpes Virus

Kaposi's sarcoma (KS) is the most common cancer among HIV-positive patients. Histogenetic origin of KS has long been elusive due to a mixed expression of both blood and lymphatic endothelial markers in KS tumor cells. However, we and others discovered that Kaposi's sarcoma herpes virus (KSHV) induces lymphatic reprogramming of blood vascular endothelial cells by upregulating PROX1, which functions as the master regulator for lymphatic endothelial differentiation. Here, we demonstrate that the KSHV latent gene kaposin-B enhances the PROX1 mRNA stability and plays an important role in KSHV-mediated PROX1 upregulation. We found that PROX1 mRNA contains a canonical AU-rich element (ARE) in its 3′-untranslated region that promotes PROX1 mRNA turnover and that kaposin-B stimulates cytoplasmic accumulation of the ARE-binding protein HuR through activation of the p38/MK2 pathway. Moreover, HuR binds to and stabilizes PROX1 mRNA through its ARE and is necessary for KSHV-mediated PROX1 mRNA stabilization. Together, our study demonstrates that kaposin-B plays a key role in PROX1 upregulation during lymphatic reprogramming of blood vascular endothelial cells by KSHV

The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

The blood and lymphatic systems are the two major circulatory systems in our body. Although the blood system has been studied extensively, the lymphatic system has received much less scientific and medical attention because of its elusive morphology and mysterious pathophysiology. However, a series of landmark discoveries made in the past decade has begun to change the previous misconception of the lymphatic system to be secondary to the more essential blood vascular system. In this article, we review the current understanding of the development and pathology of the lymphatic system. We hope to convince readers that the lymphatic system is no less essential than the blood circulatory system for human health and well-being

Smart Patch for Skin Temperature: Preliminary Study to Evaluate Psychometrics and Feasibility

There is a need for continuous, non-invasive monitoring of biological data to assess health and wellbeing. Currently, many types of smart patches have been developed to continuously monitor body temperature, but few trials have been completed to evaluate psychometrics and feasibility for human subjects in real-life scenarios. The aim of this feasibility study was to evaluate the reliability, validity and usability of a smart patch measuring body temperature in healthy adults. The smart patch consisted of a fully integrated wearable wireless sensor with a multichannel temperature sensor, signal processing integrated circuit, wireless communication feature and a flexible battery. Thirty-five healthy adults were recruited for this test, carried out by wearing the patches on their upper chests for 24 h and checking their body temperature six times a day using infrared forehead thermometers as a gold standard for testing validity. Descriptive statistics, one-sampled and independent t-tests, Pearson’s correlation coefficients and Bland-Altman plot were examined for body temperatures between two measures. In addition, multiple linear regression, receiver operating characteristic (ROC) and qualitative content analysis were conducted. Among the 35 participants, 29 of them wore the patch for over 19 h (dropout rate: 17.14%). Mean body temperature measured by infrared forehead thermometers and smart patch ranged between 32.53 and 38.2 °C per person and were moderately correlated (r = 0.23–0.43) overall. Based on a Bland-Altman plot, approximately 94% of the measurements were located within one standard deviation (upper limit = 4.52, lower limit = −5.82). Most outliers were identified on the first measurement and were located below the lower limit. It is appropriate to use 37.5 °C in infrared forehead temperature as a cutoff to define febrile conditions. Users’ position while checking and ambient temperature and humidity are not affected to the smart patch body temperature. Overall, the participants showed high usability and satisfaction on the survey. Few participants reported discomfort due to limited daily activity, itchy skin or detaching concerns. In conclusion, epidermal electronic sensor technologies provide a promising method for continuously monitoring individuals’ body temperatures, even in real-life situations. Our study findings show the potential for smart patches to monitoring non-febrile condition in the community

Small scale renal dosimetry for alpha particle radiopharmaceutical therapy of metastatic breast cancer with 225Ac-7.16.4

Metastatic disease requires a systemic approach to therapy. Alpha particle radiopharmaceutical therapy (Alpha-RPT) is a new modality that is figuring prominently in pre-clinical and clinical studies. 225Ac-7.16.4 for pulmonary metastases in a murine metastatic breast cancer model showed high therapeutic efficacy. Despite a low calculated absorbed dose to the whole kidney, renal toxicity was observed in the treated animals. Renal toxicity thresholds established by external beam and targeted radiopeptide therapy is 25-30 Gy. The purpose was to use histological and Alpha Camera images to determine the activity concentration and distribution for 225Ac-7.16.4 and unbound 213Bi at sub organ level. Alpha Camera imaging was performed for small scale dosimetry of the kidneys using a previously developed nephron-based dosimetry model.JRC.E.5-Nuclear chemistr

ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4

RationaleLymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown.ObjectiveWe aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation.Methods and resultsPrimary endothelial cells from dermal blood and lymphatic vessels (blood vascular endothelial cells and lymphatic endothelial cells [LECs]) were exposed to low-rate steady laminar flow. Shear stress-induced molecular and cellular responses were defined and verified using various mutant mouse models. Steady laminar flow induced the classic shear stress responses commonly in blood vascular endothelial cells and LECs. Surprisingly, however, only LECs showed enhanced cell proliferation by regulating the vascular endothelial growth factor (VEGF)-A, VEGF-C, FGFR3, and p57/CDKN1C genes. As an early signal mediator, ORAI1, a pore subunit of the calcium release-activated calcium channel, was identified to induce the shear stress phenotypes and cell proliferation in LECs responding to the fluid flow. Mechanistically, ORAI1 induced upregulation of Krüppel-like factor (KLF)-2 and KLF4 in the flow-activated LECs, and the 2 KLF proteins cooperate to regulate VEGF-A, VEGF-C, FGFR3, and p57 by binding to the regulatory regions of the genes. Consistently, freshly isolated LECs from Orai1 knockout embryos displayed reduced expression of KLF2, KLF4, VEGF-A, VEGF-C, and FGFR3 and elevated expression of p57. Accordingly, mouse embryos deficient in Orai1, Klf2, or Klf4 showed a significantly reduced lymphatic density and impaired lymphatic development.ConclusionsOur study identified a molecular mechanism for laminar flow-activated LEC proliferation