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IntroductionResearch has shown that speech analysis demonstrates sensitivity in detecting early Alzheimer’s disease (AD), but the relation between linguistic features and cognitive tests or biomarkers remains unclear. This study aimed to investigate how linguistic features help identify cognitive impairments in patients in the early stages of AD.MethodThis study analyzed connected speech from 80 participants and categorized the participants into early-AD and normal control (NC) groups. The participants underwent amyloid-β positron emission tomography scans, brain magnetic resonance imaging, and comprehensive neuropsychological testing. Participants’ speech data from a picture description task were examined. A total of 15 linguistic features were analyzed to classify groups and predict cognitive performance.ResultsWe found notable linguistic differences between the early-AD and NC groups in lexical diversity, syntactic complexity, and language disfluency. Using machine learning classifiers (SVM, KNN, and RF), we achieved up to 88% accuracy in distinguishing early-AD patients from normal controls, with mean length of utterance (MLU) and long pauses ratio (LPR) serving as core linguistic indicators. Moreover, the integration of linguistic indicators with biomarkers significantly improved predictive accuracy for AD. Regression analysis also highlighted crucial linguistic features, such as MLU, LPR, Type-to-Token ratio (TTR), and passive construction ratio (PCR), which were sensitive to changes in cognitive function.ConclusionFindings support the efficacy of linguistic analysis as a screening tool for the early detection of AD and the assessment of subtle cognitive decline. Integrating linguistic features with biomarkers significantly improved diagnostic accuracy.

This review describes advances in understanding and forecasting tropical cyclone (TC) subseasonal variability during the past four years. A large effort by the scientific community has been in understanding the sources of predictability at subseasonal timescales beyond the well-known modulation of TC activity by the Madden-Julian Oscillation (MJO). In particular, the strong modulation of TC activity over the western North Pacific by the Boreal Summer Intra-Seasonal Oscillation (BSISO) has been documented. Progress has also been realized in understanding the role of tropical-extratropical interactions in improving subseasonal forecasts. In addition, several recent publications have shown that extratropical wave breaking may have a role in the genesis and development of TCs. Analyses of multi-model ensemble data sets such as the Subseasonal to Seasonal (S2S) and Subseasonal Experiment (SubX) have shown that the skill of S2S models in predicting the genesis of TCs varies strongly among models and regions but is often tied to their ability to simulate the MJO and its impacts. The skill in select models has led to an increase over the past four years in the number of forecasting centers issuing subseasonal TC forecasts using various techniques (statistical, statistical-dynamical and dynamical). More extensive verification studies have been published over the last four years, but often only for the North Atlantic and eastern North Pacific.

Abstract An open‐source, physics‐based tropical cyclone (TC) downscaling model is developed, in order to generate a large climatology of TCs. The model is composed of three primary components: (a) a random seeding process that determines genesis, (b) an intensity‐dependent beta‐advection model that determines the track, and (c) a non‐linear differential equation set that determines the intensification rate. The model is entirely forced by the large‐scale environment. Downscaling ERA5 reanalysis data shows that the model is generally able to reproduce observed TC climatology, such as the global seasonal cycle, genesis locations, track density, and lifetime maximum intensity distributions. Inter‐annual variability in TC count and power‐dissipation is also well captured, on both basin‐wide and global scales. Regional TC hazard estimated by this model is also analyzed using return period maps and curves. In particular, the model is able to reasonably capture the observed return period curves of landfall intensity in various sub‐basins around the globe. The incorporation of an intensity‐dependent steering flow is shown to lead to regionally dependent changes in power dissipation and return periods. Advantages and disadvantages of this model, compared to other downscaling models, are also discussed.

Abstract This manuscript discusses the challenges in detecting and attributing recently observed trends in the Atlantic tropical cyclone (TC) and the epistemic uncertainty we face in assessing future risk. We use synthetic storms downscaled from five CMIP5 models by the Columbia HAZard model (CHAZ), and directly simulated storms from high‐resolution climate models. We examine three aspects of recent TC activity: the upward trend and multi‐decadal oscillation of the annual frequency, the increase in storm wind intensity, and the decrease in forward speed. Some data sets suggest that these trends and oscillation are forced while others suggest that they can be explained by natural variability. Projections under warming climate scenarios also show a wide range of possibilities, especially for the annual frequencies, which increase or decrease depending on the choice of moisture variable used in the CHAZ model and on the choice of climate model. The uncertainties in the annual frequency lead to epistemic uncertainties in TC risk assessment. Here, we investigate the potential for reduction of these epistemic uncertainties through a statistical practice, namely likelihood analysis. We find that historical observations are more consistent with the simulations with increasing frequency than those with decreasing frequency, but we are not able to rule out the latter. We argue that the most rational way to treat epistemic uncertainty is to consider all outcomes contained in the results. In the context of risk assessment, since the results contain possible outcomes in which TC risk is increasing, this view implies that the risk is increasing.

Abstract Introduction Mitral regurgitation (MR) is characterized by systolic blood flow reversal from the left ventricle to the left atrium. A 2019 study indicated that in the USA, clinically significant MR (sMR) is associated with a substantial healthcare cost burden. In Taiwan, few data are available to describe the clinical characteristics, treatment patterns, and economic burden of patients with sMR. Methods Using the National Health Insurance Research Database (NHIRD), a national, detailed claims database of all 23 million residents of Taiwan, we conducted a retrospective cohort study to identify patients with sMR and quantify the impact of the disease on Taiwan’s healthcare system. We classified patients with sMR into three cohorts based on disease etiology: functional MR (sFMR), degenerative MR (sDMR), and uncharacterized MR (sUMR). Results We compared patient characteristics across cohorts and estimated attributable healthcare utilization and costs during the 12-month follow-up period. Our research shows that in Taiwan, patients with sFMR were older, sicker, and presented at casualty (emergency department) more frequently than those with sDMR and sUMR. Meanwhile, patients with sDMR had the highest 12-month healthcare expenditures across the cohorts. Conclusion These findings are inconsistent with what has been shown in the USA, which warrants further investigation.

Various synthetic tropical cyclone datasets exist for risk assessment purposes. Here, the authors conduct a global dataset comparison to assess their suitability and applicability in answering different impact-related questions.

Most studies on word repetition have demonstrated that repeated stimuli yield reductions in brain activity. Despite the well-known repetition reduction effect, some literature reports repetition enhancements in electroencephalogram (EEG) activities. However, although studies of object and face recognition have consistently demonstrated both repetition reduction and enhancement effects, the results of repetition enhancement effects were not consistent in studies of visual word recognition. Therefore, the present study aimed to further investigate the repetition effect on the P200, an early event-related potential (ERP) component that indexes the coactivation of lexical candidates during visual word recognition. To achieve a high signal-to-noise ratio, EEG signals were decomposed into various modes by using the Hilbert–Huang transform. Results demonstrated a repetition enhancement effect on P200 activity in alpha-band oscillation and that lexicality and orthographic neighborhood size would influence the magnitude of the repetition enhancement effect on P200. These findings suggest that alpha activity during visual word recognition might reflect the coactivation of orthographically similar words in the early stages of lexical processing. Meantime, there were repetition reduction effects on ERP activities in theta-delta band oscillation, which might index that the lateral inhibition between lexical candidates would be omitted in repetition.

IntroductionSpeech comprehension involves context-based lexical predictions for efficient semantic integration. This study investigated how noise affects the predictability effect on event-related potentials (ERPs) such as the N400 and late positive component (LPC) in speech comprehension.MethodsTwenty-seven listeners were asked to comprehend sentences in clear and noisy conditions (hereinafter referred to as “clear speech” and “noisy speech,” respectively) that ended with a high-or low-predictability word during electroencephalogram (EEG) recordings.ResultsThe study results regarding clear speech showed the predictability effect on the N400, wherein low-predictability words elicited a larger N400 amplitude than did high-predictability words in the centroparietal and frontocentral regions. Noisy speech showed a reduced and delayed predictability effect on the N400 in the centroparietal regions. Additionally, noisy speech showed a predictability effect on the LPC in the centroparietal regions.DiscussionThese findings suggest that listeners achieve comprehension outcomes through different neural mechanisms according to listening conditions. Noisy speech may be comprehended with a second-pass process that possibly functions to recover the phonological form of degraded speech through phonetic reanalysis or repair, thus compensating for decreased predictive efficiency.

ObjectiveAortic stenosis (AS) is a heart valve disease characterized by left ventricular outflow fixed obstruction. It can be managed by surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). However, real-world evidence for TAVI or SAVR outcomes is lacking in Taiwan. This study aimed to compare the clinical outcomes of TAVI and SAVR for treating of AS in Taiwan.Materials and methodsThe National Health Insurance Research Database is a nationally representative cohort that contains detailed registry and claims data from all 23 million residents of Taiwan. This retrospective cohort study used this database to compare patients who underwent SAVR (bioprosthetic valves) or TAVI from 2017 to 2019. Survival outcomes and length of hospital stay (LOS) and intensive care unit (ICU) stay between TAVI and SAVR in the matched cohort. A Cox proportional hazards model was performed to identify the effect of treatment type on survival rates while controlling variables including age, gender, and comorbidities.ResultsWe identified 475 and 1605 patients who underwent TAVI and SAVR with a bioprosthetic valve, respectively. Patients who underwent TAVI were older (82.19 vs. 68.75 y/o) and more likely to be female (55.79% vs. 42.31%) compared with patients who underwent SAVR. Propensity score matching (PSM) on age, gender, and Elixhauser Comorbidity Index (ECI) score revealed that 375 patients who underwent TAVI were matched with patients who underwent SAVR. A significant difference was found in survival rates between TAVI and SAVR. The 1-year mortality rate was 11.44% with TAVI and 17.55% with SAVR. Both the mean total LOS (19.86 vs. 28.24 days) and mean ICU stay (6.47 vs. 11.12 days) for patients who underwent TAVI were shorter than those who underwent SAVR.ConclusionPatients who had undergone TAVI had better survival outcomes and shorter LOS compared with patients who had undergone SAVR in Taiwan.

BackgroundDrug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease.MethodsHere, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC50 = 0.4 μM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms.ResultsOur in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals.ConclusionsWe demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.

Abstract Background Full-thickness macular hole (FTMH) is a rare complication in retinitis pigmentosa (RP) patients and may increase intraoperative challenges. Furthermore, lens capsular flap transplantation and inverted internal limiting membrane (ILM) flap were reported to close complicated FTMH successfully. Here, we present a case of bilateral advanced RP complicated by a FTMH treated with a novel lens capsular flap transplantation and inverted internal limiting membrane flap. Case presentation A 46-year-old presented to our hospital with a complaint of progressively blurred vision and metamorphopsia in both eyes. Spectral-domain optical coherence tomography revealed a FTMH with retinoschisis in the right eye and another FTMH in the left eye. ILM peeling with inverted ILM flap technique was performed on the right eye and ILM peeling with anterior lens capsular flap technique was performed on the left eye. Post-operative follow-up showed successful closure of the FTMH and improved vision in both eyes. Conclusions In our present case, flap-assisted techniques for retinitis pigmentosa with macular hole result in excellent visual and anatomic outcomes.

Abstract This study presents a new storm surge hazard potential index (SSHPI) for estimating tropical cyclone (TC) induced peak surge levels at a coast. The SSHPI incorporates parameters that are often readily available at real-time: intensity in 10-min maximum wind speed, radius of 50-kt wind, translation speed, coastal geometry, and bathymetry information. The inclusion of translation speed and coastal geometry information lead to improvements of the SSHPI to other existing surge indices. A retrospective analysis of SSHPI using data from 1978–2019 in Japan suggests that this index captures historical events reasonably well. In particular, it explains ~ 66% of the observed variance and ~ 74% for those induced by TCs whose landfall intensity was larger than 79-kt. The performance of SSHPI is not sensitive to the type of coastal geometry (open coasts or semi-enclosed bays). Such a prediction methodology can decrease numerical computation requirements, improve public awareness of surge hazards, and may also be useful for communicating surge risk.

Innate and learned fear can induce rapid changes in body temperature of mammals. The authors identify the posterior subthalamic nucleus as a major thermoregulatory hub that connects the external lateral parabrachial subnucleus to the nucleus of the solitary tract to mediate fear-evoked hypothermia.

Matsuo et al. report that thiazoline-related innate fear-eliciting compounds activate the spinal trigeminal nucleus (Sp5) and the nucleus of the solitary tract (NTS) via vagal/trigeminal TRPA1 to induce robust physiological alterations, enabling long time survival in a lethal hypoxic environment.

How climate change affects the translation speed of tropical cyclones has been the subject of intensive debate. Here, the authors use models to show that future regional changes in the steering winds lead to faster-moving tropical cyclones as they make landfall in Texas.

Abstract The frequency with which tropical cyclones (TCs) occur controls all other aspects of tropical cyclone risk since a storm that does not occur can do no harm. Yet this frequency is poorly understood. There is no accepted theory that explains the average number of TCs that occur each year on the Earth, nor how that number will change with global warming. Arguments based on global budgets of heat or moisture do not yet appear helpful, nor does a detailed understanding of the physical processes of TC genesis. Empirical indices that predict TC frequency as a function of large‐scale environmental variables can explain some of its relative variations in space and time, but not its absolute value. Global numerical models with horizontal grid spacings on the order of 25–50 km have allowed much improved simulations of TC activity, however. Many such models project a decrease in frequency with warming, but some project an increase. Idealized simulations, including those at higher resolutions, offer promise by allowing a systematic, deductive investigation of the roles of individual environmental factors. In addition to the larger‐scale environmental modulation of genesis likelihood, precursor disturbances, or “seeds”, may exert an independent influence on TC frequency.

Purpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. To extend the observation period, we generated the Ret conditional knockout Chx10-Cre;C-Retlx/lx mouse model and analyzed the retinal function and morphological changes in mature and aging Chx10-Cre;C-Retlx/lx mice.Methods: Retina-specific depletion of Ret was achieved using mice with floxed alleles of the Ret gene with CHX10-driven Cre recombinase; floxed mice without Cre expression were used as controls. Retinal function was examined using electroretinography (ERG), and 2-, 4-, 12-, and 24-month-old mice were analyzed by hematoxylin staining and immunohistochemistry to evaluate retinal morphological alterations. The ultrastructure of photoreceptor synapses was evaluated using electron microscopy.Results: The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Retlx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Retlx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon.Conclusion: Our results provide evidence of the role of Ret in maintaining the function of the retina, which was essential for preserving the structure of the synaptic ribbon and supporting the integrity of the outer plexiform layer.

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.

Studies have suggested that visually presented words are obligatorily decomposed into constituents that could be mapped to language representations. The present study aims to elucidate how orthographic processing of one constituent affects the other and vice versa during a word recognition task. Chinese orthographic system has characters representing syllables and meanings instead of suffixation roles, and the majority of Chinese characters are phonograms that can be further decomposed into phonetic radical and semantic radical. We propose that semantic radical combinability indexed by semantic radicals and the effect of phonological consistency indexed by phonetic radicals would interact with each other during the reading of Chinese phonograms. Twenty-six right-handed native Chinese speakers were recruited to the study. Participants were presented with phonograms divided into four conditions following their semantic radical combinability (large vs. small) and phonological consistency (high vs. low). EEG signals were recorded throughout the covert naming task. Our results show that there is an interaction effect between phonological consistency and semantic radical combinability on the right hemisphere N170 activity while reading phonograms. Semantic radical combinability influenced the right hemisphere N170 during the process of low-consistency character reading but not high-consistency character reading. On the other hand, the left hemisphere N170 revealed a more significant activity during reading high-consistency characters and was not affected by radical combinability. In addition, while low-consistency characters revealed a larger P200 than high-consistency characters, the semantic radical combinability effect on P200 was only significant when participants were reading high-consistency characters but not low-consistency characters. These results provide new information about how ERPs are involved in word recognition within the context of interaction among orthographic and phonological dimensions.

This study aims to disclose how the magnetic resonance imaging (MRI) neuroimaging approach has been applied in education studies, and what kind of learning themes has been investigated in the reviewed MRI neuroimaging research. Based on the keywords “brain or neuroimaging or neuroscience” and “MRI or diffusion tensor imaging (DTI) or white matter or gray matter or resting-state,” a total of 25 papers were selected from the subject areas “Educational Psychology” and “Education and Educational Research” from the Web of Science and Scopus from 2000 to 2019. Content analysis showed that MRI neuroimaging and learning were studied under the following three major topics and nine subtopics: cognitive function (language, creativity, music, physical activity), science education (mathematical learning, biology learning, physics learning), and brain development (parenting, personality development). As for the type of MRI neuroimaging research, the most frequently used approaches were functional MRI, followed by structural MRI and DTI, although the choice of approach was often motivated by the specific research question. Research development trends show that the neural plasticity theme has become more prominent recently. This study concludes that in educational research, the MRI neuroimaging approach provides objective and empirical evidence to connect learning processes, outcomes, and brain mechanisms.

Doxorubicin (Dox) is a widely known chemotherapeutic drug that has been encapsulated into liposomes for clinical use, such as Doxil® and Myocet®. Both of these are prepared via remote loading methods, which require multistep procedures. Additionally, their antitumor efficacy is hindered due to the poor drug release from PEGylated liposomes in the tumor microenvironment. In this study, we aimed to develop doxorubicin-loaded lipid-based nanocarriers (LNC-Dox) based on electrostatic interaction using microfluidic technology. The resulting LNC-Dox showed high loading capacity, with a drug-to-lipid ratio (D/L ratio) greater than 0.2, and high efficacy of drug release in an acidic environment. Different lipid compositions were selected based on critical packing parameters and further studied to outline their effects on the physicochemical characteristics of LNC-Dox. Design of experiments was implemented for formulation optimization. The optimized LNC-Dox showed preferred release in acidic environments and better therapeutic efficacy compared to PEGylated liposomal Dox in vivo. Thus, this study provides a feasible approach to efficiently encapsulate doxorubicin into lipid-based nanocarriers fabricated by microfluidic rapid mixing.

Sleep disturbances have been recognized as a core symptom of post-traumatic stress disorders (PTSD). However, the neural basis of PTSD-related sleep disturbances remains unclear. It has been challenging to establish the causality link between a specific brain region and traumatic stress-induced sleep abnormalities. Here, we found that single prolonged stress (SPS) could induce acute changes in sleep/wake duration as well as short- and long-term electroencephalogram (EEG) alterations in the isogenic mouse model. Moreover, the medial prefrontal cortex (mPFC) showed persistent high number of c-fos expressing neurons, of which more than 95% are excitatory neurons, during and immediately after SPS. Chemogenetic inhibition of the prelimbic region of mPFC during SPS could specifically reverse the SPS-induced acute suppression of delta power (1–4 Hz EEG) of non-rapid-eye-movement sleep (NREMS) as well as most of long-term EEG abnormalities. These findings suggest a causality link between hyper-activation of mPFC neurons and traumatic stress-induced specific sleep–wake EEG disturbances.

TMT is a chemical that evokes innate defensive behaviors yet the molecular mechanisms are not well understood. Here the authors perform a large-scale forward genetics screen in mice and identify Trpa1, a pungency/irritancy receptor, as a chemosensor for predator odor-evoked innate fear and defensive behaviors.

Summary: T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs and the reutilization of biomolecules, processes that require active participation of metabolite transporters. Here, we show that equilibrative nucleoside transporter 3 (ENT3) is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells. ENT3 deficiency leads to an enlarged and disturbed lysosomal compartment, resulting in accumulation of surplus mitochondria, elevation of intracellular reactive oxygen species, and DNA damage in T cells. Our results identify ENT3 as a vital metabolite transporter that supports T cell homeostasis and activation by regulating lysosomal integrity and the availability of nucleosides. Moreover, we uncovered that T cell lysosomes are an important source of salvaged metabolites for survival and proliferation. : A sufficient supply of biomaterials is essential during T cell differentiation and proliferation. Wei et al. reveal that the nucleoside transporter ENT3 is necessary for maintaining T cell homeostasis and survival by regulating lysosome function and nucleoside availability. Keywords: T cell, metabolism, nucleoside, nucleoside transporter, ENT3, Slc29a3, lysosome

Abstract A new statistical‐dynamical model is developed for estimating the long‐term hazard of rare, high impact tropical cyclones events globally. There are three components representing the complete storm lifetime: an environmental index‐based genesis model, a beta‐advection track model, and an autoregressive intensity model. All three components depend upon the local environmental conditions, including potential intensity, relative sea surface temperature, 850 and 250 hPa steering flow, deep‐layer mean vertical shear, 850 hPa vorticity, and midlevel relative humidity. The hazard model, using 400 realizations of a 32 year period (approximately 3,000 storms per realization), captures many aspects of tropical cyclone statistics, such as genesis and track density distribution. Of particular note, it simulates the observed number of rapidly intensifying storms, a challenging issue in tropical cyclone modeling and prediction. Using the return period curve of landfall intensity as a measure of local tropical cyclone hazard, the model reasonably simulates the hazard in the western north Pacific (coastal regions of the Philippines, China, Taiwan, and Japan) and the Caribbean islands. In other regions, the observed return period curve can be captured after a local landfall frequency adjustment that forces the total number of landfalls to be the same as that observed while allowing the model to freely simulate the distribution of intensities at landfall.

Tropical cyclones rarely achieve high intensities gradually. Here, the authors show that rapid intensification is relevant not only to short-term weather forecasting, but also to the relationship between tropical cyclones and climate.

This study explores the development of mismatch responses (MMRs) to Mandarin lexical tone changes in infants at 12, 18, and 24 months of age using the multi-deviant oddball paradigm with the low dipping Tone 3 (T3) as the standard, the high level Tone 1 (T1) as the large, and the high rising Tone 2 (T2) as the small deviant. The results show that the large acoustic change between T1/T3 elicited mismatch negativity (MMN) in all three age groups. The small acoustic change between T2/T3 elicited a positive mismatch response (P-MMR) at 12 and 18 months of age, but no MMR was found to the T2/T3 change at 24 months. The coexistence of MMN and P-MMR in the same age group implies that different mechanisms were used for discriminating large and small deviants. Infants were able to detect the T1/T3 change automatically and showed adult-like MMN as early as 6 months of age. However, the detection of the T2/T3 change remains effortful in infants under 24 months of age. These findings support the notion that MMN and P-MMR may be used to index the maturation of speech perception.

In English, an extensive body of work in both behavioral and neuropsychological domains has produced strong evidence that homonymy (words with many distinct meanings) and polysemy (many related senses) are represented, retrieved, and processed differently in the human brain. In Chinese, most words are compounds, and the constituent characters within a compound word can have different meanings and/or related senses on their own. Thus, in order to resolve lexical ambiguity in Chinese, one has to consider the composition of constituent characters, as well as how they contribute to whole word reading, known as “sublexical ambiguity.” This study investigates how two types of sublexical ambiguity affect Chinese word processing. The number of meanings (NOM) and the number of senses (NOS) corresponding to the first character of Chinese compounds were manipulated in a lexical decision task. The interactions between NOM and NOS were observed in both behavioral results and N400s, in which NOM disadvantage effect was found for words with few-senses only. On the other hand, the NOS facilitation effect was significant for words with multiple-meanings (NOM > 1) only. The sublexical ambiguity disadvantage suggested that semantically unrelated morphemes are represented as separate entries. For characters with multiple meanings, one orthographic form is associated with more than one morphemic representation. In contrast, the sublexical sense advantage supported the idea that semantically related senses that shared a morphological root are represented within a single entry. The more senses listed in a morphological root, the stronger representation will be formed. These results suggest that two types of sublexical ambiguities are represented and processed differently in Chinese word recognition models and also demonstrate that how they interact with each other in the mental lexicon.

Spontaneous pneumomediastinum (SPM), while rare, is probably underestimated in children. Treatments for SPM target the underlying disease and trigger factors. This study aimed to analyze the etiology of SPM in different age groups. Methods: A total of 18 children with SPM were analyzed in the Children's Medical Center at China Medical University Hospital between 1997 and 2007. Results: The incidence of SPM in children was 1:8,302 patients at the Department of Pediatric Emergency Medicine. A bimodal peak in incidence occurred in those younger than 4 years old and in those aged 15-18 years. Characteristic symptoms were dyspnea (77.8%), followed by chest pain (66.7%) and neck pain (44.4%); common specific physical signs were subcutaneous emphysema (55.6%) and Hammer's sign (11.1%). Trigger factors were infection (44.4%), with a mean age of 5.8 ± 5.0 years, and diabetic ketoacidosis (5.6%), with a mean age of 18 years. Idiopathic SPM accounted for 50.0% of patients, with mean age 14.4 ± 1.8 years. In terms of the age distribution, five (27.8%; males/females = 4:1) preschoolers (< 6 years old) developed SPM, mostly due to infectious disease. Two girls aged less than 10 years developed asthma in later years. All eight male adolescents (≥ 10 years) developed SPM due to idiopathic factors. Of nine boys with idiopathic SPM, six underwent strenuous exercise before developing SPM. Mean hospitalization was 7.9 ± 11.5 days and 11 (61.1%) patients needed intensive care. Nearly all of the patients had complete resolution on chest radiography before discharge. Conclusion: Clinicians should be alert to the risk of SPM based on the presence of these symptoms. The etiology of SPM varies with age. Treatment of SPM must target the trigger factors or the underlying disease.

Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs) conjugated with antibodies (i.e., targeted biotin-MBs). Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs), which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+)) and MDA-MB-453 cells (CD44-), which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+) is a commonly used cancer-stem-cell biomarker, our targeted biotin-MBs could be a potent tool to sort cancer stem cells from dissected tumor tissue for use in preclinical experiments and clinical trials.

We focus on the role of CD8(+) Treg cell in Intravenous methyl-prednisolone (IVMP) pulse therapy in forty patients with active Class III/IV childhood lupus nephritis (LN) with heavy proteinuria. IVMP therapy for five days. From peripheral blood mononuclear cells (PBMCs) and renal tissues, we saw IVMP therapy definitely restoring both CD4(+)CD25(+)FoxP3(+) and CD8(+)CD25(+)Foxp3(+) Treg cell number plus greater expression with intracellular IL-10 and granzyme B in CD8(+)FoxP3(+) Treg from PBMCs. IVMP-treated CD8(+)CD25(+) Treg cells directly suppressed CD4(+) T proliferation and induced CD4(+)CD45RO(+) apoptosis. Histologically, CD4(+)FoxP3(+) as well as CD8(+)FoxP3(+) Treg cells appeared in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8(+)FoxP3(+) Treg cells increased in 10 follow-up renal biopsy specimens after IVMP. Reverse correlation of serum anti-C1q antibody and FoxP3(+) Treg cells in PBMNCs (r = -0.714, P

The long-term toxicity effects of gold nanoparticles (GNPs) on the proliferation and differentiation of a progenitor cell line, MG63 osteoblast-like cells, was investigated. These cells were treated for 20 hours with two media that contained 10 nm GNPs at concentrations of 1 ppm and 10 ppm. The mitosis of the GNP-treated MG63 was observed after at least 21 hours using dark-field and fluorescence microscopy. The TEM, LSCM and dark-field hyperspectral images indicated that the late endosomes in cells that contained aggregated GNPs were caused by vesicle fusion. Subsequently, after 21 days of being cultured in fresh medium, the specific nodule-like phenotypes and bone-associated gene expression of the treated MG63 cells exhibited the same behaviors as those of the control group. Statistically, after 21 days, the viability of the treated cells was identical to that of the untreated ones. During the cell death program analysis, the apoptosis and necrosis percentages of cells treated for 8 or fewer days were also observed to exhibit no significant difference with those of the untreated cells. In summary, our experiments show that the long-term toxicity of GNPs on the osteogenetic differentiation of MG63 is low. In addition, because of their low toxicity and non-biodegradability, GNPs can potentially be used as biomarkers for the long-term optical observation of the differentiation of progenitor or stem cells based on their plasmonic light-scattering properties.

Most current climate models predict that the equatorial Pacific will evolve under greenhouse gas--induced warm-ing to a more El Niño-like state over the next several decades, with a reduced zonal sea surface temperature gradient and weakened atmospheric Walker circulation. Yet, observations over the last 50 y show the opposite trend, toward a more La Niña-like state. Recent research provides evidence that the discrepancy cannot be dis-missed as due to internal variability but rather that the models are incorrectly simulating the equatorial Pacific response to greenhouse gas warming. This implies that projections of regional tropical cyclone activity may be incorrect as well, perhaps even in the direction of change, in ways that can be understood by analogy to historical El Niño and La Niña events: North Pacific tropical cyclone projections will be too active, North Atlantic ones not active enough, for example. Other perils, including severe convective storms and droughts, will also be projected erroneously. While it can be argued that these errors are transient, such that the models' responses to green-house gases may be correct in equilibrium, the transient response is relevant for climate adaptation in the next several decades. Given the urgency of understanding regional patterns of climate risk in the near term, it would be desirable to develop projections that represent a broader range of possible future tropical Pacific warming scenarios--including some in which recent historical trends continue--even if such projections cannot cur-rently be produced using existing coupled earth system models. [ABSTRACT FROM AUTHOR]