MRUNet-3D: A multi-stride residual 3D UNet for lung nodule segmentation.

Obtaining an accurate segmentation of the pulmonary nodules in computed tomography (CT) images is challenging. This is due to: (1) the heterogeneous nature of the lung nodules; (2) comparable visual characteristics between the nodules and their surroundings. A robust multi-scale feature extraction mechanism that can effectively obtain multi-scale representations at a granular level can improve segmentation accuracy. As the most commonly used network in lung nodule segmentation, UNet, its variants, and other image segmentation methods lack this robust feature extraction mechanism. In this study, we propose a multi-stride residual 3D UNet (MRUNet-3D) to improve the segmentation accuracy of lung nodules in CT images. It incorporates a multi-slide Res2Net block (MSR), which replaces the simple sequence of convolution layers in each encoder stage to effectively extract multi-scale features at a granular level from different receptive fields and resolutions while conserving the strengths of 3D UNet. The proposed method has been extensively evaluated on the publicly available LUNA16 dataset. Experimental results show that it achieves competitive segmentation performance with an average dice similarity coefficient of 83.47 % and an average surface distance of 0.35 mm on the dataset. More notably, our method has proven to be robust to the heterogeneity of lung nodules. It has also proven to perform better at segmenting small lung nodules. Ablation studies have shown that the proposed MSR and RFIA modules are fundamental to improving the performance of the proposed model.

PET/CT-based deep learning grading signature to optimize surgical decisions for clinical stage I invasive lung adenocarcinoma and biologic basis under its prediction: a multicenter study.

PURPOSE: No consensus on a grading system for invasive lung adenocarcinoma had been built over a long period of time. Until October 2020, a novel grading system was proposed to quantify the whole landscape of histologic subtypes and proportions of pulmonary adenocarcinomas. This study aims to develop a deep learning grading signature (DLGS) based on positron emission tomography/computed tomography (PET/CT) to personalize surgical treatments for clinical stage I invasive lung adenocarcinoma and explore the biologic basis under its prediction. METHODS: A total of 2638 patients with clinical stage I invasive lung adenocarcinoma from 4 medical centers were retrospectively included to construct and validate the DLGS. The predictive performance of the DLGS was evaluated by the area under the receiver operating characteristic curve (AUC), its potential to optimize surgical treatments was investigated via survival analyses in risk groups defined by the DLGS, and its biological basis was explored by comparing histologic patterns, genotypic alternations, genetic pathways, and infiltration of immune cells in microenvironments between risk groups. RESULTS: The DLGS to predict grade 3 achieved AUCs of 0.862, 0.844, and 0.851 in the validation set (n = 497), external cohort (n = 382), and prospective cohort (n = 600), respectively, which were significantly better than 0.814, 0.810, and 0.806 of the PET model, 0.813, 0.795, and 0.824 of the CT model, and 0.762, 0.734, and 0.751 of the clinical model. Additionally, for DLGS-defined high-risk population, lobectomy yielded an improved prognosis compared to sublobectomy p = 0.085 for overall survival [OS] and p = 0.038 for recurrence-free survival [RFS]) and systematic nodal dissection conferred a superior prognosis to limited nodal dissection (p = 0.001 for OS and p = 0.041 for RFS). CONCLUSION: The DLGS harbors the potential to predict the histologic grade and personalize the surgical treatments for clinical stage I invasive lung adenocarcinoma. Its applicability to other territories should be further validated by a larger international study.

PET/CT based cross-modal deep learning signature to predict occult nodal metastasis in lung cancer.

Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

PURPOSE: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. METHODS: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. RESULTS: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. CONCLUSION: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Transcranial magnetic stimulation cortical oscillations and improve cognition in obstructive sleep apnea patients.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive tool to improve cognition. Relevant clinical studies are mainly focused on neurological and psychiatric diseases. However, cognition decline and psychiatric disorders are popular in obstructive sleep apnea (OSA) patients. We aimed to investigate the effect of TMS over the left dorsolateral prefrontal cortex (DLPFC) on cognition test performance and to compare the changes in quantitative electroencephalogram (EEG) before and after stimulation for OSA. METHODS: This study recruited 42 OSA patients diagnosed with polysomnography according to American Academy of Sleep Medicine guidelines. TMS (intermittent theta-burst stimulation paradigm; 2 s on, 8 s off, 600 pulses*3, intermittent 15 min) was performed on the DLPFC. Cambridge Automated Neuropsychological Test Battery was used to assess cognitive performance. EEG oscillations were computed via power spectral density with MATLAB software. RESULTS: Real-TMS group displayed a significant improvement in visual memory, sustain attention performance, as well as the outcome of working memory. However, the executive function of latency was changed in both groups. Furthermore, TMS resulted in a significant increase in the relative power spectral density of the theta band and beta band in the parietal, temporal, and anterior regions, respectively. CONCLUSIONS: In summary, our findings indicate that TMS can safely modulate cortical oscillations and improve cognition in OSA patients. In the future, TMS can be utilized as an alternative treatment option to improve cognition in OSA patients.

Three cases of acute chlorfenapyr poisoning / 中华劳动卫生职业病杂志

This paper reported 3 cases of poisoning caused by chlorfenagyr. Chlorfenapyr poisoning has gradually increased in clinical practice. The early stage after poisoning is digestive tract symptoms, followed by sweating, high fever, changes in consciousness, changes in myocardial enzymology, etc. Its main mechanism of intoxication is uncoupling oxidative phosphorylation. Since there is no specific antidote after poisoning, the fatality rate of chlorfenapyr poisoning remains high. The therapeutic measures are early gastrointestinal decontamination, symptomatic and supportive treatments, and early blood purification may be an effective treatment.

High-Performance Aqueous Zinc-Ion Batteries Enabled by Binder-Free and Ultrathin V2O5-x@Graphene Aerogels with Intercalation Pseudocapacitance.

As a result of the absence of solid-state diffusion limitation, intercalation pseudocapacitance behavior is emerging as an attractive charge-storage mechanism that can greatly facilitate the ion kinetics to boost the rate capability and cycle stability of batteries; however, related research in the field of zinc-ion batteries (ZIBs) is still in the initial stage and only found in limited cathode materials. In this study, a novel V2O5-x@rGO hybrid aerogel consisting of ultrathin V2O5 nanosheets (∼1.26 nm) with abundant oxygen vacancies (Vö) and a three-dimensional (3D) graphene conductive network was specifically designed and used as a freestanding and binder-free electrode for ZIBs. As expected, the ideal microstructure of both the material and the electrode enable fast electron/ion diffusion kinetics of the electrode, which realize a typical intercalation pseudocapacitance behavior as demonstrated by the simulation calculation of cyclic voltammetry (CV), ex situ X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and first-principles density functional theory (DFT) calculation. Thanks to the elimination of solid-state diffusion limitation, the V2O5-x@rGO electrode delivers a high reversible rate capacity of 153.9 mAh g-1 at 15 A g-1 and 90.6% initial capacity retention at 0.5 A g-1 after 1050 cycles in ZIBs. The intercalation pseudocapacitance behavior is also realized in the assembled soft-pack battery, showing promising practical application prospects.

Factors associated with COVID-19 vaccination intent in Singapore, Australia and Hong Kong.

BACKGROUND: COVID-19 pandemic has caused significant morbidity and mortality globally. As vaccines have been developed under expedited conditions, their safety and efficacy are being questioned by some populations leading to vaccine hesitancy, resulting in delayed vaccine uptake and herd immunity. This study aims to adopt a combination of Health Belief Model and other independent risk factors associated with high vaccine acceptance. METHODS: An anonymized cross-sectional survey was distributed between 15 January and 3 February 2021 across Singapore, Hong Kong and Australia among adult respondents through a certified online panel. Exploratory factor analysis and confirmatory factor analysis were carried out to assess perception constructs followed by multivariate regression modelling to assess factors associated with high vaccine acceptance against SARS_CoV-2. RESULTS: A total of 3,133 anonymised participants from Singapore (n = 1,009), Australia (n = 1,118) and Hong Kong (n = 1,006) completed the survey. While age and gender were not significantly associated, Asian ethnicity, current smokers and self-efficacy were significant associated factors of increased vaccine acceptance. While specific practices like taking micronutrients more frequently, cleaning and disinfecting their house more often were positively associated with increased vaccine acceptance, seeking medical help for COVID-19 symptoms like loss of smell/taste and overall COVID-19 knowledge score were negatively associated. Increased likelihood of vaccine acceptance was seen among those that obtained COVID-19 information less frequently and used digital media or non-health-related sources like influencers as a source of information. Among the eight perception constructs, perceived susceptibility and perceived response efficacy were positively associated, while perceived barriers were negatively associated with high vaccine acceptance. CONCLUSION: While demographic parameters have weak association with vaccine acceptance, perceptions and practices parameters can help to better understand and influence vaccine acceptance. Study findings should provide guidance on the risk communication strategy to enhance vaccine acceptance for vaccination and boosters against new SARS-CoV-2 variants.

Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostic Tests for Border Screening During the Very Early Phase of Coronavirus Disease 2019 Pandemic: A Systematic Review and Meta-Analysis.

Diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during border screening among returning residents and prioritized travelers during the early phase of a pandemic can reduce the risk of importation and transmission in the community. This study aimed to compare the accuracy of various SARS-CoV-2 diagnostics and assess their potential utility as border screening for infection and immunity. Systematic literature searches were conducted in six electronic databases for studies reporting SARS-CoV-2 diagnostics (up to April 30, 2020). Meta-analysis and methodological assessment were conducted for all included studies. The performance of the diagnostic tests was evaluated with pooled sensitivity, specificity, and their respective 95% confidence intervals. A total of 5,416 unique studies were identified and 95 studies (at least 29,785 patients/samples) were included. Nucleic acid amplification tests (NAAT) consistently outperformed all other diagnostic methods regardless of the selected viral genes with a pooled sensitivity of 98% and a pooled specificity of 99%. Point-of-care (POC) serology tests had moderately high pooled sensitivity (69%), albeit lower than laboratory-based serology tests (89%), but both had high pooled specificity (96-98%). Serology tests were more sensitive for sampling collected at ≥ 7 days than ≤ 7 days from the disease symptoms onset. POC NAAT and POC serology tests are suitable for detecting infection and immunity against the virus, respectively as border screening. Independent validation in each country is highly encouraged with the preferred choice of diagnostic tool/s.

Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction.

AIMS: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. METHODS AND RESULTS: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. CONCLUSION: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.

Reduction of SIRT1 Mediates Monosodium Iodoacetate-Induced Osteoarthritic Pain by Upregulating p53 Expression in Rats.

BACKGROUND: Clinically, chronic pain is the most common and disabling symptom of osteoarthritis (OA). OA pain is associated with OA lesion of the knee and the plastic changes in the peripheral and central nervous systems. However, the central mechanisms involved at the spinal cord level are not fully understood. OBJECTIVES: The aim of this study was to identify the mechanism underlying the role of spinal cord Sirtuin 1 (SIRT1) in OA pain induced by intraarticular injection of monosodium iodoacetate (MIA) in rats. STUDY DESIGN: Controlled animal study. METHODS: MIA was injected intraarticularly into the rat knee joint for the induction of OA. The OA lesion of the knee was assessed by histopathological examination. The mechanical allodynia were measured over 21 days post-injection by von Frey filaments. The messenger RNA and protein levels of SIRT1 and p53 were determined by real-time quantitative polymerase chain reaction and western blotting, respectively. Involvement of SIRT1-mediated p53 expression in the development of MIA-persistent pain was studied using intrathecal (i.t.) injection of the SIRT1-activating molecule resveratrol and intraperitoneal (i.p.) injection of the p53 inhibitor pifithrin-mu (PTF-µ). RESULTS: MIA induced mechanical allodynia, decreased the expression of SIRT1, and upregulated the expression of p53 in the spinal dorsal horn. Consecutive i.t. injection of resveratrol or i.p. injection of PTF-µ alleviated the MIA-induced mechanical allodynia. Upregulation of dorsal horn SIRT1 expression by i.t. injection of resveratrol also inhibited the increase of dorsal horn p53 induced by MIA. Moreover, silencing of dorsal horn SIRT1 expression by i.t. administration of small interfering RNA SIRT1 into normal rats induced the mechanical allodynia and upregulation of p53 expression in the dorsal horn. LIMITATIONS: More underlying mechanism(s) of the role of p53 signaling pathway in OA pain need to be explored in future research. CONCLUSIONS: These findings suggest that the reduction of dorsal horn SIRT1 mediated upregulation of p53 expression, which plays a critical role in persistent pain induced by OA. The i.t. drug delivery treatments targeting the spinal cord SIRT1/p53 pathway might be novel therapeutic options for OA-induced persistent pain.

Electroencephalographic Activity and Cognitive Function in Middle-Aged Patients with Obstructive Sleep Apnea Before and After Continuous Positive Airway Pressure Treatment.

PURPOSE: To investigate the effect of continuous positive airway pressure (CPAP) on sleep electroencephalogram (EEG) activity in patients with obstructive sleep apnea (OSA) and to examine the correlation between quantitative EEG changes and cognitive function. PATIENTS AND METHODS: A total of 69 men and 11 women were collected with an average age of 39.61 ± 7.67 years old from among middle-aged patients who had first visits with snoring as their main complaint. All of them completed sleep questionnaires, neurocognitive tests and night polysomnography (PSG). The patients in the OSA group also completed the second night of PSG monitoring under CPAP after pressure titration. A power spectrum analysis of EEG was used, and the correlation between the frequency powers of EEG and the scores of the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA) were further analyzed. RESULTS: Compared with the control group, the delta/alpha power ratio (DAR) and the (delta + theta)/(alpha + beta) power ratio (the slowing ratio, TSR) of the OSA group before CPAP were higher (P < 0.05). The DAR and TSR of the OSA patients decreased significantly after CPAP. ESS scores were correlated with parameters such as respiratory-related microarousal index (RRMAI), apnea hypopnea index (AHI), and the average absolute power of delta, DAR and TSR (P < 0.05). The PSQI, MMSE and MoCA scores were not correlated with the average absolute power of each frequency band, DAR or TSR (P > 0.05). CONCLUSION: Patients with OSA have greater slow frequency EEG activity during sleep than the control group. CPAP treatment reversed the slow frequency EEG activity in patients with OSA.

Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries.

INTRODUCTION: Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic. OBJECTIVES: In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic. METHODS: A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail. RESULTS: Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance. CONCLUSIONS: We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

Epidemiological and clinical characteristics of non-severe and severe pediatric and adult COVID-19 patients across different geographical regions in the early phase of pandemic: a systematic review and meta-analysis of observational studies.

This systematic and meta-review aimed to compare clinical presentation, outcomes, and care management among patients with COVID-19 during the early phase of the pandemic. A total of 77 peer-reviewed publications were identified between January 1, 2020 and April 9, 2020 from PubMed, Google Scholar, and Chinese Medical Journal databases. Subsequently, meta-analysis of 40 non-overlapping studies, comprising of 4844 patients from seven countries, was conducted to see differences in clinical characteristics and laboratory outcomes across patients from different geographical regions (Wuhan, other parts of China and outside China), severity (non-severe, severe and fatal) and age groups (adults and children). Patients from Wuhan had a higher mean age (54.3 years) and rates of dyspnea (39.5%) compared with patients from other parts of China and outside China. Myalgia, fatigue, acute respiratory distress syndrome (ARDS) and fatalities were also significantly more prevalent among Wuhan patients. A significant dose-response increase in prevalence of diabetes, D-dimer, white blood cells, neutrophil levels and ARDS was seen from non-severe to severe and fatal outcomes. A significant increase in mean duration of symptom onset to admission was seen between non-severe cases (4.2 days) and severe and fatal cases (6.3 days and 8.8 days, respectively). Proportion of asymptomatic cases was higher in children (20%) compared with adults (2.4%). In conclusion, patients with COVID-19 from Wuhan displayed more severe clinical disease during the early phase of the pandemic, while disease severity was significantly lesser among pediatric cases. This review suggests that biomarkers at admission may be useful for prognosis among patients with COVID-19.

The C-terminal of the α1b-adreneroceptor is a key determinant for its structure integrity and biological functions.

The C-terminal of G protein-coupled receptors is now recognized as being important for G protein activation and signaling function. To detect the role of C-terminal tail in receptor activation, we used the α1b-AR, which has a long C-terminal of 164 amino acids. We constructed the intramolecular FRET sensors, in which the C-terminal was truncated to 10 (∆C-10), 20 (∆C-20), 30 (∆C-30), 50 (∆C-50), 70 (∆C-70), or 90 (∆C-90). The truncated mutants of ∆C-10, ∆C-20, or ∆C-30 cannot induce FRET signal changes and downstream ERK1/2 phosphorylation. However, the truncated mutants of ∆C-50, ∆C-70, or ∆C-90 induce significant FRET signal changes and downstream ERK1/2 phosphorylation, especially ∆C-90. This is particularly true in the case of the ∆C-90, ∆C-70, or ∆C-50 which retained the potential phosphorylation sites (Ser401, Ser404, Ser408, or Ser410). The ∆C-90 showed an increase in agonist-induced FRET signal changes and ERK1/2 phosphorylation in PKC- or endocytosis-dependent and EGFR-, src-, or ß-arrestin2-independent.

Weather Factors Associated with Reduced Risk of Dengue Transmission in an Urbanized Tropical City.

This study assessed the impact of weather factors, including novel predictors-pollutant standards index (PSI) and wind speed-on dengue incidence in Singapore between 2012 and 2019. Autoregressive integrated moving average (ARIMA) model was fitted to explore the autocorrelation in time series and quasi-Poisson model with a distributed lag non-linear term (DLNM) was set up to assess any non-linear association between climatic factors and dengue incidence. In DLNM, a PSI level of up to 111 was positively associated with dengue incidence; incidence reduced as PSI level increased to 160. A slight rainfall increase of up to 7 mm per week gave rise to higher dengue risk. On the contrary, heavier rainfall was protective against dengue. An increase in mean temperature under around 28.0 °C corresponded with increased dengue cases whereas the association became negative beyond 28.0 °C; the minimum temperature was significantly positively associated with dengue incidence at around 23-25 °C, and the relationship reversed when temperature exceed 27 °C. An overall positive association, albeit insignificant, was observed between maximum temperature and dengue incidence. Wind speed was associated with decreasing relative risk (RR). Beyond prevailing conclusions on temperature, this study observed that extremely poor air quality, high wind speed, minimum temperature ≥27 °C, and rainfall volume beyond 12 mm per week reduced the risk of dengue transmission in an urbanized tropical environment.

HDAC1-Smad3-mSin3A complex is required for Smad3-induced transcriptional inhibition of hepatocyte growth factor receptor in human lung cancers.

c-Met hyperactivity has been observed in numerous neoplasms. Several researchers have shown that the abnormal activation of c-Met is mainly caused by transcriptional activation. However, the molecular mechanism behind this transcriptional regulation is poorly understood. Here, we suggest that Smad3 negatively regulates the expression and activation of c-Met via a transcriptional mechanism. We explore the molecular mechanisms that underlie Smad3-induced c-Met transcription inhibition. We found in contrast to the high expression of c-Met, Smad3 showed low protein and mRNA levels. Smad3 and c-Met expressions were inconsistent between lung cancer tissues and cell lines. We also found that Smad3 overexpression suppresses whereas Smad3 knockdown significantly promotes Epithelial-Mesenchymal Transition and production of the angiogenic factors VEGF, CTGF and COX-2 through the ERK1/2 pathway. In addition, Smad3 overexpression decreases whereas Smad3 knockdown significantly increases protein and mRNA levels of invasion-related ß-catenin and FAK through the PI3K/Akt pathway. Furthermore, using the chromatin immunoprecipitation analysis method, we demonstrate that a transcriptional regulatory complex consisting of HDAC1, Smad3 and mSin3A binds to the promoter of the c-Met gene. By either silencing endogenous mSin3A expression with siRNA or by pretreating cells with a specific HDAC1 inhibitor (MS-275), Smad3-induced transcriptional suppression of c-Met could be effectively attenuated. These results demonstrate that Smad3-induced inhibition of c-Met transcription depends on of a functional transcriptional regulatory complex that includes Smad3, mSin3A and HDAC1 at the c-Met promoter. Collectively, our findings reveal a new regulatory mechanism of c-Met signaling, and suggest a potential molecular target for the development of anticancer drugs.

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson's Disease.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson's disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD. METHODS: We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment. RESULTS: A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS. CONCLUSIONS: Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.

Epidemiological and Clinical Characteristics of Cases During the Early Phase of COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Background: On 29th December 2019, a cluster of cases displaying the symptoms of a "pneumonia of unknown cause" was identified in Wuhan, Hubei province of China. This systematic review and meta-analysis aims to review the epidemiological and clinical characteristics of COVID-19 cases in the early phase of the COVID-19 pandemic. Methods: The search strategy involved peer-reviewed studies published between 1st January and 11th February 2020 in Pubmed, Google scholar and China Knowledge Resource Integrated database. Publications identified were screened for their title and abstracts according to the eligibility criteria, and further shortlisted by full-text screening. Three independent reviewers extracted data from these studies, and studies were assessed for potential risk of bias. Studies comprising non-overlapping patient populations, were included for qualitative and quantitative synthesis of results. Pooled prevalence with 95% confidence intervals were calculated for patient characteristics. Results: A total of 29 publications were selected after full-text review. This comprised of 18 case reports, three case series and eight cross-sectional studies on patients admitted from mid-December of 2019 to early February of 2020. A total of 533 adult patients with pooled median age of 56 (95% CI: 49-57) and a pooled prevalence of male of 60% (95% CI: 52-68%) were admitted to hospital at a pooled median of 7 days (95% CI: 7-7) post-onset of symptoms. The most common symptoms at admission were fever, cough and fatigue, with a pooled prevalence of 90% (95% CI: 81-97%), 58% (95% CI: 47-68%), and 50% (95% CI: 29-71%), respectively. Myalgia, shortness of breath, headache, diarrhea and sore throat were less common with pooled prevalence of 27% (95% CI: 20-36%), 25% (95% CI: 15-35%), 10% (95% CI: 7-13%), 8% (95% CI: 5-13%), and 7% (95% CI: 1-15%), respectively. ICU patients had a higher proportion of shortness of breath at presentation, as well as pre-existing hypertension, cardiovascular disease and COPD, compared to non-ICU patients in 2 studies (n = 179). Conclusion: This study highlights the key epidemiological and clinical features of COVID-19 cases during the early phase of the COVID-19 pandemic.