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Background: Several epidemiological studies have reported the protective role of caffeine on health outcomes; however, it remained debatable on caffeine consumption and brain amyloid positivity. Objective: We aimed to determine the relationship between caffeine consumption and brain amyloid pathology in cognitively normal older adults. Methods: The dataset used for analysis in this cross-sectional study was selected from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. Multivariable logistic regression analyses were performed to explore the association between caffeine consumption and amyloid positivity using odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 4,394 participants were included in the final analysis. No significant association between caffeine consumption and amyloid positivity was observed in the whole participants (OR, 0.95; 95% CI, 0.78–1.14; p = 0.558). Subgroup analysis showed that caffeine intake was significantly associated with decreased amyloid positivity in males (OR, 0.72; 95% CI, 0.54–0.97; p = 0.032) but not in females (OR, 1.14; 95% CI, 0.90–1.46; p = 0.280), and the association between caffeine and amyloid positivity was not affected by age or APOE genotypes. In addition, different levels of caffeine were not associated with amyloid positivity. Conclusion: The findings suggest that caffeine consumption was not significantly associated with amyloid positivity in the whole sample. However, caffeine consumption may be inversely associated with amyloid positivity among males but not females. More studies are needed to explore the mechanisms underlying caffeine consumption and brain amyloid positivity.

Surface and subsurface fire in municipal solid waste landfills (including dumpsites) is a complex and intricate phenomenon, frequency of which is expected to increase due to climate change. Partial or incomplete combustion of landfill waste at low temperatures during fires leads to the generation of toxic compounds, including hydrocarbons, particulate matter and hazardous gases, which contaminate the surrounding geoenvironment and ultimately pose severe health hazards to living entities. Under these circumstances, it is the need of the hour to understand the (a) occurrence mechanisms of landfill fires, (b) waste properties and operational conditions that may favour landfill fires and (c) strengths and limitations of the available detection techniques to provide recommendations for detecting such incidences at an early stage and plan emergency measures. Hence, the present review paper critically assimilates the literature on landfill fires and discusses the (a) conditions under which the initiation and sustenance of landfill fires take place; (b) ecotoxicological (geoenvironmental) hazards of landfill fires, in both the short and the long term; and (c) detection techniques for an early warning system. Finally, a discussion on the coupled multi-physics interactions occurring in the waste matrix during landfill fires is presented, which is crucial to mastering this subject.

A novel type of homogeneous catalyst KIm was developed and applied to the reaction of PC and MeOH to synthesize DMC.

Low temperature poly-crystalline silicon thin-film transistors (LTPS-TFTs) and indium-gallium-zinc-oxide TFTs (IGZO-TFTs) are potential candidates for future technology of various displays. Due to its simple manufacturing process, low cost and good uniformity, IGZO-TFTs have been developed as main stream display technology. From the viewpoint of device electrical characteristics, a-IGZO TFTs have better field-effect mobility (>10 cm2/V * s), larger Ion/Ioff ratio (>106), smaller subthreshold swing (S.S) and good stability. In this study, atmospheric-pressure PECVD (AP-PECVD) is used to deposit a-IGZO active layer, during the deposition process In-Situ hydrogenation is applied to enhance the layer characteristics. Also, the layer is then surface oxidation treated by neutral beam system (NBS). The optimal TFTs device characteristics is reached with In-Situ hydrogenation of H2 90 sccm, and surface oxidation of 400 W NBS treatment. The field-effect mobility is 34.05 cm2/V * s, threshold voltage is 1.74 V, subthreshold swing is 62 mV/decade, and current ratio Ion/Ioff is 2.04×107. Compared with conventional plasma, NBS used in this study provides charge-free plasma which could enhance device electric characteristics.

The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM).We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China.A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035).This study demonstrated that species identification helps to guide therapy and predict outcomes.

This study believes that effective local government regulation is the key to achieving successful household registration governance, that is, in the system creation and policy formulation, tool rationality returns to value rationality. The characteristics of “political people” and “economic people” in local governments encourage them to make rational decisions in the reform of the household registration system, resulting in household registration policies that are often highly directional and purposeful, making it difficult to consider development efficiency and social fairness. Chengdu’s “dual-track parallel” settlement strategy is a behavior choice for local governments to return to value rationality, reflecting Chengdu municipal government’s “social people” feature. It achieves a balance between meeting the needs of talents and building a healthy household registration proportion by correlating “conditional entry” and “integral entry.” This not only realizes the absorption of high-quality talents, but also provides settlement channels for outsiders with limited conditions.

Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression.

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

Motivation Precise prediction of cancer subtypes is of significant importance in cancer diagnosis and treatment. Disease etiology is complicated existing at different omics levels; hence integrative analysis provides a very effective way to improve our understanding of cancer. Results We propose a novel computational framework, named Deep Subspace Mutual Learning (DSML). DSML has the capability to simultaneously learn the subspace structures in each available omics data and in overall multi-omics data by adopting deep neural networks, which thereby facilitates the subtype’s prediction via clustering on multi-level, single-level and partial-level omics data. Extensive experiments are performed in five different cancers on three levels of omics data from The Cancer Genome Atlas. The experimental analysis demonstrates that DSML delivers comparable or even better results than many state-of-the-art integrative methods. Availability and implementation An implementation and documentation of the DSML is publicly available at https://github.com/polytechnicXTT/Deep-Subspace-Mutual-Learning.git.

ContextGlucocorticoids have potent effects on the central nervous system. However, while patients with Cushing syndrome frequently report impairments in cognitive function, studies investigating cognitive function in patients with autonomous cortisol secretion (ACS) in adrenal incidentalomas (AIs) are scarce.ObjectiveThe aim of the present study was to evaluate neurocognitive function in patients with ACS.MethodsWe prospectively recruited 63 patients with AI, 36 patients with nonfunctional adrenal adenoma (NFA) (46.5 ± 10.5 years), and 27 patients with ACS (48.6 ± 9.1 years); these patients underwent a battery of validated neuropsychological tests. ACS was diagnosed when serum cortisol levels after a 1-mg dexamethasone suppression test (cortisol1 mg DST) ≥ 50 nmol/L.ResultsPatients with ACS had higher frequency of subjective memory complaints (40.7% vs 13.9%, P < 0.05) and higher proportion of mild cognitive impairment (22.2% vs 2.8%, P < 0.05) than patients with NFA. Furthermore, patients with ACS had worse performance on working memory and the visuospatial/constructional domain than patients with NFA (all P < 0.05). Serum cortisol1 mg DST was negatively correlated with working memory and visuospatial/constructional domains (r = −0.307 and −0.306, respectively, all P < 0.05). Performance on working memory and visuospatial/constructional domains gradually deteriorated with increases in serum cortisol1 mg DST (all P values for trend < 0.05). Multivariate linear regression analysis showed that serum cortisol1 mg DST was a significant risk factor for impairment of working memory and visuospatial/constructional domains (B = −0.006 and −0.043, respectively, all P < 0.05).ConclusionThis study is the first to report that ACS is accompanied by impaired cognitive function. Consequently, cognitive function assessment should be incorporated into the clinical evaluation of patients with ACS.Clinical trial registration numberNCT05357456.

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na–CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na–CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.

Background Raised intracranial pressure (ICP) and insufficient antifungal regimens are the two main factors result to unsatisfactory outcomes in non-HIV cryptococcal meningitis (CM) patients. In this study, we try to discuss that whether triple therapy of amphotericin B (AmB), fluconazole, 5-flucytosine (5-FC) plus ventriculoperitoneal shunts (VPS) is superior to AmB, 5-FC, fluconazole plus intermittent lumbar puncture in induction therapy in non-HIV CM patients with increased ICP. Methods We reviewed 66 clinical records from non-HIV CM patients with increased ICP. The demographic and clinical characteristics, BMRC staging, cerebrospinal fluid profiles (CSF), brain magnetic resonance imaging, treatment, and outcomes of these individuals were retrospectively analyzed. All non-HIV CM patients with increased ICP (≥ 25 cmH2O) were divided into two groups, including 27 patients treated with triple antifungal agents and 39 patients treated with the same triple therapy plus VPS. Results Triple therapy plus VPS group had more satisfactory outcomes, more CSF sterilization at 10 weeks follow-up, lower CSF opening pressure, lower BMRC staging scores one week after VPS, less CSF C. neoformans counts and CSF culture positive. Besides, these patients had shorter hospital stay than triple therapy group. Conclusions Triple antifungal agents combined with VPS could effectively reduce ICP, had faster rate of clearance of C. neoformans counts, more improved neurological function, shorten hospitalization time and better outcomes in non-HIV CM patients with increased ICP. Our study indicated that triple therapy plus early VPS may be an optimal treatment for non-HIV CM patients with increased ICP.

Type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) regulates the intracellular Ca2+ release from endoplasmic reticulum in human embryonic stem cells (hESCs), cardiovascular progenitor cells (CVPCs), and mammalian cardiomyocytes. However, the role of IP3R2 in human cardiac development is unknown and its function in mammalian cardiomyocytes is controversial. hESC-derived cardiomyocytes have unique merits in disease modeling, cell therapy, and drug screening. Therefore, understanding the role of IP3R2 in the generation and function of human cardiomyocytes would be valuable for the application of hESC-derived cardiomyocytes. In the current study, we investigated the role of IP3R2 in the differentiation of hESCs to cardiomyocytes and in the hESC-derived cardiomyocytes. By using IP3R2 knockout (IP3R2KO) hESCs, we showed that IP3R2KO did not affect the self-renewal of hESCs as well as the differentiation ability of hESCs into CVPCs and cardiomyocytes. Furthermore, we demonstrated the ventricular-like myocyte characteristics of hESC-derived cardiomyocytes. Under the α1-adrenergic stimulation by phenylephrine (10 μmol/L), the amplitude and maximum rate of depolarization of action potential (AP) were slightly affected in the IP3R2KO hESC-derived cardiomyocytes at differentiation day 90, whereas the other parameters of APs and the Ca2+ transients did not show significant changes compared with these in the wide-type ones. These results demonstrate that IP3R2 has minimal contribution to the differentiation and function of human cardiomyocytes derived from hESCs, thus provide the new knowledge to the function of IP3R2 in the generation of human cardiac lineage cells and in the early cardiomyocytes.

Effective drugs for treating dementia are still rare. Danggui-Shaoyao San (DSS), a traditional Chinese medicine, has been widely used in oriental countries for the treatment of various gynecological diseases. Many studies reported that DSS could ameliorate cognitive impairment. In this study, we aimed to investigate the underlying mechanism of DSS on vascular cognitive impairment (VCI) rats. Chronic cerebral hypoperfusion (CCH) is one of the main causes of VCI. CCH resulted in a chain of pathological process, including neuroinflammation, neuronal apoptosis, and oxidative stress. The most widely used animal model of VCI is permanent bilateral common carotid artery occlusion in rats. In this research, we determined whether DSS attenuated cognitive impairment by targeting I kappa B kinase (IKK)/nuclear factor of kappa B (NF-κB) signal pathway in VCI rats. Morris water maze and fear conditioning tests results indicated that DSS [7.2 g/(kg·d)] could improve learning and memory ability in VCI rats. We also found DSS significantly elevated the levels of low-density lipoprotein receptor-related protein 1 (LRP1) in the brain of VCI rats and this might indirectly target the IKK/NF-κB signal pathway to exert inhibitory effect on neuroinflammation, neuronal apoptosis, and oxidative stress in VCI rats. The present researches indicated that DSS might attenuate cognitive impairment by targeting IKK/NF-κB signal pathway in VCI rats and DSS might be a promising agent on VCI.

Selecting a proper set of covariates is one of the most important factors that influence the accuracy of digital soil mapping (DSM). The statistical or machine learning methods for selecting DSM covariates are not available for those situations with limited samples. To solve the problem, this paper proposed a case-based method which could formalize the covariate selection knowledge contained in practical DSM applications. The proposed method trained Random Forest (RF) classifiers with DSM cases extracted from the practical DSM applications and then used the trained classifiers to determine whether each one potential covariate should be used in a new DSM application. In this study, we took topographic covariates as examples of covariates and extracted 191 DSM cases from 56 peer-reviewed journal articles to evaluate the performance of the proposed case-based method by Leave-One-Out cross validation. Compared with a novices’ commonly-used way of selecting DSM covariates, the proposed case-based method improved more than 30% accuracy according to three quantitative evaluation indices (i.e., recall, precision, and F1-score). The proposed method could be also applied to selecting the proper set of covariates for other similar geographical modeling domains, such as landslide susceptibility mapping, and species distribution modeling.

Due to more extreme weather events and accelerating sea-level rise, coastal sand dunes are subjected to more frequent storm wave inundation and surge impacts, which contribute to widespread coastal erosion problems. In this study, two novel bio-mediated methods, microbial-induced carbonate precipitation (MICP) and enzymatic-induced carbonate precipitation (EICP), were investigated and compared for their effectiveness in mitigating sand dune erosion under wave attack. Small-scale laboratory model tests were performed on MICP-treated, EICP-treated, and untreated sand dunes at dune slope angles and two wave intensities for up to 2 h. The cross-shore profile was captured continuously during the course of the erosion test. The erosion volume above the still water level (SWL) and landward retreat distance at the SWL were calculated based on the captured bed profiles. The results show that both EICP and MICP could substantially reduce sand dune erosion at mild-to-moderate wave and dune slope conditions. However, the effectiveness of MICP treatment deteriorated at steeper dune slopes with longer period of wave attack. Under the most adverse condition (i.e., steepest dune slope, biggest wave, and longest period of wave attack), neither EICP nor MICP could effectively mitigate erosion. Fundamentally, the variable effectiveness of MICP and EICP treatment for sand dune erosion control was attributed to the spatial distribution pattern of formed calcite precipitation, which was determined by the way how EICP and MICP were applied. The calcite precipitation was relatively uniform in EICP-treated sand dunes. In MICP-treated ones, however, substantial calcite precipitation concentrated in the shallow surface layer as confirmed by the surface penetration test and SEM observation.

We compare the equilibria under Bertrand and Cournot competition in the spatial barbell model where spatial barriers and process R&D are involved. We show that when the market becomes more competitive by switching from Cournot to Bertrand competition, R&D investment may increase (decrease) depending upon a low (high) transport rate. Next, we find that under Cournot competition total output, consumer surplus, and welfare are higher, but profit is lower than is true for Bertrand competition, when the transport rate is high, which overturns the traditional result.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.