Characteristics of non-stenotic carotid plaque in embolic stroke of undetermined source compared with cardiogenic embolism: a retrospective cross-sectional observational study.

BACKGROUND: Non-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS. METHODS: This is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People's Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS. RESULTS: We had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45-12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55-16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727-0.896; p < 0.001). CONCLUSION: Our results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.

Influence of Pre-Existing Cerebral Small Vessel Disease on the Outcome of Acute Cardioembolic Stroke: A Retrospective Study.

Purpose: This study was to explore the role of pre-existing small vessel disease (SVD) on the 3-month outcomes of acute cardioembolic stroke (CES) patients. Patients and Methods: Data of 189 consecutive acute CES patients at a single center were retrospectively enrolled. SVD imaging markers of lacunes, white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) were evaluated and their total burden score (0-3 points) was calculated. Patients were divided into the good functional outcome group (modified Rankin scale, mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3) at 3 months after stroke onset. The effect of each single SVD marker and its total burden score on the outcome was identified using binary logistic regression. Results: Overall, 100 (52.9%), 52 (27.1%), 28 (14.8%) and 9 (4.8%) patients had 0, 1, 2 and 3 SVD imaging markers. Patients with a total SVD burden score of 2 and 3 were significantly older and had higher baseline National Institutes of Health Stroke Scale (NIHSS) score than those with a score of 0 and 1 (P<0.01). Forty-seven (24.9%) patients had a poor outcome. Patients in the poor outcome group had significantly higher baseline NIHSS score, increased incidence of stroke associated pneumonia, and heavier burden of lacunes, WMH and EPVS, and thus had elevated total SVD burden score than those in good outcome group (P<0.05). After adjusting for potential confounders, the WMH (odds ratio [OR] = 2.6777, 95% confidence interval [CI] = 1.052-6.812, P = 0.039) and the total SVD burden score (OR = 1.717, 95% CI = 1.072-2.749, P = 0.024) were, respectively, independent risk factors for a poor outcome. Conclusion: The pre-existing SVD may be associated with the 3-month prognosis of CES.

Analysis of the effect of NEKs on the prognosis of patients with non-small-cell lung carcinoma based on bioinformatics.

NEKs are proteins that are involved in various cell processes and play important roles in the formation and development of cancer. However, few studies have examined the role of NEKs in the development of non-small-cell lung carcinoma (NSCLC). To address this problem, the Oncomine, UALCAN, and the Human Protein Atlas databases were used to analyze differential NEK expression and its clinicopathological parameters, while the Kaplan-Meier, cBioPortal, GEPIA, and DAVID databases were used to analyze survival, gene mutations, similar genes, and biological enrichments. The rate of NEK family gene mutation was high (> 50%) in patients with NSCLC, in which NEK2/4/6/8/ was overexpressed and significantly correlated with tumor stage and nodal metastasis status. In addition, the high expression of NEK2/3mRNA was significantly associated with poor prognosis in patients with NSCLC, while high expression of NEK1/4/6/7/8/9/10/11mRNA was associated with good prognosis. In summary, these results suggest that NEK2/4/6/8 may be a potential prognostic biomarker for the survival of patients with NSCLC.

Association between YKL-40 and asthma: a systematic meta-analysis.

PURPOSE: Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. METHODS: The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. RESULTS: The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p < 0.05). YKL-40 levels were significantly different between chronic obstructive pulmonary disease (COPD) and asthma, and also between asthma-COPD overlap syndrome (ACO) and asthma (p < 0.05). CONCLUSION: YKL-40 may act as a potential serological marker for the diagnosis of asthma, assessment of severity, indicator of the disease state, and differential diagnosis of COPD, ACO, and asthma.

Analysis of Risk Factors for Poor Short-Term Outcomes in Acute Cardioembolic Stroke Patients without Reperfusion Therapy.

PURPOSE: Few clinical indicators of a poor outcome have been defined in acute cardioembolic stroke (CES) patients. We would like to explore practical clinical factors that can predict poor outcomes of CES in the early stage. PATIENTS AND METHODS: In this single-center, retrospective, observational study, 251 consecutive patients with acute CES who did not undergo reperfusion therapy were evaluated. On the basis of the modified Rankin Scale (mRS) score at 3 months, patients were divided into the good functional outcome group (mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3). Risk factors were analyzed and the independent indicators for a poor outcome were identified using a binary logistic regression model. RESULTS: One hundred (39.8%) patients had a poor outcome. Patients in the poor outcome group were significantly older (P = 0.002) and had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) score compared with those with a good outcome (P < 0.001). After adjusting for potential confounders, the baseline NIHSS score (P < 0.001), moderate to severe leukoaraiosis (P = 0.011), non-symptomatic intracranial hemorrhage (P = 0.019), stroke-associated pneumonia (P = 0.001), and fasting glucose (P = 0.040) were independent risk factors for a poor outcome. CONCLUSION: The short-term outcome in acute CES patients without reperfusion therapy can be predicted by using five practical clinical factors. These indicators should attract more attention.

Influence of white matter lesions on the prognosis of acute cardioembolic stroke without reperfusion therapy.

BACKGROUND: Few studies have investigated the influence of white matter lesions (WMLs) on the prognosis of acute cardioembolic stroke (CES). We aimed to explore the role of WMLs in predicting 3-month prognosis of CES without reperfusion therapy. METHODS: A number of 251 acute CES patients without reperfusion therapy at a single center were retrospectively recruited. The severity of WMLs was evaluated by Fazekas scale and patients were divided into mild WMLs group (188 cases, Fazekas ≤ 2 points) and moderate to severe WMLs group (63 cases, Fazekas ≥ 3 points) accordingly. General data and clinical features of the two groups were compared. Functional outcomes of patients were followed up for 3 months using the modified Rankin scale (mRS) and patients were divided into poor outcome group (mRS ≥ 3) and favorable outcome group (mRS ≤ 2). The effect of WMLs on the prognosis was identified by binary logistic regression. RESULTS: Patients in moderate to severe WMLs group were older (P < 0.001). Also, they had higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) and elevated incidence of asymptomatic cerebral hemorrhage (P = 0.040) and stroke associated pneumonia (P = 0.001) than those in mild WMLs group. At 3 months, there were 100 cases in the poor outcome group. Patients in poor outcome group had higher baseline NIHSS score, increased proportion of moderate to severe WMLs, and elevated incidence of stroke associated pneumonia than those in favorable outcome group (P < 0.001). Binary logistic regression analysis showed that moderate to severe WMLs (odds ratio [OR] = 4.105, 95 % confidence interval [CI] = 1.447-11.646), baseline NIHSS score (OR = 1.368, 95 % CI = 1.240-1.511), and stroke-associated pneumonia (OR = 4.840, 95 %CI = 1.889-12.400) were independent risk factors for poor outcome. CONCLUSIONS: Moderate to severe WMLs is an independent risk factor for prognosis of CES patients without reperfusion therapy.

Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis.

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Tweaking the Molecular Geometry of a Tetraperylenediimide Acceptor.

Partial flattening of the spatially extended molecular scaffold has been employed as an effective tactic to improve the device performance of a perylenediimide (PDI)-based small-molecule acceptor because the less twisted yet not completely planar molecular geometry is anticipated to improve the molecular packing and thereby attain a more suitable balance between the carrier transport ability and phase domain size. A small-molecule acceptor BF-PDI comprising four α-substituted PDI units attached around a 9,9'-bifluorenylidene (BF) central moiety is designed and studied in polymer solar cells. The BF group is deemed a ring-fused analogue of the tetraphenylethylene (TPE) unit. Due to the less twisted and better conjugated BF skeleton, BF-PDI displays more delocalized lowest unoccupied molecular orbital. By virtue of both the electronic and steric effects, BF-PDI is suggested to bring about superior intermolecular stacking and donor-acceptor phase separation morphology in blend films. Indeed, the experimental results show that BF-PDI displays improved charge transport ability and a higher power-conversion efficiency of 8.05% than that of TPE-PDI. Grazing-incidence wide-angle X-ray diffraction and resonant soft X-ray scattering confirm the more compact and ordered molecular packing as well as smaller domain sizes in the P3TEA/BF-PDI blend.

Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Aspirin cooperates with p300 to activate the acetylation of H3K9 and promote FasL-mediated apoptosis of cancer stem-like cells in colorectal cancer.

Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor growth and relapse in colorectal cancer (CRC), and therefore, they are promising targets for cancer therapy. Epidemiological evidence has suggested that the daily use of aspirin reduces overall mortality of CRC and the risk of distant metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC. Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell model and patient samples. Chemically modified aspirin and immunoprecipitation were adopted to detect the target proteins of aspirin. A locus-specific light-inducible epigenetic modification system based on CRISPR technology was constructed to verify the causal relationship in these molecular events. In vivo characterization was performed in a xenograft model. Results: We found that aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor progression, and enhances the anti-neoplastic effects of chemotherapeutic agents. Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9 acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs. Notably, these effects of aspirin are absent in non-CSCs since H3K9 is hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant therapy. Conclusions: Taken together, we revealed a unique epigenetic and cox-independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates colorectal CSCs. These findings establish an innovative framework of the therapeutic significance of aspirin.

Improved Electron Transport with Reduced Contact Resistance in N-Doped Polymer Field-Effect Transistors with a Dimeric Dopant.

Attaining control on charge injection properties is significant for meaningful applications of organic field-effect transistors (OFETs). Here, molecular electron-doping is applied with an air-stable dimer dopant for n-type OFETs based on (naphthalene diimide-diketopyrrolopyrrole) polymer hosts. Through investigating the doping effect on contact and transport properties, it is found that the electron transport increases in n-doped OFETs at low doping regime with remaining large on/off ratios. These favorable meliorations are reconciled by the mitigated impacts of contact resistance and interfacial traps, as well as the surface morphology exhibiting features of increased ordering. The occurrence of doping in the presence of dimer dopants is evidenced by the observed shift of Fermi level toward vacuum level coupled with compositional analysis. Without applying vacuum-deposition-based contact doping, charge injection efficiencies are gained without losing OFET characteristics using the solution-based methodology.

Improved Performance of All-Polymer Solar Cells Enabled by Naphthodiperylenetetraimide-Based Polymer Acceptor.

A new polymer acceptor, naphthodiperylenetetraimide-vinylene (NDP-V), featuring a backbone of altenating naphthodiperylenetetraimide and vinylene units is designed and applied in all-polymer solar cells (all-PSCs). With this polymer acceptor, a new record power-conversion efficiencies (PCE) of 8.59% has been achieved for all-PSCs. The design principle of NDP-V is to reduce the conformational disorder in the backbone of a previously developed high-performance acceptor, PDI-V, a perylenediimide-vinylene polymer. The chemical modifications result in favorable changes to the molecular packing behaviors of the acceptor and improved morphology of the donor-acceptor (PTB7-Th:NDP-V) blend, which is evidenced by the enhanced hole and electron transport abilities of the active layer. Moreover, the stronger absorption of NDP-V in the shorter-wavelength range offers a better complement to the donor. All these factors contribute to a short-circuit current density (J sc ) of 17.07 mA cm-2 . With a fill factor (FF) of 0.67, an average PCE of 8.48% is obtained, representing the highest value thus far reported for all-PSCs.

A Vinylene-Bridged Perylenediimide-Based Polymeric Acceptor Enabling Efficient All-Polymer Solar Cells Processed under Ambient Conditions.

All-polymer solar cells with 7.57% power conversion efficiency are achieved via a new perylenediimide-based polymeric acceptor. Furthermore, the device processed in ambient air without encapsulation can still reach a high power conversion efficiency (PCE) of 7.49%, which is a significant economic advantage from an industrial processing perspective. These results represent the highest PCE achieved from perylenediimide-based polymers.

A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons.

AMP-activated protein kinase (AMPK) plays an important role in regulating food intake. The downstream AMPK substrates and neurobiological mechanisms responsible for this, however, are ill defined. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus regulate hunger. Their firing increases with fasting, and once engaged they cause feeding. AgRP neuron activity is regulated by state-dependent synaptic plasticity: fasting increases dendritic spines and excitatory synaptic activity; feeding does the opposite. The signaling mechanisms underlying this, however, are also unknown. Using neuron-specific approaches to measure and manipulate kinase activity specifically within AgRP neurons, we establish that fasting increases AMPK activity in AgRP neurons, that increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and excitatory synaptic activity, and that the AMPK phosphorylation target mediating this plasticity is p21-activated kinase. This provides a signaling and neurobiological basis for both AMPK regulation of energy balance and AgRP neuron state-dependent plasticity.

Flow-enhanced solution printing of all-polymer solar cells.

Morphology control of solution coated solar cell materials presents a key challenge limiting their device performance and commercial viability. Here we present a new concept for controlling phase separation during solution printing using an all-polymer bulk heterojunction solar cell as a model system. The key aspect of our method lies in the design of fluid flow using a microstructured printing blade, on the basis of the hypothesis of flow-induced polymer crystallization. Our flow design resulted in a ∼90% increase in the donor thin film crystallinity and reduced microphase separated donor and acceptor domain sizes. The improved morphology enhanced all metrics of solar cell device performance across various printing conditions, specifically leading to higher short-circuit current, fill factor, open circuit voltage and significantly reduced device-to-device variation. We expect our design concept to have broad applications beyond all-polymer solar cells because of its simplicity and versatility.

Disambiguation in the biomedical domain: the role of ambiguity type.

Word Sense Disambiguation (WSD), the automatic identification of the meanings of ambiguous terms in a document, is an important stage in text processing. We describe a WSD system that has been developed specifically for the types of ambiguities found in biomedical documents. This system uses a range of knowledge sources. It employs both linguistic features, such as local collocations, and features derived from domain-specific knowledge sources, the Unified Medical Language System (UMLS) and Medical Subject Headings (MeSH). This system is applied to three types of ambiguities found in Medline abstracts: ambiguous terms, abbreviations with multiple expansions and names that are ambiguous between genes. The WSD system is applied to the standard NLM-WSD data set, which consists of ambiguous terms from Medline abstracts, and was found to perform well in comparison with previously reported results. The system's performance and the contribution of each knowledge source depends upon the type of lexical ambiguity. 87.9% of the ambiguous terms are correctly disambiguated using a combination of linguistic features and MeSH terms, 99% of abbreviations are disambiguated by combining all knowledge sources, while 97.2% of ambiguous gene names are disambiguated using the MeSH terms alone. Analysis reveals that these differences are caused by the nature of each ambiguity type. These results should be taken into account when deciding which information to use for WSD and the level of performance that can be expected.

Disambiguation of ambiguous biomedical terms using examples generated from the UMLS Metathesaurus.

Researchers have access to a vast amount of information stored in textual documents and there is a pressing need for the development of automated methods to enable and improve access to this resource. Lexical ambiguity, the phenomena in which a word or phrase has more than one possible meaning, presents a significant obstacle to automated text processing. Word Sense Disambiguation (WSD) is a technology that resolves these ambiguities automatically and is an important stage in text understanding. The most accurate approaches to WSD rely on manually labeled examples but this is usually not available and is prohibitively expensive to create. This paper offers a solution to that problem by using information in the UMLS Metathesaurus to automatically generate labeled examples. Two approaches are presented. The first is an extension of existing work (Liu et al., 2002 [1]) and the second a novel approach that exploits information in the UMLS that has not been used for this purpose. The automatically generated examples are evaluated by comparing them against the manually labeled ones in the NLM-WSD data set and are found to outperform the baseline. The examples generated using the novel approach produce an improvement in WSD performance when combined with manually labeled examples.

Building a semantically annotated corpus of clinical texts.

In this paper, we describe the construction of a semantically annotated corpus of clinical texts for use in the development and evaluation of systems for automatically extracting clinically significant information from the textual component of patient records. The paper details the sampling of textual material from a collection of 20,000 cancer patient records, the development of a semantic annotation scheme, the annotation methodology, the distribution of annotations in the final corpus, and the use of the corpus for development of an adaptive information extraction system. The resulting corpus is the most richly semantically annotated resource for clinical text processing built to date, whose value has been demonstrated through its use in developing an effective information extraction system. The detailed presentation of our corpus construction and annotation methodology will be of value to others seeking to build high-quality semantically annotated corpora in biomedical domains.

Associations of polymorphism within the GHSR gene with growth traits in Nanyang cattle.

GH secretagogue receptor (ghrelin receptor, GHSR) is known to be involved in the control of GH release by mediating the strong stimulatory effect of the endogenous ligand, ghrelin, on GH secretion. Associations between the GHSR gene polymorphism and the growth traits were revealed in Nanyang cattle. The mutations at nt456(G > A) and nt667(C > T) were complete linkage and located in exon 1 of the coding region of the GHSR gene. Least squares analysis revealed a significant statistical effect (P < 0.05) of the GHSR gene different genotypes on body weight and average daily gain at 6 months of age in Nanyang cattle. Individuals with GHSR-MM genotype showed higher body weight and average daily gain than individuals with GHSR-MN genotype.