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Displacement damage effects in backside illuminated CMOS image sensors (BSI CISs) are investigated. Several BSI CISs with distinct epitaxial layer thicknesses are irradiated by several protons and neutrons to study the influence of technology parameters and radiation parameters on the radiation response of these imagers. A significant degradation in quantum efficiency (QE) is observed for thick epitaxial layer at the absorbed dose of 1230 TeV/g. Dark-current damage factor of 0.141 e⁻·s⁻¹·μ m⁻³·(TeV/g)⁻¹ is determined in BSI CIS. The influence of particle types, particle energy, and radiation fluence on dark current distributions is presented at the same displacement damage dose (DDD). Dark current random telegraph signal (DC-RTS) is reported and the variation in epitaxial layer thickness has no influence on DC-RTS behavior. This work highlights the relationship between key parameters and DDD: the limiting factors of the imager performance are single pixel [hot pixel and random telegraph signal (RTS) pixel] at a low DDD range, mean dark current and single pixel at a medium DDD range, and mean dark current in the high DDD case, respectively.

STAT3 is constitutively activated in multiple malignant tumors. Compared with regular estrogen receptor (ER)-positive breast cancers, the patients with tamoxifen-resistant breast cancers often exhibit higher levels of STAT3 phosphorylation. Narciclasine (Nar) possesses strong inhibiting effects against a variety of cancer cells; however, the underlying antitumor target(s)/mechanism(s) remains barely understood. In this study, we successfully identified the STAT3 was the direct target of Nar through the combination strategies of connectivity map and drug affinity responsive target stability. In MCF7 cells, Nar could suppress phosphorylation, activation, dimerization, and nuclear translocation of STAT3 by directly binding with the STAT3 SH2 domain. In addition, Nar could specifically degrade total STAT3 via the proteasome pathway in MCF-7/TR (tamoxifen-resistant MCF-7) cells. This distinct mechanism of Nar-targeting STAT3 was mainly attributed to the various levels of reactive oxygen species in regular and tamoxifen-resistant ER-positive breast cancer cells. Meanwhile, Nar-loaded nanoparticles could markedly decrease the protein levels of STAT3 in tumors, resulting in significantly increased MCF-7/TR xenograft tumor regression without obvious toxicity. Our findings successfully highlight the STAT3 as the direct therapeutic target of Nar in ER-positive breast cancer cells, especially, Nar leaded STAT3 degradation as a promising strategy for the tamoxifen-resistant breast cancer treatment., Graphical abstract, Nar-targeting STAT3 had distinct mechanisms in MCF-7 cells and MCF-7/TR cells. Nar directly bound to STAT3 protein and suppress STAT3 phosphorylation and activation in MCF-7 cells, but in MCF-7/TR cells could specifically promote total STAT3 degradation via a ROS-dependent proteasome pathway.

Robustness of GaN power diodes must consider the device ruggedness against out of safe-operating-area events, especially the transient spikes in voltage and current. In this work, intriguing resistive energy dissipating capability against transients was realized in the AlGaN/GaN Schottky barrier diodes (SBDs), delivering a kilowatt-level sustaining power, which alternatively overcomes the technological bottleneck of non-avalanche behavior in AlGaN/GaN SBDs. In particular, the GaN SBDs achieved a high dissipating energy of 1.5 mJ and a low transient voltage of 445 V, thanks to the partially metallized anode design. Together with rugged repetitive sustaining capability and high-temperature stability, the GaN SBDs with this advanced technical design present enormous potential in high-power, and high-reliability applications.

OBJECTIVE: This study was undertaken to investigate the COVID-19 vaccine uptake rate and possible postvaccination effects in adults with epilepsy. METHODS: We invited adults with epilepsy attending three centers in China from July 24 to August 31, 2021 to participate in this study. We also asked age- and sex-matched controls among people attending for other chronic neuropsychiatric conditions and healthy controls accompanying people with illness attending the hospitals to participate. We excluded people who, under the national guidelines, had evident contradictions to vaccination. Participants were interviewed face-to-face using questionnaires. Vaccine uptake and postvaccine adverse events among the people with epilepsy were compared with those with neuropsychiatric conditions and controls. We also compared the willingness and reasons for hesitancy among unvaccinated participants. RESULTS: We enrolled 981 people, of whom 491 had epilepsy, 217 had other neuropsychiatric conditions, and 273 were controls. Forty-two percent of those with epilepsy had had the first dose of a vaccine, compared with 93% of controls and 84% of the people with neuropsychiatric conditions (p

Space non-cooperative object visual tracking (SNCOVT) with monocular or binocular camera is one of the most significant tasks for on-orbit services. In recent years, most of vision-based trackers utilized in spacecraft are based on hand-crafted features (e.g. point, edge and color), which are vulnerable to the dynamic and harsh environment in space. Although various correlation filter and deep learning based generic object trackers with high performance have been proposed in tracking community. To verify the availability of those generic trackers in aerospace domain, we present a moderate and simulated space non-cooperative object visual tracking dataset, which contains 60 binocular video sequences with manual annotations, 54742 frames in total. Meanwhile, a new evaluation protocol that is more appropriate to the practical scenario and some novel metrics are adopted into our SNCOVT evaluation toolkit. We implement extensive monocular and binocular experiments with state-of-the-art trackers on our dataset. Finally, we make a comprehensive analysis to those algorithms and experiment results for future SNCOVT research.

This letter presents a novel ultraviolet photon counting system based on a SiC SPAD array. The detector is made of 4H-SiC with a fairly low dark current in pA level and the array size is $1\times 128$ . In order to reduce the influence of dark count on image quality, this letter proposes an adaptive sampling readout circuit system, which can automatically adjust the SPAD hold-off time according to the photon density of the applications. Aiming at the nonuniform breakdown voltage of SPADs in a linear array, an adjustable bias voltage circuit is adopted to realize the accurate adjustment of pixel SPAD’s bias voltage. The ROIC is taped out in TSMC 0.18 $\mu {\mathrm{ m}}$ standard CMOS process and connected to the SPAD array by a gold bonding package. Based on the self-developed imaging system, UV photon counting imaging and deep violet- visible light fusion imaging are realized for the first time.

Girls and women constitute nearly 50% of all epilepsy cases. Apart from the disease symptoms, epilepsy and antiseizure medications (ASMs) may also affect the reproductive function, pregnancy and even the health of their offspring. Therefore, it is very important to identify and summarize the problems and risks for women with epilepsy (WWE) of childbearing age, and offer internationally recognized methods through multidisciplinary collaboration. In this review, we summarize the reproduction-related problems with WWE and propose multidisciplinary management by epileptologists, gynecologists and obstetricians, as well as other experts, from preconception to delivery. Large, multicenter registries are needed to advance our knowledge on new ASMs and their effects on WWE and their offspring.

In this letter, we achieved significantly enhanced avalanche ruggedness and surge current capability in GaN junction barrier Schottky (JBS) diode for highly reliable power operation. Based on the selective Mg-ion implantation technology, the GaN JBS diode obtains superior electrostatic performances, including 830-V breakdown voltage, 150-mΩ specific on -state resistance, and 0.5-V turning on voltage. Meanwhile, zero reverse recovery behaviors are observed even under extreme switching conditions of 600 V/10 A. During the reliability evaluation in the inductive load circuits, crucial avalanche capability with avalanche breakdown voltage over 965 V, avalanche energy up to 57.8 mJ, and more than 10 000 repetitive avalanche breakdown events are demonstrated. Together with the surge current tolerance up to 65 A and surge energy of 6.0 J, a large safe-operation-area under both forward and reverse inductive spikes is realized for the GaN-based rectifier.

Background: Loeys-Dietz syndrome (LDS) is an inherited disorder predisposing individuals to thoracic aortic aneurysm and dissection. Currently, there are no medical treatments except surgical resection. Although the genetic basis of LDS is well-understood, molecular mechanisms underlying the disease remain elusive, impeding the development of a therapeutic strategy. In addition, aortic smooth muscle cells (SMCs) have heterogenous embryonic origins, depending on their spatial location, and lineage-specific effects of pathogenic variants on SMC function, likely causing regionally constrained LDS manifestations, have been unexplored. Methods: We identified an LDS family with a dominant pathogenic variant in the TGFBR1 gene ( TGFBR1 A230T ) causing aortic root aneurysm and dissection. To accurately model the molecular defects caused by this mutation, we used human induced pluripotent stem cells from a subject with normal aorta to generate human induced pluripotent stem cells carrying TGFBR1 A230T , and corrected the mutation in patient-derived human induced pluripotent stem cells using CRISPR-Cas9 gene editing. After their lineage-specific SMC differentiation through cardiovascular progenitor cell (CPC) and neural crest stem cell lineages, we used conventional molecular techniques and single-cell RNA sequencing to characterize the molecular defects. The resulting data led to subsequent molecular and functional rescue experiments using activin A and rapamycin. Results: Our results indicate the TGFBR1 A230T mutation impairs contractile transcript and protein levels, and function in CPC-SMC, but not in neural crest stem cell–SMC. Single-cell RNA sequencing results implicate defective differentiation even in TGFBR1 A230T/+ CPC-SMC including disruption of SMC contraction and extracellular matrix formation. Comparison of patient-derived and mutation-corrected cells supported the contractile phenotype observed in the mutant CPC-SMC. TGFBR1 A230T selectively disrupted SMAD3 (SMAD family member 3) and AKT (AKT serine/threonine kinase) activation in CPC-SMC, and led to increased cell proliferation. Consistently, single-cell RNA sequencing revealed molecular similarities between a loss-of-function SMAD3 mutation ( SMAD3 c.652delA/+ ) and TGFBR1 A230T/+ . Last, combination treatment with activin A and rapamycin during or after SMC differentiation significantly improved the mutant CPC-SMC contractile gene expression and function, and rescued the mechanical properties of mutant CPC-SMC tissue constructs. Conclusions: This study reveals that a pathogenic TGFBR1 variant causes lineage-specific SMC defects informing the etiology of LDS-associated aortic root aneurysm. As a potential pharmacological strategy, our results highlight a combination treatment with activin A and rapamycin that can rescue the SMC defects caused by the variant.

Aims Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin–ASK1 pathway, not the classical calcineurin–nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. Methods and results Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. Conclusion Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.

BACKGROUND: Smoking is a risk factor for many diseases. PURPOSE: This study explored the relationship between current or past smoking and pressure injury (PI) risk through a systematic review and meta-analysis. METHODS: The databases PubMed, Web of Science, and China National Knowledge Infrastructure were searched for the years between 2001 and 2020. Quality of evidence was estimated by the Newcastle-Ottawa Scale. The random effects model was applied to assess the odds ratios (OR) and 95% confidence intervals (CI); pooled adjusted OR and 95% CI, subgroup analysis, publication bias, sensitivity analyses, and meta-regression analysis were performed. RESULTS: Fifteen (15) studies (12 retrospective and 3 prospective) comprising data on 11 304 patients were eligible for inclusion in the review. The meta-analysis demonstrated that smoking increased the risk of PI (OR = 1.498; 95% CI, 1.058-2.122), and the pooled adjusted OR (1.969) and 95% CI (1.406-2.757) confirmed this finding. Publication bias was not detected by funnel plot, Begg’s test (P = .322), or Egger’s test (P = .666). Subgroup analyses yielded the same observations in both retrospective (OR = 1.607; 95% CI, 1.043-2.475) and prospective (OR = 1.218; 95% CI, 0.735-2.017) studies. The results were consistent across sensitivity analyses (OR = 1.07; 95% CI, 1.043-2.475). Relevant heterogeneity moderators were not identified by meta-regression analysis with PI incidence (P = .466), years of patient data included (P = .637), mean patient age (P = .650), and diabetes mellitus diagnosis (P = .509). CONCLUSION: This study found that individuals who are current or formers smokers have an almost 1.5 times higher risk of PI development than do those who do not smoke.

Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as the hippocampus. However, it remains unclear how the functional features of white matter are altered in TLE. In the current study, resting-state functional magnetic resonance imaging (fMRI) was performed on 71 left TLE (LTLE) patients, 79 right TLE (RTLE) patients and 47 healthy controls (HC). Clustering analysis was used to identify fourteen white matter networks (WMN). The functional connectivity (FC) was calculated among WMNs and between WMNs and grey matter. Furthermore, the FC laterality of hemispheric WMNs was assessed. First, both patient groups showed decreased FCs among WMNs. Specifically, cerebellar white matter illustrated decreased FCs with the cerebral superficial WMNs, implying a dysfunctional interaction between the cerebellum and the cerebral cortex in TLE. Second, the FCs between WMNs and the ipsilateral hippocampus (grey matter foci) were also reduced in patient groups, which may suggest insufficient functional integration in unilateral TLE. Interestingly, RTLE showed more severe abnormalities of white matter FCs, including links to the bilateral hippocampi and temporal white matter, than LTLE. Taken together, these findings provide functional evidence of white matter abnormalities, extending the understanding of the pathological mechanism of white matter impairments in unilateral TLE.

Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration biopsy as initial sampling approaches of mediastinal lymph nodes for lung cancer staging. However, the small sample volume might restrict the diagnostic utility of needle aspiration in certain mediastinal diseases. We have recently shown that transbronchial mediastinal cryobiopsy, which is capable of providing larger amounts of intact tissue, improves diagnostic yield in rare tumors and benign diseases compared to EBUS-TBNA. Here, we present a case of mediastinal nodular lymphocyte predominant Hodgkin lymphoma successfully diagnosed by endoscopic transesophageal cryobiopsy.

Background Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient. Case presentation A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient’s symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p p Conclusions A combination of structural MRI, functional MRI, and brain PET-CT has higher diagnostic and prognostic value than conventional MRI in patients with suspected anti-Tr/DNER encephalitis.

The coronavirus disease 2019 (COVID‐19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID‐19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well‐being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID‐19 pandemic, including access to health services and impact on mental health, including the 6‐item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new‐onset seizures or an exacerbation of seizures in the context of COVID‐19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well‐being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

OBJECTIVES Anterior communicating artery (ACoA) aneurysm is one of the most common intracranial aneurysms, and it is also the aneurysm with the highest rupture rate. With the improvement of endoscopic techniques, it is possible to use an endoscopic endonasal approach (EEA) to clip ACoA aneurysms. For further analysis of the EEA for clipping ACoA aneurysms, we used cadaver heads and three-dimensional (3D)-printed models to finish the anatomical study, and we finally selected 1 clinical case to complete the clipping through the EEA. MATERIALS AND METHODS We first collected 3 cadaver heads to simulate the EEA. Then, the imaging data of 29 real cases of ACoA aneurysm were collected, and the model of an aneurysm was prepared by 3D printing technology; then, the EEA was used to simulate the clipping of the aneurysm model. Finally, a clinical case with 2 ACoA aneurysms was selected to adopt the EEA for clipping. RESULTS Both the cadaver head and 3D-printed aneurysm model could simulate aneurysm clipping with the EEA. The clinical case of the selected ACoA aneurysm can successfully complete the clipping through the EEA. CONCLUSIONS 3D-printed models are a good method to study the anatomical characteristics of a surgical approach. For specially selected ACoA aneurysms, the EEA is relatively simple method that can be used to clip the aneurysm successfully. The EEA for clipping ACoA aneurysms is a useful complement to the current traditional craniotomy approaches and endovascular embolization.

Objective To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. Methods Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long-term outcomes. The patients were followed up for 15-53 months. We performed a cost-of-illness study and analyzed the cost contributors with a generalized linear model. Results In total, the cases of 154 TBM patients (95 males, 59 females, aged 14-82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822-67,285), with a mean direct medical cost of USD 8,901 (range 1,189-67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845-52,921) and USD 1,967 (range 0-60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33-3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6-152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0-2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long-term outcome. Conclusions Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

Background To investigate the association between impairment of consciousness and risk of death in people with COVID‐19. Methods In this multicentre retrospective study, we enrolled people with confirmed COVID‐19 from 44 hospitals in Wuhan and Sichuan, China, between 18 January and 30 March 2020. We extracted demographics, clinical, laboratory data and consciousness level (as measured by the Glasgow Coma Scale (GCS) score) from medical records. We used Cox proportional hazards regression, structural equation modelling and survival time analysis to compare people with different progressions of impaired consciousness. Results We enrolled 1,143 people (average age 51.3 ± standard deviation 17.1‐year‐old; 50.3% males), of whom 76 died. Increased mortality risk was identified in people with GCS score between 9 and 14 (hazard ratio (HR) 46.76, p 2 days, p = .028) had shorter survival times. Conclusion Altered consciousness and its progression had a direct link with death in COVID‐19. Interactions with age, oxygen saturation level and pH suggest possible pathophysiology. Further work to confirm these findings explore prevention strategies and interventions to decrease mortality is warranted.

Cross-lingual Open Domain Question Answering (Cross-lingual Open-QA) has been developed since it was proposed in the mid-1990s. It can be divided into two mainstream tasks according to the training corpus used in the answer extraction stage. One is that both of the training and testing data are in the target language. The other is that the training data is in the source language, and the testing data is in the target language. For a long time, the former has been studied mainly through translation based approaches. Until 2019, the latter appeared and non-translation based approaches become available thanks to multilingual BERT model. Therefore, the two tasks have been discussed separately, which encourages our work on whether it is possible to achieve these two tasks simultaneously without any additional transformation. It is observed that the existence of the multilingual BERT model makes a solution to establish a unified framework. However, there are two problems with using the multilingual BERT model directly. The one is in the document retrieval stage, directly working multilingual pretraining model for similarity calculation will result in insufficient retrieval accuracy. The other is in the answer extraction stage, the answers will involve different levels of abstraction related to retrieved documents, which needs deep exploration. This paper puts forward a multi-granularity semantic space learning based approach for cross-lingual Open-QA. It consists of the Match-Retrieval module and the Multi-granularity-Extraction module. The matching network in the retrieval module makes heuristic adjustment and expansion on the learned features to improve the retrieval quality. In the answer extraction module, the reuse of deep semantic features is realized at the network structure level through cross-layer concatenation, and it enables us to learn multi-granularity semantic space. Experimental results on two public cross-lingual Open-QA datasets show the superiority of our proposed approach over the state-of-the-art methods.

Driving behavior plays a key role in the interaction between vehicle and driver in transportation systems. Some applications about driving behavior in Advanced Driver Assistance Systems (ADAS) improve driving safety significantly. This paper introduces the driving context and models driving behavior in a combination of cognitive perspective and data-driven perspective. First, we use a cognitive fusion method by adding a delay time module to fuse the environmental information and inside information. To better capture the driving context relationship between outside and inside features, we transfer the behavior prediction task to the sequence labeling task by introducing the visual inertia hypothesis. We propose the Predictive-Bi-LSTM-CRF algorithm which used the Bidirectional Long-Short Term Memory Networks (Bi-LSTM) and Conditional Random Field (CRF) as the loss layer to model the driving behavior. Besides, we define a new comprehensive evaluation metric for the prediction task considering F1-score and the prediction time before maneuver together. Our experiment results achieve the state of art performance on the Brain4Cars dataset and demonstrate the applicability of our theory.

Summary Background and aims Malnutrition is prevalent among individuals with acute ischaemic stroke (AIS) and may worsen clinical outcomes. There is no consensus on the best tool for nutritional screening in this population. The present study compared four screening tools and one diagnostic tool in terms of their prognostic significance in predicting short-term and long-term outcomes in AIS patients. Methods We included patients admitted to five major hospitals in Wenzhou and diagnosed with a primary diagnosis of AIS from October 1 to December 31, 2018. The Controlling Nutritional Status (CONUT) score, the Geriatric Nutritional Risk Index (GNRI), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening Tool 2002 (NRS-2002) and the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM) were assessed at admission. The clinical outcomes were evaluated by the modified Rankin Scale (mRS) and mortality at 3 months and 12 months after discharge. Results Five hundred and ninety-three patients were included in our prospective study. The mean age was 67.3 ± 12.0 years. Based on the mRS score, 125 patients exhibited poor functional recovery (an mRS ≥3) at 3 months after discharge. Seventeen patients died during the 3-month follow-up period, and the other 25 did not survive 12 months. Multivariate binary logistic regression revealed that inadequate nutritional status at admission, as determined by the CONUT, GNRI, MUST, NRS-2002 and ESPEN-DCM, were independently associated with poor outcomes in AIS patients 3 months after discharge. Both MUST ≥2 and NRS-2002 ≥ 3 showed significant associations with poor outcomes at 12-month post-discharge. Further analysis with the receiver operator characteristic (ROC) curve showed similar results, where all the tools predicted the poor outcomes at 3 months while only the NRS-2002 and MUST scores were significantly associated with the mRS at 12 months post-discharge. Moreover, the area under the curve (AUC) of MUST and NRS-2002 were significantly larger than those for the other tools. The optimal cut-off values of the MUST and NRS-2002 to predict poor outcomes were scores of ≥2 and ≥ 3 points, respectively. Conclusions Our data supported a deleterious effect of inadequate nutrition, as evidenced by the nutrition screening tools or ESPEN-DCM, on clinical outcomes during and beyond the acute phase of AIS. We recommended the use of the MUST and NRS-2002 in guiding nutritional support in AIS patients, as they have higher predictive power and can predict both short-term and long-term outcomes.

This study explores the relationship between internet use during non-working hours and marriage well-being and channels through which internet use operates on marital satisfaction. With a 2-year nationwide micro panel data, our main results reveal negative effects of internet experience on overall marriage satisfaction, satisfaction towards spousal contribution in housework and marital stability. Empirically, we adopt linear as well as nonlinear models, use propensity score matching approach, and implement parametric as well as semiparametric analyses. Evidence further show that active internet users can use the internet to chat with strangers and easily access potential romantic partners. Its social function leads to a substantial reduction in search cost and raised reservation value of partner contribute to a lower level of spousal satisfaction. Moreover, it was also found that internet use partially weakens traditional Chinese views of family gender roles. And gender ideology changes through internet’s educational function has increased spousal dissatisfaction in China. In addition, it is found that internet use crowds out time spent on housework as well as other investment in current marriage, and hence increases spousal dissatisfaction.

In this study, we propose a technique for diagnosing both type 1 and type 2 diabetes in a quick, noninvasive way by using equipment that is easy to transport. Diabetes mellitus is a chronic disease that affects public health globally. Although diabetes mellitus can be accurately diagnosed using conventional methods, these methods require the collection of data in a clinical setting and are unlikely to be feasible in areas with few medical resources. This technique combines an analysis of fundus photography of the physical and physiological features of the patient, namely, the tongue and the pulse, which are used in Traditional Chinese Medicine. A random forest algorithm was used to analyze the data, and the accuracy, precision, recall, and F1 scores for the correct classification of diabetes were 0.85, 0.89, 0.67, and 0.76, respectively. The proposed technique for diabetes diagnosis offers a new approach to the diagnosis of diabetes, in that it may be convenient in regions that lack medical resources, where the early detection of diabetes is difficult to achieve.

Background Ezrin-radixin-moesin (ERM) have been explored in many cancer processes. Moesin, as its component, has also been found to play an important role in the prognosis of cancer patients, tumor metastasis, drug resistance, and others. Especially in regulating the immunity, but most results came from direct studies on immune cells, there is no clear conclusion on whether moesin has similar effects in tumor cells. And moesin has certain research results in many cancers in other aspects, but there are few about moesin in lung adenocarcinoma (LUAD). Methods We detect the expression of moesin in 82 LUAD and matched normal tissue samples by immunohistochemistry. Besides, for the pathological feature, we did a detailed statistical analysis. And with the help of various databases, we have done in-depth exploration of moesin’s ability to enhance the extent of immune lymphocyte infiltration. Results Moesin is a poor expression in lung cancer tissues than the corresponding normal samples. And this phenomenon had a strongly associated with the prognosis and TNM stage of these LUAD patients. Moesin can enhance the infiltration of multiple immune lymphocytes in lung cancer. And this may be related to the interaction between moesin and various inflammatory molecules. Conclusions Moesin is a newly index for the prognosis of LUAD and improves the prognosis of LUAD patients by regulating a variety of inflammation-related molecules to enhance immune lymphocytes infiltration.

BACKGROUND Malignant pheochromocytoma with cerebral and skull metastasis is a very rare disease. Combining our case with 16 previously reported cases identified from a PubMed search, an analysis of 17 cases of malignant cerebral pheochromocytoma was conducted. This literature review aimed to provide information on clinical manifestations, radiographic and histopathological features, and treatment strategies of this condition. CASE SUMMARY A 60-year-old man was admitted with a progressive headache and enlarging scalp mass lasting for 3 mo. Radiographic images revealed a left temporal biconvex-shaped epidural mass and multiple lytic lesions. The patient underwent a left temporal craniotomy for resection of the temporal tumor. Histopathological analysis led to identification of the mass as malignant pheochromocytoma. The patient’s symptoms were alleviated at the postoperative 3-mo clinical follow-up. However, metastatic pheochromocytoma lesions were found on the right 6th rib and the 6th to 9th thoracic vertebrae on a 1-year clinical follow-up computed tomography scan. CONCLUSION Magnetic resonance spectroscopy and histopathological examination are necessary to make an accurate differential diagnosis between malignant cerebral pheochromocytoma and meningioma. Surgery is regarded as the first choice of treatment.

Objective Focal cortical dysplasia (FCD) appears to be strongly associated with intractable epilepsy. Although patients with FCD are candidates for epilepsy surgery, gray matter structural abnormalities can extend beyond the primary lesion, which makes surgery less effective. The objective of this study was to evaluate functional connectivity patterns in epilepsy associated with FCD to explore the underlying pathological mechanism of this disorder. Methods A total of 34 patients (14 men) with FCD and epilepsy [mean age ± standard deviation (SD), 24.5 ± 9.8 years; range, 8–47 years] and 34 age-matched healthy controls (14 men, 24.6 ± 9.7 years) underwent functional magnetic resonance imaging. Independent component analysis (ICA), seed-based functional connectivity, and graph theory were applied to analyze functional connectivity patterns in the brain. Results Patients showed more connections among dorsal attention network, anterior default mode network, and sensorimotor brain networks than healthy controls based on ICA. Analysis of connectivity between regions of interest (ROIs) showed greater functional connectivity in patients between frontal and temporal regions, but lower connectivity between the cerebellum and frontal regions. The normalized characteristic path length was significantly higher in group of patients, but the two groups showed no significant differences in global or regional efficiency, clustering coefficient or characteristic path length. Conclusions Analysis of ICA-derived and ROI-based functional connectivity suggests that disrupted interactions and dysconnectivity in large-scale neural networks and frontotemporal-cerebellar regions may contribute to underlying pathological mechanisms in FCD-related epilepsy.

As mainstream optical imaging electronic devices, image sensors are widely used in space missions under complex radiation environments. This study investigated the effects 60 and 10 MeV proton irra...

Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China. In this study, we investigated the protective effect and underlying mechanisms GXB in type II diabetes with acute myocardial ischemia (T2DM-AMI) rats. We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells (EPCs) apoptosisviaactivating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling. Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type II diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI). Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination. The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry. Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis. The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose, muscular enzymes, and blood lipids, and reduced oxidative stress. Furthermore, EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K, Akt, and eNOS compared to the controls. Conversely, T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis, combined with increased mRNA and protein levels of PI3K, Akt, and eNOS compared to those of untreated T2DM-AMI rats. Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.

Background Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1. Case presentation In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband’s mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes. Conclusions Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.

The coronavirus disease 2019 is still continuing and may affect stroke emergency care. We aim to investigate the impact of pandemic on stroke treatment in tertiary stroke centers in western China, and to quantitatively evaluate the worldwide influence with a meta-analysis. The original part was conducted in three tertiary stroke centers in Sichuan province. We compared emergency visits and efficiency of stroke treatment pre-, early, peak and late pandemic. Single-center analysis was further conducted in the largest local hospital and one hospital located close to the epicenter respectively. Relevant studies were searched in PubMed, Ovid Embase and Cochrane Library for English publications from December 2019 to July 2020 for systematic review. Fixed-and random-effect meta-analysis was performed to calculate the overall rates. Totally current original study showed fewer time of hospital admission and significantly higher rates of mechanical thrombectomy during the early and peak epidemic periods, compared with pre-epidemic time. The largest local hospital had significantly higher mechanical thrombectomy rates during the whole crisis and less daily admission during early and peak epidemic periods. The hospital located close to the epicenter presented higher proportions of intravenous thrombolysis since outbreak, and more favorable outcomes after reperfusion therapies than later (all P values

Electroreduction of CO2 to produce chemicals and fuels is recognized as a promising technology to reduce greenhouse gas emissions, particularly by using renewable energy. In doing so, it is possible to achieve net-zero or negative emissions. A catalyst, however, is needed to facilitate the electroreduction of CO2 under ambient conditions. Recently, metal–organic frameworks (MOFs) and their derivatives have gained growing attention in materials research due largely to their high surface area, unique local chemical structures, and extraordinary properties. MOF-based electrocatalysts are of particular interest for CO2 conversion with high activity, selectivity, and stability. The intent of this article is to provide an overview of the structures and performances of these electrocatalysts, as well as the perspectives and future trends in this field.

Organic-inorganic hybrid perovskite has been verified as a suitable semiconductor for hot carrier solar cells via transient absorption spectroscopy. Recently, an internally photoemitted hot carrier (IPHC) solar cell with a novel and innovative structure based on organic-inorganic hybrid perovskite has been achieved. This is a breakthrough in hot carrier study based on perovskite material. To further improve the performance of this newly developed hot electron collection device, a simple and efficient method of adding lithium fluoride (LiF) surface modification layer was applied onto the outmost perovskite layer that benefits both reduction of the trap states and formation of interface dipoles. The IPHC device with LiF modification layer shows a remarkable increase of the short-circuit current density with 20.31% increment. This successful interface engineering proposes a new guideline for further optimizing the performance IPHC and also traditional solar cells based on perovskite.

Covering: up to 2020 Treatment resistance and drug-induced refractory malignancies pose significant challenges for current chemotherapy drugs. There have been increasing research efforts aimed at developing novel chemotherapeutics, especially from natural products and related derivatives. Natural cytotoxic peptides, an emerging source of chemotherapeutics, have exhibited the advantage of overcoming drug resistance and displayed broad-spectrum antitumor activities in the clinic. This highlight examines the increasingly popular cytotoxic peptides from isolated natural products. In-depth review of several peptides provides examples for how this novel strategy can lead to the improved anti-tumor effects. The mechanisms and current application of representative natural cytotoxic peptides (NCPs) have also been discussed, with a particular focus on future directions for interdisciplinary research.

Rationale: This case report presents the diagnosis and etiology of hilar/mediastinal lymphadenopathy in a male patient. Patient concerns: A 49-year-old man presented with fever and dyspnea after physical exertion. Diagnosis: The patient was diagnosed with melioidosis by cultivation of lymph node aspirate on blood agar using the VITEK 2 compact system. Interventions: The patient was treated with ceftazidime intravenously, combined with trimethoprim/sulfamethoxazole orally for 1 week. Once the patient was discharged, he began a 12-week course of trimethoprim/sulfamethoxazole. Outcomes: The patient recovered after treatment with ceftazidime and trimethoprim/sulfamethoxazole. Conclusions: Melioidosis is an infectious disease that mainly occurs in tropical regions. It can cause severe sepsis and pneumonia, and the infection in some patients may become chronic. Endobronchial ultrasound-transbronchial needle aspiration is a useful technique in the diagnosis of patients with hilar/mediastinal lymphadenopathy.

As the major feature of pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma poses a significant obstacle for treatment. Recent studies revealed that connective tissue growth factor (CTGF) aggravates the fibrotic environment and drives cancer initiation and progression, thus suggesting CTGF as a novel target for PDAC treatment.

CMOS image sensors were irradiated by protons of 50 and 70 MeV and the dark current random telegraph signal (RTS) is investigated. After exposure to the protons, the experimental results provide ne...

The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

Ibrutinib‐based combination therapy with high‐dose methotrexate (HD‐MTX) has recently shown clinical activity against relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL). Herein, we report our real‐world experience of treating 11 newly diagnosed PCNSL patients with the ibrutinib/MTX combination. HD‐MTX was given at 3.5 g/m2 every 2‐week for eight doses. Ibrutinib was held upon HD‐MTX infusion until clearance and was administered daily post‐induction until disease progression, intolerable toxicity, or death. Nine out of 11 patients completed the induction phase and received ibrutinib as maintenance therapy. An objective response rate (ORR) of 82% (9/11) was observed including complete response (64%) and partial response (18%). The median progression‐free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The ibrutinib/MTX combination was well tolerated in these treatment‐naïve PCNSL patients with an acceptable safety profile. Moreover, the longitudinal analysis of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) revealed that CSF ctDNA detection was closely associated with tumor response, and sustained tumor responses correlated with the clearance of ctDNA from the CSF. In sum, our data not only demonstrated the clinical benefit of the ibrutinib and HD‐MTX combination regimen in treating newly diagnosed PCNSL patients in a real‐world setting, but also highlighted the significance of liquid biopsy including CSF ctDNA in tracing tumor burden and assessing treatment response., Our real‐world experience demonstrated the clinical benefit of the ibrutinib‐based combination therapy in treating newly diagnosed PCNSL patients, in complement to the activity of the drug combination reported for relapse/refractory PCNSL. Our data also underscored the clinical significance of liquid biopsy including cerebrospinal fluid ctDNA in tracing tumor burden and evaluating treatment response.

Urinary metabolomics is a useful non-invasive tool for large-scale screening of disease-related metabolites. However, no comprehensive urinary metabolomic analysis of vitiligo is presently available. To investigate the urine metabolic pattern of vitiligo patients, we conducted a combined cross-sectional and prospective self-control cohort study and an untargeted urinary metabolomic analysis. In the cross-sectional study, 295 vitiligo patients and 192 age‐ and sex‐matched controls were enrolled, and 71 differential metabolites between two groups were identified. Pathway enrichment analysis revealed that drug metabolism-cytochrome P450, biopterin metabolism, vitamin B9 (folate) metabolism, selenoamino acid metabolism, and methionine and cysteine metabolism showed significant enrichment in vitiligo patients compared with the status in healthy controls. In the self-control cohort, 46 active vitiligo patients were recruited to analyse the urinary metabolic signatures after treatment. All of these patients were asked to undertake follow-up visits every 2 months three times after first consulting and the disease stage was evaluated compared with that at the last visit. Folate metabolism, linoleate metabolism, leukotriene metabolism, alkaloid biosynthesis, and tyrosine metabolism were predicted to be involved in vitiligo activity. Our study is the first attempt to reveal urinary metabolic signatures of vitiligo patients and provides new insights into the metabolic mechanisms of vitiligo.

BACKGROUND The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

To evaluate and compare the surgical outcomes and complications of the modified circumcision using disposable circumcision suture device (device group) and the conventional dorsal slit circumcision (conventional group) in children.A total of 284 patients were randomized to either device group or conventional group. All patients were preoperatively assessed and evaluated at 4 weeks after surgery. The perioperative data and postoperative outcomes were compared between the 2 groups.No statistical differences were observed in the average age and indications between the 2 groups preoperatively (P.05). Compared with the conventional group, patients in the device group were shorter mean operative time, less blood loss, lower intraoperative and postoperative pain score, faster incision healing time and a higher satisfaction rate of penile cosmetic appearance (P.01). Similarly, the incidences of complication were significantly lower in the device group than in the conventional group (4.3% vs 12.3%, P.05).The modified circumcision using disposable circumcision suture device is a simple, safe, faster, and effective procedure and may become the attractive alternative to the conventional technique for the children, with a relatively lower complication rate and better cosmetic results. With the improvement of disposable circumcision suture device, the modified circumcision using disposable circumcision suture device has the potential to be widely used in the world.

China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

It is traditionally believed that cerebral amyloid-beta (Aβ) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aβ. The role of peripherally produced Aβ in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aβ to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aβ in the blood, and caused AD phenotypes including Aβ plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aβ levels, and alleviated brain Aβ burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aβ plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aβ can decrease brain Aβ deposition and represents a novel therapeutic approach for AD.

Background Some authors state that above-normal surface electromyography (SEMG) levels during mandibular rest (MR) are a general sign of temporomandibular disorders (TMD). Objective The aim was to compare SEMG levels in the masseter and anterior temporalis areas during MR between patients with disc displacement (DD) and subjects identified as healthy. The hypothesis was that average SEMG levels would be higher in the patients during MR before and after repeated clenches with maximal effort. Methods Thirty-six healthy subjects, and 42 patients with DD, were included. SEMG levels were recorded bilaterally in the temporalis and masseter areas during MR before clenching and after repeated clenches with maximal effort. Multivariate analysis of variance (MANOVA) was used to compare the means of the log-transformed SEMG-values for the subject groups. Results The mean MR levels in the four areas before clenching ranged from -0.19 log (µV) to 1.20 log(µV) in healthy subjects and from -0.22 log(µV) to 0.96 log(µV) in patients. The mean MR levels in the four areas after repeated clenches ranged from -0.19 log (µV) to 1.04 log(µV) in healthy subjects and from -0.27 log(µV) to 0.93 log(µV) in patients. The MANOVA test showed no significant differences in the means for MR for the four areas between the groups at the 5% significance level. Conclusion The hypothesis that jaw muscle SEMG levels during MR are on average generally higher in TMD patients is not supported. A possible explanation for the previous findings is that activity in other muscles was mislabelled as jaw muscle activity.