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Abstract Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster vaccination using M1.2 elicited potent and broad nAbs against Wuhan-Hu-1 (D614G) and some Omicron subvariants. Strong spike-specific T cell responses against Wuhan-Hu-1 and Omicron subvariants, including JN.1, were also induced. Vaccination with M1.2 protected animals from Wuhan-Hu-1 and multiple Omicron subvariants challenges. Interestingly, protection against XBB.1.5 lung infection did not correlate with nAb levels. These results indicate that M1.2 generated a broadly protective immune response against antigenically distant Omicron subvariants, and spike-specific T cells probably contributed to the breadth of the protection.

Abstract Background Uterine arteriovenous malformation (UAVM) is a relatively rare but potentially life-threatening situations abnormal vascular connections between the uterine arterial and venous systems. Lack of recognized guidelines and clinic experience, there is a lot of clinic problems about diagnosis and treatment. By analyzing the clinical data of patients with pregnancy-related UAVM, we aim to confirm the safety of direct surgeries and the benefit of pretreatment (uterine artery embolization or medical therapy) before surgery, and to explore more optimal therapies for patients with pregnancy-related UAVM. Methods A total of 106 patients in Qilu Hospital of Shandong University from January 2011 to December 2021 diagnosed of pregnancy-related UAVM were involved in this study. Depending on whether preoperative intervention was performed, the patients were divided into direct surgery group and pretreatment group (uterine artery embolization or medical management). Clinical characteristics, operative related factors and prognosis were analyzed. Results The most common symptom of pregnancy-related UAVM was vaginal bleeding (82.5%), which could also be accompanied by abdominal pain. Pretreatments (uterine artery embolization or medical therapy) had no obvious benefit to the subsequent surgeries, but increased the hospital stay and hospital cost. Direct surgery group had satisfactory success rate and prognosis compared to pretreatment group. Conclusion For pregnancy-related UAVM, direct surgery has good effects and high safety with shorter hospital stays and less hospital cost. What is more, without uterine artery embolization and other medical therapy, patients could remain better fertility in future.

Abstract Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, $$n=42$$ n = 42 ) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke’s area during the processing of negative emotional language. Compared to HCs, people with SZ ( $$n=41$$ n = 41 ) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders.

Abstract Background The aim was to develop a personalized survival prediction deep learning model for cervical adenocarcinoma patients and process personalized survival prediction. Methods A total of 2501 cervical adenocarcinoma patients from the surveillance, epidemiology and end results database and 220 patients from Qilu hospital were enrolled in this study. We created our deep learning (DL) model to manipulate the data and evaluated its performance against four other competitive models. We tried to demonstrate a new grouping system oriented by survival outcomes and process personalized survival prediction by using our DL model. Results The DL model reached 0.878 c-index and 0.09 Brier score in the test set, which was better than the other four models. In the external test set, our model achieved a 0.80 c-index and 0.13 Brier score. Thus, we developed prognosis-oriented risk grouping for patients according to risk scores computed by our DL model. Notable differences among groupings were observed. In addition, a personalized survival prediction system based on our risk-scoring grouping was developed. Conclusions We developed a deep neural network model for cervical adenocarcinoma patients. The performance of this model proved to be superior to other models. The results of external validation supported the possibility that the model can be used in clinical work. Finally, our survival grouping and personalized prediction system provided more accurate prognostic information for patients than traditional FIGO stages.

Abstract The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.

Background: This study aimed to compare the severity of psychological impact, anxiety and depression between people from two developing countries, Iran and China, and to correlate mental health parameters with variables relating to the COVID-19 pandemic. Although China and Iran are developing countries based on the World Bank’s criteria, these two countries are different in access to resources and health care systems. We hypothesized that Iranians would show higher levels of depression, anxiety and stress as compared to Chinese. Methods: This study collected information related to the COVID-19 pandemic including physical health, precautionary measures and knowledge about the pandemic. We also used validated questionnaires such as the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21) to assess the mental health status. Results: There were a total of 1411 respondents (550 from Iran; 861 from China). The mean IES-R scores of respondents from both countries were above the cut-off for post-traumatic stress disorder (PTSD) symptoms. Iranians had significantly higher levels of anxiety and depression (p < 0.01). Significantly more Iranians believed COVID-19 was transmitted via contact, practised hand hygiene, were unsatisfied with health information and expressed less confidence in their doctors, but were less likely to wear a facemask (p < 0.001). Significantly more Iranians received health information related to COVID-19 via television while Chinese preferred the Internet (p < 0.001). Conclusions: This cross-country study found that Iranians had significantly higher levels of anxiety and depression as compared to Chinese. The difference in reported measures between respondents from Iran and China were due to differences in access to healthcare services and governments’ responses to the pandemic.

Objective: The differences between the physical and mental health of people living in a lower-middle-income country (LMIC) and upper-middle-income country (UMIC) during the COVID-19 pandemic was unknown. This study aimed to compare the levels of psychological impact and mental health between people from the Philippines (LMIC) and China (UMIC) and correlate mental health parameters with variables relating to physical symptoms and knowledge about COVID-19.Methods: The survey collected information on demographic data, physical symptoms, contact history, and knowledge about COVID-19. The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21).Findings: The study population included 849 participants from 71 cities in the Philippines and 861 participants from 159 cities in China. Filipino (LMIC) respondents reported significantly higher levels of depression, anxiety, and stress than Chinese (UMIC) during the COVID-19 (p < 0.01) while only Chinese respondents' IES-R scores were above the cut-off for PTSD symptoms. Filipino respondents were more likely to report physical symptoms resembling COVID-19 infection (p < 0.05), recent use of but with lower confidence on medical services (p < 0.01), recent direct and indirect contact with COVID (p < 0.01), concerns about family members contracting COVID-19 (p < 0.001), dissatisfaction with health information (p < 0.001). In contrast, Chinese respondents requested more health information about COVID-19. For the Philippines, student status, low confidence in doctors, dissatisfaction with health information, long daily duration spent on health information, worries about family members contracting COVID-19, ostracization, and unnecessary worries about COVID-19 were associated with adverse mental health. Physical symptoms and poor self-rated health were associated with adverse mental health in both countries (p < 0.05).Conclusion: The findings of this study suggest the need for widely available COVID-19 testing in MIC to alleviate the adverse mental health in people who present with symptoms. A health education and literacy campaign is required in the Philippines to enhance the satisfaction of health information.

In this manuscript, we have launched a study on the completely nonsymmetric freeform optical system with neither rotational symmetry nor planar symmetry. An off-axis three-mirror freeform optical system with nonsymmetric geometry is proposed and a direct design method is developed for the nonsymmetric freeform optical system. The design field points are sampled across the full FOV to control the imaging quality and object–image relationship. In this system, the center of the image plane is greatly away from the plane determined by the centers of the three mirrors. This nonsymmetric system with F/1.3, a focal length of 50 mm, and an 8° × 6° field of view can achieve imaging quality close to the diffraction limit. This work provides a feasible nonsymmetric system design idea for the optical community.

The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p

BackgroundThe physical and mental health of citizens living in a country that encouraged face masks (China) and discouraged face masks (Poland) during the initial stage of the COVID-19 pandemic remained unknown. We conducted a cross-country study to compare the psychological impact of the COVID-19 pandemic on Poles and Chinese. This study aimed to compare the levels of psychological impact of pandemic and levels of anxiety and depression between China and Poland.MethodsThe survey collected information on demographic data, physical symptoms, contact history, and precautionary measures. The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). The chi-squared test was used to analyze the differences in categorical variables between the two populations. Linear regression was used to calculate the bivariate associations between independents variables (e.g., physical symptoms and precautionary measures) and dependent variables (e.g., mental health outcomes).ResultsThis study included a total of 2,266 respondents from both countries (1,056 Poles and 1,210 Chinese). There were significantly less Polish respondents who wore face masks (Poles: 35.0%; Chinese: 96.8% p < 0.001). Significantly more Polish respondents reported physical symptoms resembling COVID-19 infection (p < 0.001), recent medical consultation (p < 0.01), recent COVID-19 testing (p < 0.001), and hospitalization (p < 0.01). Furthermore, Polish respondents had significantly higher levels of anxiety, depression and stress (p < 0.001) than Chinese. The mean IES-R scores of Poland and China were above the cut-off for post-traumatic stress disorder (PTSD) symptoms. Besides precautionary measures, unemployment, retirement, physical symptoms resembling COVID-19 infection, recent medical consultation or COVID-19 testing, and long daily duration of home confinement were risk factors for PTSD symptoms, anxiety, depression, or stress for Polish respondents.ConclusionUse of face masks at the community level may safeguard better physical and mental health during the COVID-19 pandemic. There is a need of health education with scientific information from Polish health authority on the proper use of face masks and reduce social stigma. This study was limited by the respondent sampling method that had compromised the representativeness of samples.

Abstract Quasi-phase matching (QPM) is a technique extensively utilized in nonlinear optics for enhancing the efficiency and stability of frequency conversion processes. However, the conventional QPM relies on periodically poled ferroelectric crystals, which are limited in availability. The 3R phase of molybdenum disulfide (3R-MoS2), a transition metal dichalcogenide (TMDc) with the broken inversion symmetry, stands out as a promising candidate for QPM, enabling efficient nonlinear process. Here, we experimentally demonstrate the QPM at nanoscale, utilizing van der Waals stacking of 3R-MoS2 layers with specific orientation to realize second harmonic generation (SHG) enhancement beyond the non QPM limit. We have also demonstrated enhanced spontaneous parametric down-conversion (SPDC) via QPM of 3R-MoS2 homo-structure, enabling more efficient generation of entangled photon pairs. The tunable capacity of 3R-MoS2 van der Waals stacking provides a platform for tuning phase-matching condition. This technique opens interesting possibilities for potential applications in nonlinear process and quantum technology.

Abstract Entangled photon-pair sources are at the core of quantum applications like quantum key distribution, sensing, and imaging. Operation in space-limited and adverse environments such as in satellite-based and mobile communication requires robust entanglement sources with minimal size and weight requirements. Here, we meet this challenge by realizing a cubic micrometer scale entangled photon-pair source in a 3R-stacked transition metal dichalcogenide crystal. Its crystal symmetry enables the generation of polarization-entangled Bell states without additional components and provides tunability by simple control of the pump polarization. Remarkably, generation rate and state tuning are decoupled, leading to equal generation efficiency and no loss of entanglement. Combining transition metal dichalcogenides with monolithic cavities and integrated photonic circuitry or using quasi-phasematching opens the gate towards ultrasmall and scalable quantum devices.

Abstract A new Parkinson’s disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PDpRBD–, representing the brain-first subtype), PD patients with possible premotor RBD (PDpRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.

Abstract Background Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson’s disease (PD) is hardly extensively researched. Methods A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. Results Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P

Abstract Objectives We aimed to develop a combined model based on clinical and radiomic features to classify fracture age. Methods We included 1219 rib fractures from 239 patients from our center between March 2016 and September 2022. We created an external dataset using 120 rib fractures from 32 patients from another center between October 2019 and August 2023. According to tasks (fracture age between 12 weeks), the internal dataset was randomly divided into training and internal test sets. A radiomic model was built using radiomic features. A combined model was constructed using clinical features and radiomic signatures by multivariate logistic regression, visualized as a nomogram. Internal and external test sets were used to validate model performance. Results For classifying fracture age between 12 weeks, the combined model had higher AUCs than the radiomic model in the training model (0.848 vs 0.837, p = 0.12) and internal test sets (0.818 vs 0.793, p

Abstract Giant cell myocarditis (GCM) is a rare and fatal inflammatory disorder induced by T-lymphocytes, typically affecting young adults. Generally, this disease presents with a rapidly progressive course and a very poor prognosis. In recent years, atrial GCM (aGCM) has been recognized as a clinicopathological entity distinct from classical GCM. As described by retrievable case reports, although its histopathological manifestations are highly similar to those of classical GCM, this entity is characterized by preserved left ventricular function and atrial arrhythmias, without ventricular arrhythmias. aGCM tends to show benign disease progression with a better clinical prognosis compared with the rapid course and poor prognosis of vGCM. We report a patient with aGCM with a history of renal abscess whose persistent myocardial injury considered to be associated with a history of renal abscess. Infection could be a potential trigger for the development of aGCM in this patient. An extensive literature review was also performed and the following three aspects were summarized: (1) Epidemiology and histopathological characteristics of aGCM; (2) The role of imaging in the evaluation of aGCM; (3) Diagnostic points and therapeutic decisions in aGCM.

BackgroundThe impact of decreased bone mineral density (BMD) on traumatic rib fractures remains unknown. We combined computed tomography (CT) and artificial intelligence (AI) to measure BMD and explore its impact on traumatic rib fractures and their patterns.MethodsThe retrospective cohort comprised patients who visited our hospital from 2017–2018; the prospective cohort (control group) was consecutively recruited from the same hospital from February–June 2023. All patients had blunt chest trauma and underwent CT. Volumetric BMD of L1 vertebra was measured by using an AI software. Analyses were done by using BMD categorized as osteoporosis (120 mg/cm3). Pearson’s χ2, Fisher’s exact, or Kruskal–Wallis tests and Bonferroni correction were used for comparisons. Negative binomial, and logistic regression analyses were used to assess the associations and impacts of BMD status. Sensitivity analyses were also performed.FindingsThe retrospective cohort included 2,076 eligible patients, of whom 954 (46%) had normal BMD, 806 (38.8%) had osteopenia, and 316 (15.2%) had osteoporosis. After sex- and age-adjustment, osteoporosis was significantly associated with higher rib fracture rates, and a higher likelihood of fractures in ribs 4–7. Furthermore, both the osteopenia and osteoporosis groups demonstrated a significantly higher number of fractured ribs and fracture sites on ribs, with a higher likelihood of fractures in ribs 1–3, as well as flail chest. The prospective cohort included 205 eligible patients, of whom 92 (44.9%) had normal BMD, 74 (36.1%) had osteopenia, and 39 (19.0%) had osteoporosis. The findings observed within this cohort were in concurrence with those in the retrospective cohort.InterpretationTraumatic rib fractures are associated with decreased BMD. CT-AI can help to identify individuals who have decreased BMD and a greater rib fracture rate, along with their fracture patterns.

Summary: Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy with diverse clinical phenotypes. Previous post-mortem studies examined tau deposition sequences in PSP, but in vivo scrutiny is lacking. Methods: We conducted [18F]Florzolotau tau positron emission tomography (PET) scans on 148 patients who were clinically diagnosed with PSP and 20 healthy controls. We employed the Subtype and Stage Inference (SuStaIn) algorithm to identify PSP subtype/stage and related tau patterns, comparing clinical features across subtypes and assessing PSP stage-clinical severity association. We also evaluated functional connectivity differences among subtypes through resting-state functional magnetic resonance imaging. Findings: We identified two distinct subtypes of PSP: Subtype1 and Subtype2. Subtype1 typically exhibits a sequential progression of the disease, starting from subcortical and gradually moving to cortical regions. Conversely, Subtype2 is characterized by an early, simultaneous onset in both regions. Interestingly, once the disease is initiated, Subtype1 tends to spread more rapidly within each region compared to Subtype2. Individuals categorized as Subtype2 are generally older and exhibit less severe dysfunctions in areas such as cognition, bulbar, limb motor, and general motor functions compared to those with Subtype1. Moreover, they have a more favorable prognosis in terms of limb motor function. We found significant correlations between several clinical variables and the identified PSP SuStaIn stages. Furthermore, Subtype2 displayed a remarkable reduction in functional connectivity compared to Subtype1. Interpretation: We present the evidence of distinct in vivo spatiotemporal tau trajectories in PSP. Our findings can contribute to precision medicine advancements for PSP. Funding: This work was supported by grants from the National Natural Science Foundation of China (number 82272039, 81971641, 82021002, and 92249302); Swiss National Science Foundation (number 188350); the STI2030-Major Project of China (number 2022ZD0211600); the Clinical Research Plan of Shanghai Hospital Development Center of China (number SHDC2020CR1038B); and the National Key R&D Program of China (number 2022YFC2009902, 2022YFC2009900), the China Scholarship Council (number 202006100181); the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198).

Tang, Liang, Shen, et al. assessed whether the use of a health management app by people with Parkinson’s disease before and after a COVID-19 lockdown in China had an impact on their quality of life (QoL). They show that these social distancing measures reduced the QoL overall, but the reduction was less pronounced if adherence to the app was high.

Abstract Glial fibrillary acidic protein (GFAP) has been suggested as a biomarker for reactive astrogliosis. We measured the levels of plasma GFAP by Simoa in 60 patients with PD with normal cognition, 63 with mild cognitive impairment (PD-MCI), 24 with dementia (PDD) and 15 healthy controls. A subgroup of patients with PD-MCI (n = 31) was followed up for 4.1 ± 2.3 years. Compared with healthy controls, plasma GFAP levels were elevated in patients with PDD (adjusted P

Abstract Objective New subtyping classification systems of Parkinson’s disease (PD) have been proposed for phenotyping patients into three different subtypes: mild motor‐predominant (PD‐MMP), intermediate (PD‐IM) and diffuse malignant (PD‐DM). The quality of life (QoL) underlying the novel PD clinical subtypes is unknown. This study aimed explore the feasibility of the classification in Chinese PD patients and to investigate the potential heterogeneous determinants of QoL among the three subtypes. Methods 298 PD patients were enrolled, including 129 PD‐MMP patients, 121 PD‐IM patients and 48 PD‐DM patients. All patients completed the QoL assessment, clinical evaluations and neuropsychological tests. Univariate linear analysis and multiple stepwise regression analysis were performed to identify determinants of QoL. Results Compared to PD‐MMP patients, PD‐IM and PD‐DM patients had more impaired QoL. The Geriatric Depression Rating Scale (GDS) score, Non‐Motor Symptoms Questionnaire (NMSQ) score, Unified Parkinson’s Disease Rating Scale part III (UPDRS‐III) score and Epworth Sleepiness Score (ESS) were independent contributors to QoL in PD‐MMP patients. The GDS score, ESS and sniffin’ sticks screening 12 test score were independent contributors to QoL in PD‐IM patients. The GDS score and Mini Mental State Examination score were independent contributors to QoL in PD‐DM patients. Interpretation The new novel subtyping classification is feasible for Chinese PD patients. Although depression was the most crucial determinant for QoL in PD‐MMP, PD‐IM and PD‐DM patients, the other contributors of QoL in the three subtypes were heterogeneous. These findings may prompt clinicians to target specific factors for improving QoL depending on PD subtypes.

ObjectiveAlthough the seasonal variation of motor and non-motor symptoms in Parkinson's disease (PD) has been reported, the association between seasonal change and quality of life in patients with Parkinson's disease remains to be explored.MethodsWe recruited 1,036 patients with PD in this cross-sectional retrospective study. The patients were divided into four groups based on their date of assessment, according to the classical four seasons: group 1: March to May (n = 241); group 2: June to August (n = 259); group 3: September to November(n = 273); group 4: December to February (n = 263). The 39-item Parkinson's Disease Questionnaire (PDQ-39) and other clinical evaluation scales for motor and non-motor symptoms were administered. The determinants of the quality of life (QoL) were analyzed by multiple stepwise regression analyses.ResultsA significant difference in PDQ-39 was found between group 1 (spring months) and group 3 (autumn months) after correction (p = 0.002). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score was higher in group 1 (spring months) than in group 3 (the autumn months) (p = 0.033). The most severe determinant of QoL was the UPDRS-III score in group 1 and the Geriatric Depression Scale (GDS) score in groups 2, 3, and 4.InterpretationThe current study reported seasonal fluctuation of QoL in patients with PD, with higher scores during the spring months and lower scores in the autumn months. Since the determinants for QoL also vary by season, clinicians might need to focus on specific factors across seasons before initiating therapy.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain dopaminergic neurons. The miR-29s family, including miR-29a and miR-29b1 as well as miR-29b2 and miR-29c, are implicated in aging, metabolism, neuronal survival, and neurological disorders. In this study, the roles of miR-29a/b1 in aging and PD were investigated. miR-29a/b1 knockout mice (named as 29a KO hereafter) and their wild-type (WT) controls were used to analyze aging-related phenotypes. After challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dopaminergic injuries, glial activation, and mouse behaviors were evaluated. Primary glial cells were further cultured to explore the underlying mechanisms. Additionally, the levels of miR-29s in the cerebrospinal fluid (CSF) of PD patients (n = 18) and healthy subjects (n = 17) were quantified. 29a KO mice showed dramatic weight loss, kyphosis, and along with increased and deepened wrinkles in skins, when compared with WT mice. Moreover, both abdominal and brown adipose tissues reduced in 29a KO mice, compared to their WT counterpart. However, in MPTP-induced PD mouse model, the deficiency of miR-29a/b1 led to less severe damages of dopaminergic system and mitigated glial activation in the nigrostriatal pathway, and subsequently alleviated the motor impairments in 3-month-old mice. Eight-month-old mutant mice maintained such a resistance to MPTP intoxication. Mechanistically, the deficiency of miR-29a/b-1 promoted the expression of neurotrophic factors in 1-Methyl-4-phenylpyridinium (MPP+)-treated primary mixed glia and primary astrocytes. In lipopolysaccharide (LPS)-treated primary microglia, knockout of miR-29a/b-1 inhibited the expression of inflammatory factors, and promoted the expression of anti-inflammatory factors and neurotrophic factors. Knockout of miR-29a/b1 increased the activity of AMP-activated protein kinase (AMPK) and repressed NF-κB/p65 signaling in glial cells. Moreover, we found miR-29a level was increased in the CSF of patients with PD. Our results suggest that 29a KO mice display the peripheral premature senility. The combined effects of less activated glial cells might contribute to the mitigated inflammatory responses and elicit resistance to MPTP intoxication in miR-29a/b1 KO mice.

ObjectiveThere is a lack of longitudinal studies that directly compare the quality of life (QoL) and investigate the impact of clinical factors on QoL across different excessive daytime sleepiness (EDS) statuses in Parkinson’s disease (PD); therefore, we aimed to compare QoL and reveal the potential heterogeneous predictors of QoL between patients with PD with and without EDS.MethodsWe collected clinical data among 306 patients with PD over 2 years. EDS was assessed by the Epworth Sleepiness Scale and QoL was measured with the 39-item Parkinson’s Disease Questionnaire.ResultsWe found that at both baseline and follow-up, patients with PD with EDS had poorer QoL and suffered more non-motor symptoms including depression and clinical probable rapid eye movement sleep behavior disorder (cpRBD). The generalized linear mixed model analysis indicated that the major predictors of QoL in PD with EDS were the akinetic-rigid type, disease duration, and total levodopa equivalent dose, while in PD without EDS, the primary determinants of QoL were Hoehn and Yahr, Mini-Mental State Examination (MMSE), and cpRBD.ConclusionPatients with PD with EDS presented with poorer QoL. Besides, the baseline predictors of future QoL differed between patients with PD with and without EDS. These findings remind clinicians to target specific clinical factors when attempting to improve QoL among patients with PD.

We aimed to detect acute aortic syndromes (AAS) on non-contrast computed tomography (NCCT) images using a radiomics-based machine learning model. A total of 325 patients who underwent aortic CT angiography (CTA) were enrolled retrospectively from 2 medical centers in China to form the internal cohort (230 patients, 60 patients with AAS) and the external testing cohort (95 patients with AAS). The internal cohort was divided into the training cohort (n = 135), validation cohort (n = 49), and internal testing cohort (n = 46). The aortic mask was manually delineated on NCCT by a radiologist. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used to filter out nine feature parameters; the Support Vector Machine (SVM) model showed the best performance. In the training and validation cohorts, the SVM model had an area under the curve (AUC) of 0.993 (95% CI, 0.965–1); accuracy (ACC), 0.946 (95% CI, 0.877–1); sensitivity, 0.9 (95% CI, 0.696–1); and specificity, 0.964 (95% CI, 0.903–1). In the internal testing cohort, the SVM model had an AUC of 0.997 (95% CI, 0.992–1); ACC, 0.957 (95% CI, 0.945–0.988); sensitivity, 0.889 (95% CI, 0.888–0.889); and specificity, 0.973 (95% CI, 0.959–1). In the external testing cohort, the ACC was 0.991 (95% CI, 0.937–1). This model can detect AAS on NCCT, reducing misdiagnosis and improving examinations and prognosis.

The discovery of 2D organic semiconductors of atomically thin structures has attracted great attention due to their emerging optical, electronic, optoelectronic and mechatronic properties. Recent progress in such organic nanostructures has opened new opportunities for engineering material properties in many ways, such as, 0D/1D/2D nanoparticles hybridization, strain engineering, atomic doping etc. Moreover, 2D organic nanostructures exhibit a unique feature of bio–functionality and are highly sensitive to bio-analytes. Such peculiar behavior in 2D organics can be utilized to design highly-efficient bio-sensors. Also, a bio-molecular integrated electronic/optoelectronic device with enhanced performance can be attained. Furthermore, the bio-degradable, biocompatible, bio-metabolizable, non-toxic behaviour and natural origin of organic nanomaterials can address the current ecological concerns of increasing inorganic material based electronic waste. This review highlights the benefits of 2D organic semiconductors. Considering the importance of strategic techniques for growing thin 2D organic layers, this review summarizes progress towards this direction. The possible challenges for long-time stability and future research directions in 2D organic nano electronics/optoelectronics are also discussed. We believe that this review article provides immense research interests in organic 2D nanotechnology for exploiting green technologies in the future. Keywords: 2D organic semiconductor, Green nanotechnology, OTFTs, OLEDs, Photo-diodes, Organic solar cell, Optical wave guide

BackgroundAccruing positron emission tomography (PET) studies have suggested that dopaminergic functioning and metabolic changes are correlated with cognitive dysfunction in Parkinson’s disease (PD). Yet, the relationship between dopaminergic or cerebral metabolism and different cognitive domains in PD is poorly understood. To address this scarcity, we aimed to investigate the interactions among dopaminergic bindings, metabolic network changes, and the cognitive domains in PD patients.MethodsWe recruited 41 PD patients, including PD patients with no cognitive impairment (PD-NC; n = 21) and those with mild cognitive impairment (PD-MCI; n = 20). All patients underwent clinical evaluations and a schedule of neuropsychological tests and underwent both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) PET imaging.Results11C-CFT imaging revealed a significant positive correlation between executive function and striatal dopamine transporter (DAT) binding at both the voxel and regional levels. Metabolic imaging revealed that executive function correlated with 18F-FDG uptake, mainly in inferior frontal gyrus, putamen, and insula. Further analysis indicated that striatal DAT binding correlated strictly with metabolic activity in the temporal gyrus, medial frontal gyrus, and cingulate gyrus.ConclusionOur findings might promote the understanding of the neurobiological mechanisms underlying cognitive impairment in PD.

BackgroundQuality of life (QoL) was worse in Parkinson’s disease patients with mild cognitive impairment (PD-MCI) or dementia (PDD) than PD patients with normal cognition (PD-NC). The aim of this study was to investigate and compare the potential heterogeneous determinants of QoL in PD patients with different cognitive statuses.MethodsWe recruited 600 PD patients, including 185 PD-NC patients, 336 PD-MCI patients and 79 PDD patients, in this cross-sectional study. All patients completed the QoL assessment by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), as well as clinical evaluations and neuropsychological tests. The determinants of the QoL were analyzed by multiple stepwise regression analysis.ResultsQoL was more impaired across the three groups (PD-NC < PD-MCI < PDD). The Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score, Geriatric Depression Rating Scale (GDS) score and daily levodopa equivalent dose (LED) were independent variables of PDQ-39 in PD-NC patients. The GDS score, disease duration, UPDRS-III score, Epworth Sleepiness Score (ESS) and sex were independent variables of PDQ-39 in PD-MCI patients. The GDS score and disease duration were independent variables of PDQ-39 in PDD patients.ConclusionThe determinants of QoL in PD-NC, PD-MCI and PDD patients were heterogeneous. Motor function was considered to be the most crucial determinant for QoL in PD-NC, while depression was indicated to be the most vital determinant for PD-MCI and PDD. For QoL improvement, clinicians might need to focus more on motor function in PD-NC patients and on depression in PD-MCI and PDD patients.

The pathological hallmarks of Parkinson's disease (PD) are the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of overactivated glial cells and neuroinflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) c-Rel subunit is closely related in the pathological progress of PD, however the roles and mechanisms of c-Rel in PD development remain unclear. Here, in neurotoxins-induced PD models, the dynamic changes of NF-κB c-Rel and its functions were evaluated. We found that c-Rel was rapidly activated in the nigrostriatal pathway, which mainly occurred in dopaminergic neurons and microglia. c-Rel could maintain neuronal survival by initiating the anti-apoptotic gene expression in MPP+-treated SH-SY5Y cells and it could inhibit microglial overactivation by suppressing the inflammatory gene expression in LPS-challenged BV2 cells. c-Rel inhibitor IT901 aggravated the damage of MPTP on dopaminergic neurons and promoted the activation of microglia in the nigrostriatal pathway of mice. Moreover, the expression of c-Rel in blood samples of PD patients decreased dramatically. Our results indicate that the NF-κB/c-Rel subunit plays an important role in neuroprotection and neuroinflammation inhibition during PD progression. Keywords: Parkinson's disease, NF-κB/c-Rel, Dopaminergic neurons, Microglia, Neuroprotection, Inflammation

Abstract There is currently no reliable and easily applicable diagnostic marker for Parkinson’s disease (PD). The aims of the present study were to compare the expression profiles of the microRNA29 family (miR-29s) in blood serum from patients with PD with healthy controls and to clarify whether the expression of miR-29s is correlated with disease severity, duration or L-dopa therapy and whether expression depends on the gender and age of patients. The levels of blood serum miR-29s in 80 patients with PD and 80 unaffected controls were assessed by reverse transcription-quantitative real-time PCR. The PCR products were confirmed by cloning and sequencing. Additionally, the expression of miR-7 in the blood serum from PD patients and control subjects was assessed. Serum miR-29 levels were significantly downregulated in PD patients compared to healthy controls. The serum miR-29 levels in female PD patients were markedly higher than in male PD patients. The expression of serum miR-29a and miR-29c expression tended to decrease with disease severity. Moreover, we found that serum miR-7 levels did not differ between PD patients and control subjects. Therefore, the reduction of serum miR-29 levels, particularly miR-29a and miR-29c, warrants further investigation of its potential serving as biomarkers for PD.

PURPOSE:To characterize cerebral glucose metabolism associated with different cognitive states in Parkinson's disease (PD) using 18F-fluorodeoxyglucose (FDG) and Positron Emission Tomography (PET). METHODS:Three groups of patients were recruited in this study including PD patients with dementia (PDD; n = 10), with mild cognitive impairment (PD-MCI; n = 20), and with no cognitive impairment (PD-NC; n = 30). The groups were matched for age, sex, education, disease duration, motor disability, levodopa equivalent dose and Geriatric Depression Rating Scale (GDS) score. All subjects underwent a FDG-PET study. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM5). RESULTS:PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and parahippocampal gyrus compared with the PD-NC patients (p < 0.01). PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01), and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01). CONCLUSIONS:Compared with PD-NC patients, hypometabolism was much higher in the PDD patients than in PD-MCI patients, mainly in the posterior cortical areas. The result might suggest an association between posterior cortical hypometabolism and more severe cognitive impairment. PD-MCI might be important for early targeted therapeutic intervention and disease modification.

Ice storm is known to play a role in determining forest succession and litter dynamics constitute an important aspect of nutrient cycling in forest ecosystems. However, ice storm effects on amount and pattern of litterfall are not clearly understood. We investigated litter production and litter leaf nutrient dynamic in a moso bamboo plantation in China following an extreme disturbance of ice storm in 2008. The litterfall in on-years was significantly lower than in off-years. Ice storm caused total litterfall increasing from 16.68% to 35.60% and greatly disturbed the litterfall peak rhythm especially in the on-year. The litter leaf nutrient concentrations at two latitudes significantly fluctuated after ice-snow disaster in 2008, litter leaf stoichiometric traits indicated that litter leaf chemistry showed more easily decomposition with higher C/P ratio, N/P ratio, and lower C/N ratio. It is clear from this study that litterfall restoration dynamic would result in long-term changes in litter nutrient cycling and may help predicting below ground carbon dynamic in future research as well as subtropical forest inventories following extreme disturbance.