Notes

Utilization of Benzodiazepines and Risk of Episode Dementia: A Retrospective Cohort Research.
ospective studies are needed to confirm these findings and analyze the association of frailty with other PMR disease outcomes.The mechanism of action of deep brain stimulation (DBS) to the basal ganglia for Parkinson's disease remains unclear. Studies have shown that DBS decreases pathological beta hypersynchrony between the basal ganglia and motor cortex. However, little is known about DBS's effects on long range corticocortical synchronization. Here, we use machine learning combined with graph theory to compare resting-state cortical connectivity between the off and on-stimulation states and to healthy controls. We found that turning DBS on increased high beta and gamma band synchrony (26 to 50 Hz) in a cortical circuit spanning the motor, occipitoparietal, middle temporal, and prefrontal cortices. The synchrony in this network was greater in DBS on relative to both DBS off and controls, with no significant difference between DBS off and controls. Turning DBS on also increased network efficiency and strength and subnetwork modularity relative to both DBS off and controls in the beta and gamma band. Thus, unlike DBS's subcortical normalization of pathological basal ganglia activity, it introduces greater synchrony relative to healthy controls in cortical circuitry that includes both motor and non-motor systems. This increased high beta/gamma synchronization may reflect compensatory mechanisms related to DBS's clinical benefits, as well as undesirable non-motor side effects.
To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission.

At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at < 2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose-reduction and discontinuation of MTX or bDMARD. At end of year 1, patients who achieved DAS28(ESR)<3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR)<2.6 at year 1 and 2, respectively.

Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR)<2.6 (continuation, 85.2%; MTX-dose-reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD-dose-reduction, 73.9%), although the rate was significantly different between theescalation of MTX had no impacts on disease control but decreased adverse events in year 2.Long non-coding RNAs (lncRNAs) play a crucial role in gastric cancer (GC) progression. And understanding the role of N6-methyladenosine (m6A) in tumorigenesis is an emerging field in cancer research. Here, we identified a novel oncogene, lncRNA LINC02253, in GC. LINC02253 expression was found to be significantly increased in GC. And LINC02253 expression was closely correlated with tumor size, lymph node metastasis and TNM stage of GC. Besides, GC patients with higher LINC02253 expression had worse 5-year overall survival. Additionally, LINC02253 promoted GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, we determined that LINC02253 increased KRT18 expression through enhancing the stability of KRT18 mRNA. Furthermore, LINC02253 increased m6A modification of KRT18 mRNA to stabilize KRT18 mRNA by recruiting m6A writer METTL3. And, rescue experiments revealed that KRT18 mediated the effects of LINC02253 on growth, migration and invasion of GC cells through activating MAPK/ERK signaling pathway. In conclusion, we demonstrates that oncogenic lncRNA LINC02253 positively regulates GC growth and metastasis via increasing METTL3-mediated mRNA stability of KRT18, extending the understanding of GC pathogenesis regulated by lncRNAs.
Human brain network is organized as a hierarchical organization, exhibiting various connectome gradients. The principal gradient is anchored by the modality-specific primary areas and the transmodal regions. Previous studies have suggested that the unimodal-transmodal gradient in the functional connectome may offer an overarching framework for high-order cognitions of human brain. However, there is still a lacking of direct evidence to associate these two.

Therefore, we aim to explore the association between creativity, a typical human high-order cognitive function, and unimodal-transmodal gradient, using two independent datasets of young adults.

For each individual, we identified the unimodal-transmodal gradient in functional connectome and calculated its global measures. Then we correlated the individual creativity score with measures of unimodal-transmodal gradient at global-brain, subsystem, and regional level.

The results suggested that better creative performance was associated with greater distance between primary areas and transmodal regions in gradient axes, and less distance between ventral attention network and default mode network. Individual creativity was also found positively correlated with regional gradients in ventral attention network, and negatively correlated with gradients of regions in visual cortex.

Together, these findings directly link the unimodal-transmodal gradient to individual creativity, providing empirical evidence for the cognitive implications of functional connectome gradient.
Together, these findings directly link the unimodal-transmodal gradient to individual creativity, providing empirical evidence for the cognitive implications of functional connectome gradient.One key reason for T cell exhaustion is continuous antigen exposure. Early exhausted T cells can reverse exhaustion and differentiate into fully functional memory T cells if removed from persisting antigen stimulation. Therefore, this study viewed T cell exhaustion as an over-activation status induced by chronic antigen stimuli. This study hypothesized that blocking TCR signal intermittently to terminate over-activation signal can defer the developmental process of T cell exhaustion. In this study, melanoma-bearing mice were treated with tacrolimus (FK506) every 5 days. The tumor size and tumor-infiltrating lymphocytes (TILs) were analyzed. We found that intermittent administration of tacrolimus significantly inhibited tumor growth, and this effect was mediated by CD8+T cells. Intermittent tacrolimus treatment facilitated the infiltration of CD8+TILs. RNA-seq and quantitative RT-PCR of sorted CD8+TILs showed the expression of Nr4a1 (an exhaustion-related transcription factor) and Ctla4 (a T cell inhibitory receptor) was remarkably downregulated. These results indicated that intermittently blocking TCR signal by tacrolimus can promote anti-tumor immunity and inhibit the tumor growth in melanoma-bearing mice, inhibiting the transcription of several exhaustion-related genes, such as Nr4a1 and Ctla4.
Electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation is a minimally invasive technology for treating pulmonary lesions. This study analysed the short-term safety and efficacy of ENB-guided microwave ablation in multiple pulmonary nodules (MPNs).

This retrospective study reports a single-centre experience with ENB-guided microwave ablation for MPNs. Clinical, surgical and pathological data were obtained for patients who underwent ENB-guided microwave ablation from 23 December 2019 to 23 June 2021. The primary end points were technical safety and efficiency.

The study assessed 65 patients who underwent ENB-guided microwave ablation, 57 of whom simultaneously underwent video-assisted thoracic surgery. In total, 216 nodules were treated. Of 96 nodules treated by ENB-guided microwave ablation, 94 nodules had ground-glass opacity. Epigenetics inhibitor Ablation efficiency was confirmed by hybrid cone-beam computed tomography. Of 120 nodules surgically removed, 106 nodules had ground-glass opacity. The mean nodule size was 7.9 mm in ablated nodules and 10.2 mm in resected nodules. Distance between nodules and pleura or fissure was 17.45 mm in ablated nodules and 7.29 mm in resected nodules. The overall malignancy rate was 47.7% (103/216); the complication rate was low (65 patients). At short-term follow-up, the post-ablation target zone shrank by 1 week and stabilized after 4-6 months. No local recurrence or enlargement of other pulmonary nodules was noted.

To treat MPNs, ENB-guided microwave ablation is safe and efficient. The combination of this treatment and video-assisted thoracic surgery is a potential application, which can preserve as much pulmonary function as possible and treat MPNs to the maximum extent.
To treat MPNs, ENB-guided microwave ablation is safe and efficient. The combination of this treatment and video-assisted thoracic surgery is a potential application, which can preserve as much pulmonary function as possible and treat MPNs to the maximum extent.
The incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with non-pharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case counts in Germany in 2020-2021.

IPD cases through November 30, 2021 were stratified by age group, serotype, or geographic location. IPD surveillance data in 2020-2021 were compared with 1) IPD surveillance data from 2015-2019, 2) mobility data during 2020 and 2021, and 3) NPI stringency data in 2020 and 2021.

IPD began to return towards baseline values among children 0 to 4 years old in April 2021 and exceeded baseline levels by June 2021 (a 9% increase over the average monthly values for 2015-2019). Children 5 to 14, adults aged 15-34 and adults 80 years and older showed increases in IPD cases which went over baseline values starting in July 2021, with increases also starting in Spring 2021. The age distribution and proportion of vaccine serotype IPD remained comparable to previous years despite lower overall case counts in 2020 and 2021. The percent change in IPD incidence compared to the previous five years correlated with changes in mobility and with NPI stringency.

IPD levels began to return to and exceed seasonal levels in Spring/Summer 2021 in Germany following sharp declines in 2020 that coincided with NPIs related to the COVID-19 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020-2021.
IPD levels began to return to and exceed seasonal levels in Spring/Summer 2021 in Germany following sharp declines in 2020 that coincided with NPIs related to the COVID-19 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020-2021.
The DESIRES trial showed that rituximab is effective in treating skin sclerosis in systemic sclerosis. However, which patient groups are likely to benefit from rituximab is unknown.

We performed post-hoc analysis on prospective data from 54 patients who received rituximab or placebo in the DESIRES trial. Twenty-seven baseline factors were used to investigate subpopulations with different magnitudes of rituximab effect on modified Rodnan Skin Score (mRSS) change at 24 weeks. Based on a machine-learning algorithm called the causal tree, we explored the combination of predictors needed to identify subpopulations that would respond to rituximab and have good treatment outcomes.

Three factors were identified as branches of the decision tree "peripheral blood CD19-positive cell counts", "mRSS", and "serum surfactant protein D (SP-D) levels". Only in the subpopulation of patients with CD19-positive cell counts < 57/μl, rituximab did not show a significant improvement in mRSS vs placebo. In the subpopulation of patients with CD19-positive cell counts ≥ 57/μl and mRSS ≥ 17, mRSS was most improved with rituximab (difference -17.
Website: https://www.selleckchem.com/products/Trichostatin-A.html