The Effects Of Long-Term Treadmill Exercise Training On Amyloid-Beta Plaque Levels and Behavioral Profile in 15-Month Tg2576 Mice

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that is characterized by progressive loss of memory and cognitive function. The causative factors of this disease include modifications in neuronal cell metabolism, such as the progression of neurotic injury by amyloid beta (Aβ), and tau tangle deposition in the brain. Recent studies show that brain atrophy and other pathologic conditions are responsible for dementia in older individuals (80 years of age or older). Non-pharmacological interventions may have a role in both the prevention and slowing disease progression in AD. The role of exercise training in disease prevention has been evaluated in large epidemiological studies even though much less is known about the potential benefit of exercise training in patients already diagnosed with AD. Several studies in transgenic mouse models of AD suggest exercise training reduces soluble and insoluble Aβ levels in the brain. This study assessed the effectiveness of long-term exercise training (12-months) in an AD transgenic mouse model, Tg2576. Amyloid plaque levels and behavioral profile of mice were evaluated after 12 months of training. Mice that received daily exercise training demonstrated beneficial behavioral profile and reduced plaque counts in a dose-dependent manner

Impact and perceived value of the revolutionary advent of artificial intelligence in research and publishing among researchers: a survey-based descriptive study

Purpose This study was conducted to understand the perceptions and awareness of artificial intelligence (AI) in the academic publishing landscape. Methods We conducted a global survey entitled “Role and impact of AI on the future of academic publishing” to understand the impact of the AI wave in the scholarly publishing domain. This English-language survey was open to all researchers, authors, editors, publishers, and other stakeholders in the scholarly community. Conducted between August and October 2021, the survey received responses from around 212 universities across 54 countries. Results Out of 365 respondents, about 93% belonged to the age groups of 18–34 and 35–54 years. While 50% of the respondents selected plagiarism detection as the most widely known AI-based application, image recognition (42%), data analytics (40%), and language enhancement (39%) were some other known applications of AI. The respondents also expressed the opinion that the academic publishing landscape will significantly benefit from AI. However, the major challenges restraining the large-scale adoption of AI, as expressed by 93% of the respondents, were limited knowledge and expertise, as well as difficulties in integrating AI-based solutions into existing IT infrastructure. Conclusion The survey responses reflected the necessity of AI in research and publishing. This study suggests possible ways to support a smooth transition. This can be best achieved by educating and creating awareness to ease possible fears and hesitation, and to actualize the promising benefits of AI

Peripheral Inflammation, \u3cem\u3eApolipoprotein E4\u3c/em\u3e, and Amyloid-β Interact to Induce Cognitive and Cerebrovascular Dysfunction

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of 5 Familial Alzheimer’s disease (5xFAD) mutations. Here, we utilized EFAD carriers [5xFAD+/−/APOE+/+ (EFAD+)] and noncarriers [5xFAD−/−/APOE+/+ (EFAD−)] to compare the effects of peripheral inflammation in the presence or absence of human Aβ overproduction. Low-level, chronic repeated peripheral inflammation was induced in EFAD mice via systemic administration of lipopolysaccharide (LPS; 0.5 mg/kg/wk i.p.) from 4 to 6 months of age. In E4FAD+ mice, peripheral inflammation caused cognitive deficits and lowered post-synaptic protein levels. Importantly, cerebrovascular deficits were observed in LPS-challenged E4FAD+ mice, including cerebrovascular leakiness, lower vessel coverage, and cerebral amyloid angiopathy-like Aβ deposition. Thus, APOE4, Aβ, and peripheral inflammation interact to induce cerebrovascular damage and cognitive deficits

Exercise training results in lower amyloid plaque load and greater cognitive function in an intensity dependent manner in the Tg2576 mouse model of Alzheimer\u27s disease

Three months of exercise training (ET) decreases soluble A

User experiences of an American-adapted moderated online social media platform for first-episode psychosis : Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

User experiences of an American-adapted moderated online social media platform for first-episode psychosis: Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

Mgmt Function Determines the Differential Response of Atr Inhibitors With DNA-Damaging Agents in Glioma Stem Cells for GBM Therapy

BACKGROUND: The most prevalent cancer treatments cause cell death through DNA damage. However, DNA damage response (DDR) repair pathways, initiated by tumor cells, can withstand the effects of anticancer drugs, providing justification for combining DDR inhibitors with DNA-damaging anticancer treatments. METHODS: Cell viability assays were performed with CellTiter-Glo assay. DNA damage was evaluated using Western blotting analysis. RNA-seq and single-cell level expression were used to identify the DDR signatures. In vivo, studies were conducted in mice to determine the effect of ATris on TMZ sensitization. RESULTS: We found a subpopulation of glioma sphere-forming cells (GSCs) with substantial synergism with temozolomide (TMZ) using a panel of 3 clinical-grade ataxia-telangiectasia- and Rad3-related kinase inhibitors (ATRis), (elimusertib, berzosertib, and ceralasertib). Interestingly, most synergistic cell lines had O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, indicating that ATRi mainly benefits tumors with no MGMT repair. Further, TMZ activated the ATR-checkpoint kinase 1 (Chk1) axis in an MGMT-dependent way. TMZ caused ATR-dependent Chk1 phosphorylation and DNA double-strand breaks as shown by increased γH2AX. Increased DNA damage and decreased Chk1 phosphorylation were observed upon the addition of ATRis to TMZ in MGMT-methylated (MGMT-) GSCs. TMZ also improved sensitivity to ATRis in vivo, as shown by increased mouse survival with the TMZ and ATRi combination treatment. CONCLUSIONS: This research provides a rationale for selectively targeting MGMT-methylated cells using ATRis and TMZ combination. Overall, we believe that MGMT methylation status in GBM could serve as a robust biomarker for patient selection for ATRi combined with TMZ

Towards a cosmic ray composition measurement with the IceAct telescopes at the IceCube Neutrino Observatory

The IceCube Neutrino Observatory is equipped with the unique possibility to measure cosmic ray induced air showers simultaneously by their particle footprint on the surface with the IceTop detector and by the high-energy muonic shower component at a depth of more than 1.5 km. Since 2019 additionally, two Imaging Air Cherenkov Telescopes, called IceAct, measure the electromagnetic component of air showers in the atmosphere above the IceCube detector. This opens the possibility to measure air shower parameters in three independent detectors and allows to improve mass composition studies with the IceCube data. One IceAct camera consists of 61 SiPM pixels in a hexagonal grid. Each pixel has a field of view of 1.5 degree resulting in an approximately 12-degree field of view per camera. A single telescope tube has a diameter of 50 cm, is built robust enough to withstand the harsh Antarctic conditions, and is able to detect cosmic ray particles with energies above approximately 10 TeV. A Graph Neural Network (GNN) is trained to determine the air shower properties from IceAct data. The composition analysis is then performed using Random Forest Regression (RF). Since all three detectors have a different energy threshold, we train several RFs with different inputs, combining the different detectors and taking advantage of the lower energy threshold of the IceAct telescopes. This will result in composition measurements for different detector combinations and enables cross-checks of the results in overlapping energy bands. We present the method, parameters for data selection, and the status of this analysis

Three-year performance of the IceAct telescopes at the IceCube Neutrino Observatory

IceAct is an array of compact Imaging Air Cherenkov Telescopes at the ice surface as part of the IceCube Neutrino Observatory. The telescopes, featuring a camera of 61 silicon photomultipliers and fresnel-lens-based optics, are optimized to be operated in harsh environmental conditions, such as at the South Pole. Since 2019, the first two telescopes have been operating in a stereoscopic configuration in the center of IceCube\u27s surface detector IceTop. With an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of improving current cosmic-ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors. First simulations indicate that the added information of a single telescope leads, e.g., to an improved discrimination between flux contributions from different primary particle species in the sensitive energy range. We review the performance and detector operations of the telescopes during the past 3 years (2020-2022) and give an outlook on the future of IceAct

TXS 0506+056 with Updated IceCube Data

Past results from the IceCube Collaboration have suggested that the blazar TXS 0506+056 is a potential source of astrophysical neutrinos. However, in the years since there have been numerous updates to event processing and reconstruction, as well as improvements to the statistical methods used to search for astrophysical neutrino sources. These improvements in combination with additional years of data have resulted in the identification of NGC 1068 as a second neutrino source candidate. This talk will re-examine time-dependent neutrino emission from TXS 0506+056 using the most recent northern-sky data sample that was used in the analysis of NGC 1068. The results of using this updated data sample to obtain a significance and flux fit for the 2014 TXS 0506+056 "untriggered" neutrino flare are reported