Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier.

The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non-specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.

Influence of γ-PGA on greenhouse gas emissions and grain yield from paddy rice under different rice varieties.

BACKGROUND: Significant efforts have been devoted to assess the effects of the poly-gamma-glutamic acid (γ-PGA) on crop growth, yield and quality, soil water retention and fertilizer use efficiency. However, few studies have evaluated the effects of γ-PGA on greenhouse gas (GHG) emissions and grain yield from paddy fields with different rice varieties. METHODS: In the present study, a split-plot field experiment was performed to comprehensively evaluate the effects of γ-PGA concentrations (i.e., no application [P0] and 25.0 kg ha-1 of γ-PGA fermentation solution [P1]) and rice varieties (i.e., conventional rice [Huanghuazhan, H], red rice [Gangteyou 8024, R] and black rice [Black indica rice, B]) on the grain yield, GHG emissions, global warming potential (GWP), greenhouse gas intensity (GHGI), net ecosystem economic profit (NEEP) and carbon footprint (CF) during 2022 and 2023 rice-growing seasons in central China. RESULTS: Application of γ-PGA significantly affected the GHGs emissions, NEEP and CF. Compared with P0 treatments, P1 treatments significantly increased the NEEP by 1.2-11.2 %, and decreased the GWP by 12.9-35.4 %, the GHGI by 16.5-35.9 % and the CF by 13.8-26.2 % in 2022-2023. Application of γ-PGA showed a tendency to increase the yield. Under γ-PGA application condition, R treatment exhibited the lowest GWP, GHGI and CF, and the highest yield and NEEP compared with B and H treatments. CONCLUSION: Our results suggest that γ-PGA application is an ecological agricultural management to increase rice yield, reduce greenhouse gas emission and increase economic benefit, and its advantage is more significant for red rice than for other rice varieties.

Intensive chemotherapy with dual induction and ALL-like consolidation for childhood acute myeloid leukemia: a respective report from multiple centers in China.

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed. Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation. Design: Retrospective, single-arm study. Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023. Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%). Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort. Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.

Anion Exchange Membrane with Pendulous Piperidinium on Twisted All-Carbon Backbone for Fuel Cell.

As a central component for anion exchange membrane fuel cells (AEMFCs), the anion exchange membrane is now facing the challenge of further improving its conductivity and alkali stability. Herein, a twisted all-carbon backbone is designed by introducing stereo-contorted units with piperidinium groups dangled at the twisted sites. The rigid and twisted backbone improves the conduction of hydroxide and brings down the squeezing effect of the backbone on piperidine rings. Accordingly, an anion exchange membrane prepared through this method exhibits adapted OH- conductivity, low swelling ratio and excellent alkali stability, even in high alkali concentrations. Further, a fuel cell assembled with a such-prepared membrane can reach a power density of 904.2 mW/cm2 and be capable of continuous operation for over 50 h. These results demonstrate that the designed membrane has good potential for applications in AEMFCs.

Study protocol for a non-inferiority, multicenter, randomized study to evaluate a smartphone app-based follow-up program after bariatric surgery (BELLA plus trial).

INTRODUCTION: Adherence to follow-up (FU) care after bariatric surgery is poor despite strong recommendations. In our pilot Bella trial, we demonstrated that a completely remote follow-up program via smartphone is feasible and safe for patients after bariatric surgery. Building on this, we aim to verify our results in a multicenter, randomized controlled setting. METHODS: This trial plans to enroll 410 participants undergoing primary bariatric surgery in seven German bariatric centers. Participants are randomized into two groups: a control group receiving in-person FU according to the standard in the bariatric centers, and an interventional group monitored using a smartphone application (app). The app sends standardized questionnaires and reminders regarding regular vitamin intake and exercises. The built-in messaging function enables patients to communicate remotely with medical care professionals. After one year, all participants are evaluated at their primary bariatric centers. The primary outcome is weight loss 12 months after surgery. The secondary outcomes include obesity-related comorbidities, quality of life, serum values of vitamins and minerals, body impedance analysis, visits to the emergency department or readmission, patient compliance, and medical staff workload. DISCUSSION: The current study is the first prospective, individually randomized-controlled, multicenter trial where a mobile application completely replaces traditional in-person visits for post-bariatric surgery follow-ups in bariatric centers.

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

OBJECTIVE: The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. METHODS: One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. RESULTS: Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. CONCLUSION: The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA.

The current paradigm about the function of T cell immune checkpoints is that these receptors switch on inhibitory signals upon cognate ligand interaction. We here revisit this simple switch model and provide evidence that the T cell lineage protein THEMIS enhances the signaling threshold at which the immune checkpoint BTLA (B- and T-lymphocyte attenuator) represses T cell responses. THEMIS is recruited to the cytoplasmic domain of BTLA and blocks its signaling capacity by promoting/stabilizing the oxidation of the catalytic cysteine of the tyrosine phosphatase SHP-1. In contrast, THEMIS has no detectable effect on signaling pathways regulated by PD-1 (Programmed cell death protein 1), which depend mainly on the tyrosine phosphatase SHP-2. BTLA inhibitory signaling is tuned according to the THEMIS expression level, making CD8+ T cells more resistant to BTLA-mediated inhibition than CD4+ T cells. In the absence of THEMIS, the signaling capacity of BTLA is exacerbated, which results in the attenuation of signals driven by the T cell antigen receptor and by receptors for IL-2 and IL-15, consequently hampering thymocyte positive selection and peripheral CD8+ T cell maintenance. By characterizing the pivotal role of THEMIS in restricting the transmission of BTLA signals, our study suggests that immune checkpoint operability is conditioned by intracellular signal attenuators.

Sub-pixel marking and depth-based correction methods for the elimination of voxel drifting in integral imaging display.

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

Incorporating machine learning and PPI networks to identify mitochondrial fission-related immune markers in abdominal aortic aneurysms.

Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.

Construction of cyclobutane-fused tetracyclic skeletons via substrate-dependent EnT-enabled dearomative [2+2] cycloaddition of benzofurans (benzothiophenes)/maleimides.

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

A novel variant in a Chinese boy with lysinuric protein intolerance: A case report and literature review.

We report a case of a 4-year-old boy with lysinuric protein intolerance in China. The patient presented with interstitial lung disease with obvious clubbing of the fingers and toes. During the course of diagnosis and treatment, we found he was averse to a high-protein diet, intolerant to activity, and had a history of diarrhea and fractures. Physical examination revealed hepatosplenomegaly and clubbing of the fingers and toes. Next-generation sequencing revealed compound heterozygous mutations (c.1387delG, c.958T > C) in SLC7A7, which was confirmed as a disease-causing gene for lysinuric protein intolerance. After a literature review, we found that c.958T > C had not been previously reported, and summarized the clinical and genetic characteristics of patients from different continents. His symptoms improved significantly after 3 months of being on a low-protein diet, supplementation with lysine, citrulline, carnitine, and trace elements, and oral corticosteroid treatment for 2 months. The patient is still under follow-up.

Feasibility of a Mobile Health Intervention for Providing a Continuum of HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in China.

BACKGROUND: Men who have sex with men (MSM) in China have a high risk for HIV infection but experience suboptimal rates of HIV testing and service engagement due to various social and structural barriers. We developed a mobile health (mHealth) intervention entitled "WeTest-Plus" (WeTest+) as a user-centered "one-stop service" approach for delivering access to comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention, confirmatory testing, treatment, and care. OBJECTIVE: The goal of the current study was to investigate the feasibility of WeTest+ to provide continuous HIV services to high-risk MSM. METHODS: Participants completed a 3-week pilot test of WeTest+ to examine acceptability, feasibility, and recommendations for improvement. Participants completed a structured online questionnaire and qualitative exit interviews facilitated by project staff. "Click-through" rates were assessed to examine engagement with online content. RESULTS: 28 participants were included, and the average age was 27.6 years (standard deviation = 6.8). Almost all participants (96.4%) remained engaged with the WeTest+ program over a 3-week observational period. The majority (92.9%) self-administered the HIV self-test and submitted their test results through the online platform. Overall click-through rates were high (average 67.9%). Participants provided favorable comments about the quality and relevance of the WeTest+ information content, the engaging style of information presentation, and the user-centered features. CONCLUSION: This pilot assessment of WeTest+ supports the promise of this program for promoting HIV self-testing and linkage to in-person services for MSM in China. Findings underscore the utility of a user-centered approach to mHealth program design.

The enhancement of nonlinear optical properties of azulene-based nanographene by N atoms: a finishing touch.

Nonlinear optical (NLO) materials play an increasingly important role in optoelectronic devices, biomedicine, micro-nano processing, and other fields. The development of organic materials with strong second or (and) third NLO properties and a high stability is still challenging due to the unknown strategies for obtaining enhanced high order NLO properties. In the present work, π-conjugated systems are constructed by doping boron or (and) nitrogen atoms in the azulene moiety of azulene-based nanographenes (formed with an azulene chain with two bridging HCCHs at the two sides of the connecting CC bonds between azulenes, A1A2A3), and the NLO properties are predicted with time-dependent density functional theory based methods and a sum-over-states model. The doping of heteroatoms induces charge redistribution, tunes the frontier molecular orbital energy gap, changes the composition of some frontier molecular orbitals, and affects the NLO properties of those nanographenes. Among the designed nanographenes, the azulene-based nanographene with two nitrogen atoms at the two ends has the largest static first hyperpolarizability (91.30 × 10-30 esu per heavy atom), and the further introduction of two N atoms at the two ends of the central azulene moiety of this nanographene results in a large static second hyperpolarizability while keeping the large static first hyperpolarizability.

Photomediated Hydro(deutero)acylation of Olefins by Decarboxylative Addition of α-Oxocarboxylic Acids.

Acyl radicals have been generated from the decarboxylation of α-oxocarboxylic acids by using a readily accessible organic pyrimidopteridine photoredox catalyst under ultraviolet-A (UV-A) light irradiation. These reactive acyl radicals were smoothly added to olefins such as styrenes and diverse Michael acceptors, with the assistance of H2O/D2O as hydrogen donors, enabling easy access to a diverse range of ketones/ß-deuterio ketones. A wide range of α-oxocarboxylic acids are compatible with this reaction, which shows a reliable, atom-economical, and eco-friendly protocol. Furthermore, postsynthetic diversifications and applications are presented.

Advancing Adolescent and Young Adult HIV Prevention and Care and Treatment Through Use of Multi-level Theories and Frameworks: A Scoping Review and Adapted HIV Ecological Framework.

While multi-level theories and frameworks have become a cornerstone in broader efforts to address HIV inequities, little is known regarding their application in adolescent and young adult (AYA) HIV research. To address this gap, we conducted a scoping review to assess the use and application of multi-level theories and frameworks in AYA HIV prevention and care and treatment empirical research. We systematically searched five databases for articles published between 2010 and May 2020, screened abstracts, and reviewed eligible full-text articles for inclusion. Of the 5890 citations identified, 1706 underwent full-text review and 88 met the inclusion criteria: 70 focused on HIV prevention, with only 14 on care and treatment, 2 on both HIV prevention and care and treatment, and 2 on HIV-affected AYA. Most authors described the theory-based multi-level framework as informing their data analysis, with only 12 describing it as informing/guiding an intervention. More than seventy different multi-level theories were described, with 38% utilizing socio-ecological models or the eco-developmental theory. Findings were used to inform the adaptation of an AYA World Health Organization multi-level framework specifically to guide AYA HIV research.

Therapeutic effects of long-term HBOT on Alzheimer's disease neuropathologies and cognitive impairment in APPswe/PS1dE9 mice.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with the pathological hallmarks of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) in the brain. Although there is a hope that anti-amyloid monoclonal antibodies may emerge as a new therapy for AD, the high cost and side effect is a big concern. Non-drug therapy is attracting more attention and may provide a better resolution for the treatment of AD. Given the fact that hypoxia contributes to the pathogenesis of AD, hyperbaric oxygen therapy (HBOT) may be an effective intervention that can alleviate hypoxia and improve AD. However, it remains unclear whether long-term HBOT intervention in the early stage of AD can slow AD progression and ultimately prevent cognitive impairment in this disease. In this study we applied consecutive 3-month HBOT interventions on 3-month-old APPswe/PS1dE9 AD mice which represent the early stage of AD. When the APPswe/PS1dE9 mice at 9-month-old which represent the disease stage we measured cognitive function, 24-h blood oxygen saturation, Aß and tau pathologies, vascular structure and function, and neuroinflammation in APPswe/PS1dE9 mice. Our results showed that long-term HBOT can attenuate the impairments in cognitive function observed in 9-month-old APPswe/PS1dE9 mice. Most importantly, HBOT effectively reduced the progression of Aß plaques deposition, hyperphosphorylated tau protein aggregation, and neuronal and synaptic degeneration in the AD mice. Further, long-term HBOT was able to enhance blood oxygen saturation level. Besides, long-term HBOT can improve vascular structure and function, and reduce neuroinflammation in AD mice. This study is the first to demonstrate that long-term HBOT intervention in the early stage of AD can attenuate cognitive impairment and AD-like pathologies. Overall, these findings highlight the potential of long-term HBOT as a disease-modifying approach for AD treatment.