bluuebunny/crossref_metadata_2025 huggingface dataset:
The Spatial Correlation Between Green High-Quality Development and Technology Finance
Authors: Jiang Lili , Wang Hui , Wang Shaowen , Hu Zhifei , Tong Aihua , Wang Yifeng
Published: May 2022

Based on an analysis of the function of technology finance for green high-quality development, this paper selects 35 basic indicators from the five dimensions of innovation, coordination, greenness, openness, and sharing to construct an Green High-quality Development Index. Moreover, 14 basic indicators are selected from the three dimensions of technology finance resources level, technology finance input level, and technology finance output level to construct a technology finance development evaluation system. Then, using the entropy method, panel data from the period 2000–2020 from China’s 30 provinces was employed to assess the Economic Quality Development Index and the Technology Finance Development Index. The results show that provinces and cities with a good economic development level have a relatively high level of strong economic and technology finance development, including Beijing, Shanghai, and Jiangsu. Moreover, the results reveal a certain gap between different provinces. Multiple regression, static panel regression, dynamic panel regression, the static space Dubin model, the dynamic space Dubin model, and the semi-parametric space lag model were used to test the effect of technology finance on China’s green high-quality development. This study found that technology finance has significantly enhanced green high-quality development of China’s as a whole through a non-linear promotion effect. To better promote green high-quality development, the following measures are recommended: 1) improving the level of technological and financial development, 2) increasing the scale of government expenditures, 3) strengthening infrastructure construction, 4) accelerating the construction of new urbanization, and 5) improving the level of human capital.
Analysis of Groundwater Chemical Characteristics and Spatiotemporal Evolution Trends of Influencing Factors in Southern Beijing Plain
Authors: Li Chen , Men Bao-Hui , Yin Shi-Yang
Published: May 2022

During the rapid urbanisation of Beijing in the past two decades, the original natural underlying surface has been changed, and the groundwater recharge and discharge processes had undergone great changes. Therefore, whether these natural and human factors affect the evolution of groundwater chemical composition, and how these influences evolve, need to be studied urgently. In this study, the Daxing District was taken as a typical area to understand the evolution rules of the chemical characteristics of shallow groundwater in the plain areas of Beijing. By collecting monitoring data on shallow groundwater from 2006 to 2016, the spatiotemporal evolution trends of the chemical characteristics and influencing factors of shallow groundwater in Daxing District were studied using the hydrochemical analysis methods and principal component analysis–partial connection number method. The results show the following: 1) The cations and anions of groundwater in the study area increased with time, indicating that the groundwater quality tends to deteriorate. 2) The hydrochemical type and anion and cation components changed accordingly with the change in NO3−, indicating the profound impact of NO3− on the evolution of groundwater components. 3) The groundwater has always been affected by human factors and natural factors. Natural factors have dominated, but the influence of human factors on hydrochemical components has been increasing. From the spatial distribution of the impact of human factors and natural factors on groundwater composition, regions with higher urbanisation degrees are highly affected by human factors and vice versa. This study can provide a theoretical and methodological reference for regional groundwater management and industrial layout.
Revealing the Critical Regulators of Modulated Smooth Muscle Cells in Atherosclerosis in Mice
Authors: Zhou Wenli , Bai Yongyi , Chen Jianqiao , Li Huiying , Zhang Baohua , Liu Hongbin
Published: May 2022

Background: There are still residual risks for atherosclerosis (AS)-associated cardiovascular diseases to be resolved. Considering the vital role of phenotypic switching of smooth muscle cells (SMCs) in AS, especially in calcification, targeting SMC phenotypic modulation holds great promise for clinical implications.

Methods: To perform an unbiased and systematic analysis of the molecular regulatory mechanism of phenotypic switching of SMCs during AS in mice, we searched and included several publicly available single-cell datasets from the GEO database, resulting in an inclusion of more than 80,000 cells. Algorithms implemented in the Seurat package were used for cell clustering and cell atlas depiction. The pySCENIC and SCENIC packages were used to identify master regulators of interested cell groups. Monocle2 was used to perform pseudotime analysis. clusterProfiler was used for Gene Ontology enrichment analysis.

Results: After dimensionality reduction and clustering, reliable annotation was performed. Comparative analysis between cells from normal artery and AS lesions revealed that three clusters emerged as AS progression, designated as mSMC1, mSMC2, and mSMC3. Transcriptional and functional enrichment analysis established a continuous transitional mode of SMCs’ transdifferentiation to mSMCs, which is further supported by pseudotime analysis. A total of 237 regulons were identified with varying activity scores across cell types. A potential core regulatory network was constructed for SMC and mSMC subtypes. In addition, module analysis revealed a coordinate regulatory mode of regulons for a specific cell type. Intriguingly, consistent with gain of ossification-related transcriptional and functional characteristics, a corresponding small set of regulators contributing to osteochondral reprogramming was identified in mSMC3, including Dlx5, Sox9, and Runx2.

Conclusion: Gene regulatory network inference indicates a hierarchical organization of regulatory modules that work together in fine-tuning cellular states. The analysis here provides a valuable resource that can provide guidance for subsequent biological experiments.
Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial
Authors: Ryan Rebecca , Mussa Aamirah , Singtaa-Madliki Mandisa , Batting Joanne , Balakrishna Yusentha , Morroni Chelsea , Hofmeyr G. Justus
Published: May 2022

Introduction

Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18–35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial.

Methods

Women were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135).

Results

Baseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152–455), IUD 235 (168–426) and LNG 216 (153–419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163–467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97–193) pmol/L] was significantly lower than in both IUD (p < 0.0001) and implant (p = 0.005) groups; and level in the implant group [156 (112–250) pmol/L] was significantly lower than in the IUD group (p = 0.004).

Conclusions

At 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods.

ECHO Study Registration

ClinicalTrials.gov, identifier: NCT02550067.
Immunogenicity of CAR-T Cell Therapeutics: Evidence, Mechanism and Mitigation
Authors: Khan Aalia N. , Chowdhury Ambalika , Karulkar Atharva , Jaiswal Ankesh Kumar , Banik Ankit , Asija Sweety , Purwar Rahul
Published: May 2022

Chimeric antigen receptor T cell (CAR-T) therapy demonstrated remarkable success in long-term remission of cancers and other autoimmune diseases. Currently, six products (Kymriah, Yescarta, Tecartus, Breyanzi, Abecma, and Carvykti) are approved by the US-FDA for treatment of a few hematological malignancies. All the six products are autologous CAR-T cell therapies, where delivery of CAR, which comprises of scFv (single-chain variable fragment) derived from monoclonal antibodies for tumor target antigen recognition is through a lentiviral vector. Although available CAR-T therapies yielded impressive response rates in a large number of patients in comparison to conventional treatment strategies, there are potential challenges in the field which limit their efficacy. One of the major challenges is the induction of humoral and/or cellular immune response in patients elicited due to scFv domain of CAR construct, which is of non-human origin in majority of the commercially available products. Generation of anti-CAR antibodies may lead to the clearance of the therapeutic CAR-T cells, increasing the likelihood of tumor relapse and lower the CAR-T cells efficacy upon reinfusion. These immune responses influence CAR-T cell expansion and persistence, that might affect the overall clinical response. In this review, we will discuss the impact of immunogenicity of the CAR transgene on treatment outcomes. Finally, this review will highlight the mitigation strategies to limit the immunogenic potential of CARs and improve the therapeutic outcome.
Retention of Donor T Cells in Lymphohematopoietic Tissue and Augmentation of Tissue PD-L1 Protection for Prevention of GVHD While Preserving GVL Activity
Authors: Song Qingxiao , Nasri Ubaydah , Nakamura Ryotaro , Martin Paul J. , Zeng Defu
Published: May 2022

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative therapy for hematological malignancies (i.e., leukemia and lymphoma) due to the graft-versus-leukemia (GVL) activity mediated by alloreactive T cells that can eliminate residual malignant cells and prevent relapse. However, the same alloreactive T cells can cause a serious side effect, known as graft-versus-host disease (GVHD). GVHD and GVL occur in distinct organ and tissues, with GVHD occurring in target organs (e.g., the gut, liver, lung, skin, etc.) and GVL in lympho-hematopoietic tissues where hematological cancer cells primarily reside. Currently used immunosuppressive drugs for the treatment of GVHD inhibit donor T cell activation and expansion, resulting in a decrease in both GVHD and GVL activity that is associated with cancer relapse. To prevent GVHD, it is important to allow full activation and expansion of alloreactive T cells in the lympho-hematopoietic tissues, as well as prevent donor T cells from migrating into the GVHD target tissues, and tolerize infiltrating T cells via protective mechanisms, such as PD-L1 interacting with PD-1, in the target tissues. In this review, we will summarize major approaches that prevent donor T cell migration into GVHD target tissues and approaches that augment tolerization of the infiltrating T cells in the GVHD target tissues while preserving strong GVL activity in the lympho-hematopoietic tissues.
Quantifying Per-Cell Chlorophyll a in Natural Picophytoplankton Populations Using Fluorescence-Activated Cell Sorting
Authors: Bock Nicholas , Subramaniam Ajit , Juhl Andrew R. , Montoya Joseph , Duhamel Solange
Published: May 2022

Marine phytoplankton play a central role in global biogeochemical cycling, carbon export, and the overall functioning of marine ecosystems. While chlorophyll a (Chl a) is widely used as a proxy for phytoplankton biomass, identifying the proportion of Chl a attributable to different phytoplankton groups remains a major challenge in oceanography, especially for the picophytoplankton groups that often represent the majority of phytoplankton biomass in the open ocean. We describe a method for measuring picophytoplankton per-cell Chl a in field samples using fluorescence-activated cell sorting followed by solvent-based Chl a extraction and fluorescence quantification. Applying this method to surface samples from the Gulf of Mexico, we determined per-cell Chl a to be 0.24 ± 0.07, 0.6 ± 0.33, and 26.36 ± 20.9 fg Chl a cell-1 for Prochlorococcus, Synechococcus, and PPE, respectively (mean ± SD). Measurements of per-cell Chl a using this method are precise to within 1.7, 2.1, and 3.1% for Prochlorococcus, Synechococcus, and PPE, respectively. We demonstrate that this approach can be used to obtain estimates of group-specific Chl a for Prochlorococcus, Synechococcus, and picophytoeukaryotes, the latter two of which cannot be captured by existing methods. We also demonstrate that measurements of per-cell Chl a made using this method in field samples are sufficiently precise to capture relationships between per-cell Chl a and cytometer red fluorescence, providing a bridge between biomass estimates from cell counts and bulk measurements of total Chl a.
P-Limitation Promotes Carbon Accumulation and Sinking of Emiliania huxleyi Through Transcriptomic Reprogramming
Authors: Wang Cong , Wang Jingtian , Li Ling , Wang Yujie , Lin Senjie
Published: May 2022

Global warming is expected to cause decreases in nutrient availability, photosynthesis, and potentially carbon export in the ocean. But how, and by what molecular mechanisms, nutrient limitation affects biological pump (BP) efficiency of phytoplankton are poorly understood. Here, using transcriptomics, miRNAomics, and physiological measurements, we report that phosphorus (P)-limitation increased cellular carbon and calcium contents and sinking rate of the cosmopolitan phytoplankton Emiliania huxleyi. Under P-limitation, when photosynthesis was depressed, there were substantial increases in cellular organic (3.4-fold) and inorganic (fivefold) carbon contents due to cell division arrest and, as our transcriptomic data suggest, CO2 incorporation into C4 compounds. Furthermore, calcification was increased by 46% through transcriptional and epigenetic regulations. An increase in sinking rate by 37-44% was detected. Although calcification releases equivalent amounts of CO2, the considerable increase in cellular carbon content and sinking rate far outweighed the CO2 release, leading to an elevated efficiency of carbon export by E. huxleyi, which would partially offset the decrease in BP capacity resulting from lower growth rate under P deficiency. However, how the observed sinking rate and its increase under P limitation on the laboratory cultures will translate into BP efficiency still requires further examination using in situ or mesocosm experiments.
A Decade of South Africa’s Acoustic Tracking Array Platform: An Example of a Successful Ocean Stewardship Programme
Authors: Murray Taryn S. , Elston Chantel , Parkinson Matthew C. , Filmalter John D. , Cowley Paul D.
Published: May 2022

The Blue Economy is a global initiative aimed at using marine resources to create economic viability and environmental sustainability. While successes have been reported, for example, in Europe and China, examples of African successes are notably missing. Abject poverty, unemployment and food insecurity are everyday concerns on the African continent; however, its large latitudinal coverage gives rise to extremely biodiverse marine fauna, which could promote socio-economic development of coastal communities through initiatives such as sustainably-managed fisheries. In order to improve sustainability via improved management, information on a species and its habitat is needed, particularly how it moves and in which areas it occurs. Acoustic telemetry is a powerful tool used to determine the movements of aquatic animals, the success of which has led to the development of several large-scale networks throughout the globe, including South Africa’s Acoustic Tracking Array Platform. This network, formally in place for the last decade, has now matured, and data are revealing insights into residency, habitat connectivity and transboundary movements of a multitude of animals, with some species having been continually detected for the past 10 years. These data are also actively being incorporated into marine spatial planning efforts, with the aim of protecting threatened and endemic species. Due to knowledge generation, successful benefit-sharing arrangements, and dedication to engage with the public and other stakeholder groups, the ATAP represents a highly successful example of ocean stewardship in Africa.
Vasopressors and Risk of Acute Mesenteric Ischemia: A Worldwide Pharmacovigilance Analysis and Comprehensive Literature Review
Authors: Jozwiak Mathieu , Geri Guillaume , Laghlam Driss , Boussion Kevin , Dolladille Charles , Nguyen Lee S.
Published: May 2022

Vasodilatory shock, such as septic shock, requires personalized management which include adequate fluid therapy and vasopressor treatments. While these potent drugs are numerous, they all aim to counterbalance the vasodilatory effects of a systemic inflammatory response syndrome. Their specific receptors include α- and β-adrenergic receptors, arginine-vasopressin receptors, angiotensin II receptors and dopamine receptors. Consequently, these may be associated with severe adverse effects, including acute mesenteric ischemia (AMI). As the risk of AMI depends on drug class, we aimed to review the evidence of plausible associations by performing a worldwide pharmacovigilance analysis based on the World Health Organization database, VigiBase®. Among 24 million reports, 104 AMI events were reported, and disproportionality analyses yielded significant association with all vasopressors, to the exception of selepressin. Furthermore, in a comprehensive literature review, we detailed mechanistic phenomena which may enhance vasopressor selection, in the course of treating vasodilatory shock.
The Downregulated Lipo-Related Gene Expression Pattern in Keloid Indicates Fat Graft Is a Potential Clinical Option for Keloid
Authors: Li Xueqing , Zhu Zhaowei , Xu Yangbin , Xu Shuqia
Published: May 2022

Background

Keloids are a common complication of wounds, often manifesting with continuous hyperplasia and aggressive growth. Keloids also have a high recurrence rate and are largely resistant to treatment, making them clinically incurable, highlighting the need to translate basic research into clinical practice.

Materials and Methods

We used GSE158395 and GSE92566 as discovery datasets to identify specific enriched hub genes and lncRNAs associated with keloid development and progression. This data was then used to identify the competing endogenous RNAs (ceRNAs) in these pathways by using a bidirectional selection method. Then, all hub genes and lncRNAs in ceRNAs were validated using GSE90051, GSE178562, and GSE175866, which describe the transcriptional profiles of keloid tissues, fibroblasts from pathological scars, and keloid fibroblast subpopulations, respectively. The keloid tissues were measured with qPCR.

Results

Both fat-associated biological processes and fat cell differentiation were enriched in the downregulated gene set. Further evaluation revealed that all 11 hub genes were lipo-related, and most of these were differentially expressed in all three validation datasets. We then identified a clear ceRNA network within the data comprising six hub genes and four lncRNAs. Evaluations of the validation datasets confirmed that all six of these hub genes and two of the four lncRNAs were downregulated in keloid tissues; two hub genes and one lncRNA were downregulated in fibroblasts from pathological scars; and five hub genes and one lncRNA were significantly downregulated in mesenchymal subpopulation. Three genes had statistical difference and eight genes showed downregulated trend through qPCR of the keloid tissue.

Conclusion

Our results suggest that keloid development relies on the downregulation of lipo-related genes and pre-adipocytes in diseased tissues and may be one of the key mechanisms underlying fat grafting-mediated treatment of pathological scarring.
Rare Taxa Drive the Response of Soil Fungal Guilds to Soil Salinization in the Taklamakan Desert
Authors: Lin Litao , Jing Xin , Lucas-Borja Manuel Esteban , Shen Congcong , Wang Yugang , Feng Wenting
Published: May 2022

Salinization poses great threats to soil fungal communities that would cause the losses of ecosystems services. Soil fungal communities are composed of different functional guilds such as saprotrophic, symbiotrophic, and pathotrophic fungi, and each guild includes many rare taxa and a few abundant taxa. Despite of low abundance, rare taxa may be crucial in determining the responses of entire soil fungal communities to salinization. However, it remains poorly understood how rare taxa mediate the impacts of soil salinization on soil fungal community structure. Here, we took advantage of a salinity gradient in a desert ecosystem ranging from 0.60 to 31.09 g kg−1that was created by a 12-year saline-water irrigation and assessed how the rare vs. abundant taxa of soil saprotrophic, symbiotrophic, and pathotrophic fungi respond to soil salinization through changes in the community biodiversity and composition. We found that the rare taxa of soil saprotrophic, symbiotrophic, and pathographic fungi were more sensitive to changes in soil salinity compared to the abundant taxa. In addition, the community composition of rare taxa of the saprotrophic and pathotrophic fungi not the symbiotrophic fungi was positively associated with soil salinity change. However, the symbiotrophic fungi showed greater variations in the species richness along the salinity gradient. These findings highlight the importance to differentiate rare taxa in predicting how the biodiversity and functional groups of soil fungal communities respond to soil salinization.
Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
Authors: Jeitler R. , Glader C. , Tetyczka C. , Zeiringer S. , Absenger-Novak M. , Selmani A. , Fröhlich E. , Roblegg E.
Published: May 2022

Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have to be applied. This is a prerequisite for the reliable and predictable performance of in-vitro biological studies. Here, we showed that solid lipid nanoparticles (SLN, palmitic acid) and nanostructured lipid carriers (NLC, palmitic acid and oleic acid in different ratios) with a size of 250 nm, a negative zeta potential, and a polydispersity index (PdI) of less than 0.3 can be reproducibly prepared by high-pressure homogenization using quality by design and a predictive model. SLN and NLC were colloidally stable after contact with physiological fluid and did not form agglomerates. The in-vitro studies clearly showed that besides particle size, surface charge and hydrophobicity, matrix composition had a significant effect. More specifically, the addition of the liquid lipid oleic acid increased the cellular uptake capacity without changing the underlying uptake mechanism. Regardless of the matrix composition, caveolin-mediated endocytosis was the major route of uptake, which was confirmed by particle localization in the endoplasmic reticulum. Thus, this work provides useful insights into the optimal composition of lipid carrier systems to enhance the intracellular uptake capacity of drugs into the oral mucosa.
Eosinophils, Stroke-Associated Pneumonia, and Outcome After Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Guo Zhiliang , Hou Jie , Yu Shuai , Zhang Hang , Yu Shuhong , Wang Huaishun , Xu Jiaping , You Shoujiang , Huang Zhichao , Xiao Guodong , Cao Yongjun , Liu Chun-Feng
Published: May 2022

Background

Eosinophils contribute to antibacterial defense by releasing mitochondrial DNA, which are decreased in patients with acute ischemic stroke (AIS). However, the impact of eosinophils on stroke-associated pneumonia (SAP) among patients with AIS remains unclear. Moreover, whether SAP is in the path of the association between eosinophils and clinical outcomes also remains unclear. We aimed to assess the relationships between eosinophils, SAP, and clinical outcome after mechanical thrombectomy in patients with AIS.

Methods

A total of 328 consecutive patients with AIS who underwent mechanical thrombectomy between May 2017 and March 2021 were analyzed. Their baseline data and peripheral eosinophil counts were recorded on admission. Regression analysis was used to assess the effect of eosinophils on SAP, and its effect on poor outcome is defined as a modified Rankin Scale score of 3–6 at month 3 after admission. Mediation analysis was utilized to assess the proportion of the total effect of SAP on the association between eosinophils and poor outcomes.

Results

Multivariate analysis revealed that eosinophils was independently associated with SAP after adjusting for potential confounders (odds ratio, 0.00; 95% CI, 0.00–0.38; P = 0.0267), which are consistent with the result of eosinophils (dichotomous) as a categorical variable (odds ratio, 0.54; 95% CI, 0.31–0.96; P = 0.0342). A non-linear relationship was detected between eosinophils and SAP, whose inflection point was 0.06. Subgroup analyses further confirmed these associations. Eosinophils were also associated with poor outcomes (odds ratio, 0.00; 95% CI, 0.00–0.14; P = 0.0124). Additionally, mediation analysis found that SAP partially mediated the negative relationship between eosinophils and poor outcome (indirect effect = −0.169; 95% CI:−0.339 –−0.040, P < 0.001).

Conclusion

Our findings suggested that a lower eosinophil level was associated with higher SAP and poorer outcome, and SAP might play an important effect in the association between eosinophils and poor outcomes.
Graph Theoretical Analysis of Structural Covariance Reveals the Relevance of Visuospatial and Attentional Areas in Essential Tremor Recovery After Stereotactic Radiosurgical Thalamotomy
Authors: Bolton Thomas A. W. , Van De Ville Dimitri , Régis Jean , Witjas Tatiana , Girard Nadine , Levivier Marc , Tuleasca Constantin
Published: May 2022

Essential tremor (ET) is the most common movement disorder. Its pathophysiology is only partially understood. Here, we leveraged graph theoretical analysis on structural covariance patterns quantified from morphometric estimates for cortical thickness, surface area, and mean curvature in patients with ET before and one year after (to account for delayed clinical effect) ventro-intermediate nucleus (Vim) stereotactic radiosurgical thalamotomy. We further contrasted the observed patterns with those from matched healthy controls (HCs). Significant group differences at the level of individual morphometric properties were specific to mean curvature and the post-/pre-thalamotomy contrast, evidencing brain plasticity at the level of the targeted left thalamus, and of low-level visual, high-level visuospatial and attentional areas implicated in the dorsal visual stream. The introduction of cross-correlational analysis across pairs of morphometric properties strengthened the presence of dorsal visual stream readjustments following thalamotomy, as cortical thickness in the right lingual gyrus, bilateral rostral middle frontal gyrus, and left pre-central gyrus was interrelated with mean curvature in the rest of the brain. Overall, our results position mean curvature as the most relevant morphometric feature to understand brain plasticity in drug-resistant ET patients following Vim thalamotomy. They also highlight the importance of examining not only individual features, but also their interactions, to gain insight into the routes of recovery following intervention.
Effects of Intermittent Hypoxia in Training Regimes and in Obstructive Sleep Apnea on Aging Biomarkers and Age-Related Diseases: A Systematic Review
Authors: Tessema Belay , Sack Ulrich , König Brigitte , Serebrovska Zoya , Egorov Egor
Published: May 2022

Several studies have assessed the effects of intermittent hypoxia-normoxia training (IHNT), intermittent hypoxia-hyperoxia training (IHHT), and obstructive sleep apnea (OSA) on aging and age-related diseases in humans; however, the results remain contradictory. Therefore, this review aims to systematically summarize the available studies on the effects of IHNT, IHHT, and OSA on aging and age-related diseases. Relevant studies were searched from PubMed, Google Scholar, Cochrane Library databases, and through manual searching from reference lists of eligible studies. A total of 38 eligible studies were included in this systematic review. IHHT and IHNT provide positive effects on several age-related parameters including quality of life, cognitive and physical functions, plasma level of glucose and cholesterol/LDL, systolic blood pressure, red blood cells, and inflammation. Moreover, moderate intermittent hypoxia induces telomerase reverse transcriptase (TERT) activity and telomere stabilization, delays induction of senescence-associated markers expression and senescence-associated β-galactosidase, upregulates pluripotent marker (Oct4), activates a metabolic shift, and raises resistance to pro-apoptotic stimuli. On the contrary, intermittent hypoxia in OSA causes hypertension, metabolic syndrome, vascular function impairment, quality of life and cognitive scores reduction, advanced brain aging, increase in insulin resistance, plasma hydrogen peroxide, GSH, IL-6, hsCRP, leptin, and leukocyte telomere shortening. Thus, it can be speculated that the main factor that determines the direction of the intermittent hypoxia action is the intensity and duration of exposure. There is no direct study to prove that IHNT/IHHT actually increases life expectancy in humans. Therefore, further study is needed to investigate the actual effect of IHNT/IHHT on aging in humans.

Systematic Review Registration

www.crd.york.ac.uk/prospero, identifier CRD42022298499.
Cannabinoid 1/2 Receptor Activation Induces Strain-Dependent Behavioral and Neurochemical Changes in Genetic Absence Epilepsy Rats From Strasbourg and Non-epileptic Control Rats
Authors: De Deurwaerdère Philippe , Casarrubea Maurizio , Cassar Daniel , Radic Manuela , Puginier Emilie , Chagraoui Abdeslam , Crescimanno Giuseppe , Crunelli Vincenzo , Di Giovanni Giuseppe
Published: May 2022

Childhood absence epilepsy (CAE) is characterized by absence seizures, which are episodes of lack of consciousness accompanied by electrographic spike-wave discharges. About 60% of children and adolescents with absence seizures are affected by major neuropsychological comorbidities, including anxiety. Endocannabinoids and monoamines are likely involved in the pathophysiology of these CAE psychiatric comorbidities. Here, we show that the synthetic cannabinoid receptor type 1/2 (CB1/2R) agonist WIN 55,212-2 (2 mg/kg) has a strain-dependent effect on anxiety-like and motor behavior when assess in the hole board test and cerebral monoaminergic levels in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and their non-epileptic control (NEC) rat strain. Using quantitative and Temporal pattern (T-pattern) analyses, we found that WIN 55,212-2 did not affect the emotional status of GAERS, but it was anxiolytic in NEC. Conversely, WIN 55,212-2 had a sedative effect in GAERS but was ineffective in NEC. Moreover, vehicle-treated GAERS more motivated to explore by implementing more complex and articulated strategies. These behavioral changes correlate with the reduction of 5-HT in the hippocampus and substantia nigra (SN) and noradrenaline (NA) in the entopeduncular nucleus (EPN) in vehicle-treated GAERS compared to NEC rats, which could contribute to their low anxiety status and hypermotility, respectively. On the other hand, the increased level of NA in the EPN and 5-HT in the SN is consistent with an activation of the basal ganglia output-mediated motor suppression observed in WIN 55,212-2-treated GAERS rats. These data support the view of a strain-dependent alteration of the endocannabinoid system in absence epilepsy by adding evidence of a lower emotional responsiveness and a basal ganglia hypersensitivity to cannabinoids in GAERS compared to NEC rats.
Case Report: Stent Retriever Thrombectomy of Acute Basilar Artery Occlusion via the Type 1 Proatlantal Intersegmental Artery
Authors: Zhao Lei , Yang Lijun , Liu Xiaosong , Wang Xiaoliang , Zhang Gengshen , Wu Jianliang
Published: May 2022

Stent retriever thrombectomy (SRT) is one of the most effective methods for the recanalization of acute basilar artery occlusion (ABAO). The proatlantal intersegmental artery (PIA) is a rare carotid-vertebrobasilar anastomosis. Recognition of this rare form of anastomosis is particularly important for the rapid establishment of positive blood flow in patients with ABAO. In this case, the patient had a rare, left type 1 PIA. The right vertebral artery (VA) was tenuous and did not enter the cranium. We performed a thrombectomy of the ABAO by inserting a catheter via the type 1 PIA. The complete recanalization of basilar artery (BA) flow was achieved following two stent retractions; however, the patient eventually died of brain stem hemorrhage.
Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report
Authors: Lu Yue , Qiu Chang , Chang Lei , Luo Bei , Dong Wenwen , Zhang Wenbin , Sun Hai-Hua
Published: May 2022

Background and Importance

Deep brain stimulation (DBS) has been approved to treat a variety of movement disorders, including Parkinson's disease (PD), essential tremor, and dystonia. Following the DBS surgery, some perioperative and even delayed complications due to intracranial and hardware-related events could occur, which may be life-threatening and require immediate remedial measures.

Clinical Presentation

We report a case of an older woman with advanced PD who developed the unique complication of unilateral cyst formation at the tip of the DBS electrode after undergoing bilateral placement of subthalamic nucleus DBS. After a period of controlled motor symptoms, the patient showed new neurological deficits related to right peri-lead edema. However, the new neurological symptoms regressed quickly over several days with stereotactic implantation of a puncture needle to drain the cyst fluid without removing the affected lead.

Conclusion

The occurrence of an intraparenchymal cyst following DBS surgery is a rare but life-threatening complication that could relate to edema around the electrodes or cerebrospinal fluid tracking. Stereotactic aspiration makes the intracranial cyst regress safely and effectively and ensures that the electrode is in the optimal position of the target nucleus to achieve an effective DBS surgery.
The Clinical Utility of the MOCA in iNPH Assessment
Authors: Wesner Eric , Etzkorn Lacey , Bakre Shivani , Chen Jinyu , Davis Alexander , Zhang Yifan , Yasar Sevil , Rao Aruna , Luciano Mark , Wang Jiangxia , Moghekar Abhay
Published: May 2022

Objectives

We sought to estimate reliable change thresholds for the Montreal Cognitive Assessment (MoCA) for older adults with suspected Idiopathic Normal Pressure Hydrocephalus (iNPH). Furthermore, we aimed to determine the likelihood that shunted patients will demonstrate significant improvement on the MoCA, and to identify possible predictors of this improvement.

Methods

Patients (N = 224) presenting with symptoms of iNPH were given a MoCA assessment at their first clinic visit, and also before and after tap test (TT) or extended lumbar drainage (ELD). Patients who were determined to be good candidates for shunts (N = 71, 31.7%) took another MoCA assessment following shunt insertion. Reliable change thresholds for MoCA were derived using baseline visit to pre-TT/ELD assessment using nine different methodologies. Baseline characteristics of patients whose post-shunt MoCA did and did not exceed the reliable change threshold were compared.

Results

All nine of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 16 to 22 (38.4% of patients). Furthermore, a majority of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 14 to 25. Reliable change thresholds varied across methods from 4 to 7 points for patients outside of this range. 10.1% had at least a 5-point increase from baseline to post-TT/ELD. Compared to patients who did not receive a shunt, patients who received a shunt did not have lower average MoCA at baseline (p = 0.88) or have better improvement in MoCA scores after the tap test (p = 0.17). Among shunted patients, 23.4% improved by at least 5 points on the MoCA from baseline to post-shunt. Time since onset of memory problems and post-TT/ELD gait function were the only clinical factors significantly associated with having a reliable change in MoCA after shunt insertion (p = 0.019; p = 0.03, respectively).

Conclusions

In patients with iNPH, clinicians could consider using a threshold of 5 points for determining whether iNPH-symptomatic patients have experienced cognitive benefits from cerebrospinal fluid drainage at an individual level. However, a reliable change cannot be detected for patients with a baseline MoCA of 26 or greater, necessitating a different cognitive assessment tool for these patients.
Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland
Authors: Ardila Jurado Elena , Sturm Veit , Brugger Florian , Nedeltchev Krassen , Arnold Marcel , Bonati Leo H. , Carrera Emmanuel , Michel Patrik , Cereda Carlo W. , Bolognese Manuel , Albert Sylvan , Medlin Friedrich , Berger Christian , Schelosky Ludwig , Renaud Susanne , Niederhauser Julien , Bonvin Christophe , Mono Marie-Luise , Rodic Biljana , Tarnutzer Alexander A. , Schwegler Guido , Salmen Stephan , Luft Andreas R. , Peters Nils , Vehoff Jochen , Kägi Georg ,   The Swiss Stroke Registry Investigators
Published: May 2022

Background and Purpose

Central retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO.

Methods

(1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland.

Results

Three hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy.

Conclusions

CRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.
Upper Limb Stroke Rehabilitation Using Surface Electromyography: A Systematic Review and Meta-Analysis
Authors: Munoz-Novoa Maria , Kristoffersen Morten B. , Sunnerhagen Katharina S. , Naber Autumn , Alt Murphy Margit , Ortiz-Catalan Max
Published: May 2022

Background

Upper limb impairment is common after stroke, and many will not regain full upper limb function. Different technologies based on surface electromyography (sEMG) have been used in stroke rehabilitation, but there is no collated evidence on the different sEMG-driven interventions and their effect on upper limb function in people with stroke.

Aim

Synthesize existing evidence and perform a meta-analysis on the effect of different types of sEMG-driven interventions on upper limb function in people with stroke.

Methods

PubMed, SCOPUS, and PEDro databases were systematically searched for eligible randomized clinical trials that utilize sEMG-driven interventions to improve upper limb function assessed by Fugl-Meyer Assessment (FMA-UE) in stroke. The PEDro scale was used to evaluate the methodological quality and the risk of bias of the included studies. In addition, a meta-analysis utilizing a random effect model was performed for studies comparing sEMG interventions to non-sEMG interventions and for studies comparing different sEMG interventions protocols.

Results

Twenty-four studies comprising 808 participants were included in this review. The methodological quality was good to fair. The meta-analysis showed no differences in the total effect, assessed by total FMA-UE score, comparing sEMG interventions to non-sEMG interventions (14 studies, 509 participants, SMD 0.14, P 0.37, 95% CI –0.18 to 0.46, I255%). Similarly, no difference in the overall effect was found for the meta-analysis comparing different types of sEMG interventions (7 studies, 213 participants, SMD 0.42, P 0.23, 95% CI –0.34 to 1.18, I273%). Twenty out of the twenty-four studies, including participants with varying impairment levels at all stages of stroke recovery, reported statistically significant improvements in upper limb function at post-sEMG intervention compared to baseline.

Conclusion

This review and meta-analysis could not discern the effect of sEMG in comparison to a non-sEMG intervention or the most effective type of sEMG intervention for improving upper limb function in stroke populations. Current evidence suggests that sEMG is a promising tool to further improve functional recovery, but randomized clinical trials with larger sample sizes are needed to verify whether the effect on upper extremity function of a specific sEMG intervention is superior compared to other non-sEMG or other type of sEMG interventions.
Heuristic Vetoing: Top-Down Influences of the Anchoring-and-Adjustment Heuristic Can Override the Bottom-Up Information in Visual Images
Authors: Branch Fallon , Park Erin , Hegdé Jay
Published: May 2022

When making decisions under uncertainty, human subjects do not always act as rational decision makers, but often resort to one or more mental “shortcuts”, or heuristics, to arrive at a decision. How do such “top-down” processes affect real-world decisions that must take into account empirical, “bottom-up” sensory evidence? Here we use recognition of camouflaged objects by expert viewers as an exemplar case to demonstrate that the effect of heuristics can be so strong as to override the empirical evidence in favor of heuristic information, even though the latter is random. We provided the viewers a random number that we told them was the estimate of a drone reconnaissance system of the probability that the visual image they were about to see contained a camouflaged target. We then showed them the image. We found that the subjects’ own estimates of the probability of the target in the image reflected the random information they were provided, and ignored the actual evidence in the image. However, when the heuristic information was not provided, the same subjects were highly successful in finding the target in the same set of images, indicating that the effect was solely attributable to the availability of heuristic information. Two additional experiments confirmed that this effect was not idiosyncratic to camouflage images, visual search task, or the subjects’ prior training or expertise. Together, these results demonstrate a novel aspect of the interaction between heuristics and sensory information during real-world decision making, where the former can be strong enough to veto the latter. This ‘heuristic vetoing’ is distinct from the vetoing of sensory information that occurs in certain visual illusions.
Coupling of in vitro Neocortical-Hippocampal Coculture Bursts Induces Different Spike Rhythms in Individual Networks
Authors: Chang ChihHsiang , Furukawa Takuma , Asahina Takahiro , Shimba Kenta , Kotani Kiyoshi , Jimbo Yasuhiko
Published: May 2022

Brain-state alternation is important for long-term memory formation. Each brain state can be identified with a specific process in memory formation, e.g., encoding during wakefulness or consolidation during sleeping. The hippocampal-neocortical dialogue was proposed as a hypothetical framework for systems consolidation, which features different cross-frequency couplings between the hippocampus and distributed neocortical regions in different brain states. Despite evidence supporting this hypothesis, little has been reported about how information is processed with shifts in brain states. To address this gap, we developed an in vitro neocortical-hippocampal coculture model to study how activity coupling can affect connections between coupled networks. Neocortical and hippocampal neurons were cultured in two different compartments connected by a micro-tunnel structure. The network activity of the coculture model was recorded by microelectrode arrays underlying the substrate. Rhythmic bursting was observed in the spontaneous activity and electrical evoked responses. Rhythmic bursting activity in one compartment could couple to that in the other via axons passing through the micro-tunnels. Two types of coupling patterns were observed: slow-burst coupling (neocortex at 0.1–0.5 Hz and hippocampus at 1 Hz) and fast burst coupling (neocortex at 20–40 Hz and hippocampus at 4–10 Hz). The network activity showed greater synchronicity in the slow-burst coupling, as indicated by changes in the burstiness index. Network synchronicity analysis suggests the presence of different information processing states under different burst activity coupling patterns. Our results suggest that the hippocampal-neocortical coculture model possesses multiple modes of burst activity coupling between the cortical and hippocampal parts. With the addition of external stimulation, the neocortical-hippocampal network model we developed can elucidate the influence of state shifts on information processing.