bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequelae and mortality in patients with HIV/AIDS and Progressive Multifocal Leukoencephalopathy: Systematic review and case series in the Brazilian Amazon
Authors: Valente Jefferson , Del-Tejo Paola López , Cubas-Vega Nadia Carolina , Rodrigues Maria Gabriela de Almeida , de Barros Francisco Railson Bispo , Alexandre Márcia Araújo , Arêas Guilherme Peixoto Tinoco , Bastos Michele , Pinto Sérgio Damasceno , Barros Camila Miriam S. S. , Marinho Eveny Perlize , Mello Sabrina , Ferreira Ewerton , Aprigio Valderjane , Monte Rossiclea Lins , Sampaio Vanderson , Lacerda Marcus , Baia-da-Silva Djane Clarys , Val Fernando
Published: March 2023

Background

Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic neurological disease that mainly affects individuals with HIV/AIDS and has high morbidity and mortality, due to its demyelinating characteristic. This co-infection has been reported since the begging of HIV/Aids epidemic with increasing unfavorable outcomes, however, factors associated to sequelae and death are greatly unknown. In this study we aimed to understand factors associated with the main outcomes of individuals diagnosed with PML and HIV/AIDS, in addition to reporting the characteristics of patients presenting to a referral center in infectious diseases in the Brazilian Amazon.

Methods

A systematic review was performed until July 2022, following the PRISMA guidelines, at Medline/Pubmed, Web of Science, Lilacs and Scielo databases using combinations of HIV, Aids, JC Virus and Progressive Multifocal Leukoencephalopathy, with no restriction to publication date. Additional cases, meeting the eligibility criteria, were added from our hospital database, which consisted of patients presenting PML/HIV between 2010 and 2022. A meta-analysis aiming to explore factors associated to sequelae and death was performed. Baseline characteristics were described using mean and standard deviation, or median and interquartile range when appropriate; multivariate analysis was performed to study factors associated to death and sequelae outcomes.

Results

Eighteen patients were diagnosed between 2010 and 2022, of these, 10 had positive PCR for JC virus. In the Systematic Review, 216 studies yielded 235 confirmed cases of co-infection. A total of 245 were included for analysis. The rates of death and sequelae were, respectively, 47.1% (114/242) and 41.2% (54/131). The use of antiretroviral therapy was more associated with a lower chance of death (OR 0.30, 95% CI: 0.11-0.83), while muscle weakness (OR 4.82, 95% CI: 2.07-11.21) and muscle spasms (OR 6.12, 95% CI: 1.05-35.76) were associated with greater chances of sequelae.

Conclusion

Those on antiretroviral therapy appear to be less likely to die, and among those who survive, those who have muscle weakness as a symptom on admission are more likely to develop sequelae. Adherence to ART, as well as a comprehensive clinical evaluation and follow-up may help to improve clinical outcomes and awareness of morbidities.
Soil organic carbon storage in Liaohe River Estuary Wetlands under restoration and multiple management strategies, based on landscape patterns
Authors: Wang Guanxun , Pan Jingyu , Yu Jing , Yan Wenwen , Gu Dongqi , Du Jun
Published: March 2023

Introduction

Management of coastal wetlands has resulted in extensive conservation of this natural resource; however, changes in carbon storage function are not yet known. There is a direct link between landscape and soil carbon storage. Predicting future changes in the landscape and carbon storage in coastal wetlands is important for developing wetland management policies.

Method

Here, remote sensing and physical methods were used to measure and calculate the landscape and surface soil carbon stocks of the Liaohe River Estuary Wetland (LREW). The changes in the landscape and soil carbon stocks under three scenarios: natural development, strict protection, and culture pond transfer, were then predicted using the PLUS model.

Result

The results indicate that the surface soil organic carbon storage was 2107.97×103 t, while soil organic carbon density decreased from land to sea. Anthropogenic activity was found to be the main driver of the current landscape evolution. However, the impact of sea level rise is increasing. By 2030, considerably more storage will be gained under the culture pond transfer scenario than at present.

Discussion

Our results reveal that some of the methods of ecological restoration may diminish the carbon storage capacity of coastal wetlands. Making full use of areas with high carbon storage potential may be an effective wetland carbon sink management strategy. Governments should consider more comprehensively for a better carbon pool when developing restoration strategies.
Post-COVID-19 polyautoimmunity – Fact or coincidence: A case report
Authors: Shorbagi Ali Ibrahim , Obaideen Abdulmunhem , Jundi Majd
Published: March 2023

COVID-19 exhibits diverse and systemic clinical symptoms, much like systemic autoimmune diseases, and there are notable similarities in the immune responses seen in both conditions. There are rare reports of ulcerative colitis and autoimmune hepatitis triggered by COVID-19 infection. Reported herein is a case of a previously healthy patient who was diagnosed with chronic colitis resembling ulcerative colitis, autoimmune pancreatitis, and suspected immune-mediated hepatitis (AIH-like hepatitis) 2 months after a COVID-19 infection. A 33-year-old COVID-19-vaccinated male, presented with abdominal pain, nausea, and vomiting for 2 days. He also had bloody diarrhea that persisted for 2 months after recovering from a COVID-19 infection. A diagnosis of acute pancreatitis was confirmed by markedly elevated serum amylase and lipase and a CT scan of the abdomen. Colonoscopy and histopathology findings also confirmed a diagnosis of chronic colitis resembling ulcerative colitis (Mayo Endoscopy Subscore 3). Marked improvement in bloody diarrhea was observed within 72 h of treatment with IV prednisolone. MRI of the abdomen performed due to an unresolved clinical picture of pancreatitis revealed a bulky pancreas showing delayed diffuse homogenous enhancement, findings possibly consistent with autoimmune pancreatitis. Investigation for elevated liver transaminases showed high titers of antinuclear antibodies and anti-smooth muscle (anti-actin) antibodies while viral hepatitis markers were negative. The patient had already been started on steroid therapy before the lab results were available, with rapid normalization of liver enzymes following treatment. A liver biopsy was not performed. The patient is currently on mesalazine 4 gr/day, and azathioprine 100 mg/day – oral steroids had been tapered and discontinued. Seven months after the initial diagnosis, the patient remains symptom-free. A high level of suspicion for autoimmune disorders is required when assessing patients with a history of COVID-19 infection, although diagnostic pathways remain the same, with generally good response and remission rates to conventional treatment.
Characteristics and patients’ portrayals of Norwegian social media memes. A mixed methods analysis
Authors: Jarmund Anders Hagen , Tollefsen Sofie Eline , Ryssdal Mariell , Jensen Audun Bakke , Sakshaug Baard Cristoffer , Unneland Eirik , Solberg Berge , Mjølstad Bente Prytz
Published: March 2023

Background

Despite reports on troublesome contents created and shared online by healthcare professionals, a systematic inquiry of this potential problem has been missing. Our objective was to characterize the content of healthcare-associated social media memes in terms of common themes and how patients were portrayed.

Materials and methods

This study applied a mixed methods approach to characterize the contents of Instagram memes from popular medicine- or nursing-associated accounts in Norway. In total, 2,269 posts from 18 Instagram accounts were included and coded for thematic contents. In addition, we conducted a comprehensive thematic analysis of 30 selected posts directly related to patients.

Results

A fifth of all posts (21%) were related to patients, including 139 posts (6%) related to vulnerable patients. Work was, however, the most common theme overall (59%). Nursing-associated accounts posted more patient-related contents than medicine-associated accounts (p < 0.01), but the difference may be partly explained by the former focusing on work life rather than student life. Patient-related posts often thematized (1) trust and breach of trust, (2) difficulties and discomfort at work, and (3) comical aspects of everyday life as a healthcare professional.

Discussion

We found that a considerable number of Instagram posts from healthcare-associated accounts included patients and that these posts were diverse in terms of contents and offensiveness. Awareness that professional values also apply online is important for both healthcare students and healthcare providers. Social media memes can act as an educational resource to facilitate discussions about (e-)professionalism, the challenges and coping of everyday life, and ethical conflicts arising in healthcare settings.
Incorporating circulating cytokines into the idiopathic inflammatory myopathy subclassification toolkit
Authors: De Paepe Boel
Published: March 2023

Extensive diagnostic delays and deferred treatment impact the quality of life of patients suffering from an idiopathic inflammatory myopathy. In-depth subtyping of patients is a necessary effort to engage appropriate disease management and may require specialized and elaborate evaluation of the complex spectrum of clinical and pathological disease features. Blood samples are routinely taken for diagnostic purposes, with creatine kinase measurement and autoantibody typing representing standard diagnostic tools in the clinical setting. However, for many patients the diagnostic odyssey includes the invasive and time-consuming procedure of taking a muscle biopsy. It is proposed that further implementation of blood-based disease biomarkers represents a convenient alternative approach with the potential to reduce the need for diagnostic muscle biopsies substantially. Quantification of judicious combinations of circulating cytokines could be added to the diagnostic flowchart, and growth differentiation factor 15 and C-X-C motif chemokine ligand 10 come forward as particularly good candidates. These biomarkers can offer complementary information for diagnosis indicative of disease severity, therapeutic response and prognosis.
Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota
Authors: Wang Haiying , Wang Qiang , Liang Cuimei , Pan Liang , Hu Hui , Fang Hongjuan
Published: March 2023

Background

Intestinal dysbiosis has been increasingly implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Acupuncture has been shown to have beneficial effects on NAFLD, but the mechanism is not yet clear. This study explores the potential beneficial effects of acupuncture on intestinal microbiota in NAFLD.

Methods

An NAFLD model in Sprague Dawley rats was established using a high-fat diet (HFD) for 10  weeks. NAFLD rats were randomly divided into control, model, and acupuncture groups. Following acupuncture treatment over 6 weeks, automated biochemical analysis was used to measure serum lipid metabolism parameters, including levels of alanine transferase, aspartate transferase, alkaline phosphatase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The level of serum inflammatory factors interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay. The characteristics of steatosis were evaluated using quantitative computed tomography, hematoxylin and eosin staining, and Oil Red O staining in the liver, while the intestinal microbiota was determined using 16S rRNA gene sequencing.

Results

Acupuncture decreased the systemic inflammatory response, ameliorated dyslipidemia, and improved liver function indexes in NAFLD model rats. Tomography and staining indicated that acupuncture reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that acupuncture reduced the Firmicutes to Bacteroidetes (F/B) ratio, increased the abundance of microbiota, including Bacteroidales_S24-7_group, Prevotellaceae, Bacteroidaceae, Blautia, norank_f_Bacteroidales_S24-7_group, Bacteroides, and Prevotella_9, and decreased the abundance of Ruminococcaceae_UCG-014. Correlation analysis suggested a close correlation between lipid metabolism, inflammation factors, hepatic steatosis, and the changed intestinal microbiota.

Conclusion

Acupuncture can significantly improve lipid metabolism and the systemic inflammatory response in HFD-induced NAFLD rats, potentially by regulating intestinal microbiota composition.
Taxonomy and phylogeny of brown-rot corticioid fungi in China: Coniophora beijingensis and Veluticeps subfasciculata spp. nov.
Authors: Li Yue , He Shuang-Hui
Published: March 2023

Brown-rot fungi account for a small portion of the wood-decaying fungi. There are a few corticioid genera causing brown rot of wood, and their species diversity is still under investigated and studied, especially in subtropical and tropical areas. Two new brown-rot corticioid fungi, Coniophora beijingensis and Veluticeps subfasciculata were found during the investigation of corticioid fungi in China. Phylogenetic analyses of the two genera were carried out separately based on ITS-28S sequence data. Coniophora beijingensis was collected from Beijing, north China, from different kinds of angiosperm and gymnosperm trees, and is characterized by possessing a monomitic hyphal system with colorless hyphae and relatively small pale yellow basidiospores 7–8.6 μm× 4.5–6 μm. Veluticeps subfasciculata was collected from Guizhou and Sichuan Provinces, southwestern China, on Cupressus and is characterized by the resupinate to effused-reflexed basidiomes with a colliculose hymenophore, nodose-septate generative hyphae, fasciculate skeletocystidia and subcylindrical to subfusiform basidiospores 8–11 μm × 2.5–3.5 μm. Descriptions and illustrations are provided for the two new species, and identification keys to Coniophora and Veluticeps species in China are given. Coniophora fusispora is reported in China for the first time.
Bioengineering of fungal endophytes through the CRISPR/Cas9 system
Authors: Verma Vinita , Batta Arpita , Singh Harikesh B. , Srivastava Alok , Garg Sanjay Kumar , Singh Vijay Pal , Arora Pankaj Kumar
Published: March 2023

The CRISPR/Cas9 system is a genome-editing tool that allows for precise and efficient modifications to the DNA of a cell. This technology can be used in endophytic fungi, which live within plants and can have beneficial effects on their host, making them important for agriculture. Using CRISPR/Cas9, researchers can introduce specific genetic changes into endophytic fungal genomes, allowing them to study the function of genes, improve their plant-growth-promoting properties, and create new, more beneficial endophytes. This system works by using the Cas9 protein, which acts as a pair of molecular scissors, to cut DNA at specific locations determined by a guide RNA. Once the DNA is cut, the cell’s natural repair mechanisms can be used to insert or delete specific genes, allowing for precise editing of the fungal genome. This article discusses the mechanism and applications of CRISPR/Cas9 to fungal endophytes.
Genetic characterization of human adenoviruses in patients using metagenomic next-generation sequencing in Hubei, China, from 2018 to 2019
Authors: Fang Bin , Lai Juan , Liu Yongfeng , Yu Tian-tian , Yu Xiao , Li Xiang , Dong Lijun , Zhang Xin , Yang Wei , Yan Qin , Sun Lei , Liu Lin-lin
Published: March 2023

Objectives

This study aimed to characterize the genomic epidemiology of human adenoviruses (HAdVs) in Hubei, China, using metagenomic next-generation sequencing (mNGS).

Methods

In total, 25 HAdV-positive samples collected from 21 pediatric patients were sequenced and subjected to mNGS using the NextSeq 550 and GenoLab M sequencing platforms. The metagenomic data were assembled de novo for molecular typing, phylogenetic and recombination analyzes.

Results

We assembled 50 HAdV genomes, 88% (22/25) genomes from GenoLab M, and 84% (21/25) genomes from NextSeq 550 have perfect alignments to reference genomes with greater than 90%. The most fully assembled 25 genomes were categorized into 7 HAdV genotypes, the most abundant of which were HAdV-B3 (9/25) and HAdV-C2 (6/25). Phylogenetic analyzes revealed that the newly isolated HAdV-B3 strains diverged into separate clusters according to their genotypes. Vigilance is needed that HAdV-B3 isolates have begun to form new distinct clusters. High nucleotide identity was observed in the whole genome level within the same HAdV genotypes, while marked differences of three capsid genes across HAdV genotypes were noted. The high nucleotide diversity regions were concordant with the reported hypervariable regions. Further, three recombinant strains were identified: S64 and S71 originated from the parental strains HAdV-B14 and HAdV-B11, and S28 originated from HAdV-C1, HAdV-C5, and HAdV-CBJ113. GenoLab M and NextSeq 550 showed comparable performance with respect to data yield, duplication rate, human ratio, and assembly completeness.

Conclusion

The sequencing quality and assembly accuracy showed that mNGS assembled genomes can be used for subsequently HAdV genotyping and genomic characterization. The high nucleotide diversity of capsid genes and high frequency of recombination events has highlighted the necessity for HAdV epidemiological surveillance in China.
Modulation of plant acetyl-CoA synthetase activity by post-translational lysine acetylation
Authors: Sofeo Naazneen , Winkelman Dirk C. , Leung Karina , Nikolau Basil J.
Published: March 2023

Acetyl-CoA synthetase (ACS) is one of several enzymes that generate the key metabolic intermediate, acetyl-CoA. In microbes and mammals ACS activity is regulated by the post-translational acetylation of a key lysine residue. ACS in plant cells is part of a two-enzyme system that maintains acetate homeostasis, but its post-translational regulation is unknown. This study demonstrates that the plant ACS activity can be regulated by the acetylation of a specific lysine residue that is positioned in a homologous position as the microbial and mammalian ACS sequences that regulates ACS activity, occurring in the middle of a conserved motif, near the carboxyl-end of the protein. The inhibitory effect of the acetylation of residue Lys-622 of the Arabidopsis ACS was demonstrated by site-directed mutagenesis of this residue, including its genetic substitution with the non-canonical N-ε-acetyl-lysine residue. This latter modification lowered the catalytic efficiency of the enzyme by a factor of more than 500-fold. Michaelis-Menten kinetic analysis of the mutant enzyme indicates that this acetylation affects the first half-reaction of the ACS catalyzed reaction, namely, the formation of the acetyl adenylate enzyme intermediate. The post-translational acetylation of the plant ACS could affect acetate flux in the plastids and overall acetate homeostasis.
G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters
Authors: Roy Shuvra Shekhar , Sharma Shalu , Rizvi Zaigham Abbas , Sinha Dipanjali , Gupta Divya , Rophina Mercy , Sehgal Paras , Sadhu Srikanth , Tripathy Manas Ranjan , Samal Sweety , Maiti Souvik , Scaria Vinod , Sivasubbu Sridhar , Awasthi Amit , Harshan Krishnan H. , Jain Sanjeev , Chowdhury Shantanu
Published: March 2023

The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across >5 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA-approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ or PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, in vitro G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in Vero cell cultures were clear in case of both CPZ and PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against viruses like SARS-CoV-2, which spread fast and accumulate mutations quickly.
Retinal fingerprints of ALS in patients: Ganglion cell apoptosis and TDP-43/p62 misplacement
Authors: Pediconi Natalia , Gigante Ylenia , Cama Silvia , Pitea Martina , Mautone Lorenza , Ruocco Giancarlo , Ghirga Silvia , Di Angelantonio Silvia
Published: March 2023

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neuron function. Although ophthalmic deficits are not considered a classic symptom of ALS, recent studies suggest that changes in retinal cells, similar to those in the spinal cord motor neurons, have been observed in postmortem human tissues and animal models.

Methods

In this study, we examined by immunofluorescence analysis the retinal cell layers of sporadic ALS patients in post-mortem retinal slices. We evaluated the presence of cytoplasmic TDP-43 and SQSTM1/p62 aggregates, activation of the apoptotic pathway, and microglia and astrocytes reactivity.

Results

We found in the retinal ganglion cell layer of ALS patients the increase of mislocalized TDP-43, SQSTM1/p62 aggregates, activation of cleaved caspase-3, and microglia density, suggesting that retinal changes can be used as an additional diagnostic tool for ALS.

Discussion

The retina is considered part of the central nervous system, and neurodegenerative changes in the brain may be accompanied by structural and possibly functional changes in the neuroretina and ocular vasculature. Therefore, using in vivo retinal biomarkers as an additional diagnostic tool for ALS may provide an opportunity to longitudinally monitor individuals and therapies over time in a noninvasive and cost-effective manner.
Natural bioactive compounds in Alzheimer's disease: From the perspective of type 3 diabetes mellitus
Authors: Huang Juan , Huang Nanqu , Mao Qianhua , Shi Jingshan , Qiu Yu
Published: March 2023

There is a close relationship between Alzheimer's disease (AD) and diabetes mellitus (DM), and the link between the two is often referred to as type 3 diabetes mellitus (T3DM). Many natural bioactive compounds have shown the potential to treat AD and diabetes. We mainly review the polyphenols represented by resveratrol (RES) and proanthocyanidins (PCs) and alkaloids represented by berberine (BBR) and Dendrobium nobile Lindl. alkaloids (DNLA) from the perspective of T3DM to review the neuroprotective effects and molecular mechanisms of natural compounds in AD.
Environmental enrichment promotes resilience to neuropathic pain-induced depression and correlates with decreased excitability of the anterior cingulate cortex
Authors: Falkowska Marta , Ntamati Niels R. , Nevian Natalie E. , Nevian Thomas , Acuña Mario A.
Published: March 2023

Depression is a common comorbidity of chronic pain with many patients being affected. However, efficient pharmacological treatment strategies are still lacking. Therefore, it is desirable to find additional alternative approaches. Environmental enrichment has been suggested as a method to alleviate pain-induced depression. However, the neuronal mechanisms of its beneficial effects are still elusive. The anterior cingulate cortex (ACC) plays a central role in processing pain-related negative affect and chronic pain-induced plasticity in this region correlates with depressive symptoms. We studied the consequences of different durations of environmental enrichment on pain sensitivity and chronic pain-induced depression-like behaviors in a mouse model of neuropathic pain. Furthermore, we correlated the behavioral outcomes to the activity levels of pyramidal neurons in the ACC by analyzing their electrophysiological properties ex vivo. We found that early exposure to an enriched environment alone was not sufficient to cause resilience against pain-induced depression-like symptoms. However, extending the enrichment after the injury prevented the development of depression and reduced mechanical hypersensitivity. On the cellular level, increased neuronal excitability was associated with the depressive phenotype that was reversed by the enrichment. Therefore, neuronal excitability in the ACC was inversely correlated to the extended enrichment-induced resilience to depression. These results suggest that the improvement of environmental factors enhanced the resilience to developing chronic pain-related depression. Additionally, we confirmed the association between increased neuronal excitability in the ACC and depression-like states. Therefore, this non-pharmacological intervention could serve as a potential treatment strategy for comorbid symptoms of chronic pain.
The therapeutic effects of lacosamide on epilepsy-associated comorbidities
Authors: He Zihua , Li Jinmei
Published: March 2023

Epilepsy is a chronic neurological disorder associated with severe social and psychological effects, and most epilepsy patients often report at least one comorbidity. Accumulating evidence have suggested that lacosamide, a new generation of anti-seizure medications, may exhibit efficacy in the management of both epilepsy and its related comorbidities. Therefore, this narrative review aimed to elucidate the recent advancements regarding the therapeutic role of lacosamide in epilepsy-associated comorbidities. The possible pathophysiological mechanisms between epilepsy and epilepsy-associated comorbidities have been also partially described. Whether lacosamide improves cognitive and behavioral functions in patients with epilepsy has not been conclusively established. Some studies support that lacosamide may alleviate anxiety and depression in epilepsy patients. In addition, lacosamide has been found to be safe and effective in the treatment of epilepsy in people with intellectual disabilities, epilepsy of cerebrovascular etiology, and epilepsy associated with brain tumors. Moreover, lacosamide treatment has demonstrated fewer side effects on other systems. Hence, future larger and higher quality clinical studies are needed to further explore both the safety and efficacy of lacosamide in the treatment of epilepsy-associated comorbidities.
Necessity and timing of angioplasty in acute large-vessel occlusion strokes due to intracranial atherosclerotic disease: A cohort analysis with data from the angel-ACT registry
Authors: Deng Yiming , Yao Yunchu , Tong Xu , Yin Yue , Wang Anxin , Zhang Yijun , Jia Baixue , Huo Xiaochuan , Luo Gang , Ma Ning , Mo Dapeng , Song Ligang , Sun Xuan , Gao Feng , Chen Duanduan
Published: March 2023

Background

The effects of angioplasty on intracranial atherosclerotic disease (ICAD)-related acute large-vessel occlusion stroke (LVOS) are unknown. We analyzed the efficacy and safety of angioplasty or stenting for ICAD-related LVOS and the optimal treatment duration.

Methods

Patients with ICAD-related LVOS from a prospective cohort of the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemia Stroke registry were classified as follows: the early intraprocedural angioplasty and/or stenting (EAS) group was defined as the strategy using angioplasty or stenting without mechanical thrombectomy (MT) or one attempt of MT; the non-angioplasty and/or stenting (NAS) group, MT procedure without any angioplasty; and the late intraprocedural angioplasty and/or stenting (LAS) group, using same angioplasty techniques following two or more passes of MT. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days. Other efficacy outcomes included mRS scores 0–1, mRS 0–2, and successful recanalization. Death within 90 days, and symptomatic ICH were safety endpoints. We use propensity score method to diminish the effect of treatment-selection bias. The odds ratio of recanalization rate and mRS score among EAS, NAS, and LAS groups were examined by unadjusted and adjusted logistic regression analysis among unweighted samples and inverse probability of treatment weighting (IPTW) samples.

Results

We divided 475 cases into three groups. Functional outcomes at 90 days were better in the EAS group than in the NAS and LAS groups. The proportion of mRS 0–1, mRS 0–2, and successful recanalization cases were the highest in the EAS group. However, after IPTW, mortality rate among the three groups were similar (EAS vs. NAS vs. LAS: 19.0 vs. 18.1 vs. 18.7%, p = 0.98) as well as symptomatic intracranial hemorrhage within 24 h however, mortality rate and symptomatic intracranial hemorrhage among the three groups were similar. Logistic regression analysis in unweighted samples and IPTW samples both showed that EAS group had better outcomes. IPTW-adjusted logistic regression analysis demonstrated that the EAS group had better outcomes (mRS 0–1) than the NAS group (adjusted odds ratio [aOR], 0.55; 95% confidence interval [CI]: 0.34–0.88, p = 0.01) and LAS (aOR, 0.39; 95% CI: 0.22–0.68, p = 0.001).

Conclusions

Angioplasty and/or stenting should be performed at an early stage for ICAD-related acute LVOS.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.
Influence of the constraint-induced method of constraint-induced movement therapy on improving lower limb outcomes after stroke: A meta-analysis review
Authors: Zhang Jing , Feng Hongsheng , Lin Jinpeng , Zhai Hua , Shen Xia
Published: March 2023

Background

Constraint-induced movement therapy (CIMT) targeting the lower limb function uses various methods. The influence of CIMT methods on lower limb outcomes after stroke has rarely been examined.

Objectives

This study aimed to examine CIMT effects on lower limb outcomes and explore the influence of CIMT methods on treatment effects after stroke, with other potential factors considered as covariates.

Methods

PubMed, Web of Science, Cochrane Library, Academic Search PremierviaEBSCOHost, and PEDro databases were searched until September 2022. We included randomized control trials with CIMT targeting the lower limb function and dosage-matched active control. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of each study. Hedges' g was used to quantify the effect size of CIMT on outcomes compared to the active control. Meta-analyses were conducted across all studies. A mixed-variable meta-regression analysis was used to investigate the influence of CIMT methods on treatment effects after stroke, with other potential factors considered as covariates.

Results

Twelve eligible randomized controlled trials with CIMT were included in the meta-analysis, where 10 trials were with a low risk of bias. A total of 341 participants with stroke were involved. For the treatment effects on the lower limb function, CIMT showed a moderate short-term effect size [Hedges' g = 0.567;P> 0.05; 95% confidence interval (CI): 0.203–0.931], but a small and insignificant long-term effect size (Hedges' g = 0.470;P> 0.05; 95%CI: −0.173 to 1.112), compared with conventional treatment. The CIMT method of using a weight strapped around the non-paretic leg and the ICF outcome category of the movement function were identified as significant factors contributing to the heterogeneity of short-term effect sizes across studies (β = −0.854 and 1.064, respectively,R2= 98%,P> 0.05). Additionally, using a weight strapped around the non-paretic leg had a significant contribution to the heterogeneity of long-term effect sizes across studies as well (β = −1.000,R2= 77%,P> 0.05).

Conclusion

Constraint-induced movement therapy is superior to conventional treatment for improvement of lower limb function in the short-term but not in the long-term. The CIMT method of using a weight strapped around a non-paretic leg contributed negatively to the treatment effect, and therefore might not be recommended.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021268681.
The association between blood pressure variability and perihematomal edema after spontaneous intracerebral hemorrhage
Authors: Sondag Lotte , Wolsink Axel , Jolink Wilmar M. T. , Voigt Sabine , van Walderveen Marianne A. A. , Wermer Marieke J. H. , Klijn Catharina J. M. , Schreuder Floris H. B. M.
Published: March 2023

Background

Perihematomal edema (PHE) after spontaneous intracerebral hemorrhage (sICH) is associated with clinical deterioration, but the etiology of PHE development is only partly understood.

Aims

We aimed to investigate the association between systemic blood pressure (BP) variability (BPV) and formation of PHE.

Methods

From a multicenter prospective observational study, we selected patients with sICH who underwent 3T brain MRI within 21 days after sICH, and had at least 5 BP measurements available in the first week after sICH. Primary outcome was the association between coefficient of variation (CV) of systolic BP (SBP) and edema extension distance (EED) using multivariable linear regression, adjusting for age, sex, ICH volume and timing of the MRI. In addition, we investigated the associations of mean SBP, mean arterial pressure (MAP), their CVs with EED and absolute and relative PHE volume.

Results

We included 92 patients (mean age 64 years; 74% men; median ICH volume 16.8 mL (IQR 6.6–36.0), median PHE volume 22.5 mL (IQR 10.2–41.4). Median time between symptom onset and MRI was 6 days (IQR 4–11), median number of BP measurements was 25 (IQR 18–30). Log-transformed CV of SBP was not associated with EED (B = 0.050, 95%-CI −0.186 to 0.286, p = 0.673). Furthermore, we found no association between mean SBP, mean and CV of MAP and EED, nor between mean SBP, mean MAP or their CVs and absolute or relative PHE.

Discussion

Our results do not support a contributing role for BPV on PHE, suggesting mechanisms other than hydrostatic pressure such as inflammatory processes, may play a more important role.
Evidence of clinical efficacy and pharmacological mechanism of N-butylphthalide in the treatment of delayed encephalopathy after acute carbon monoxide poisoning
Authors: Song Huiping , Yue Aochun , Zhou Xudong , Han Wei , Li Qin
Published: March 2023

Objective

Based on network meta-analysis (NMA) and network pharmacology approaches, we explored the clinical efficacy of different regimens, and clarified the pharmacological mechanisms of N-butylphthalide (NBP) in the treatment of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

Methods

Firstly, NMA was conducted to obtain the ranking of the efficacy of different regimens for the treatment of DEACMP. Secondly, the drug with a relatively high efficacy ranking was selected and its mechanism of treatment for DEACMP was identified through a network pharmacology analysis. By the use of protein interaction and enrichment analysis, the pharmacological mechanism was predicted, and molecular docking was subsequently carried out to verify the reliability of the results.

Results

A total of 17 eligible randomized controlled trials (RCTs) involving 1293 patients and 16 interventions were eventually included in our analysis from NMA. Mesenchymal stem cells (MSCs) + NBP significantly increased mini-mental state examination (MMSE) and Barthel index (BI) scores; NBP + dexamethasone (DXM) was the most effective treatment in improving the activity of daily living (ADL) scores; NBP significantly decreased national institutes of health stroke scale (NIHSS) scores; Xingzhi-Yinao granules (XZYN) had more advantages in improving Montreal cognitive assessment (MoCA) scores, translational direct current stimulation (tDCS) had a significant effect in improving P300 latency and P300 amplitude and Kinnado + Citicoline had the most obvious effect in improving malondialdehyde (MDA). Meanwhile, by network pharmacology analysis, 33 interaction genes between NBP and DEACMP were obtained, and 4 of them were identified as possible key targets in the process of MCODE analysis. 516 Gene ontology (GO) entries and 116 Kyoto Encyclopedia of Gene and Genome (KEGG) entries were achieved by enrichment analysis. Molecular docking showed that NBP had good docking activity with the key targets.

Conclusion

The NMA screened for regimens with better efficacy for each outcome indicator in order to provide a reference for clinical treatment. NBP can stably bind ALB, ESR1, EGFR, HSP90AA1, and other targets, and may play a role in neuroprotection for patients with DEACMP by modulating Lipid and atherosclerosis, IL-17 signaling pathway, MAPK signaling pathway, FoxO signaling pathway, PI3K/AKT signaling pathway.
Urinary proteome profiles associated with cognitive decline in community elderly residents—A pilot study
Authors: Watanabe Yumi , Hirao Yoshitoshi , Kasuga Kensaku , Kitamura Kaori , Nakamura Kazutoshi , Yamamoto Tadashi
Published: March 2023

Non-invasive and simple methods enabling easy identification of individuals at high risk of cognitive decline are needed as preventive measures against dementia. This pilot study aimed to explore protein biomarkers that can predict cognitive decline using urine, which can be collected non-invasively. Study subjects were selected from participants in a cohort study of middle-aged and older community-dwelling adults who underwent cognitive testing using the Mini-Mental State Examination and provided spot urine samples at two time points with an interval of approximately 5 years. Seven participants whose cognitive function declined 4 or more points from baseline (Group D) and 7 sex- and age-matched participants whose cognitive function remained within the normal range during the same period (Group M) were selected. Urinary proteomics using mass spectrometry was performed and discriminant models were created using orthogonal partial least squares-discriminant analysis (OPLS-DA). OPLS-DA yielded two models that significantly discriminated between the two groups at baseline and follow-up. Both models had ORM1, ORM2, and SERPINA3 in common. A further OPLS-DA model using baseline ORM1, ORM2, and SERPINA3 data showed similar predictive performance for data at follow-up as it did for baseline data (sensitivity: 0.85, specificity: 0.85), with the receiver operating characteristic curve analysis yielding an area under the curve of 0.878. This prospective study demonstrated the potential for using urine to identify biomarkers of cognitive decline.
Neurophysiological and clinical biomarkers of secondary progressive multiple sclerosis: A cross-sectional study
Authors: Tartaglia Matteo , Canevelli Marco , Malimpensa Leonardo , Belvisi Daniele , Baione Viola , Ferrazzano Gina , Leodori Giorgio , Berardelli Alfredo , Conte Antonella
Published: March 2023

Timely diagnosis of secondary progressive multiple sclerosis (SPMS) represents a clinical challenge. The Frailty Index, a quantitative frailty measure, and the Neurophysiological Index, a combined measure of sensorimotor cortex inhibitory mechanism parameters, have recently emerged as promising tools to support SPMS diagnosis. The aim of this study was to explore the possible relationship between these two indices in MS. MS participants underwent a clinical evaluation, Frailty Index administration, and neurophysiological assessment. Frailty and Neurophysiological Index scores were found to be higher in SPMS and correlated with each other, thus suggesting that they may capture similar SPMS-related pathophysiological mechanisms.
Participating in innovative medicines initiative funded neurodegenerative disorder projects—An impact analysis conducted as part of the NEURONET project
Authors: Hawksworth Claire , Salih Fatima , Cresswell Katharine , Steukers Lennert , Diaz Carlos , Killin Lewis , Pradier Laurent , Bradshaw Angela , Dawoud Dalia
Published: March 2023

The European Commission's Innovative Medicines Initiative (IMI) has funded many projects focusing on neurodegenerative disorders (ND) that aimed to improve the diagnosis, prevention, treatment and understanding of NDs. To facilitate collaboration across this project portfolio, the IMI funded the “NEURONET” project between March 2019 and August 2022 with the aim of connecting these projects and promoting synergies, enhancing the visibility of their findings, understanding the impact of the IMI funding and identifying research gaps that warrant more/new funding. The IMI ND portfolio currently includes 20 projects consisting of 270 partner organizations across 25 countries. The NEURONET project conducted an impact analysis to assess the scientific and socio-economic impact of the IMI ND portfolio. This was to better understand the perceived areas of impact from those directly involved in the projects. The impact analysis was conducted in two stages: an initial stage developed the scope of the project, defined the impact indicators and measures to be used. A second stage designed and administered the survey amongst partners from European Federation of Pharmaceutical Industries and Associations (EFPIA) organizations and other partners (hereafter, referred to as “non-EFPIA” organizations). Responses were analyzed according to areas of impact: organizational, economic, capacity building, collaborations and networking, individual, scientific, policy, patient, societal and public health impact. Involvement in the IMI ND projects led to organizational impact, and increased networking, collaboration and partnerships. The key perceived disadvantage to project participation was the administrative burden. These results were true for both EFPIA and non-EFPIA respondents. The impact for individual, policy, patients and public health was less clear with people reporting both high and low impact. Overall, there was broad alignment between EFPIA and non-EFPIA participants' responses apart from for awareness of project assets, as part of scientific impact, which appeared to be slightly higher among non-EFPIA respondents. These results identified clear areas of impact and those that require improvement. Areas to focus on include promoting asset awareness, establishing the impact of the IMI ND projects on research and development, ensuring meaningful patient involvement in these public-private partnership projects and reducing the administrative burden associated with participation in them.
Impact of dataset size and long-term ECoG-based BCI usage on deep learning decoders performance
Authors: Śliwowski Maciej , Martin Matthieu , Souloumiac Antoine , Blanchart Pierre , Aksenova Tetiana
Published: March 2023

Introduction

In brain-computer interfaces (BCI) research, recording data is time-consuming and expensive, which limits access to big datasets. This may influence the BCI system performance as machine learning methods depend strongly on the training dataset size. Important questions arise: taking into account neuronal signal characteristics (e.g., non-stationarity), can we achieve higher decoding performance with more data to train decoders? What is the perspective for further improvement with time in the case of long-term BCI studies? In this study, we investigated the impact of long-term recordings on motor imagery decoding from two main perspectives: model requirements regarding dataset size and potential for patient adaptation.

Methods

We evaluated the multilinear model and two deep learning (DL) models on a long-term BCI & Tetraplegia (ClinicalTrials.gov identifier: NCT02550522) clinical trial dataset containing 43 sessions of ECoG recordings performed with a tetraplegic patient. In the experiment, a participant executed 3D virtual hand translation using motor imagery patterns. We designed multiple computational experiments in which training datasets were increased or translated to investigate the relationship between models' performance and different factors influencing recordings.

Results

Our results showed that DL decoders showed similar requirements regarding the dataset size compared to the multilinear model while demonstrating higher decoding performance. Moreover, high decoding performance was obtained with relatively small datasets recorded later in the experiment, suggesting motor imagery patterns improvement and patient adaptation during the long-term experiment. Finally, we proposed UMAP embeddings and local intrinsic dimensionality as a way to visualize the data and potentially evaluate data quality.

Discussion

DL-based decoding is a prospective approach in BCI which may be efficiently applied with real-life dataset size. Patient-decoder co-adaptation is an important factor to consider in long-term clinical BCI.
Examining resting-state network connectivity in children exposed to perinatal maternal adversity using anatomically weighted functional connectivity (awFC) analyses; A preliminary report
Authors: Ayyash Sondos , Sunderji Aleeza , Gallant Heather D. , Hall Alexander , Davis Andrew D. , Pokhvisneva Irina , Meaney Michael J. , Silveira Patricia Pelufo , Sassi Roberto B. , Hall Geoffrey B.
Published: March 2023

Introduction

Environmental perturbations during critical periods can have pervasive, organizational effects on neurodevelopment. To date, the literature examining the long-term impact of early life adversity has largely investigated structural and functional imaging data outcomes independently. However, emerging research points to a relationship between functional connectivity and the brain’s underlying structural architecture. For instance, functional connectivity can be mediated by the presence of direct or indirect anatomical pathways. Such evidence warrants the use of structural and functional imaging in tandem to study network maturation. Accordingly, this study examines the impact of poor maternal mental health and socioeconomic context during the perinatal period on network connectivity in middle childhood using an anatomically weighted functional connectivity (awFC) approach. awFC is a statistical model that identifies neural networks by incorporating information from both structural and functional imaging data.

Methods

Resting-state fMRI and DTI scans were acquired from children aged 7–9 years old.

Results

Our results indicate that maternal adversity during the perinatal period can affect offspring’s resting-state network connectivity during middle childhood. Specifically, in comparison to controls, children of mothers who had poor perinatal maternal mental health and/or low socioeconomic status exhibited greater awFC in the ventral attention network.

Discussion

These group differences were discussed in terms of the role this network plays in attention processing and maturational changes that may accompany the consolidation of a more adult-like functional cortical organization. Furthermore, our results suggest that there is value in using an awFC approach as it may be more sensitive in highlighting connectivity differences in developmental networks associated with higher-order cognitive and emotional processing, as compared to stand-alone FC or SC analyses.