bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: Report from a U.S. regional collaborative
Authors: Treadwell Marsha J. , Du Lisa , Bhasin Neha , Marsh Anne M. , Wun Theodore , Bender M. A. , Wong Trisha E. , Crook Nicole , Chung Jong H. , Norman Shannon , Camilo Nicolas , Cavazos Judith , Nugent Diane
Published: August 2022

Sickle cell disease (SCD) is an inherited blood disorder that affects about 100,000 people in the U.S., primarily Blacks/African-Americans. A multitude of complications negatively impacts quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD, but is underutilized. Negative and uninformed perceptions of hydroxyurea and barriers to its use hinder adherence and promotion of the medication. As the largest real-world study to date that assessed hydroxyurea use for children and adults with SCD, we gathered and analyzed perspectives of providers, individuals with SCD, and families. Participants provided information about socio-demographics, hospital and emergency admissions for pain, number of severe pain episodes interfering with daily activities, medication adherence, and barriers to hydroxyurea. Providers reported on indications for hydroxyurea, reasons not prescribed, and current laboratory values. We found that hydroxyurea use was reported in over half of eligible patients from this large geographic region in the U.S., representing a range of sickle cell specialty clinical settings and practices. Provider and patient/caregiver reports about hydroxyurea use were consistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers. Using the intentional and unintentional medication nonadherence framework, we found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and “tried and it did not work” were important barriers for young adults and adults. For providers, diagnoses other than HgbSS or HgbS-β0 thalassemia were associated with lower odds of prescribing, consistent with evidence-based guidelines. Our results support strengthening provider understanding and confidence in implementing existing SCD guidelines, and the importance of shared decision making. Our findings can assist providers in understanding choices and decisions of families; guide individualized clinical discussions regarding hydroxyurea therapy; and help with developing tailored interventions to address barriers. Addressing barriers to hydroxyurea use can inform strategies to minimize similar barriers in the use of emerging and combination therapies for SCD.
Bioinformatic workflow fragment discovery leveraging the social-aware knowledge graph
Authors: Diao Jin , Zhou Zhangbing , Xue Xiao , Zhao Deng , Chen Shengpeng
Published: August 2022

Constructing a novel bioinformatic workflow by reusing and repurposing fragments crossing workflows is regarded as an error-avoiding and effort-saving strategy. Traditional techniques have been proposed to discover scientific workflow fragments leveraging their profiles and historical usages of their activities (or services). However, social relations of workflows, including relations between services and their developers have not been explored extensively. In fact, current techniques describe invoking relations between services, mostly, and they can hardly reveal implicit relations between services. To address this challenge, we propose a social-aware scientific workflow knowledge graph (S2KG) to capture common types of entities and various types of relations by analyzing relevant information about bioinformatic workflows and their developers recorded in repositories. Using attributes of entities such as credit and creation time, the union impact of several positive and negative links inS2KGis identified, to evaluate the feasibility of workflow fragment construction. To facilitate the discovery of single services, a service invoking network is extracted formS2KG, and service communities are constructed accordingly. A bioinformatic workflow fragment discovery mechanism based on Yen’s method is developed to discover appropriate fragments with respect to certain user’s requirements. Extensive experiments are conducted, where bioinformatic workflows publicly accessible at the myExperiment repository are adopted. Evaluation results show that our technique performs better than the state-of-the-art techniques in terms of the precision, recall, andF1.
Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection
Authors: Zheng Wenjiang , Yan Qian , Li Zonghui , Wang Xianyang , Wu Peng , Liao Feng , Lao Zizhao , Jiang Yong , Liu Xiaohong , Zhan Shaofeng , Li Geng
Published: August 2022

Background

Dengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear.

Methods

A model of dengue disease was established in IFNAR−/− C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR−/− mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury.

Results

We observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease.

Conclusions

The interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.
Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4+ T cells: A pooled data-analysis
Authors: Inderbitzin Anne , Loosli Tom , Opitz Lennart , Rusert Peter , Metzner Karin J.
Published: August 2022

The main obstacle to cure HIV-1 is the latent reservoir. Antiretroviral therapy effectively controls viral replication, however, it does not eradicate the latent reservoir. Latent CD4+ T cells are extremely rare in HIV-1 infected patients, making primary CD4+ T cell models of HIV-1 latency key to understanding latency and thus finding a cure. In recent years several primary CD4+ T cell models of HIV-1 latency were developed to study the underlying mechanism of establishing, maintaining and reversing HIV-1 latency. In the search of biomarkers, primary CD4+ T cell models of HIV-1 latency were used for bulk and single-cell transcriptomics. A wealth of information was generated from transcriptome analyses of different primary CD4+ T cell models of HIV-1 latency using latently- and reactivated HIV-1 infected primary CD4+ T cells. Here, we performed a pooled data-analysis comparing the transcriptome profiles of latently- and reactivated HIV-1 infected cells of 5 in vitro primary CD4+ T cell models of HIV-1 latency and 2 ex vivo studies of reactivated HIV-1 infected primary CD4+ T cells from HIV-1 infected individuals. Identifying genes that are differentially expressed between latently- and reactivated HIV-1 infected primary CD4+ T cells could be a more successful strategy to better understand and characterize HIV-1 latency and reactivation. We observed that natural ligands and coreceptors were predominantly downregulated in latently HIV-1 infected primary CD4+ T cells, whereas genes associated with apoptosis, cell cycle and HLA class II were upregulated in reactivated HIV-1 infected primary CD4+ T cells. In addition, we observed 5 differentially expressed genes that co-occurred in latently- and reactivated HIV-1 infected primary CD4+ T cells, one of which, MSRB2, was found to be differentially expressed between latently- and reactivated HIV-1 infected cells. Investigation of primary CD4+ T cell models of HIV-1 latency that mimic the in vivo state remains essential for the study of HIV-1 latency and thus providing the opportunity to compare the transcriptome profile of latently- and reactivated HIV-1 infected cells to gain insights into differentially expressed genes, which might contribute to HIV-1 latency.
Structural and functional analysis of the small GTPase ARF1 reveals a pivotal role of its GTP-binding domain in controlling of the generation of viral inclusion bodies and replication of grass carp reovirus
Authors: Zhang Jie , Li Pengwei , Lu Riye , Ouyang Songying , Chang Ming Xian
Published: August 2022

Grass carp reovirus (GCRV) is the most pathogenic double-stranded (ds) RNA virus among the isolated aquareoviruses. The molecular mechanisms by which GCRV utilizes host factors to generate its infectious compartments beneficial for viral replication and infection are poorly understood. Here, we discovered that the grass carp ADP ribosylation factor 1 (gcARF1) was required for GCRV replication since the knockdown of gcARF1 by siRNA or inhibiting its GTPase activity by treatment with brefeldin A (BFA) significantly impaired the yield of infectious viral progeny. GCRV infection recruited gcARF1 into viral inclusion bodies (VIBs) by its nonstructural proteins NS80 and NS38. The small_GTP domain of gcARF1 was confirmed to be crucial for promoting GCRV replication and infection, and the number of VIBs reduced significantly by the inhibition of gcARF1 GTPase activity. The analysis of gcARF1-GDP complex crystal structure revealed that the 27AAGKTT32 motif and eight amino acid residues (A27, G29, K30, T31, T32, N126, D129 and A160), which were located mainly within the GTP-binding domain of gcARF1, were crucial for the binding of gcARF1 with GDP. Furthermore, the 27AAGKTT32 motif and the amino acid residue T31 of gcARF1 were indispensable for the function of gcARF1 in promoting GCRV replication and infection. Taken together, it is demonstrated that the GTPase activity of gcARF1 is required for efficient replication of GCRV and that host GTPase ARF1 is closely related with the generation of VIBs.
Etanercept/celecoxib on improving MRI inflammation of active ankylosing spondylitis: A multicenter, open-label, randomized clinical trial
Authors: Tu Liudan , Zhao Minjing , Wang Xiaohong , Kong Qingcong , Chen Zena , Wei Qiujing , Li Qiuxia , Yu Qinghong , Ye Zhizhong , Cao Shuangyan , Lin Zhimin , Liao Zetao , Lv Qing , Qi Jun , Jin Ou , Pan Yunfeng , Gu Jieruo
Published: August 2022

Objective

To investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active ankylosing spondylitis (AS) patients with etanercept and celecoxib alone/combined treatment.

Methods

A randomized controlled trial was conducted in three medical centers in China. Adult AS patients with BASDAI ≥4 or ASDAS ≥2.1, CRP >6 mg/L, or ESR 28 mm/1st hour were randomly assigned (1:1:1 ratio) to celecoxib 200 mg bid or etanercept 50 mg qw or combined therapy for 52 weeks. The primary outcomes were SPARCC change of the sacroiliac joint (SIJ) and spine and the proportion of patients achieving ASAS20 response at 52 weeks.

Results

Between September 2014 and January 2016, we randomly assigned 150 patients (mean age, 32.4 years; mean disease duration, 109 months), and 133 (88.6%) completed the study. SPARCC inflammation scores of the SIJ and spine decreased in the three groups, and significant differences were found between the combined group and the celecoxib group [between-group difference: −6.33, 95% CI (−10.56, −2.10) for SIJ; −9.53, 95% CI (−13.73, −5.33) for spine] and between the etanercept group and the celecoxib group [between-group difference: −5.02, 95% CI (−9.29, −0.76) for SIJ; −5.80, 95% CI (−10.04, −1.57) for spine]. The ASAS20 response rates were 44%, 58%, and 84% in the celecoxib, etanercept, and combined groups, respectively, and a significant difference was only found between the combined and the celecoxib groups.

Conclusion

Etanercept with or without celecoxib decreases inflammation detected by MRI at 1 year compared to celecoxib alone in active AS patients. The combination of etanercept and celecoxib was superior to celecoxib alone for the primary clinical response.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT01934933.
Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer
Authors: Xia Yan , Zhang Rongzheng , Wang Mingzhu , Li Jiaqi , Dong Jianming , He Kaitong , Guo Ting , Ju Xiaomei , Ru Jiaqiu , Zhang Shuyun , Sun Yihua
Published: August 2022

Necroptosis is a novel type of regulated cell death that is intimately associated with a variety of tumors. However, how necroptosis affects the identification of gastric cancer (GC) remains unclear. Here we seek to find new potential necroptosis-related biomarkers to predict GC prognosis and immunotherapy effect. We used Cox analysis to obtain shared prognostic markers related to necroptosis from five datasets (TCGA and four GEO datasets). Then, a necroptosis-related gene prognostic score (NRGPS) system was constructed using LASSO Cox regression, NRGPS consisting of three necroptosis-related mRNAs (AXL, RAI14, and NOX4) was identified, 31 pairs of GC and adjacent normal tissues from the Second Hospital of Harbin Medical University were collected and Real-Time Quantitative PCR (RT-qPCR) was used to detect the relative expression levels of the three necroptosis-related mRNAs, and external validation was performed on four GEO datasets (GSE84437, GSE26901, GSE62254 and GSE15459). In this study, Overall survival (OS) in the high-NRGPS group was significantly lower than in the low-NRGPS group. Cox regression analyses showed that NRGPS was an independent prognostic variable. Tumor-mutation-burden (TMB), tumor microenvironment (TME), microsatellite instability (MSI), and Tumor Immune Dysfunction and Exclusion (TIDE) scoring were used as predictors of the immunotherapy response. A cancer-friendly immune microenvironment, a high TIDE score, a low TMB, and a low MSI were all characteristics of the high-NRGPS group, and they all consistently showed that the issues seen there are related to immune escape in GC. The combination of three candidate genes may be an effective method for diagnostic assessment of GC prognosis and immunotherapy efficacy.
Anti-SARS-COV-2 specific immunity in HIV immunological non-responders after mRNA-based COVID-19 vaccination
Authors: Sisteré-Oró Marta , Andrade Naina , Wortmann Diana D.J. , Du Juan , Garcia-Giralt Natalia , González-Cao María , Güerri-Fernández Robert , Meyerhans Andreas
Published: August 2022

Individuals infected with the human immunodeficiency virus type 1 (HIV-1) belong to the group of people most vulnerable to SARS-CoV-2 infections and the associated disease COVID-19. Here we describe SARS-CoV-2-specific antibody and cellular immune responses in a small cohort of immunological non-responder HIV-1 patients (HIV-INRs) after receiving the COVID-19 mRNA-based BioNTech/Pfizer vaccine. Compared to the control group of vaccinated healthy individuals that all developed a virus-specific immune response, 5 of 10 vaccinated HIV-1 patients showed insufficient immune responses. The lack of response was not directly correlated with patients CD4 cell counts. Three of the five non-responders that agreed to receive a booster vaccination subsequently generated a virus-specific response. Thus, even HIV-INRs can be efficiently vaccinated against COVID-19 but may require a follow-up by virus-specific immune monitoring to guarantee clinical vaccine benefits.
Sexually transmitted pathogens causing urethritis: A mini-review and proposal of a clinically based diagnostic and therapeutic algorithm
Authors: Sadoghi Birgit , Kränke Birger , Komericki Peter , Hutterer Georg
Published: August 2022

The purpose of this mini-review was to provide the latest information and concepts on diagnosis and treatment of the most common sexually transmitted pathogens causing urethritis. The incidence of several sexually transmitted infections that cause urethritis is increasing, and this genitourinary syndrome is among the most common reason young men see clinical care. The authors performed a literature search including the currently valid guidelines, and an overview of the most relevant pathogens is given. Moreover, the authors developed a clinically applicable diagnostic and therapeutic algorithm, because early diagnosis and correct treatment can sometimes prevent infected individuals from significant morbidity. Future research will focus on new methods to combat pathogens that cause urethritis, including vaccination.
Association between grip strength and non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Han Liu , Fu Shifeng , Li Jianglei , Liu Deliang , Tan Yuyong
Published: August 2022

Background

The association between grip strength (GS) and non-alcoholic fatty liver disease (NAFLD) has been reported by recent epidemiological studies, however, the results of these studies are inconsistent. This meta-analysis was conducted to collect all available data and estimate the risk of NAFLD among people with low GS, as well as the risk of low GS among patients with NAFLD.

Methods

We systematically searched several literature databases including PubMed, Web of Science, Cochrane Library, and Embase from inception to March 2022. These observational studies reported the risk of NAFLD among people with low GS and/or the risk of low GS among patients with NAFLD. Qualitative and quantitative information was extracted, statistical heterogeneity was assessed using the I2 test, and potential for publication bias was assessed qualitatively by a visual estimate of a funnel plot and quantitatively by calculation of the Begg’s test and the Egger’s test.

Results

Of the citations, 10 eligible studies involving 76,676 participants met inclusion criteria. The meta-analysis of seven cross-section studies (69,757 participants) showed that people with low GS had increased risk of NAFLD than those with normal GS (summary OR = 3.32, 95% CI: 1.91–5.75). In addition, the meta-analysis of four studies (14,920 participants) reported that the risk of low GS patients with NAFLD was higher than those in normal people (summary OR = 3.31, 95% CI: 2.45–4.47).

Conclusion

In this meta-analysis, we demonstrated a strong relationship between low GS and NAFLD. We found an increased risk of NAFLD among people with low GS, and an increased risk of lower GS among NAFLD patients.

Systematic review registration

[www.crd.york.ac.uk/prospero], identifier [CRD42022334687].
Molecular epidemiology and genetic characterization of SARS-CoV-2 in Kuwait: A descriptive study
Authors: Madi Nada , Safar Hussain A. , Mustafa Abu Salim , Chehadeh Wassim , Asadzadeh Mohammad , Sadeq Mohammed , Alawadhi Ebaa , Al-Muhaini Ali , Benthani Fahad A.
Published: August 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been fatal to human health, affecting almost the entire world. Here we reported, for the first time, characterization of the genetic variants of SARS-CoV-2 circulating in Kuwait to understand their genetic diversity and monitor the accumulation of mutations over time. This study randomly enrolled 209 COVID-19 patients whose nasopharyngeal swabs were positive for SARS-CoV-2 between February 2020 and June 2021 using RT-PCR. The whole genomes of SARS-CoV-2 from the nasopharyngeal swabs were sequenced using the Oxford Nanopore sequencing technology following the ARTIC network protocol. Whole-genome sequencing has identified different clades/sub-clades circulating in Kuwait, mimicking the virus’s global spread. Clade 20A was dominant from February 2020 until January 2021, and then clade 20I (Alpha, V1) emerged and dominated. In June 2021, the number of cases infected with clades 21I, 21A, and 21 J (Delta) increased and dominated. We detected several known clade-defining missense and synonymous mutations and other missense mutations in the genes encoding important viral proteins, including ORF1a, S, ORF3a, ORF8 regions and a novel mutation in the N region. ORF1ab region harbored more mutations and deletions (n = 62, 49.2%) compared to the other 12 gene regions, and the most prevalent missense mutations were P314L (97%) in ORF1b and D614G (97%) in the S glycoprotein regions. Detecting and analyzing mutations and monitoring the evolution of SARS-CoV-2 over time is essential to help better understand the spread of various clades/strains of SARS-CoV-2 and their implications for pathogenesis. In addition, knowledge of the circulating variants and genome sequence variability of SARS-CoV-2 may potentially influence the development of vaccines and antiviral drugs to control the COVID-19 pandemic.
High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study
Authors: Parbie Prince Kofi , Abana Christopher Zaab-Yen , Kushitor Dennis , Asigbee Theodore Worlanyo , Ntim Nana Afia Asante , Addo-Tetebo Gifty , Ansong Maclean Richard Darko , Ofori Sampson Badu , Mizutani Taketoshi , Runtuwene Lucky Ronald , Nishizawa Masako , Ishikawa Koichi , Kiyono Hiroshi , Ampofo William Kwabena , Matano Tetsuro , Bonney Evelyn Yayra , Kikuchi Tadashi
Published: August 2022

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS “95-95-95” target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)—M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)—K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.
Develop a diagnostic tool for dementia using machine learning and non-imaging features
Authors: Wang Huan , Sheng Li , Xu Shanhu , Jin Yu , Jin Xiaoqing , Qiao Song , Chen Qingqing , Xing Wenmin , Zhao Zhenlei , Yan Jing , Mao Genxiang , Xu Xiaogang
Published: August 2022

Background

Early identification of Alzheimer’s disease or mild cognitive impairment can help guide direct prevention and supportive treatments, improve outcomes, and reduce medical costs. Existing advanced diagnostic tools are mostly based on neuroimaging and suffer from certain problems in cost, reliability, repeatability, accessibility, ease of use, and clinical integration. To address these problems, we developed, evaluated, and implemented an early diagnostic tool using machine learning and non-imaging factors.

Methods and results

A total of 654 participants aged 65 or older from the Nursing Home in Hangzhou, China were identified. Information collected from these patients includes dementia status and 70 demographic, cognitive, socioeconomic, and clinical features. Logistic regression, support vector machine (SVM), neural network, random forest, extreme gradient boosting (XGBoost), least absolute shrinkage and selection operator (LASSO), and best subset models were trained, tuned, and internally validated using a novel double cross validation algorithm and multiple evaluation metrics. The trained models were also compared and externally validated using a separate dataset with 1,100 participants from four communities in Zhejiang Province, China. The model with the best performance was then identified and implemented online with a friendly user interface. For the nursing dataset, the top three models are the neural network (AUROC = 0.9435), XGBoost (AUROC = 0.9398), and SVM with the polynomial kernel (AUROC = 0.9213). With the community dataset, the best three models are the random forest (AUROC = 0.9259), SVM with linear kernel (AUROC = 0.9282), and SVM with polynomial kernel (AUROC = 0.9213). The F1 scores and area under the precision-recall curve showed that the SVMs, neural network, and random forest were robust on the unbalanced community dataset. Overall the SVM with the polynomial kernel was found to be the best model. The LASSO and best subset models identified 17 features most relevant to dementia prediction, mostly from cognitive test results and socioeconomic characteristics.

Conclusion

Our non-imaging-based diagnostic tool can effectively predict dementia outcomes. The tool can be conveniently incorporated into clinical practice. Its online implementation allows zero barriers to its use, which enhances the disease’s diagnosis, improves the quality of care, and reduces costs.
Effects of different physical activities on brain-derived neurotrophic factor: A systematic review and bayesian network meta-analysis
Authors: Zhou Bojun , Wang Zhisheng , Zhu Lianghao , Huang Gang , Li Bing , Chen Chaofan , Huang Junda , Ma Fuhai , Liu Timon Chengyi
Published: August 2022

Background

Emerging evidence suggests that exercise is a simple and effective method for maintaining brain function.

Aims

This review evaluates the effects of five physical exercises, including aerobic training (AT), high-intensity interval training (HIIT), combined training (CT), resistance training (RT), and AT+RT, on the serum level of brain-derived neurotrophic factor (BDNF) in healthy and non-healthy populations.

Methods

We searched CNKI, PubMed, Embase, Scopus, Medline, Web of Science, and Cochrane Library databases to review randomized controlled studies on exercise interventions for BDNF. Quantitative merging analysis of the resulting data using Bayesian network meta-analysis.

Results

The screening and exclusion of the searched literature resulted in the inclusion of 39 randomized controlled trials containing 5 exercise interventions with a total of 2031 subjects. The AT, RT, AT+RT, HIIT, and CT groups (intervention groups) and the CG group (conventional control group) were assigned to 451, 236, 102, 84, 293, and 865 subjects, respectively. The Bayesian network meta-analysis ranked the effect of exercise on BDNF level improvement in healthy and non-healthy subjects as follows: RT > HIIT > CT > AT+RT > AT > CG. Better outcomes were observed in all five intervention groups than in the CG group, with RT having the most significant effect [MD = 3.11 (0.33, 5.76),p< 0.05].

Conclusions

RT at moderate intensity is recommended for children and older adults in the case of exercise tolerance and is effective in maintaining or modulating BDNF levels for promoting brain health.

Systematic Review Registration

https://inplasy.com, INPLASY202250164.
Disentangling Aging and Mood Effects on Emotional Memory
Authors: Tamera Kylee , Kannampuzha Courtney , Ta Viviane , Hot Pascal , Davidson Patrick S. R.
Published: August 2022

Older adults tend to be in a more positive mood than young adults, and tend to remember positive information more often than negative information, yet the link between their positive mood and their positive memory bias has not often been explored. In this study, we manipulated young and older adults’ moods prior to their completing an emotional memory task. For mood manipulation, young (n= 147) and older (n= 111) adults viewed a positive, negative, or neutral video lasting 3 min. To validate the mood induction, we collected self-reported ratings of valence and arousal (affective slider;Betella and Verschure, 2016) at baseline, after the video, and after the memory task. The memory task consisted of incidental encoding of 30 intermixed pictures (10 positive, 10 negative, 10 neutral valence), followed by free recall. The mood manipulation changed people’s self-reported valence, yet it did not influence self-reported arousal. The memory task revealed a consistent negativity bias in young adults. Older adults recalled negative and positive pictures equally well in all conditions. After viewing a negative video, they recalled positive pictures more often than neutral pictures, but did not show the same advantage for negative pictures over neutral pictures. This positive memory advantage was weaker in the positive mood condition. Therefore, mood manipulation influenced in part older adults’ emotional memory bias, showing some signs of mood incongruence which we discuss in terms of emotion regulation. This shows the importance of accounting for mood differences in studies on aging and memory. The robust age group differences support the view that the positivity effect in aging is the result of a negativity bias that fades with age.
Case report: Acute vestibular syndrome and cerebellitis in anti-Yo paraneoplastic syndrome
Authors: Kherallah Bassil , Samaha Elias , Bach Sarah E. , Guede Cindy , Kattah Jorge C.
Published: August 2022

Background

We define acute vestibular syndrome (AVS) as a sudden onset vertigo, nausea, vomiting, and head motion intolerance, more frequently associated with an acute peripheral and unilateral vestibulopathy. About 10–20% of all cases with central vestibulopathy are secondary to stroke. We report three patients evaluated over the past decade with an acute AVS along with subtle downbeat nystagmus (DBN), followed by dysarthria and progressive truncal and limb ataxia, as well as increasing DBN intensity.

Methods

All patients underwent neurologic examination, video-oculography, MRI, serum cancer markers, spinal fluid examination, paraneoplastic panel testing, and oncologic workup. With a consolidated diagnosis of cancer/paraneoplastic syndrome, we treated with plasma exchange (PLEX), high-dose steroids, surgery, and oncologic investigation. We additionally provided oncotherapy in one out of three patients.

Results

All three patients had an acute AVS, downbeat nystagmus DBN, and inability to perform tandem gait. Two of three patients had a normal head impulse test (HIT). As acute vertigo, nausea, and vomiting subsided, a progressive cerebellar syndrome ensued characterized by persistent DBN, impaired horizontal and vertical pursuit, impaired VOR suppression, truncal and limb ataxia, and dysarthria. All patients had normal MRI brain studies excluding stroke. CSF studies demonstrated lymphocytic pleocytosis and elevated protein. One patient had confirmed ovarian cancer with high CA-125 serum levels; another had undifferentiated cancer of unknown primary with high CA-125 and one patient with esophageal cancer. All had a positive PCA-1 antibody titer, also known as anti-Yo antibody. In one patient with expeditious immunosuppression, the ataxia progression slowed for 18 months, whereas the other two patients with delayed initiation of treatment had more rapidly progressive ataxia.

Discussion

Paraneoplastic encephalitis related to PCA-1 antibody (Anti-Yo) targets Purkinje cells and cells in the granular layer of the cerebellar cortex. Clinically, our patients had a central AVS characterized by DBN and followed with progressive ataxia and unremarkable neuroimaging studies. Rapid initiation of treatment may offer a greater chance to prevent further neurologic decline. Any patient with an AVS as well as DBN and normal MRI should have an expeditious workup to rule out metabolic, toxic, and infectious causes just prior to considering prompt treatment with high-dose steroids and plasma exchange (PLEX) to mitigate the risk of rapidly progressive and irreversible neurologic decline.
A visualized nomogram to online predict futile recanalization after endovascular thrombectomy in basilar artery occlusion stroke
Authors: Lin ShiTeng , Lin XinPing , Zhang Juan , Wan Meng , Chen Chen , Jie Qiong , Wu YueZhang , Qiu RunZe , Cui XiaoLi , Jiang ChunLian , Zou JianJun , Zhao ZhiHong
Published: August 2022

Background and purpose

Futile recanalization occurs in a significant proportion of patients with basilar artery occlusion (BAO) after endovascular thrombectomy (EVT). Therefore, our goal was to develop a visualized nomogram model to early identify patients with BAO who would be at high risk of futile recanalization, more importantly, to aid neurologists in selecting the most appropriate candidates for EVT.

Methods

Patients with BAO with EVT and the Thrombolysis in Cerebral Infarction score of ≥2b were included in the National Advanced Stroke Center of Nanjing First Hospital (China) from October 2016 to June 2021. The exclusion criteria were lacking the 3-month Modified Rankin Scale (mRS), age <18 years, the premorbid mRS score >2, and unavailable baseline CT imaging. Potential predictors were selected for the construction of the nomogram model and the predictive and calibration capabilities of the model were assessed.

Results

A total of 84 patients with BAO were finally enrolled in this study, and patients with futile recanalization accounted for 50.0% (42). The area under the curve (AUC) of the nomogram model was 0.866 (95% CI, 0.786–0.946). The mean squared error, an indicator of the calibration ability of our prediction model, was 0.025. A web-based nomogram model for broader and easier access by clinicians is available online at https://trend.shinyapps.io/DynNomapp/.

Conclusion

We constructed a visualized nomogram model to accurately and online predict the risk of futile recanalization for patients with BAO, as well as assist in the selection of appropriate candidates for EVT.
Optical coherence tomography angiography biomarkers of microvascular alterations in RVCL-S
Authors: Al-Nofal Mays , de Boer Irene , Agirman Seda , Wilms Anne E. , Zamanipoor Najafabadi Amir H. , Terwindt Gisela M. , Notting Irene C.
Published: August 2022

Background

The brain and retina share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in patients with a monogenic vasculopathy using optical coherence tomography angiography (OCTA). OCT-A is a novel precise non-invasive imaging method that may provide biomarkers suitable for diagnosis and follow-up of small vessel diseases.

Methods

In this exploratory cross-sectional study, eleven RVCL-S patients and eleven age-matched healthy control participants were included. The size of the foveal avascular zone (FAZ) and the vascular density of the superficial capillary networks in the retina were measured by OCT-A.

Results

The symptomatic and presymptomatic patients showed significantly lower vascular density values than controls in the foveal region [median (IQR) 18.2% (15.8–18.6) vs. 24.4% (21.5–26.8) (p < 0.001), 29.8% (29.6–30.8) vs. 33.2% (32.0–33.6) (p = 0.002), respectively]. The FAZ was significantly larger in the symptomatic RVCL-S patients than in the control group [13,416 square pixels [7,529–22,860] vs. 1,405 square pixels [1,344–2,470] (p < 0.001)]. No significant difference was identified in measurements of FAZ comparing presymptomatic and controls.

Conclusion

Our findings with OCT-A demonstrated that RVCL-S causes an increase in the size of the FAZ in symptomatic RVCL-S patients compared to healthy participants. Moreover, there is a decrease in vessel density in the superficial capillary networks in both symptomatic and presymptomatic patients. In the future, newly developed precise objective instruments such as OCT (-A) may provide important tools in determining disease activity for follow up of common small vessel diseases.
Inter-brain plasticity as a biological mechanism of change in psychotherapy: A review and integrative model
Authors: Sened Haran , Zilcha-Mano Sigal , Shamay-Tsoory Simone
Published: August 2022

Recent models of psychopathology and psychotherapy highlight the importance of interpersonal factors. The current review offers a biological perspective on these interpersonal processes by examining inter-brain synchrony—the coupling of brain activity between people interacting with one another. High inter-brain synchrony is associated with better relationships in therapy and in daily life, while deficits in the ability to achieve inter-brain synchrony are associated with a variety of psychological and developmental disorders. The review suggests that therapy improves patients’ ability to achieve such synchrony through inter-brain plasticity—a process by which recurring exposure to high inter-brain synchrony leads to lasting change in a person’s overall ability to synchronize. Therapeutic sessions provide repeated situations with high inter-brain synchrony. This can lead to a long-term increase in the ability to synchronize, first with the therapist, then generalized to other interpersonal relationships, ultimately leading to symptom reduction. The proposed inter-brain plasticity model offers a novel biological framework for understanding relational change in psychotherapy and its links to various forms of psychopathology and provides testable hypotheses for future research. Understanding this mechanism may help improve existing psychotherapy methods and develop new ones.
Using transfer learning for automated microbleed segmentation
Authors: Dadar Mahsa , Zhernovaia Maryna , Mahmoud Sawsan , Camicioli Richard , Maranzano Josefina , Duchesne Simon
Published: August 2022

Introduction

Cerebral microbleeds are small perivascular hemorrhages that can occur in both gray and white matter brain regions. Microbleeds are a marker of cerebrovascular pathology and are associated with an increased risk of cognitive decline and dementia. Microbleeds can be identified and manually segmented by expert radiologists and neurologists, usually from susceptibility-contrast MRI. The latter is hard to harmonize across scanners, while manual segmentation is laborious, time-consuming, and subject to interrater and intrarater variability. Automated techniques so far have shown high accuracy at a neighborhood (“patch”) level at the expense of a high number of false positive voxel-wise lesions. We aimed to develop an automated, more precise microbleed segmentation tool that can use standardizable MRI contrasts.

Methods

We first trained a ResNet50 network on another MRI segmentation task (cerebrospinal fluid vs. background segmentation) using T1-weighted, T2-weighted, and T2* MRIs. We then used transfer learning to train the network for the detection of microbleeds with the same contrasts. As a final step, we employed a combination of morphological operators and rules at the local lesion level to remove false positives. Manual segmentation of microbleeds from 78 participants was used to train and validate the system. We assessed the impact of patch size, freezing weights of the initial layers, mini-batch size, learning rate, and data augmentation on the performance of the Microbleed ResNet50 network.

Results

The proposed method achieved high performance, with a patch-level sensitivity, specificity, and accuracy of 99.57, 99.16, and 99.93%, respectively. At a per lesion level, sensitivity, precision, and Dice similarity index values were 89.1, 20.1, and 0.28% for cortical GM; 100, 100, and 1.0% for deep GM; and 91.1, 44.3, and 0.58% for WM, respectively.

Discussion

The proposed microbleed segmentation method is more suitable for the automated detection of microbleeds with high sensitivity.
Modulation of thalamic network connectivity using transcranial direct current stimulation based on resting-state functional magnetic resonance imaging to improve hypoxia-induced cognitive impairments
Authors: Dalong Guo , Yufei Qin , Lei Yang , Pengfei Li , Anqi Ye , Zichuan Guo , Cong Wang , Yubin Zhou
Published: August 2022

Hypoxic conditions at high altitudes severely affect cognitive functions such as vigilance, attention, and memory and reduce cognitive ability. Hence, there is a critical need to investigate methods and associated mechanisms for improving the cognitive ability of workers at high altitudes. This study aimed to use transcranial direct current stimulation (tDCS) to modulate thalamic network functional connectivity to enhance cognitive ability. We recruited 20 healthy participants that underwent hypoxia exposure in a hypoxic chamber at atmospheric pressure to simulate a hypoxic environment at 4,000 m. Participants received both sham and real stimulation. tDCS significantly improved the participants’ emotional status, including depression, fatigue, and energy level. These effects were sustained for more than 6 h (P < 0.05 at the second to fifth measurements). In addition, tDCS enhanced vigilance, but this was only effective within 2 h (P < 0.05 at the second and third measurements). Central fatigue was significantly ameliorated, and cerebral blood oxygen saturation was increased within 4 h (P < 0.05 at the second, third, and fourth measurements). Furthermore, functional connectivity results using the thalamus as a seed revealed enhanced connectivity between the thalamus and hippocampus, cingulate gyrus, and amygdala after tDCS. These results indicated that tDCS increased local cerebral blood oxygen saturation and enhanced thalamic network connectivity in a hypoxic environment, thereby improving vigilance, depression, fatigue, and energy levels. These findings suggest that tDCS may partially rescue the cognitive decline caused by hypoxia within a short period. This approach affords a safe and effective cognitive enhancement method for all types of high-altitude workers with a large mental load.
Whole-brain monosynaptic outputs and presynaptic inputs of GABAergic neurons in the vestibular nuclei complex of mice
Authors: Shi Xun-Bei , Wang Jing , Li Fei-Tian , Zhang Yi-Bo , Qu Wei-Min , Dai Chun-Fu , Huang Zhi-Li
Published: August 2022

GABAergic neurons in the vestibular nuclei (VN) participate in multiple vital vestibular sensory processing allowing for the maintenance and rehabilitation of vestibular functions. However, although the important role of GABA in the central vestibular system has been widely reported, the underlying neural circuits between VN GABAergic neurons and other brain functional regions remain elusive, which limits the further study of the underlying mechanism. Hence, it is necessary to elucidate neural connectivity based on outputs and inputs of GABAergic neurons in the VN. This study employed a modified rabies virus retrograde tracing vector and cre-dependent adeno-associated viruses (AAVs) anterograde tracing vector, combined with a transgenic VGAT-IRES-Cre mice, to map the inputs and outputs of VN GABAergic neurons in the whole brain. We found that 51 discrete brain regions received projections from VN GABAergic neurons in the whole brain, and there were 77 upstream nuclei innervating GABAergic neurons in the VN. These nuclei were mainly located in four brain regions, including the medulla, pons, midbrain, and cerebellum. Among them, VN GABAergic neurons established neural circuits with some functional nuclei in the whole brain, especially regulating balance maintenance, emotion control, pain processing, sleep and circadian rhythm regulation, and fluid homeostasis. Therefore, this study deepens a comprehensive understanding of the whole-brain neural connectivity of VN, providing the neuroanatomical information for further research on the neural mechanism of the co-morbidities with vestibular dysfunction.
Acupuncture for menstruation-related migraine prophylaxis: A multicenter randomized controlled trial
Authors: Liu Lu , Zhang Claire-Shuiqing , Liu Hui-Lin , He Fan , Lyu Tian-Li , Zeng Lin , Zhao Luo-Peng , Wang Mi-Na , Qu Zheng-Yang , Nie Li-Min , Guo Jia , Zhang Xiao-Zhe , Lu Yong-Hui , Wang Ke-Lun , Li Bin , Jing Xiang-Hong , Wang Lin-Peng
Published: August 2022

Objective

The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM).

Patients and methods

This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1−3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1−3 and 4−6.

Results

A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17–0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82–1.07) in the acupuncture group and 0.61 (95% CI, 0.50–0.71) in the medication group over cycles 1−3.

Conclusion

This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles.

Clinical trial registration

[https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606].