bluuebunny/crossref_metadata_2025 huggingface dataset:
Polypill for atherosclerotic cardiovascular disease prevention in Haiti: Eligibility estimates in a low-income country
Authors: Yan Lily D. , Rouzier Vanessa , Pierre Jean Lookens , Dade Eliezer , Sufra Rodney , Huffman Mark D. , Apollon Alexandra , St Preux Stephano , Metz Miranda , Sabwa Shalom , Morisset Béatrice , Deschamps Marie , Pape Jean W. , McNairy Margaret L.
Published: July 2022

Background

Multidrug therapy is a World Health Organization “best buy” for the prevention and control of noncommunicable diseases. CVD polypills, including ≥2 blood pressure medications, and a statin with or without aspirin, are an effective, scalable strategy to close the treatment gap that exists in many low- and middle-income countries, including Haiti. We estimated the number of Haitian adults eligible for an atherosclerotic CVD (ASCVD) polypill, and the number of potentially preventable CVD events if polypills were implemented nationally.

Methods

We used cross-sectional data from the Haiti CVD Cohort, a population-based cohort of 3,005 adults ≥18 years in Port-au-Prince, to compare two polypill implementation strategies: high-risk primary prevention and secondary prevention. High-risk primary prevention included three scenarios: (a) age ≥40 years, (b) hypertension, or (c) predicted 10-year ASCVD risk ≥7.5%. Secondary prevention eligibility included history of stroke or myocardial infarction. We then used the 2019 Global Burden of Disease database and published polypill trials to estimate preventable CVD events, defined as nonfatal MI, nonfatal stroke, and cardiovascular death over a 5-year timeline.

Results

Among 2,880 participants, the proportion of eligible adults for primary prevention were: 51.6% for age, 32.5% for hypertension, 19.3% for high ASCVD risk, and 5.8% for secondary prevention. Based on current trends, an estimated 462,509 CVD events (95% CI: 369,089–578,475) would occur among adults ≥40 years in Haiti from 2019–2024. Compared with no polypill therapy, we found 32% or 148,003 CVD events (95% CI: 70,126–248,744) could be prevented by a combined primary and secondary prevention approach in Haiti if polypills were fully implemented over 5 years.

Conclusion

These modeling estimates underscore the potential magnitude of preventable CVD events in low-income settings like Haiti. Model calibration using observed CVD events, costs, and implementation assumptions are future directions.

Clinical trial registration

clinicaltrials.gov, identifier: NCT03892265.
Linking animal behavior to ecosystem change in disturbed environments
Authors: Rahman Tawfiqur , Candolin Ulrika
Published: July 2022

Environmental disturbances often cause individuals to change their behavior. The behavioral responses can induce a chain of reactions through the network of species interactions,viaconsumptive and trait mediated connections. Given that species interactions define ecosystem structure and functioning, changes to these interactions often have ecological repercussions. Here, we explore the transmission of behavioral responses through the network of species interactions, and how the responses influence ecological conditions. We describe the underlying mechanisms and the ultimate impact that the behavioral responses can have on ecosystem structure and functioning, including biodiversity and ecosystems stability and services. We explain why behavioral responses of some species have a larger impact than that of others on ecosystems, and why research should focus on these species and their interactions. With the work, we synthesize existing theory and empirical evidence to provide a conceptual framework that links behavior responses to altered species interactions, community dynamics, and ecosystem processes. Considering that species interactions link biodiversity to ecosystem functioning, a deeper understanding of behavioral responses and their causes and consequences can improve our knowledge of the mechanisms and pathways through which human activities alter ecosystems. This knowledge can improve our ability to predict the effects of ongoing disturbances on communities and ecosystems and decide on the interventions needed to mitigate negative effects.
Quantitative relationship between cladocera and cyanobacteria: A study based on field survey
Authors: Li Daikui , He Ping , Liu Cunqi , Xu Jie , Hou Liping , Gao Xiuli , Wang Dewang , Wang Jiawen
Published: July 2022

Cyanobacteria are a widely distributed phytoplankton that can bloom and produce algal toxins in the eutrophicated water bodies. Large cladocerans are a group of zooplankton that presents higher grazing efficiency on algae. Studying the quantitative relationship between cyanobacteria and cladocera, especially in unmanipulated and unpredictable natural ecosystems in the wild, provides the key to revealing the mechanism of cyanobacterial blooms and finding effective control and prevention methods. This paper proposes a research method to detect the threshold for cladocera to control cyanobacteria by using the path of “edge scatter-segment regression.” Based on the field survey data from 242 sample sites in shallow and slow-flowing rivers in North China, the quantitative relationship between the main groups of zooplankton and phytoplankton was analyzed, and the standard deviation and coefficient of variation were used to test the threshold. This paper finally compares the roles of body size and cladocera abundance in cyanobacteria control. The results showed that in natural ecosystems, cladocera were the best group for controlling the abundance of cyanobacteria among zooplankton. The control effect of cladocera on the abundance of cyanobacteria is not linear but non-linear, and cladocera can only have a stable control effect under certain conditions. The total phosphorus concentrations and water temperatures did not interfere with the analysis results in this paper. In wild ecosystems, the predation process of cladocera on cyanobacteria basically follows the “size-efficiency” hypothesis, but when cladocera successfully control cyanobacterial abundances, it is often due to “win by quantity” rather than “win by size.” The phenomenon of non-linear variation in the cladocera density-cyanobacteria density relationship fits well with the description of the transition from a stable to chaotic state in chaos theory. This paper reveals the complex quantitative relationships of plankton food chains in wild aquatic ecosystems. The ecological threshold detection of the cladocera-cyanobacterial abundances provides a quantitative basis for early warning, control and prevention of cyanobacteria blooms. The non-linear variations in cladocera density-cyanobacteria density revealed in this paper provide insight and evidence for understanding the complex changes in aquatic ecosystems.
Recent Recovery of the World’s Rarest Primate Is Not Directly Linked to Increasing Habitat Quality
Authors: Zou Yike , Turvey Samuel T. , Cui Jie , Zhang Hui , Gong Wenfeng
Published: July 2022

Due to habitat loss and hunting, the Hainan gibbon (Nomascus hainanus), the world’s rarest primate, was reduced to only two social groups and seven known individuals in 1978. Following the establishment of Bawangling National Natural Reserve (BNNR), gibbon forest habitat increased within this landscape from 56 km2 in 1980 to 300 km2, and the species had increased to five groups and 35 individuals by 2021. It is important to assess whether the large increase in habitat area was responsible for gibbon population increase, or whether gibbon recovery was associated with other factors. Here we use a 21-year longitudinal dataset of Hainan gibbon population change and habitat change, combined with vegetation survey plot data for 2021, to establish an accurate distribution baseline for natural tropical broadleaf forest across the BNNR landscape from 400 to 1300 m (the elevational range of gibbons at BNNR) and within the home range for each of the five Hainan gibbon social groups. We then utilized Landsat time-series images and analysis to compute non-linear causal relationships between forest dynamics and gibbon population growth from 2000 to 2021, both across BNNR and within each gibbon group home range. Metrics of forest dynamics include change in total forest area and forest fragmentation, and metrics of gibbon population dynamics include variation in total number of individuals for the entire population and within each social group, and variation in total number of groups. Our results demonstrate that overall gibbon population growth shows a positive relationship with improved habitat quality, with a one-year time lag of population response. However, changes in numbers of individuals within social groups do not show a similar relationship with improving habitat quality, suggesting that increasing forest cover and connectivity within the BNNR landscape are not direct determinants of Hainan gibbon recovery and that other environmental and/or anthropogenic factors are likely to be involved.
Structural Characterization of the Acer ukurunduense Chloroplast Genome Relative to Related Species in the Acer Genus
Authors: Ren Weichao , Liu Chi , Yan Song , Jiang Zhehui , Wang Tianhao , Wang Zhen , Zhang Meiqi , Liu Meiqi , Sun Jiaying , Gao Jinhui , Ma Wei
Published: July 2022

Acer ukurunduense refers to a deciduous tree distributed in Northeast Asia and is a widely used landscaping tree species. Although several studies have been conducted on the species’ ecological and economic significance, limited information is available on its phylo-genomics. Our study newly constitutes the complete chloroplast genome of A. ukurunduense into a 156,645-bp circular DNA, which displayed a typical quadripartite structure. In addition, 133 genes were identified, containing 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. In total, 107 simple sequence repeats and 49 repetitive sequences were observed. Thirty-two codons indicated that biased usages were estimated across 20 protein-coding genes (CDS) in A. ukurunduense. Four hotspot regions (trnK-UUU/rps16, ndhF/rpl32, rpl32/trnL-UAG, and ycf1) were detected among the five analyzed Acer species. Those hotspot regions may be useful molecular markers and contribute to future population genetics studies. The phylogenetic analysis demonstrated that A. ukurunduense is most closely associated with the species of Sect. Palmata. A. ukurunduense and A. pubipetiolatum var. pingpienense diverged in 22.11 Mya. We selected one of the hypervariable regions (trnK-UUU/rps16) to develop a new molecular marker and designed primers and confirmed that the molecular markers could accurately discriminate five Acer species through Sanger sequencing. By sequencing the cp genome of A. ukurunduense and comparing it with the relative species of Acer, we can effectively address the phylogenetic problems of Acer at the species level and provide insights into future research on population genetics and genetic diversity.
Catching Nucleosome by Its Decorated Tails Determines Its Functional States
Authors: Sehrawat Parveen , Shobhawat Rahul , Kumar Ashutosh
Published: July 2022

The fundamental packaging unit of chromatin, i.e., nucleosome, consists of ∼147 bp of DNA wrapped around a histone octamer composed of the core histones, H2A, H2B, H3, and H4, in two copies each. DNA packaged in nucleosomes must be accessible to various machineries, including replication, transcription, and DNA damage repair, implicating the dynamic nature of chromatin even in its compact state. As the tails protrude out of the nucleosome, they are easily accessible to various chromatin-modifying machineries and undergo post-translational modifications (PTMs), thus playing a critical role in epigenetic regulation. PTMs can regulate chromatin states via charge modulation on histones, affecting interaction with various chromatin-associated proteins (CAPs) and DNA. With technological advancement, the list of PTMs is ever-growing along with their writers, readers, and erasers, expanding the complexity of an already intricate epigenetic field. In this review, we discuss how some of the specific PTMs on flexible histone tails affect the nucleosomal structure and regulate the accessibility of chromatin from a mechanistic standpoint and provide structural insights into some newly identified PTM–reader interaction.
Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds
Authors: Sun Jia-Xue , Xu Xiang-Hong , Jin Liping
Published: July 2022

Macrophages are versatile immune cells associated with various diseases, and their phenotypes and functions change on the basis of the surrounding environments. Reprogramming of metabolism is required for the proper polarization of macrophages. This review will focus on basic metabolic pathways, the effects of key enzymes and specific products, relationships between cellular metabolism and macrophage polarization in different diseases and the potential prospect of therapy targeted key metabolic enzymes. In particular, the types and characteristics of macrophages at the maternal-fetal interface and their effects on a successful conception will be discussed.
Two Step Selection for Bias in β Chain V-J Pairing
Authors: Levi Reut , Louzoun Yoram
Published: July 2022

Theβchain rearrangement in T cells is a two-step process where firstDβandJβbind, and only thenVβis joined to the complex. We here show that the frequency of human and mouseVβJβcombinations deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional (F) rearrangements, but also slightly in non-functional (NF) rearrangements. PreferredVβJβcombinations in F clones are shared between donors and samples, suggesting a common structural mechanism for these biases in addition to any host-specific antigen-induced peripheral selection. The sharing holds even in clones with Jβ1 that share the sameDβ1 gene.VβJβusage is correlated with the Molecular Weight and Isoelectric Point in F clones. The pairing is also observed in the Double Positive cells in mice thymocytes, suggesting that the selection leading to such a pairing occurs before thymic selection. These results suggest an additional structural checkpoint in the beta chain development prior to thymic selection during the T cell receptor expression. Understanding this structural selection is important for the distinction between normal and aberrant T cell development, and crucial for the design of engineered TCRs.
The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
Authors: Gonzales Gerone A. , Canton Johnathan
Published: July 2022

Phagocytes, such as macrophages and dendritic cells, possess the ability to ingest large quantities of exogenous material into membrane-bound endocytic organelles such as macropinosomes and phagosomes. Typically, the ingested material, which consists of diverse macromolecules such as proteins and nucleic acids, is delivered to lysosomes where it is digested into smaller molecules like amino acids and nucleosides. These smaller molecules can then be exported out of the lysosomes by transmembrane transporters for incorporation into the cell’s metabolic pathways or for export from the cell. There are, however, exceptional instances when undigested macromolecules escape degradation and are instead delivered across the membrane of endocytic organelles into the cytosol of the phagocyte. For example, double stranded DNA, a damage associated molecular pattern shed by necrotic tumor cells, is endocytosed by phagocytes in the tumor microenvironment and delivered to the cytosol for detection by the cytosolic “danger” sensor cGAS. Other macromolecular “danger” signals including lipopolysaccharide, intact proteins, and peptidoglycans can also be actively transferred from within endocytic organelles to the cytosol. Despite the obvious biological importance of these processes, we know relatively little of how macromolecular “danger” signals are transferred across endocytic organelle membranes for detection by cytosolic sensors. Here we review the emerging evidence for the active cytosolic transfer of diverse macromolecular “danger” signals across endocytic organelle membranes. We will highlight developing trends and discuss the potential molecular mechanisms driving this emerging phenomenon.
Effects of Internal Climate Variability on Historical Ocean Wave Height Trend Assessment
Authors: Casas-Prat Mercè , Wang Xiaolan L. , Mori Nobuhito , Feng Yang , Chan Rodney , Shimura Tomoya
Published: July 2022

This study assesses the effects of internal climate variability on wave height trend assessment using the d4PDF-WaveHs, the first single model initial-condition large ensemble (100-member) of significant wave height (Hs) simulations for the 1951–2010 period, which was produced using sea level pressure taken from Japan’s d4PDF ensemble of historical climate simulations. Here, the focus is on assessing trends in annual mean and maximumHs. The result is compared with other model simulations that account for other sources of uncertainty, and with modern wave reanalyses. It is shown that the trend variability arising from internal climate variability is comparable to the variability caused by other factors, such as climate model uncertainty. This study also assesses the likelihood to mis-estimate trends when using only one ensemble member and therefore one possible realization of the climate system. Using single member failed to detect the statistically significant notable positive trend shown in the ensemble in some areas of the Southern Ocean. The North Atlantic Ocean is found to have large internal climate variability, where different ensemble-members can show trends of the opposite signs for the same area. The minimum ensemble size necessary to effectively reduce the risk of mis-assessingHstrends is estimated to be 10; but this largely depends on the specific wave statistic and the region of interest, with larger ensembles being required to assess extremes. The results also show that wave reanalyses are not suitable for analyzingHstrends due to temporal inhomogeneities therein, in agreement with recent studies.
Advection and Composition of Dinophysis spp. Populations Along the European Atlantic Shelf
Authors: Hariri Saeed , Plus Martin , Le Gac Mickael , Séchet Véronique , Revilla Marta , Sourisseau Marc
Published: July 2022

The main objective was to study relationships between the regional biogeography ofDinophysisspecies and water masses circulation along the European Atlantic coast. Hydrodynamic connectivities were estimated with a Lagrangian approach. Available and validated physical hindcasts from regional hydrodynamical models, with different resolutions were used. The target area is the Bay of Biscay (NE Atlantic) and connectivity was evaluated between a set of spatially distributed stations and during temporally specified periods. Different indexes related to connectivity properties such as mean, median, most frequent transit times were calculated. To illustrate the dispersion pattern, a molecular approach was jointly set-up to describe the species composition of this genus. At the seasonal scale, a high connectivity within the Bay of Biscay was observed with a slight northward connectivity from Galicia coastal waters to the Shelf of the Bay of Biscay. By comparison to the connectivity between shelf waters of French Brittany and English Channel waters, a higher connectivity between shelf waters of French Brittany and the Celtic Sea shelf was observed. The species mixing in the Bay of Biscay from Galicia waters to the Celtic Sea was confirmed by the genetic analyses despite the absence ofDinophysis sacculusin natural samples. The molecular methodology developed for this work, permitting at least the description of the species composition, also highlights, at the European scale, an unexpected low genetic variability which echoes the complex taxonomic classification inside the genus and the difficulties encountered by national monitoring programs to reach a taxonomic resolution at species level. It is now necessary to start some monitoring at the species level before realizing mid- or long-term forecasts.
Benefits and Challenges of a Stakeholder-Driven Shellfish Toxicity Forecast in Coastal Maine
Authors: Record Nicholas R. , Evanilla Johnathan , Kanwit Kohl , Burnell Craig , Cartisano Carmen , Lewis Bryant J. , MacLeod Jill , Tupper Benjamin , Miller David W. , Tracy Adrienne T. , White Carol , Moretti Matt , Hamilton Ben , Barner Cameron , Archer Stephen D.
Published: July 2022

Paralytic shellfish poison (PSP) is a human health concern for shellfish aquaculture and wild harvest. This paper discusses lessons learned from a forecasting program for PSP in coastal Maine, USA, designed based on stakeholder input, and run in an operational mode for the 2021 season. The forecast uses a deep learning algorithm to make site-specific, probabilistic forecasts at a weekly forecast range for toxin levels measured in shellfish tissue. Forecasts had high accuracy in the 2021 season, correctly predicting closure events and locations despite a highly unusual season. Stakeholders reported a positive view of the forecast system, and stakeholder input continues to be of key importance as further modifications are made to the system. There are benefits and challenges to the stakeholder-based design of the system.
Discovery of Novel Tyrosinase Inhibitors From Marine Cyanobacteria
Authors: He Yifan , Suyama Takashi L. , Kim Hyunwoo , Glukhov Evgenia , Gerwick William H.
Published: July 2022

Tyrosinase, an important oxidase involved in the primary immune response in humans, can sometimes become problematic as it can catalyze undesirable oxidation reactions. Therefore, for decades there has been a strong pharmaceutical interest in the discovery of novel inhibitors of this enzyme. Recent studies have also indicated that tyrosinase inhibitors can potentially be used in the treatment of melanoma cancer. Over the years, many new tyrosinase inhibitors have been discovered from various natural sources; however, marine natural products (MNPs) have contributed only a small number of promising candidates. Therefore, in this study we focused on the discovery of new MNP tyrosinase inhibitors of marine cyanobacterial and algal origins. A colorimetric tyrosinase inhibitory assay was used to screen over 4,500 marine extracts against mushroom tyrosinase (A. bisporus). Our results revealed that scytonemin monomer (ScyM), a pure compound from our compound library and also the monomeric last-step precursor in the biosynthesis of the well-known cyanobacterial sunscreen pigment “scytonemin,” consistently showed the highest tyrosinase inhibitory score. Determination of the half maximal inhibitory concentration (IC50) further indicated that ScyM is more potent than the commonly used commercial inhibitor standard “kojic acid” (KA; IC50 of ScyM: 4.90 μM vs. IC50 of KA: 11.31 μM). After a scaled-up chemical synthesis of ScyM as well as its O-methyl analog (ScyM-OMe), we conducted a series of follow-up studies on their structures, inhibitory properties, and mode of inhibition. Our results supported ScyM as the second case ever of a novel tyrosinase inhibitory compound based on a marine cyanobacterial natural product. The excellent in vitro performance of ScyM makes it a promising candidate for applications such as a skin-whitening agent or an adjuvant therapy for melanoma cancer treatment.
A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19
Authors: Heidary Mohsen , Kaviar Vahab Hassan , Shirani Maryam , Ghanavati Roya , Motahar Moloudsadat , Sholeh Mohammad , Ghahramanpour Hossein , Khoshnood Saeed
Published: July 2022

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified in Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing a safe and efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts to produce efficient vaccines inexhaustibly are ongoing. At present time, according to the COVID-19 vaccine tracker and landscape provided by World Health Organization (WHO), there are 161 vaccine candidates in different clinical phases all over the world. In between, protein subunit vaccines are types of vaccines that contain a viral protein like spike protein or its segment as the antigen assumed to elicit humoral and cellular immunity and good protective effects. Previously, this technology of vaccine manufacturing was used in a recombinant influenza vaccine (RIV4). In the present work, we review protein subunit vaccines passing their phase 3 and 4 clinical trials, population participated in these trials, vaccines manufactures, vaccines efficiency and their side effects, and other features of these vaccines.
Recognition of Freezing of Gait in Parkinson’s Disease Based on Machine Vision
Authors: Li Wendan , Chen Xiujun , Zhang Jintao , Lu Jianjun , Zhang Chencheng , Bai Hongmin , Liang Junchao , Wang Jiajia , Du Hanqiang , Xue Gaici , Ling Yun , Ren Kang , Zou Weishen , Chen Cheng , Li Mengyan , Chen Zhonglue , Zou Haiqiang
Published: July 2022

Background

Freezing of gait (FOG) is a common clinical manifestation of Parkinson’s disease (PD), mostly occurring in the intermediate and advanced stages. FOG is likely to cause patients to fall, resulting in fractures, disabilities and even death. Currently, the pathogenesis of FOG is unclear, and FOG detection and screening methods have various defects, including subjectivity, inconvenience, and high cost. Due to limited public healthcare and transportation resources during the COVID-19 pandemic, there are greater inconveniences for PD patients who need diagnosis and treatment.

Objective

A method was established to automatically recognize FOG in PD patients through videos taken by mobile phone, which is time-saving, labor-saving, and low-cost for daily use, which may overcome the above defects. In the future, PD patients can undergo FOG assessment at any time in the home rather than in the hospital.

Methods

In this study, motion features were extracted from timed up and go (TUG) test and the narrow TUG (Narrow) test videos of 50 FOG-PD subjects through a machine learning method; then a motion recognition model to distinguish between walking and turning stages and a model to recognize FOG in these stages were constructed using the XGBoost algorithm. Finally, we combined these three models to form a multi-stage FOG recognition model.

Results

We adopted the leave-one-subject-out (LOSO) method to evaluate model performance, and the multi-stage FOG recognition model achieved a sensitivity of 87.5% sensitivity and a specificity of 79.82%.

Conclusion

A method to realize remote PD patient FOG recognition based on mobile phone video is presented in this paper. This method is convenient with high recognition accuracy and can be used to rapidly evaluate FOG in the home environment and remotely manage FOG-PD, or screen patients in large-scale communities.
Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor
Authors: Müller-Nedebock Amica C. , Pfaff Abigail L. , Pienaar Ilse S. , Kõks Sulev , van der Westhuizen Francois H. , Elson Joanna L. , Bardien Soraya
Published: July 2022

Mitochondrial DNA (mtDNA), a potential source of mitochondrial dysfunction, has been implicated in Parkinson’s disease (PD). However, many previous studies investigating associations between mtDNA population variation and PD reported inconsistent or contradictory findings. Here, we investigated an alternative hypothesis to determine whether mtDNA variation could play a significant role in PD risk. Emerging evidence suggests that haplogroup-defining mtDNA variants may have pathogenic potential if they occur “out-of-place” on a different maternal lineage. We hypothesized that the mtDNA of PD cases would be enriched for out-of-place variation in genes encoding components of the oxidative phosphorylation complexes. We tested this hypothesis with a unique dataset comprising whole mitochondrial genomes of 70 African ancestry PD cases, two African ancestry control groups (n = 78 and n = 53) and a replication group of 281 European ancestry PD cases and 140 controls from the Parkinson’s Progression Markers Initiative cohort. Significantly more African ancestry PD cases had out-of-place variants than controls from the second control group (P < 0.0125), although this association was not observed in the first control group nor the replication group. As the first mtDNA study to include African ancestry PD cases and to explore out-of-place variation in a PD context, we found evidence that such variation might be significant in this context, thereby warranting further replication in larger cohorts.
Subclinical Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Relation to Office and Ambulatory Blood Pressure Measurements
Authors: Melgarejo Jesus D. , Maestre Gladys E. , Gutierrez Jose , Thijs Lutgarde , Mena Luis J. , Gaona Ciro , Leendertz Reinier , Lee Joseph H. , Chávez Carlos A. , Calmon Gustavo , Silva Egle , Wei Dongmei , Terwilliger Joseph D. , Vanassche Thomas , Janssens Stefan , Verhamme Peter , Bos Daniel , Zhang Zhen-Yu
Published: July 2022

Background

Twenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD).

Methods

A subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each +10-mmHg increment in the office and ambulatory systolic BP measurements. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R2 statistic.

Results

Office and ambulatory systolic BP measurements were related to log-WMH (β-correlation coefficients ≥0.08; P < 0.001). Lacunes and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10-1.55] to 1.46 [1.17–1.84], P ≤ 0.003). Accounted for daytime systolic BP, both the 24-h (β-correlation, 0.170) and nighttime (β-correlation, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with lacunes (ORs, 1.05–1.06; 95% CIs, ≥1.01 to ≤ 1.13), whereas the 24-h and daytime systolic BP levels were not associated with lacunes after adjustments for nighttime systolic BP (ORs, ≤ 0.88; 95% CI, ≥0.77 to ≤ 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (1.05% ≥ R2 ≤ 3.82%). Compared to 24-h and daytime systolic BP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46 vs. 1.05%) and lacunes (3.06 vs. ≤ 2.05%).

Conclusions

Twenty-four-hour and nighttime systolic BP were the more robust BP measurements associated with CSVD, but the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD.
Clinical Spectrum of Tauopathies
Authors: Olfati Nahid , Shoeibi Ali , Litvan Irene
Published: July 2022

Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve in vivo diagnosis. Although the typical phenotypic clinical presentations lead us to suspect specific underlying pathologies, it is still challenging to differentiate pathology accurately based on clinical findings due to large phenotypic overlaps. Larger pathology-confirmed studies to validate the use of different biomarkers and prospective longitudinal cohorts evaluating detailed clinical, biofluid, and imaging protocols in subjects presenting with heterogenous phenotypes reflecting a variety of suspected underlying pathologies are fundamental for a better understanding of the clinicopathological correlations.
Case Report: The Coronal Magnetic Resonance Imaging of Three-Dimensional Fast-Field Echo With Water-Selective Excitation Can Identify the Wrapping of Spinal Nerve Fibers Into Subdural Tumors Prior to Operation
Authors: Tang Tao , Yuan Jinghong , Yin Jianhua , Zhu Junchao , Jia Jingyu , Cheng Xigao
Published: July 2022

Purpose

In the present study, the authors intend to identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina prior to operation using the coronal MRI of three-dimensional fast-field echo with water-selective excitation (CMRI).

Methods

In total, 30 case series with surgically and pathologically verified subdural tumors were enrolled in the present study. The spatial relationship between subdural tumors and spinal nerve fibers of the cauda equina was assessed via conventional MRI and CMRI by three experts prior to operation. The spatial relationship between subdural tumors and spinal nerve fibers of the cauda equina was classified using CMRI. The accuracy of imaging observation was determined via intraoperative observation.

Results

Though conventional MRI and gadolinium (Gd)-enhanced MRI (Gd MRI) cannot identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina in all cases, CMRI can identify it prior to operation and divide the spatial relationship of spinal nerve fibers of cauda equina with subdural tumors into three types. CMRI shows higher sensitivity (97.44%) and specificity (90.47%) in identifying the spatial relationship of spinal nerve fibers of cauda equina with subdural tumors. Additionally, CMRI also showed a substantial agreement with a kappa value of 0.78.

Conclusion

Herein, the authors first describe a potential novel application that CMRI can successfully identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina prior to operation, which play an essential role in making a prudent surgical plan and preventing postoperative nerve damage.

Intraoperative observation confirms spinal nerve fibers of cauda equina are often wrapped into subdural tumors of the thoracolumbar and lumbar region, which can result in a high rate of sensory and motor dysfunction after the operation due to the unconscious about the wrapping of nerves into subdural tumors prior to operation. To date, there is not an effective strategy to identify the wrapping before operation.
Humanoid Robot Walking in Maze Controlled by SSVEP-BCI Based on Augmented Reality Stimulus
Authors: Zhang Shangen , Gao Xiaorong , Chen Xiaogang
Published: July 2022

The application study of robot control based brain-computer interface (BCI) not only helps to promote the practicality of BCI but also helps to promote the advancement of robot technology, which is of great significance. Among the many obstacles, the importability of the stimulator brings much inconvenience to the robot control task. In this study, augmented reality (AR) technology was employed as the visual stimulator of steady-state visual evoked potential (SSVEP)-BCI and the robot walking experiment in the maze was designed to testify the applicability of the AR-BCI system. The online experiment was designed to complete the robot maze walking task and the robot walking commands were sent out by BCI system, in which human intentions were decoded by Filter Bank Canonical Correlation Analysis (FBCCA) algorithm. The results showed that all the 12 subjects could complete the robot walking task in the maze, which verified the feasibility of the AR-SSVEP-NAO system. This study provided an application demonstration for the robot control base on brain–computer interface, and further provided a new method for the future portable BCI system.
Flavor and Other Quality Traits of Tomato Cultivars Bred for Diverse Production Systems as Revealed in Organic Low-Input Management
Authors: Erika Cut , Ulrich Detlef , Naumann Marcel , Smit Inga , Horneburg Bernd , Pawelzik Elke
Published: July 2022

This study was conducted to determine the volatile organic compounds (VOCs) associated with fruit flavor in diverse tomato cultivars (salad and cocktail cultivars) under organic low-input production. For this objective, 60 cultivars deriving from very diverse breeding programs 1880–2015 were evaluated in 2015, and a subset of 20 cultivars was selected for further evaluation in 2016. The diversity of instrumentally determined traits, especially for VOCs concentration and sensory properties (fruit firmness, juiciness, skin firmness, sweetness, sourness, aroma, and acceptability), was investigated at two harvest dates. The evaluation of the cultivars exhibited a wide range of variation for all studied traits, with the exception of a few VOCs. Cultivar had the most important effect on all instrumentally determined traits, while the influence of cultivar × harvest date × year interaction was significant for 17 VOCs, but not for total soluble solid (TSS) and titratable acidity (TA). The VOCs with the highest proportion (>8%) were hexanal, 6-methyl-5-heptene-2-one, 2-isobutylthiazole, and (E)-2-hexenal, which were identified in all cultivars. Twelve VOCs significantly correlated with one or more sensory attributes and these VOCs also allowed differentiation of the fruit type. Among these VOCs, phenylethyl alcohol and benzyl alcohol positively correlated with acceptability in the cocktail cultivars, whereas 2-isobuthylthiazole and 6-methyl-5-hepten-2-ol negatively correlated with acceptability in the salad cultivars. As a result of this study, organic breeders are recommended to use cultivars from a wide range of breeding programs to improve important quality and agronomic traits. As examples, salad tomatoes “Campari F1”, “Green Zebra”, and “Auriga”, as well as cocktail tomatoes “Supersweet 100 F1”, “Sakura F1”, and “Black Cherry” showed higher scores for the sensory attributes aroma and acceptability under organic low-input growing conditions. It remains a challenge for breeders and growers to reduce the trade-off of yield and quality.
Preliminary Application of Magnetization Transfer Imaging in the Study of Normal Uterus and Uterine Lesions
Authors: Bi Qiu , Li Qing , Yang Jing , Yang Junyu , Du Ji , Ding Fan , Wu Yunzhu , Wang Shaoyu , Zhao Ying
Published: July 2022

Purpose

The aim of this study is to evaluate the utility of magnetization transfer (MT) imaging in the study of normal uterus and common uterine lesions.

Methods

This prospective study enrolled 160 consecutive patients with suspected uterine lesions. MT ratio (MTR) map was obtained by pelvic MT imaging on a 3.0T MRI scanner. Patients confirmed by pathology were divided into microscopic lesion group and lesion group, according to whether the maximum diameter of the lesion was less than 5 mm. After evaluating and eliminating patients with poor image quality by a three-point Likert scale, MTR values of lesions and normal endometrium, myometrium, and cervix were independently measured on the MTR map by two radiologists. Inter-reader agreement was evaluated. MTR values were compared among different uterine lesions and normal uterine structures using the Mann–Whitney U test with Bonferroni correction. Receiver operating characteristic curve was performed. The correlations between age and MTR values were explored by Pearson correlation analyses.

Results

A total of 96 patients with 121 uterine lesions in the lesion group and 41 patients in the microscopic lesion group were measured. The MTR values among normal endometrium, myometrium, and cervix were statistical significant differences (P < 0.05). There were significant differences between endometrial cancer and normal endometrium and between cervical cancer and normal cervix (both P ≤ 0.001). Area under the curve (AUC) for diagnosing endometrial and cervical cancer were 0.73 and 0.86. Myometrial lesions had significantly higher MTR values than endometrial lesions and cervical cancer (both P < 0.001), and the AUC for differentiating myometrial lesions from them were 0.89 and 0.94. MTR values of endometrial cancer were significantly higher than those of cervical cancer (P = 0.02). There was a critical correlation between age and MTR values in endometrial cancer (r = 0.81, P = 0.04).

Conclusions

MTR values showed significant differences among normal uterine structures. It was valuable for diagnosing and differentiating uterine cancer. MTR values could differentiate myometrial lesions from endometrial or cervical lesions.
Radiomic Signatures for Predicting EGFR Mutation Status in Lung Cancer Brain Metastases
Authors: Zheng Lie , Xie Hui , Luo Xiao , Yang Yadi , Zhang Yijun , Li Yue , Yin Shaohan , Li Hui , Xie Chuanmiao
Published: July 2022

Background

Lung cancer is the most common primary tumor metastasizing to the brain. A significant proportion of lung cancer patients show epidermal growth factor receptor (EGFR) mutation status discordance between the primary cancer and the corresponding brain metastases, which can affect prognosis and therapeutic decision-making. However, it is not always feasible to obtain brain metastases samples. The aim of this study was to establish a radiomic model to predict the EGFR mutation status of lung cancer brain metastases.

Methods

Data from 162 patients with resected brain metastases originating from lung cancer (70 with mutant EGFR, 92 with wild-type EGFR) were retrospectively analyzed. Radiomic features were extracted using preoperative brain magnetic resonance (MR) images (contrast-enhanced T1-weighted imaging, T1CE; T2-weighted imaging, T2WI; T2 fluid-attenuated inversion recovery, T2 FLAIR; and combinations of these sequences), to establish machine learning-based models for predicting the EGFR status of excised brain metastases (108 metastases for training and 54 metastases for testing). The least absolute shrinkage selection operator was used to select informative features; radiomics models were built with logistic regression of the training cohort, and model performance was evaluated using an independent test set.

Results

The best-performing model was a combination of 10 features selected from multiple sequences (two from T1CE, five from T2WI, and three from T2 FLAIR) in both the training and test sets, resulting in classification area under the curve, accuracy, sensitivity, and specificity values of 0.85 and 0.81, 77.8% and 75.9%, 83.7% and 73.1%, and 73.8% and 78.6%, respectively.

Conclusions

Radiomic signatures integrating multi-sequence MR images have the potential to noninvasively predict the EGFR mutation status of lung cancer brain metastases.
Multiple Myeloma With Amplification of Chr1q: Therapeutic Opportunity and Challenges
Authors: Sklavenitis-Pistofidis Romanos , Getz Gad , Ghobrial Irene , Papaioannou Maria
Published: July 2022

Multiple myeloma (MM) is an incurable plasma cell malignancy with a heterogeneous genetic background. Each MM subtype may have its own therapeutic vulnerabilities, and tailored therapy could improve outcomes. However, the cumulative frequency of druggable targets across patients is very low, which has precluded the widespread adoption of precision therapy for patients with MM. Amplification of the long arm of chromosome 1 (Amp1q) is one of the most frequent genetic alterations observed in patients with MM, and its presence predicts inferior outcomes in the era of proteasome inhibitors and immunomodulatory agents. Therefore, establishing precision medicine for MM patients with Amp1q stands to benefit a large portion of patients who are otherwise at higher risk of relapse. In this article, we review the prevalence and clinical significance of Amp1q in patients with MM, its pathogenesis and therapeutic vulnerabilities, and discuss the opportunities and challenges for Amp1q-targeted therapy.
Nintedanib Alleviates Experimental Colitis by Inhibiting CEBPB/PCK1 and CEBPB/EFNA1 Pathways
Authors: Li Hailong , Li Jinhe , Xiao Ting , Hu Yayue , Yang Ying , Gu Xiaoting , Jin Ge , Cao Hailong , Zhou Honggang , Yang Cheng
Published: July 2022

The super-enhancer, a cluster of enhancers with strong transcriptional activity, has become one of the most interesting topics in recent years. This study aimed to investigate pathogenic super-enhancer–driven genes in IBD and screen therapeutic drugs based on the results. In this study, through the analysis of differentially expressed genes in colitis patients from the GEO database and the analysis of the super-enhancer–associated database, we found that the super-enhancer pathogenic genes PCK1 and EFNA1 were simultaneously regulated by transcription factor CEBPB through two super-enhancers (sc-CHR20-57528535 and sc-CHR1-155093980). Silencing CEBPB could significantly inhibit the expression of PCK1 and EFNA1 and enhance the expression of epithelial barrier proteins claudin-1, occludin, and ZO-1. In LPS-induced Caco-2 cells, drugs commonly used in clinical colitis including tofacitinib, oxalazine, mesalazine, and sulfasalazine inhibited mRNA levels of CEBPB, PCK1, and EFNA1. In the drug screening, we found that nintedanib significantly inhibited the mRNA and protein levels of CEBPB, PCK1, and EFNA1. In vivo experiments, nintedanib significantly alleviated DSS-induced colitis in mice by inhibiting CEBPB/PCK1 and CEBPB/EFNA1 signaling pathways. At the genus level, nintedanib improved the composition of the gut microbiota in mice with DSS-induced experimental colitis. In conclusion, we found that PCK1 and EFNA1 are highly expressed in colitis and they are regulated by CEBPB through two super-enhancers, and we further demonstrate their role in vivo and in vitro. Nintedanib may be a potential treatment for IBD. Super-enhancers may be a new way to explore the pathogenesis of colitis.