bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Molecular-Weight Fractions of Spruce and Eucalyptus Lignin as a Perspective Nanoparticle-Based Platform for a Therapy Delivery in Liver Cancer
Authors: Pylypchuk Ievgen V. , Suo Huizhen , Chucheepchuenkamol Chanakarn , Jedicke Nils , Lindén Pär A. , Lindström Mikael E. , Manns Michael P. , Sevastyanova Olena , Yevsa Tetyana
Published: February 2022

The natural polymer, lignin, possesses unique biodegradable and biocompatible properties, making it highly attractive for the generation of nanoparticles for targeted cancer therapy. In this study, we investigated spruce and eucalyptus lignin nanoparticles (designated as S-and E-LNPs, respectively). Both LNP types were generated from high-molecular-weight (Mw) kraft lignin obtained as insoluble residues after a five-step solvent fractionation approach, which included ethyl acetate, ethanol, methanol, and acetone. The resulting S-and E-LNPs ranged in size from 16 to 60 nm with uniform spherical shape regardless of the type of lignin. The preparation of LNPs from an acetone-insoluble lignin fraction is attractive because of the use of high-Mw lignin that is otherwise not suitable for most polymeric applications, its potential scalability, and the consistent size of the LNPs, which was independent of increased lignin concentrations. Due to the potential of LNPs to serve as delivery platforms in liver cancer treatment, we tested, for the first time, the efficacy of newly generated E-LNPs and S-LNPs in two types of primary liver cancer, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), in vitro. Both S-LNPs and E-LNPs inhibited the proliferation of HCC cells in a dose-dependent manner and did not affect CCA cell line growth. The inhibitory effect toward HCC was more pronounced in the E-LNP-treated group and was comparable to the standard therapy, sorafenib. Also, E-LNPs induced late apoptosis and necroptosis while inhibiting the HCC cell line. This study demonstrated that an elevated number of carbohydrates on the surface of the LNPs, as shown by NMR, seem to play an important role in mediating the interaction between LNPs and eukaryotic cells. The latter effect was most pronounced in E-LNPs. The novel S- and E-LNPs generated in this work are promising materials for biomedicine with advantageous properties such as small particle size and tailored surface functionality, making them an attractive and potentially biodegradable delivery tool for combination therapy in liver cancer, which still has to be verified in vivo using HCC and CCA models.
Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort
Authors: Xu Jingran , Li Li , Ren Jie , Zhong Xuemei , Xie Chengxin , Zheng Aifang , Abudukadier Ayiguzali , Tuerxun Maimaitiaili , Zhang Sujie , Tang Lifeng , Hairoula Dilare , Zou Xiaoguang
Published: February 2022

Genetic factors are important factors in chronic obstructive pulmonary disease (COPD) onset. Plenty of risk and new causative genes for COPD have been identified in patients of the Chinese Han population. In contrast, we know considerably little concerning the genetics in the Kashi COPD population (Uyghur). This study aims at clarifying the genetic maps regarding COPD susceptibility in Kashi (China). Whole-exome sequencing (WES) was used to analyze three Uyghur families with COPD in Kashi (eight patients and one healthy control). Sanger sequencing was also used to verify the WES results in 541 unrelated Uyghur COPD patients and 534 Uyghur healthy controls. WES showed 72 single nucleotide variants (SNVs), two deletions, and small insertions (InDels), 26 copy number variants (CNVs), and 34 structural variants (SVs), including g.71230620T > A (rs12449210T > A, NC_000,016.10) in the HYDIN axonemal central pair apparatus protein (HYDIN) gene and g.61190482A > G (rs777591A > G, NC_000002.12) in the ubiquitin-specific protease 34 (USP34) gene. After Sanger sequencing, we found that rs777591“AA” under different genetic models except for the dominant model (adjusted OR = 0.8559, 95%CI 0.6568–1.115, p > .05), could significantly reduce COPD risk, but rs12449210T > A was not related to COPD. In stratified analysis of smoking status, rs777591“AA” reduced COPD risk significantly among the nonsmoker group. Protein and mRNA expression of USP34 in cigarette smoke extract-treated BEAS-2b cells increased significantly compared with those in the control group. Our findings associate the USP34 rs777591“AA” genotype as a protector factor in COPD.
CaFe-Based Layered Double Oxides With Superior Iron Alloy Corrosion Inhibition Behaviors in Aggressive Seawater Environment
Authors: Park Ji Young , Yoo Su Been , Cho Hong-Baek , Lee Han-Seung , Choa Yong-Ho
Published: February 2022

Reinforced concrete is among the most multifaceted materials used in the construction field. Maintaining the resistance of reinforced concrete to weathering, abrasion, and chemical attack, particularly in aggressive natural conditions such as seawater environments, is challenging. The main factor in the degradation of reinforced-concrete durability is chloride penetration, which accelerates iron alloy corrosion and facilitates structural degradation. In this study, calcium-iron-based layered double hydroxides (CaFe-LDHs) were fabricated at room temperature, followed by structural modulation, and their effectiveness in mitigating iron alloy corrosion due to chloride ions (in 3.5 wt% of NaCl) was investigated. The synthesized CaFe-LDHs with phase transfer notably improved the Cl− removal capacity (Qmax) to 881.83 mg/g, which is more than three times that reported based on previous studies. The novelty of this research lies in the sophisticated structural and phase transformations of the as-synthesized CaFe-LDHs, determination of crucial factors for chloride ion removal, and suggestion of calcium-iron-based layered double oxide (CaFe-LDO)-based chloride ion removal mechanisms considering chemical and ion-exchange reactions. Moreover, when the phase-transformed LDHs, C-700 LDOs, were applied to inhibit iron alloy corrosion, a noticeable inhibition efficiency of 98.87% was obtained, which was an 11-fold improvement compared to the case of iron alloys without LDOs. We believe this work can provide new insights into the design of CaFe-LDOs for the enhancement of the lifespan of reinforced concrete structures.
Assessing Population Genetic Status for Designing Plant Translocations
Authors: Van Rossum Fabienne , Le Pajolec Sarah , Raspé Olivier , Godé Cécile
Published: February 2022

Assisted gene flow interventions such as plant translocations are valuable complementary techniques to habitat restoration. Bringing new genetic variants can contribute to increasing genetic diversity and evolutionary resilience, counteract inbreeding depression and improve plant fitness through heterosis. Large, highly genetically variable populations are usually recommended as sources for translocation. Unfortunately, many critically endangered species only occur as small populations, which are expected to show low genetic variation, high inbreeding level, paucity of compatible mates in self-incompatible species, and increased genetic divergence. Therefore, assessment of population genetic status is required for an appropriate choice of the source populations. In this paper, we exemplify the different analyses relevant for genetic evaluation of populations combining both molecular (plastid and nuclear) markers and fitness-related quantitative traits. We assessed the genetic status of the adult generation and their seed progeny (the potential translocation founders) of small populations of Campanula glomerata (Campanulaceae), a self-incompatible insect-pollinated herbaceous species critically endangered in Belgium. Only a few small populations remain, so that the species has been part of a restoration project of calcareous grasslands implementing plant translocations. In particular, we estimated genetic diversity, inbreeding levels, genetic structure in adults and their seed progeny, recent bottlenecks, clonal extent in adults, contemporary gene flow, effective population size (Ne), and parentage, sibship and seed progeny fitness variation. Small populations of C. glomerata presented high genetic diversity, and extensive contemporary pollen flow within populations, with multiple parentage among seed progenies, and so could be good seed source candidates for translocations. As populations are differentiated from each other, mixing the sources will not only optimize the number of variants and of compatible mates in translocated populations, but also representativeness of species regional genetic diversity. Genetic diversity is no immediate threat to population persistence, but small Ne, restricted among-population gene flow, and evidence of processes leading to genetic erosion, inbreeding and inbreeding depression in the seed progeny require management measures to counteract these trends and stochastic vulnerability. Habitat restoration facilitating recruitment, flowering and pollination, reconnecting populations by biological corridors or stepping stones, and creating new populations through translocations in protected areas are particularly recommended.
Home-Based Long-Term Physical Endurance and Inspiratory Muscle Training for Children and Adults With Fontan Circulation—Initial Results From a Prospective Study
Authors: Dirks Stefan , Kramer Peter , Schleiger Anastasia , Speck Hans-Martin , Wolfarth Bernd , Thouet Thomas , Berger Felix , Sallmon Hannes , Ovroutski Stanislav
Published: February 2022

Background

Patients with congenital heart disease (CHD)—including those after Fontan operation—are encouraged to be physically active.

Aim

To prospectively determine the effects of an individually adapted, home-based cycle ergometer endurance training in combination with inspiratory muscle training (IMT) in pediatric and adult Fontan patients. We, herein, report the results of the initial 10-months follow-up (phase 1).

Methods

18 patients (median age 16.5 years; range 10-43 years) completed baseline check-ups, and 4 and 10 months follow-up visits, which each included cardiopulmonary exercise testing (CPET), bodyplethysmography (including measurement of respiratory muscle strength), and a quality of life questionnaire (PedsQL™). The training program consisted of a home-based cycle ergometer endurance training on a “Magbike® AM-5i/3i” (DKN Technology®, Clermont-Ferrand, France) and IMT with a handheld “POWERbreathe® Medic plus” device. Patients performed 90 min of endurance training per week in addition to IMT (30 breaths per day, 6-7 times per week). After the first 4 months, patients underwent additional interval training.

Results

After 10 months of training, we observed significant increases in maximum relative workload (W/kg, p = 0.003) and in maximum inspiratory (MIP, p = 0.002) and expiratory (MEP, p = 0.008) pressures. Peak VO2 values did not increase significantly as compared to baseline (p = 0.12) in the entire cohort (n = 18), but reached statistical significance in a subgroup analysis of teenage/adult patients (n = 14; p = 0.03). Patients' subjective quality of life did not show any significant changes after 10 months of training.

Discussion

In Fontan patients, an individually adapted home-based training is safe and associated with improvements in some CPET variables. However, these improvements did not translate into an improved QoL after 10 months. With an unclear, but most likely negative, impact of the COVID-19 pandemic, improvements in QoL may become evident during further follow-up (phase 2 of the study).
Association Between Serum Galectin-3 Levels and Coronary Stenosis Severity in Patients With Coronary Artery Disease
Authors: Li Mingxing , Guo Kai , Huang Xuansheng , Feng Li , Yuan Yong , Li Jiewen , Lao Yi , Guo Zhigang
Published: February 2022

Background

The relationship between galectin-3 (Gal-3) and coronary artery disease (CAD) has not been fully elucidated.

Aim

This study aimed to determine the relationship between the presence and severity of CAD and serum Gal-3 levels.

Patients and Methods

Three-hundred thirty-one consecutive CAD patients were enrolled as the study group. An additional 62 patients without CAD were enrolled as the control group. Serum Gal-3 levels were separately compared between the non-CAD and CAD groups, among the stable CAD and Acute coronary syndrome (ACS) groups, and between CAD patients with low and high SYNTAX scores (SSs). The 1-year cumulative rate of major adverse cardiac events (MACEs) was also compared among ACS patients by Gal-3 levels.

Results

Serum Gal-3 was significantly higher in the CAD group than in the non-CAD group 3.89 (0.16–63.67) vs. 2.07 (0.23–9.38) ng/ml, P < 0.001. Furthermore, serum Gal-3 was significantly higher in the non-ST-segment elevation ACS (NSTE-ACS) group than that in the stable CAD group, 4.72 (1.0–16.14) vs. 2.23 (0.65–23.8) ng/ml, P = 0.04 and higher in the ST-segment elevation myocardial infarction (STEMI) group than that in the stable CAD group 7.87 (0.59–63.67) vs. 2.23 (0.65–23.8) ng/ml, P < 0.001. Serum Gal-3 level was an independent predictor of ACS compared with stable CAD group (OR = 1.131, 95% CI: 1.051–1.217, P = 0.001) as well as high SS (OR = 1.030, 95% CI: 1.021–1.047, P = 0.038) after adjust other confounding risk factors. Acute coronary syndrome patients with Gal-3 levels above the median (gal-3 = 4.78 ng/ml) showed a higher cumulative MACE rate than those with Gal-3 levels below the median. After adjusting other confounding risk factors, Gal-3 remained an independent risk factor for the cumulative rate of MACEs in ACS patients (6% higher rate of MACEs incidence per 1 ng/ml increment of Gal-3).

Conclusion

Galectin-3 correlated with the presence of CAD as well as coronary stability and complexity. Galectin-3 may be valuable in predicting mid-term prognosis in ACS patients.
Dynamics of Loneliness Among Older Adults During the COVID-19 Pandemic: Pilot Study of Ecological Momentary Assessment With Network Analysis
Authors: Badal Varsha D. , Lee Ellen E. , Daly Rebecca , Parrish Emma M. , Kim Ho-Cheol , Jeste Dilip V. , Depp Colin A.
Published: February 2022

Objective

The COVID-19 pandemic has had potentially severe psychological implications for older adults, including those in retirement communities, due to restricted social interactions, but the day-to-day experience of loneliness has received limited study. We sought to investigate sequential association, if any, between loneliness, activity, and affect.

Methods

We used ecological momentary assessment (EMA) with dynamic network analysis to investigate the affective and behavioral concomitants of loneliness in 22 residents of an independent living sector of a continuing care retirement community (mean age 80.2; range 68–93 years).

Results

Participants completed mean 83.9% of EMA surveys (SD = 16.1%). EMA ratings of loneliness were moderately correlated with UCLA loneliness scale scores. Network models showed that loneliness was contemporaneously associated with negative affect (worried, anxious, restless, irritable). Negative (but not happy or positive) mood tended to be followed by loneliness and then by exercise or outdoor physical activity. Negative affect had significant and high inertia (stability).

Conclusions

The data suggest that EMA is feasible and acceptable to older adults. EMA-assessed loneliness was moderately associated with scale-assessed loneliness. Network models in these independent living older adults indicated strong links between negative affect and loneliness, but feelings of loneliness were followed by outdoor activity, suggesting adaptive behavior among relatively healthy adults.
Experimental Study on Fracturing Characteristics of Double-Hole Blasting Under Static Stresses
Authors: Chen Hui , Qiu Xianyang , Shi Xiuzhi , Zhang Junhui , Huo Xiaofeng , Li Dongping
Published: February 2022

This study aims to investigate the fracturing characteristics of double-hole blasting under the action of coupled static stress and delayed time explosion. A total of thirteen explosive tests were carried out on rectangular concrete blocks with different constraints. The test blocks were wrapped in steel mesh in the test bed to prevent flying away of the cracked blocks after blasting. After blasting, the surface area of the crater was measured, and all pieces of the cracked blocks were collected, screened, and analyzed. The experimental results show that (1) the shape of free-surface craters was affected by static stress. The surface area and overall volume of the craters increased in the direction of loading stress. (2) The crater under simultaneous initiation was larger than that under delayed initiation when the tested block had a single free surface. (3) The fragmentation of blasting is closely related to the static confining pressure and delay initiation applied on the tested specimens. It is believed that this research will contribute to the design of multi-hole blasting in the deep geological body in the respect of the theoretical analysis.
EZH2 Mediates Proliferation, Migration, and Invasion Promoted by Estradiol in Human Glioblastoma Cells
Authors: Del Moral-Morales Aylin , González-Orozco Juan Carlos , Hernández-Vega Ana María , Hernández-Ortega Karina , Peña-Gutiérrez Karla Mariana , Camacho-Arroyo Ignacio
Published: February 2022

Glioblastomas (GBM) are the most frequent and aggressive brain tumors. 17β-estradiol (E2) increases proliferation, migration, and invasion of human GBM cells; however underlying mechanisms are no fully understood. Zeste 2 Enhancer Homologous enzyme (EZH2) is a methyltransferase part of Polycomb 2 repressor complex (PRC2). In GBM, EZH2 is overexpressed and involved in the cell cycle, migration, and invasion processes. We studied the role of EZH2 in the pro-oncogenic actions of E2 in human GBM cells. EZH2 gene silencing and pharmacological inhibition of EZH2 blocked proliferation, migration, and invasion of GBM cells induced by E2. We identified in silico additional putative estrogen response elements (EREs) at the EZH2 promoter, but E2 did not modify EZH2 expression. In silico analysis also revealed that among human GBM samples, EZH2 expression was homogeneous; in contrast, the heterogeneous expression of estrogen receptors (ERs) allowed the classification of the samples into groups. Even in the GBM cluster with high expression of ERs and those of their target genes, the expression of PCR2 target genes did not change. Overall, our data suggest that in GBM cells, pro-oncogenic actions of E2 are mediated by EZH2, without changes in EZH2 expression and by mechanisms that appear to be unrelated to the transcriptional activity of ERs.
Animal Foetal Models of Obesity and Diabetes – From Laboratory to Clinical Settings
Authors: Grzęda Emilia , Matuszewska Julia , Ziarniak Kamil , Gertig-Kolasa Anna , Krzyśko- Pieczka Izabela , Skowrońska Bogda , Sliwowska Joanna H.
Published: February 2022

The prenatal period, during which a fully formed newborn capable of surviving outside its mother’s body is built from a single cell, is critical for human development. It is also the time when the foetus is particularly vulnerable to environmental factors, which may modulate the course of its development. Both epidemiological and animal studies have shown that foetal programming of physiological systems may alter the growth and function of organs and lead to pathology in adulthood. Nutrition is a particularly important environmental factor for the pregnant mother as it affects the condition of offspring. Numerous studies have shown that an unbalanced maternal metabolic status (under- or overnutrition) may cause long-lasting physiological and behavioural alterations, resulting in metabolic disorders, such as obesity and type 2 diabetes (T2DM). Various diets are used in laboratory settings in order to induce maternal obesity and metabolic disorders, and to alter the offspring development. The most popular models are: high-fat, high-sugar, high-fat-high-sugar, and cafeteria diets. Maternal undernutrition models are also used, which results in metabolic problems in offspring. Similarly to animal data, human studies have shown the influence of mothers’ diets on the development of children. There is a strong link between the maternal diet and the birth weight, metabolic state, changes in the cardiovascular and central nervous system of the offspring. The mechanisms linking impaired foetal development and adult diseases remain under discussion. Epigenetic mechanisms are believed to play a major role in prenatal programming. Additionally, sexually dimorphic effects on offspring are observed. Therefore, further research on both sexes is necessary.
Dimensionality Reduction and Louvain Agglomerative Hierarchical Clustering for Cluster-Specified Frequent Biomarker Discovery in Single-Cell Sequencing Data
Authors: Seth Soumita , Mallik Saurav , Bhadra Tapas , Zhao Zhongming
Published: February 2022

The major interest domains of single-cell RNA sequential analysis are identification of existing and novel types of cells, depiction of cells, cell fate prediction, classification of several types of tumor, and investigation of heterogeneity in different cells. Single-cell clustering plays an important role to solve the aforementioned questions of interest. Cluster identification in high dimensional single-cell sequencing data faces some challenges due to its nature. Dimensionality reduction models can solve the problem. Here, we introduce a potential cluster specified frequent biomarkers discovery framework using dimensionality reduction and hierarchical agglomerative clustering Louvain for single-cell RNA sequencing data analysis. First, we pre-filtered the features with fewer number of cells and the cells with fewer number of features. Then we created a Seurat object to store data and analysis together and used quality control metrics to discard low quality or dying cells. Afterwards we applied global-scaling normalization method “LogNormalize” for data normalization. Next, we computed cell-to-cell highly variable features from our dataset. Then, we applied a linear transformation and linear dimensionality reduction technique, Principal Component Analysis (PCA) to project high dimensional data to an optimal low-dimensional space. After identifying fifty “significant”principal components (PCs) based on strong enrichment of low p-value features, we implemented a graph-based clustering algorithm Louvain for the cell clustering of 10 top significant PCs. We applied our model to a single-cell RNA sequential dataset for a rare intestinal cell type in mice (NCBI accession ID:GSE62270, 23,630 features and 1872 samples (cells)). We obtained 10 cell clusters with a maximum modularity of 0.885 1. After detecting the cell clusters, we found 3871 cluster-specific biomarkers using an expression feature extraction statistical tool for single-cell sequencing data, Model-based Analysis of Single-cell Transcriptomics (MAST) with a   log 2FC threshold of 0.25 and a minimum feature detection of 25%. From these cluster-specific biomarkers, we found 1892 most frequent markers, i.e., overlapping biomarkers. We performed degree hub gene network analysis using Cytoscape and reported the five highest degree genes (Rps4x, Rps18, Rpl13a, Rps12 and Rpl18a). Subsequently, we performed KEGG pathway and Gene Ontology enrichment analysis of cluster markers using David 6.8 software tool. In summary, our proposed framework that integrated dimensionality reduction and agglomerative hierarchical clustering provides a robust approach to efficiently discover cluster-specific frequent biomarkers, i.e., overlapping biomarkers from single-cell RNA sequencing data.
Impaired Self-Referential Cognitive Processing in Bipolar Disorder: A Functional Connectivity Analysis
Authors: Zhang Jian , Liu Tiantian , Shi Zhongyan , Tan Shuping , Suo Dingjie , Dai Chunyang , Wang Li , Wu Jinglong , Funahashi Shintaro , Liu Miaomiao
Published: February 2022

Patients with bipolar disorder have deficits in self-referenced information. The brain functional connectivity during social cognitive processing in bipolar disorder is unclear. Electroencephalogram (EEG) was recorded in 23 patients with bipolar disorder and 19 healthy comparison subjects. We analyzed the time-frequency distribution of EEG power for each electrode associated with self, other, and font reflection conditions and used the phase lag index to characterize the functional connectivity between electrode pairs for 4 frequency bands. Then, the network properties were assessed by graph theoretic analysis. The results showed that bipolar disorder induced a weaker response power and phase lag index values over the whole brain in both self and other reflection conditions. Moreover, the characteristic path length was increased in patients during self-reflection processing, whereas the global efficiency and the node degree were decreased. In addition, when discriminating patients from normal controls, we found that the classification accuracy was high. These results suggest that patients have impeded integration of attention, memory, and other resources of the whole brain, resulting in a deficit of efficiency and ability in self-referential processing.
Self-Reported Sleep Quality Across Age Modulates Resting-State Functional Connectivity in Limbic and Fronto-Temporo-Parietal Networks: An Exploratory Cross-Sectional fMRI Study
Authors: Federico Giovanni , Alfano Vincenzo , Garramone Federica , Mele Giulia , Salvatore Marco , Aiello Marco , Cavaliere Carlo
Published: February 2022

Sleep problems are increasingly present in the general population at any age, and they are frequently concurrent with—or predictive of—memory disturbances, anxiety, and depression. In this exploratory cross-sectional study, 54 healthy participants recruited in Naples (Italy; 23 females; mean age = 37.1 years, range = 20–68) completed the Pittsburgh Sleep Quality Index (PSQI) and a neurocognitive assessment concerning both verbal and visuospatial working memory as well as subjective measures of anxiety and depression. Then, 3T fMRI images with structural and resting-state functional sequences were acquired. A whole-brain seed-to-seed functional connectivity (FC) analysis was conducted by contrasting good (PSQI score <5) vs. bad (PSQI score ≥5) sleepers. Results highlighted FC differences in limbic and fronto-temporo-parietal brain areas. Also, bad sleepers showed an anxious/depressive behavioural phenotype and performed worse than good sleepers at visuospatial working-memory tasks. These findings may help to reveal the effects of sleep quality on daily-life cognitive functioning and further elucidate pathophysiological mechanisms of sleep disorders.
Transcranial Direct Current Stimulation on Different Targets to Modulate Cortical Activity and Dual-Task Walking in Individuals With Parkinson’s Disease: A Double Blinded Randomized Controlled Trial
Authors: Wong Pei-Ling , Yang Yea-Ru , Huang Shih-Fong , Fuh Jong-Ling , Chiang Han-Lin , Wang Ray-Yau
Published: February 2022

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation to modulate cortical activity for improving motor function. However, the information of tDCS stimulation on different brain regions for dual-task walking and cortical modulation in Parkinson’s disease (PD) has not yet been compared.

Objective

The objective of this study was to investigate the effects of different tDCS targets on dual-task gait performance and cortical activity in patients with PD.

Methods

A total of 36 participants were randomly assigned to primary motor cortex (M1) tDCS, dorsal lateral prefrontal cortex (DLPFC) tDCS, cerebellum tDCS, or Sham tDCS group. Each group received 20 min of tDCS stimulation, except for the Sham group. Gait performance was measured by the GAITRite system during dual-task walking and single walking. Corticomotor activity of the tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). The functional mobility was assessed using the timed up and go (TUG) test.

Results

All participants showed no significant differences in baseline data. Following the one session of tDCS intervention, M1 (p = 0.048), DLPFC (p < 0.001), and cerebellum (p = 0.001) tDCS groups demonstrated significant improvements in dual-task gait speed compared with a pretest. The time × group interaction [F(3, 32) = 5.125, p = 0.005] was detected in dual-task walking speed. The post hoc Tukey’s test showed that the differences in gait speed were between the Sham tDCS group and the DLPFC tDCS group (p = 0.03). Moreover, DLPFC tDCS also increased the silent period (SP) more than M1 tDCS (p = 0.006) and Sham tDCS (p = 0.002).

Conclusion

The results indicate that DLPFC tDCS exerted the most beneficial effects on dual-task walking and cortical modulation in participants with PD.

Clinical trial registration

[http://www.thaiclinicaltrials.org/show/TCTR20200909005], Thai Clinical Trials Registry [TCTR20200909005].
Knowledge, Attitudes, Behavioural Practises, and Psychological Impact Relating to COVID-19 Among People Living With Spinal Cord Injury During In-Patient Rehabilitation in Bangladesh
Authors: Hossain Mohammad Anwar , Hossain K. M. Amran , Sakel Mohamed , Kabir Md. Feroz , Saunders Karen , Faruqui Rafey , Hossain Mohammad Sohrab , Uddin Zakir , Kader Manzur , Walton Lori Maria , Haque Md. Obaidul , Shafin Rubayet , Chakrovorty Sonjit Kumar , Jahid Iqbal Kabir
Published: February 2022

Aim

The aim of this research is to focus on gaining an insight into the knowledge, attitudes, behavioural practises (KAP), and psychological impact relating to COVID-19 among the people living with spinal cord injury receiving in-patient rehabilitation.

Methods

A prospective, cross-sectional survey of people with SCI (N = 207), who were in active in-patient rehabilitation from two tertiary SCI Rehabilitation Centres in Bangladesh. Data were collected via face-to-face interviews, after voluntary consent, using a pretested, language validated questionnaire on Knowledge, Attitude and Behavioural practises (KAP) and the Depression, Anxiety, Stress Scale (DASS-21). Ethical approval and trial registration were obtained prospectively.

Results

A total of 207 people with SCI responded, among which 87% were men and 13% were women, with a mean age of 34.18 ± 12.9 years. Within the sample group, people living with tetraplegia comprised 33.8%, and people living with paraplegia comprised 66.2%. Overall, 63.8% of the participants were diagnosed with an SCI categorised as ASIA-A. Overall, the “knowledge score” was 8.59 ± 2.3 out of 12, “depression” was 11.18 ± 8, “anxiety” was 7.72 ± 5.1, and “stress” was 9.32 ± 6.7 from a total of 21 scores each category. The strong correlation was between knowledge, DASS scores, and age (p < 0.05). In addition, there was a strong correlation between knowledge, gender (p < 0.05) and education (p < 0.01). Binary logistic regression found a stronger association of knowledge and DASS scores with gender, young age, illiteracy (p < 0.01), and rural residence (p < 0.05). A positive relationship was found between depression and anxiety scores (p < 0.01) and a moderate positive relationship was found between depression and stress scores (p < 0.01). A positive attitude was reported by the majority of participants (p < 0.05). In terms of behavioural practises, participants reported both self and caregiver had followed health advice with regard to consulting health professionals (65.7%), implementing isolation (63.8%), taking droplet precaution care (87.4%), and hygiene care (90.3%).

Conclusion

Participants in this study reported high levels of knowledge, adoption of positive attitudes, and the practise of positive health advisory behaviours related to COVID-19 prevention procedures. However, high levels of depression, anxiety, and stress were also reported. Overall, women and younger participants were more likely to have high KAP, whereas those living in rural areas and with literacy challenges were less likely to report high knowledge scores.
Theoretical and Therapeutic Implications of the Spasticity-Plus Syndrome Model in Multiple Sclerosis
Authors: Bruno Antonio , Dolcetti Ettore , Centonze Diego
Published: February 2022

In patients with multiple sclerosis (MS), a typical pattern of muscle tone alteration, known as spasticity, is frequently observed in combination with other signs or symptoms such as spasms, cramps, pain, bladder dysfunction, sleep disturbances, fatigue, and tremor. Recently, the concept of spasticity-plus syndrome (SPS) has been proposed to take into account the frequent coexistence of all these complaints in patients with MS and a common pathophysiological basis for this putative new clinical entity has been proposed. Muscle tone, sleep, bladder function, and the pain pathway are controlled by cannabinoid CB1 (CB1R) and CB2 receptors (CB2R) that are particularly enriched in the brainstem. Axons with smaller diameters are particularly susceptible to conduction block and the irritative, ephaptic, consequences of demyelination and their involvement in the demyelination process caused by MS in the brainstem might underlie the various clinical manifestations of SPS. The adoption of SPS in clinical practice could be useful to improve symptomatic treatments in a significant proportion of patients with MS, possibly limiting the adverse events produced by polypharmacotherapy.
Case Report: A Patient Diagnosed With Miller Fisher Syndrome and Myasthenia Gravis at the Same Time
Authors: Chen Nan , Cai Hanyu , Cheng Jianhua
Published: February 2022

In this case report, we describe a patient who was first diagnosed with Miller Fisher syndrome (MFS) combined with myasthenia gravis (MG). A 58-year-old male patient presented with acute dysarthria with dizziness, ophthalmoplegia, absence of deep tendon reflexes in the extremities, and ataxia. Lumbar puncture 1 week after onset showed albuminocytologic dissociation and serum antibodies against GQ1b and GT1a turned out to be positive. Ultimately, the patient was diagnosed with MFS, which is a rare variant of Guillain-Barre syndrome. Because the clinical manifestations of the patient could not exclude MG, electromyography, and serum muscle weakness antibody profile were performed. The results showed positive for axillary nerve repetitive electrical stimulation and antibodies against acetylcholine receptor (AChR) and titin were detected, so the patient was diagnosed with MG at the same time. Even though only five cases of overlapping MFS and MG so far have been described, two different autoimmune diseases may coexist. When one disease presents with uncommon symptoms, careful identification of the presence or absence of other comorbid diseases should be required.
Autoimmune Encephalitis in the Philippines: A Scoping Review on the Treatment Gaps, Challenges, and Current State of Care
Authors: Pagaling Gerald T. , Turalde Christian Wilson R. , Jamora Roland Dominic G.
Published: February 2022

Objectives

We reviewed the current health service delivery for individuals with Autoimmune Encephalitis (AE) in the Philippines and to identify the gaps and challenges in its management.

Methodology

We conducted a scoping review of pertinent literature AE in the Philippines using the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines. We extracted data on epidemiology, legislation, health financing, information systems, pharmacotherapy, and healthcare services related to the management of AE in the local setting.

Discussion

The epidemiology of AE is still unknown. Out-of-pocket expenses contribute to most of the healthcare expenditure despite government-led programs to reduce the financial burden. The access to diagnostic examinations such as magnetic resonance imaging, electroencephalogram, and antibody testing is limited by the geographic distribution of the facilities and costs. The acute and long-term management of AE are cost-prohibitive and are not readily available. There are significant treatment gaps in the care of individuals with AE in the Philippines in terms of disease recognition, resource allocation, access to satisfactory diagnostic evaluation, and provision of prognosis-changing therapeutics. We proposed core strategies that can address these treatment gaps such as increasing awareness, improving access to health resources, adequate healthcare financing, and availability of support systems.
Limited Ability to Adjust N2 Amplitude During Dual Task Walking in People With Drug-Resistant Juvenile Myoclonic Epilepsy
Authors: Yam Mor , Glatt Sigal , Nosatzki Shai , Mirelman Anat , Hausdorff Jeffrey M. , Goldstein Lilach , Giladi Nir , Fahoum Firas , Maidan Inbal
Published: February 2022

Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndromes; it is estimated to affect 1 in 1,000 people worldwide. Most people with JME respond well to medication, but up to 30% of them are drug-resistant. To date, there are no biomarkers for drug resistance in JME, and the poor response to medications is identified in retrospect. People with JME have frontal dysfunction manifested as impaired attention and difficulties in inhibiting habitual responses and these dysfunctions are more pronounced in drug-resistant individuals. Frontal networks play an important role in walking and therefore, gait can be used to overload the neural system and expose subtle changes between people with drug-responsive and drug-resistant JME. Electroencephalogram (EEG) is a promising tool to explore neural changes during real-time functions that combine a cognitive task while walking (dual tasking, DT). This exploratory study aimed to examine the alteration in electrical brain activity during DT in people with drug-responsive and drug-resistant JME. A total of 32 subjects (14 males and 18 females) participated: 11 drug-responsive (ages: 31.50 ± 1.50) and 8 drug-resistant (27.27 ± 2.30) people with JME, and 13 healthy controls (29.46 ± 0.69). The participants underwent EEG examination during the performance of the visual Go/NoGo (vGNG) task while sitting and while walking on a treadmill. We measured latencies and amplitudes of N2 and P3 event-related potentials, and the cognitive performance was assessed by accuracy rate and response time of Go/NoGo events. The results demonstrated that healthy controls had earlier N2 and P3 latencies than both JME groups (N2: p = 0.034 and P3: p = 0.011), however, a limited ability to adjust the N2 amplitude during walking was noticeable in the drug-resistant compared to drug-responsive. The two JME groups had lower success rates (drug-responsive p < 0.001, drug-resistant p = 0.004) than healthy controls, but the drug-resistant showed longer reaction times compared to both healthy controls (p = 0.033) and drug-responsive (p = 0.013). This study provides the first evidence that people with drug-resistant JME have changes in brain activity during highly demanding tasks that combine cognitive and motor functions compared to people with drug-responsive JME. Further research is needed to determine whether these alterations can be used as biomarkers to drug response in JME.
A Functional Near-Infrared Spectroscopy Examination of the Neural Correlates of Mental Rotation for Individuals With Different Depressive Tendencies
Authors: Wang Liusheng , Ke Jingqi , Zhang Haiyan
Published: February 2022

The present study aimed to examine the neural mechanisms underlying the ability to process the mental rotation with mirrored stimuli for different depressive tendencies with psychomotor retardation. Using functional near-infrared spectroscopy (fNIRS), we measured brain cortex activation of participants with higher and lower depressive tendencies while performing a left-right paradigm of object mental rotation or a same-different paradigm of subject mental rotation. Behavioral data revealed no differences in reaction time and rotation speed. The fNIRS data revealed a higher deactivation of oxyhemoglobin (HbO) change for the higher depression group in the perceptual stage of object mental rotation with mirrored stimuli in the superior external frontal cortex (BA46), inferior frontal gyrus (BA45), premotor cortex (BA6), and primary motor cortex (BA4) (study 1). In addition, there existed a significant difference between the two groups in premotor cortex (BA6) in subject mental rotation with mirrored stimuli (study 2). These results suggest that the neural mechanism of higher depression individuals connected with psychomotor retardation exists in the frontal and motor areas when processing object mental rotation with mirrored stimuli, and the motor cortex when processing subject mental rotation.
Not Only in Sensorimotor Network: Local and Distant Cerebral Inherent Activity of Chronic Ankle Instability—A Resting-State fMRI Study
Authors: Shen Yiyuan , Wang Weiwei , Wang Yin , Yang Liqin , Yuan Chengjie , Yang Yang , Wu Fei , Wang Junlong , Deng Yan , Wang Xu , Liu Hanqiu
Published: February 2022

Background

Increasing evidence has proved that chronic ankle instability (CAI) is highly related to the central nervous system (CNS). However, it is still unclear about the inherent cerebral activity among the CAI patients.

Purpose

To investigate the differences of intrinsic functional cerebral activity between the CAI patients and healthy controls (HCs) and further explore its correlation with clinical measurement in CAI patients.

Materials and Methods

A total of 25 CAI patients and 39 HCs were enrolled in this study. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to detect spontaneous cerebral activity. The metrics of amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of the two groups were compared by two-sample t-test. The brain regions that demonstrated altered functional metrics were selected as the regions of interest (ROIs). The functional connectivity (FC) was analyzed based on the ROIs. The Spearman correlation was calculated between rs-fMRI metrics and clinical scale scores.

Results

Compared with HCs, CAI patients showed higher ALFF and ReHo values in the right postcentral gyrus, the right precentral gyrus, and the right middle frontal gyrus, while lower fALFF values in the orbital-frontal cortex (OFC, p < 0.01 after correction). Increasing FC between the right precentral gyrus and the right postcentral gyrus while decreasing FC between the right precentral gyrus and the anterior cingulum cortex (ACC), the right middle frontal gyrus and the left middle temporal gyrus, and the OFC and left inferior parietal lobule (IPL) was observed. In addition, in the CAI group, the ReHo value negatively correlated with the Cumberland Ankle Instability Tool score in the right middle frontal gyrus (r = −0.52, p = 0.007).

Conclusion

The CAI patients exhibited enhanced and more coherent regional inherent neuronal activity within the sensorimotor network while lower regional inherent activity in pain/emotion modulation related region. In addition, the information exchanges were stronger within the sensorimotor network while weaker between distant interhemispheric regions. Besides, the increased inherent activity in the right middle frontal gyrus was related to clinical severity. These findings may provide insights into the pathophysiological alteration in CNS among CAI patients.
Association Between Red and Processed Meat Consumption and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Nouri-Majd Saeedeh , Salari-Moghaddam Asma , Aminianfar Azadeh , Larijani Bagher , Esmaillzadeh Ahmad
Published: February 2022

Background

Debate on the potential carcinogenic effects of meat intake is open and the relationship between meat consumption and risk of prostate cancer remains uncertain. This meta-analysis was conducted to summarize earlier prospective studies on the association of meat consumption with risk of prostate cancer.

Methods

Relevant studies were identified by exploring PubMed/Medline, Scopus, Web of Science, EMBASE, and Google Scholar databases up to December 2020. Fixed-effects and random-effects meta-analyses were used for pooling the relative risks (RRs). Heterogeneity across studies was evaluated using the Q-statistic and I-square (I2). A funnel plot and Egger's test was used to detect publication bias. Linear and non-linear dose-response analyses were performed to estimate the dose-response relations between meat intake and risk of prostate cancer.

Results

Twenty-five prospective studies were included in this meta-analysis. Totally, 1,900,910 participants with 35,326 incident cases of prostate cancer were investigated. Pooling the eligible effect sizes, we observed that high consumption of processed meat might be associated with an increased risk of “total prostate cancer” (RR: 1.06; 95% CI: 1.01, 1.10; I2 = 1.5%, P = 0.43) and “advanced prostate cancer” (1.17; 1.09, 1.26; I2 = 58.8%, P = 0.01). However, the association between processed meat and “advanced prostate cancer” was not significant in the random-effects model: 1.12 (95% CI: 0.98, 1.29). A linear dose-response analysis indicated that an increment of 50 grams per day of processed meat intake might be related to a 4% greater risk of “total prostate cancer” (1.04; 1.00, 1.08; I2 = 0.0%, P = 0.51). “Total meat intake” was marginally associated with all outcomes of prostate cancer risk (1.04; 1.01, 1.07; I2 = 58.4%, P < 0.001).

Conclusions

This systematic review and meta-analysis of prospective studies indicated that increased consumption of “total meat” and “processed meat” might be associated with a higher risk of prostate cancer.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230824, identifier: CRD42021230824.
SRSF3 Promotes Angiogenesis in Colorectal Cancer by Splicing SRF
Authors: Chen Yinshuang , Yang Man , Meng Fanyi , Zhang Yawen , Wang Mengmeng , Guo Xuqin , Yang Jie , Zhang Hongjian , Zhang Haiyang , Sun Jing , Wang Weipeng
Published: February 2022

SRSF3, an important member of the serine/arginine-rich protein (SRp) family, is highly expressed in various tumors and plays an important role in tumor cell proliferation, migration and invasion. However, it is still unclear whether SRSF3 is involved in tumor angiogenesis. In this study, we first revealed that SRSF3 regulated the expression of numerous genes related to angiogenesis, including proangiogenic SRF. Then, we confirmed that SRSF3 was highly expressed in colorectal cancer (CRC) and was positively correlated with SRF. Mechanistic studies revealed that SRSF3 directly bound to the “CAUC” motif in exon 6 of SRF and induced the exclusion of introns. Knockdown of SRSF3 significantly reduced the secretion of VEGF from CRC cells. Conditioned medium from SRSF3-knockdown CRC cells significantly inhibited the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, SRF silencing inhibited angiogenesis, while SRF overexpression reversed the antiangiogenic effects of SRSF3 knockdown on tube formation. These findings indicate that SRSF3 is involved in the splicing of SRF and thereby regulates the angiogenesis of CRC, which offers novel insight into antiangiogenic therapy in CRC.
Clinical Response to Venetoclax and Decitabine in Acute Promyelocytic Leukemia With a Novel RARA-THRAP3 Fusion: A Case Report
Authors: Song Baoquan , Wang Xin , Kong Xin , Wang Man , Yao Li , Shen Hongjie , Zhang Jian , Qiu Huiying
Published: February 2022

Variant acute promyelocytic leukemia (APL) showed quite different aspects, and the current treatments remained challenged at present. Venetoclax, a selective inhibitor of B-cell lymphoma 2 (BCL-2), is a small molecule that has been studied in several hematologic malignancies as both monotherapy and in combination with other agents. However, there is little of its use in the treatment of APL or variant APL. In this report, we identified THRAP3 as novel RARA fusion in resembling APL, which was resistant to all-trans retinoic acid (ATRA) combined arsenic trioxide (ATO) chemotherapy. Then, the patient was salvaged by low-dose venetoclax and decitabine. The treatment in this case demonstrates the potential ability of venetoclax in variant APL, thus providing a new treatment option for all kinds of APL.