Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic criteria for idiopathic small fiber neuropathy: A systematic review

Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was performed to assess the published screening and diagnostic criteria for iSFN, excluding studies where SFN was of well‐established etiology. Eighty‐four clinical studies and seven guideline/review publications were included in this systematic review. Substantial heterogeneity existed in iSFN diagnostic criteria. The most common set of criteria to diagnose iSFN [presence of any symptoms of iSFN, absence of large fiber involvement, and reduced intraepidermal nerve fiber density (IENFD)] was used in only 14% of studies. Mandatory individual criteria to confirm iSFN included any sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced IENFD (38% of studies), and autonomic symptoms (1% of studies). This review highlights a clear need for standardized, evidence‐based guidelines for diagnosing iSFN.
Dependence of the Optical Constant Parameters of p-Toluene Sulfonic Acid-Doped Polyaniline and Its Composites on Dispersion Solvents

The optical constants of Para-Toluene sulfonic acid-doped polyaniline (PANI), PANIchitosan composites, PANI-reduced graphene-oxide composites and a ternary composite comprising of PANI, chitosan and reduced graphene-oxide dispersed in diluted p-toluene sulfonic acid (PTSA) solution and N-Methyl-2-Pyrrolidone (NMP) solvent have been evaluated and compared. The optical constant values were extracted from the absorbance spectra of thin layers of the respective samples. The potential utilization of the materials as the active sensing materials of surface plasmon resonance biosensors has also been assessed in terms of the estimated value of the penetration depth through a dielectric medium. The results show a reasonable dependence of the optical constant parameters on the solvent type. Higher real part refractive index (n) and real part complex dielectric permittivity (ε’) values were observed for the samples prepared using PTSA solution, while higher optical conductivity values were observed for the NMP-based samples due to their relatively higher imaginary part refractive index (k) and imaginary part complex dielectric permittivity (ε″) values. In addition, NMP-based samples show improvement in terms of the penetration depth through a dielectric medium by around 9.5, 1.6, 4.4 and 2.9 times compared to PTSA-based samples for the PANI, PANI-chitosan, PANI-RGO and the ternary composites, respectively. Based on these, it is concluded that preparation of these materials using different dispersion solvents could produce materials of different optical properties. Thus, the variation of the dispersion solvent will allow the flexible utilization of the PANI and the composites for diverse applications.
Effects of Standardized Green Tea Extract and Its Main Component, EGCG, on Mitochondrial Function and Contractile Performance of Healthy Rat Cardiomyocytes

We recently showed that the long-term in vivo administration of green tea catechin extract (GTE) resulted in hyperdynamic cardiomyocyte contractility. The present study investigates the mechanisms underlying GTE action in comparison to its major component, epigallocatechin-3-gallate (EGCG), given at the equivalent amount that would be in the entirety of GTE. Twenty-six male Wistar rats were given 40 mL/day of a tap water solution with either standardized GTE or pure EGCG for 4 weeks. Cardiomyocytes were then isolated for the study. Cellular bioenergetics was found to be significantly improved in both GTE- and EGCG-fed rats compared to that in controls as shown by measuring the maximal mitochondrial respiration rate and the cellular ATP level. Notably, the improvement of mitochondrial function was associated with increased levels of oxidative phosphorylation complexes, whereas the cellular mitochondrial mass was unchanged. However, only the GTE supplement improved cardiomyocyte mechanics and intracellular calcium dynamics, by lowering the expression of total phospholamban (PLB), which led to an increase of both the phosphorylated-PLB/PLB and the sarco-endoplasmic reticulum calcium ATPase/PLB ratios. Our findings suggest that GTE might be a valuable adjuvant tool for counteracting the occurrence and/or the progression of cardiomyopathies in which mitochondrial dysfunction and alteration of intracellular calcium dynamics constitute early pathogenic factors.
Fullerene Formation via Pyrolysis of Ragged Single-wall Carbon Nanotubes

A new path of fullerene formation via pyrolysis of ragged single-wall carbon nanotubes (r-SWNTs) which were treated by ultrasonication with an organic solvent followed by heating in oxygen gas is reported. Mass spectrum and high-performance liquid chromatography results indicated that C60, C70, and higher fullerenes existed in products obtained through the pyrolysis of the r-SWNTs at above 800 °C in vacuum. We suggest that the pyrolysis of r-SWNTs originates from holes and defects in the r-SWNTs.
Unmet care needs of older people: A scoping review

The aim was to synthesize the findings of empirical research about the unmet nursing care needs of older people, mainly from their point of view, from all settings, focusing on (1) methodological approaches, (2) relevant concepts and terminology and (3) type, nature and ethical issues raised in the investigations. A scoping review after Arksey and O’Malley. Two electronic databases, MEDLINE/PubMed and CINAHL (from earliest to December 2019) were used. Systematic search protocol was developed using several terms for unmet care needs and missed care. Using a three-step retrieval process, peer-reviewed, empirical studies concerning the unmet care needs of older people in care settings, published in English were included. An inductive content analysis was used to analyse the results of the included studies (n = 53). The most frequently used investigation method was the questionnaire survey seeking the opinions of older people, informal caregivers or healthcare professionals. The unmet care needs identified using the World Health Organization classification were categorized as physical, psychosocial and spiritual, and mostly described individuals’ experiences, though some discussed unmet care needs at an organizational level. The ethical issues raised related to the clinical prioritization of tasks associated with failing to carry out nursing care activities needed. The unmet care needs highlighted in this review are related to poor patient outcomes. The needs of institutionalized older patients remain under-diagnosed and thus, untreated. Negative care outcomes generate a range of serious practical issues for older people in care institutions, which, in turn, raises ethical issues that need to be addressed. Unmet care needs may lead to marginalization, discrimination and inequality in care and service delivery. Further studies are required about patients’ expectations when they are admitted to hospital settings, or training of nurses in terms of understanding the complex needs of older persons.
Genetic landscape and autoimmunity of monocytes in developing Vogt–Koyanagi–Harada disease

Significance Vogt–Koyanagi–Harada (VKH) disease is one of the most common and severe vision-threatening autoimmune uveitis in Asians. However, the functional heterogeneity among subsets in human blood monocytes and the VKH disease-relevant populations remains elusive. This study encoded the landscape of human monocytes, clustered six subsets with distinct functions, and revealed two populations, using single-cell RNA sequencing. Surprisingly, we discovered a disease-specific subset, proinflammatory monocytes, implicating immune activation in VKH disease. We also identified a cell type-specific transcriptional signature in subset ISG15, which might be corresponded with treatment response. These data highlight advanced understanding of pathogenesis, mapping an atlas of autoimmune monocytes and potential therapeutic targets in autoimmune uveitis. Vogt–Koyanagi–Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11,259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes, identified six subpopulations—including S100A12, HLA, CD16, proinflammatory, megakaryocyte-like, and NK-like monocyte subsets—and uncovered two previously unidentified subsets: HLA and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16 and proinflammatory monocyte subpopulations. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into a pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, whose production might reflect the treatment response. Taken together, in this study, we present discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes. Therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH, as well as other autoimmune diseases.
Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

The role of autophagy in colorectal cancer (CRC) pathogenesis appears to be crucial. Autophagy acts both as a tumor suppressor, by removing redundant cellular material, and a tumor-promoting factor, by providing access to components necessary for growth, metabolism, and proliferation. To date, little is known about the expression of genes that play a basal role in the autophagy in CRC. In this study, we aimed to compare the expression levels of 46 genes involved in the autophagy pathway between tumor-adjacent and tumor tissue, employing large RNA sequencing (RNA-seq) and microarray datasets. Additionally, we verified our results using data on 38 CRC cell lines. Gene set enrichment analysis revealed a significant deregulation of autophagy-related gene sets in CRC. The unsupervised clustering of tumors using the mRNA levels of autophagy-related genes revealed the existence of two major clusters: microsatellite instability (MSI)-enriched and -depleted. In cluster 1 (MSI-depleted), ATG9B and LAMP1 genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by DRAM1 upregulation. CRC cell lines were also clustered according to MSI-enriched/-depleted subgroups. The moderate deregulation of autophagy-related genes in cancer tissue, as compared to adjacent tissue, suggests a prominent field cancerization or early disruption of autophagy. Genes differentiating these clusters are promising candidates for CRC targeting therapy worthy of further investigation.
Plasma Lipidomics Reveals Insights into Anti-Obesity Effect of Chrysanthemum morifolium Ramat Leaves and Its Constituent Luteolin in High-Fat Diet-Induced Dyslipidemic Mice

The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.
Antioxidative Activity and Protective Effect of Fermented Plant Extract on Ethanol-induced Damage to Rat Gastric Mucosa

植物エキス発酵液は約50種類の植物を原料として製造される。 植物エキス発酵液のアルコール性胃粘膜障害の抑制効果についてラットで調査したところ, アルコール性胃粘膜障害の抑制効果が200mg/体重kgの投与で認められた。 DPPHに対する活性を指標に Amberlite XAD-2およびODSカラムを用いたHPLCにより抗酸化物質を単離し, MSおよびNMR分析により構造解析したところクロロゲン酸とコーヒー酸を同定した。 また, クロロゲン酸とコーヒー酸は100-200mg/体重kgの投与でアルコール性胃粘膜障害の抑制効果を示した。 以上のことから, 植物エキス発酵液は, 抗酸化活性とアルコール性胃粘膜障害の抑制作用を有することが明らかとなり, これらの作用にクロロゲン酸とコーヒー酸が関与していることが示唆された。
The role of palmitoylation in the pathogenesis of Huntington disease

ii PREFACE . iii TABLE OF CONTENTS . v LIST OF TABLES . x LIST OF FIGURES . xi LIST OF SYMBOLS AND ABBREVIATIONS . xiii ACKNOWLEDGEMENTS . xvi DEDICATION . xviii 1 INTRODUCTION . 1 1.1 PROTEIN PALMITOYLATION: GENERAL OVERVIEW . 1 1.1.1 A primer on protein palmitoylation . 1 1.1.2 Functional consequences of palmitoylation . 3 1.1.3 Dynamic palmitoylation regulates neuronal activity . 5 1.1.4 Interplay between palmitoylation and post-translational and transcriptional modifications . 7 1.2 METHODS TO DETECT PALMITOYLATION . 9 1.2. 1 Bioorthoginal labeling . 9 1.2. 2 Acyl-biotin exchange assay . 11 1.2. 3 Proteomics approaches . 12 1.3 ENZYMES THAT MODIFY PROTEIN PALMITOYLATION . 13 1.3. 1 Palmitoyl acyltransferases (PATs) . 14 1.3. 2 Enzymes promoting depalmitoylation of proteins . 18 1.4 INVOLVEMENT OF PALMITOYLATION IN DISEASES AFFECTING THE NERVOUS SYSTEM . 21 1.4. 1 Alzheimer disease . 24 1.4. 2 Amyotrophic lateral sclerosis . 28 1.4. 3 Schizophrenia . 29 1.4. 4 Mental retardation . 30 1.4. 5 Neuronal cereoid lipofuscinosis . 30 1.4. 6 Huntington disease . 32 1.4. 6.1 Discovery of the huntingtin interacting proteins: HIP14 and HIP14L . 32 1.4. 6.2 Evidence for aberrant palmitoylation in Huntington disease . 33 1.5 HIP14 AND HIP14L: EXPRESSION, FUNCTION, AND STRUCTURE . 35 1.5. 1 HIP14 and HIP14L are widely expressed . 35
The Role of Spinal Orthoses in Osteoporotic Vertebral Fractures of the Elderly Population (Age 60 Years or Older): Systematic Review

Study Design: Systematic review. Objective: Spinal orthoses have been generally used in the management of osteoporotic vertebral fractures in the elderly population with purported positive biomechanical and functional effects. To our knowledge, this is the first systematic review of the literature examining the role of spinal orthoses in osteoporotic elderly patients who sustain low energy trauma vertebral fractures. Methods: A systematic literature review adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Methodical searches utilizing MEDLINE, EMBASE, Google Scholar, and Cochrane Databases was performed. Results: Of the 2019 articles initially retrieved, 7 published articles (4 randomized controlled trials and 3 prospective cohort studies) satisfied the inclusion criteria. Five studies reported improvement in quantitative measurements of spinal column stability when either a rigid or semirigid orthosis was used, while 1 study was equivocal. The studies also showed the translation of biomechanical benefit into significant functional improvement as manifested by improved postural stability and reduced body sway. Subjective improvement in pain scores and quality of life was also noted with bracing. Conclusion: The use of spinal orthoses in neurologically intact elderly patients aged 60 years and older with osteoporotic compression vertebral fractures results in improved biomechanical vertebral stability, reduced kyphotic deformity, enhanced postural stability, greater muscular strength and superior functional outcomes.
Dietary Sodium Intake and Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-Analysis

Dietary sodium intake has received considerable attention as a potential risk factor of cardiovascular disease. However, evidence on the dose-response association between dietary sodium intake and cardiovascular disease risk is unclear. Embase and PubMed were searched from their inception to 17 August 2020 and studies that examined the association between sodium intake and cardiovascular disease in adolescents were not included in this review. We conducted a meta-analysis to estimate the effect of high sodium intake using a random effects model. The Newcastle-Ottawa Scale assessment was performed. A random-effects dose-response model was used to estimate the linear and nonlinear dose-response relationships. Subgroup analyses and meta-regression were conducted to explain the observed heterogeneity. We identified 36 reports, which included a total of 616,905 participants, and 20 of these reports were also used for a dose-response meta-analysis. Compared with individuals with low sodium intake, individuals with high sodium intake had a higher adjusted risk of cardiovascular disease (Rate ratio: 1.19, 95% confidence intervals = 1.08–1.30). Our findings suggest that there is a significant linear relationship between dietary sodium intake and cardiovascular disease risk. The risk of cardiovascular disease increased up to 6% for every 1 g increase in dietary sodium intake. A low-sodium diet should be encouraged and education regarding reduced sodium intake should be provided.
Constraint‐induced movement therapy promotes motor recovery after neonatal stroke in the absence of neural precursor activation

Neonatal stroke is a leading cause of long‐term disability and currently available rehabilitation treatments are insufficient to promote recovery. Activating neural precursor cells (NPCs) in adult rodents, in combination with rehabilitation, can accelerate functional recovery following stroke. Here, we describe a novel method of constraint‐induced movement therapy (CIMT) in a rodent model of neonatal stroke that leads to improved functional outcomes, and we asked whether the recovery was correlated with expansion of NPCs. A hypoxia/ischemia (H/I) injury was induced on postnatal day 8 (PND8) via unilateral carotid artery ligation followed by systemic hypoxia. One week and two weeks post‐H/I, CIMT was administered in the form of 3 botulinum toxin (Botox) injections, which induced temporary paralysis in the unaffected limb. Functional recovery was assessed using the foot fault task. NPC proliferation was assessed using the neurosphere assay and EdU immunohistochemistry. We found that neonatal H/I injury alone expands the NPC pool by >2.5‐fold relative to controls. We determined that using Botox injections as a method to provide CIMT results in significant functional motor recovery after H/I. However, CIMT does not lead to enhanced NPC activation or migration into the injured parenchyma in vivo. At the time of functional recovery, increased numbers of proliferating inflammatory cells were found within the injured motor cortex. Together, these findings suggest that NPC activation following CIMT does not account for the observed functional improvement and suggests that CIMT‐mediated modification of the CNS inflammatory response may play a role in the motor recovery.
The science behind programming algorithms for sacral neuromodulation

Sacral neuromodulation (SNM) is a widely adopted treatment for overactive bladder, non‐obstructive urinary retention and faecal incontinence. In the majority, it provides sustained clinical benefit. However, it is recognized that, even for these patients, stimulation parameters (such as amplitude, electrode configuration, frequency and pulse width) may vary at both initial device programming and at reprogramming, the latter often being required to optimize effectiveness. Although some recommendations exist for SNM programming, the scientific data to support them are understood by few clinicians.
Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.