Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-tunneled versus short-tunneled external ventricular drainage: Prospective experience from a developing country

Background: External ventricular drains (EVD) are commonly utilized for temporary diversion of cerebrospinal fluid (CSF). Many neurosurgeons prefer long-tunneled EVDs in their routine practice. However, it is still unclear whether this extended tunneling helps in reducing CSF infection. Keeping this in mind, we decided to compare infection rates in long-tunneled versus short-tunneled EVDs in the setting of a developing country. Materials and Methods: A prospective study of 60 patients was conducted. Consenting patients who underwent short-tunneled (Group A) or long-tunneled (Group B) EVDs between January 2008 and June 2009 were followed during the course of their inpatient care. All operational protocol was standardized during the trial. Serial samples of CSF were analyzed to detect infection. Results: Mean age of patients was 33.6 years with 32 males (53.3%). Mean duration of long-tunneled EVD was 13.4 ± 7.2 days, whereas that of short-tunneled EVD was 5.3 ± 2.7 days (P < 0.001). Three patients with long-tunneled EVD (10.0%), whereas one patient with short-tunneled EVD (3.3%) developed drain-related infections; however, this was non-significant (P = 0.301). However, patients with short-tunneled EVD got infected earlier on day 3when compared with the long-tunneled EVDs, which got infected after a mean duration of 7.3 days. The overall risk of infection for long-tunneled EVDs was 7.46 per 1,000 ventricular drainage days which was comparable to the risk of 6.33 per 1,000 ventricular drainage days seen for short-tunneled EVDs. Conclusion: Long-tunneled EVDs appear to only delay potential infections without having any effect on the actual risk of infection. Long-tunneled EVD in a resource-limited setting is technically challenging and may not yield additional benefits to the patient. However, larger and prospective studies are needed to establish the rate of infections and other complications.
Long-acting Muscarinic Antagonist Versus Inhaled Corticosteroid when Added to Long-acting β-agonist for COPD: A Meta-analysis

ABSTRACT The purpose of this study was to systematically review the efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist (LABA/LAMA) and LABA/inhaled corticosteroid (ICS) combinations in patients with advanced chronic obstructive pulmonary disease (COPD). Randomized clinical trials of at least 12 weeks of duration comparing LABA/LAMA and LABA/ICS combinations were included. We chose forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score, Transitional Dyspnea Index (TDI), COPD Assessment Test (CAT) score, COPD exacerbations, mortality, and other safety parameters as outcome assessment criteria. We included six randomized controlled trials with a total of 4,319 patients. Most patients did not have a history of exacerbation. LABA/LAMA was associated with greater improvement in FEV1 than LABA/ICS (mean difference (MD) 0.09L, 95%confidence interval (CI) 0.07 to 0.11L; high certainty). Two treatments appeared clinically equivalent in improving SGRQ (MD −0.12, 95%CI −1.16 to 0.92; high certainty), TDI (MD 0.15, 95%CI −0.05 to 0.35; high certainty), and CAT scores (MD 0.28 95%CI −0.29 to 0.85; moderate certainty). LABA/LAMA was associated with an absolute reduction of approximately 8% in the incidence of pneumonia compared with LABA/ICS (risk ratio 0.41, 95%CI 0.18 to 0.94; moderate certainty). There was no significant difference in safety and exacerbation outcomes. However, equivalence of two treatments could not be concluded due to imprecision especially for mortality, cardiac serious adverse events, and severe exacerbations. Our findings support the use of dual long-acting bronchodilators for patients with advanced COPD but without frequent exacerbations given the excess risk of pneumonia with LABA/ICS.
Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance. The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients. Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study. Meta-regression was used to further explore the influence of study level variables on heterogeneity. Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02–0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04–0.06) showed similar proportions of indeterminate results; pooled risk difference was−0.01 (95% CI −0.03 to 0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients (p < 0.001). Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results.
Autophagy Mediates Astrogenesis in Adult Hippocampal Neural Stem Cells

Neural stem cells (NSCs) have the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes. Highly dynamic nature of NSC differentiation requires the intimate involvement of catabolic processes such as autophagy. Autophagy is a major intracellular degradation pathway necessary for cellular homeostasis and remodeling. Autophagy is important for mammalian development and its role in neurogenesis has recently drawn much attention. However, little is known about how autophagy is associated with differentiation of NSCs into other neural lineages. Here, we report that autophagy plays a critical role in differentiation of adult rat hippocampal neural stem (HCN) cells into astrocytes. During differentiation, autophagy flux peaked at early time points, and remained high. Pharmacological or genetic suppression of autophagy by stable knockdown of Atg7, LC3 or CRISPR-Cas9-mediated knockout (KO) of p62 impaired astrogenesis, while reintroduction of p62 recovered astrogenesis in p62 KO HCN cells. Taken together, our findings suggest that autophagy plays a key role in astrogenesis in adult NSCs.
Age- and Experience-Related Plasticity of ATP-Mediated Signaling in the Neocortex

There is growing recognition of the important role of interaction between neurons and glial cells for brain longevity. The extracellular ATP have been shown to bring significant contribution into bi-directional glia-neuron communications, in particular into astrocyte-driven modulation of synaptic plasticity. To elucidate a putative impact of brain aging on neuron-glia networks, we explored the aging-related plasticity of the purinoreceptors-mediated signaling in cortical neurons and astrocytes. We investigated the age- and experience-related alterations in purinergic components of neuronal synaptic currents and astroglial calcium signaling in the layer2/3 of neocortex of mice exposed to the mild caloric restriction (CR) and environmental enrichment (EE) which included ad libitum physical exercise. We observed the considerable age-related decline in the neuronal P2X receptor-mediated miniature spontaneous currents which originated from the release of ATP from both synapses and astrocytes. We also found out that purinergic astrocytic Ca2+-signaling underwent the substantial age-related decline but EE and CR rescued astroglial signaling, in particular mediated by P2X1, P2X1/5, and P2Y1 receptors. Our data showed that age-related attenuation in the astroglial calcium signaling caused a substantial decrease in the exocytosis of ATP leading to impairment of astroglia-derived purinergic modulation of excitatory synaptic currents and GABAergic tonic inhibitory currents. On a contrary, exposure to EE and CR, which enhanced purinergic astrocytic calcium signaling, up-regulated the excitatory and down-regulated the inhibitory currents in neurons of old mice, thus counterbalancing the impact of aging on synaptic signaling. Combined, our results strongly support the physiological importance of ATP-mediated signaling for glia-neuron interactions and brain function. Our data also show that P2 purinoreceptor-mediated communication between astrocytes and neurons in the neocortex undergoes remodeling during brain aging and decrease in the ATP release may contribute to the age-related impairment of synaptic transmission.
iTRAQ-Based Quantitative Proteomic Profiling of Staphylococcus aureus Under Different Osmotic Stress Conditions

Staphylococcus aureus (S. aureus) is an extremely halotolerant pathogenic bacterium with high osmotic stress tolerance, and it is frequently encountered in aquatic production and preservation. However, the mechanism underlying the extremely high osmotic stress tolerance of S. aureus remains unclear. In this study, the isobaric tags for relative and absolute quantification (iTRAQ) method was used to identify the differentially expressed proteins (DEPs) under different sodium chloride (NaCl) concentrations. Compared with the control group (0% NaCl), the 10 and 20% NaCl groups had 484 DEPs and 750 DEPs, respectively. Compared with the 10% NaCl group, the 20% NaCl group had 361 DEPs. Among the DEPs, proteins involved in fatty acid synthesis, proline/glycine betaine biosynthesis and transportation, stress tolerance, cell wall biosynthesis and the TCA cycle were upregulated, whereas proteins associated with biofilm formation and pathogenic infections were downregulated. The results obtained in this study indicate that under extremely high osmotic stress, modification of the cell membrane structure, increased biosynthesis and transportation of osmotic protectants, and redistribution of energy metabolism contribute to the osmotic stress tolerance of S. aureus, and the infectious ability of the bacteria may be limited. The aim of this study was to provide new insight into how S. aureus tolerates the high-salt conditions involved in aquatic production and preservation.
Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis

Background: Monoamine oxidases (MAOs) were discovered nearly a century ago. This article aims to analyze the research literature landscape associated with MAOs as privileged class of neuronal enzymes (neuroenzymes) with key functions in the processes of neurodegeneration, serving as important biological targets in neuroscience. With the accumulating publications on this topic, we aimed to evaluate the publication and citation performance of the contributors, reveal the popular research themes, and identify its historical roots. Methods: The electronic database of Web of Science (WoS) Core Collection was searched to identify publications related to MAOs, which were analyzed according to their publication year, authorship, institutions, countries/regions, journal title, WoS category, total citation count, and publication type. VOSviewer was utilized to visualize the citation patterns of the words appearing in the titles and abstracts, and author keywords. CRExplorer was utilized to identify seminal references cited by the MAO publications. Results: The literature analysis was based on 19,854 publications. Most of them were original articles (n = 15,148, 76.3%) and reviews (n = 2,039, 10.3%). The top five WoS categories of the analyzed MAO publications were Pharmacology/Pharmacy (n = 4,664, 23.5%), Neurosciences (n = 4,416, 22.2%), Psychiatry (n = 2,906, 14.6%), Biochemistry/Molecular Biology (n = 2,691, 13.6%), and Clinical Neurology (n = 1,754, 8.8%). The top 10 institutions are scattered in the United States, UK, France, Sweden, Canada, Israel, and Russia, while the top 10 countries/regions with the most intensive research on the field of MAOs are the United States, followed by European and Asian countries. More highly cited publications generally involved neurotransmitters, such as dopamine (DA), serotonin, and norepinephrine (NE), as well as the MAO-A inhibitors moclobemide and clorgyline, and the irreversible MAO-B inhibitors selegiline and rasagiline. Conclusion: Through decades of research, the literature has accumulated many publications investigating the therapeutic effects of MAO inhibitors (MAOIs) on various neurological conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression. We envision that MAO literature will continue to grow steadily, with more new therapeutic candidates being tested for better management of neurological conditions, in particular, with the development of multi-target acting drugs against neurodegenerative diseases.
Serum tumour markers in patients with chronic kidney disease

Objective. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19‐9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21‐1, neuron‐specific enolase (NSE) and squamous cell carcinoma antigen (SCC‐Ag). Material and methods. 232 non‐dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The non‐dialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr ⩽25 mL/min; group 2 = 25.1–49.9 mL/min; group 3 = Ccr ⩾50 mL/min. For comparison, we chose 37 non‐dialysis patients with similar Ccr, age and same gender as controls. Results. The serum concentrations of CA19‐9, CA125 (male), CYFRA 21‐1, NSE and SCC‐Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag showed no differences between hemodialysis patients and non‐dialysis controls (p>0.017). Conclusions. The increase in the serum levels of CA19‐9, CA125 (in males), CYFRA 21‐1, NSE and SCC‐Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag.
Glucocorticoid Therapy of Multiple Sclerosis Patients Induces Anti-inflammatory Polarization and Increased Chemotaxis of Monocytes

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the infiltration of mononuclear cells into the CNS and a subsequent inflammation of the brain. Monocytes are implicated in disease pathogenesis not only in their function as potential antigen-presenting cells involved in the local reactivation of encephalitogenic T cells but also by independent effector functions contributing to structural damage and disease progression. However, monocytes also have beneficial effects as they can exert anti-inflammatory activity and promote tissue repair. Glucocorticoids (GCs) are widely used to treat acute relapses in MS patients. They act on a variety of cell types but their exact mechanisms of action including their modulation of monocyte function are not fully understood. Here we investigated effects of the therapeutically relevant GC methylprednisolone (MP) on monocytes from healthy individuals and MS patients in vitro and in vivo. The monocyte composition in the blood was different in MS patients compared to healthy individuals, but it was only marginally affected by MP treatment. In contrast, application of MP caused a marked shift toward an anti-inflammatory monocyte phenotype in vitro and in vivo as revealed by an altered gene expression profile. Chemotaxis of monocytes toward CCL2, CCL5, and CX3CL1 was increased in MS patients compared to healthy individuals and further enhanced by MP pulse therapy. Both of these migration-promoting effects were more pronounced in MS patients with an acute relapse than in those with a progressive disease. Interestingly, the pro-migratory GC effect was independent of chemokine receptor levels as exemplified by results obtained for CCR2. Collectively, our findings suggest that GCs polarize monocytes toward an anti-inflammatory phenotype and enhance their migration into the inflamed CNS, endowing them with the capacity to suppress the pathogenic immune response.
How Do Price and Quantity Promotions Affect Hedonic Purchases? An ERPs Study

Due to consuming hedonic products unnecessary to basic well-being, consumers need justifications for pleasure. However, different justifications have differential influences in promoting hedonic purchases, such as price and quantity promotions (PP and QP), the difference being that the latter requires purchasing additional units to get the same discount as the former. In the present study, even-related potentials (ERPs) was applied to reveal the timing of brain activities to further understand how promotion information consisting of promotion type (PP and QP) and discount depth, deep and shallow discounts (DD and SD) on hedonic products was processed. Behaviorally, consumers were more willing to purchase items in PP and DD conditions than QP and SD conditions, respectively, and spent more time making final purchase decisions in QP and DD condition or PP and SD condition compared to PP and DD condition. Neurophysiologically, DD automatically recruited more attentional resources than SD and led to a higher P2 amplitude. QP and DD condition or PP and SD condition evoked a larger N2 amplitude and enhanced perceptual conflict compared to PP and DD condition. During late stage, PP and DD elicited a more positive LPP amplitude in contrast to QP and SD, respectively, indicating that people have stronger purchase intention and positive affect in PP and DD contexts. These findings provided evidence for the differential influences between PP and QP and what ultimately made consumers buy hedonic products or not.
Neural Activations Associated With Friction Stimulation on Touch-Screen Devices

Tactile sensation largely influences human perception, for instance when using a mobile device or a touch screen. Active touch, which involves tactile and proprioceptive sensing under the control of movement, is the dominant tactile exploration mechanism compared to passive touch (being touched). This paper investigates the role of friction stimulation objectively and quantitatively in active touch tasks, in a real human-computer interaction on a touch-screen device. In this study, 24 participants completed an active touch task involved stroking the virtual strings of a guitar on a touch-screen device while recording the electroencephalography (EEG) signal. Statistically significant differences in beta and gamma oscillations in the middle frontal and parietal areas at the late period of the active touch task are found. Furthermore, stronger beta event-related desynchronization (ERD) and rebound in the presence of friction stimulation in the contralateral parietal area are observed. However, in the ipsilateral parietal area, there is a difference in beta oscillation only at the late period of the motor task. As for implicit emotion communication, a significant increase in emotional responses for valence, arousal, dominance, and satisfaction is observed when the friction stimulation is applied. It is argued that the friction stimulation felt by the participants' fingertip in a touch-screen device further induces cognitive processing compared to the case when no friction stimulation is applied. This study provides objective and quantitative evidence that friction stimulation is able to affect the bottom-up sensation and cognitive processing.
Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways

BACKGROUND Qingjie Fuzheng granules (QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer (CRC). However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs’ anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways. AIM To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8. METHOD First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase (LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21, Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3K/AKT and ERK signaling pathways was examined using the western blot assay to investigate the possible mechanism. RESULTS MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by (6.90% ± 1.03%)–(59.70% ± 1.51%) (HCT-116; P < 0.05) and (5.56% ± 4.52%)–(49.44% ± 2.47%) (HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002 (HCT-116; P < 0.01) and from 0.56 ± 0.054 to 0.81 ± 0.044 (HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells. QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3K, AKT and ERK. CONCLUSION These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3K/AKT and ERK signaling pathways.