Miracle-dz/UniFAR-FTUs huggingface dataset:
A chromosome-scale assembly of the axolotl genome

The axolotl (Ambystoma mexicanum) provides critical models for studying regeneration, evolution, and development. However, its large genome (∼32 Gb) presents a formidable barrier to genetic analyses. Recent efforts have yielded genome assemblies consisting of thousands of unordered scaffolds that resolve gene structures, but do not yet permit large-scale analyses of genome structure and function. We adapted an established mapping approach to leverage dense SNP typing information and for the first time assemble the axolotl genome into 14 chromosomes. Moreover, we used fluorescence in situ hybridization to verify the structure of these 14 scaffolds and assign each to its corresponding physical chromosome. This new assembly covers 27.3 Gb and encompasses 94% of annotated gene models on chromosomal scaffolds. We show the assembly's utility by resolving genome-wide orthologies between the axolotl and other vertebrates, identifying the footprints of historical introgression events that occurred during the development of axolotl genetic stocks, and precisely mapping several phenotypes including a large deletion underlying the cardiac mutant. This chromosome-scale assembly will greatly facilitate studies of the axolotl in biological research.
The effects of thyroid hormones on memory impairment and Alzheimer's disease

Thyroid hormones (THs) have a wide and important range of effects within the central nervous system beginning from fetal life and continuing throughout the adult life. Thyroid disorders are one of the major causes of cognitive impairment including Alzheimer's disease (AD). Several studies in recent years have indicated an association between hypothyroidism or hyperthyroidism and AD. Despite available evidence for this association, it remains unclear whether thyroid dysfunction results from or contributes to the progression of AD. This review discusses the role of THs in learning and memory and summarizes the studies that have linked thyroid function and AD. Eventually, we elaborate how THs may be effective in treating AD by putting forward potential mechanisms.
Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy

Abstract Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in the posttransplant setting; however, it is increasingly recognized in pediatric leukemia during chemotherapy. This study assessed the prevalence and associated factors of CMV infection in pediatric non-transplant leukemia patients. This was a cross-sectional study of 50 pediatric acute lymphoblastic leukemia (ALL) patients receiving chemotherapy at Ramathibodi Hospital from December 2015 to December 2016. CMV viral load quantified by DNA polymerase chain reaction (PCR) was monitored in different phases of chemotherapy: enrolment, post-induction, post-consolidation, post-intensification, and maintenance. One hundred forty one blood tests were evaluated from 50 patients. Overall prevalence of CMV DNAemia (≥20 copies/mL) and high-level CMV DNAemia (≥1000 copies/mL) was 52% (26 of 50) and 16.0% (8 of 50), respectively. All patients with high-level CMV DNAemia were in the maintenance phase of chemotherapy. One patient had CMV retinitis, while the rest had no end-organ CMV diseases. Increased lymphocyte count was significantly associated with protection from high-level CMV DNAemia (odds ratio 0.997, P = .02). Receiver operating characteristic curve identified a cut-off value of 798 cells/mm3 of absolute lymphocyte count (ALC) as a discriminator for the presence of high-level CMV DNAemia (area under the curve 0.756, 95% CI 0.645–0.867, P = .001) with 88.9% sensitivity and 50.4% specificity. CMV infection predominantly occurred during maintenance chemotherapy. Low ALC was significantly associated with high-level CMV DNAemia. CMV infection surveillance by quantitative CMV DNA PCR during maintenance chemotherapy in patients with ALC <800 cells/mm3 may be considered.
Rehabilitative devices for a top-down approach

ABSTRACT Introduction: In recent years, neurorehabilitation has moved from a ‘bottom-up’ to a ‘top down’ approach. This change has also involved the technological devices developed for motor and cognitive rehabilitation. It implies that during a task or during therapeutic exercises, new ‘top-down’ approaches are being used to stimulate the brain in a more direct way to elicit plasticity-mediated motor re-learning. This is opposed to ‘Bottom up’ approaches, which act at the physical level and attempt to bring about changes at the level of the central neural system. Areas covered: In the present unsystematic review, we present the most promising innovative technological devices that can effectively support rehabilitation based on a top-down approach, according to the most recent neuroscientific and neurocognitive findings. In particular, we explore if and how the use of new technological devices comprising serious exergames, virtual reality, robots, brain computer interfaces, rhythmic music and biofeedback devices might provide a top-down based approach. Expert commentary: Motor and cognitive systems are strongly harnessed in humans and thus cannot be separated in neurorehabilitation. Recently developed technologies in motor-cognitive rehabilitation might have a greater positive effect than conventional therapies.
Nitric Oxide and the Neuroendocrine Control of the Osmotic Stress Response in Teleosts

The involvement of nitric oxide (NO) in the modulation of teleost osmoresponsive circuits is suggested by the facts that NO synthase enzymes are expressed in the neurosecretory systems and may be regulated by osmotic stimuli. The present paper is an overview on the research suggesting a role for NO in the central modulation of hormone release in the hypothalamo-neurohypophysial and the caudal neurosecretory systems of teleosts during the osmotic stress response. Active NOS enzymes are constitutively expressed by the magnocellular and parvocellular hypophysiotropic neurons and the caudal neurosecretory neurons of teleosts. Moreover, their expression may be regulated in response to the osmotic challenge. Available data suggests that the regulatory role of NO appeared early during vertebrate phylogeny and the neuroendocrine modulation by NO is conservative. Nonetheless, NO seems to have opposite effects in fish compared to mammals. Indeed, NO exerts excitatory effects on the electrical activity of the caudal neurosecretory neurons, influencing the amount of peptides released from the urophysis, while it inhibits hormone release from the magnocellular neurons in mammals.
Reducing pediatric asthma hospital length of stay through evidence-based quality improvement and deployment of computerized provider order entry

Abstract Objective: Evaluate the impact of multi-component quality improvement for pediatric asthma care focusing on serial use of an evidence-based clinical pathway via paper order sets, pathway integration into computerized provider order entry (CPOE), use of a clinical respiratory score (CRS) and a discharge checklist. Methods: Outcomes were assessed over three intervention periods and 50 months on: time to beta-agonist and steroid first administration, frequency of readmissions and hospital length of stay. A general linear model estimated mean log(LOS) over time and between study periods. Time to discharge was transformed using the natural logarithm. Results: No improvements in time to first beta-agonist or steroid administration were observed. There was a reduction in 100-day readmissions (p = 0.008): decreasing from 7.4 to 2.1% after introduction of paper order sets and CRS (adjusted p = 0.04); to 3.9% after CPOE implementation (adjusted p = 0.53) and to 2.2% when a discharge checklist was added (adjusted p = 0.01). There was a statistically significant reduction in LOS between study periods (p = 0.015). The geometric mean LOS in hours during study periods 1–4 were: 34.8 (95% CI: 32.2, 37.6), 29.3 (95% CI: 27.5, 31.3), 29.0 (95% CI: 27.0, 31.3) and 23.1 (95% CI: 22.1, 24.2). Pair-wise comparisons between periods were statistically significant (adjusted p ≤ 0.003), except for Periods 2 and 3 (adjusted p = 0.83). Conclusions: Hospital length of stay and 100-day readmissions rate in a predominantly Hispanic, Medicaid patient population were reduced by utilization of an evidence-based best practices asthma management pathway and CRS within CPOE, combined with a checklist to expedite discharge.
Isorhamnetin, Hispidulin, and Cirsimaritin Identified in Tamarix ramosissima Barks from Southern Xinjiang and Their Antioxidant and Antimicrobial Activities

As a natural potential resource, Tamarix ramosissima has been widely used as barbecue skewers for a good taste and unique flavor. The polyphenolics in the branch bark play a key role in the quality improvement. The purposes of the present work were to explore the polyphenolic composition of T. ramosissima bark extract and assess their potential antioxidant and antimicrobial activities. Hispidulin and cirsimaritin from T. ramosissima bark extract were first identified in the Tamarix genus reported with UPLC-MS analysis. Isorhamnetin (36.91 μg/mg extract), hispidulin (28.79 μg/mg extract) and cirsimaritin (13.35 μg/mg extract) are rich in the bark extract. The extract exhibited promising antioxidant activity with IC50 values of 117.05 μg/mL for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 151.57 μg/mL for hydroxyl radical scavenging activities, as well as excellent reducing power with an EC50 of 93.77 μg/mL. The bark extract showed appreciable antibacterial properties against foodborne pathogens. Listeria monocytogenes was the most sensitive microorganism with the lowest minimum inhibitory concentration (MIC) value of 5 mg/mL and minimum bactericidal concentration (MBC) value of 10 mg/mL followed by S. castellani and S. aureus among the tested bacteria. The T. ramosissima bark extract showed significantly stronger inhibitory activity against Gram-positive than Gram-negative bacteria. Nevertheless, this extract failed to show any activity against tested fungi. Overall, these results suggested that T. ramosissima shows potential in improving food quality due to its highly efficacious antioxidant and antibacterial properties.
Effects of acupuncture on patients with Alzheimer's disease

Background: Alzheimer's disease (AD) is the leading progressive neurodegenerative disease worldwide, accompanied with nonreversible cognitive impairments. Acupuncture, as the traditional Chinese technique, is widely applied in clinical trials for AD. The aim of this review is to evaluate the efficacy and safety of acupuncture in the aspect of antidementia. Methods: Randomized controlled trials (RCTs) related to acupuncture treatment targeting AD will be collected. We will search the following 4 databases of electronic English resources, including PubMed, Embase, MEDLINE, Web of Science, and 4 Chinese databases, namely CNKI, CBM, VIP, and Wanfang database. All the RCTs will be searched from their inception to November 2018. After screening the studies, a meta-analysis of RCTs will be carried out. Subsequently, the assessment of bias risk, data synthesis, subgroup analysis will be conducted using RevMan V.5. 3.5 software if the setting condition is met. Results: This systematic view and meta-analysis will assess the efficacy and safety of acupuncture intervention on AD patients, which is fundamentally based on current published evidence, and provide a high-quality synthesis for clinical practitioners of treating AD with acupuncture, Conclusion: The summary of our systematic view will determine whether acupuncture intervention could be an efficient and feasible approach to the treatment of AD patients.
Rationale and budget impact of bimonthly use of Cetuximab in patients with recurrent and/or metastatic head and neck cancer

In recurrent and/or metastatic head and neck squamous cell cancer, Cetuximab is administered once a week, followed by weekly doses. We present the clinical rationale of a different schedule of maintenance Cetuximab and we estimate the potential economic benefits on the health care budget from a societal perspective in Italy.
Estimation of auditory steady-state responses based on the averaging of independent EEG epochs

The amplitude of the auditory steady-state responses (ASSRs) generated in the brainstem exponentially decreases over the averaging of subsequent EEG epochs. This behavior is partially due to the adaptation of the auditory response to the continuous and monotonous stimulation. We analyzed the potential clinical relevance of the ASSR adaptation. Specifically, we compare the ASSR amplitude computed in two conditions: (1) when the auditory responses -embedded in the EEG epochs that are averaged in the estimation procedure- are influenced by the previous stimulation; and (2) when they are independent of the previous stimulation. ASSR were elicited in eight anesthetized adult rats by 8-kHz tones, modulated in amplitude at 115 Hz. ASSR amplitudes were computed using three averaging methods (standard, weighted and sorted averaging). We evaluated the ASSR amplitude as a function of sub-set of epochs selected for the averaging and the improvement in the ASSR detection resulting from averaging independent epochs. Due to adaptation, the ASSR amplitude computed by averaging dependent EEG epochs relied upon the averaging method. Lower ASSR amplitudes were obtained as EEG segments containing unadapted responses were systematically excluded from the averaging. In the absence of EEG artifacts, the ASSR amplitudes did not depend on the averaging method when they were computed from independent EEG epochs. The amplitude of independent ASSRs were up to 35% higher than those obtained by processing dependent EEG segments. Extracting the ASSR amplitude from independent epochs halved the number of EEG segments needed to be averaged to achieve the maximum detection rate of the response. Acquisition paradigm based on a discrete acoustic stimulation (in which segments of AM-sounds of several seconds in length are presented after a given inter stimulus interval), in combination with appropriated averaging methods might increase the accuracy of audiological tests based on ASSRs.
[Application of Flipped classroom combined with case-based learning in resident training of endodontics].

PURPOSE To apply Flipped classroom combined with case-based learning(CBL) in resident training of endodontics, in order to improve training efficiency. METHODS Fifty-one residents from China Medical University, School of Stomatology were randomly divided into 2 groups, twenty-six students in the experimental group were trained with Flipped classroom combined with CBL, the other twenty-five students in the control group were trained with traditional teaching method. At the end of the course, exams and questionnaires were conducted to evaluate the training quality of two different methods. The exams consisted of didactic and operational assessment. The data were analyzed with SPSS 13.0 software package. RESULTS The results of didactic exam and comprehensive evaluation indicated that experimental group was significantly higher than the control group(P<0.05). The results of questionnaires indicated that residents showed much more satisfied with Flipped classroom combined with CBL (P<0.05). However, there was no significant difference in operational assessment(P>0.05). CONCLUSIONS Compared with traditional teaching method, Flipped classroom combined with CBL can achieve better training effect, which is worthy of further application in dental resident training.
Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells

Insulin-resistance is a characteristic feature of type 2 diabetes (T2D) and plays a major role in the pathogenesis of this disease. Skeletal muscles are quantitatively the biggest glucose users in response to insulin and are considered as main targets in development of insulin-resistance. It is now clear that circulating fatty acids (FA), which are highly increased in T2D, play a major role in the development of muscle insulin-resistance. In healthy individuals, excess FA are stored as lipid droplets in adipocytes. In situations like obesity and T2D, FA from lipolysis and food are in excess and eventually accumulate in peripheral tissues. High plasma concentrations of FA are generally associated with increased risk of developing diabetes. Indeed, ectopic fat accumulation is associated with insulin-resistance; this is called lipotoxicity. However, FA themselves are not involved in insulin-resistance, but rather some of their metabolic derivatives, such as ceramides. Ceramides, which are synthetized de novo from saturated FA like palmitate, have been demonstrated to play a critical role in the deterioration of insulin sensitivity in muscle cells. This review describes the latest progress involving ceramides as major players in the development of muscle insulin-resistance through the targeting of selective actors of the insulin signaling pathway.
Immediate Versus Delayed Loading of Dental Implants Supporting Fixed Full-Arch Maxillary Prostheses: A 10-year Follow-up Report.

PURPOSE To compare clinical outcomes of immediate vs delayed implant loading in edentulous maxillae with full-arch fixed prostheses. MATERIALS AND METHODS Two patient groups were identified for this study: (1) the test group (TG), which included 34 patients (19 women, 15 men; mean age 56.7 years) treated with the Columbus Bridge Protocol with 4 to 6 postextractive implants loaded within 24 hours (163 implants total); and (2) the control group (CG), which included 15 patients (6 women, 9 men; mean age 59.96 years) treated with a traditional two-stage delayed loading rehabilitation using 6 to 9 implants inserted in healed sites (97 implants total). All patients were rehabilitated with full-arch fixed prostheses in the maxilla. RESULTS At the 10-year follow-up, no difference in the implant cumulative survival rate between the TG (93.25%) and CG (94.85%) was found. Mean bone loss was significantly lower in the TG (mean: 2.11 mm) compared to the CG (mean: 2.65 mm). All original prostheses were maintained and functioning satisfactorily. CONCLUSION Maxillary full-arch immediate loading represents a valid alternative to the traditional delayed loading rehabilitation.
T-Cell Response to Viral Hemorrhagic Fevers

Viral hemorrhagic fevers (VHF) are a group of clinically similar diseases that can be caused by enveloped RNA viruses primarily from the families Arenaviridae, Filoviridae, Hantaviridae, and Flaviviridae. Clinically, this group of diseases has in common fever, fatigue, dizziness, muscle aches, and other associated symptoms that can progress to vascular leakage, bleeding and multi-organ failure. Most of these viruses are zoonotic causing asymptomatic infections in the primary host, but in human beings, the infection can be lethal. Clinical and experimental evidence suggest that the T-cell response is needed for protection against VHF, but can also cause damage to the host, and play an important role in disease pathogenesis. Here, we present a review of the T-cell immune responses to VHF and insights into the possible ways to improve counter-measures for these viral agents.
Presynaptic Diversity Revealed by Ca2+-Permeable AMPA Receptors at the Calyx of Held Synapse

GluA2-lacking Ca2+-permeable AMPARs (CP-AMPARs) play integral roles in synaptic plasticity and can mediate excitotoxic cellular signaling at glutamatergic synapses. However, the developmental profile of functional CP-AMPARs at the auditory brainstem remains poorly understood. Through a combination of electrophysiological and live-cell Ca2+ imaging from mice of either sex, we show that the synaptic release of glutamate from the calyx of Held nerve terminal activates CP-AMPARs in the principal cells of the medial nucleus of the trapezoid body in the brainstem. This leads to significant Ca2+ influx through these receptors before the onset of hearing at postnatal day 12 (P12). Using a selective open channel blocker of CP-AMPARs, IEM-1460, we estimate that ∼80% of the AMPAR population are permeable to Ca2+ at immature P4–P5 synapses. However, after the onset of hearing, Ca2+ influx through these receptors was greatly reduced. We estimate that CP-AMPARs comprise approximately 40% and 33% of the AMPAR population at P18–P22 and P30–P34, respectively. By quantifying the rate of EPSC block by IEM-1460, we found an increased heterogeneity in glutamate release probability for adult-like calyces (P30–P34). Using tetraethylammonium (TEA), a presynaptic potassium channel blocker, we show that the apparent reduction of CP-AMPARs in more mature synapses is not a consequence of presynaptic action potential (AP) speeding. Finally, through postsynaptic AP recordings, we show that inhibition of CP-AMPARs reduces spike fidelity in juvenile synapses, but not in more mature synapses. We conclude that the expression of functional CP-AMPARs declines over early postnatal development in the calyx of Held synapse. SIGNIFICANCE STATEMENT The calyx of Held synapse is pivotal to the circuitry that computes sound localization. Postsynaptic Ca2+ influx via AMPARs may be critical for signaling the maturation of this brainstem synapse. The GluA4 subunit may dominate the AMPAR complex at mature synapses because of its fast gating kinetics and large unitary conductance. The expectation is that AMPARs dominated by GluA4 subunits should be highly Ca2+ permeable. However, we find that Ca2+-permeable AMPAR expression declines during postnatal development. Using the rate of EPSC block by IEM-1460, an open channel blocker of Ca2+-permeable AMPARs, we propose a novel method to determine glutamate release probability and uncover an increased heterogeneity in release probability for more mature calyces of Held nerve terminals.
A systematic review and meta-analysis of randomized controlled trials

Background: Several studies have reported the benefits of traditional Chinese exercises (TCEs) on hypertension; however, a consensus regarding the effectiveness and safety of TCEs for patients with hypertension has not been reached. Methodsand results:Only randomized controlled trials were included in our study. A total of 16 articles involving 1164 patients with hypertension met the inclusion criteria. The results showed that TCEs can reduce BP, blood lipids (including total cholesterol and triglyceride levels) and endothelin levels and improves quality of life in hypertensive patients, however, the low-quality of the included studies made the results be of questionable significance. Conclusions: The results of this review suggest that there is no firm evidence to support the objective effectiveness and safety of TCEs for hypertension because of the poor quality of the studies. Well-designed, randomized placebo-controlled trial with objective outcome measures should be conducted in the future. Abbreviations: CHEP = Canadian Hypertension Education Program, COPD = chronic obstructive pulmonary disease, CVD = cardiovascular disease, DBP = diastolic blood pressure, FEV1 = forced expiratory volume in one second, HR = heart rate, JNC8 = Eighth Joint National Committee, LDL-C = Low-density lipoprotein cholesterol, NO = nitric oxide, RCT = randomized controlled trial, SBP = systolic blood pressure, TC = total cholesterol, TCEs = traditional Chinese exercises, TG = triglyceride.