Miracle-dz/UniFAR-FTUs huggingface dataset:
Hand-held Colorimetry Sensor Platform for Determining Salivary α-Amylase Activity and Its Applications for Stress Assessment

This study develops a hand-held stress assessment meter with a chemically colorimetric strip for determining salivary α-amylase activity, using a 3,5 dinitrosalicylic acid (DNS) assay to quantify the reducing sugar released from soluble starch via α-amylase hydrolysis. The colorimetric reaction is produced by heating the strip with a mini polyester heater plate at boiling temperature to form a brick red colored product, which measured at 525 nm wavelength. This investigation describes in detail the design, construction, and performance evaluation of a hand-held α-amylase activity colorimeter with a light emitted diode (LED) and photo-detector with built-in filters. The dimensions and mass of the proposed prototype are only 120 × 60 × 60 mm3 and 200 g, respectively. This prototype has an excellent correlation coefficient (>0.995), comparable with a commercial ultraviolet–visible spectroscope, and has a measurable α-amylase activity range of 0.1–1.0 U mL−1. The hand-held device can measure the salivary α-amylase activity with only 5 μL of saliva within 12 min of testing. This sensor platform effectively demonstrates that the level of salivary α-amylase activity increases more significantly than serum cortisol, the other physiological stressor biomarker, under physiologically stressful exercise conditions. Thus, this work demonstrates that the hand-held α-amylase activity meter is an easy to use and cost-effective stress assessment tool for psychoneuroendocrinology research.
Interleukin‐8 enhances myocilin expression, Akt‐FoxO3 signaling and myogenic differentiation in rat skeletal muscle cells

Interleukin (IL)‐8 is released both in visceral adipose tissue and in contracting skeletal muscles. In this study, we examined cellular pathways associated with muscle hypertrophy, chosen on the basis of microRNA profiling, in differentiating rat primary skeletal muscle cells (RSkMC) treated with IL‐8 (1 ng/ml) for 11 days. IL‐8 increased myocilin expression, Akt phosphorylation, FoxO3 dispersion throughout the cytoplasm, and reduced FoxO3 level. IL‐8 decreased the expression of atrogin and MuRF1 and increased myotube length and diameter. We concluded that IL‐8 present in extracellular environment of myoblasts induced to differentiation stimulates expression of myocilin, a protein important for skeletal muscle hypertrophy. This phenomenon was associated with: (a) activation of myogenic transcription, (b) increased phosphorylation and activation of PKB/Akt, leading to (c) cytoplasm distribution and degradation of a transcription factor FoxO3, (d) decreased expression of gene markers of proteolysis, atrogin and Murf1, and (e) increased myotube length and diameter. In this regard, IL‐8 affects skeletal muscle cells similarly to IGF‐I and can be considered as a potent anticatabolic factor for skeletal muscle.
Redescription of Dichelyne (Cucullanellus) Dichelyneformis (Nematoda: Cucullanidae) and Description of a New Congeneric Species in Eleginops maclovinus (Pisces: Eleginopsidae) Collected in the Bay of Corral, Chile

ABSTRACT Dichelyne (Cucullanellus) dichelyneformis (Szidat, 1950) Petter, 1974, was collected in the intestine of the rock cod, Eleginops maclovinus, in the Bay of Corral, Chile, and redescribed based on light and scanning electron microscopy. The correct arrangement of caudal papillae and post deirids, the shape of gubernaculum, and the morphology and number of denticles surrounding the oral opening are described for the first time. These characteristics along with the excretory pore position, size of spicules, and presence of a nodular thickening near the distal end of the spicules differentiate D. (C.) dichelyneformis from the other congeners reported in South America and in the Antarctic. The new congeneric species found in E. maclovinus differs from D. (C.) dichelyneformis based on the larger males, larger and more numerous denticles with a smooth surface, weakly developed sclerotized plates in esophastome, excretory pore and deirids posterior to nerve ring, shorter gubernaculum and spicules with no thickening on their distal region, lower spicules/body length ratio (10.4–15.1%), and a papilla-like phasmids closer to pairs 8 and 10.
THE EFFECTS OF HYPNOSIS AND HYPNOTIC SUGGESTIONS ON THE MISMATCH NEGATIVITY IN HIGHLY HYPNOTIZABLE SUBJECTS

Abstract The neural mechanisms associated with hypnosis were investigated in a group of 9 high hypnotizable subjects by measuring the mismatch negativity (MMN) component of the auditory event-related potential (ERP). ERPs were recorded using a passive oddball paradigm to sinusoidal standard and deviant tone stimuli of 500 and 520 Hz, respectively, in four conditions: prehypnosis, neutral hypnosis, hypnotic suggestion for altering the tone perception, and posthypnotic conditions. Earlier studies have indicated that hypnosis and hypnotic suggestions might have an effect on MMN, but the results of our study contradict these results: No statistically significant differences were found between the conditions in the MMN amplitudes.
Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains

Carbapenem-resistant Klebsiella pneumoniae (CRKP) increasingly cause high-mortality outbreaks in hospital settings globally. Following a patient fatality at a hospital in Beijing due to a blaKPC-2-positive CRKP infection, close monitoring was put in place over the course of 14 months to characterize all blaKPC-2-positive CRKP in circulation in the hospital. Whole genome sequences were generated for 100 isolates from blaKPC-2-positive isolates from infected patients, carriers and the hospital environment. Phylogenetic analyses identified a closely related cluster of 82 sequence type 11 (ST11) isolates circulating in the hospital for at least a year prior to admission of the index patient. The majority of inferred transmissions for these isolates involved patients in intensive care units. Whilst the 82 ST11 isolates collected during the surveillance effort all had closely related chromosomes, we observed extensive diversity in their antimicrobial resistance (AMR) phenotypes. We were able to reconstruct the major genomic changes underpinning this variation in AMR profiles, including multiple gains and losses of entire plasmids and recombination events between plasmids, including transposition of blaKPC-2. We also identified specific cases where variation in plasmid copy number correlated with the level of phenotypic resistance to drugs, suggesting that the number of resistance elements carried by a strain may play a role in determining the level of AMR. Our findings highlight the epidemiological value of whole genome sequencing for investigating multi-drug-resistant hospital infections and illustrate that standard typing schemes cannot capture the extraordinarily fast genome evolution of CRKP isolates.
Waves of Misery After Index Creation

After creation of a new b-tree, the ordinary course of database updates and index maintenance causes waves of node splits. Thus, a new index may at first speed up database query processing but then the first “wave of misery” requires effort for frequent node splits and imposes spikes of buffer pool contention and of I/O. Waves of misery continue over multiple instances although eventually the waves widen, flatten, and spread further apart. Free space in each node left during index creation fails to prevent the problem; it merely delays the onset of the first wave. We have found a theoretically sound way to avoiding these waves of misery as well as some simple and practical means to reduce their amplitude to negligible levels. Experiments demonstrate that these techniques are also effective. Waves of misery occur in databases and in key-value stores, in primary and in secondary b-tree indexes, after load operations, and after b-tree reorganization or rebuild. The same remedies apply with equal effect.
The Economic Burden of Elevated Blood Glucose Levels in 2017: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes Mellitus, and Prediabetes

OBJECTIVE This study was conducted to update national estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes mellitus (GDM) in the United States for year 2017 and provide state-level estimates. Combined with published estimates for diagnosed diabetes, these updated statistics provide a detailed picture of the economic costs associated with elevated blood glucose levels. RESEARCH DESIGN AND METHODS This study estimated medical expenditures exceeding levels occurring in the absence of diabetes or prediabetes and the indirect economic burden associated with reduced labor force participation and productivity. Data sources analyzed included Optum medical claims for ∼5.8 million commercially insured patients continuously enrolled from 2013 to 2015, Medicare Standard Analytical Files containing medical claims for ∼2.8 million Medicare patients in 2014, and the 2014 Nationwide Inpatient Sample containing ∼7.1 million discharge records. Other data sources were the U.S. Census Bureau, Centers for Disease Control and Prevention, and Centers for Medicare & Medicaid Services. RESULTS The economic burden associated with diagnosed diabetes (all ages), undiagnosed diabetes and prediabetes (adults), and GDM (mothers and newborns) reached nearly $404 billion in 2017, consisting of $327.2 billion for diagnosed diabetes, $31.7 billion for undiagnosed diabetes, $43.4 billion for prediabetes, and nearly $1.6 billion for GDM. Combined, this amounted to an economic burden of $1,240 for each American in 2017. Annual burden per case averaged $13,240 for diagnosed diabetes, $5,800 for GDM, $4,250 for undiagnosed diabetes, and $500 for prediabetes. CONCLUSIONS Updated statistics underscore the importance of reducing the burden of prediabetes and diabetes through better detection, prevention, and treatment.
Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological study.

The various forms of Alexander disease (AD) have been linked to heterozygous point mutations in the coding region of the HUMAN GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) gene. The aim of this study was to confirm and characterise an adult variant of AD based on the presence of Rosenthal fibres, which were identified at brain autopsy. We performed histological and immunohistochemical studies and mutation screening by cycle sequencing of exons 1, 4, 6, and 8. A heterozygous D128N GFAP mutation, previously described in three other cases of adult-onset AD (AOAD), was genetically confirmed. The mutation was seemingly sporadic. Symptoms of the female, 65-year-old patient started with occasionally asymmetric motor impairment and concluded, 23 months later, with a lack of spontaneous movement in all four limbs, reduced consciousness, an acute respiratory problem, and eventually lethal exitus. The most striking characteristics were a cerebellar syndrome with subsequent clinical signs due to brainstem and spinal cord involvement. The final diagnosis was based on a complete autopsy, detection of Rosenthal fibres, GFAP, vimentin, alpha B-crystallin, ubiquitin, hsp27, neurofilament, and synaptophysin, and the identification of the corresponding GFAP gene mutation. Blood analyses were positive for ANA and rheumatoid factor. In conclusion, this work describes sporadic, rapidly advancing AOAD in a female patient and links it with other published cases with the same mutation. Reflections are provided on the influence of vasculitis and ANA in AD as well as the presence of Rosenthal fibres in the neurohypophysis.
4.2 mW GaInNAs long-wavelength VCSEL grown by metalorganic chemical vapor deposition

We achieved high output power GaInNAs vertical-cavity surface-emitting lasers (VCSELs) emitting at 1261.5 nm by means of decreasing the incorporation of aluminum into the GaInNAs well layers. The continuous wave (CW) output power at room temperature reached 4.2 mW, with a slope efficiency of 0.52 W/A. Secondary ion mass spectrometry (SIMS) analysis revealed that the aluminum incorporated into the GaInNAs layer did not originate from diffusion from the adjacent layers of GaInNAs, but from residual aluminum in the reactor.
Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery

Cryptophycins are potent tubulin polymerization inhibitors with picomolar antiproliferative potency in vitro and activity against multidrug-resistant (MDR) cancer cells. Because of neurotoxic side effects and limited efficacy in vivo, cryptophycin-52 failed as a clinical candidate in cancer treatment. However, this class of compounds has emerged as attractive payloads for tumor-targeting applications. In this study, cryptophycin was conjugated to the cyclopeptide c(RGDfK), targeting integrin αvβ3, across the protease-cleavable Val-Cit linker and two different self-immolative spacers. Plasma metabolic stability studies in vitro showed that our selected payload displays an improved stability compared to the parent compound, while the stability of the conjugates is strongly influenced by the self-immolative moiety. Cathepsin B cleavage assays revealed that modifications in the linker lead to different drug release profiles. Antiproliferative effects of Arg-Gly-Asp (RGD)–cryptophycin conjugates were evaluated on M21 and M21-L human melanoma cell lines. The low nanomolar in vitro activity of the novel conjugates was associated with inferior selectivity for cell lines with different integrin αvβ3 expression levels. To elucidate the drug delivery process, cryptophycin was replaced by an infrared dye and the obtained conjugates were studied by confocal microscopy.
Comparison of the fecal microbiota of two free-ranging Chinese subspecies of the leopard (Panthera pardus) using high-throughput sequencing

The analysis of gut microbiota using fecal samples provides a non-invasive approach to understand the complex interactions between host species and their intestinal bacterial community. However, information on gut microbiota for wild endangered carnivores is scarce. The goal of this study was to describe the gut microbiota of two leopard subspecies, the Amur leopard (Panthera pardus orientalis) and North Chinese leopard (Panthera pardus japonensis). Fecal samples from the Amur leopard (n = 8) and North Chinese leopard (n = 13) were collected in Northeast Tiger and Leopard National Park and Shanxi Tieqiaoshan Provincial Nature Reserve in China, respectively. The gut microbiota of leopards was analyzed via high-throughput sequencing of the V3–V4 region of bacterial 16S rRNA gene using the Life Ion S5™ XL platform. A total of 1,413,825 clean reads representing 4,203 operational taxonomic units (OTUs) were detected. For Amur leopard samples, Firmicutes (78.4%) was the dominant phylum, followed by Proteobacteria (9.6%) and Actinobacteria (7.6%). And for the North Chinese leopard, Firmicutes (68.6%), Actinobacteria (11.6%) and Fusobacteria (6.4%) were the most predominant phyla. Clostridiales was the most diverse bacterial order with 37.9% for Amur leopard and 45.7% for North Chinese leopard. Based on the beta-diversity analysis, no significant difference was found in the bacterial community composition between the Amur leopard and North Chinese leopard samples. The current study provides the initial data about the composition and structure of the gut microbiota for wild Amur leopards and North Chinese leopards, and has laid the foundation for further investigations of the health, dietary preferences and physiological regulation of leopards.
Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China

Abstract Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin’s lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.
Differential localization of histone variant TH2B during the first round compared with subsequent rounds of spermatogenesis

Male germ cells are unique because they express a substantial number of variants of the general DNA binding proteins, known as histones, yet the biological significance of these variants is still unknown. In the present study, we aimed to address the expression pattern of the testis‐specific histone H2B variant (TH2B) and the testis‐specific histone H2A variant (TH2A) within the neonatal mouse testis.
Combining deep neural networks and engineered features for cardiac arrhythmia detection from ECG recordings

Objective: We aim to combine deep neural networks and engineered features (hand-crafted features based on medical domain knowledge) for cardiac arrhythmia detection from short single-lead ECG recordings. Approach: We propose a two-stage method named ENCASE for cardiac arrhythmia detection. The first stage is feature extraction and the second stage is classifier building. In the feature extraction stage, we extract both deep features and engineered features. Deep features are obtained by modifying deep neural networks into a deep feature extractor. Engineered features are extracted by summarizing existing approaches into four feature groups. Then, we propose a feature aggregation approach to combine these features. In the classifier building stage, we build multiple gradient boosting decision trees and combine them to get the final detector. Main results: Experiments are performed on the PhysioNet/Computing in Cardiology Challenge 2017 dataset (Clifford et al 2017 Computing in Cardiology vol 44). Using F1 scores reported on the hidden test set as measurements, ENCASE got 0.9117 on Normal (F1N), 0.8128 on Atrial Fibrillation (AF) (F1A), 0.7505 on Others (F1O), and 0.5671 on Noise (F1P). It placed 5th in the Challenge and 8th in the follow-up challenge (ranked by considering the average of Normal, AF, and Others (F1NAO = 0.825)). When rounding to two decimal places, we were part a three-way tie for 1st place and were part a seven-way tie for 2nd place in the follow-up challenge. Further experiments show that combined features perform better than individual features, and deep features show more importance scores than other features. Significance: ENCASE can benefit from both feature engineering-based methods and recent deep neural networks. It is flexible and can easily assimilate the ability of new cardiac arrhythmia detection methods.
Production of an aberrant splice variant of CCL5 is not caused by genetic mutation in the mammary glands of mastitis-infected Holstein cows

Genetic mutations, including single nucleotide polymorphisms (SNPs), result in aberrant alternatively splicing of gene and involves in susceptibility of inflammatory diseases, including bovine mastitis. C-C motif chemokine ligand 5 (CCL5) is an immune-associated gene, but its alternative splicing (AS) mechanism of gene expression has not yet been understood. The present study identified the splice variant of CCL5 and the compared differential expression of various transcripts between healthy and mastitic mammary gland tissue from cows. A novel transcript lacking exon 2 with a deletion of 112 bp (referred to as CCL5-AS) was identified in the mammary gland. The expression of CCL5-AS was lower compared with CCL5-reference in the healthy and mastitic mammary tissues. A total of two novel SNPs (g.1647 C>T and g.1804 G>A) were identified in exon 2 of CCL5. Using the splicing mini-gene reporter assay in bovine mammary epithelial cells (MAC-T) and 293T cells, it was confirmed that the production of CCL5-AS was not caused by the two SNPs. The present findings suggested that alternative splicing is one of the mechanisms of CCL5 expression regulation and is involved in mastitis infection, but that genetic mutation was not responsible for the generation of the abnormal transcript of CCL5 in cows.
Next-generation sequencing analysis of the human T-cell and B-cell receptor repertoire diversity before and after hepatitis B vaccination

ABSTRACT The hepatitis B (HB) vaccine effectively prevents the incidence of hepatitis B virus (HBV) infection. However, vaccine failure occurs in 5–10% of the recipients. The precise mechanisms leading to responsiveness to the HB vaccine are poorly understood. High-throughput sequencing (HTS) may help clarify the immune response to the HB vaccine, so we applied this method to investigate whether the HB vaccine induced a specific change in the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires. We conducted HTS of the TCR β chain and BCR IgG heavy (H) chain complementary determining region 3 (CDR3) repertoires in five volunteers before and after the second and third immunizations with the HB vaccine. The HB surface antibody (HBsAb) levels were >10 mIU/ml after the third vaccination in all five participants. The TCR β chain CDR3 repertoire diversity significantly increased, while the BCR IgG H chain CDR3 repertoire diversity significantly decreased after the second vaccination. Although there was no marked inter-individual variation in terms of the numbers of unique reads, it is possible that the TCR β chain and BCR IgG H chain CDR3 repertoires may have changed within the same numbers of unique reads. Our data failed to identify the specific dominant clones that responded to the HB vaccine. In summary, the TCR β chain CDR3 repertoire diversity significantly increased, while the BCR IgG H chain CDR3 repertoire diversity significantly decreased, after the second HB vaccination. These diversity changes might be associated with a better response to the HB vaccine.