Miracle-dz/UniFAR-FTUs huggingface dataset:
HDAC3 deficiency promotes liver cancer through a defect in H3K9ac/H3K9me3 transition.

DNA damage triggers diverse cancers, particularly hepatocellular carcinoma (HCC), but the intrinsic link between DNA damage and tumorigenesis remains unclear. Due to its role as an epigenetic and transcriptional regulator, histone deacetylase 3 (HDAC3) is essential for DNA damage control and is often aberrantly expressed in human HCC. In this study, we used individual class I HDAC member-deficient mice to demonstrate that K9 in histone H3 (H3K9), which is the critical site for the assembly of DNA damage response complexes, is exclusively targeted by HDAC3. Ablation of HDAC3 disrupted the deacetylation and consequent trimethylation of H3K9 (H3K9me3), the first step in double-strand break (DSB) repair, and led to the accumulation of damaged DNA. Simultaneously, hyperacetylated H3K9 (H3K9ac) served as a transcriptional activator and enhanced multiple signaling pathways to promote tumorigenesis. Together these results show that HDAC3 targets the H3K9ac/H3K9me3 transition to serve as a critical regulator that controls both DNA damage repair and the transcription of many tumor-related genes. Moreover, these findings provide novel insights into the link between DNA damage and transcriptional reprogramming in tumorigenesis.
Factors Influencing Young People’s Intention toward Municipal Solid Waste Sorting

With the rapid growth of urban economy and population in China, the output of municipal solid waste (MSW) has dramatically increased becoming a constant threat to residents’ living environment and health. The classification intention of residents plays a pivotal role in solving the problem of MSW disposal. While numerous studies have examined the classification behavior of MSW from the perspective of ordinary residents and households, few studies have attempted to understand young people’s sorting intention. The novelty of this research is to explore the determinants that affect young people’s intention toward municipal solid waste sorting (MSWS) by extending the predictive factors of environmental concern and personal moral obligation into the theory of planned behavior (TPB). A sample of 524 young respondents from Hebei Province in China were used to conduct a structural equation model (SEM) validation. The empirical results revealed that, according to the rankings of significance, personal moral obligation, perceived behavioral control, and subjective norm had positive influences on young people’s intention toward MSWS, while attitude and environmental concern did not. Furthermore, the multi-group comparison showed that, compared with the male and rural group, the intention of female and urban respondents to classify MSW was not affected by subjective norms. Some targeted managerial implications were ultimately proposed to promote young people’s intention toward MSWS. This study contributes to the existing knowledge system of MSWS by revealing the classification intention of young people as a group. The findings and implications provide the government with useful insights for encouraging young people to actively participate in MSWS.
Fetal surveillance.

The primary objective of fetal surveillance is to prevent antenatal fetal deaths, which still account for greater than one half of perinatal mortality. Several techniques for assessing fetal well-being are available to the practicing obstetrician, including fetal movement counting, nonstress testing, contraction stress testing, fetal biophysical assessment with real-time sonography, and Doppler ultrasonography for measuring umbilical and fetal blood flow. Despite several unanswered questions regarding fetal surveillance, identification of high-risk pregnancies allows appropriate fetal evaluation that can reduce intrauterine fetal death rates.
Optimal length, calcium sensitivity and twitch characteristics of skeletal muscles from mdm mice with a deletion in N2A titin

ABSTRACT During isometric contractions, the optimal length of skeletal muscles increases with decreasing activation. The underlying mechanism for this phenomenon is thought to be linked to length dependence of Ca2+ sensitivity. Muscular dystrophy with myositis (mdm), a recessive titin mutation in mice, was used as a tool to study the role of titin in activation dependence of optimal length and length dependence of Ca2+ sensitivity. We measured the shift in optimal length between tetanic and twitch stimulation in mdm and wild-type muscles, and the length dependence of Ca2+ sensitivity at short and long sarcomere lengths in mdm and wild-type fiber bundles. The results indicate that the mdm mutation leads to a loss of activation dependence of optimal length without the expected change in length dependence of Ca2+ sensitivity, demonstrating that these properties are not linked, as previously suggested. Furthermore, mdm muscles produced maximum tetanic stress during sub-optimal filament overlap at lengths similar to twitch contractions in both genotypes, but the difference explains less than half of the observed reduction in active force of mdm muscles. Mdm muscles also exhibited increased electromechanical delay, contraction and relaxation times, and decreased rate of force development in twitch contractions. We conclude that the small deletion in titin associated with mdm in skeletal muscles alters force production, suggesting an important regulatory role for titin in active force production. The molecular mechanisms for titin's role in regulating muscle force production remain to be elucidated. Summary: Skeletal muscles with a deletion in titin exhibit no activation dependence of optimal length, but typical length dependence of Ca2+ sensitivity, suggesting that these properties are not necessarily linked.
An immunoproteomic approach to identifying immunoreactive proteins in Leishmania infantum amastigotes using sera of dogs infected with canine visceral leishmaniasis

ABSTRACT Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is caused by Leishmania donovani and Leishmania infantum. The infected dogs with canine visceral leishmaniasis (CVL) are important reservoirs for VL in humans, so the diagnosis, treatment and vaccination of the infected dogs will ultimately decrease the rate of human VL. Proteomics and immunoproteomics techniques have facilitated the introduction of novel drug, vaccine and diagnostic targets. Our immunoproteomic study was conducted to identify new immunoreactive proteins in amastigote form of L. infantum. The strain of L. infantum (MCAN/IR/07/Moheb-gh) was obtained from CVL-infected dogs. J774 macrophage cells were infected with the L. infantum promastigotes. The infected macrophages were ruptured, and pure amastigotes were extracted from the macrophages. After protein extraction, two-dimensional gel electrophoresis was employed for protein separation followed by Western blotting. Western blotting was performed, using symptomatic and asymptomatic sera of the infected dogs with CVL. Thirteen repeatable immunoreactive spots were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Some, including prohibitin, ornithine aminotransferase, annexin A4, and apolipoprotein A-I, have been critically involved in metabolic pathways, survival, and pathogenicity of Leishmania parasites. Further investigations are required to confirm our identified immunoreactive proteins as a biomarker for CVL. GRAPHICAL ABSTRACT
Microrheological study of ternary surfactant‐biosurfactant mixtures

The main objective of this paper is to understand the rheological impact of rhamnolipids biosurfactant (mono/dirhamnolipids mixture, CCB) on a common personal care mixed surfactants system: anionic sodium laureth sulfate (SLES) and zwitterionic cocamidopropyl betaine (CAPB). The ternary biosurfactant/surfactants mixtures were evaluated at three different formulation conditions. The experimental results can provide a formulation guideline when applying rhamnolipids in cosmetics and personal care products.
Performance of alternative measures to body mass index in the assessment of moderate and severe under-nutrition among acutely unwell patients hospitalized in a TB ward in the Philippines: A cross-sectional study

Body mass index (BMI) kg/m2 is a key screening tool for under-nutrition in adults, but difficult to obtain in immobile or unwell patients, particuarly in low resource settings, due to inability to accurately measure both weight and height. Mid-upper arm circumference (MUAC) is used to assess under-nutrition in children under 5 years but no standardised cut-off values exist for adults. In a cohort of adult Filipino patients admitted to a tuberculosis ward we assessed (i) cut-offs for MUAC to predict moderate under-nutrition (BMI <17kg/m2), (ii) the performance of limb lengths to predict height and; (iii) associations of body fat percentage from skinfolds and hand grip-strength with BMI. In 303 patients with MUAC and BMI at admission, aged 18–80 years (mean = 45.5, SD:14.8), BMI ranged from 11.2–30.6 kg/m2 and 141 (46.5%) had BMI <17.0 kg/m2. Using receiver operator curves, MUAC cut-offs were identified as <20.5cm for males (sensitivity: 89%, specificity: 84%) and <18.5cm for females (sensitivity: 91%, specificity: 89%), for BMI<17.0 kg/m2. Using published equations, knee height had the lowest mean difference between predicted and measured heights compared to ulnar or demi-span: (-0.98 cm, 95% CI: -1.51/-0.44). Both grip-strength and body fat percentage were positively associated with BMI, in separate linear regression models with exposure-age-sex interactions (adjusted-R-squared values: 0.15, 0.66, respectively). MUAC can predict moderate acute under-nutrition with high positive predictive value. Further research is required to determine the performance of alternative measures to BMI to predict mortality or adverse outcomes in acutely unwell patients.
A comparative evaluation of signal quality between a research-grade and a wireless dry-electrode mobile EEG system

Objective. Electroencephalography (EEG) is widely used by clinicians, scientists, engineers and other professionals worldwide, with an increasing number of low-cost, commercially-oriented EEG systems that have become available in recent years. One such system is the Cognionics Quick-20 (Cognionics Inc., San Diego, USA), which uses dry electrodes and offers the convenience of portability thanks to its built-in amplifier and wireless connection. Because of such characteristics, this system has been used in several applications for both clinical and basic research studies. However, an investigation of the quality of the signals that are recorded using this system has not yet been reported. Approach. To bridge this gap, here we conducted a systematic comparison of signal quality between the Cognionics Quick-20 system and the Brain Products actiCAP/actiCHamp (Brain Products GmbH, Munich, Germany), a state-of-the-art, wet-electrode, research-oriented EEG system. Resting-state EEG data were recorded from twelve human participants at rest in eyes open and eyes closed conditions. For both systems we evaluated the similarity of mean recorded power spectral density, and detection of alpha suppression associated with eyes open relative to eyes closed. Main results. Power spectral densities were highly correlated across systems, with only minor topographical variability across the scalp. Both systems recorded alpha suppression during eyes open relative to eyes closed conditions. Significance. These results attest to the robustness and reliability of the dry-electrode Cognionics system relatively to the widely used Brain Products laboratory EEG system, and thus validate its utility for clinical and basic research purposes, at least in studies in which participants do not move.
Raman microspectroscopic study of low-pH-induced changes in DNA structure of polytene chromosomes.

The effects of low-pH treatments on DNA structure in polytene chromosomes of Chironomus thummi thummi have been studied by Raman microspectroscopy. Measurements were carried out on chromosomes at low pH and on chromosomes reneutralized after a short exposure to low pH. Protonation of adenine residues and subsequent unpairing of adenine (A) and thymine (T) were found to commence already above pH 3.6 and are completed at pH 2.2. Protonation of the cytosine-guanine base pair also starts above pH 3.6. It leads to an intermediate protonated, most likely Hoogsteen-type, guanine-cytosine base pair. Unpairing of G and C residues starts between pH 2.6 and 2.2 and continues below pH 2.2. Brief treatment of chromosomes at a pH < or = 2.2, i.e., at a pH where both AT and GC base pairs are disrupted, was found to lead to irreversible changes in DNA conformation upon return to neutral pH. These were most pronounced after treatment with 45% acetic acid. More than 10% of the A and T residues was found to have adopted a non-B-DNA conformation. Evidence was found for denaturation of the B-form backbone. The amount of protein extracted from the chromosomes was strongly pH-dependent. Treatment at pH 3.6 did not cause noticeable protein extraction, while treatment with 45% acetic acid extracted more than 50% (by weight) of the chromosomal proteins.
Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation

Significance Phosphate (Pi) is essential for life; thus, serum Pi level is kept constant under tight regulation by fibroblast growth factor (FGF) 23. Conversely, serum FGF23 levels are also controlled by sensing Pi alterations in serum, but this Pi-sensing mechanism remains elusive. In this study, we found that unliganded FGFR is activated by high Pi, leading to an increase in serum FGF23 level by skeletal induction of an FGF23 O-glycosylation enzyme that results in FGF23 proteolytic protection. Thus, the present study elucidates a Pi-sensing mechanism in the control of serum FGF23 levels and provides a molecular basis for a better understanding of hypo- or hyperphosphatemic diseases. Fibroblast growth factor (FGF) 23 produced by bone is a hormone that decreases serum phosphate (Pi). Reflecting its central role in Pi control, serum FGF23 is tightly regulated by serum Pi alterations. FGF23 levels are regulated by the transcriptional event and posttranslational cleavage into inactive fragments before its secretion. For the latter, O-glycosylation of FGF23 by GALNT3 gene product prevents the cleavage, leading to an increase in serum FGF23. However, the molecular basis of Pi sensing in the regulation of serum FGF23 remains elusive. In this study, we showed that high Pi diet enhanced the skeletal expression of Galnt3, but not Fgf23, with expected increases in serum FGF23 and Pi in mice. Galnt3 induction by high Pi was further observed in osteoblastic UMR 106 cells, and this was mediated by activation of the extracellular signal-regulated kinase (ERK) pathway. Through proteomic searches for the upstream sensor for high Pi, we identified one subtype of the FGF receptor (FGFR1c), which was phosphorylated by high Pi in the absence of FGFs. The mode of unliganded FGFR activation by high Pi appeared different from that of FGFR bound to a canonical FGFR ligand (FGF2) when phosphorylation of the FGFR substrate 2α and ERK was monitored. Finally, we showed that an FGFR inhibitor and conditional deletion of Fgfr1 in osteoblasts/osteocytes abrogated high Pi diet-induced increases in serum FGF23 and femoral Galnt3 expression in mice. Thus, these findings uncover an unrecognized facet of unliganded FGFR function and illustrate a Pi-sensing pathway involved in regulation of FGF23 production.
Adjunct Therapy in Type 1 Diabetes: A Survey to Uncover Unmet Needs and Patient Preferences Beyond HbA1c Measures

Abstract Background: Adjunct therapy can help patients with type 1 diabetes achieve glycemic goals while potentially mitigating some of the side effects of insulin. In this study, we used a patient survey to identify the unmet needs in type 1 diabetes therapy, patient views of treatment benefit–risk trade-offs, and patient preferences for the use of an adjunct therapy. Methods: A quantitative survey was sent to 2084 adults with type 1 diabetes in November 2017. “Jobs-to-be-done” and conjoint analyses were performed on survey responses to identify unmet needs and the importance of treatment-associated benefits and risks to patients. A 5-point Likert scale measured the importance and satisfaction with patients' current therapy, and with gaps relating to unmet needs. In the conjoint analysis, patients were asked to choose between “packages” of attributes of two doses of adjunct therapy (200 and 400 mg) and placebo, based on established benefits and side effects. Results: A total of 1313 patients (63%) responded. The greatest unmet needs identified were simplifying treatment, lowering/maintaining glycated hemoglobin (HbA1c), reducing mental effort, and increasing time in range (TIR). Conjoint analysis showed that reductions in body weight and TIR had the highest attribute importance (25% and 18%, respectively). The majority (93%) of patients had a preference for the adjunct therapy (either dose) over placebo. Conclusions: This survey highlights the importance of measures beyond HbA1c, such as treatment simplification and TIR, and patient preference for adjunct therapies that help address unmet needs in type 1 diabetes treatment.
Retinal and choroidal abnormalities identified by multispectral imaging in patients with uveitis

Introduction: Multispectral imaging (MSI) shows increasing strengths in detection of retinal and choroidal disease. The aim of this study was to evaluate the capacity of javascript:void(0), detecting retinal and choroidal abnormalities of uveitis which have not been described previously. Patient concerns: The first case was a 49-year-old male patient who presented with visual disturbance and metamorphopsia in both eyes for 5 days, companying by a history of headache and hearing loss recently. The second case was related to a 45-year-old female patient who complained of blurred vision and a dark shadow before her right eye for 3 months. The third case corresponded to a 36-year-old male patient who presented with blurred vision and slight pain in his left eye for >1 week, and his blood tested positive for syphilis. Diagnosis: Three Chinese patients with representative kind of uveitis were described in the study, including Vogt–Koyanagi–Harada syndrome, posterior uveitis with choroidal neovascularization, and syphilis-infected uveitis. Each affected eye had corresponding retinal and choroidal abnormalities evaluated by multiple ophthalmologic examinations. Interventions: Case 1 was treated with oral prednisone at a dose of 1 mg/kg/d started at the early stage and then slowed tapering of the prednisone dose based on follow-up examinations. Case 2 received anti-VEGF treatment. Case 3 received the standard treatment for neurosyphilis. Outcomes: Due to timely diagnosis and treatment, all patients had a better prognosis. Conclusion: MSI provides a novel way to view retinal and choroidal abnormalities of uveitis, and may provide a supplemental method to morphological changes.
A protocol of a systematic review and meta-analysis

Background: Esophageal cancer is one of the most common malignant tumors, characterized by early metastasis and high degree of malignancy. Its morbidity ranks 7th among all malignant tumors and its mortality ranks 6th. Postoperative adjuvant therapy after esophagectomy can significantly improve the overall survival rate of patients with locally resectable esophageal cancer. With the breakthrough and progress of immunotherapy, the possibility of cure of esophageal cancer is greatly improved. Some clinical trials have reported that programmed death 1 (PD1) and programmed death ligand 1 (PDL1) inhibitors alone, compared with traditional platinum-based chemotherapy, can benefit patients and effectively extend the overall survival period of patients. We will conduct a systematic review and meta-analysis on the comparison of the efficacy of immunotherapy (PD1 and PDL1 inhibitors) alone and traditional platinum-based chemotherapy, so as to provide a reliable basis for clinicians to formulate the best chemotherapy regimen for patients with esophageal cancer after esophagectomy. Methods: We will search Pubmed, Medline, Embase, Web of Science, Cancerlit, Google Scholar, and the Cochrane Central Register of Controlled Trials for related studies published before December 1, 2019 without language restrictions. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) or quasi-RCTs, and prospective cohort studies will be included. We will perform subgroup analysis in sex, age, ethnicity, and tumor stage of esophageal cancer patients. Results: The results of this study will be published in a peer-reviewed journal. Conclusion: The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for esophageal patients, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. PROSPERO registration number: CRD42019125000. Abbreviations: CI = confidence interval, PD-1 = programmed death 1, PD-L1 = programmed death ligand 1, PRISMA = preferred reporting items for systematic reviews andmeta-analyses, PRISMA-P= preferred reporting items for systematic review and meta-analysis protocols, RCTs = randomized controlled trials.
Novel Robust Stability Criteria for Stochastic Hopfield Neural Networks With Time Delays

In this paper, the problem of asymptotic stability for stochastic Hopfield neural networks (HNNs) with time delays is investigated. New delay-dependent stability criteria are presented by constructing a novel Lyapunov-Krasovskii functional. Moreover, the results are further extended to the delayed stochastic HNNs with parameter uncertainties. The main idea is based on the delay partitioning technique, which differs greatly from most existing results and reduces conservatism. Numerical examples are provided to illustrate the effectiveness and less conservativeness of the developed techniques.
Prognostic implications of mean platelet volume on short- and long-term outcomes among patients with non-ST-segment elevation myocardial infarction treated with percutaneous coronary intervention: A single-center large observational study

Abstract Background: Mean platelet volume (MPV) is a simple and reliable indicator of platelet size that correlates with platelet activation and their ability to aggregate. We studied the predictive value of MPV in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention (PCI). Methods: We analyzed the consecutive records of 1001 patients who were hospitalized due to NSTEMI at our center. The primary end point was a composite end point that included the rates of all-cause death, non-fatal myocardial infarction, and acute coronary syndrome (ACS) driven revascularization at 12 months. The enrolled patients were stratified according to the quartile of the MPV level at admission. Results: Along with the increasing quartile of MPV, the 12-month composite end point increased significantly (p = 0.010), and this association remained significant after the risk-adjusted analyses (per 1 fL higher MPV; adjusted hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.02–1.27; p = 0.026). In the multivariate analysis, the MPV was also an independent factor of all-cause mortality (per 1 fL increase; adjusted HR 1.34; 95% CI 1.12–1.61; p = 0.0014) and death or non-fatal myocardial infarction (per 1 fL increase; adjusted HR 1.16; 95% CI 1.03–1.31; p = 0.017). Conclusion: In patients with NSTEMI treated with PCI, a high MPV value was associated with a significantly increased incidence of long-term adverse events, particularly for all-cause mortality.