Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylation deficiency of chromatin proteins is a non-mutational and epigenetic-like trait in evolved lines of the archaeon Sulfolobus solfataricus

Archaea are a distinct and deeply rooted lineage that harbor eukaryotic-like mechanisms, including several that manage chromosome function. In previous work, the thermoacidophilic crenarchaeon, Sulfolobus solfataricus, was subjected to adaptive laboratory evolution to produce three strains, called SARC, with a new heritable trait of super acid resistance. These strains acquired heritable conserved transcriptomes, yet one strain contained no mutations. Homologous recombination without allele replacement at SARC acid resistance genes caused changes in both phenotype and expression of the targeted gene. As recombination displaces chromatin proteins, their involvement was predicted in the SARC trait. Native chromatin proteins are basic and highly abundant and undergo post-translational modification through lysine monomethylation. In this work, their modification states were investigated. In all SARC lines, two chromatin proteins, Cren7 and Sso7d, were consistently undermethylated, whereas other chromatin proteins were unaltered. This pattern was heritable in the absence of selection and independent of transient exposure to acid stress. The bulk of Sso7d was undermethylated at three contiguous N-terminal lysine residues but not at central or C-terminal regions. The N-terminal region formed a solvent-exposed patch located on the opposite side of the binding domain associated with the DNA minor groove. By analogy to eukaryotic histones, this patch could interact with other chromosomal proteins and be modulated by differential post-translational modification. Previous work established an epigenetic-like mechanism of adaptation and inheritance in S. solfataricus. The identification of heritable epigenetic marks in this work further supports the occurrence of an epigenetic process in archaea.
Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome

Objective To determine safety, tolerability, and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are available. Methods This was a phase 2, multicenter, double-blind, placebo-controlled, parallel-group study, in which safety/tolerability, pharmacokinetics, and clinical response to trofinetide were characterized in 82 children/adolescents with RTT, aged 5 to 15 years. Sixty-two participants were randomized 1:1:1:1 to receive placebo twice a day (bid) for 14 days, followed by placebo, 50, 100, or 200 mg/kg bid of trofinetide for 42 days. Following blinded safety data review, 20 additional participants were randomized 1:1 to the 200 mg/kg or placebo bid groups. Safety assessments included adverse events, clinical laboratory tests, physical examinations, and concomitant medications. Clinician- and caregiver-based efficacy measurements assessed clinically relevant, phenotypic dimensions of impairment of RTT. Results All dose levels were well tolerated and generally safe. Trofinetide at 200 mg/kg bid showed statistically significant and clinically relevant improvements relative to placebo on the Rett Syndrome Behaviour Questionnaire, RTT-Clinician Domain Specific Concerns–Visual Analog Scale, and Clinical Global Impression Scale–Improvement. Exploratory analyses suggested that observed changes correlated with trofinetide exposure. Conclusion These results, together with those from a previous adolescent/adult trial, indicate trofinetide's potential for treating core RTT symptoms and support further trials. Classification of evidence This study provides Class I evidence that for children/adolescents with RTT, trofinetide was safe, well-tolerated, and demonstrated improvement over placebo at 200 mg/kg bid in functionally important dimensions of RTT.
Bucillamine-induced Pneumonitis in a Patient with Rheumatoid Arthritis-associated Interstitial Pneumonia: A Case Report and Review of the Literature

An 81-year-old woman with rheumatoid arthritis (RA) who had been treated with bucillamine presented with dyspnea. Computed tomography of the chest showed ground-glass opacities and consolidations in both lungs and honeycombing in both basal lung areas. An elevation of the serum Krebs von den Lungen-6 level and hypoxemia were seen. Lymphocytosis with a decreased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. A transbronchial lung biopsy specimen showed organizing pneumonia. Based on a diagnosis of bucillamine-induced pneumonitis (BIP) with RA-associated pre-existing interstitial pneumonia, she was successfully treated with the cessation of bucillamine and systemic corticosteroid therapy. The risk factors and prognosis of BIP are discussed.
Letter by Sporns et al Regarding Article, "Predictive Value of Susceptibility Vessel Sign for Arterial Recanalization and Clinical Improvement in Ischemic Stroke".

To the Editor: Recently, we have read the article by Darcourt et al, “Predictive Value of Susceptibility Vessel Sign for Arterial Recanalization and Clinical Improvement in Ischemic Stroke. ” In their retrospective series of 180 patients, the authors report that a positive susceptibility vessel sign (SVS) is associated with a higher rate of successful recanalization and better early clinical improvement after mechanical thrombectomy. The theory behind the imaging appearance of clots is that thrombi with a high level of red blood cells appear hyperdense on computed tomography and with a low signal intensity known as a SVS on T2*-gradient echo imaging sequences which is associated with the presence of deoxyhemoglobin. The findings of Darcourt et al are very interesting; however, as the authors point out themselves, the literature regarding this topic is controversial. In fact, larger studies did not find a significant association of SVS and successful recanalization even though imaging parameters were similar and interrater agreements were at least satisfactory in all studies. In their brief report, Darcourt et al do not provide a hypothesis why this may be the case. Another recent study by our group, even though based on computed tomography, likewise did not find any association of thrombus characteristics with rates of recanalization. This study also included histological parameters—which may be considered as underlying gold standard when talking about clot imaging characteristics. In conclusion, Darcourt et al provide an interesting study, but an emerging question is which clinical consequences the appearance of SVS on admission imaging might have. How would the authors use SVS in admission magnetic resonance imaging for triage of ischemic stroke patients?
Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.
Atrial Fibrillation Catheter Ablation Increases the Left Atrial Pressure

Background: We previously reported that a high left atrial (LA) pressure is associated with LA stiffness and poor rhythm outcomes after de novo catheter ablation of atrial fibrillation. Herein, we investigated whether radiofrequency catheter ablation generally changes the LA pressure among patients undergoing repeat procedures. Methods: Among 1848 patients who underwent atrial fibrillation catheter ablation, we measured the LA pressure during sinus rhythm in 1687 patients before the de novo ablation (59±11 years, 72.4% men, 72.8% paroxysmal atrial fibrillation) and in 142 with second procedures. We measured the LA pressure immediately after the transseptal puncture at the beginning of the procedure. Results: In the same 142 patients, the degree of LA stiffness, reflected by the LA pulse pressure (LApp), was significantly higher in the second procedure than in the de novo procedure (P<0.001). The degree of the LApp increase (&Dgr;LApp) was significantly higher in patients who underwent additional extrapulmonary vein LA ablation than in those who underwent circumferential pulmonary vein isolation alone (P=0.010). Extrapulmonary vein LA ablation was independently associated with the &Dgr;LApp (&bgr;=5.70 [0.12–11.27]; P=0.045). An increased LApp during repeat procedures was independently associated with a reduced diastolic function (&bgr;=2.01 [0.08–3.93]; P=0.041) without a worsening symptoms (EuroQol-five dimensions) score, 22.2±17.9 months after the de novo ablation. Conclusions: Atrial fibrillation catheter ablation, especially extrapulmonary vein LA ablation, increased the LA stiffness and was associated with a worsening postablation diastolic function. However, the symptom score did not significantly change. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT02138695.
Overview of Models of Cognitive Aging

This chapter reviews major theories of cognitive aging. Theories such as the sensory de ﬁ cit hypothesis, speed of processing, and inhibitory de ﬁ cit hypothesis are based largely on behavioral ﬁ ndings and focus on a single process that is purported to account for a number of cognitive changes with age. Speci ﬁ c to memory, theories focus on age de ﬁ cits in recollection and binding. Over the past twenty-ﬁ ve years, brain-based models have begun to pervade the literature. These have focused on concepts such as compensation, dedifferentiation, and suppression of the default mode network. The scaffolding theory of aging and cognition integrates many of these concepts into a single comprehensive model, including consideration of enrichment and depletion factors that operate over the life span. We conclude the chapter with some debates, critiques, and consideration of future directions, particularly considering the contributions of cognitive neuroscience methods.
Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin

The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1α) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1α expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1α as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC.
Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health

The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.
Using automated computer vision and machine learning to code facial expressions of affect and arousal: Implications for emotion dysregulation research

Abstract As early as infancy, caregivers’ facial expressions shape children's behaviors, help them regulate their emotions, and encourage or dissuade their interpersonal agency. In childhood and adolescence, proficiencies in producing and decoding facial expressions promote social competence, whereas deficiencies characterize several forms of psychopathology. To date, however, studying facial expressions has been hampered by the labor-intensive, time-consuming nature of human coding. We describe a partial solution: automated facial expression coding (AFEC), which combines computer vision and machine learning to code facial expressions in real time. Although AFEC cannot capture the full complexity of human emotion, it codes positive affect, negative affect, and arousal—core Research Domain Criteria constructs—as accurately as humans, and it characterizes emotion dysregulation with greater specificity than other objective measures such as autonomic responding. We provide an example in which we use AFEC to evaluate emotion dynamics in mother–daughter dyads engaged in conflict. Among other findings, AFEC (a) shows convergent validity with a validated human coding scheme, (b) distinguishes among risk groups, and (c) detects developmental increases in positive dyadic affect correspondence as teen daughters age. Although more research is needed to realize the full potential of AFEC, findings demonstrate its current utility in research on emotion dysregulation.
Null models for animal social network analysis and data collected via focal sampling: Pre‐network or node network permutation?

In social networks analysis, two different approaches have predominated in creating null models for hypothesis testing, namely pre‐network and node network permutation approaches. Although the pre‐network permutation approach appears more advantageous, its use has mainly been restricted to data on associations and sampling methods such as ‘group follows’. The pre‐network permutation approach has recently been adapted to data on interactions and the focal sampling method, but its performance in different scenarios has not been thoroughly explored. Here, we assessed the performance of the pre‐network and node network permutation approach in several simulated scenarios based on proneness to false positive or false negatives and with or without observation bias. Our results showed that the pre‐network permutation was sensitive to false positives in scenarios with or without observation bias. The node network permutation approach produced fewer false positives and negatives than the pre‐network approach, but only in scenarios without observation bias. In scenarios with observation bias, the node network permutation approach was outperformed by pre‐network permutation. Caution should be taken when using the pre‐network and node network permutations to create null models with data collected via focal sampling. This study provides future methodological research perspectives for social network analyses.
Socioeconomic inequalities in obesity among Korean women aged 19-79 years: the 2016 Korean Study of Women’s Health-Related Issues

OBJECTIVES While the prevalence of obesity in Asian women has remained stagnant, studies of socioeconomic inequalities in obesity among Asian women are scarce. This study aimed to examine the recent prevalence of obesity in Korean women aged between 19 years and 79 years and to analyze socioeconomic inequalities in obesity. METHODS Data were derived from the 2016 Korean Study of Women’s Health-Related Issues. The chi-square test and logistic regression analysis were used to analyze the associations between socioeconomic factors and obesity using Asian standard body mass index (BMI) categories: low (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23.0-24.9 kg/m2 ), and obese (≥25.0 kg/ m2 ). As inequality-specific indicators, the slope index of inequality (SII) and relative index of inequality (RII) were calculated, with adjustment for age and self-reported health status. RESULTS Korean women were classified into the following BMI categories: underweight (5.3%), normal weight (59.1%), overweight (21.2%), and obese (14.4%). The SII and RII revealed substantial inequalities in obesity in favor of more urbanized women (SII, 4.5; RII, 1.4) and against of women who were highly educated (SII, -16.7; RII, 0.3). Subgroup analysis revealed inequalities in obesity according to household income among younger women and according to urbanization among women aged 65-79 years. CONCLUSIONS Clear educational inequalities in obesity existed in Korean women. Reverse inequalities in urbanization were also apparent in older women. Developing strategies to address the multiple observed inequalities in obesity among Korean women may prove essential for effectively reducing the burden of this disease.
The epidemiology of hepatitis B virus infection in Korea

The global burden of hepatitis B virus (HBV) infection is profound, and represents a public health threat as chronic infection can lead to liver cirrhosis, hepatocellular carcinoma, and death. The risk factors for chronic hepatitis B-related liver disease differ according to HBV endemicity, hepatitis B e-antigen seropositivity, and viral load. It is important to identify these risk factors and start antiviral treatment at an appropriate time according to current guidelines. The most crucial step in reducing HBV infection is prevention in infancy or early childhood, as infection at an early stage may lead to chronicity. South Korea was formerly an HBV-endemic area, but the epidemiology of HBV infection was changed by the introduction of vaccination in 1983 and nationwide immunization in 1995. The government and the private sector made efforts to reduce the prevalence of HBV infection, and Korea is on target to meet the World Health Organization goal of eliminating viral hepatitis by 2030. To eliminate hepatitis worldwide, the costs of antiviral treatment to prevent perinatal HBV transmission in pregnant women with high viremia should be covered by a national program, and strategies to reduce the prevalence of HBV infection in immigrant populations are needed.
A Trust-Based Predictive Model for Mobile Ad Hoc Network in Internet of Things †

The Internet of things (IoT) is a heterogeneous network of different types of wireless networks such as wireless sensor networks (WSNs), ZigBee, Wi-Fi, mobile ad hoc networks (MANETs), and RFID. To make IoT a reality for smart environment, more attractive to end users, and economically successful, it must be compatible with WSNs and MANETs. In light of this, the present paper discusses a novel quantitative trust model for an IoT-MANET. The proposed trust model combines both direct and indirect trust opinion in order to calculate the final trust value for a node. A Beta probabilistic distribution is used to combine different trust evidences and direct trust has been calculated. The theory of ARMA/GARCH has been used to combine the recommendation trust evidences and predict the resultant trust value of each node in multi-step ahead. Further, a routing protocol has been designed to ensure the secure and reliable end-to-end delivery of packets by only considering trustworthy nodes in the path. Simulation results show that our proposed trust model outperforms similar existing trust models.
Competition between N–H bending vibration and α-helix polarization under 50 Hz magnetic field in SH-SY5Y neuronal-like cells

Abstract The aim of this study is to investigate the causes of the different response of Amide I and Amide II bands in neuronal-like cells under an applied magnetic field at extremely low frequency and intensity. A Lumos IR microscope of Bruker Optics coupled with a FTIR spectrometer equipped with a wide-band liquid nitrogen cooled mercury–cadmium–telluride detector were used to acquire images and FTIR spectra of SH-SY5Y neuronal-like cells under exposure to 50 Hz magnetic fields at the intensity of 1.4 mT, generated by two Helmholtz coils driven by an AC voltage and placed into an incubator in a 5% CO2/95% air humidified at 37 °C. Using this experimental setup resulted that the Amide II vibration band in neuronal-like cells increased significantly more than Amide I band after 6 h exposure to 50 Hz magnetic fields. This result can be explained assuming that the following mechanisms occurred simultaneously after exposure to 50 Hz magnetic fields: the alignment of proteins α-helices in cellular membrane toward the direction of applied magnetic field and a significant increasing of N-H bending vibration in proteins structure.