Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Coffee Consumption with Hearing and Tinnitus Based on a National Population-Based Survey

Coffee is the one of the most common beverages worldwide and has received considerable attention for its beneficial health effects. However, the association of coffee with hearing and tinnitus has not been well studied. The aim of this study was to investigate the association of coffee with hearing and tinnitus based on a national population-based survey. We evaluated hearing and tinnitus data from the 2009–2012 Korean National Health and Nutrition Examination Survey and their relationship with a coffee consumption survey. All patients underwent a medical interview, physical examination, hearing test, tinnitus questionnaire and nutrition examination. Multivariable logistic regression models were used to examine the associations between coffee and hearing loss or tinnitus. We evaluated 13,448 participants (≥19 years) participants. The frequency of coffee consumption had a statistically significant inverse correlation with bilateral hearing loss in the 40–64 years age group. Daily coffee consumers had 50–70% less hearing loss than rare coffee consumers, which tended to be a dose-dependent relationship. In addition, the frequency of coffee consumption had an inverse correlation with tinnitus in the 19–64 years age group but its association was related with hearing. Brewed coffee had more of an association than instant or canned coffee in the 40–64 years age group. These results suggest a protective effect of coffee on hearing loss and tinnitus.
Reward-associated distractors can harm cognitive performance

When people carry out cognitive tasks, they sometimes suffer from distractions, that is, drops in performance that occur close in time to task-irrelevant stimuli. In this research, we examine how the pursuit of rewards contributes to distractions. In two experiments, participants performed a math task (in which they could earn monetary rewards vs. not) while they were exposed to task-irrelevant stimuli (that were previously associated with monetary rewards vs. not). In Experiment 1, irrelevant cues that were previously associated with rewards (vs. not) impaired performance. In Experiment 2, this effect was only replicated when these reward-associated distractors appeared relatively early during task performance. While the results were thus somewhat mixed, they generally support the idea that reward associations can augment the negative effect of distractors on performance.
Adaptive Anatomical Specialization of the Intestines of Alpacas Taking into Account their Original Habitat and Feeding Behaviour

The gastrointestinal tract of the alpaca (Vicugna pacos) is most efficiently adapted to its habitat at high altitudes. Alpacas, just like ruminants, feed on hardly digestible forage. However, it has been demonstrated that the anatomy of the camelid digestive tract has developed independently of ruminants and not in homology to them. Despite a long history of domestication and an increasing number of animals worldwide, little research has been done on the intestinal anatomy of alpacas. The purpose of this study was to describe the anatomical features of the alpaca's intestines and to explain anatomical peculiarities in the context of evolutionary function and morphology. Another goal of this study was the demonstration of weaknesses of the intestinal anatomy predisposing alpacas to certain clinical presentations. Six animals were used for dissection. The basic structure of the intestines was comparable to that in ruminants. However, a number of characteristic peculiarities were found in alpacas, like the duodenal ampulla and the proximal and distal loop of the ascending colon. The jejunum and ileum, unlike those of ruminants, had their own mesentery largely separated from the ascending mesocolon. The main blood supply was provided by the cranial and caudal mesenteric artery. The particular lymph nodes were located along the branches of these two arteries. The spiral colon seemed to play a major role in intestinal digestion and water resorption. The size of the distal fermentation chamber allows the presumption that alpacas belong to the group of animals practicing a fractionated fermentation in the proximal and distal fermentation chambers. Anat Rec, 301:1840–1851, 2018. © 2018 Wiley Periodicals, Inc.
Quantifying Waddington’s epigenetic landscape: a comparison of single-cell potency measures

Over 60 years ago Waddington proposed an epigenetic landscape model of cellular differentiation, whereby cell-fate transitions are modelled as canalization events, with stable cell states occupying the basins or attractor states1, 2. A key ingredient of this landscape is the energy potential, or height3, which correlates with cell-potency. To date, very few explicit biophysical models for estimating single-cell potency have been proposed. Using 9 independent experiments, encompassing over 6,600 high-quality single-cell RNA-Seq profiles, we here demonstrate that single-cell potency can be approximated as the graph entropy of a Markov Chain process on a model signaling network. Our analysis highlights that other proposed single-cell potency measures are not robust, whilst also revealing that integration with orthogonal systems-level information improves potency estimates. Thus, this study provides a foundation for an improved systems-level understanding of single-cell potency, which may have profound implications for the discovery of novel stem-and progenitor cell phenotypes.
Predictors of mitochondrial DNA copy number and damage in a mercury‐exposed rural Peruvian population near artisanal and small‐scale gold mining: An exploratory study

Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood cells have been proposed as effect biomarkers for pollutant exposures. Studies have shown that mercury accumulates in mitochondria and affects mitochondrial function and integrity; however, these data are derived largely from experiments in model systems, rather than human population studies that evaluate the potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and damage in white blood cells (WBCs) from 83 residents of nine communities in the Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal and small‐scale gold mining. Prior research from this region reported high levels of mercury in fish and a significant association between food consumption and human total hair mercury level of residents. We observed that mtDNA CN and damage were both associated with consumption of fruit and vegetables, higher diversity of fruit consumed, residential location, and health characteristics, suggesting common environmental drivers. Surprisingly, we observed negative associations of mtDNA damage with both obesity and age. We did not observe any association between total hair mercury or, in contrast to previous results, age, with either mtDNA damage or CN. The results of this exploratory study highlight the importance of combining epidemiological and laboratory research in studying the effects of stressors on mitochondria, suggesting that future work should incorporate nutritional and social characteristics, and caution should be taken when applying conclusions from epidemiological studies conducted in the developed world to other regions, as results may not be easily translated. Environ. Mol. Mutagen. 60: 197–210, 2019. © 2018 Wiley Periodicals, Inc.
Dulaglutide, a GLP-1 receptor agonist, for the treatment of type 2 diabetes

The prevalence of diabetes continues to rise worldwide. Over the past five years, available treatment options have expanded to allow individualized management of patients with diabetes. The glucagon-like peptide-1 (GLP-1) receptor agonists have become an essential tool in the management of type 2 diabetes mellitus (T2DM). This class provides several advantages for glycemic control with minimal risk of hypoglycemia. Based on the most recent guidelines for T2DM, GLP-1 receptor agonists can be prescribed as monotherapy or in combination with oral antidiabetic agents or insulin for the management of T2DM. Dulaglutide has become the most recent and available GLP-1 receptor agonist on the market. Dulaglutide is a once-weekly GLP-1 receptor agonist that can be used as monotherapy or as a second-line agent for T2DM. This review article summarizes the efficacy, safety, and clinical attributes of dulaglutide among patients with T2DM.
The prevalence of depression and insomnia symptoms among patients with rheumatoid arthritis and osteoarthritis in Poland: a case control study

ABSTRACT The objective of the study was to assess the prevalence of symptoms of depression and insomnia among patients with rheumatoid arthritis and osteoarthritis in comparison with individuals without chronic diseases. The study was carried out at National Institute of Geriatrics, Rheumatology and Rehabilitation, included 229 persons. The participants were divided into the following groups: group I – 120 patients with rheumatoid arthritis, group II – 58 patients with osteoarthritis, group III – 51 healthy individuals no confirmed depression (control group). Symptoms of depression were confirmed by a multiple-choice self-reported Beck Depression Inventory questionnaire. Symptoms of depression confirmed with depression inventory≥ 10 occurred as follows: patients with rheumatoid arthritis – 75.83%, patients with osteoarthritis – 50%, control group – 23.53% (p<0.0001), with the prevalence of insomnia (AIS≥6) at: 71%, 32% and 33%, respectively (p<0.001). In group I mean values of FIRST and AIS were 23.06 and 8.36 respectively, with group II: 21.71 and 7.84, respectively. In all subjects with AIS≥6, the depression inventory was statistically significantly (p<0.005) higher than in the subjects with AIS<6 (respectively: 17.02 vs 12.13; 15.6 vs 8.05; 5.45 vs 1.81). Patients with rheumatoid arthritis find it difficult to cope with stress. Insomnia as a reaction to stress occurs more often in this group.
Epigenetic treatment of multiple myeloma mediates tumor intrinsic and extrinsic immunomodulatory effects

ABSTRACT Immune evasion is an important driver of disease progression in the plasma cell malignancy multiple myeloma. Recent work highlights the potential of epigenetic modulating agents as tool to enhance anti-tumor immunity. The immune modulating effects of the combination of a DNA methyltransferase inhibitor and a histone deacetylase inhibitor in multiple myeloma is insufficiently characterized. Therefore, we used the murine immunocompetent 5T33MM model to investigate hallmarks of immunogenic cell death as well as alterations in the immune cell constitution in the bone marrow of diseased mice in response to the DNA methyltransferase inhibitor decitabine and the histone deacetylase inhibitor quisinostat. Vaccination of mice with 5T33 cells treated with epigenetic compounds delayed tumor development upon a subsequent tumor challenge. In vitro, epigenetic treatment induced ecto-calreticulin and CD47, as well as a type I interferon response. Moreover, treated 5T33vt cells triggered dendritic cell maturation. The combination of decitabine and quisinostat in vivo resulted in combinatory anti-myeloma effects. In vivo, epigenetic treatment increased tumoral ecto-calreticulin and decreased CD47 and PD-L1 expression, increased dendritic cell maturation and reduced CD11b positive cells. Moreover, epigenetic treatment induced a temporal increase in presence of CD8-positive and CD4-positive T cells with naive and memory-like phenotypes based on CD62L and CD44 expression levels, and reduced expression of exhaustion markers PD-1 and TIM3. In conclusion, a combination of a DNA methyltransferase inhibitor and a histone deacetylase inhibitor increased the immunogenicity of myeloma cells and altered the immune cell constitution in the bone marrow of myeloma-bearing mice.
Lifestyle Intervention for the Prevention of Diabetes in Women With Previous Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background: Type 2 diabetes is increasing among the young, and gestational diabetes (GDM) offers a unique opportunity for diabetes prevention. We aimed to systematically review postpartum randomized trials to summarize the benefits of lifestyle interventions for women with previous GDM. Methods:We searched for RCTs involving women with previous GDM that compared lifestyle interventions—diet, physical activity or breastfeeding—at postpartum with usual care up to May 2018. Results:Of 1,895 abstracts identified, we selected 15 studies investigating incidence of diabetes or changes in glycemia. Most interventions focused on changes in diet and physical activity, only one also on incentive to breastfeeding. Meta-analysis of 8 studies investigating incidence of diabetes revealed a homogeneous (I2 = 10%), reduction of 25% (RR = 0.75; 95%CI: 0.55–1.03) borderline statistically significant. Only trials offering intervention soon after delivery (< 6 months post-partum) were effective (RR = 0.61; 95%CI: 0.40–0.94; p for subgroup comparison = 0.11). Overall, no benefit was found regarding measures of glycemia. Although moderate reductions in weight (MD = −1.07 kg; −1.43−0.72 kg); BMI (MD = −0.94 kg/m2; −1.79 −0.09 kg/m2); and waist circumference (MD = −0.98 cm; −1.75 −0.21 cm) were observed, effects were larger with longer follow-up. Conclusions:Summary results of the available evidence support benefits of lifestyle interventions at postpartum for women with previous GDM. Benefits, although smaller than those of major trials based in older subjects receiving intensive interventions, appear clinically relevant for this young subset of woman. Further studies are needed to improve the quality of the evidence and to further tailor interventions to this specific setting.
Granuloma multiforme: an uncommon differential for leprosy

Granuloma multiforme (GM) is a chronic granulomatous skin condition which is clinically characterised by annular lesions mainly over sun-exposed areas and histologically by focal necrobiosis and histiocytic granulomas. Its significance lies in the fact that it can clinically resemble tuberculoid leprosy and hence it can be missed. Here, we report a case of GM from India in a 55-year-old female agriculturist, with multiple asymptomatic large annular rings of papules over the photo-distributed areas. Histopathology helps in confirming the diagnosis and in differentiating it from similar clinical and histologic mimics such as granuloma annulare, tuberculoid leprosy, interstitial granulomatous dermatitis or annular sarcoid. Though a high degree of suspicion is needed to diagnose GM, it should be considered as a differential for various annular conditions.
Multi-directional geodesic neural networks via equivariant convolution

We propose a novel approach for performing convolution of signals on curved surfaces and show its utility in a variety of geometric deep learning applications. Key to our construction is the notion of directional functions defined on the surface, which extend the classic real-valued signals and which can be naturally convolved with with real-valued template functions. As a result, rather than trying to fix a canonical orientation or only keeping the maximal response across all alignments of a 2D template at every point of the surface, as done in previous works, we show how information across all rotations can be kept across different layers of the neural network. Our construction, which we call multi-directional geodesic convolution, or directional convolution for short, allows, in particular, to propagate and relate directional information across layers and thus different regions on the shape. We first define directional convolution in the continuous setting, prove its key properties and then show how it can be implemented in practice, for shapes represented as triangle meshes. We evaluate directional convolution in a wide variety of learning scenarios ranging from classification of signals on surfaces, to shape segmentation and shape matching, where we show a significant improvement over several baselines.
Changes in English Past Tense Use by Bilingual School-Age Children With and Without Developmental Language Disorder.

Purpose The purpose of this study is to examine changes in English past tense accuracy and errors among Spanish-English bilingual children with typical development (TD) and developmental language disorder (DLD). Method Thirty-three children were tested before and after 1 year to examine changes in clinically relevant English past tense errors using an elicited production task. A mixed-model linear regression using age as a continuous variable revealed a robust effect for age. A 4-way repeated-measures analysis of variance was conducted with age (young, old) and language ability group (TD, DLD) as between-subjects variables, time (Time 1, Time 2) and verb type (regular, irregular, and novel verbs) as within-subject variables, and percent accuracy as the dependent variable. Subsequently, a 4-way repeated-measures analysis of variance was conducted to measure the overall distribution of verb errors across 2 time points. Results Overall, children produced regular and novel verb past tense forms with higher accuracy than irregular past tense verbs in an elicitation task. Children with TD were more accurate than children with DLD. Younger children made more improvement than older children from Time 1 to Time 2, especially in the regular and novel verb conditions. Bare stem and overregularization were the most common errors across all groups. Errors consisting of stem + ing were more common in children with DLD than those with TD in the novel verb condition. Discussion Contrary to an earlier report (Jacobson & Schwartz, 2005), the relative greater difficulty with regular and novel verbs was replaced by greater difficulty for irregular past tense, a pattern consistent with monolingual impairment. Age was a contributing factor, particularly for younger children with DLD who produced more stem + ing errors in the novel verb condition. For all children, and particularly for those with DLD, an extended period for irregular past tense learning was evident. The results support a usage-based theory of language acquisition and impairment.
Biochemical significance of limonene and its metabolites: future prospects for designing and developing highly potent anticancer drugs

Monocyclic monoterpenes have been recognized as useful pharmacological ingredients due to their ability to treat numerous diseases. Limonene and perillyl alcohol as well as their metabolites (especially perillic acid and its methyl ester) possess bioactivities such as antitumor, antiviral, anti-inflammatory, and antibacterial agents. These therapeutic properties have been well documented. Based on the aforementioned biological properties of limonene and its metabolites, their structural modification and development into effective drugs could be rewarding. However, utilization of these monocyclic monoterpenes as scaffolds for the design and developments of more effective chemoprotective agents has not received the needed attention by medicinal scientists. Recently, some derivatives of limonene metabolites have been synthesized. Nonetheless, there have been no thorough studies on their pharmacokinetic and pharmacodynamic properties as well as their inhibition against isoprenylation enzymes. In this review, recent research progress in the biochemical significance of limonene and its metabolites was summarized with emphasis on their antitumor effects. Future prospects of these bioactive monoterpenes for drug design and development are also highlighted.
CircZNF609 promotes breast cancer cell growth, migration, and invasion by elevating p70S6K1 via sponging miR-145-5p

Background Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer. Methods A total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms. Results CircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circ-ZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=–0.597, P<0.001), whereas a positive correlation between circZNF609 and p70S6K1 expression (r=0.319, P<0.001). Conclusion These data suggest that circZNF609 contributes to breast cancer progression, at least partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential therapeutic target for breast cancer.
Efficacy and safety of de-escalation bone- modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis

Background Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy. Methods A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses. Results A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87–1.12; P=0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness. Conclusion In this meta-analysis of randomized clinical trials, the results “appeared” to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.
Rapid therapeutic advances in CFTR modulator science

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by variants in the gene encoding the cystic fibrosis transmembrane conduction regulator (CFTR) protein. Loss of CFTR function disrupts chloride, bicarbonate and regulation of sodium transport, producing a cascade of mucus obstruction, inflammation, pulmonary infection, and ultimately damage in numerous organs. Established CF therapies treat the downstream consequences of CFTR dysfunction and have led to steady improvements in patient survival. A class of drugs termed CFTR modulators has recently entered the CF therapeutic landscape. These drugs differ fundamentally from prior therapies in that they aim to improve the function of disease‐causing CFTR variants. This review summarizes the science behind CFTR modulators, including their targets, mechanism of action, clinical benefit, and future directions in the field. CFTR modulators have dramatically changed how CF is treated, validated CFTR as a therapeutic target, and opened the door to truly personalized therapies and treatment regimens.