Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Established Thyroid-stimulating Hormone and Free Thyroxine Genetic Variants with Hashimoto’s Thyroiditis

ABSTRACT Hashimoto’s thyroiditis (HT), the most frequent autoimmune thyroid disease (AITD), is characterized by chronic inflammation of the thyroid gland that usually results in hypothyroidism. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels are used as clinical determinants of thyroid function. The main aim of this study was to explore the association of established TSH and FT4 genetic variants with HT. We performed a case–control analysis using 23 genetic markers in 200 HT patients and 304 controls. Additionally, we tested the association of selected variants with several thyroid-related quantitative traits in HT cases only. Two genetic variants showed nominal association with HT: rs11935941 near NR3C2 gene (p = 0.0034, OR = 0.57, 95% CI = 0.39–0.83) and rs1537424 near MBIP gene (p = 0.0169, OR = 0.72, 95% CI = 0.55–0.94). Additionally, three SNPs showed nominal association with thyroglobulin antibody (TgAb) levels: rs4804416 in INSR gene (p = 0.0073, β = −0.51), rs6435953 near IGFBP5 gene (p = 0.0081, β = 0.75), and rs1537424 near MBIP gene (p = 0.0117, β = 0.49). GLIS3 genetic variant rs10974423 showed nominal association with thyroid peroxidase antibody (TPOAb) levels (p = 0.0465, β = −0.56) and NRG1 genetic variant rs7825175 was nominally associated with thyroid gland volume (p = 0.0272, β = −0.18). All detected loci were previously related to thyroid function or pathology. Findings from our study suggest biological relevance of NR3C2 and MBIP with HT, although these loci require additional confirmation in a larger replication study.
Task-Specific Fatigue Among Older Primary Care Patients

Objective: Fatigue is a common condition contributing to disability among older patients. We studied self-reported task-specific fatigue and its relation with mobility task performance among community-dwelling primary care patients. Method: Cross-sectional analysis of baseline demographic and health data from a prospective cohort study of 430 primary care patients aged 65 years or older. Fatigue was measured using the Avlund Mobility–Tiredness Scale. Performance tasks included rising from a chair, walking 4 m, and climbing two flights of stairs. Results: Among demographic and health factors, pain was the only attribute consistently predictive of fatigue status. Self-reported chair rise fatigue and walking fatigue were associated with specific task performance. Stair climb fatigue was not associated with stair climb time. Discussion: Pain is strongly associated with fatigue while rising from a chair, walking indoors, and climbing stairs. This study supports the validity of self-reported chair rise fatigue and walking fatigue as individual test items.
A self-healing, adaptive and conductive polymer composite ink for 3D printing of gas sensors

A self-healing conductive polymer composite ink was formulated for 3D extrusion printing of flexible electronics. It was composed of a polyborosiloxane (PBS) matrix and 5 vol% of electrochemically exfoliated graphene. The printability was derived from the chemical-activated mechanically adaptive properties (MAPs) of PBS. The MAPs of PBS and the composite ink were studied through rheological measurements, and the non-Newtonian nature was analyzed using the Carreau–Yasuda model. With methanol vapor as a representative stimulus, the underpinning mechanism of the MAPs of PBS, which involved the methanol-induced alcoholysis of the cross-linking boron/oxygen dative bonds in PBS, was further investigated by infrared spectroscopy. The self-healing, adaptive and conductive composite ink could be used to print 3D structures and devices on a common polydimethylsiloxane flexible substrate. A 3D-printed gas sensor with responses to various chemical vapors was demonstrated as a potential application of this novel composite ink.
Being an optimist or a pessimist and its relationship with morning cortisol release and past life review in healthy older people

Objective : Investigate the relationship between optimism and pessimism and the cortisol awakening response (CAR) and past life review in healthy older people. Design : 76 older volunteers summarised their lives, highlighting the most important events, impressions and experiences. Cortisol saliva samples were collected on two consecutive weekdays. High and low optimism and pessimism groups were computed by mean split. Main Outcome Measures : Percentages of positive (PE) and negative events (NE) and positive (PCE) and negative cognitions and emotions (NCE) were obtained. Optimism and pessimism were measured with the Life Orientation Test Revised. The areas under the curve with respect to the ground and with respect to the increase were computed, with the latter understood as the CAR. Results : The high pessimism group reported more NE and NCE and less PE and PCE (p’s < 0.041). No significant differences in CAR were found between high and low optimism and pessimism groups after removing suspected non-adherent participants (p’s > 0.116). Higher CAR was related to lower PCE, but higher NCE (both p < 0.008). Conclusion : Pessimism seems to increase the focus on negative aspects of the past, which may lead to a worse perception of life in ageing, whereas optimism contributes to a healthier CAR.
Seed dispersal as an ecosystem service: frugivore loss leads to decline of a socially valued plant, Capsicum frutescens

Abstract Species interactions, both mutualistic and antagonistic, are widely recognized as providing important ecosystem services. Fruit‐eating animals influence plant recruitment by increasing germination during gut passage and moving seeds away from conspecifics. However, relative to studies focused on the importance of frugivores for plant population maintenance, few studies target frugivores as ecosystem service providers, and frugivores are underappreciated as ecosystem service providers relative to other mutualists such as pollinators. Here, we use an accidental experiment to elucidate the role of seed dispersal by frugivores for maintaining a culturally and economically important plant, the donne’ sali chili (Capsicum frutescens) in the Mariana Islands. One of the islands (Guam) has lost nearly all of its native forest birds due to an invasive snake (Boiga irregularis), whereas nearby islands have relatively intact bird populations. We hypothesized that frugivore loss would influence chili recruitment and abundance, which could have economic and cultural impacts. By using video cameras, we confirmed that birds were the primary seed dispersers. We used captive bird feeding trials to obtain gut‐passed seeds to use in a seedling emergence experiment. The experiment showed that gut‐passed seeds emerged sooner and at a higher proportion than seeds from whole fruits. Consistent with our findings that birds benefit chilies, we observed lower chili abundance on Guam than on islands with birds. In a survey questionnaire of island residents, the majority of residents reported an association between the wild chili and local cultural values and traditions. In addition, we identified a thriving market for chili products, suggesting benefits of wild chilies to people in the Marianas both as consumers and producers. Our study therefore documents seed dispersal as both a cultural and a supporting ecosystem service. We provide a comprehensive case study on how seed‐dispersed plants decline in the absence of their disperser, and how to apply mixed‐methods in ecosystem service assessments. Furthermore, we suggest that scientists and resource managers may utilize fruit–frugivore mutualisms concerning socially valuable plants to gather support for frugivore and forest conservation efforts.
Use and Adaptation of Open Source Software for Capacity Building to Strengthen Health Research in Low- and Middle-Income Countries

Health research capacity strengthening is of importance to reach health goals. The ARCADE projects' aim was to strengthen health research across Africa and Asia using innovative educational technologies. In the four years of the EU funded projects, challenges also of technical nature were identified. This article reports on a study conducted within the ARCADE projects. The study focused on addressing challenges of video conferencing in resource constrained settings and was conducted using action research. As a result, a plugin for the open source video conferencing system minisip was implemented and evaluated. The study showed that both the audio and video streams could be improved by the introduced plugin, which addressed one technical challenge.
Lsd1 prevents age-programed loss of beige adipocytes

Significance Over time, beige adipocytes gain a white adipocyte morphology and lose their thermogenic activity. Here we show that levels of the epigenetic eraser lysine-specific demethylase 1 (Lsd1) decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Maintaining adipocyte-specific expression of Lsd1 in transgenic mice preserves the pool of beige adipocytes in old mice. Vice versa, using GFP reporter mice, we traced the fate of beige adipocytes and showed that adipocyte-specific loss of Lsd1 results in a premature beige-to-white adipocyte transition in vivo. Maintenance of beige adipocytes is mediated by the Lsd1 target gene peroxisome proliferator-activated receptor α (Ppara) and pharmacological activation of Ppara rescues the loss of beige adipocytes in Lsd1-KO mice. Together, we identified Lsd1 as a regulator of beige adipocyte maintenance. Aging is accompanied by major changes in adipose tissue distribution and function. In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. Here we show that Lsd1 levels decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Accordingly, adipocyte-specific increase of Lsd1 expression is sufficient to rescue the age-related transition of beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates it. Lsd1 maintains beige adipocytes by controlling the expression of peroxisome proliferator-activated receptor α (Ppara), and treatment with a Ppara agonist is sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation. In summary, our data provide insights into the mechanism controlling the age-related beige-to-white adipocyte transition and identify Lsd1 as a regulator of beige fat cell maintenance.
A Spanish-Catalan Translator Using Statistical Methods

The development of a Spanish-Catalan statistical machine translation system is described in this paper. The methodology used attempts to solve the problem using a purely inductive approach, without using linguistic knowledge. To obtain the translator we use the following steps: First, we obtain a bilingual corpus from the internet. Second, we fragment the corpus into units (sentences and tokens). Third, we align the sentences from the two different languages and we use the aligned corpus to train statistical models. We use a tri-gram model as the target language model and a phrase-based model as translation model. Finally, we use these models to translate. In other words, given a source sentence, we search for the most probable target sentence. We have compared our translator with the most commonly used Spanish-Catalan translators and we have obtained similar translation results to the other commercial systems.
Cations Stiffen Actin Filaments by Adhering a Key Structural Element to Adjacent Subunits

Ions regulate the assembly and mechanical properties of actin filaments. Recent work using structural bioinformatics and site-specific mutagenesis favors the existence of two discrete and specific divalent cation binding sites on actin filaments, positioned in the long axis between actin subunits. Cation binding at one site drives polymerization, while the other modulates filament stiffness and plays a role in filament severing by the regulatory protein, cofilin. Existing structural methods have not been able to resolve filament-associated cations, and so in this work we turn to molecular dynamics simulations to suggest a candidate binding pocket geometry for each site and to elucidate the mechanism by which occupancy of the “stiffness site” affects filament mechanical properties. Incorporating a magnesium ion in the “polymerization site” does not seem to require any large-scale change to an actin subunit’s conformation. Binding of a magnesium ion in the “stiffness site” adheres the actin DNase-binding loop (D-loop) to its long-axis neighbor, which increases the filament torsional stiffness and bending persistence length. Our analysis shows that bound D-loops occupy a smaller region of accessible conformational space. Cation occupancy buries key conserved residues of the D-loop, restricting accessibility to regulatory proteins and enzymes that target these amino acids.
Rifaximin Fails to Prevent Campylobacteriosis in the Human Challenge Model: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Campylobacter species are a leading cause of diarrheal disease globally with significant morbidity. Primary prevention efforts have yielded limited results. Rifaximin chemoprophylaxis decreases rates of travelers' diarrhea and may be suitable for high-risk persons. We assessed the efficacy of rifaximin in the controlled human infection model for Campylobacter jejuni. Methods Twenty-eight subjects were admitted to an inpatient facility and randomized to a twice-daily dose of 550 mg rifaximin or placebo. The following day, subjects ingested 1.7 × 105 colony-forming units of C. jejuni strain CG8421. Subjects continued prophylaxis for 3 additional days, were followed for campylobacteriosis for 144 hours, and were subsequently treated with azithromycin and ciprofloxacin. Samples were collected to assess immunologic responses to CG8421. Results There was no difference (P = 1.0) in the frequency of campylobacteriosis in those receiving rifaximin (86.7%) or placebo (84.6%). Additionally, there were no differences in the clinical signs and symptoms of C. jejuni infection to include abdominal pain/cramps (P = 1.0), nausea (P = 1.0), vomiting (P = .2), or fever (P = 1.0) across study groups. Immune responses to the CG8421 strain were comparable across treatment groups. Conclusions Rifaximin did not prevent campylobacteriosis in this controlled human infection model. Given the morbidity associated with Campylobacter infection, primary prevention efforts remain a significant need. Clinical Trials Registration NCT02280044.
Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication

Herpesviruses persist indefinitely in their host through complex and poorly defined interactions that mediate latent, chronic or productive states of infection. Human cytomegalovirus (CMV or HCMV), a ubiquitous β-herpesvirus, coordinates the expression of two viral genes, UL135 and UL138, which have opposing roles in regulating viral replication. UL135 promotes reactivation from latency and virus replication, in part, by overcoming replication-suppressive effects of UL138. The mechanism by which UL135 and UL138 oppose one another is not known. We identified viral and host proteins interacting with UL138 protein (pUL138) to begin to define the mechanisms by which pUL135 and pUL138 function. We show that pUL135 and pUL138 regulate the viral cycle by targeting that same receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR). EGFR is a major homeostatic regulator involved in cellular proliferation, differentiation, and survival, making it an ideal target for viral manipulation during infection. pUL135 promotes internalization and turnover of EGFR from the cell surface, whereas pUL138 preserves surface expression and activation of EGFR. We show that activated EGFR is sequestered within the infection-induced, juxtanuclear viral assembly compartment and is unresponsive to stress. Intriguingly, these findings suggest that CMV insulates active EGFR in the cell and that pUL135 and pUL138 function to fine-tune EGFR levels at the cell surface to allow the infected cell to respond to extracellular cues. Consistent with the role of pUL135 in promoting replication, inhibition of EGFR or the downstream phosphoinositide 3-kinase (PI3K) favors reactivation from latency and replication. We propose a model whereby pUL135 and pUL138 together with EGFR comprise a molecular switch that regulates states of latency and replication in HCMV infection by regulating EGFR trafficking to fine tune EGFR signaling.
Global substrate specificity profiling of post‐translational modifying enzymes

Enzymes that modify the proteome, referred to as post‐translational modifying (PTM) enzymes, are central regulators of cellular signaling. Determining the substrate specificity of PTM enzymes is a critical step in unraveling their biological functions both in normal physiological processes and in disease states. Advances in peptide chemistry over the last century have enabled the rapid generation of peptide libraries for querying substrate recognition by PTM enzymes. In this article, we highlight various peptide‐based approaches for analysis of PTM enzyme substrate specificity. We focus on the application of these technologies to proteases and also discuss specific examples in which they have been used to uncover the substrate specificity of other types of PTM enzymes, such as kinases. In particular, we highlight our multiplex substrate profiling by mass spectrometry (MSP‐MS) assay, which uses a rationally designed, physicochemically diverse library of tetradecapeptides. We show how this method has been applied to PTM enzymes to uncover biological function, and guide substrate and inhibitor design. We also briefly discuss how this technique can be combined with other methods to gain a systems‐level understanding of PTM enzyme regulation and function.
A novel line search method for nonsmooth optimization problems

In this paper, we propose a novel exact/successive line search method for stepsize calculation in iterative algorithms for nonsmooth optimization problems. The proposed approach is to perform line search over a properly constructed differ-entiable function based on the original nonsmooth objective function, and it outperforms state-of-the-art techniques from the perspective of convergence speed, computational complexity and signaling burden. When applied to LASSO, the proposed exact line search is shown, either analytically or numerically, to exhibit several desirable advantages, namely: it is implementable in closed-form, converges fast and is robust with respect to the choice of problem parameters.
The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer

Aim The aim of this study was to evaluate whether adenomyosis had an effect on myometrial tumor invasion, stage of the disease, and survival in endometrial cancer. Methods Endometrial cancer patients encountered between 2007 and 2016 were identified from pathology records. Patients who underwent suboptimal surgical or medical treatment or with insufficient clinical or surgical data were excluded. Patients diagnosed as having concurrent adenomyosis constituted the study group. Control group patients were randomly selected in a paired design according to the tumor grades in the study group, and for each tumor grade, 4 times as many as patients were included. Tumor stage, histologic type and grade, myometrial invasion, lymphovascular space invasion, presence and location of the adenomyosis in myometrial wall, distance from endometrial line, tumor in adenomyosis, adjuvant treatment, and relapse were primary outcomes. Age, body mass index, medical comorbidities, and type of operation were also recorded. Univariate and multivariate Cox proportional hazards regression models were performed for overall survival. Results Of those 1242 endometrial cancer patients, 80 with concurrent adenomyosis were identified and compared with 320 patients without adenomyosis following a paired selection based on tumor grade. Higher rates of myometrial invasion, lymphovascular space invasion, tumor diameter, and adjuvant treatments were found in the nonadenomyosis group compared with adenomyosis group (P ≤ 0.001). In patients with adenomyosis, rates of early-stage disease and overall survival were significantly higher compared with the control group (P = 0.001 and 0.01, respectively). Conclusions Our results showed that adenomyosis is significantly associated with lower stage in endometrial cancer that may suggest a possible limiting effect on endometrial cancer spread. In addition, despite similar rates in disease-free survival and endometrial cancer–related death, overall survival rate was significantly higher in the presence of adenomyosis and might be considered as a good prognostic factor for endometrial cancer.
Comparative Analysis of the WISC between Two ADHD Subgroups

Objective The prevalence of attention deficit/hyperactivity disorder (ADHD) in school-age children is 7.2%, and ADHD is divided into clinical subtypes. Methods The current study explored whether specific cognitive profiles as assessed using the Wechsler Intelligence Scale for Children (WISC)-IV could be obtained for each clinical ADHD subtype (ADHD-Inattentive type and ADHD-Combined type) and investigated the correlation between WISC scores and parental age at their children’s birth or birthweight. The enrolled sample comprised 12 ADHD-I and 15 ADHD-C subjects. Results An impaired Processing Speed Index was found in ADHD-I. The age of the father at the child’s birth and birthweight positively correlated with the full scale intelligence quotient (FSIQ) score in the WISC assessment. Conclusion Inattentiveness within the behaviors of the children with ADHD-I is partly due to the impaired processing speed, therefore effective support for ADHD will be conducted if educator decreases their speaking speed. Since biological basis of ADHD is still largely unknown, future studies using both psychological and biological methods will reveal the etiology of ADHD. These scientific assessments will provide information for more effective approaches in the care of children with ADHD.