Miracle-dz/UniFAR-FTUs huggingface dataset:
Uracil–DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil

Abstract UNG is the major uracil-DNA glycosylase in mammalian cells and is involved in both error-free base excision repair of genomic uracil and mutagenic uracil-processing at the antibody genes. However, the regulation of UNG in these different processes is currently not well understood. The UNG gene encodes two isoforms, UNG1 and UNG2, each possessing unique N-termini that mediate translocation to the mitochondria and the nucleus, respectively. A strict subcellular localization of each isoform has been widely accepted despite a lack of models to study them individually. To determine the roles of each isoform, we generated and characterized several UNG isoform-specific mouse and human cell lines. We identified a distinct UNG1 isoform variant that is targeted to the cell nucleus where it supports antibody class switching and repairs genomic uracil. We propose that the nuclear UNG1 variant, which in contrast to UNG2 lacks a PCNA-binding motif, may be specialized to act on ssDNA through its ability to bind RPA. RPA-coated ssDNA regions include both transcribed antibody genes that are targets for deamination by AID and regions in front of the moving replication forks. Our findings provide new insights into the function of UNG isoforms in adaptive immunity and DNA repair.
Negatively phrased items of the Autism Spectrum Quotient function differently for groups with and without autism

The Autism Spectrum Quotient is a widely used instrument for the detection of autistic traits. However, the validity of comparisons of Autism Spectrum Quotient scores between groups may be threatened by differential item functioning. Differential item functioning entails a bias in items, where participants with equal values of the latent trait give different answers because of their group membership. In this article, items of the Autism Spectrum Quotient were studied for differential item functioning between different groups within a single sample (N = 408). Three analyses were conducted. First, using a Rasch mixture model, two latent groups were detected that show differential item functioning. Second, using a Rasch regression tree model, four groups were found that show differential item functioning: men without autism, women without autism, people 50 years and younger with autism, and people older than 50 years with autism. Third, using traditional methods, differential item functioning was detected between groups with and without autism. Therefore, group comparisons with the Autism Spectrum Quotient are at risk of being affected by bias. Eight items emerged that consistently show differences in response tendencies between groups across analyses, and these items were generally negatively phrased. Two often-used short forms of the Autism Spectrum Quotient, the AQ-28 and AQ-10, may be more suitable for group comparisons.
Patterns of community assembly in the developing chicken microbiome reveal rapid primary succession

The fine‐scale temporal dynamics of the chicken gut microbiome are unexplored, but thought to be critical for chicken health and productivity. Here, we monitored the fecal microbiome of healthy chickens on days 1–7, 10, 14, 21, 28, and 35 after hatching, and performed 16S rRNA amplicon sequencing in order to obtain a high‐resolution census of the fecal microbiome over time. In the period studied, the fecal microbiomes of the developing chickens showed a linear‐log increase in community richness and consistent shifts in community composition. Three successional stages were detected: the first stage was dominated by vertically transmitted or rapidly colonizing taxa including Streptococcus and Escherichia/Shigella; in the second stage beginning on day 4, these taxa were displaced by rapid‐growing taxa including Lachnospiraceae and Ruminococcus‐like species variants; and in the third stage, starting on day 10, slow‐growing, specialist taxa including Candidatus Arthrobacter and Romboutsia were detected. The patterns of displacement and the previously reported ecological characteristics of many of the dominant taxa observed suggest that resource competition plays an important role in regulating successional dynamics in the developing chicken gut. We propose that the boundaries between successional stages (3–4 and 14–21 days after hatching) may be optimal times for microbiome interventions.
Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P–N (phosphoramidate), P–S (phosphorothioate), and P–C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P–N, P–S, and P–C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (N- and S-phosphorylation) and reviews the natural phosphorothioate (P–S) and phosphoramidate (P–N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P–N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.
Assessment of Sleep Impairment in Persistent Allergic Rhinitis Patients Using Polysomnography

Background: Although questionnaires have demonstrated an association between impairment of quality of sleep and symptoms in allergic rhinitis (AR) patients, to date there is no report of an objective assessment of sleep in patients with persistent allergic rhinitis (PER) as defined by ARIA guidelines. The aim of the present study was therefore to assess sleep disturbance in PER patients by polysomnography (PSG). Methods: Ninety-eight PER patients with moderate-to-severe nasal obstruction and 30 healthy volunteers were included in the study. All patients underwent PSG during nocturnal sleep to assess the presence and severity of sleep disorders. Peak nasal inspiratory flow (PNIF) was also measured to assess nasal resistance. Results: There were statistically significant, though clinically modest, differences between PER patients and healthy controls in most PSG parameters including sleep efficiency, arousal index, average SaO2, lowest SaO2, time spent with a saturation below 90%, and snoring time. Although the apnea-hypopnea index (AHI) was not significantly different between the 2 groups, 17 subjects (17.3%) in the PER group but none of the control subjects had an AHI >5. Patients with higher T5SS scores (12 ≤ T5SS ≤ 15) had a greater tendency to snore than did patients with lower scores (8 ≤ T5SS ≤ 11). Finally, PNIF in the PER group was significantly lower than in the control group. Weak correlations between the arousal index and PNIF, average SaO2, and PNIF were found. Conclusion: PSG showed modest changes in PER patients versus control subjects.
Specific Gut and Salivary Microbiota Patterns Are Linked With Different Cognitive Testing Strategies in Minimal Hepatic Encephalopathy.

OBJECTIVES Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE. METHODS Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis. RESULTS Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One hundred twelve patients also provided saliva samples. Depending on the modality, 59%-82% of patients had MHE. Intertest Kappa for MHE was 0.15-0.35. Stool and salivary microbiota profiles with MHE were different from those without MHE. Individual microbiota signatures were associated with MHE in specific modalities. However, the relative abundance of Lactobacillaceae in the stool and saliva samples was higher in MHE, regardless of the modality used, whereas autochthonous Lachnospiraceae were higher in those without MHE, especially on PHES. On logistic regression, stool and salivary Lachnospiraceae genera (Ruminococcus and Clostridium XIVb) were associated with good cognition independent of clinical variables. CONCLUSIONS Specific stool and salivary microbial signatures exist for individual cognitive testing strategies in MHE. The presence of specific taxa associated with good cognitive function regardless of modality could potentially be used to circumvent MHE testing.
Daidzein Intake Is Associated with Equol Producing Status through an Increase in the Intestinal Bacteria Responsible for Equol Production

Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the status of equol production and the gut microbiota has not been fully investigated. The aim of this study was to compare the intestinal bacteria responsible for equol production in gut microbiota between equol producer and non-producer subjects regarding the intake of daidzein. A total of 1044 adult subjects who participated in a health survey in Hirosaki city were examined. The concentration of equol in urine was measured by high-performance liquid chromatography. The relative abundances of 8 bacterial species responsible for equol production in the gut microbiota was assessed using 16S rRNA amplification. There were 458 subjects identified as equol producers. The proportion of equol production status and the intake of daidzein increased with age. Daily intake of daidzein was larger in equol-producer. The intestinal bacteria, which convert daidzein to equol were present in both equol producers and non-producers. However, the relative abundance and the prevalence of Asaccharobacter celatus and Slackia isoflavoniconvertens were significantly higher in equol producers than those in equol non-producers. The intestinal bacteria that convert daidzein to equol are present in not only the equol producers but also in the non-producers. The daidzein intake is associated with the equol production status through an increase of A. celatus and S. isoflavoniconvertens in the gut microbiota.
The Challenges in Personal Health Record Adoption

EXECUTIVE SUMMARY Communication between patient and healthcare provider is an essential part of care planning. A patient’s personal health record (PHR) contains medical information that can be easily accessed, updated, and used via the Internet to facilitate and improve treatment plans. However, PHRs are not widely adopted. The goal of this study was to explore the challenges and design a roadmap to adoption. Data were collected via semistructured face-to-face interviews and analyzed with a qualitative approach. This study included 35 subjects selected from a sample of CEOs, chief information officers (CIOs), and health informatics project managers (HIPMs); the sample included key executives and project managers in the health information technology business. This study revealed that executives see the PHR as a tool to improve communication and patient care and reduce cost. However, a lack of electronic health record (EHR) systems, poor PHR integration with EHR systems, lack of user experience, and computer and health illiteracy were identified as barriers to PHR adoption. Therefore, adoption was not found to be a top priority for executives. Nevertheless, the PHR ought to be part of the information technology strategy in every hospital. Effective staff training, better patient orientation, and dedicated health informaticians can ensure a smooth and safe journey toward a useful PHR.
Steroid hormones and pregnancy

Abstract Pregnancy is associated with physiological adjustments in order to allow adequate growth and fetal development. In particular, steroids are necessary to maintain in balance numerous functions during gestation. Steroidogenesis in the maternal, placental and fetal compartments and the biological effects of progestins and estrogens that play a pivotal role before and during pregnancy are described. Although it is well-known that androgens are considered as substrate for estrogens biosynthesis, their biosynthesis and functionality in placental and other tissues have been questioned. As compared with healthy pregnancy, steroid hormones levels have been found altered in complicated pregnancies and hormonal treatments have been used is some pathologies. Therefore, the aim of this work was to review the biosynthesis, function and regulation of progestins, androgens and estrogens during gestation. Furthermore, steroid hormones concentrations during healthy and complicated pregnancy as well hormonal therapies for the prevention of miscarriages and preterm deliveries are discussed in the present review.
How does the emotional experience evolve? Feeling generation as evidence accumulation.

How do people answer the question "How do you feel? " In the present work, participants were given 2 tasks in each trial. They first indicated whether a picture made them feel pleasant (or was supposed to be felt as pleasant, in another group), and then made gender decisions regarding faces. Evidence accumulation modeling showed that (a) reporting genuine feeling is qualitatively different from reporting the supposed feeling; (b) reporting one's feeling is remarkably similar to gender decisions; and (c) evidence regarding negative feelings accumulates more quickly than in positive feelings. These results support the assumption that when asked, participants report genuine as opposed to supposed feelings and strengthen the analogy between feeling reports and perceptual decisions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Time dependence of cellular responses to dynamic and complex strain fields

Exposing cells to an unconventional sequence of physical cues can reveal subtleties of cellular sensing and response mechanisms. We investigated the mechanoresponse of cyclically-stretched fibroblasts under a spatially non-uniform strain field which was subjected to repeated changes in stretching directions over 55 hours. A polydimethylsiloxane microfluidic stretcher array optimized for complex staining procedures and imaging was developed to generate biologically relevant strain and strain gradient amplitudes. We demonstrated that cells can successfully reorient themselves repeatedly, as the main cyclical stretching direction is consecutively switched between two perpendicular directions every 11 hours. Importantly, from one reorientation to the next, the extent to which cells reorient themselves perpendicularly to the local strain direction progressively decreases, while their tendency to align perpendicularly to the strain gradient direction tends to increase. We demonstrate that these results are consistent with our finding that cellular responses to strains and strain gradients occur on two distinct time scales, the latter being slower. Overall, our results reveal the absence of major irreversible cellular changes that compromise the ability to sense and reorient to changing strain directions under the conditions of this experiment. On the other hand, we show how the history of strain field dynamics can influence the cellular realignment behavior, due to the interplay of complex time-dependent responses.
Development of motivational interviewing skills in immunization (MISI): a questionnaire to assess MI learning, knowledge and skills for vaccination promotion

ABSTRACT Objective: Vaccine hesitancy is a complex problem. We previously demonstrated that motivational interviewing (MI) could be helpful to enhance parents’ motivation to vaccinate their child. The aim of this study is to develop a new, simple and robust evaluation tool that is suitable for evaluating MI learning of vaccination health professionals. Methods: We designed the Motivational Interviewing Skills in Immunization (MISI), a short written questionnaire to evaluate the MI knowledge and skills of participants in an immunization context. It covers three key areas: knowledge of MI, ability to apply MI-related skills, participant self-confidence in using MI. Questionnaire content and face validity were assessed by MI experts and internal consistency, reliability and effect size were analyzed using a multiple pretest-posttest design. Results: Psychometric measures showed good to excellent internal consistency of the questionnaire for all three areas (Cronbach’s and KR coefficient: 0.70 to 0.88). Test-retest reliability showed good measurement stability (ICC: 0.53). Good sensitivity to change was also obtained (Cohen’s d: 0.80 to 1.66). Conclusion: The MISI questionnaire is the first paper/pencil evaluation method to assess MI training specific to immunization. Psychometric measures showed high reliability. Practice implications: This questionnaire could provide a convenient and inexpensive method to evaluate knowledge and competencies following immunization-specific MI training.
Pediatric Pulmonology

Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany Department of Internal Medicine (Pulmonology), Universities of Giessen and Marburg Lung Center, member of The German Center for Lung Research (DZL), Giessen, Germany Institute of Virology, Philipps University Marburg, Marburg, Germany Division of General Pediatrics and Neonatology, University Children’s Hospital Giessen, Justus Liebig, University, Giessen, Germany
Li and Na Adsorption on Graphene and Graphene Oxide Examined by Density Functional Theory, Quantum Theory of Atoms in Molecules, and Electron Localization Function

Adsorption of Li and Na on pristine and defective graphene and graphene oxide (GO) is studied using density functional theory (DFT) structural and electronic calculations, quantum theory of atoms in molecules (QTAIM), and electron localization function (ELF) analyses. DFT calculations show that Li and Na adsorptions on pristine graphene are not stable at all metal coverages examined here. However, the presence of defects on graphene support stabilizes both Li and Na adsorptions. Increased Li and Na coverages cause metal nucleation and weaken adsorption. Defective graphene is associated with the presence of band gaps and, thus, Li and Na adsorptions can be used to tune these gaps. Electronic calculations show that Li– and Na–graphene interactions are Coulombic: as Li and Na coverages increase, the metal valences partially hybridize with the graphene bands and weaken metal–graphene support interactions. However, for Li adsorption on single vacancy graphene, QTAIM, ELF, and overlap populations calculations show that the Li-C bond has some covalent character. The Li and Na adsorptions on GO are significantly stronger than on graphene and strengthen upon increased coverages. This is due to Li and Na forming bonds with both carbon and oxygen GO atoms. QTAIM and ELF are used to analyze the metal–C and metal–metal bonds (when metal nucleation is present). The Li and Na clusters may contain both covalent and metallic intra metal–metal bonds: This effect is related to the adsorption support selection. ELF bifurcation diagrams show individual metal–C and metal–metal interactions, as Li and Na are adsorbed on graphene and GO, at the metal coverages examined here.
Chronic long‐term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort

Cadmium, due to its estrogen‐like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long‐term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System‐based metric, which included subject's residence‐to‐cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41–0.95, ptrend = 0.043) and for ER−/PR− breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40–0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42–1.07, ptrend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.
Fine‐needle aspiration cytology of metastatic spindle cell follicular thyroid carcinoma: A case report

Follicular thyroid carcinoma, spindle cell variant is extremely rare. The tumor is predominantly composed of spindle cells with a fusiform appearance that are arranged in intersecting fascicles. Fine‐needle aspiration biopsy of this entity has not been previously described. We report a case of a 58‐year‐old woman who presented with metastasis to a left neck lymph node 15 years after the original diagnosis. Fine‐needle aspiration cytology showed numerous bland, spindled to epithelioid cells with thin, elongated, and plump nuclei with finely granular chromatin and inconspicuous nucleoli. The tumor cells had a moderate amount of cytoplasm with occasional elongated cytoplasmic tails. The cells were arranged in irregular aggregates with a fascicular pattern or singly dispersed. The tumor cells demonstrated positive staining for pan‐keratin, PAX8, thyroid transcription factor‐1, and thyroglobulin, which confirmed thyroid primary origin.