Miracle-dz/UniFAR-FTUs huggingface dataset:
STAT3‐mutated hyperimmunoglobulin E syndrome with perianal skin tags and erosions: A case report

Dear Editor, STAT3-mutated hyperimmunoglobulin E syndrome (STAT3 HIES) is a rare primary immunodeficiency disease characterized by elevated serum IgE level and recurrent skin and pulmonary infections [1-3]. A sixteen-year-old girl presented to our clinic with complaints of a longstanding history of pruritic lesions on the scalp, skin folds, and perianal regions. At physical examination, diffuse papuloerosive lesions, reminiscent of Sevestre-Jacquet syphiloid were observed on gluteal, genital, and perianal regions, but closer observation revealed also multiple fibromatous skin tags (Figure 1). The patient had been diagnosed atopic dermatitis from the first years of life and prescribed cycles of oral prednisolone and betamethasone lotion. Chronic steroids selfmedication for the severe itching on the genital areas could explain the severe erosive dermatitis, with eventual superinfections, but past medical history also revealed recurrent episodes of pneumonia and chest pain, alerting on the possibility of a subjacent immunodeficiency. Blood count revealed a slight anemia (hemoglobin of 11.3 mg/dL, mean corpuscular volume of 78.4 fL) and leukocytosis with eosinophilia (total leukocyte count of 14 000/mm; neutrophils 47%, lymphocytes 13%, monocytes 1%, eosinophils 39%; platelet 329 000/mm). Serum IgE was 21.800 g/L (normal range is 0-200 g/L), while serum IgG, IgA, and IgM were within normal limits. Serology for syphilis, herpes simplex virus and HIV infections was negative. In microbiological examinations from skin swabs, candida infections had been excluded. The liver and renal function tests were normal, as well as stool examination and urine analysis. Chest X-ray revealed mediastinal widening because of aortic arch dilation. Total colonoscopy was normal. Skin biopsy from anal skin tags demonstrated a partially ulcerated and markedly acanthotic epidermis, eosinophilic spongiosis, and abundant neutrophils pustulation, but no granuloma formation, neither koilocytosis nor epidermal dysplasia suggestive of human papilloma virus infection. Besides, Gram-positive cocci superinfection was depicted on skin pathology with specific staining. Based on skin and pulmonary chronic involvement, with hyper-IgE and eosinophilia ascertainment the suspect of Job's syndrome was suspected, and genetic consultation requested, which identified a STAT3 mutation. The patient was asked to use dilute bleach baths for about 10 minutes three times a week with partial improvement of the lesions. Prophylactic antibiotics against Staph with cephalexin 20 mg/kg/dose PO twice daily was started for the patient. Of all the etiologies identified for HIES, a heterozygous mutations in STAT3 is implicated the defects in JAK/STAT signaling pathway in the pathogenesis of this disease. [4]. Genetic inheritance is associated with different phenotypic expression. Diagnostic guidelines for STAT3 HIES have recently been proposed [5]. Specific criteria include IgE > 1000 IU/mL and a weighted score of five clinical features: pneumonias, newborn papulopustular eruption, pathologic bone fractures,
Eating behaviors moderate the associations between risk factors in the first 1000 days and adiposity outcomes at 6 years of age.

BACKGROUND Several risk factors in the first 1000 d are linked with increased obesity risk in later childhood. The role of potentially modifiable eating behaviors in this association is unclear. OBJECTIVES This study examined whether the association between cumulated risk factors in the first 1000 d and adiposity at 6 y is moderated by eating behaviors. METHODS Participants were 302 children from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) cohort. Risk factors included maternal prepregnancy and paternal overweight, excessive gestational weight gain, raised fasting plasma glucose during pregnancy, short breastfeeding duration, and early introduction of solid foods. Composite risk scores reflecting the prevalence and the importance of the risk factors present were computed. Adiposity outcomes were child BMI and sum of skinfolds (SSF), and candidate eating behavior moderators were portion size, eating rate, and energy intake during lunch and in an eating in the absence of hunger task. RESULTS Higher composite risk score predicted higher BMI z scores (B = 0.08; 95% CI: 0.04, 0.13) and larger SSF (0.70 mm; 0.23, 1.18 mm), and was associated with larger self-served food portions (5.03 kcal; 0.47, 9.60 kcal), faster eating rates (0.40 g/min; 0.21, 0.59 g/min), and larger lunch intakes (7.05 kcal; 3.37, 10.74 kcal). Importantly, the association between composite risk score and adiposity was moderated by eating behaviors. The composite risk score was unrelated to SSF in children who selected smaller food portions, ate slower, and consumed less energy, but was positively associated with SSF among children who selected larger food portions, ate faster, and consumed more energy (eating behavior × risk score interactions: P < 0.05). CONCLUSIONS The association between risk factors in the first 1000 d and adiposity at 6 y varies by eating behaviors, highlighting modifiable behavioral targets for interventions.This trial was registered at clinicaltrials.gov as NCT01174875.
Dynamic Navigation in Dental Implantology: The Influence of Surgical Experience on Implant Placement Accuracy and Operating Time. An in Vitro Study

Aim: the aim of this in vitro study was to test whether the implant placement accuracy and the operating time can be influenced by the operator’s experience. Materials and methods: sixteen models underwent a (Cone Beam Computer Tomography) CBCT and implant positioning was digitally planned on this. The models were randomly assigned to four operators with different levels of surgical experience. One hundred and twelve implant sites were drilled using a dynamic navigation system and operating times were measured. Based on postoperative CBCTs, dental implants were virtually inserted and superimposed over the planned ones. Two-dimensional and 3D deviations between planned and virtually inserted implants were measured at the entry point and at the apical point. Angular and vertical errors were also calculated. Results: considering coronal and apical 3D deviations, no statistically significant differences were found between the four operators (p = 0.27; p = 0.06). Some vectorial components of the deviation at the apical point and the angular errors of some operators differed from each other. Conclusions: within the limitations of this study, dynamic navigation can be considered a reliable technique both for experienced and novice clinicians.
Emerging roles of cytoskeletal proteins in regulating gene expression and genome organization during differentiation

ABSTRACT In the eukaryotic cell nucleus, cytoskeletal proteins are emerging as essential players in nuclear function. In particular, actin regulates chromatin as part of ATP-dependent chromatin remodeling complexes, it modulates transcription and it is incorporated into nascent ribonucleoprotein complexes, accompanying them from the site of transcription to polyribosomes. The nuclear actin pool is undistinguishable from the cytoplasmic one in terms of its ability to undergo polymerization and it has also been implicated in the dynamics of chromatin, regulating heterochromatin segregation at the nuclear lamina and maintaining heterochromatin levels in the nuclear interiors. One of the next frontiers is, therefore, to determine a possible involvement of nuclear actin in the functional architecture of the cell nucleus by regulating the hierarchical organization of chromatin and, thus, genome organization. Here, we discuss the repertoire of these potential actin functions and how they are likely to play a role in the context of cellular differentiation.
Maternal glycemia during pregnancy and offspring abdominal adiposity measured by MRI in the neonatal period and preschool years: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective mother-offspring birth cohort study.

BACKGROUND Gestational diabetes is associated with unfavorable body fat distribution in offspring. However, less is known about the effects across the range of maternal gestational glycemia on offspring abdominal adiposity (AA) in infancy and early childhood. OBJECTIVES This study determined the association between gestational glycemia and offspring AA measured by MRI in the neonatal period and during the preschool years. METHODS Participants were mother-offspring pairs from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) prospective cohort study. Children who underwent MRI within 2 wk postdelivery (n = 305) and/or at preschool age, 4.5 y (n = 273), and whose mothers had a 2-h 75-g oral-glucose-tolerance test (OGTT) at 26-28 weeks of gestation were included. AA measured by adipose tissue compartment volumes-abdominal superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue-was quantified from MRI images. RESULTS Adjusting for potential confounders including maternal prepregnancy BMI, each 1-mmol/L increase in maternal fasting glucose was associated with higher SD scores for sSAT (0.66; 95% CI: 0.45, 0.86), dSAT (0.65; 95% CI: 0.44, 0.87), and IAT (0.64; 95% CI: 0.42, 0.86) in neonates. Similarly, each 1-mmol/L increase in 2-h OGTT glucose was associated with higher neonatal sSAT (0.11; 95% CI: 0.03, 0.19) and dSAT (0.09; 95% CI: 0.00, 0.17). These associations were stronger in female neonates but only persisted in girls between fasting glucose, and sSAT and dSAT at 4.5 y. CONCLUSIONS A positive association between maternal glycemia and neonatal AA was observed across the whole range of maternal mid-gestation glucose concentrations. These findings may lend further support to efforts toward optimizing maternal hyperglycemia during pregnancy. The study also provides suggestive evidence on sex differences in the impact of maternal glycemia, which merits further confirmation in other studies.This trial was registered at clinicaltrials.gov as NCT01174875.
Sex differences in the structure and function of rat middle cerebral arteries

Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause. NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).
Does Playing Video Games Increase Emotional Creativity?

Emotional creativity (EC), which constitutes a main aspect of the general creativity concept, is often shown to be substantially related to positive emotional experiences, effective motivation, and innovation at the workplace as well as at school. However, little is known about the relationship between emotional creativity and the time people tend to spend playing video games. Nowadays, video games and virtual reality have become an important aspect of public health and psychological research. They constitute a key element of popular culture and generate considerable economic profit as part of the public entertainment industry. Our study is based on the results of an emotional creativity inventory (ECI) survey that was administered at a snowball and convenient sample of 453 respondents (aged 18–60 years, M ± SD: 23.68 ± 6.36; 66.40% women, 20.00% with higher education) from the Czech Republic who were questioned about their habits and the time they devote to playing video games. The sample country was selected as one with a long tradition of homebrew video gaming going back to the 1980s. We employed a set of multinomial regression analyses, which revealed that more time devoted to playing video games is associated with lower emotional creativity, in general, as well as with lower novelty, preparedness, and effectiveness components of emotional creativity. The negative association above was less pronounced for women than for men. Moreover, in a sample containing only women, a longer time devoted to playing video games was associated with the higher novelty component of emotional creativity (the associations with the other two components were not statistically significant for women only). Our findings might considerably contribute to the study of the general overall long-term effect of video games and the use of digital technologies in general on public health.
Therapeutic potential of microRNA in tendon injuries.

INTRODUCTION The regulatory role of microRNA (miRNA) in several conditions has been studied, but their function in tendon healing remains elusive. This review summarizes how miRNAs are related to the pathogenesis of tendon injuries and highlights their clinical potential, focusing on the issues related to their delivery for clinical purposes. SOURCES OF DATA We searched multiple databases to perform a systematic review on miRNA in relation to tendon injuries. We included in the present work a total of 15 articles. AREAS OF AGREEMENT The mechanism of repair of tendon injuries is probably mediated by resident tenocytes. These maintain a fine equilibrium between anabolic and catabolic events of the extracellular matrix. Specific miRNAs regulate cytokine expression and orchestrate proliferation and differentiation of stromal cell lines involved in the composition of the extracellular matrix. AREAS OF CONTROVERSY The lack of effective delivery systems poses serious obstacles to the clinical translation of these basic science findings. GROWING POINT In vivo studies should be planned to better explore the relationship between miRNA and tendon injuries and evaluate the most suitable delivery system for these molecules. AREAS TIMELY FOR DEVELOPING RESEARCH Investigations ex vivo suggest therapeutic opportunities of miRNA for the management of tendon injuries. Given the poor pharmacokinetic properties of miRNAs, these must be delivered by an adequate adjuvant transport system.
The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programs

In this study, Ignatova et al. performed a systematic screen to uncover new RNA methyltransferases, and demonstrate that the methyltransferase-like 5 (METTL5) protein catalyzes m6A in 18S rRNA at position A1832. Their biochemical, molecular, and in vivo characterization of METTL5 highlights the importance of m6A in rRNA in stemness, differentiation, development, and diseases.
Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Nutrient oversupply and mitochondrial dysfunction play central roles in nonalcoholic fatty liver disease (NAFLD). The mitochondria are the major sites of β-oxidation, a catabolic process by which fatty acids are broken down. The mitochondrial quality control (MQC) system includes mitochondrial fission, fusion, mitophagy and mitochondrial redox regulation, and is essential for the maintenance of the functionality and structural integrity of the mitochondria. Excessive and uncontrolled production of reactive oxygen species (ROS) in the mitochondria damages mitochondrial components, including membranes, proteins and mitochondrial DNA (mtDNA), and triggers the mitochondrial pathway of apoptosis. The functionality of some damaged mitochondria can be restored by fusion with normally functioning mitochondria, but when severely damaged, mitochondria are segregated from the remaining functional mitochondrial network through fission and are eventually degraded via mitochondrial autophagy, also called as mitophagy. In this review, we describe the functions and mechanisms of mitochondrial fission, fusion, oxidative stress and mitophagy in the development and progression of NAFLD.
Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex

Caught in the act Proton-coupled electron transfer (PCET) is an important process for moving electrons through proteins and requires precise positioning of suitable proton and electron carriers. Kang et al. determined a cryo–electron microscopy structure of the active complex formed by ribonucleotide reductase that allows for PCET between two protein subunits over a total distance of ∼35 angstroms. Several interventions that stabilized the radical en route also stabilized the complex and allowed for visualization of the interface between the two subunits and the full network of residues that permit PCET. Science, this issue p. 424 A structure of the long-range radical transfer pathway within a ribonucleotide reductase is reported. Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs, this process involves a long-range radical transfer between two subunits, α and β. Because of the transient subunit association, an atomic resolution structure of an active α2β2 RNR complex has been elusive. We used a doubly substituted β2, E52Q/(2,3,5)-trifluorotyrosine122-β2, to trap wild-type α2 in a long-lived α2β2 complex. We report the structure of this complex by means of cryo–electron microscopy to 3.6-angstrom resolution, allowing for structural visualization of a 32-angstrom-long radical transfer pathway that affords RNR activity.
Perinatal Risk Factors Influencing Neonatal Hypoxic Ischemic Encephalopathy in Southern China: A Case–Control Study

Abstract Objective In this study, our objective was to explore the relevant influencing factors of neonatal hypoxic-ischemic encephalopathy (HIE) in Southern China and provide scientific basis for improving the quality of life for neonates. Study Design A retrospective analysis of 306 cases with HIE neonates who were admitted during April 2015 to October 2017 was conducted. A total of 306 non-HIE patients admitted to the same hospital during the same period were also included as controls. The basic clinical characteristics were analyzed, and the risk factors for HIE were assessed by logistic regression analysis. Results Univariate analysis showed that the differences in medicals during pregnancy, placenta previa, fetal distress during labor, cesarean section, amniotic fluid contamination, abnormal labor stage, and Apgar showed significantly different in the case group and the control group (p < 0.05). The multivariate logistic regression analysis revealed that the placenta previa, medicals during pregnancy, fetal distress, abnormal labor stage, Apgar's score, amniotic fluid contamination, and cesarean section were independent risk factors for HIE. Conclusion The placenta previa, medicals during pregnancy, fetal distress, and abnormal labor stage can increase the risk of HIE. Early detection, early diagnosis, and treatment might make great achievement in improving the life quality of HIE neonates.
Feasible assessment of recovery and cardiovascular health: accuracy of nocturnal HR and HRV assessed via ring PPG in comparison to medical grade ECG

Objective: To validate the accuracy of the Oura ring in the quantification of resting heart rate (HR) and heart rate variability (HRV). Background: Wearable devices have become comfortable, lightweight, and technologically advanced for assessing health behavior. As an example, the novel Oura ring integrates daily physical activity and nocturnal cardiovascular measurements. Ring users can follow their autonomic nervous system responses to their daily behavior based on nightly changes in HR and HRV, and adjust their behavior accordingly after self-reflection. As wearable photoplethysmogram (PPG) can be disrupted by several confounding influences, it is crucial to demonstrate the accuracy of ring measurements. Approach: Nocturnal HR and HRV were assessed in 49 adults with simultaneous measurements from the Oura ring and the gold standard ECG measurement. Female and male participants with a wide age range (15–72 years) and physical activity status were included. Regression analysis between ECG and the ring outcomes was performed. Main results: Very high agreement between the ring and ECG was observed for nightly average HR and HRV (r2 = 0.996 and 0.980, respectively) with a mean bias of −0.63 bpm and −1.2 ms. High agreement was also observed across 5 min segments within individual nights in (r2 = 0.869 ± 0.098 and 0.765 ± 0.178 in HR and HRV, respectively). Significance: Present findings indicate high validity of the Oura ring in the assessment of nocturnal HR and HRV in healthy adults. The results show the utility of this miniaturised device as a lifestyle management tool in long-term settings. High quality PPG signal results prompt future studies utilizing ring PPG towards clinically relevant health outcomes.
Interoceptive accuracy and its impact on neuronal responses to olfactory stimulation in the insular cortex

The insular cortex plays a key role in the integration of multimodal information and in interoceptive and exteroceptive processing. For instance, neurons in the central dorsal insula that are active during interoceptive tasks, also show an adaptation to gustatory stimulation. We tested the link between interoception and exteroception for the olfactory system (i.e., the second domain of chemosensation). In a sample of 31 participants, olfactory function was assessed in a two dimensional approach while the Heartbeat Perception Task served as a measurement for cardiac interoceptive accuracy. Subsequent fMRI sessions were performed on a 3‐Tesla MR scanner containing 12–15 olfactory stimulation trials with a mildly pleasant food‐related odor (coffee). Persons scoring high in the cardiac interoceptive accuracy task presented stronger smelling abilities as well as enhanced BOLD responses following olfactory stimulation. The olfactory stimulation triggered enhanced insular activation patterns in the central dorsal insular cortex. Consistent with prior findings on the coherence of gustatory and interoceptive processing in the central dorsal insula, these results base the insula as a common region for the integration of interoception and exteroception. We propose an explanatory model of how exteroception triggers the integration of intero‐ and exteroceptive sensations in the central dorsal insular cortex.