Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypothalamic injury patterns after resection of craniopharyngiomas and correlation to tumor origin: A study based on endoscopic observation

The precise understanding of hypothalamic injury (HI) patterns and their relationship with different craniopharyngioma (CP) classifications remains poorly addressed. Here, four HI patterns after CP resection based on endoscopic observation were introduced. A total of 131 CP cases treated with endoscopic endonasal approach (EEA) were reviewed retrospectively and divided into four HI patterns: no‐HI, mild‐HI, unilateral‐HI and bilateral‐HI, according to intraoperative findings. The outcomes were evaluated and compared between groups in terms of weight gain, endocrine status, electrolyte disturbance and neuropsychological function before and after surgery. A systematic correlation was found between CP origin and subsequent HI patterns. The majority of intrasellar and suprasellar stalk origins lead to a no‐HI pattern, the central‐type CP mainly develops a mild or bilateral HI pattern, and the majority of tumors with hypothalamic stalk origins result in unilateral HI and sometimes bilateral HI patterns. The proportion of tumors with a maximum diameter >3 cm in the no‐HI group was higher than that in the mild‐HI group, BMI and quality of life in the no‐HI group showed better results than those in the other groups. The incidence of new‐onset diabetes insipidus in the bilateral‐HI group was significantly higher than that in the other groups. Memory difficulty was observed mainly in the unilateral‐HI and bilateral‐HI groups. However, the outcomes of electrolyte disturbance, sleep, and cognitive disorder in the unilateral‐HI group were significantly better than those in the bilateral‐HI group. This study suggests the possibility of using pre‐ and intraoperative observation of CP origin to predict four HI patterns and even subsequent outcomes after tumor removal.
Could early tweet counts predict later citation counts? A gender study in Life Sciences and Biomedicine (2014–2016)

In this study, it was investigated whether early tweets counts could differentially benefit female and male (first, last) authors in terms of the later citation counts received. The data for this study comprised 47,961 articles in the research area of Life Sciences & Biomedicine from 2014–2016, retrieved from Web of Science’s Medline. For each article, the number of received citations per year was downloaded from WOS, while the number of received tweets per year was obtained from PlumX. Using the hurdle regression model, I compared the number of received citations by female and male (first, last) authored papers and then I investigated whether early tweet counts could predict the later citation counts received by female and male (first, last) authored papers. In the regression models, I controlled for several important factors that were investigated in previous research in relation to citation counts, gender or Altmetrics. These included journal impact (SNIP), number of authors, open access, research funding, topic of an article, international collaboration, lay summary, F1000 Score and mega journal. The findings showed that the percentage of papers with male authors in first or last authorship positions was higher than that for female authors. However, female first and last-authored papers had a small but significant citation advantage of 4.7% and 5.5% compared to male-authored papers. The findings also showed that irrespective of whether the factors were included in regression models or not, early tweet counts had a weak positive and significant association with the later citations counts (3.3%) and the probability of a paper being cited (21.1%). Regarding gender, the findings showed that when all variables were controlled, female (first, last) authored papers had a small citation advantage of 3.7% and 4.2% in comparison to the male authored papers for the same number of tweets.
Mechanism of ligand recognition by human ACE2 receptor

Angiotensin converting enzyme 2 (ACE2) plays a key role in renin-angiotensin system regulation and amino acid homeostasis. Human ACE2 acts as the receptor for severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2. ACE2 is also widely expressed in epithelial cells of lungs, heart, kidney and pancreas. It is considered an important drug target for treating SARS-CoV-2, as well as pulmonary diseases, heart failure, hypertension, renal diseases and diabetes. Despite the critical importance, the mechanism of ligand binding to the human ACE2 receptor remains unknown. Here, we address this challenge through all-atom simulations using a novel ligand Gaussian accelerated molecular dynamics (LiGaMD) method. Microsecond LiGaMD simulations have successfully captured both binding and unbinding of the MLN-4760 inhibitor in the ACE2 receptor. In the ligand unbound state, the ACE2 receptor samples distinct Open, Partially Open and Closed conformations. Ligand binding biases the receptor conformational ensemble towards the Closed state. The LiGaMD simulations thus suggest a conformational selection mechanism for ligand recognition by the ACE2 receptor. Our simulation findings are expected to facilitate rational drug design of ACE2 against coronaviruses and other related human diseases.
The performance of the alarmin HMGB1 in pediatric diseases: From lab to clinic

The ubiquitously expressed nonhistone nuclear protein high‐mobility group box protein 1 (HMGB1) has different functions related to posttranslational modifications and cellular localization. In the nucleus, HMGB1 modulates gene transcription, replication and DNA repair as well as determines chromosomal architecture. When the post‐transcriptional modified HMGB1 is released into the extracellular space, it triggers several physiological and pathological responses and initiates innate immunity through interacting with its reciprocal receptors (i.e., TLR4/2 and RAGE). The effect of HMGB1‐mediated inflammatory activation on different systems has received increasing attention. HMGB1 is now considered to be an alarmin and participates in multiple inflammation‐related diseases. In addition, HMGB1 also affects the occurrence and progression of tumors. However, most studies involving HMGB1 have been focused on adults or mature animals. Due to differences in disease characteristics between children and adults, it is necessary to clarify the role of HMGB1 in pediatric diseases.
Parental practices, body dissatisfaction and weight control practices in female adolescents from public schools in southern Brazil

Abstract The objective was to verify the association between body dissatisfaction (BD) – constituted by the desire to lose weight – with family and personal aspects related to the shape of the body and weight control practices in female adolescents. A cross-sectional, observational epidemiological study with adolescents aged 12–19 years, enrolled in classes of the 8th and 9th years of public schools belonging to the urban area of the city of Caxias do Sul/Rio Grande do Sul, Brazil, was conducted. A self-applicable questionnaire was used. BD was assessed using a silhouette scale. Multivariate regression was performed using Poisson regression with robust variation, hierarchically using a pre-established conceptual model, using the prevalence ratio (PR) adjusted with 95 % CI as a measure of effect. A significance level of 5 % (P ≤ 0·05) was considered. Among the 685 female students, 77·2 % had BD. The father’s incentive to diet sometimes (PR 1·19; 95 % CI 1·07, 1·32; P ≤ 0·001) and always (PR 1·15; 95 % CI 1·03, 1·28; P ≤ 0·001), trying to lose weight (PR 1·63; 95 % CI 1·33, 1·99; P ≤ 0·001), dieting five times or more (PR 1·22; 95 % CI 1·09, 1·36; P ≤ 0·001) and skipping meals less than once a week (PR 1·16; 95 % CI 1·04, 1·29; P = 0·026) increased the chances of having BD. In conclusion, among the investigated parents’ behaviours, only the father’s incentive to go on a diet was associated with BD. Adolescent weight control practices increased the chances of having BD. Thus, it facilitates the identification of this condition at an early stage, enabling adequate treatment and prevention of health complications.
Age Related Changes in Motor Function (II). Decline in Motor Performance Outcomes

Abstract Age-related impairments in motor performance are caused by a deterioration in mechanical and neuromuscular functions, which have been investigated from the macro-level of muscle-tendon unit to the micro-level of the single muscle fiber. When compared to the healthy young skeletal muscle, aged skeletal muscle is: (1) weaker, slower and less powerful during the performance of voluntary contractions; (2) less steady during the performance of isometric contractions, particularly at low levels of force; and (3) less susceptible to fatigue during the performance of sustained isometric contractions, but more susceptible to fatigue during the performance of high-velocity dynamic contractions. These impairments have been discussed to be mainly the result of: a) loss of muscle mass and selective atrophy of type II muscle fibers; b) altered tendon mechanical properties (decreased tendon stiffness); c) reduced number and altered function of motor units; d) slower muscle fiber shortening velocity; e) increased oscillation in common synaptic input to motor neurons; and f) altered properties and activity of sarcoplasmic reticulum. In this second part of a two-part review we have detailed the age-related impairments in motor performance with a reference to the most important mechanical and neuromuscular contributing factors.
Patient preferences for elagolix and leuprolide for treating endometriosis-related pain in the United States

ABSTRACT Introduction We evaluated elagolix and leuprolide from the patient’s perspective for the treatment of endometriosis-related pain. Area covered Preference weights from a published discrete choice experiment were used to evaluate preferences for treatment profiles simulating elagolix (150 mg/day and 200 mg/twice-daily dosages) and leuprolide for the treatment of moderate to severe endometriosis-related pain. Sensitivity analyses were conducted by varying the range of risk for pregnancy-related problems, moderate to severe hot flashes, and bone fracture across scenarios. Expert opinion The 200 mg twice daily dosage of elagolix is more likely to be preferred over leuprolide by patients with moderate to severe endometriosis-related pain in all scenarios explored in the evaluation and sensitivity analyses. The probability that an average respondent would select a treatment was sensitive to increases in risk of moderate to severe hot flashes for leuprolide and possible variations in the risk of pregnancy-related problems for both treatments but was not influenced by an increased risk of bone fracture. Conclusions Patients’ preferences for treatment of endometriosis-related pain should be evaluated using the benefits and risks of each pharmacological option. Respondents were more likely to prefer the treatment profile similar to 200 mg twice daily elagolix over that of leuprolide in all scenarios.
Non-Invasive Measurement of Drug and 2-HG Signals Using 19F and 1H MR Spectroscopy in Brain Tumors Treated with the Mutant IDH1 Inhibitor BAY1436032

Simple Summary Targeted therapies are of growing interest to physicians in cancer treatment. These drugs target specific genes and proteins involved in the growth and survival of cancer cells. Brain tumor therapy is complicated by the fact that not all drugs can penetrate the blood brain barrier and reach their target. We explored the non-invasive method, Magnetic Resonance Spectroscopy, for monitoring drug penetration and its effects in live animals bearing brain tumors. We were able to show the presence of the investigated drug in mouse brains and its on-target activity. Abstract Background: BAY1436032 is a fluorine-containing inhibitor of the R132X-mutant isocitrate dehydrogenase (mIDH1). It inhibits the mIDH1-mediated production of 2-hydroxyglutarate (2-HG) in glioma cells. We investigated brain penetration of BAY1436032 and its effects using 1H/19F-Magnetic Resonance Spectroscopy (MRS). Methods: 19F-Nuclear Magnetic Resonance (NMR) Spectroscopy was conducted on serum samples from patients treated with BAY1436032 (NCT02746081 trial) in order to analyze 19F spectroscopic signal patterns and concentration-time dynamics of protein-bound inhibitor to facilitate their identification in vivo MRS experiments. Hereafter, 30 mice were implanted with three glioma cell lines (LNT-229, LNT-229 IDH1-R132H, GL261). Mice bearing the IDH-mutated glioma cells received 5 days of treatment with BAY1436032 between baseline and follow-up 1H/19F-MRS scan. All other animals underwent a single scan after BAY1436032 administration. Mouse brains were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Results: Evaluation of 1H-MRS data showed a decrease in 2-HG/total creatinine (tCr) ratios from the baseline to post-treatment scans in the mIDH1 murine model. Whole brain concentration of BAY1436032, as determined by 19F-MRS, was similar to total brain tissue concentration determined by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), with a signal loss due to protein binding. Intratumoral drug concentration, as determined by LC-MS/MS, was not statistically different in models with or without R132X-mutant IDH1 expression. Conclusions: Non-invasive monitoring of mIDH1 inhibition by BAY1436032 in mIDH1 gliomas is feasible.
Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series

Abstract Context Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. Methods We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. Results Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566*) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. Conclusions Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.
Biodegradability and biodegradation kinetics of creosote compounds in a biofilm in a fractured clay flow model

If contaminated sites are situated in moraine clay areas, there may be a risk that the leachate is penetrating fractures to the underlying groundwater and thereby compromising the water quality. This study addresses the biodegradability and biodegradation kinetics of creosote compounds in a model fracture system. Eleven compounds typical of the water-soluble fraction of creosote were added to a mineral medium, each in a concentration of 0.5–1 mg/L: phenol, o-cresol, 2,4- and 3,5-dimethylphenol, naphthalene, 1-methylnaphthalene, 2,3-dimethylnaphthalene, indole, quinoline, benzothiophene, and dibenzofuran. The total concentration was around 7 mg/L. All the compounds were removed biologically by a biofilm in the model fracture under aerobic conditions. The compounds could be divided into readily biodegradable, moderately biodegradable and partly biodegradable compounds. The first order surface removal rates, k 1,a , were in the range 0.02–0.1 m/d.
Analysis of improved nutritional composition of bee pollen (
 Brassica campestris
 L.) after different fermentation treatments

Microbial fermentation as an excellent food processing technology has been used for improving the flavour and nutritional feature of food material. In this study, we compared the differences in the nutrient profile of bee pollen (rape bee pollen, Brassica campestris L., BP) fermented with different species of microbes, such as lactic acid bacteria (LAB), yeast, and the two mixed. Based on the nutritional components and multivariate statistical analysis, yeast fermentation has more advantage for BP than fermentation with LAB or mixed microbes. The yeast‐fermented BP has an 83.5% reduction in fructose and 87.4% reduction in glucose, while phenolic compounds, oligopeptides and fatty acids were increased by 9.3%, 68.8% and 18.2%, respectively, compared with the BP without fermentation. The contents of riboflavin, nicotinic acid, nicotinamide and free amino acids in the pollen fermented by yeast were 2.4, 39.6, 4.6 and 4.8 times higher than those in raw BP, respectively. Additionally, in the fermentation process, wall‐breaking pollen showed more advantages in the transformation of nutrients, free amino acid increased by 11% at least, more low molecular weight peptides produced and nicotinic acid and nicotinamide increased by 7% at least, compared with fermented BP. Taken together, these results showed that BP with yeast fermentation has great potential in obtaining high available nutritional products.
Characterization of E-cigarette coil temperature and toxic metal analysis by infrared temperature sensing and scanning electron microscopy – energy-dispersive X-ray

Abstract Introduction Electronic cigarettes (e-cigarettes) have rapidly evolved since their introduction to the U.S. market. The rebuildable atomizer (RBA) offers user-driven modification to the heating element (coil) and wicking systems. Different coil materials can be chosen based on user needs and preferences. However, the heating element of an e-cigarette is believed to be one-source for toxic metal exposure. Methods E-cigarette coils from Kanthal and nichrome wires were constructed in a contact and non-contact configuration and heated at four voltages. The maximum temperatures of the coils were measured by infrared temperature sensing when dry and when saturated with 100% vegetable glycerin or 100% propylene glycol. The metal composition of each coil was analyzed with Scanning Electron Microscopy-Energy-Dispersive X-Ray (SEM-EDX) when new, and subsequently after 1, 50, and 150 heat cycles when dry. Results The coils reached temperatures above 1000 °C when dry, but were below 300 °C in both liquid-saturated mediums. Metal analysis showed a decrease of 9–19% chromium and 39–58% iron in Kanthal wire and a decrease of 12–14% iron and 39–43% nickel in nichrome wire after 150 heat cycles. Significant metal loss was observed after one heat cycle for both coil alloys and configurations. Conclusions The loss of metals from these heat cycles further suggests that the metals from the coils are potentially entering the aerosol of the e-cigarette, which can be inhaled by the user.
Contrasting patterns of naturalized plant richness in the Americas: Numbers are higher in the North but expected to rise sharply in the South

With increasing availability of plant distribution data, the information about global plant diversity is improving rapidly. Recently, Ulloa Ulloa et al. (2017) presented the first comprehensive overview of the native vascular flora of the Americas, yielding a total count of 124,993 native species. Of these, 51,241 occur in North America and 82,052 in South America. By combining these data with the information in the Global Naturalized Alien Flora (GloNAF) database of naturalized alien floras, we point out that for a complete picture of the regional and continental plant richness, the naturalized alien species need to be considered. Ignoring this novel component of regional floras can lead to an inaccurate picture of overall change in biodiversity in the Anthropocene. We show that North and South America might face contrasting challenges in terms of potential threats to biodiversity posed by alien plant species, because of the different past and present dynamics of invasions and predictions of future development. In total, there are 7,042 naturalized alien plants occurring in the Americas, with 6,122 recorded in North America and 2,677 in South America; if only introductions from other continents are considered additions to the native continental flora make up 6.9 and 1.4 %, respectively. Nevertheless, predictions of naturalized plant trajectories based on global trade dynamics and climate change suggest that considerable increases in naturalized plant numbers are expected in the next 20 years for emerging South American economies, which could reverse the present state.
Gating Patterns to Proprioceptive Stimulation in Various Cortical Areas: An MEG Study in Children and Adults using Spatial ICA

Abstract Proprioceptive paired-stimulus paradigm was used for 30 children (10–17 years) and 21 adult (25–45 years) volunteers in magnetoencephalography (MEG). Their right index finger was moved twice with 500-ms interval every 4 ± 25 s (repeated 100 times) using a pneumatic-movement actuator. Spatial-independent component analysis (ICA) was applied to identify stimulus-related components from MEG cortical responses. Clustering was used to identify spatiotemporally consistent components across subjects. We found a consistent primary response in the primary somatosensory (SI) cortex with similar gating ratios of 0.72 and 0.69 for the children and adults, respectively. Secondary responses with similar transient gating behavior were centered bilaterally in proximity of the lateral sulcus. Delayed and prolonged responses with strong gating were found in the frontal and parietal cortices possibly corresponding to larger processing network of somatosensory afference. No significant correlation between age and gating ratio was found. We confirmed that cortical gating to proprioceptive stimuli is comparable to other somatosensory and auditory domains, and between children and adults. Gating occurred broadly beyond SI cortex. Spatial ICA revealed several consistent response patterns in various cortical regions which would have been challenging to detect with more commonly applied equivalent current dipole or distributed source estimates.