Miracle-dz/UniFAR-FTUs huggingface dataset:
Continuous Multidisciplinary Care for Patients With Orofacial Clefts—Should the Follow-up Interval Depend on the Cleft Entity?

Objective The multidisciplinary follow-up of patients with cleft lip with or without palate (CL/P) is organized differently in specialized centers worldwide. The aim of this study was to evaluate the different treatment needs of patients with different manifestations of CL/P and to potentially adapt the frequency and timing of checkup examinations accordingly. Design We retrospectively analyzed the data of all patients attending the CL/P consultation hour at a tertiary care center between June 2005 and August 2020 (n = 1126). We defined 3 groups of cleft entities: (1) isolated clefts of lip or lip and alveolus (CL/A), (2) isolated clefts of the hard and/or soft palate, and (3) complete clefts of lip, alveolus and palate (CLP). Timing and type of therapy recommendations given by the specialists of different disciplines were analyzed for statistical differences. Results Patients with CLP made up the largest group (n = 537), followed by patients with cleft of the soft palate (n = 371) and CL ± A (n = 218). There were significant differences between the groups with regard to type and frequency of treatment recommendations. A therapy was recommended in a high proportion of examinations in all groups at all ages. Conclusion Although there are differences between cleft entities, the treatment need of patients with orofacial clefts is generally high during the growth period. Patients with CL/A showed a similarly high treatment demand and should be monitored closely. A close follow-up for patients with diagnosis of CL/P is crucial and measures should be taken to increase participation in follow-up appointments.
Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer

Purpose: In metastatic castration-resistant prostate cancer (mCRPC) low serum androgens prior to starting abiraterone acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on androgens in castration-resistant prostate cancer (CRPC) metastases and associations of intratumoral androgens with response. Experimental Design: We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2,000 mg at progression. Results: Twenty-nine of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (P < 0.001). Serum and tissue dehydroepiandrosterone sulfate (DHEAS) remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pretreatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on-therapy) associated with rapid progression (20 vs. 48 weeks, P = 0.0018; 20 vs. 52 weeks, P = 0.0003; 14 vs. 40 weeks, P = 0.0001; 20 vs. 56 weeks, P = 0.02, respectively). One of 16 men escalating to 2,000 mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild-type (WT) PTEN status associated with longer response (61 vs. 33 weeks, P = 0.02). Conclusions: Low-circulating adrenal androgen levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. Patients with CRPC with higher serum DHEAS levels may benefit from dual androgen receptor (AR)-pathway inhibition, while those in the lowest quartile may require combinations with non–AR-directed therapy.
Characterization of the association between cigarette smoking intensity and urinary concentrations of 2-hydroxyethyl mercapturic acid among exclusive cigarette smokers in the National Health and Nutrition Examination Survey (NHANES) 2011–2016

Abstract Background 2-Hydroxyethyl mercapturic acid (2HEMA, N-acetyl-S-(2-hydroxyethyl)-L-cysteine) is a urinary metabolite of several volatile organic compounds including acrylonitrile and ethylene oxide, which are found in cigarette smoke. Methods We measured 2HEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey (2011–2016) from eligible participants aged >12 years (N = 7,416). We developed two multiple linear regression models to characterize the association between cigarette smoking and 2HEMA concentrations wherein the dependent variable was 2HEMA concentrations among participants who exclusively smoked cigarettes at the time of specimen collection and the independent variables included sex, age, race/ethnicity, creatinine, diet, and either cigarettes smoked per day (CPD) or serum cotinine. Results We detected 2HEMA in 85% of samples tested among exclusive cigarette smokers, and only 40% of specimens from non-smokers. When compared to exclusive cigarette smokers who smoked 1–9 CPD, smoking 10–19 CPD was associated with 36% higher 2HEMA (p < 0.0001) and smoking >19 CPD was associated with 61% higher 2HEMA (p < 0.0001). Additionally, 2HEMA was positively associated with serum cotinine. Conclusions This study demonstrates that cigarette smoking intensity is associated with higher urinary 2HEMA concentrations and is likely a major source of acrylonitrile and/or ethylene oxide exposure.
Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer

Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. Experimental Design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38). Results: MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC–targeted immunotherapy. Conclusions: This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
Description of Total Population Hospital Admissions for Treacher Collins Syndrome in Australia

Objective To describe patterns and demographic characteristics of total-population hospital admissions with a diagnosis of Treacher Collins syndrome (TCS) in Australia. Data Source Population summary data for inpatient hospitals admissions (public and private) with a principal diagnosis of TCS (ICD10-AM-Q87.04) were obtained from the Australian Institute of Health and Welfare National Hospital Morbidity Database for a 11-year period (2002-2013). Main Outcome Measures The primary outcome was hospital separation rate (HSR), calculated by dividing the number of hospital separations by estimated resident population per year. Trends in HSR s adjusted for age and sex were investigated by negative binomial regression presented as annual percent change and the association of rates with age and sex was expressed as incidence rate ratio. Results In 244 admissions identified, we observed an increase of 4.55% (95% confidence interval [CI] −1.78, 11.29) in HSR's over the 11-year period. Rates were higher during infancy (1.87 [95% CI 1.42, 2.42]), declining markedly with increasing age. The average length of hospital stay was 6.09 days (95% CI 5.78, 6.40) per episode, but longer for females and infants. Conclusions Findings indicate an increase in hospitalization rates, especially among infants and females which potentially relates to early airway intervention procedures possibly influenced by sex specific-disease severity and phenotypic variability of TCS. Awareness of the TCS phenotype and improved access to genetic testing may support more personalized and efficient care. Total-population administrative data offers a potential to better understand the health burden of rare craniofacial diseases.
Motivational Salience Guides Attention to Valuable and Threatening Stimuli: Evidence from Behavior and Functional Magnetic Resonance Imaging

Abstract Rewarding and aversive outcomes have opposing effects on behavior, facilitating approach and avoidance, although we need to accurately anticipate each type of outcome to behave effectively. Attention is biased toward stimuli that have been learned to predict either type of outcome, and it remains an open question whether such orienting is driven by separate systems for value- and threat-based orienting or whether there exists a common underlying mechanism of attentional control driven by motivational salience. Here, we provide a direct comparison of the neural correlates of value- and threat-based attentional capture after associative learning. Across multiple measures of behavior and brain activation, our findings overwhelmingly support a motivational salience account of the control of attention. We conclude that there exists a core mechanism of experience-dependent attentional control driven by motivational salience and that prior characterizations of attention as being value driven or supporting threat monitoring need to be revisited.
A neural substrate of compulsive alcohol use

Inhibitory PKCδ-expressing neurons in the central nucleus of the amygdala promote compulsive alcohol use in rats. Alcohol intake remains controlled in a majority of users but becomes “compulsive,” i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.
Hydroxyapatite as a scavenger of reactive radiolysis species in graphene liquid cells for in situ electron microscopy

Liquid cell electron microscopy is an imaging technique allowing for the investigation of the interaction of liquids and solids at nanoscopic length scales. Such in situ observations are increasingly in-demand in an array of fields, from biological sciences to medicine to batteries. Graphene liquid cells (GLCs), in particular, have generated a great interest as a low-scattering window material with the potential for increasing the quality of both imaging and spectroscopy. However, preserving the stability of the liquid and of the sample in the GLC remains a considerable challenge. In the present work we encapsulate water and hydroxyapatite (HAP), a pH-sensitive biological material, in GLCs to observe the interactions between the graphene, HAP, and the electron beam. HAP was chosen for several reasons. One is its ubiquity in biological specimens such as bones and teeth, and the second is the presence of phosphate ions in common buffer solutions. Finally, there is its sensitivity to changes in pH, which result from beam-induced hydrolysis in liquid cells. A dynamic process of dissolution and recrystallization of HAP was observed, which correlated with the production of H+ ions by the beam during imaging. In addition, a large increase in the stability of the GLC under irradiation was noted. Specifically, no stable hydrogen bubbles were detected under the electron fluxes routinely exceeding 170 e− Å−2 s−1. With the measured threshold dose for the bubble formation in pure water equaling 9 e− Å−2 s−1, it was concluded that the presence of HAP increases the resistance of water against radiolysis in the GLC by more than an order of magnitude. These results confirm the possibility of using biological materials, such as HAP, as stabilizers in liquid cell electron microscopy. They outline a potential route for stabilization of specimens in liquid cells through the addition of a scavenger of reactive species generated by the beam-induced hydrolysis of water. These improvements are essential for enhancing both the resolution of imaging and the available imaging time, as well as avoiding the beam-induced artifacts.
Association between fasting blood glucose levels and stroke events: a large-scale community-based cohort study from China

Objectives Diabetes mellitus has been associated with stroke. However, the association between fasting blood glucose (FBG) and stroke risk in a general population remains not clear. The purpose of our study was to examine the FBG levels on subsequent stroke risk in a community-based cohort in China. Design Prospective cohort study, employing Cox proportional hazard model to analyse the association of FBG levels with stroke risk. Setting A community-based cohort study included adults participating in a baseline survey conducted in 2013 in Changshu, eastern China. Participants 16 113 participants were recruited with a multistage sampling method, excluding participants with severe disability, severe cancer, severe psychiatric disturbance or previous stroke before enrolment. Primary outcome measures Stroke events. Results During a median follow-up of 5.5 years, 417 incident cases of stroke were identified. The adjusted HR for total and ischaemic stroke for participants in the fourth quartile of FBG compared with the first quartile was 1.44 (95% CI 1.07 to 1.94) and 1.57 (95% CI 1.11 to 2.21), respectively. FBG levels of ≥7.0 mmol/L were associated with an increased risk of stroke based on two clinical classifications (American Diabetes Association: 1.68 (1.24 to 2.27); WHO: 1.62 (1.21, 2.13)). In stratified analyses, risk associations existed in women (HR: 1.92, 95% CI 1.22 to 3.01) and postmenopausal women (HR: 1.68, 95% CI 1.06 to 2.68) for the fourth quartile versus the first. More importantly, the meta-analysis observed a positive association between FBG levels and stroke risk (pooled HR: 1.70, 95% CI 1.27 to 2.29; n=7)). Conclusions Higher FBG level was independently associated with an increased risk of stroke in Chinese adults, especially significant in women.
Responders and non‐responders to aerobic exercise training: beyond the evaluation of V˙O2max

The evaluation of the maximal oxygen uptake ( V˙O2max ) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention ( V˙O2max ), also do not improve in other health‐related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V˙O2max responsiveness. Healthy sedentary participants engaged in a 6‐week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non‐responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V˙O2max , a greater increase in microvascular responsiveness in responders compared to non‐responders was observed. Additionally, responders and non‐responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome.
Optical monitoring of cell migration processes in a 3D scaffold

Three-dimensional (3D) polymeric scaffolds are utilized in tissue engineering to provide biomechanical support for the seeded cells until they are organized into a functional tissue. Studies of cell migration are important for understanding a variety of physiological and pathological processes in tissue regeneration. Optical techniques can be employed for monitoring cell migration processes in 3D scaffolds. In particular, two-photon microscopy (TPM) can be used for monitoring these processes for living cells also at considerable depths. In the present work, the cell migration process of alive chondrocytes labelled with vital PKH67 in 3D collagen-based scaffold has been monitored at different times from the seeding process. The results show that TPM can evidence the presence of living cells in different spatial regions whose localizations depend on the location and time elapsed from the seeding.
Factors associated with pyomyositis: A systematic review and meta‐analysis

Pyomyositis, an acute bacterial infection of skeletal muscle usually resulting in abscess formation, is well recognised in tropical regions where it can account for up to 4% of adult surgical admissions. It is increasingly being reported from high‐income temperate countries. Pyomyositis occurs across all ages and in both sexes. Mortality ranges from 1% to 23%. Many risk factors have been suggested. We aimed to identify factors associated with pyomyositis.
Evaluation of Mansonia spp. Infestation on Aquatic Plants in Lentic and Lotic Environments of the Madeira River Basin in Porto Velho, Rondônia, Brazil.

The females of Mansonia are voraciously hematophagous. The spiracular apparatus of the immature, larval, and pupal forms is adapted to perforate submerged aquatic vegetation, from whose aeriferous aerenchyma they obtain the oxygen necessary for breathing. The proliferation of aquatic plants, in some cases linked to anthropic modifications that reduce water flow and/or increase organic matter content, may therefore contribute to the spread of these mosquitoes. This study aims to assess the presence of immature individuals of Mansonia in different aquatic plants of the Madeira River basin in 10 lentic and lotic environments and correlate their population density with abiotic factors such as water pH, dissolved O2, conductivity, and temperature. The sampling lasted from February 2016 to June 2018, a 29-month period during which 31,287 specimens belonging to the genus Mansonia were captured. Of the 12 species of macrophytes inspected, Eichhornia crassipes made up 70.1% of the samples. Lentic environments accounted for 58.9% of the samples and lotic environments for 41.1%. Immature individuals were most commonly found on Eichhornia crassipes, with this plant accounting for an average of 96.2% of all individuals, with a percentage ranging between 58.2% and 77.1% in different breeding areas. Only at the Foz do Igarapé Jirau site was a different distribution observed, with the number of aquatic plants more nearly equal: 83.3% of the larvae were found in Eichhornia crassipes, 9.2% in Ceratopteris pteridoides, 3.6% in E. azurea, 2.0% in Salvinia sp. , and 1.9% in Pistia sp. The greatest richness was found in Iguapé do Raul. Concerning the larval/plant relationship, although less frequent, E. azurea had a higher larval density of Mansonia spp. It is important to emphasize that this finding may indicate a possible selection for this plant. Egg deposition by Mansonia spp. was more abundant in sample areas with Eichhornia crassipes and Pistia sp. The number of specimens collected was positively correlated with temperature, pH, and conductivity. These correlations showed a marked increase in the rainy season. Therefore, we were able to establish preliminary parameters of how environmental changes influence the ecology of this important genus of mosquitoes, the species of which are critical disease vectors.
Exploring reported genes of microglia RNA‐sequencing data: Uses and considerations

The advent of RNA‐sequencing techniques has made it possible to generate large, unbiased gene expression datasets of tissues and cell types. Several studies describing gene expression data of microglia from Alzheimer's disease or multiple sclerosis have been published, aiming to generate more insight into the role of microglia in these neurological diseases. Though the raw sequencing data are often deposited in open access databases, the most accessible source of data for scientists is what is reported in published manuscripts. We observed a relatively limited overlap in reported differentially expressed genes between various microglia RNA‐sequencing studies from multiple sclerosis or Alzheimer's diseases. It was clear that differences in experimental set up influenced the number of overlapping reported genes. However, even when the experimental set up was very similar, we observed that overlap in reported genes could be low. We identified that papers reporting large numbers of differentially expressed microglial genes generally showed higher overlap with other papers. In addition, though the pathology present within the tissue used for sequencing can greatly influence microglia gene expression, often the pathology present in samples used for sequencing was underreported, leaving it difficult to assess the data. Whereas reanalyzing every raw dataset could reduce the variation that contributes to the observed limited overlap in reported genes, this is not feasible for labs without (access to) bioinformatic expertise. In this study, we thus provide an overview of data present in manuscripts and their supplementary files and how these data can be interpreted.