Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal whole blood mRNA signatures identify women at risk of early preeclampsia: a longitudinal study

Abstract Purpose To determine whether previously established mRNA signatures are predictive of early preeclampsia when evaluated by maternal cellular transcriptome analysis in samples collected before clinical manifestation. Materials and methods We profiled gene expression at exon-level resolution in whole blood samples collected longitudinally from 49 women with normal pregnancy (controls) and 13 with early preeclampsia (delivery <34 weeks of gestation). After preprocessing and removal of gestational age-related trends in gene expression, data were converted into Z-scores based on the mean and standard deviation among controls for six gestational-age intervals. The average Z-scores of mRNAs in each previously established signature considered herein were compared between cases and controls at 9–11, 11–17, 17–22, 22–28, 28–32, and 32–34 weeks of gestation. Results: (1) Average expression of the 16-gene untargeted cellular mRNA signature was higher in women diagnosed with early preeclampsia at 32–34 weeks of gestation, yet more importantly, also prior to diagnosis at 28–32 weeks and 22–28 weeks of gestation, compared to controls (all, p < .05). (2) A combination of four genes from this signature, including a long non-protein coding RNA [H19 imprinted maternally expressed transcript (H19)], fibronectin 1 (FN1), tubulin beta-6 class V (TUBB6), and formyl peptide receptor 3 (FPR3) had a sensitivity of 0.85 (0.55–0.98) and a specificity of 0.92 (0.8–0.98) for prediction of early preeclampsia at 22–28 weeks of gestation. (3) H19, FN1, and TUBB6 were increased in women with early preeclampsia as early as 11–17 weeks of gestation (all, p < .05). (4) After diagnosis at 32–34 weeks, but also prior to diagnosis at 11–17 weeks, women destined to have early preeclampsia showed a coordinated increase in whole blood expression of several single-cell placental signatures, including the 20-gene signature of extravillous trophoblast (all, p < .05). (5) A combination of three mRNAs from the extravillous trophoblast signature (MMP11, SLC6A2, and IL18BP) predicted early preeclampsia at 11–17 weeks of gestation with a sensitivity of 0.83 (0.52–0.98) and specificity of 0.94 (0.79–0.99). Conclusions Circulating early transcriptomic markers for preeclampsia can be found either by untargeted profiling of the cellular transcriptome or by focusing on placental cell-specific mRNAs. The untargeted cellular mRNA signature was consistently increased in early preeclampsia after 22 weeks of gestation, and individual mRNAs of this signature were significantly increased as early as 11–17 weeks of gestation. Several single-cell placental signatures predicted future development of the disease at 11–17 weeks and were also increased in women already diagnosed at 32–34 weeks of gestation.
Reversibility of impaired brain structures after transsphenoidal surgery in Cushing's disease: a longitudinal study based on an artificial intelligence-assisted tool.

OBJECTIVE Cushing's disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis. METHODS Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence-assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery. RESULTS Widespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05). CONCLUSIONS This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.
Positive behaviour support in frontotemporal dementia: A pilot study

ABSTRACT Frontotemporal dementia (FTD) is a progressive neurodegenerative brain condition clinically characterized by marked changes in behaviour that impact the individuals’ relationships and community participation, and present challenges for families. Family carers of individuals with FTD find apathy and disinhibition particularly challenging leading to high levels of stress and burden. Positive behaviour support (PBS) as a behaviour intervention framework has never been trialled in FTD. This pilot study examined the functional basis of apathetic and disinhibited behaviours in four FTD dyads and explored the acceptability of a PBS intervention. The PBS programme was provided by an occupational therapist in the participants’ homes. Measures collected at baseline and post-intervention (M = 3.9 months) assessed: function of behaviours, challenging behaviours, and qualitative outcomes pertaining to the acceptability of the PBS approach. PBS was an acceptable intervention for all four dyads. “Sensory” and “tangible” were the most common functions contributing to the maintenance of behaviour changes, and aspects of apathetic and disinhibited behaviours improved following intervention. This study demonstrates the acceptability and potential benefit of a PBS programme to provide support in FTD. A more rigorous trial will be an important next step in developing improved services tailored to the needs of this unique population.
BHLHE40 Promotes TH2 Cell–Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines

Key Points BHLHE40 is required for protective immunity to the helminth H. polygyrus. BHLHE40 is required for normal TH2 gene transcription and cytokine production. CSF2RB-dependent cytokines can compensate for each other during type 2 immunity. The transcription factor BHLHE40 is an emerging regulator of the immune system. Recent studies suggest that BHLHE40 regulates type 2 immunity, but this has not been demonstrated in vivo. We found that BHLHE40 is required in T cells for a protective TH2 cell response in mice infected with the helminth Heligmosomoides polygyrus bakeri. H. polygyrus elicited changes in gene and cytokine expression by lamina propria CD4+ T cells, many of which were BHLHE40 dependent, including production of the common β (CSF2RB) chain family cytokines GM-CSF and IL-5. In contrast to deficiency in GM-CSF or IL-5 alone, loss of both GM-CSF and IL-5 signaling impaired protection against H. polygyrus. Overall, we show that BHLHE40 regulates the TH2 cell transcriptional program during helminth infection to support normal expression of Csf2, Il5, and other genes required for protection and reveal unexpected redundancy of common β chain–dependent cytokines previously thought to possess substantially divergent functions.
Expanding the role of bitter taste receptor in extra oral tissues: TAS2R38 is expressed in human adipocytes

ABSTRACT Increasing evidence indicates that taste receptors mediate a variety of functions in extra-oral tissues. The present study investigated the expression of bitter taste receptor TAS2R38 in human adipocytes, the possible link with genetic background and the role of TAS2R38 in cell delipidation and lipid accumulation rate in vitro. Subcutaneous (SAT) and visceral (VAT) adipose tissues were collected in 32 obese and 18 lean subjects. The TAS2R38 gene expression and protein content were examined in whole tissues, differentiated adipocytes and stroma-vascular fraction cells (SVF). The P49A SNP of TAS2R38 gene was determined in each collected sample. The effect of two bitter agonists (6-n-propylthiouracil and quinine) was tested. TAS2R38 mRNA was more expressed in SAT and VAT of obese than lean subjects and the expression/protein content was greater in mature adipocytes. The expression levels were not linked to P49A variants. In in vitro differentiated adipocytes, bitter agonists induced a significant delipidation. Incubation with 6-n-propylthiouracil induced an inhibition of lipid accumulation rate together with an increase in TAS2R38 and a decrease in genes involved in adipocyte differentiation. In conclusion, TAS2R38 is more expressed in adipocytes of obese than lean subjects and is involved in differentiation and delipidation processes.
Opioids on Twitter: A Content Analysis of Conversations regarding Prescription Drugs on Social Media and Implications for Message Design

As many as 130 lives are lost every day in the United States due to prescription drug misuse. The opioid crisis is gripping the country and disrupting the lives of millions. Not surprisingly, health organizations are desperately seeking solutions to educate and inform people regarding the issue, often seeking the help of various social media platforms. In this study, we do a content analysis of Twitter messages related to opioids in order to understand the factors that are most likely to influence content sharing. Our findings indicate that structure, source, and the actual content of the post all influence the likelihood of the content’s being shared. Specifically, certain types of content enhanced the likelihood of content sharing whereas use of the term “addiction” discouraged retweeting. Theoretical and practical implications for message design are discussed.
Allergin-1 Immunoreceptor Suppresses House Dust Mite–Induced Allergic Airway Inflammation

Key Points Allergin-1 inhibits HDM-induced Syk activation via SHP-1 in CD11b+ DC. Allergin-1 suppresses Th2 response by inhibiting Syk-mediated PGE2 production in DC. Visual Abstract House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow–chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1–deficient CD11b+ bone marrow–derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.
Altered Gut Microbiota is Present in Newly Diagnosed Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS Clinical and experimental data suggest that gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine intestinal microbiota in newly diagnosed patients with inflammatory bowel disease and to compare it to patients' healthy siblings who share same genetic and environmental background and to healthy unrelated controls. METHODS Molecular approach targeting 16S ribosomal RNA was employed for analyzing the gut microbiota of participants' stool samples. Terminal restriction fragment length polymorphphism analysis was performed. RESULTS Newly diagnosed pediatric patients with inflammatory bowel disease (n = 19, 68.4% CD, mean age 14.8 ± 0.65 years), their unaffected healthy siblings (n = 20, mean age 12.8 ± 0.85 years) and unrelated healthy controls (n = 19, mean age 10.7 ± 0.8 years) were included. Microbial diversity differed significantly between inflammatory bowel disease patients, healthy siblings and healthy controls (p = 0.018 for MspI-digestion, p = 0.013 for HhaI-digestion). No significant difference in microbial diversity was found between healthy siblings and healthy controls. In patients reduced presence of genus Eubacterium, Lactobacillus, Enterobacter and Clostridium, and increased presence of genus Streptococcus, Prevotella and Escherichia, compared to healthy siblings and healthy controls, was found. CONCLUSION Newly diagnosed pediatric patients with inflammatory bowel disease show significantly less diverse microbiota and microbial composition compared to healthy siblings and healthy controls.
Age dependence of modern clinical risk groups for localized prostate cancer – a population-based study

Background Optimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening. Objective Determine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories. Design, Setting, and Participants All men diagnosed with PCa in Norway in 2014-2017 (n=20,356). Outcome Measurements and Statistical Analysis Patients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category. Results Older age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years. Conclusions Risk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.
Habitat partitioning in native Geranium species through reproductive interference.

BACKGROUND AND AIMS Heterospecific pollen transfer may reduce fitness of recipient species, a phenomenon known as reproductive interference. A theoretical study has predicted that distributions of species pairs affected by reproductive interference may be syntopic under negligible reproductive interference, sympatric but with partitioning at small spatial scale (i.e., allotopic) under weak interference, or exclusive, when reproductive interference is strong. Verifying these predictions is essential for evaluation of the applicability of reproductive interference as a general assembly rule of biological communities. The aim of this study was to test these predictions in two sympatrically distributed wild Geranium species, G.thunbergii and G. wilfordii. METHODS To measure the effect of reproductive interference, the association between the relative abundance of the counterpart species and seed set in the focal species, and seed set reduction following the mixed pollination, were analysed. The possibility of hybridization with viable offspring was examined by genotyping plants in the field and after mixed pollination. Fertility of putative hybrids was based on their seed set and the proportion of pollen grains with apertural protrusions. A transect study was conducted to examine spatial partitioning, and possible influences of environmental conditions (canopy openness and soil moisture content) on partitioning between the species were analysed. KEY RESULTS Neither abundance of the counterpart species nor heterospecific pollen deposition significantly affected seed set in the focal species, and hybridization between species was almost symmetric. Putative hybrids had low fertility. The two species were exclusively distributed at small scale, although environmental conditions were not significantly different between them. CONCLUSIONS The allotopy of the two species may be maintained by relatively weak reproductive interference through bidirectional hybridization. Re-evaluation of hybridization may allow ongoing or past reproductive interference to be recognized and provide insight into the distributional relationships between the interacting plants.
Comparative Study of Microbiological Profile and Management Outcomes of Acute Endophthalmitis after Microincision Vitrectomy Surgery versus Intravitreal Injections

ABSTRACT Purpose: The aim of this study was to evaluate and compare incidence and outcomes of management of acute endophthalmitis after microincision vitrectomy surgery (MIVS) and intravitreal injections (IVIs). Methods: Medical records were retrospectively reviewed from January 2012 to December 2017, and the incidence, clinical and microbiological profiles of acute endophthalmitis were documented. Results: Of 26,332 MIVS and 24,143 IVI performed, incidence of acute endophthalmitis in MIVS group was 0.027% (1 in 3761 cases) against 0.054% (1 in 1857 cases) in IVI. Gram-positive organisms were causative in post IVI group as against gram-negative organisms in MIVS group. Conclusion: Incidence of endophthalmitis after IVI is almost twice that after MIVS. A trend toward poorer outcomes in MIVS eyes was observed. Both MIVS and IVI being pars plana procedures warrant similar kind of aseptic precautions.
Nanowrinkled Carbon Aerogels Embedded with FeNx Sites as Effective Oxygen Electrodes for Rechargeable Zinc-Air Battery

Rational design of single-metal atom sites in carbon substrates by a flexible strategy is highly desired for the preparation of high-performance catalysts for metal-air batteries. In this study, biomass hydrogel reactors are utilized as structural templates to prepare carbon aerogels embedded with single iron atoms by controlled pyrolysis. The tortuous and interlaced hydrogel chains lead to the formation of abundant nanowrinkles in the porous carbon aerogels, and single iron atoms are dispersed and stabilized within the defective carbon skeletons. X-ray absorption spectroscopy measurements indicate that the iron centers are mostly involved in the coordination structure of FeN4, with a minor fraction (ca. 1/5) in the form of FeN3C. First-principles calculations show that the FeNx sites in the Stone-Wales configurations induced by the nanowrinkles of the hierarchically porous carbon aerogels show a much lower free energy than the normal counterparts. The resulting iron and nitrogen-codoped carbon aerogels exhibit excellent and reversible oxygen electrocatalytic activity, and can be used as bifunctional cathode catalysts in rechargeable Zn-air batteries, with a performance even better than that based on commercial Pt/C and RuO2 catalysts. Results from this study highlight the significance of structural distortions of the metal sites in carbon matrices in the design and engineering of highly active single-atom catalysts.
Atomic Data and Nuclear Data Tables

a CSNSM, CNRS/IN2P3, Université Paris-Sud, Bât. 108, F-91405 Orsay Campus, France b Max-Planck-Institut für Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg, Germany c GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstrasse 1, D-64291 Darmstadt, Germany d National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824, USA e Institut d’Astronomie et d’Astrophysique, CP-226, Université Libre de Bruxelles, 1050 Brussels, Belgium f Cyclotron Institute, Texas A&M University, College Station, TX 77843, USA g Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA h University of Heidelberg, D-69120 Heidelberg, Germany i Département de Physique, Université de Montréal, Montréal, Québec, H3C 3J7, Canada j Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada k Institute of Modern Physics, CAS, 509 Nanchang Rd., Lanzhou 730000, China
Preliminary Results of Closed Loop Stimulation (CLS) During Ch

The concept of Closed Loop Stimulation (CLS) via intracardiac impedance (heart contractility) measurements was introduced around 1990 [1,2]. The CLSbased pacing rate adaptation had the potential not only to increase the functional capacity of chronotropically incompetent patients during physical exercise, but also to significantly improve overall quality of life of the patients. The reason for such expectations was a unique CLS feature capable of detecting any change in circulatory demands and, regardless of the origin of the stress (physical, mental, emotional, thermal, etc.), to support it with an adequate cardiac output. Large-scale clinical studies in Europe and Latin America demonstrated appropriate performance of the CLS rate adjustment principle and illustrated potential advantages of the CLS over conventional rate-responsive systems utilizing sensors of acceleration, body vibration, and minute ventilation [3-10]. Pacemaker self-initialization following implantation and continuous automatic adaptation of CLS on a daily basis are new features available in the Inos2 CLS dualchamber pacemakers (BIOTRONIK, Germany). This design was intended to ensure optimal performance of the Inos2 CLS pacemaker in each patient and to simplify follow-up procedure by leaving only two rateresponsive parameters to be programmed: a basic pacing rate and a maximum CLS pacing rate.