Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide association study on coronary artery disease in type 1 diabetes suggests beta-defensin 127 as a risk locus.

AIMS Diabetes is a known risk factor for coronary artery disease. There is accumulating evidence that coronary artery disease pathogenesis differs for individuals with type 1 diabetes. However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing coronary artery disease susceptibility especially in type 1 diabetes, to examine the function of these discoveries and to study the role of the known risk loci in type 1 diabetes. METHODS AND RESULTS We performed the largest genome-wide association study to date for coronary artery disease in type 1 diabetes, comprising 4869 individuals with type 1 diabetes (cases/controls: 941/3928). Two loci reached genome-wide significance, rs1970112 in CDKN2B-AS1 (OR = 1.32, p=1.50 × 10-8), and rs6055069 on DEFB127 promoter (OR = 4.17, p=2.35 × 10-9), with consistent results in survival analysis. The CDKN2B-AS1 variant replicated (p=0.04) when adjusted for diabetic kidney disease in three additional type 1 diabetes cohorts (cases/controls: 434/3123). Furthermore, we explored the function of the lead discoveries with a cardio-phenome-wide analysis. Among the eight suggestive loci (p<1 × 10-6), rs70962766 near B3GNT2 associated with central blood pressure, rs1344228 near CNTNAP5 with intima media thickness, and rs2112481 on GRAMD2B promoter with serum leucocyte concentration. Finally, we calculated genetic risk scores for individuals with type 1 diabetes with the known susceptibility loci. General population risk variants were modestly but significantly associated with coronary artery disease also in type 1 diabetes (p=4.21 × 10-7). CONCLUSIONS While general population coronary artery disease risk loci had limited effect on the risk in type 1 diabetes, for the first time, variants at the CDKN2B-AS1 locus were robustly associated with coronary artery disease in individuals with type 1 diabetes. The novel finding on β-defensin DEFB127 promoter provides a link between diabetes, infection susceptibility and coronary artery disease, although pending on future confirmation. TRANSLATIONAL PERSPECTIVE Genetic association studies enable the discovery of novel genes and genetic pathways associated with the disease. Thus, this study provides an insight into coronary artery disease mechanisms specific to type 1 diabetes. The DEFB127 discovery may lead to a therapeutic target and improve patient care, if replicated in the future. Furthermore, genetic studies on coronary artery disease in type 1 diabetes are required for accurate personalized treatment plans achieved through genetic data for those with type 1 diabetes.
Adherence to healthy lifestyles and incidence of diabetes and mortality among individuals with diabetes: a systematic review and meta-analysis of prospective studies

Introduction Lifestyle factors in combination have been hypothesised to be associated with the prevention of type 2 diabetes (T2D) and mortality among individuals with T2D. The aim was to conduct a systematic review and meta-analysis to quantify the association between lifestyle indices and incident T2D as well as mortality in individuals with T2D. Methods PubMed and Web of Science were searched up to September 2019. We included prospective cohort studies investigating at least three lifestyle factors in association with T2D, or all-cause mortality in individuals with diabetes. We conducted pairwise and dose-response meta-analyses to calculate summary relative risks (SRR) by using random effects model. Results In total, 19 studies were included. Adhering to a healthy lifestyle (mostly favourable diet, physical activity, non-smoking, moderate alcohol intake and normal weight) was associated with a reduced SRR of 78% for T2D (SRR: 0.22; 95% CI: 0.16 to 0.32; n=14) and 57% for mortality (SRR: 0.43; 95% CI: 0.31 to 0.58; n=5) compared with low adherence to a healthy lifestyle. In dose-response analyses, the adherence to every additional healthy lifestyle factor was associated with a reduced relative risk of 32% (95% CI: 28% to 36%) for T2D and 21% (95% CI: 15% to 26%) for mortality. Conclusions Our findings underline the importance of the joint adherence to healthy lifestyle factors to prevent T2D and improve survival among individuals with diabetes. Adherence to every additional health lifestyle factor play a role in the T2D prevention and progression. PROSPERO registration number CRD42018091409.
Traumatic experiences, family functioning, and mood disorder development in bipolar offspring

Objectives Studies in children of patients affected with bipolar disorder (BD; bipolar offspring) are at high risk to develop mood disorders. Our aim is to investigate how environmental factors such as childhood trauma and family functioning relate to the development of mood disorders in offspring at familial risk for BD. Design The current study is part of a longitudinal prospective cohort study among offspring of parents with BD. Methods The current study is part of the Dutch Bipolar Offspring Study, an ongoing prospective cohort study among adolescent offspring of a parent with BD. Bipolar offspring were psychiatrically evaluated at baseline and at 1‐, 5‐, and 12‐year follow‐up. Complete follow‐up data over de 12‐year follow‐up were available for 102 offspring. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ) and filled out by the offspring. Family functioning was reported by the mother with the 130‐item Questionnaire for Family Problems (QFP). Results Emotional maltreatment was significantly associated (HR = 1.82, CI 1.18–2.82, p = .007) with mood disorder onset in bipolar offspring. No association was found with the family functioning total score (HR = 1.04, CI 0.94–15, p = .085) nor its subscales. Conclusions The current study suggests that emotional maltreatment is associated with mood disorder development in bipolar offspring. Remarkably, the association of offspring‐reported emotional maltreatment and mood disorder onset was not reflected in parent‐reported family functioning (e.g., support and communication, openness or involvement). Possible explanations are discussed and warrant further study. Practitioner points Offspring of bipolar patients are at increased risk of developing mood disorders across the life‐time. Emotional trauma contributes to the likelihood of developing mood disorders in bipolar offspring. In the daily treatment of bipolar patients having children, attention should be given to parental style and difficulties. Further research using multiple informant methods on childhood trauma an family functioning is needed to further disentangle the effects of these variables on the onset of psychopathology in bipolar offspring.
Biologic therapies for the treatment of hidradenitis suppurativa

ABSTRACT Introduction: Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by inflammatory nodules, abscesses, and fistulae. Patients tend to present in young adulthood and are predominantly female. The pathogenesis of HS involves apopilosebaceous gland follicle occlusion and affected areas often occur where this type of gland predominates. Treatment selection depends on HS severity, which is included in different scoring systems. In recent years, biological therapies have been evaluated and used with increasing frequency in moderate-to-severe HS disease. Areas covered: This review focuses on biological therapies for HS as assessed in case reports, case series, and clinical trials. The efficacy, hidradenitis suppurativa scoring systems, and long-term results of these therapies are discussed depending on the studies’ endpoints. Expert opinion: Adalimumab is currently the only FDA-approved HS biological therapy. Some patients do not experience treatment efficacy with adalimumab at 40 mg/week, which may result in increasing the dose or seeking other treatments. Infliximab is the next line of HS treatment with demonstrated efficacy. Other biological therapies being studied have demonstrated efficacy in small patient groups, but lack study power. Further studies may provide answers to seeking treatment options for patients who fail to improve on current standard HS treatment.
Biological disease-modifying antirheumatic drugs in juvenile idiopathic arthritis of polyarticular course, enthesitis-related arthritis, and psoriatic arthritis: a consensus statement.

OBJECTIVES Juvenile idiopathic arthritis (JIA) is the most common type of inflammatory arthritis in children. Treatment options have been expanded since the introduction of biologics, which are highly effective. The existing local JIA treatment guideline was published more than a decade ago, when use of biologics was not as common. In this article, we review the latest evidence on using biologics in three JIA subtypes: JIA of polyarticular course (pcJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). Based on the latest information, an update on eligibility, response assessment, termination, and safety information for using biologics in these patients was performed. CONSENSUS PROCESS The JIA Work Group, which consisted of nine paediatricians experienced in managing JIA, was convened in 2016. Publications before July 2017 were screened. Eligible articles were clinical trials, extension studies, systemic reviews, and recommendations from international societies and regulatory agencies about the use of biologics in pcJIA, ERA, and PsA. Evidence extraction, appraisal, and drafting of propositions were performed by two reviewers. Extracted evidence and drafted propositions were presented and discussed at the first two meetings. Overwhelming consensus was obtained at the final meeting in May 2018. Seven practice consensus statements were formulated. Regular review should be performed to keep the practice evidence-based and up-to-date.
RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression

Statement of Retraction Yu Sun, Tiefeng Shi, Yanfei Ma, Huadong Qin and Kang Li. Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression. Cell Cycle. 2020;19(7):787-800. doi: 10.1080/15384101.2020. 1731062 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
The Role of Conformational Dynamics and Allostery in Modulating Protein Evolution.

Advances in sequencing techniques and statistical methods have made it possible not only to predict sequences of ancestral proteins but also to identify thousands of mutations in the human exome, some of which are disease associated. These developments have motivated numerous theories and raised many questions regarding the fundamental principles behind protein evolution, which have been traditionally investigated horizontally using the tip of the phylogenetic tree through comparative studies of extant proteins within a family. In this article, we review a vertical comparison of the modern and resurrected ancestral proteins. We focus mainly on the dynamical properties responsible for a protein's ability to adapt new functions in response to environmental changes. Using the Dynamic Flexibility Index and the Dynamic Coupling Index to quantify the relative flexibility and dynamic coupling at a site-specific, single-amino-acid level, we provide evidence that the migration of hinges, which are often functionally critical rigid sites, is a mechanism through which proteins can rapidly evolve. Additionally, we show that disease-associated mutations in proteins often result in flexibility changes even at positions distal from mutational sites, particularly in the modulation of active site dynamics. Expected final online publication date for the Annual Review of Biophysics, Volume 49 is May 6, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
OTUD1 Negatively Regulates Type I IFN Induction by Disrupting Noncanonical Ubiquitination of IRF3

Key Points OTUD1 restricts IRF3 activity in a nonproteolytic manner. OTUD1 deubiquitinates and inhibits DNA binding capacity of IRF3. Virus-induced K6-linked ubiquitination of IRF3 is indispensable for its DNA binding capacity. Visual Abstract IFN regulatory factor 3 (IRF3) is critical for the transcription of type I IFNs in defensing virus and promoting inflammatory responses. Although several kinds of posttranslational modifications have been identified to modulate the activity of IRF3, whether atypical ubiquitination participates in the function regulation, especially the DNA binding capacity of IRF3, is unknown. In this study, we found that the ovarian tumor domain containing deubiquitinase OTUD1 deubiquitinated IRF3 and attenuated its function. An atypical ubiquitination, K6-linked ubiquitination, was essential for the DNA binding capacity of IRF3 and subsequent induction of target genes. Mechanistically, OTUD1 cleaves the viral infection–induced K6-linked ubiquitination of IRF3, resulting in the disassociation of IRF3 from the promoter region of target genes, without affecting the protein stability, dimerization, and nuclear translocation of IRF3 after a viral infection. Otud1−/− cells as well as Otud1−/− mice produced more type I IFNs and proinflammatory cytokines after viral infection. Otud1−/− mice were more resistant to lethal HSV-1 and VSV infection. Consistent with the former investigations that IRF3 promoted inflammatory responses in LPS-induced sepsis, Otud1−/− mice were more susceptible to LPS stimulation. Taken together, our findings revealed that the DNA binding capacity of IRF3 in the innate immune signaling pathway was modulated by atypical K6-linked ubiquitination and deubiquitination process, which was regulated by the deubiquitinase OTUD1.
Comparative Analysis of In Vitro Responses and Regeneration between Diverse Bioenergy Sorghum Genotypes

Sorghum has been considered a recalcitrant plant in vitro, and suffers from a lack of regeneration protocols that function broadly and efficiently across a range of genotypes. This study was initiated to identify differential genotype-in vitro protocol responses across a range of bioenergy sorghum bioenergy parental lines, in order to characterize response profiles for use in future genetic studies. Seven bioenergy sorghum genotypes were compared, along with the common grain sorghum genotype Tx430, for their in vitro regeneration responses using two different in vitro protocols, LG and WU. All genotypes displayed some level of response during in vitro culture with both protocols. Distinct genotype-protocol responses were observed, with the WU protocol significantly better for plantlet regeneration. All bioenergy genotypes, with the exception of Chinese Amber, performed as well, if not better than Tx430, with Rio and PI329311 the top regenerating lines. Genotypes displayed protocol-dependent, differential phenolic exudation responses, as indicated by medium browning. During the callus induction phase, genotypes prone to medium browning exhibited a response on WU medium which was either equal or greater than on LG medium, with Pink Kafir and PI329311 the most prone to medium browning. Genotype- and protocol-dependent albino plantlet regeneration was also noted, with three of the bioenergy genotypes showing albino plantlet regeneration. Grassl, Rio and Pink Kafir were susceptible to albino plantlet regeneration, with the response strongly associated with the WU protocol. Pink Kafir displayed the highest albino formation, with close to 25% of regenerating explants forming albino plantlets.
P-wave anelasticity in hydrate-bearing sediments based on a triple-porosity model

P-wave anelasticity (attenuation and dispersion) of hydrate-bearing sediments depends on several factors, namely the properties of the mineral components, hydrate content and morphology, and fluid saturation. Anelasticity is analyzed with a triple-porosity model (stiff pores, clay micropores and hydrate micropores), by considering hydrate as an additional solid skeleton. We relate the hydrate volume ratio, porosity and radii of the hydrate inclusion and clay mineral to the P-wave velocity and attenuation. The model takes wave-induced local fluid flow (mesoscopic loss) at the grain contacts into account. The results are compared with those of a double-porosity and load-bearing models, and verified with well-log data from Offshore Drilling Program sites 1247B and 1250F, and data reported in Nankai Trough, Japan. Model results and data show a good agreement.
Advances in Liquid Metal-Enabled Flexible and Wearable Sensors

Sensors are core elements to directly obtain information from surrounding objects for further detecting, judging and controlling purposes. With the rapid development of soft electronics, flexible sensors have made considerable progress, and can better fit the objects to detect and, thus respond to changes more sensitively. Recently, as a newly emerging electronic ink, liquid metal is being increasingly investigated to realize various electronic elements, especially soft ones. Compared to conventional soft sensors, the introduction of liquid metal shows rather unique advantages. Due to excellent flexibility and conductivity, liquid-metal soft sensors present high enhancement in sensitivity and precision, thus producing many profound applications. So far, a series of flexible and wearable sensors based on liquid metal have been designed and tested. Their applications have also witnessed a growing exploration in biomedical areas, including health-monitoring, electronic skin, wearable devices and intelligent robots etc. This article presents a systematic review of the typical progress of liquid metal-enabled soft sensors, including material innovations, fabrication strategies, fundamental principles, representative application examples, and so on. The perspectives of liquid-metal soft sensors is finally interpreted to conclude the future challenges and opportunities.
The Floral Repressor GmFLC-like Is Involved in Regulating Flowering Time Mediated by Low Temperature in Soybean

Soybean is an important crop that is grown worldwide. Flowering time is a critical agricultural trait determining successful reproduction and yields. For plants, light and temperature are important environmental factors that regulate flowering time. Soybean is a typical short-day (SD) plant, and many studies have elucidated the fine-scale mechanisms of how soybean responds to photoperiod. Low temperature can delay the flowering time of soybean, but little is known about the detailed mechanism of how temperature affects soybean flowering. In this study, we isolated GmFLC-like from soybean, which belongs to the FLOWERING LOCUS C clade of the MADS-box family and is intensely expressed in soybean leaves. Heterologous expression of GmFLC-like results in a delayed-flowering phenotype in Arabidopsis. Additional experiments revealed that GmFLC-like is involved in long-term low temperature-triggered late flowering by inhibiting FT gene expression. In addition, yeast one-hybrid, dual-luciferase reporter assay, and electrophoretic mobility shift assay revealed that the GmFLC-like protein could directly repress the expression of FT2a by physically interacting with its promoter region. Taken together, our results revealed that GmFLC-like functions as a floral repressor involved in flowering time during treatments with various low temperature durations. As the only the FLC gene in soybean, GmFLC-like was meaningfully retained in the soybean genome over the course of evolution, and this gene may play an important role in delaying flowering time and providing protective mechanisms against sporadic and extremely low temperatures.
Notes on the cheek region of the Late Jurassic theropod dinosaur Allosaurus

Allosaurus, from the Late Jurassic of North America and Europe, is a model taxon for Jurassic basal tetanuran theropod dinosaurs. It has achieved an almost iconic status due to its early discovery in the late, 19th century, and due to the abundance of material from the Morrison Formation of the western U.S.A. , making Allosaurus one of the best-known theropod taxa. Despite this, various aspects of the cranial anatomy of Allosaurus are surprisingly poorly understood. Here, we discuss the osteology of the cheek region, comprised by the jugal, maxilla, and lacrimal. This region of the skull is of importance for Allosaurus taxonomy and phylogeny, particularly because Allosaurus has traditionally been reconstructed with an unusual cheek configuration, and because the European species Allosaurus europaeus has been said to be different from North American material in the configuration of these bones. Based on re-examination of articulated and disarticulated material from a number of repositories, we show that the jugal participates in the antorbital fenestra, contradicting the common interpretation. The jugal laterally overlies the lacrimal, and forms an extended antorbital fossa with this bone. Furthermore, we document previously unrecorded pneumatic features of the jugal of Allosaurus.