Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide analysis of coding and non-coding RNA reveals a conserved miR164-NAC regulatory pathway for fruit ripening.

Kiwifruit is a climacteric fruit with high sensitivity to ethylene, influenced by multiple ethylene-responsive structural genes and transcription factors. However, the roles of other post-transcriptional regulators (e.g. miRNAs) necessary for ripening remain elusive. We used high throughput sequencing sRNAome, degradome and transcriptome methods, to identify further contributors to ripening control in kiwifruit (Actinidia deliciosa cv 'Hayward'). Two NAM/ATAF/CUC domain transcription factors (AdNAC6 and AdNAC7), both predicted targets for miR164, showed significant up-regulation by exogenous ethylene. Gene expression analysis and luciferase reporter assays indicated that Ade-miR164 and one of its precursor miRNAs (Ade-MIR164b) were repressed by ethylene treatment and negatively correlated with AdNAC6/7 expression. Subsequent analysis indicated that both AdNAC6 and AdNAC7 proteins are transcriptional activators and physically bind the promoters of AdACS1 (1-aminocyclopropane-1-carboxylate synthase), AdACO1 (1-aminocyclopropane-1-carboxylic acid oxidase), AdMAN1 (endo-β-mannanase) and AaTPS1 (terpene synthase). Moreover, subcellular analysis indicated that the location of the AdNAC6/7 proteins was influenced by Ade-miR164. Multiple omics-based approaches revealed a novel regulatory link for fruit ripening that involved ethylene-miR164-NAC. The regulatory pathway for miR164-NAC is present in various fruit (e.g. Rosaceae fruit, citrus, grape), with implications for fruit ripening regulation.
Postinjury Complications: Retrospective Study of Causative Factors 

Background Injury care involves the complex interaction of patient, physician, and environment that impacts patient complications, level of harm, and failure to rescue (FTR). FTR represents the likelihood of a hospital to be unable to rescue patients from death after in-hospital complications. Objective This study aimed to hypothesize that error type and number of errors contribute to increased level of harm and FTR. Methods Patient information was abstracted from weekly trauma performance improvement (PI) records (from January 1, 2016, to July 19, 2017), where trauma surgeons determined the level of harm and identified the factors associated with complications. Level of harm was determined by definitions set forth by the Agency for Healthcare Research and Quality. Logistic regression was used to determine the impact of individual factors on FTR and level of harm, controlling for age, gender, Charlson score, injury severity score (ISS), error (in diagnosis, technique, or judgment), delay (in diagnosis or intervention), and need for surgery. Results A total of 2216 trauma patients presented during the study period. Of 2216 patients, 224 (224/2216, 10.10 %) had complications reported at PI meetings; of these, 31 patients (31/224, 13.8 %) had FTR. PI patients were more likely to be older (mean age 51.3 years, SE 1.58, vs 46.5 years, SE 0.51; P=.008) and have higher ISS (median 22 vs 8; P<.001), compared with patients without complications. Physician-attributable errors (odds ratio [OR] 2.82; P=.001), most commonly errors in technique, and nature of injury (OR 1.91; P=.01) were associated with higher levels of harm, whereas delays in diagnosis or intervention were not. Each additional factor involved increased level of harm (OR 2.09; P<.001) and nearly doubled likelihood of FTR (OR 1.95; P=.01). Conclusions Physician-attributable errors in diagnosis, technique, or judgment are more strongly correlated with harm than delays in diagnosis and intervention. Increasing number of errors identified in patient care correlates with an increasing level of harm and FTR.
Diagnostic value of magnetic resonance and computed tomography colonography for the diagnosis of colorectal cancer

Abstract Background: Surgical resection is the recommended procedure for colorectal cancer (CRC), but majority of the patients were diagnosed with advanced or metastatic CRC. Currently, there were inconsistent results about the diagnostic value of magnetic resonance colonography (MRC) and computed tomography colonography (CTC) in early CRC diagnosis. Our study conducted this meta-analysis to investigate the diagnostic value of MRC and CTC for CRC surveillance. Methods: A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane library to select relevant studies. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) were calculated to evaluate the diagnostic value of MRC and CTC, respectively. Result: Twenty-five studies including 2985 individuals were selected in the final analysis. Eight studies evaluated the diagnostic value of MRC, and 17 studies assessed CTC. The summary sensitivity, specificity, PLR, NLR, DOR, and AUC in MRC for early detection of CRC were 0.98 (95% confidence interval, CI: 0.80–1.00), 0.94 (95% CI: 0.85–0.97), 15.48 (95% CI: 6.30–38.04), 0.02 (95% CI: 0.00–0.25), 115.09 (95% CI: 15.37–862.01), and 0.98 (95% CI: 0.97–0.99), respectively. In addition, the sensitivity, specificity, PLR, NLR, DOR, and AUC of CTC for diagnosing CRC were 0.97 (95% CI: 0.88–0.99), 0.99 (95% CI: 0.99–1.00), 154.11 (95% CI: 67.81–350.22), 0.03 (95% CI: 0.01–0.13), 642.51 (95% CI: 145.05–2846.02), and 1.00 (95% CI: 0.99–1.00). No significant differences were found between MRC and CTC for DOR in all the subsets. Conclusion: The findings of meta-analysis indicated that MRC and CTC have higher diagnostic values for early CRC diagnosis. However, the DOR for diagnosing CRC between MRC and CTC showed no significance.
Lack of evidence regarding bone metastases of genitourinary cancers: interventions by surgery, radiotherapy, and bone-targeted systemic therapy.

The bone is a major metastatic site of genitourinary (GU) cancer, especially in prostate cancer (PCa). Around 84–91% of patients with metastatic PCa harbor bone metastases (BMs), while the rates of BMs in patients with metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma of the bladder are reportedly 29% and 16–25%, respectively (1). Among mRCC cohorts, bone is the second most common metastatic site after the lungs (2,3).
Pediatric aplastic anemia treatment patterns and responses; power in the numbers

haematologica | 2019; 104(10) 1909 cers. Notably, mining the Oncomine database additionally revealed significant overexpression of both TYRO3 and MER in various Band T-cell leukemia/lymphoma datasets, but not in AML (data not shown). This might suggest a potentially different mechanism of oncogenic signaling in lymphoid neoplasms involving all three receptor family members, as opposed to the clear role of AXL in FLT3-ITD AML; this could be a focus point for further investigations. The new study by Dumas et al. described a resistance mechanism against the FLT3 inhibitor quizartinib, where both the FLT3-ITD mutation and the GAS6-AXL axis trigger important kinase signaling cascades. Their results suggest that a combination of FLT3and AXL-specific inhibitors, or the exploitation of dual FLT3-AXL inhibitors (e.g. cabozantinib), might be beneficial in FLT3-ITD AML patients at risk of relapse. Furthermore, selective STAT5 inhibitors have the potential to become an effective tool for targeted and combinatorial therapy in AML. In summary, FLT3 inhibitors display efficacy in the treatment of FLT3-ITD-driven AML, but more efficient targeting of AML blasts remains an unresolved medical need to fight therapeutic resistance, and to improve the poor overall survival and quality of life of patients.
Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up‐regulation of MEST through NF‐κB1

Ovarian cancer (OC) is one of the major causes of cancer‐related mortality in women worldwide. Long noncoding RNAs might play a role as oncogenes or tumor suppressors. Therefore, we investigated the effect and underlying mechanisms of long intergenic noncoding RNA (LINC00) 284 on angiogenesis in OC cells. Expression of LINC00284 in OC tissues and cells was determined. Next, the interaction between LINC00284 and mesoderm‐specific transcript (MEST) was evaluated. Subsequently, OC cells were transfected with overexpressed (oe)‐LINC00284, silenced (si)‐LINC00284, si‐NF‐κB1, oe‐MEST, or si‐MEST plasmids to investigate the underlying mechanism of LINC00284 in OC. Afterwards, the expression of matrix metalloproteinase (MMP)‐2, MMP‐9, B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated protein x (Bax), VEGF, and CD31 was determined to assess the effect of LINC00284 on OC cell proliferation, invasion, migration angiogenesis, and apoptosis. Finally, the effect of LINC00284 on tumorigenesis was investigated in nude mice models of OC. LINC00284 was highly expressed in OC. si‐LINC00284 increased expression of MEST. si‐LINC00284 or si‐NF‐κB1 led to the reduction in cell proliferation, migration, invasion, tube formation, angiogenesis, and tumorigenic ability and promoted apoptosis in OC by down‐regulating MMP‐2, MMP‐9, Bcl‐2, VEGF, and CD31 and up‐regulating Bax. These effects were all reversed following the si‐MEST. In vivo experiments found the same results, confirming the aforementioned findings. Taken together, LINC00284 is involved in angiogenesis during OC development by recruiting NF‐κB1 and down‐regulating MEST. —Ruan, Z. , Zhao, D. Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up‐regulation of MEST through NF‐κB1. FASEB J. 33, 12047‐12059 (2019). www.fasebj. org
Genomics Analysis of L-DOPA Exposure in Drosophila sechellia

Drosophila sechellia is a dietary specialist fruit fly that evolved from a generalist ancestor to specialize on the toxic fruit of Morinda citrifolia. This species pair has been the subject of numerous studies where the goal has largely been to determine the genetic basis of adaptations associated with host specialization. Because one of the most striking features of M. citrifolia fruit is the production of toxic volatile compounds that kill insects, most genomic studies in D. sechellia to date have focused on gene expression responses to the toxic compounds in its food. In this study, we aim to identify new genes important for host specialization by profiling gene expression response to 3,4-dihydroxyphenylalanine (L-DOPA). Recent work found it to be highly abundant in M. citrifolia, critical for reproductive success of D. sechellia, and supplementation of diet with the downstream pathway product dopamine can influence toxin resistance phenotypes in related species. Here we used a combination of functional genetics and genomics techniques to identify new genes that are important for D. sechellia ecological adaptation to this new niche. We show that L-DOPA exposure can affect toxin resistance phenotypes, identify genes with plastic responses to L-DOPA exposure, and functionally test an identified candidate gene. We found that knock-down of Esterase 6 (Est6) in a heterologous species alters toxin resistance suggesting Est6 may play an important role in D. sechellia host specialization.
Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference.

This cohort study sought to estimate the differences in risk of delivering small and large for gestational age infants (SGA and LGA, respectively) for exercise during the first trimester of pregnancy (versus no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex and gestational age specific birthweight distributions of the 2017 U.S. Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal weight women but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA, but only among underweight and normal weight women. Any vigorous exercise reduced the risk LGA in underweight and normal weight women only, and was not associated with SGA risk.
Molecular foundations of chiropractic therapy

Background and aim: Alternative medicine is a broad term used to encompass different therapies, including chiropractic. Chiropractic was called “a science of healing without drugs” by its founder, David Daniel Palmer. It is based on the idea that the body has a powerful self-healing ability and that there is a relationship between body structure and function that affects health. In particular, chiropractic assumes that the nervous system controls the human body through nerves branching from the vertebral column and spinal cord. Researchers do not fully understand how chiropractic therapies affect pain, but chiropractic is widely used today to treat chronic pain, such as back pain. Different studies with animal models have demonstrated that chiropractic therapies mediate neuroplasticity, specifically through modulation of neurotrophins. No studies have yet been published on interaction between neurotrophin gene polymorphisms and chiropractic treatment. Methods: We searched PubMed with the following keywords: chiropractic, neuroplasticity, neurotrophin gene polymorphism for a panorama of on the molecular mechanisms of chiropractic therapy. Results: From the material collected, we identified a set of genes and some functional polymorphisms that could be correlated with better response to chiropractic therapy. Conclusions: Further association studies will be necessary to confirm hypotheses of a correlation between single nucleotide polymorphisms in specific genes and better response to chiropractic therapy. (www.actabiomedica.it)
Pathogenic Rickettsia in ticks of spur-thighed tortoise (Testudo graeca) sold in a Qatar live animal market.

Dissemination of vector arthropods harboring zoonotic pathogens through the uncontrolled transboundary trade of exotic and pet animals poses an important threat to Public Health. In the present report we describe the introduction of pathogenic Rickettsia africae and R. aeschlimanni in ticks removed from imported tortoises in Qatar. A total of 21 ticks were collected from pet spur-thighed tortoises (Testudo graeca) from Doha, May 2018, and studied for species identification and characterization of Rickettsia spp. Morphological and molecular analysis of ticks allowed their identification as Hyalomma aegyptium. Molecular analysis of partial ompA and gltA genes showed that Rickettsia sequences found on these ticks clustered with sequences classified as R. aeschilimanii and R. africae. Since pre-adult stages of H. aegyptium also feed on humans, this tick species may play a role in the transmission of R. aeschilimanii and R. africae. We alert for the introduction of non-native pets as vehicles for tick importation, known vectors for animal and human pathogenic agents. Importation of exotic species into non-autochthonous countries deserves strict control to enforce robust surveillance and mitigate potential exotic diseases epidemics.
Synthesis, Biological Activities and Docking Studies of Novel 4-(Arylaminomethyl)benzamide Derivatives as Potential Tyrosine Kinase Inhibitors

A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were designed and synthesized, and their biological activities were evaluated as potential anticancer agents. The cytotoxicity activity of the designed compounds was studied in two hematological and five solid cell lines in comparison with the reference drugs. Targeted structures against eight receptor tyrosine kinases including EGFR, HER-2, HER-4, IGF1R, InsR, KDR, PDGFRa, and PDGFRb were investigated. The majority of the compounds showed a potent inhibitory activity against the tested kinases. The analogues 11 and 13 with the (trifluoromethyl)benzene ring in the amide or amine moiety of the molecule were proven to be highly potent against EGFR, with 91% and 92% inhibition at 10 nM, respectively. The docking of synthesized target compounds for nine protein kinases contained in the Protein Data Bank (PDB) database was carried out. The molecular modeling results for analogue 10 showed that the use of the 4-(aminomethyl)benzamide as a flexible linker leads to a favorable overall geometry of the molecule, which allows one to bypass the bulk isoleucine residue and provides the necessary binding to the active center of the T315I-mutant Abl (PDB: 3QRJ).
Utility of fiberoptic bronchoscopy for difficult airway in neonates

Abstract Background Newborns diagnosed with craniofacial malformations or laryngeal and tracheal alterations may often need advanced airway-management for airway stabilization. Although fiberoptic bronchoscopy (FB) is currently the gold standard for difficult airway management, there is a scarcity of published data on the application of FB in newborns for intubation and controlled extubation (CE). Objectives This study describes a case series where FB is used for intubation and/or extubation to manage newborns with difficult airway in either urgent procedures or scheduled ones. Methods All FB were carried out on newborns with difficult airway in the neonatal unit over the period January 2005 to December 2018. Patient characteristics were collected from clinical reports, description of the technique from the procedure report. Results 66 FBs were performed from a total of 40 newborns, a median age of 25 days and a weight of 3217 g. Eighteen were ex-premature babies (45%). Six (15%) had craniocervical malformations. 17 (25.7%) FBs were performed for tracheal intubation (TI), 6 in emergency situations, 34 (51.5%) for CE, and 15 (22.7%) for precise tube placement. Clearing of the airway was achieved in all cases and thus there were no failed TIs. In 32 cases (94.1%), CE was successfully performed. In 6 cases, withdrawal of the ET midprocedure was decided to postpone as 4 of these required extra treatment prior to renewed extubation attempt and 2 needed a tracheostomy. 2 patients required subsequent FB reintubation due to airway pathology. Complications during the procedure were mild desaturations (3%) and deep desaturations (7.5%). Conclusions FB is very safe and highly useful when performing intubation in neonates with difficult airway but is essential during extubation to avoid any risk of failure with a potentially fatal outcome. Neonatal units of tertiary hospitals should provide equipment and training to manage these neonates. What is already known? A failed intubation or extubation can lead to cardiac arrest and anoxic brain damage and/or to death in a neonate. Fiberoptic bronchoscopy is recommended as the safest tool for neonates with difficult airway. However, there is little concrete data published in the current literature to support the recommendations. What is new Fiberoptic bronchoscopy is an essential tool to avoid the risk of a failed extubation in neonates with difficult airway.
A concerted metabolic shift in early forebrain alters the CSF proteome and depends on MYC downregulation for mitochondrial maturation

ABSTRACT Massive, coordinated cellular changes accompany the transition of central nervous system (CNS) progenitors from forebrain neurectodermal cells to specified neuroepithelial cells. We have previously found that MYC regulates the changing ribosomal and proteostatic landscapes in mouse forebrain precursors at embryonic days E8.5 and E10.5 (before and after neural tube closure; NTC) (Chau et al., 2018). Here, we demonstrate parallel coordinated transcriptional changes in metabolic machinery during this same stage of forebrain specification. Progenitors showed striking mitochondrial structural changes transitioning from glycolytic cristae at E8.5, to more traditional mitochondria at E10.5. Accordingly, glucose use shifted in progenitors such that E8.5 progenitors relied on glycolysis, and after NTC increasingly used oxidative phosphorylation. This metabolic shift was matched by changes in surrounding amniotic and cerebrospinal fluid proteomes. Importantly, these mitochondrial morphological shifts depend on MYC downregulation. Together, our findings demonstrate that metabolic shifting accompanies dynamic organelle and proteostatic remodeling of progenitor cells during the earliest stages of forebrain development. Highlighted Article: As neural progenitors mature from forebrain neurectodermal cells to neuroepithelial cells, the mitochondrial landscape, metabolic components and functional ability to employ glycolysis transition to favor oxidative phosphorylation.
Hysteresis Compensation in Force/Torque Sensors Using Time Series Information

The purpose of this study is to compensate for the hysteresis in a six-axis force sensor using signal processing, thereby achieving high-precision force sensing. Although mathematical models of hysteresis exist, many of these are one-axis models and the modeling is difficult if they are expanded to multiple axes. Therefore, this study attempts to resolve this problem through machine learning. Since hysteresis is dependent on the previous history, this study investigates the effect of using time series information in machine learning. Experimental results indicate that the performance is improved by including time series information in the linear regression process generally utilized to calibrate six-axis force sensors.
LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses

The interaction between LGP2 and a component of the RNA-silencing machinery enables coordination of innate immune responses. An antiviral PACT The RIG-I–like receptors (RLRs) RIG-I and MDA5 sense cytosolic viral RNAs during infection and activate signaling pathways that culminate in the production of type I interferons (IFNs) and proinflammatory cytokines as part of the antiviral immune response. LGP2, another member of the RLR family, inhibits RIG-I–mediated responses while enhancing MDA5 signaling. Sanchez David et al. found that this differential effect of LGP2 depended on its binding to PACT, a cofactor of DICER in the processing of microRNAs. Mutation of a residue in LGP2 required for the LGP2-PACT interaction resulted in loss of the regulatory effect of LGP2 over the other RLRs. Together, these data provide evidence of a connection between the RNA-silencing machinery and the innate immune response. The retinoic acid–inducible gene I (RIG-I)–like receptors (RLRs) RIG-I, MDA5, and LGP2 stimulate inflammatory and antiviral responses by sensing nonself RNA molecules produced during viral replication. Here, we investigated how LGP2 regulates the RIG-I– and MDA5-dependent induction of type I interferon (IFN) signaling and showed that LGP2 interacted with different components of the RNA-silencing machinery. We identified a direct protein-protein interaction between LGP2 and the IFN-inducible, double-stranded RNA binding protein PACT. The LGP2-PACT interaction was mediated by the regulatory C-terminal domain of LGP2 and was necessary for inhibiting RIG-I–dependent responses and for amplifying MDA5-dependent responses. We described a point mutation within LGP2 that disrupted the LGP2-PACT interaction and led to the loss of LGP2-mediated regulation of RIG-I and MDA5 signaling. These results suggest a model in which the LGP2-PACT interaction regulates the inflammatory responses mediated by RIG-I and MDA5 and enables the cellular RNA-silencing machinery to coordinate with the innate immune response.