Miracle-dz/UniFAR-FTUs huggingface dataset:
How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

Assessment of measurable residual disease, also called “minimal residual disease,” in patients with acute myeloid leukemia in morphological remission provides powerful prognostic information and complements pretreatment factors such as cytogenetics and genomic alterations. Based on data that low levels of persistent or recurrent residual leukemia are consistently associated with an increased risk of relapse and worse long-term outcomes, its routine assessment has been recommended by some experts and consensus guidelines. In addition to providing important prognostic information, the detection of measurable residual disease may also theoretically help to determine the optimal post-remission strategy for an individual patient. However, the full therapeutic implications of measurable residual disease are uncertain and thus controversy exists as to whether it should be routinely incorporated into clinical practice. While some evidence supports the use of allogeneic stem cell transplantation or hypomethylating agents for some subgroups of patients in morphological remission but with detectable residual leukemia, the appropriate use of this information in making clinical decisions remains largely speculative at present. To resolve this pressing clinical issue, several ongoing studies are evaluating measurable residual disease-directed treatments in acute myeloid leukemia and may lead to new, effective strategies for patients in these circumstances. This review examines the common technologies used in clinical practice and in the research setting to detect residual leukemia, the major clinical studies establishing the prognostic impact of measurable residual disease in acute myeloid leukemia, and the potential ways, both now and in the future, that such testing may rationally guide therapeutic decision-making.
Genome assembly provides insights into the genome evolution and flowering regulation of orchardgrass

Summary Orchardgrass (Dactylis glomerata L.) is an important forage grass for cultivating livestock worldwide. Here, we report an ~1.84‐Gb chromosome‐scale diploid genome assembly of orchardgrass, with a contig N50 of 0.93 Mb, a scaffold N50 of 6.08 Mb and a super‐scaffold N50 of 252.52 Mb, which is the first chromosome‐scale assembled genome of a cool‐season forage grass. The genome includes 40 088 protein‐coding genes, and 69% of the assembled sequences are transposable elements, with long terminal repeats (LTRs) being the most abundant. The LTRretrotransposons may have been activated and expanded in the grass genome in response to environmental changes during the Pleistocene between 0 and 1 million years ago. Phylogenetic analysis reveals that orchardgrass diverged after rice but before three Triticeae species, and evolutionarily conserved chromosomes were detected by analysing ancient chromosome rearrangements in these grass species. We also resequenced the whole genome of 76 orchardgrass accessions and found that germplasm from Northern Europe and East Asia clustered together, likely due to the exchange of plants along the ‘Silk Road’ or other ancient trade routes connecting the East and West. Last, a combined transcriptome, quantitative genetic and bulk segregant analysis provided insights into the genetic network regulating flowering time in orchardgrass and revealed four main candidate genes controlling this trait. This chromosome‐scale genome and the online database of orchardgrass developed here will facilitate the discovery of genes controlling agronomically important traits, stimulate genetic improvement of and functional genetic research on orchardgrass and provide comparative genetic resources for other forage grasses.
Carotid artery intima–media thickness, distensibility and elasticity: population epidemiology and concordance in Australian children aged 11–12 years old and their parents

Objectives To describe a well-established marker of cardiovascular risk, carotid intima–media thickness (IMT) and related measures (artery distensibility and elasticity) in children aged 11–12 years old and mid-life adults, and examine associations within parent–child dyads. Design Cross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC). Setting Assessment centres in seven Australian major cities and eight selected regional towns, February 2015 to March 2016. Participants Of all participating CheckPoint families (n=1874), 1489 children (50.0% girls) and 1476 parents (86.8% mothers) with carotid IMT data were included. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata. Outcome measures Ultrasound of the right carotid artery was performed using standardised protocols. Primary outcomes were mean and maximum far-wall carotid IMT, quantified using semiautomated edge detection software. Secondary outcomes were carotid artery distensibility and elasticity. Pearson’s correlation coefficients and multivariable linear regression models were used to assess parent–child concordance. Random effects modelling on a subset of ultrasounds (with repeated measurements) was used to assess reliability of the child carotid IMT measure. Results The average mean and maximum child carotid IMT were 0.50 mm (SD 0.06) and 0.58 mm (SD 0.05), respectively. In adults, average mean and maximum carotid IMT were 0.57 mm (SD 0.07) and 0.66 mm (SD 0.10), respectively. Mother–child correlations for mean and maximum carotid IMT were 0.12 (95% CI 0.05 to 0.23) and 0.10 (95% CI 0.03 to 0.21), respectively. For carotid artery distensibility and elasticity, mother–child correlations were 0.19 (95% CI 0.10 to 0.25) and 0.11 (95% CI 0.02 to 0.18), respectively. There was no strong evidence of father–child correlation in any measure. Conclusions We provide Australian values for carotid vascular measures and report a modest mother–child concordance. Both genetic and environmental exposures are likely to contribute to carotid IMT.
Sugammadex For Reversal of Neuromuscular Blockade: Uses and Limitations.

Sugammadex is a reversal agent that was engineered to reverse the effects of aminosteroid muscle relaxants. It is a modified gamma-cyclodextrin, i.e. a large glucose molecules bound in a ring like structure. Sugammadex, when injected intravenously, creates a concentration gradient favoring the movement of aminosteroid muscle relaxants from the neuromuscular junction back into the plasma, and then encapsulates the aminosteroid muscle relaxants within its inner structure by forming tight water soluble complexes. The dissociation of the aminosteroidal muscle relaxant from the post-synaptic acetylcholine receptors is responsible for the termination of neuromuscular blockade. This review article will present the current indication, mechanism of action, limitations, side effects and contraindications of sugammadex. An overview of monitoring of the adequacy of reversal of aminosteroid muscle relaxants with sugammadex will also be presented. The use of sugammadex in special situations, including "cannot intubate cannot oxygenate" scenarios will also be described.
Pediatric Pulmonology

Department of Pediatrics, Stavanger University Hospital, Stavanger, Norway Department of Clinical Science, University of Bergen, Norway Department of Research, Section of Biostatistics, Stavanger University Hospital, Stavanger, Norway Department of Chronic Diseases and Aging, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK Population Health Sciences, Bristol Medical School, Bristol, UK
Reducing Caesarean sections and smoking after delivery could help to tackle shorter exclusive breastfeeding duration

Breastfeeding is considered to be one of the most important ways of promoting public health worldwide and is an investment in the health of future generations. Exclusive breastfeeding with just human milk is the optimal feeding mode for the first six months of life and it provides the strongest benefits for the health of the child and mother (1). That is why it is important to study the factors that could promote or reduce exclusive breastfeeding duration. This article is protected by copyright. All rights reserved.
Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study.

OBJECTIVES In a context of life-long therapy, we asked whether it could be possible to reduce the number of antiretroviral drugs without jeopardizing viral suppression. METHODS ECOVIR was a prospective study aiming to assess whether in patients on combination ART with ≥4 antiretrovirals for ≥24 weeks and virally suppressed for ≥48 weeks, a drug-reduced (DR) regimen could be proposed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with ≤3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. RESULTS From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53-65) years, duration of treatment 24 (21-26) years and viral suppression 8 (6-11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), darunavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4-97.6, Kaplan-Meier estimate). Four patients experienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) <600 copies/mL and no emergence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. CONCLUSIONS In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug-drug interactions and a significant economic impact while ensuring virological success.
β-Thalassemia in Iran: Things Everyone Needs to Know About This Disease

Abstract Iran, as a country located in the Thalassemia Belt, has made great progress in thalassemia prevention and treatment. The thalassemia prevention program was implemented in 1995 and the country-wide thalassemia treatment network, consisting of 64 medical universities and faculties, is active. The acknowledgment of the status of thalassemia treatment and prevention in Iran can be of significance to researchers of the countries affected with thalassemia. In the present research, the database of the Treatment Deputy Office of the Ministry of Health, Treatment and Medical Education and that of the Hemovigilance Network of the Iranian Blood Transfusion Organization, were used. The data were analyzed using the Statistical Package of the Social Sciences, version 23. The findings show 90.13% reduction in the expected cases of new β-thalassemia (β-thal) births in 2015. Moreover, out of 18,983 hemoglobinopathy patients, 17,342 are β-thal major (β-TM) and β-thal intermedia (β-TI) patients covered by 198 medical centers. Out of the total number of blood donations in Iran, 19.17% are allocated to thalassemia treatment. Iran has reached an acceptable level of success in thalassemia prevention and the preparation of safe and adequate blood. Iran’s achievements can be adapted to other developing countries, particularly in the Middle East.
Autism spectrum disorder in children with Type 1 diabetes

Links between autism spectrum disorder (ASD) and autoimmune diseases, including Type 1 diabetes have been proposed. This study assessed the frequency of ASD in children with Type 1 diabetes in the T1D Exchange (T1DX) registry and the impact of ASD on characteristics of children with Type 1 diabetes.
RPE65 mutation frequency and phenotypic variation according to exome sequencing in a tertiary centre for genetic eye diseases in China

Retinoid isomerohydrolase RPE65 has received a tremendous amount of attention due to successful clinical gene therapy for Leber congenital amaurosis (LCA) cases caused by RPE65 mutations. This study aimed to evaluate the frequency of RPE65 mutations and the associated phenotypes based on exome sequencing.
μ‐Opioid receptor signalling via PI3K/Akt pathway ameliorates lipopolysaccharide‐induced acute respiratory distress syndrome

What is the central question of this study? The aim was to investigate the role of μ‐opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway. What is the main finding and its importance? Our findings show that activation of μ‐opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin.
Genome-wide identification and characterization of Gretchen Hagen3 (GH3) family genes in Brassica napus.

The hormone auxin is involved in many biological processes throughout a plant's lifecycle. However, genes in the GH3 (Gretchen Hagen3) family, one of the three major auxin-responsive gene families, have not yet been identified in oilseed rape (Brassica napus). In this study, we identified 63 BnaGH3 genes in oilseed rape using homology searches. We analyzed the chromosome locations, gene structures and phylogenetic relationships of the BnaGH3 genes, as well as the cis-elements in their promoters. Most BnaGH3 genes are located on chromosomes A03, A09, C02, C03 and C09, each with 4-7 members. In addition, we analyzed the expression patterns of BnaGH3 genes in seven tissues by transcriptome sequencing and quantitative RT-PCR analysis of plants under exogenous IAA treatment. The BnaGH3 genes showed different expression patterns in various tissues. BnaA.GH3. 2-1 and BnaC.GH3. 2-1 were expressed in the seed and seed coat during development and in response to IAA treatment. These results shed light on the possible roles of the GH3 gene family in oilseed rape.
PthA4AT, a 7.5‐repeats transcription activator‐like (TAL) effector from Xanthomonas citri ssp. citri, triggers citrus canker resistance

Summary Transcription activator‐like effectors (TALEs) are important effectors of Xanthomonas spp. that manipulate the transcriptome of the host plant, conferring susceptibility or resistance to bacterial infection. Xanthomonas citri ssp. citri variant AT (X. citri AT) triggers a host‐specific hypersensitive response (HR) that suppresses citrus canker development. However, the bacterial effector that elicits this process is unknown. In this study, we show that a 7.5‐repeat TALE is responsible for triggering the HR. PthA4AT was identified within the pthA repertoire of X. citri AT followed by assay of the effects on different hosts. The mode of action of PthA4AT was characterized using protein‐binding microarrays and testing the effects of deletion of the nuclear localization signals and activation domain on plant responses. PthA4AT is able to bind DNA and activate transcription in an effector binding element‐dependent manner. Moreover, HR requires PthA4AT nuclear localization, suggesting the activation of executor resistance (R) genes in host and non‐host plants. This is the first case where a TALE of unusually short length performs a biological function by means of its repeat domain, indicating that the action of these effectors to reprogramme the host transcriptome following nuclear localization is not limited to ‘classical’ TALEs.
Are avoidance diets still warranted in children with atopic dermatitis?

Nearly 40% of children with moderate‐to‐severe atopic dermatitis (AD) have IgE‐mediated food allergy (FA). This clinical observation has been extensively documented by experimental data linking skin inflammation in AD to FA, as well as by food challenges reproducing symptoms and avoidance diets improving AD. Although food avoidance may improve AD, avoidance diets do not cure AD, may even have detrimental effects such as progression to immediate‐type allergy including anaphylactic reactions, and may significantly reduce the quality of life of the patient and the family. AD care should focus upon optimal medical management, rather than dietary elimination. Food allergy testing is primarily indicated when immediate‐type allergic reactions are a concern. In recalcitrant AD, if food is being considered a possible chronic trigger, a limited panel of foods may be tested. An avoidance diet is only indicated in patients clearly identified as food allergic by an appropriate diagnostic food challenge, and after adequately informing the family of the limited benefits, and possible harms of an elimination diet.
Fibromyalgia and its New Lessons for Neuropsychiatry

Background Fibromyalgia (FM) is a centralized pain state that until recently has been shrouded in mystery and questionable as a disease entity in the eyes of many physicians, who considered it purely psychogenic. Fibromyalgia is now thought of as a discrete diagnosis with a clustering of symptoms characterized by central nervous system pain amplification along with anergia, memory loss, disturbances of mood, and sleep disruption. The condition is present in approximately 2% to 8% of the population. Material/Methods We review the link between inflammatory mechanisms and FM from a neuropsychiatric perspective. Results Recent studies are pointing to a neuroinflammatory etiology that may open up more effective treatment strategies in the future. Conclusions Better conceptualization of FM may also elucidate a neuropsychiatric understanding of how nociception, dysthymia, and suicidality co-develop and feed off one another.
Solving Winograd Schema Challenge : Using Semantic Parsing, Automatic Knowledge Acquisition and Logical Reasoning

Turing test has been a benchmark scale for measuring the human level intelligence in computers since it was proposed by Alan Turing in 1950. However, for last 60 years, the applications such as ELIZA, PARRY, Cleverbot and Eugene Goostman, that claimed to pass the test. These applications are either based on tricks to fool humans on a textual chat based test or there has been a disagreement between AI communities on them passing the test. This has led to the school of thought that it might not be the ideal test for predicting the human level intelligence in machines. Consequently, the Winograd Schema Challenge has been suggested as an alternative to the Turing test. As opposed to deciding the intelligent behavior with the help of chat servers, like it was done in the Turing test, the Winograd Schema Challenge is a question answering test. It consists of sentence and question pairs such that the answer to the question depends on the resolution of a definite pronoun or adjective in the sentence. The answers are fairly intuitive for humans but they are difficult for machines because it requires some sort of background or commonsense knowledge about the sentence. In this thesis, I propose a novel technique to solve the Winograd Schema Challenge. The technique has three basic modules at its disposal, namely, a Semantic Parser that parses the English text (both sentences and questions) into a formal representation, an Automatic Background Knowledge Extractor that extracts the Background Knowledge pertaining to the given Winograd sentence, and an Answer Set Programming Reasoning Engine that reasons on the given Winograd sentence and the corresponding Background Knowledge. The applicability of the technique is illustrated by solving a subset of Winograd Schema Challenge pertaining to a certain type of Background Knowledge. The technique is evaluated on the subset and a notable accuracy is achieved.
Complete blood count and penile colour doppler ultrasonography findings in erectile dysfunction: Is there a relationship?

The aim of this study was to evaluate the relationship between penile colour doppler ultrasonography (PCDUS) and complete blood count parameters in patients with erectile dysfunction (ED). The data of the patients who applied to our outpatient clinic with ED (IIEF‐5 score <22 or IIEF‐EF score <26) between January 2007 and May 2017 were retrospectively analysed. The patients who had available PCDUS results and complete blood count (CBC) values were included in the study. Patients were divided into two groups having normal (n = 530 [68.9%]) or abnormal (n = 240 [31.1%]) PCDUS findings (group 1 versus group 2 respectively). Subsequently, group 2 was divided into three subgroups according to presence of arterial insufficiency (group 2a; n = 85 [11%]), venous insufficiency (group 2b; n = 140 [18.2%]) and both of arterial and venous insufficiency (group 2c; n = 15 [1.9%]), and the four groups were compared in terms of CBC parameters. There was no statistically significant difference between the 4 groups, and between the patients with normal and abnormal PCDUS findings in terms of CBC values. CBC values were not associated with PCDUS findings in patients with ED.
The LunHab project: Muscle and bone alterations in male participants following a 10 day lunar habitat simulation

What is the central question of this study? It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance? The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest.
Clinical characteristics of synthetic cannabinoid-induced psychotic disorders: a single-center analysis of hospitalized patients

Abstract This study was designed to evaluate synthetic cannabinoid (SC)-induced psychotic disorders in terms of their structure and clinical characteristics among hospitalized patients in Russia. It was a longitudinal, observational cohort study which included a total of 46 male patients who underwent the inpatient treatment in the intensive care unit or emergency department due to the SC-induced psychoses. Data on sociodemographic and disease-related characteristics, psychometric assessment scales obtained in face-to-face interviews, were recorded in all patients. The duration of catamnestic follow-up period was 2 years, with the major focus on manifestation of the schizophrenic process. Mean (SD) age of the patients with psychotic disorders induced by the SC use was 23.2 (3.5) years. Among 46 patients, 29 (63%) were SC-dependent and 17 (37%) were diagnosed with SC abuse. Average age at onset was 16.4 for psychoactive substances and 19.7 years for SC use. Marijuana was the most common first used substance. Based on our observations, we identified four clinical variants of the SC-induced psychoses. Our findings revealed that psychotic disorders are typical for the SC intoxication and most commonly influence young adults. Based on our observations, we identified four clinical variants of the SC-induced psychoses and revealed the signs which may indicate them. This study emphasizes the role of appropriate psychiatric management of SC-induced psychoses, since often only catamnestic long-term follow-up enables clinicians to determine the correct diagnosis and reveal the manifestation of the schizophrenic process.