Biochemical probing of phloem sap defensive traits in Brassica juncea-B. fruticulosa introgression lines following Lipaphis erysimi infestation.

The lack of resistance to Lipaphis erysimi in cultivated Brassicas makes caused this pest highly devastating resulting in significant loss of rapeseed-mustard productivity in India. B. fruticulosa, a wild crucifer is known as an excellent source of resistance to L. erysimi. Therefore, we planned to assess defense associated biochemical alterations and molecular components of B. juncea-B. fruticulosa ILs to mustard aphid. Phenotypic assessment of ILs on the basis of aphid population per plant (APP) categorized genotypes into resistant (7.15-18.50 APP), moderately susceptible (42.29-53.33 APP) and susceptible (70.00-77.07 APP) genotypes. Mustard aphid infested minimally B. fruticulosa (0.80 APP) among tested genotypes. The maximum increase in catalase (CAT) activity was determined in B. fruticulosa and resistant ILs after 48 h (2.03 and 1.76-fold, respectively) and one week (2.98 and 1.79-fold, respectively) of mustard aphid infestation. The strong induction of CAT2 transcripts (19.25-fold) and CAT activity (5.88-fold) along with low aphid count in resistant IL, Ad4-64 (13.85 APP) suggested the pivotal role of CAT in resistance to mustard aphid. Guaiacol peroxidase (GPX) was significantly decreased following pest infestation at both infestation stages. The ascorbate content was highest in resistant IL, ADV-6RD (2.14-fold) after one week of aphid infestation. H2O2 content rapidly increased in B. juncea-B. fruticulosa derived lines after 48 h of aphid infestation. The negative and significant association between APP and CAT (- 0.56** and - 0.48*, respectively), glutathione (- 0.43* and - 0.40*, respectively), H2O2 (- 0.57** and - 0.43*, respectively) at both 48 h and one week infestation stages signified their role in deterring mustard aphid infestation. The positive and significant association between total sugars (0.33* at 7 DPI), reducing sugars (0.33* at 7 DPI), sucrose (0.36** at 48 h) and APP indicated that higher the sugars content, higher will be mustard aphid infestation in B. juncea derived ILs. The information being generated and key candidates (CAT2, ascorbate and H2O2) being identified may help in effective deployment of B. fruticulosa resistance in mustard breeding.

Association genetics of the parameters related to nitrogen use efficiency in Brassica juncea L.

KEY MESSAGE: Genome wide association studies allowed prediction of 17 candidate genes for association with nitrogen use efficiency. Novel information obtained may provide better understanding of genomic controls underlying germplasm variations for this trait in Indian mustard. Nitrogen use efficiency (NUE) of Indian mustard (Brassica juncea (L.) Czern & Coss.) is low and most breeding efforts to combine NUE with crop performance have not succeeded. Underlying genetics also remain unexplored. We tested 92 SNP-genotyped inbred lines for yield component traits, N uptake efficiency (NUPEFF), nitrogen utilization efficiency (NUTEFF), nitrogen harvest index (NHI) and NUE for two years at two nitrogen doses (No without added N and N100 added @100 kg/ha). Genotypes IC-2489-88, M-633, MCP-632, HUJM 1080, GR-325 and DJ-65 recorded high NUE at low N. These also showed improved crop performance under high N. One determinate mustard genotype DJ-113 DT-3 revealed maximum NUTEFF. Genome wide association studies (GWAS) facilitated recognition of 17 quantitative trait loci (QTLs). Environment specificity was high. B-genome chromosomes (B02, B03, B05, B07 and B08) harbored many useful loci. We also used regional association mapping (RAM) to supplement results from GWAS. Annotation of the genomic regions around peak SNPs helped to predict several gene candidates for root architecture, N uptake, assimilation and remobilization. CAT9 (At1g05940) was consistently envisaged for both NUE and NUPEFF. Major N transporter genes, NRT1.8 and NRT3.1 were predicted for explaining variation for NUTEFF and NUPEFF, respectively. Most significant amino acid transporter gene, AAP1 appeared associated with NUE under limited N conditions. All these candidates were predicted in the regions of high linkage disequilibrium. Sequence information of the predicted candidate genes will permit development of molecular markers to aid breeding for high NUE.

Safranal inhibits NLRP3 inflammasome activation by preventing ASC oligomerization.

NLRP3 inflammasome is involved in several chronic inflammatory diseases. The inflammatory effect of the NLRP3 inflammasome is executed through IL-1ß and IL-18. Therefore, IL-1ß is one of the primary targets in chronic inflammatory conditions. However, current treatment regimens are dependent on anti- IL-1ß biologicals. The therapies targeting IL-1ß through inhibition of NLRP3 inflammasome are thus being actively explored. We identified safranal, a small molecule responsible for the essence of saffron as a potential inhibitor of the NLRP3 inflammasome. Safranal significantly suppressed the release of IL-1ß from ATP stimulated J774A.1 and bone marrow-derived macrophages (BMDMs) by regulating CASP1 and CASP8 dependent cleavage of pro-IL-1ß. Safranal markedly suppressed the expression of NLRP3 and its ATPase activity. Safranal treatment enhanced the expression of NRF2, whereas, si-RNA mediated silencing of Nrf2 abrogated the anti-NLRP3 effect of safranal. Furthermore, safranal inhibited ASC oligomerization and formation of ASC specks. Safranal also displayed anti-NLRP3 activity in multiple mice models. Treatment of animals with safranal reduced the production of IL-1ß in ATP elicited peritoneal inflammation, MSU induced air pouch inflammation, and MSU injected foot paw edema in mice. Thus, our data projects safranal as a potential preclinical drug candidate against NLRP3 inflammasome triggered chronic inflammation.

Anchoring alien chromosome segment substitutions bearing gene(s) for resistance to mustard aphid in Brassica juncea-B. fruticulosa introgression lines and their possible disruption through gamma irradiation.

KEY MESSAGE: Heavy doses of gamma irradiation can reduce linkage drag by disrupting large sized alien translocations and promoting exchanges between crop and wild genomes. Resistance to mustard aphid (Lipaphis erysimi) infestation was significantly improved in Brassica juncea through B. juncea-B. fruticulosa introgression. However, linkage drag caused by introgressed chromatin fragments has so far prevented the deployment of this resistance source in commercial cultivars. We investigated the patterns of donor chromatin segment substitutions in the introgression lines (ILs) through genomic in situ hybridization (GISH) coupled with B. juncea chromosome-specific oligonucleotide probes. These allowed identification of large chromosome translocations from B. fruticulosa in the terminal regions of chromosomes A05, B02, B03 and B04 in three founder ILs (AD-64, 101 and 104). Only AD-101 carried an additional translocation at the sub-terminal to intercalary position in both homologues of chromosome A01. We validated these translocations with a reciprocal blast hit analysis using shotgun sequencing of three ILs and species-specific contigs/scaffolds (kb sized) from a de novo assembly of B. fruticulosa. Alien segment substitution on chromosome A05 could not be validated. Current studies also endeavoured to break linkage drag by exposing seeds to a heavy dose (200kR) of gamma radiation. Reduction in the size of introgressed chromatin fragments was observed in many M3 plants. There was a complete loss of the alien chromosome fragment in one instance. A few M3 plants with novel patterns of chromosome segment substitutions displayed improved agronomic performance coupled with resistance to mustard aphid. SNPs in such genomic spaces should aid the development of markers to track introgressed DNA and allow application in plant breeding.

Soluble Aß1-42 suppresses TNF-α and activates NLRP3 inflammasome in THP-1 macrophages.

Deposition of amyloid-ß in Alzheimer's disease is accompanied by chronic inflammation, which involves raised levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß. However, the role of Aß1-42 in the inflammatory process, before it gets deposited into aggregates has not been investigated thoroughly. Through this study, we are illustrating the dual role of soluble Aß1-42 (sAß1-42) in activating the NLRP3 inflammasome and simultaneously inhibiting TNF-α secretion. Our data suggested that the treatment of chronically induced THP-1 macrophages and N9 microglial cells with sAß1-42 can suppress the major inflammatory cytokine TNF-α without affecting the level of IL-6. However, the activation of NLRP3 inflammasome was well evidenced by secretion of IL-1ß, increased expression of NLRP3 and caspase-1, implicating sAß1-42 in enhancing and suppressing one or other type of inflammation. Further investigation revealed that sAß1-42 was able to severely abrogate the expression of NF-κB, p50 and restricting the translocation of NF-κB, p65 to nucleus by inhibiting phosphorylation of IκB-α in THP-1 macrophages. These data indicate that the sAß1-42 may play a dual role during inflammatory process, wherein, it may be involved in protecting the cells from inflammatory damage due to TNF-α. This ability of sAß1-42 might be playing some role in protecting the brain cells during the process of aging and Alzheimer's disease, where, chronic inflammatory environment plays a vital role.

Segregation for fertility and meiotic stability in novel Brassica allohexaploids.

KEY MESSAGE: Allohexaploid Brassica populations reveal ongoing segregation for fertility, while genotype influences fertility and meiotic stability. Creation of a new Brassica allohexaploid species is of interest for the development of a crop type with increased heterosis and adaptability. At present, no naturally occurring, meiotically stable Brassica allohexaploid exists, with little data available on chromosome behaviour and meiotic control in allohexaploid germplasm. In this study, 100 plants from the cross B. carinata × B. rapa (A2 allohexaploid population) and 69 plants from the cross (B. napus × B. carinata) × B. juncea (H2 allohexaploid population) were assessed for fertility and meiotic behaviour. Estimated pollen viability, self-pollinated seed set, number of seeds on the main shoot, number of pods on the main shoot, seeds per ten pods and plant height were measured for both the A2 and H2 populations and for a set of reference control cultivars. The H2 population had high segregation for pollen viability and meiotic stability, while the A2 population was characterised by low pollen fertility and a high level of chromosome loss. Both populations were taller, but had lower average fertility trait values than the control cultivar samples. The study also characterises fertility and meiotic chromosome behaviour in genotypes and progeny sets in heterozygous allotetraploid Brassica derived lines, and indicates that genotypes of the parents and H1 hybrids are affecting chromosome pairing and fertility phenotypes in the H2 population. The identification and characterisation of factors influencing stability in novel allohexaploid Brassica populations will assist in the development of this as a new crop species for food and agricultural benefit.

Development and molecular-genetic characterization of a stable Brassica allohexaploid.

KEY MESSAGE: We report first-time synthesis of a stable Brassica allohexaploid. It may evolve into a new species and also advance our understanding of pairing regulation and genome evolution in complex allopolyploids. Crop Brassicas include both monogenomic and digenomic species. A trigenomic Brassica (AABBCC) is not known to exist in nature. Past attempts to synthesize a stable allohexaploid were not successful due to aberrant meiosis and very high proportion of aneuploid plants in the selfed progenies. We report the development of a stable allohexaploid Brassica (2n = 54; AABBCC). Genomic in situ hybridization confirmed the complete assemblage of three genomes. Only allohexaploids involving B. rapa cv. R01 (2n = 20; AA) as pollinator with a set of B. carinata (2n = 34; BBCC) were stable. These exhibited a high proportion (0.78-0.94) of pollen mother cells with normal meiosis and an excellent hexaploid ratio (0.80-0.94) in the selfed progenies. Stability of two allohexaploid combinations was demonstrated from H1 to H4 generations at two very diverse locations in India. Graphical genotyping of allohexaploids allowed detection of chromosome fragment exchanges among three genomes. These were much smaller for meiotically stable allohexaploids as compared to unstable ones. The putative hexaploids were morphologically closer to the female donor, B. carinata, for leaf morphology, inflorescence structure and flower shape. The newly formed allohexaploid may also provide unique opportunities to investigate the immediate genetic and genomic consequences of a Brassica allohexaploid with three resident genomes.

Molecular-cytogenetic characterization of C-genome chromosome substitution lines in Brassica juncea (L.) Czern and Coss.

KEY MESSAGE: C genome chromosome substitution lines of B. juncea constitute a key genetic resource for increased genetic diversity and hybrid performance. C genome chromosome substitution lines were found in the progenies of derived B. juncea (2n = 36; AABB), synthesized through hybridization between B. napus and B. carinata. These were originally recognized based on the morphology and genomic in situ hybridization. Genotyping using the Brassica Illumina 60K Infinium SNP array confirmed the presence of C genome chromosomes in a large number of derived B. juncea genotypes. Three whole chromosome substitutions and 13 major C genome fragment substitutions were identified. Fragment substitutions were primarily terminal, but intercalary substitution(s) involving chromosome C1 and C2 were identified in three genotypes. The size of substituted C genome fragments varied from 0.04 Mbp (C1) to 64.85 Mbp (C3). In terms of proportions, these ranged from 0.10 % (C1) to 100 % (C1, C3 and C7) of the substituted chromosome. SSR genotyping with B genome specific primers suggested that substituting C genome chromosome(s) are likely to have replaced B genome chromosome(s). C1 was the most common substituting chromosome while substituted B chromosome seemed random. Study of the phenotypic traits underlined the importance of the substitution lines (especially of chromosome C1) for conferring superior trait performance (main shoot length and pods on the main shoot). High heterosis was also indicated in hybrid combinations of substitution lines with natural B. juncea. These substitution genotypes constituted a valuable resource for targeted gene transfer and QTL identification.

Resynthesis of Brassica napus through hybridization between B. juncea and B. carinata.

KEY MESSAGE: First report for the resynthesis of Brassica napus by recombining A and C genome from B. juncea and B. carinata , respectively. Also documents B genome introgressions in resynthesized B. napus. Resynthesis of Brassica napus (AACC) was achieved by hybridizing Brassica juncea (AABB) with Brassica carinata (BBCC). This was facilitated by spontaneous chromosome doubling in the F1 hybrid (ABBC) to yield octaploid (AABBBBCC), elimination of extra B genome chromosomes in the resulting octaploid and in subsequent selfed generations, aided with directed selection for fertile plants having B. napus morphology. Twenty-five plants with varying degrees of resemblance to natural B. napus were identified from 17 A5 progenies and assayed for cytogenetic stability and genetic diversity. Majority of these plants, except six (2n = 38) were hyperploids (2n = 40-56). The six plants with 2n = 38 were designated as derived B. napus types. These showed an expected meiotic configuration of 19II at metaphase-I, with 19-19 distribution at anaphase-I. Genotyping based on A and C genome specific primers confirmed genetic identity of six derived (2n = 38) B. napus plants with natural types whereas genotyping with B genome specific primers indicated introgression of B genome segments. This was also confirmed by genomic in situ hybridization (GISH). Strong signals of B genome probe were detected, proving hitherto unreported genetic exchanges between B and A/C chromosomes. These introgressions possibly occurred en route five generations of selfing. Derived plants yielded fertile hybrids in crosses with natural B. napus var. GSC 6. The selfed derived plants as evaluated in A6 plant to progeny rows were morphologically similar to natural B. napus, and meiotically stable. Agronomic assessment of these progenies revealed variation for key morpho-physiological traits. Of special interest were the progenies with plants having oil content exceeding 47% as against about 39-41% in existing cultivars.

Population structure and breeding value of a new type of Brassica juncea created by combining A and B genomes from related allotetraploids.

KEY MESSAGE: Derived amphiploidy helped to resynthesize agronomically superior B. juncea germplasm which showed high heterosis in crosses with natural B. juncea . This new procedure facilitates a seamless flow of variation across Brassica digenomics. Brassica digenomics, artificially resynthesized by hybridizing extant genome donor diploids, show poor breeding value due to the linkage drag associated with diploid donors. We recently developed a method that involves resynthesis through hybridization between related allotetraploids. Derived B. juncea was created by combining A and B genomes extant in B. napus and B. carinata, respectively. Large genomic and agronomic modifications resulted. Population structure analysis based on the DNA polymorphism generated using 108 locus-specific SSR primers helped to identify three pools of allelic diversity. Thirteen progenies with determinate plant growth habit were discovered, and these aligned closely with B genome of the donor species like B. nigra and B. carinata. The indeterminate group showed greater genetic affinity with extant B. juncea. Derived genotypes possessed high agronomic potential. Importantly, high heterosis was observed in crosses between derived and natural B. juncea. Some derived juncea progenies figured in heterotic combinations during both the years of F 1 hybrid evaluation. In essence, the hybrids between derived B. juncea and natural B. juncea can be considered as interspecific hybrids between B. juncea and B. napus for A genome and between B. juncea and B. carinata for B genome. This possibly explains their high heterosis-inducing potential. Integrating genetic diversity with the inherent breeding value allowed more efficient prediction of heterosis. Besides generation of new novel variability of huge economic importance and operational simplicity, the method of derived amphiploidy allows a seamless flow of heritable variation across Brassica digenomics.

A Fast-Binding, Functionally Reversible, COX-2 Radiotracer for CNS PET Imaging.

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [11C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [11C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [11C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [11C]BRD1158 human PET.

Associations of longitudinal BMI percentile classification patterns in early childhood with neighborhood-level social determinants of health.

Background: Understanding social determinants of health (SDOH) that may be risk factors for childhood obesity is important to developing targeted interventions to prevent obesity. Prior studies have examined these risk factors, mostly examining obesity as a static outcome variable. Objectives: This study aimed to identify distinct subpopulations based on BMI percentile classification or changes in BMI percentile classifications over time and explore these longitudinal associations with neighborhood-level SDOH factors in children from 0 to 7 years of age. Methods: Using Latent Class Growth (Mixture) Modelling (LCGMM) we identify distinct BMI% classification groups in children from 0 to 7 years of age. We used multinomial logistic regression to study associations between SDOH factors with each BMI% classification group. Results: From the study cohort of 36,910 children, five distinct BMI% classification groups emerged: always having obesity (n=429; 1.16%), overweight most of the time (n=15,006; 40.65%), increasing BMI% (n=9,060; 24.54%), decreasing BMI% (n=5,058; 13.70%), and always normal weight (n=7,357; 19.89%). Compared to children in the decreasing BMI% and always normal weight groups, children in the other three groups were more likely to live in neighborhoods with higher rates of poverty, unemployment, crowded households, and single-parent households, and lower rates of preschool enrollment. Conclusions: Neighborhood-level SDOH factors have significant associations with children's BMI% classification and changes in classification over time. This highlights the need to develop tailored obesity interventions for different groups to address the barriers faced by communities that can impact the weight and health of the children living within them.

Perceived Gaps in Academic Training and Expectations From Refresher Training in Primary Care Nurses at an Urban Metropolis in Northern India: A Qualitative Study.

Background Nursing professionals, comprising the largest workforce engaged in the primary healthcare system, play a pivotal role in addressing population health needs. However, gaps in the training of nurses and midwives in lower-middle-income countries may undermine their performance and necessary skill development for fulfilling key population health needs. Substantial challenges exist in improving the regular curricular and refresher training of diplomate nurses and midwives working in primary care facilities and supporting both clinical care and health promotion functions. The study objective was to conduct a gap analysis in the present nursing curriculum and training profile of general duty midwives working in urban primary health facilities and understand their expectations and preferences from the planned refresher training course.  Methods We conducted a qualitative explorative study among General Nursing midwives (GNMs) working in urban primary health facilities in the Gurugram district of Haryana, India to conduct a gap analysis in their present curriculum and training preferences.  Results A total of 17 nurses with a mean (SD) age of 33.52 (4.75) years and an average nursing work experience of 5.35 (0.56) years were interviewed in-depth. Lack of practical applicability, complex study material, inexperienced tutors, and weak English language comprehension were key barriers in the existing nursing curriculum. The nurses expressed willingness to participate in refresher training with varied expectations, although there existed a distinct preference for short, flexible, and blended online-offline modes of training.  Conclusions Strengthening GNM nursing education should be prioritized in Indian health settings with the focus on improving student comprehension through vernacular instruction when feasible, and capacity building of tutors, with avenues for continued training and education. There is also a need for strengthening the curriculum related to key emergent public health challenges related to non-communicable diseases and mental health, as also skills for client and patient counseling and communication.

Holt-Oram Syndrome: An Incidental Diagnosis.

Holt-Oram syndrome is a rare autosomal dominant disorder which occurs because of mutations in the TBX5 genes. Most notable manifestations include musculoskeletal deformities, predominantly affecting the upper limbs, and congenital heart defects. Presentation could be multifaceted leading to delay in diagnosis. We describe an interesting incidental diagnosis of Holt-Oram syndrome in a young female adult who accompanied her son to the clinic. He had undergone closure of both atrial septal defect (ASD) and patent ductus arteriosus (PDA) in his infancy. She reported progressive exertional dyspnoea, reduced exercise tolerance, and palpitations; incidentally, she was noted to have right upper limb deformities. These findings prompted further evaluation and thereafter, resulted in a diagnosis of Holt-Oram syndrome.

Thyrotoxic Periodic Paralysis: Case Presentation With Tetraparesis and Cardiac Dysrhythmia.

Thyrotoxic hypokalaemic periodic paralysis (THPP) is a rare complication of hyperthyroidism that is potentially life-threatening if not treated promptly. It is more common in Asian and Polynesian populations and very few cases have been reported to date in people of White ethnicity. We present a case report of a young male patient of White ethnicity, who was initially brought in as a stroke alert with tetraparesis which was ruled out on initial assessment, but then had a syncopal episode and was noted to be initially bradycardic and subsequently tachycardic. Blood tests showed hypokalaemia and hypophosphataemia and he was treated as a hypokalaemic periodic paralysis patient. Intravenous potassium replacement was commenced. Symptoms and ECG changes resolved with correction of potassium levels. Thyroid function tests requested later were suggestive of hyperthyroidism and the diagnosis of thyrotoxic hypokalaemic periodic paralysis was made. This is an interesting case given its rarity, and this case report highlights the importance of early diagnosis and prompt treatment.

Few-Shot Learning with Semi-Supervised Transformers for Electronic Health Records.

With the growing availability of Electronic Health Records (EHRs), many deep learning methods have been developed to leverage such datasets in medical prediction tasks. Notably, transformer-based architectures have proven to be highly effective for EHRs. Transformer-based architectures are generally very effective in "transferring" the acquired knowledge from very large datasets to smaller target datasets through their comprehensive "pre-training" process. However, to work efficiently, they still rely on the target datasets for the downstream tasks, and if the target dataset is (very) small, the performance of downstream models can degrade rapidly. In biomedical applications, it is common to only have access to small datasets, for instance, when studying rare diseases, invasive procedures, or using restrictive cohort selection processes. In this study, we present CEHR-GAN-BERT, a semi-supervised transformer-based architecture that leverages both in- and out-of-cohort patients to learn better patient representations in the context of few-shot learning. The proposed method opens new learning opportunities where only a few hundred samples are available. We extensively evaluate our method on four prediction tasks and three public datasets showing the ability of our model to achieve improvements upwards of 5% on all performance metrics (including AUROC and F1 Score) on the tasks that use less than 200 annotated patients during the training process.

Obesity Prediction with EHR Data: A deep learning approach with interpretable elements.

Childhood obesity is a major public health challenge. Early prediction and identification of the children at an elevated risk of developing childhood obesity may help in engaging earlier and more effective interventions to prevent and manage obesity. Most existing predictive tools for childhood obesity primarily rely on traditional regression-type methods using only a few hand-picked features and without exploiting longitudinal patterns of children's data. Deep learning methods allow the use of high-dimensional longitudinal datasets. In this paper, we present a deep learning model designed for predicting future obesity patterns from generally available items on children's medical history. To do this, we use a large unaugmented electronic health records dataset from a large pediatric health system in the US. We adopt a general LSTM network architecture and train our proposed model using both static and dynamic EHR data. To add interpretability, we have additionally included an attention layer to calculate the attention scores for the timestamps and rank features of each timestamp. Our model is used to predict obesity for ages between 3-20 years using the data from 1-3 years in advance. We compare the performance of our LSTM model with a series of existing studies in the literature and show it outperforms their performance in most age ranges.

An Extensive Data Processing Pipeline for MIMIC-IV.

An increasing amount of research is being devoted to applying machine learning methods to electronic health record (EHR) data for various clinical purposes. This growing area of research has exposed the challenges of the accessibility of EHRs. MIMIC is a popular, public, and free EHR dataset in a raw format that has been used in numerous studies. The absence of standardized preprocessing steps can be, however, a significant barrier to the wider adoption of this rare resource. Additionally, this absence can reduce the reproducibility of the developed tools and limit the ability to compare the results among similar studies. In this work, we provide a greatly customizable pipeline to extract, clean, and preprocess the data available in the fourth version of the MIMIC dataset (MIMIC-IV). The pipeline also presents an end-to-end wizard-like package supporting predictive model creations and evaluations. The pipeline covers a range of clinical prediction tasks which can be broadly classified into four categories - readmission, length of stay, mortality, and phenotype prediction. The tool is publicly available at https://github.com/healthylaife/MIMIC-IV-Data-Pipeline.

Flexible-Window Predictions on Electronic Health Records.

Various types of machine learning techniques are available for analyzing electronic health records (EHRs). For predictive tasks, most existing methods either explicitly or implicitly divide these time-series datasets into predetermined observation and prediction windows. Patients have different lengths of medical history and the desired predictions (for purposes such as diagnosis or treatment) are required at different times in the future. In this paper, we propose a method that uses a sequence-to-sequence generator model to transfer an input sequence of EHR data to a sequence of user-defined target labels, providing the end-users with "flexible" observation and prediction windows to define. We use adversarial and semi-supervised approaches in our design, where the sequence-to-sequence model acts as a generator and a discriminator distinguishes between the actual (observed) and generated labels. We evaluate our models through an extensive series of experiments using two large EHR datasets from adult and pediatric populations. In an obesity predicting case study, we show that our model can achieve superior results in flexible-window prediction tasks, after being trained once and even with large missing rates on the input EHR data. Moreover, using a number of attention analysis experiments, we show that the proposed model can effectively learn more relevant features in different prediction tasks.

Genome wide association studies for acid phosphatase activity at varying phosphorous levels in Brassica juncea L.

Acid phosphatases (Apases) are an important group of enzymes that hydrolyze soil and plant phosphoesters and anhydrides to release Pi (inorganic phosphate) for plant acquisition. Their activity is strongly correlated to the phosphorus use efficiency (PUE) of plants. Indian mustard (Brassica juncea L. Czern & Coss) is a major oilseed crop that also provides protein for the animal feed industry. It exhibits low PUE. Understanding the genetics of PUE and its component traits, especially Apase activity, will help to reduce Pi fertilizer application in the crop. In the present study, we evaluated 280 genotypes of the diversity fixed foundation set of Indian mustard for Apase activity in the root (RApase) and leaf (LApase) tissues at three- low (5µM), normal (250µM) and high (1mM) Pi levels in a hydroponic system. Substantial effects of genotype and Pi level were observed for Apase activity in both tissues of the evaluated lines. Low Pi stress induced higher mean RApase and LApase activities. However, mean LApase activity was relatively more than mean RApase at all three Pi levels. JM06016, IM70 and Kranti were identified as promising genotypes with higher LApase activity and increased R/S at low Pi. Genome-wide association study revealed 10 and 4 genomic regions associated with RApase and LApase, respectively. Annotation of genomic regions in the vicinity of peak associated SNPs allowed prediction of 15 candidates, including genes encoding different family members of the acid phosphatase such as PAP10 (purple acid phosphatase 10), PAP16, PNP (polynucleotide phosphorylase) and AT5G51260 (HAD superfamily gene, subfamily IIIB acid phosphatase) genes. Our studies provide an understanding of molecular mechanism of the Apase response of B. juncea at varying Pi levels. The identified SNPs and candidate genes will support marker-assisted breeding program for improving PUE in Indian mustard. This will redeem the crop with enhanced productivity under restricted Pi reserves and degrading agro-environments.