Modulation of nuclear receptor 4A1 expression improves insulin secretion in a mouse model of chronic pancreatitis.

OBJECTIVES: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to insulin secretory defects and associated metabolic alterations. Owing to lack of molecular understanding, no pharmacotherapies to treat insulin secretory defects have been approved to date. We aimed to delineate the molecular mechanism of ß-cell dysfunction in CP. METHODS: Transcriptomic analysis was conducted to identify endocrine specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis on NovaSeq 6000 of NR4A1 overexpressed (OE) MIN6 cells was performed to identify aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure. Downstream effect of NR4A1OE was examined by Fura2 AM based fluorometric and imaging studies of intracellular calcium. Mice with CP were treated with IFN-γ neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion. RESULTS: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 µg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 µg/mg protein/minute, p = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold (p = 0.03), improved insulin secretion (4.4 ± 0.2-fold, p = 0.01), associated with increased Ca2+ levels (2.39 ± 0.06-fold, p = 0.009). CONCLUSIONS: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.

Mechanistic insights into the early life stage microbiota of silver pompano (Trachinotus blochii).

Introduction: Deep investigations of host-associated microbiota can illuminate microbe-based solutions to improve production in an unprecedented manner. The poor larval survival represents the critical bottleneck in sustainable marine aquaculture practices. However, little is known about the microbiota profiles and their governing eco-evolutionary processes of the early life stages of marine teleost, impeding the development of suitable beneficial microbial management strategies. The study provides first-hand mechanistic insights into microbiota and its governing eco-evolutionary processes in early life stages of a tropical marine teleost model, Trachinotus blochii. Methods: The microbiota profiles and their dynamics from the first day of hatching till the end of metamorphosis and that of fingerling's gut during the routine hatchery production were studied using 16S rRNA amplicon-based high-throughput sequencing. Further, the relative contributions of various external factors (rearing water, live feed, microalgae, and formulated feed) to the microbiota profiles at different ontogenies was also analyzed. Results: A less diverse but abundant core microbial community (~58% and 54% in the whole microbiota and gut microbiota, respectively) was observed throughout the early life stages, supporting 'core microbiota' hypothesis. Surprisingly, there were two well-differentiated clusters in the whole microbiota profiles, ≤10 DPH (days post-hatching) and > 10 DPH samples. The levels of microbial taxonomic signatures of stress indicated increased stress in the early stages, a possible explanation for increased mortality during early life stages. Further, the results suggested an adaptive mechanism for establishing beneficial strains along the ontogenetic progression. Moreover, the highly transient microbiota in the early life stages became stable along the ontogenetic progression, hypothesizing that the earlier life stages will be the best window to influence the microbiota. The egg microbiota also crucially affected the microbial community. Noteworthily, both water and the feed microbiota significantly contributed to the early microbiota, with the feed microbiota having a more significant contribution to fish microbiota. The results illustrated that rotifer enrichment would be the optimal medium for the early larval microbiota manipulations. Conclusion: The present study highlighted the crucial foundations for the microbial ecology of T. blochii during early life stages with implications to develop suitable beneficial microbial management strategies for sustainable mariculture production.

[An abdominal wall bulging: consider a neurological cause]. / Een uitstulping van de buik.

A patient with a swelling of the abdominal wall is a regular occurrence in general practice and hospital. The diagnosis can often be made with a thorough history and physical examination. An abdominal wall hernia is characterized by an increase in swelling on standing physical examination and Valsalva maneuver, which is often reducible, and a hernia defect is palpable. If no interruption of the abdominal wall is palpable and there is hypoesthesia, there may be an abdominal wall paresis because of thoracic paramedian hernia nuclei pulposi (HNP). Where an abdominal wall hernia is treated surgically in case of symptoms, this is conservatively treated with an HNP.

Dissociation of attentional state and behavioral outcome using local field potentials.

Behavioral outcome (i.e., whether a target is detected or missed) depends on attentional state and potentially other factors related to decision-making, which could in turn modulate the power and phase of neuronal oscillations. Here we investigated whether attentional state (i.e., whether attention is inside or outside the receptive fields of neurons) and behavioral outcome are distinguishable using the power and phase of local field potential (LFP) recorded from electrode arrays in area V4 of two male rhesus monkeys performing an attentional task under different cuing conditions. Since attention also strongly modulates pairwise measures such as spike count correlation and phase consistency which are typically measured across trials, we developed novel methods to obtain single-trial estimates of these measures. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase, although single-trial gamma phase consistency provided good attentional discriminability. Our results provide a clear dissociation between the neural mechanisms that regulate attentional focus and those that govern behavioral outcome.

Impact of toothbrush head configuration and dentifrice abrasivity on non-carious cervical lesions in-vitro.

OBJECTIVE: To investigate the effect of toothbrush head configuration and dentifrice slurry abrasivity on the development of simulated non-carious cervical lesions (NCCLs) in vitro. METHODS: Extracted premolars were randomly allocated into 15 groups (n = 16) generated by the association between toothbrush head configuration (flat-trimmed, rippled, cross-angled/multilevel/rubbers added, cross-angled/multilevel/flex head, feathered) and dentifrice slurry abrasivity (low/medium/high). Teeth were mounted on acrylic blocks and had their roots partially covered with acrylic resin, leaving 2-mm root surfaces exposed. Toothbrushing was performed for 35,000 and 65,000 double-strokes. Specimens were analyzed using non-contact profilometry for dental volume loss (mm3) and lesion morphology. Data was analyzed using ANOVA with pairwise comparisons and Kruskal-Wallis tests. RESULTS: The two-way interaction between toothbrush head configuration and slurry abrasivity was significant (p = 0.02). At 35,000 strokes, the flat-trimmed and cross-angled/multilevel/rubbers added toothbrushes caused the highest loss, when associated to the high-abrasive slurry (p<0.05); whereas cross-angled/multilevel/flex head showed the least loss, when associated to the low-abrasive (p<0.05). At 65,000, more dental loss was observed for all toothbrushes when associated to the high-abrasive slurry, with flat-trimmed causing the highest loss (p < 0.05). Lower dental loss rates were observed for cross-angled/multilevel/flex head associated to the low-abrasive slurry when compared to the other toothbrushes (p < 0.05), except to feathered (p = 0.14) and rippled (p = 0.08). Flat lesions (mean internal angle ± standard-deviation: 146.2°± 16.8) were mainly associated with low-abrasive slurry, while wedge-shaped lesions (85.8°± 18.8) were more frequent with medium- and high-abrasive slurries. CONCLUSION: The development, progression and morphology of simulated NCCLs were modulated by both toothbrush head configuration and dentifrice abrasivity. CLINICAL SIGNIFICANCE: Dental professionals should consider both the type of toothbrush and dentifrice abrasivity in the management plan of patients at risk of developing NCCLs.

Formulation of herbal based hair colour from Phyllanthus reticulatus.

Synthetic oxidative hair dyes available in the market contain a combination of peroxide and ammonia. In addition, people who use synthetic dyes are at risk for skin burns, irritation to the eye and also lead to cancer. Hence, herbal-based hair dyes are safe to use. In the traditional system of medicine, different parts of Phyllanthus reticulatus were used for curing various ailments. The aqueous leaf extract showed the presence of phytochemical rich components. Herbal hair dye has been formulated by using P. reticulatus with various natural ingredients in the ratio of 5:1:1:1:1. The herbal hair dye was evaluated for its various parameters. It showed potent in vitro antimicrobial activity against various microorganisms and antioxidant activity. In the formulated product, the natural ingredients are known for their non-toxic properties and there are no added chemicals and preservatives. It offers a natural alternative, that can be used irrespective of any side effects.

Impact of Enhanced Recovery After Surgery pathway for cesarean delivery on postoperative pain.

BACKGROUND: Enhanced Recovery After Surgery pathways provide evidence-based recommendations to optimize perioperative care. OBJECTIVE: This study aimed to holistically investigate the effect of implementing an Enhanced Recovery After Surgery pathway for all cesarean deliveries on postoperative pain experience. STUDY DESIGN: This was a prepost study comparing subjective and objective measures of postoperative pain before and after the implementation of an Enhanced Recovery After Surgery pathway for cesarean delivery. The Enhanced Recovery After Surgery pathway was developed by a multidisciplinary team and included preoperative, intraoperative, and postoperative components, with emphasis on preoperative preparation, hemodynamic optimization, early mobilization, and multimodal analgesia. All individuals undergoing cesarean delivery, whether scheduled, urgent, or emergent, were included. Demographic, delivery, and inpatient pain management data were obtained through medical record review. Of note, 2 weeks after discharge, patients were surveyed about their delivery experience, analgesic usage, and complications. The primary outcome was inpatient opioid use. RESULTS: The study included 128 individuals, 56 in the preimplementation cohort and 72 in the Enhanced Recovery After Surgery cohort. Baseline characteristics between the 2 groups were similar. The survey response rate was 73% (94/128). Opioid use in the first 48 hours postoperatively was significantly lower in the Enhanced Recovery After Surgery group than the preimplementation group (9.4 vs 21.4 morphine milligram equivalents 0-24 hours after delivery [P<.001]; 14.1 vs 25.4 morphine milligram equivalents 24-48 hours after delivery [P<.001]) with no increase in either average or maximum postoperative pain scores. Individuals in the Enhanced Recovery After Surgery group used fewer opioid pills after discharge (10 vs 20; P<.001). Patient satisfaction and complication rates did not change after the implementation of an Enhanced Recovery After Surgery pathway. CONCLUSION: The implementation of an Enhanced Recovery After Surgery pathway for all cesarean deliveries decreased both inpatient and outpatient postpartum opioid use without increasing pain scores or decreasing patient satisfaction.

Non-alcoholic fatty liver disease is not associated with impairment in health-related quality of life in virally suppressed persons with human immune deficiency virus.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups. Prospectively enrolled 200 PWH and 474 participants with primary NAFLD completed the Rand SF-36 assessment which measures 8 domains of HRQOL. Individual domain scores were used to create composite physical and mental component summary scores. Univariate and multivariate analyses determined variables associated with HRQOL in PWH and in HIV- and primary NAFLD. In PWH, 48% had HIV-NAFLD, 10.2% had clinically significant fibrosis, 99.5% were on antiretroviral therapy, and 96.5% had HIV RNA <200 copies/ml. There was no difference in HRQOL in PWH with or without NAFLD. Diabetes, non-Hispanic ethnicity, and nadir CD4 counts were independently associated with impaired HRQOL in PWH. In HIV-NAFLD, HRQOL did not differ between participants with or without clinically significant fibrosis. Participants with HIV-NAFLD compared to those with primary NAFLD were less frequently cisgender females, White, more frequently Hispanic, had lower BMI and lower frequency of obesity and diabetes. HRQOL of individuals with HIV-NAFLD was not significantly different from those with primary NAFLD. In conclusion, in virally suppressed PWH, HRQOL is not different between participants with or without HIV-NAFLD. HRQOL is not different between HIV-NAFLD and primary NAFLD.

Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.

BACKGROUND AIMS: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. APPROACH RESULTS: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. CONCLUSIONS: Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

Comparative Assessment of the Efficacy of Two-Dimensional Digital Intraoral Radiography to Three-Dimensional Cone Beam Computed Tomography in the Diagnosis of Periapical Pathologies.

Background: Periapical intraoral radiographs are useful in assessing periapical pathologies; essential information often is not extracted owing to difficult interpretation and two-dimensional presentation of three-dimensional structures focusing on using cone beam CT (CBCT) and other advanced imaging modalities. Aims: The present study was conducted to comparatively assess the digital intraoral radiography to CBCT in the diagnosis of periapical pathologies. Materials and Methods: In 50 teeth, CBCT and digital imaging were compared in assessing periapical pathologies using CBCTPA and six-point scoring. The scores obtained were assessed and compared with statistical evaluation. The data were expressed in percentage and number and mean and standard deviation. The level of significance was kept at P < 0.05. Results: On comparing 3D CBCT and 2D digital imaging for assessing the study parameters, it was seen that resorption was seen in 33, 30, and 9 teeth, respectively, on 3, 2, and 1 rooted tooth on CBCT and 13, 16, and 7 teeth on digital radiography. The numbers of roots and root canals on CBCT were 45, 34, and 18 in 3, 2, and 1 rooted tooth and 50, 32, and 18 on digital imaging. Lesions were detected on CBCT in 16, 18, and 18 teeth on CBCT in 3, 2, and 1 rooted tooth, respectively, and in 14, 14, and 16 teeth on digital imaging. Comparing the five-point scale for lesions and CBPAI index for CBCT and digital imaging, the difference was statistically significant with P = 0.004 and <0.0001, respectively. Conclusion: The present study concludes that 3D CBCT is superior in accuracy to 2D imaging in diagnosing the periapical lesions, especially concerning multirooted teeth. Owing to its high radiation exposure and cost, 2D imaging can be incorporated in assessing periapical pathology for the single-rooted tooth.

The impact of dental curriculum format on student performance on the national board dental examination.

PURPOSE/OBJECTIVE: The effectiveness of different curriculum types has long been debated by dental educators aiming to provide the best education possible to their students. This study aimed to evaluate the effect of curriculum type (hybrid problem-based learning [PBL] vs. traditional) on National Board Dental Examination (NBDE) part I and II pass rates METHODS: A retrospective cohort study was conducted with a hybrid PBL cohort and traditional cohort. NBDE part I and II pass rates for the two cohorts were acquired, along with demographic and scholastic variables. Pass rates, scholastic variables, and demographic variables were compared using two-sample t-tests and chi-square tests. Associations of the variables with pass rates were analyzed using logistic regression. Significance was set at 5% RESULTS: No significant differences in pass rates for NBDE part I and II were observed between the cohorts. Cumulative dental school grade point average (GPA) was found to be an independent predictor of success for NBDE part I (odds ratio (OR): 1.40, 1.24-1.59 for 0.1 point intervals) and II (OR: 1.34, 1.18-1.52 for 0.1 point intervals), (p < 0.01). DAT biology sub-score was found to be predictive of success for NBDE part I (OR: 1.58, 1.14-2.19), (p = 0.01) CONCLUSIONS: No significant difference in NBDE part I and II pass rates between the cohorts was found. Dental school GPA was the most predictive variable for success on NBDE part I and II. These findings may be helpful considerations as institutions assess the structure of their school curricula.

Decoding of attentional state using local field potentials.

We review recent efforts to decode visual spatial attention from different types of brain signals, such as spikes and local field potentials (LFPs). Combining signals from more electrodes improves decoding, but the pattern of improvement varies considerably depending on the signal as well as the task (for example, decoding of sensory stimulus/motor intention versus location of attention). We argue that this pattern of results conveys important information not only about the usefulness of a particular brain signal for decoding attention, but also about the spatial scale over which attention operates in the brain. The spatial scale, in turn, likely depends on the extent of underlying mechanisms such as normalization, gain control via excitation-inhibition interactions, and neuromodulatory regulation of attention.

Probing the competitive inhibitor efficacy of frog-skin alpha helical AMPs identified against ACE2 binding to SARS-CoV-2 S1 spike protein as therapeutic scaffold to prevent COVID-19.

In COVID-19 infection, the SARS-CoV-2 spike protein S1 interacts to the ACE2 receptor of human host, instigating the viral infection. To examine the competitive inhibitor efficacy of broad spectrum alpha helical AMPs extracted from frog skin, a comparative study of intermolecular interactions between viral S1 and AMPs was performed relative to S1-ACE2p interactions. The ACE2 binding region with S1 was extracted as ACE2p from the complex for ease of computation. Surprisingly, the Spike-Dermaseptin-S9 complex had more intermolecular interactions than the other peptide complexes and importantly, the S1-ACE2p complex. We observed how atomic displacements in docked complexes impacted structural integrity of a receptor-binding domain in S1 through conformational sampling analysis. Notably, this geometry-based sampling approach confers the robust interactions that endure in S1-Dermaseptin-S9 complex, demonstrating its conformational transition. Additionally, QM calculations revealed that the global hardness to resist chemical perturbations was found more in Dermaseptin-S9 compared to ACE2p. Moreover, the conventional MD through PCA and the torsional angle analyses indicated that Dermaseptin-S9 altered the conformations of S1 considerably. Our analysis further revealed the high structural stability of S1-Dermaseptin-S9 complex and particularly, the trajectory analysis of the secondary structural elements established the alpha helical conformations to be retained in S1-Dermaseptin-S9 complex, as substantiated by SMD results. In conclusion, the functional dynamics proved to be significant for viral Spike S1 and Dermaseptin-S9 peptide when compared to ACE2p complex. Hence, Dermaseptin-S9 peptide inhibitor could be a strong candidate for therapeutic scaffold to prevent infection of SARS-CoV-2.

ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts.

In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy persisted with depletion of CD8+ T cells in immunocompetent mice and also was effective in immune deficient mice. Examination of ONP-302 effects on components of the tumor microenvironment (TME) were explored. ONP-302 treatment caused a gene expression shift in TAMs toward the pro-inflammatory M1 type and substantially inhibited the expression of genes associated with the pro-tumorigenic function of CAFs. ONP-302 also induced apoptosis in CAFs in the TME. Together, these data support further development of ONP-302 as a novel first-in- class anti-cancer therapeutic that can be used as a single-agent as well as in combination therapies for the treatment of solid tumors due to its ability to modulate the TME.

Decoding of Attentional State Using High-Frequency Local Field Potential Is As Accurate As Using Spikes.

Local field potentials (LFPs) in visual cortex are reliably modulated when the subject's focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spikes. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spikes was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found in rhesus monkeys that LFPs during neutral cueing were also intermediate between cued and uncued conditions. For a single electrode, attention was more discriminable using high frequency (>30 Hz) LFP power than spikes, which is expected because LFP represents a population signal and therefore is expected to be less noisy than spikes. However, previous studies have shown that when multiple electrodes are used, spikes can outperform LFPs. Surprisingly, in our study, spikes did not outperform LFPs when discriminability was computed using multiple electrodes, even though the LFP activity was highly correlated across electrodes compared with spikes. These results constrain the spatial scale over which attention operates and highlight the usefulness of LFPs in studying attention.

Time Series Forecasting of Univariate Agrometeorological Data: A Comparative Performance Evaluation via One-Step and Multi-Step Ahead Forecasting Strategies.

High-frequency monitoring of agrometeorological parameters is quintessential in the domain of Precision Agriculture (PA), where timeliness of collected observations and the ability to generate ahead-of-time predictions can substantially impact the crop yield. In this context, state-of-the-art internet-of-things (IoT)-based sensing platforms are often employed to generate, pre-process and assimilate real-time data from heterogeneous sensors and streaming data sources. Simultaneously, Time-Series Forecasting Algorithms (TSFAs) are responsible for generating reliable forecasts with a pre-defined forecast horizon and confidence. These TSFAs often rely on modelling the correlation between endogenous variables, the impact of exogenous variables on latent form and structural properties of data such as autocorrelation, periodicity, trend, pattern, and causality to approximate the model parameters. Traditionally, TSFAs such as the Holt-Winters (HW) and Autoregressive family of models (ARIMA) apply a linear and parametric approach towards model approximation, whilst models like Support Vector Regression (SVRs) and Neural Networks (NNs) adhere to a non-linear, non-parametric approach for modelling the historical data. Recently, Deep-Learning-based TSFAs such as Recurrent Neural Networks (RNNs), and Long-Short-Term-Memory (LSTMS) have gained popularity due to their capability to model long sequences of highly non-linear and stochastic data effectively. However, the evolution of TSFAs for predicting agrometeorological parameters pivots around one-step-ahead forecasting, which often overestimates the performance metrics defined for validating forecast capabilities of potential TSFAs. Hence, this paper attempts to evaluate and compare the performance of different machine learning (ML) and deep learning (DL) based TSFAs under one-step and multi-step-ahead forecast scenarios, thereby estimating the generalization capabilities of TSFA models over unseen data. The data used in this study are collected from an Automatic Weather Station (AWS), sampled at an interval of 15 min, and range over one month. Temperature (T) and Humidity (H) observations from the AWS are further converted into univariate, supervised time-series diurnal data profiles. Finally, walk-forward validation is used to evaluate recursive one-step-ahead forecasts until the desired prediction horizon is achieved. The results show that the Seasonal Auto-Regressive Integrated Moving Average (SARIMA) and SVR models outperform their DL-based counterparts in one-step and multi-step ahead settings with a fixed forecast horizon. This work aims to present a baseline comparison between different TSFAs to assist the process of model selection and facilitate rapid ahead-of-time forecasting for end-user applications.

It Is Complex: Predicting Gastroschisis Outcomes Using Prenatal Imaging.

BACKGROUND: Gastroschisis occurs in one of 2000 births with survival rates partially contingent on intestinal complications and time to establishing feeding. Enhancements in prenatal imaging have given better insight into postnatal outcomes. The goal of this study was to examine the gastroschisis patient population at a single children's hospital in the modern era and to use prenatal ultrasound (US) to develop new prenatal prognostic indicators. METHODS: We performed a retrospective review of gastroschisis patients at a quaternary-care referral children's hospital from 2010 through 2018. We recorded demographics, prenatal data and imaging, early postnatal data, operative data, and patient outcomes. We compared patients within our cohort born with complex gastroschisis (bowel atresia/perforation) to uncomplicated gastroschisis patients. Second trimester and third trimester prenatal US were evaluated for changes in amniotic fluid level, amount of external bowel, bowel dilatation, and bowel wall edema to identify prognostic indicators of the status of the bowel at birth. For categorical variables, chi-square tests were used to assess for significance. Univariate and multivariable analyses were used to assess significance between categorical and continuous variables using medians and interquartile ranges or means. RESULTS: A total of 134 patients were included in the study: complex (n = 24), uncomplicated (n = 110). Compared with uncomplicated gastroschisis, complex patients required longer median days to feeding initiation (44 versus 10; P < 0.001), full feeding (80 versus 23; P < 0.001), length of stay (83 versus 33; P < 0.001), and total parenteral nutrition at discharge (P = 0.004). Full US data were available on 81% of patients, and partial data were identified on 19%. Prenatal US analysis showed significantly more complex patients had polyhydramnios on third trimester US (23.5%-4.3%; P = 0.018). US analysis showed these additional factors to be most associated with complex gastroschisis: large amount of external bowel on third trimester US, increase in bowel edema on third trimester US, and increase in external bowel dilation on third trimester US. Multivariable logistic regression analyses revealed amniotic fluid on third trimester US to be the most significant predictor of complex gastroschisis (P = 0.01). Polyhydramnios in combination with two-thirds of the other US factors had both sensitivity and positive predictive value for predicting complex gastroschisis of 75%. Patients with two or less of these positive US factors had high specificity (96.8%) and negative predictive value (87.5%), suggesting uncomplicated disease. There were no differences in perioperative or long-term complications in the complex group when compared with the group with uncomplicated gastroschisis. CONCLUSIONS: Polyhydramnios on third trimester prenatal US on babies with gastroschisis can predict complex gastroschisis at birth, whereas the absence of markers on prenatal US can suggest uncomplicated disease. Complex gastroschisis is associated with increased time to feeds and length of stay.

SpaTemHTP: A Data Analysis Pipeline for Efficient Processing and Utilization of Temporal High-Throughput Phenotyping Data.

The rapid development of phenotyping technologies over the last years gave the opportunity to study plant development over time. The treatment of the massive amount of data collected by high-throughput phenotyping (HTP) platforms is however an important challenge for the plant science community. An important issue is to accurately estimate, over time, the genotypic component of plant phenotype. In outdoor and field-based HTP platforms, phenotype measurements can be substantially affected by data-generation inaccuracies or failures, leading to erroneous or missing data. To solve that problem, we developed an analytical pipeline composed of three modules: detection of outliers, imputation of missing values, and mixed-model genotype adjusted means computation with spatial adjustment. The pipeline was tested on three different traits (3D leaf area, projected leaf area, and plant height), in two crops (chickpea, sorghum), measured during two seasons. Using real-data analyses and simulations, we showed that the sequential application of the three pipeline steps was particularly useful to estimate smooth genotype growth curves from raw data containing a large amount of noise, a situation that is potentially frequent in data generated on outdoor HTP platforms. The procedure we propose can handle up to 50% of missing values. It is also robust to data contamination rates between 20 and 30% of the data. The pipeline was further extended to model the genotype time series data. A change-point analysis allowed the determination of growth phases and the optimal timing where genotypic differences were the largest. The estimated genotypic values were used to cluster the genotypes during the optimal growth phase. Through a two-way analysis of variance (ANOVA), clusters were found to be consistently defined throughout the growth duration. Therefore, we could show, on a wide range of scenarios, that the pipeline facilitated efficient extraction of useful information from outdoor HTP platform data. High-quality plant growth time series data is also provided to support breeding decisions. The R code of the pipeline is available at https://github.com/ICRISAT-GEMS/SpaTemHTP.

Automated discretization of 'transpiration restriction to increasing VPD' features from outdoors high-throughput phenotyping data.

BACKGROUND: Restricting transpiration under high vapor pressure deficit (VPD) is a promising water-saving trait for drought adaptation. However, it is often measured under controlled conditions and at very low throughput, unsuitable for breeding. A few high-throughput phenotyping (HTP) studies exist, and have considered only maximum transpiration rate in analyzing genotypic differences in this trait. Further, no study has precisely identified the VPD breakpoints where genotypes restrict transpiration under natural conditions. Therefore, outdoors HTP data (15 min frequency) of a chickpea population were used to automate the generation of smooth transpiration profiles, extract informative features of the transpiration response to VPD for optimal genotypic discretization, identify VPD breakpoints, and compare genotypes. RESULTS: Fifteen biologically relevant features were extracted from the transpiration rate profiles derived from load cells data. Genotypes were clustered (C1, C2, C3) and 6 most important features (with heritability > 0.5) were selected using unsupervised Random Forest. All the wild relatives were found in C1, while C2 and C3 mostly comprised high TE and low TE lines, respectively. Assessment of the distinct p-value groups within each selected feature revealed highest genotypic variation for the feature representing transpiration response to high VPD condition. Sensitivity analysis on a multi-output neural network model (with R of 0.931, 0.944, 0.953 for C1, C2, C3, respectively) found C1 with the highest water saving ability, that restricted transpiration at relatively low VPD levels, 56% (i.e. 3.52 kPa) or 62% (i.e. 3.90 kPa), depending whether the influence of other environmental variables was minimum or maximum. Also, VPD appeared to have the most striking influence on the transpiration response independently of other environment variable, whereas light, temperature, and relative humidity alone had little/no effect. CONCLUSION: Through this study, we present a novel approach to identifying genotypes with drought-tolerance potential, which overcomes the challenges in HTP of the water-saving trait. The six selected features served as proxy phenotypes for reliable genotypic discretization. The wild chickpeas were found to limit water-loss faster than the water-profligate cultivated ones. Such an analytic approach can be directly used for prescriptive breeding applications, applied to other traits, and help expedite maximized information extraction from HTP data.

Neurolathyrism in goat (Capra hircus) kid: Model development.

The present study was undertaken to develop an animal model to study neurolathyrism. For this purpose 24 goat (Capra hircus) kids (new born, 15 days old) were divided into four groups. Group I Control, Group II Low toxin (0.17 g% ß-ODAP containing grass pea), Group III high toxin (0.96 g% ß-ODAP containing grass pea) and Group IV high toxin (0.96 g% ß-ODAP containing grass pea flour (powder) fortified with 5 mg% pure ß-ODAP). The experiment was continued for 3 months. Clinical examination was carried out weekly. Muscle conduction velocity (MCV), nerve conduction velocity (NCV), blood and urinary ß-ODAP, nitrite in blood and cerebrospinal fluid (CSF) examination were performed by standard methods. Clinical examination showed neurolathyrism symptoms in three kids. The abnormal MCV and NCV were observed in all the experimental animals. Blood nitrite, blood and urine ß-ODAP levels were significantly increased in experimental groups. Three kids were affected with neurolathyrism due to consumption of grass pea irrespective of its ß-ODAP content and kid may serve as a neurolathyrism model.