Miracle-dz/UniFAR-FTUs huggingface dataset:
A computational framework for modeling functional protein‐protein interactions

Protein interactions and their assemblies assist in understanding the cellular mechanisms through the knowledge of interactome. Despite recent advances, a vast number of interacting protein complexes is not annotated by three‐dimensional structures. Therefore, a computational framework is a suitable alternative to fill the large gap between identified interactions and the interactions with known structures. In this work, we develop an automated computational framework for modeling functionally related protein‐complex structures utilizing GO‐based semantic similarity technique and co‐evolutionary information of the interaction sites. The framework can consider protein sequence and structure information as input and employ both rigid‐body docking and template‐based modeling exploiting the existing structural templates and sequence homology information from the PDB. Our framework combines geometric as well as physicochemical features for re‐ranking the docking decoys. The proposed framework has an 83% success rate when tested on a benchmark dataset while considering Top1 models for template‐based modeling and Top10 models for the docking pipeline. We believe that our computational framework can be used for any pair of proteins with higher confidence to identify the functional protein‐protein interactions.
Ischemia–Reperfusion Injury in Lung Transplantation

Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.
Adequate Urinary Iodine Concentration among Infants in the Inland Area of Norway

Considering the importance of iodine to support optimal growth and neurological development of the brain and central nervous system, this study aimed to assess and evaluate iodine status in Norwegian infants. We collected data on dietary intake of iodine, iodine knowledge in mothers, and assessed iodine concentration in mother’s breast milk and in infant’s urine in a cross-sectional study at two public healthcare clinics in the inland area of Norway. In the 130 mother–infant pairs, the estimated infant 24-h median iodine intake was 50 (IQR 31, 78) µg/day. The median infant urinary iodine concentration (UIC) was 146 (IQR 93, 250) µg/L and within the recommended median defined by the World Health Organization for this age group. Weaned infants had a higher UIC [210 (IQR 130, 330) µg/L] than exclusively breastfed infants [130 (IQR 78, 210) µg/L] and partially breastfed infants [135 (IQR 89, 250) µg/L], which suggest that the dietary data obtained in this study did not capture the accurate iodine intake of the included infants. The iodine status of infants in the inland area of Norway seemed adequate. Weaned infants had higher UIC compared to breastfed infants, suggesting early access and consumption of other sources of iodine in addition to breast milk.
Intimate partner violence , breastfeeding , breastmilk substitutes and baby bottle use in the first year of life

This article aims to investigate the relationship between intimate partner physical violence (IPPV) and breastfeeding (BF), use of breastmilk substitutes (BMS) and bottle-feeding among children aged 12 to 15 months. This is a cross-sectional study with mothers in primary care facilities of the city of Rio de Janeiro. IPPV was identified by the Brazilian version of the Conflict Tactics Scales 1-Form R and feeding practices were identified by a 24-hour Dietary Recall. Associations were verified by logistic regression with odds ratio (OR) estimates and 95% confidence intervals. BF was offered to 58.5% of the children and BMS to 88.5%. Also, 70.5% of the children used a baby bottle. Physical violence was observed in 26.7% of couples. Households where couples physically abuse each other are more likely to not breastfeed (OR=2.14, p-value=0.030), to use breastmilk substitutes (OR=5.15, p-value=0.03) and bottle-feed (OR=2.71; p-value=0.01), when compared to households without physical violence. The results highlight the need to investigate intrafamily relationships in cases where inadequate breastfeeding practices are identified, and to enable health professionals to support families in conflict situations.
Effects of Linseed Meal and Carotenoids from Different Sources on Egg Characteristics, Yolk Fatty Acid and Carotenoid Profile and Lipid Peroxidation

The present study aimed to evaluate the effect of supplementing the diet of laying hens with linseed meal and carotenoids from different sources on egg characteristics, yolk fatty acid and carotenoid profile, and lipid peroxidation. A 4-week experiment was conducted on 168 Lohmann Brown layers (43 weeks of age), assigned to four dietary treatments (42 hens/group; 21 replicate/groups with 2 birds/pen) consisting of a control diet (C) and three diets simultaneously supplemented with 6% linseed meal and 2% dried kapia pepper (E1), 2% dried sea buckthorn pomace (E2) and 2% dried carrot (E3). Every 2 weeks, 18 eggs/group/period were collected randomly from each group and used to determine the egg quality and nutritional parameters. The results showed that dietary linseed meal and carotenoids sources improved egg color, carotenoids’ accumulation in egg yolk and fatty acid profile, especially the n-3 PUFA content. Dietary carotenoids supplementation reduced, n-6/n-3 ratio, cholesterol content of the egg yolk and improved yolk pH, egg thickness and yolk oxidative stability. In conclusion, the use of these sources of carotenoids in the linseed meal enriched diets could be an effective way to improve the nutritional properties of the eggs without affecting their quality and consumer’s safety.
Differential Salt Tolerance Strategies in Three Halophytes from the Same Ecological Habitat: Augmentation of Antioxidant Enzymes and Compounds

Understanding the salt tolerance mechanism in obligate halophytes provides valuable information for conservation and re-habitation of saline areas. Here, we investigated the responses of three obligate halophytes namely Arthrocnemum macrostachyum, Sarcocornia fruticosa and Salicornia europaea to salt stress (0, 100, 200, 400 and 600 mM NaCl) during their vegetative growth with regard to biomass, ions contents (Na+, K+ and Ca2+), chlorophyll contents, carotenoids, phenolic compounds, flavonoids, and superoxide dismutase, peroxidase and esterase activities. S. europaea showed the lowest biomass, root K+ content, Chl a/b ratio, and carotenoids under salinity. This reduction of biomass is concomitant with the increase in proline contents and peroxidase activity. On the other hand, the promotion of growth under low salinity and maintenance under high salinity (200 and 400 Mm NaCl) in A. Macrostachyum and S. fruticosa are accompanied by an increase in Chl a/b ratio, carotenoids, phenolics contents, and esterase activity. Proline content was decreased under high salinity (400 and 600 mM NaCl) in both species compared to S. europaea, while peroxidase showed the lowest activity in both plants under all salt levels except under 600 mM NaCl in Arthrocnemum macrostachyum compared to S. europaea. These results suggest two differential strategies; (1) the salt tolerance is due to activation of antioxidant enzymes and biosynthesis of proline in S. europaea, (2) the salt tolerance in A. macrostachyum, S. fruticosa are due to rearrangement of chlorophyll ratio and biosynthesis of antioxidant compounds (carotenoids, phenolics and flavonoids) which their cost seem to need less energy than activation of antioxidant enzymes. The differential behavior in halophytes of the same habitat confirms that the tolerance mechanism in halophytes is species-specific which provides new insight about the restoration strategy of saline areas.
Effects of Different Scratch Mat Designs on Hen Behaviour and Eggs Laid in Enriched Cages

Simple Summary Enriched cages for laying hens must contain litter so that pecking and scratching are possible. This is typically provided using layer’s feed dispensed onto a scratch mat, however, there are no regulations on the size or materials of the mat. This study examined how different scratch mat designs and bird age affected behaviours on the mat at three times of day, and their influence on where eggs were laid and shell quality. The proportion of hens at the scratch mats did not increase during or shortly after the application of scratch feed, however, they were more likely to be foraging then. Most eggs collected were clean and laid in the nest. Of the small proportion of eggs that were cracked or dirty, the mat type did not affect dirty eggs, but eggs laid opposite the Big Dutchman mats were more likely to be cracked at 79 weeks of age than at any other mat type or age. There appeared to be no optimal scratch mat design (of those studied) and their use (during observations) was low, suggesting that mat designs were not major influencers on bird behaviour. Abstract Laying hens in the UK and EU must be provided with litter for pecking and scratching. In enriched cages, this is commonly provided by dispensing layer’s feed onto a scratch mat. Mats vary in design and size, which might affect hen behaviour and egg quality, since eggs are sometimes laid at the mats. We investigated if four different scratch mats (BD, K, V, Z) provided to hens in enriched cages resulted in differences in behaviour on the mats and external egg quality. Twenty-four 60-bird cages (6 cages/bank × 4 banks) with 2 mats/cage at one tier of a commercial enriched cage unit were used. Mats were allocated to cages in a balanced design prior to the flock arriving. Hens and eggs were studied at 30, 50 and 79 weeks of age, with three behaviour observations (before, during or after scratch feed application). The data were analysed by GLMMs or LMMs. The vast proportions of birds on the mats were standing (0.720) or sitting (0.250). Bird proportions on the mats were low overall and declined from 0.028 (30 weeks) and 0.030 (50 weeks) to 0.020 (79 weeks) (p < 0.001). The greatest proportion of hens were observed on Z (p < 0.001), which had the largest area, but relative to the available area least birds were on Z and most were on K (p < 0.001). Foraging was not affected by bird age or mat type but was greater at the second observation (p < 0.001). Most eggs were laid in the nest box and were clean. Clean eggs declined, and dirty eggs increased, significantly with age, particularly at the scratch mat (p < 0.001). Dirty eggs were not affected by mat design. Cracked eggs were highest at 79 weeks of age, particularly with BD mats (p < 0.001). Overall, scratch mat designs had minimal effects on behaviour (but few hens were seen there) and egg quality.
Mitigation of the convergence issues associated with semi‐replicated bioequivalence data

Semi‐replicated designs for investigation of bioequivalence constitute a challenge when mixed models are applied. With the commonly available packages and regardless of choice of covariance structure the software may force variance components into the covariance matrix that render it over‐specified. This may give rise to arbitrary estimates of certain variance components, lack of convergence or warnings. Classically the covariance matrix is decomposed as V = ZGZt + R, with G containing the between‐subject variance components, Z being the design matrix for the random effects and R containing the within‐subject variance components. By abandoning the definitions of G and R, and instead working directly in V, it is possible to specify a correct model with only the variance components of interest. Proof‐of‐concept for this idea is delivered with a script in the statistical language R. The script is available as supplementary material ( Data S1 ).
Evaluation of Stable LifeAct-mRuby2- and LAMP1-NeonGreen Expressing A549 Cell Lines for Investigation of Aspergillus fumigatus Interaction with Pulmonary Cells

Inhaled Aspergillus fumigatus spores can be internalized by alveolar type II cells. Cell lines stably expressing fluorescently labeled components of endocytic pathway enable investigations of intracellular organization during conidia internalization and measurement of the process kinetics. The goal of this report was to evaluate the methodological appliance of cell lines for studying fungal conidia internalization. We have generated A549 cell lines stably expressing fluorescently labeled actin (LifeAct-mRuby2) and late endosomal protein (LAMP1-NeonGreen) following an evaluation of cell-pathogen interactions in live and fixed cells. Our data show that the LAMP1-NeonGreen cell line can be used to visualize conidia co-localization with LAMP1 in live and fixed cells. However, caution is necessary when using LifeAct-mRuby2-cell lines as it may affect the conidia internalization dynamics.
Genomic Approaches to Identify Molecular Bases of Crop Resistance to Diseases and to Develop Future Breeding Strategies

Plant diseases are responsible for substantial crop losses each year and affect food security and agricultural sustainability. The improvement of crop resistance to pathogens through breeding represents an environmentally sound method for managing disease and minimizing these losses. The challenge is to breed varieties with a stable and broad-spectrum resistance. Different approaches, from markers to recent genomic and ‘post-genomic era’ technologies, will be reviewed in order to contribute to a better understanding of the complexity of host–pathogen interactions and genes, including those with small phenotypic effects and mechanisms that underlie resistance. An efficient combination of these approaches is herein proposed as the basis to develop a successful breeding strategy to obtain resistant crop varieties that yield higher in increasing disease scenarios.
Recurrent Convolutional Neural Networks for 3D Mandible Segmentation in Computed Tomography

Purpose: Classic encoder–decoder-based convolutional neural network (EDCNN) approaches cannot accurately segment detailed anatomical structures of the mandible in computed tomography (CT), for instance, condyles and coronoids of the mandible, which are often affected by noise and metal artifacts. The main reason is that EDCNN approaches ignore the anatomical connectivity of the organs. In this paper, we propose a novel CNN-based 3D mandible segmentation approach that has the ability to accurately segment detailed anatomical structures. Methods: Different from the classic EDCNNs that need to slice or crop the whole CT scan into 2D slices or 3D patches during the segmentation process, our proposed approach can perform mandible segmentation on complete 3D CT scans. The proposed method, namely, RCNNSeg, adopts the structure of the recurrent neural networks to form a directed acyclic graph in order to enable recurrent connections between adjacent nodes to retain their connectivity. Each node then functions as a classic EDCNN to segment a single slice in the CT scan. Our proposed approach can perform 3D mandible segmentation on sequential data of any varied lengths and does not require a large computation cost. The proposed RCNNSeg was evaluated on 109 head and neck CT scans from a local dataset and 40 scans from the PDDCA public dataset. The final accuracy of the proposed RCNNSeg was evaluated by calculating the Dice similarity coefficient (DSC), average symmetric surface distance (ASD), and 95% Hausdorff distance (95HD) between the reference standard and the automated segmentation. Results: The proposed RCNNSeg outperforms the EDCNN-based approaches on both datasets and yields superior quantitative and qualitative performances when compared to the state-of-the-art approaches on the PDDCA dataset. The proposed RCNNSeg generated the most accurate segmentations with an average DSC of 97.48%, ASD of 0.2170 mm, and 95HD of 2.6562 mm on 109 CT scans, and an average DSC of 95.10%, ASD of 0.1367 mm, and 95HD of 1.3560 mm on the PDDCA dataset. Conclusions: The proposed RCNNSeg method generated more accurate automated segmentations than those of the other classic EDCNN segmentation techniques in terms of quantitative and qualitative evaluation. The proposed RCNNSeg has potential for automatic mandible segmentation by learning spatially structured information.
Pancreatic Islets Exhibit Dysregulated Adaptation of Insulin Secretion after Chronic Epinephrine Exposure

Chronic adrenergic stimulation is the dominant factor in impairment of the β-cell function. Sustained adrenergic exposure generates dysregulated insulin secretion in fetal sheep. Similar results have been shown in Min6 under the elevated epinephrine condition, but impairments after adrenergic removal are still unknown and a high rate of proliferation in Min6 has been ignored. Therefore, we incubated primary rats’ islets with half maximal inhibitory concentrations of epinephrine for three days, then determined their insulin secretion responsiveness and related signals two days after removal of adrenaline via radioimmunoassay and qPCR. Insulin secretion was not different between the exposure group (1.07 ± 0.04 ng/islet/h) and control (1.23 ± 0.17 ng/islet/h), but total islet insulin content after treatment (5.46 ± 0.87 ng/islet/h) was higher than control (3.17 ± 0.22 ng/islet/h, p < 0.05), and the fractional insulin release was 36% (p < 0.05) lower after the treatment. Meanwhile, the mRNA expression of Gαs, Gαz and Gβ1-2 decreased by 42.8% 19.4% and 24.8%, respectively (p < 0.05). Uncoupling protein 2 (Ucp2), sulphonylurea receptor 1 (Sur1) and superoxide dismutase 2 (Sod2) were significantly reduced (38.5%, 23.8% and 53.8%, p < 0.05). Chronic adrenergic exposure could impair insulin responsiveness in primary pancreatic islets. Decreased G proteins and Sur1 expression affect the regulation of insulin secretion. In conclusion, the sustained under-expression of Ucp2 and Sod2 may further change the function of β-cell, which helps to understand the long-term adrenergic adaptation of pancreatic β-cell.
Observation of Intact and Proteolytically Cleaved Amyloid-Beta (1–40)-Oleuropein Noncovalent Complex at Neutral pH by Mass Spectrometry

Mass spectrometry analyses carried out on mass spectrometers equipped with soft ionization sources demonstrated their utility in the assessment of the formation of noncovalent complexes and the localization of the binding sites. Direct analyses by mass spectrometry of the noncovalent complex formed in acidic and mildly acidic environments by amyloid beta (1–40) peptide and oleuropein have been previously described, and, in several studies, the absorption, metabolism, excretion, and the implications in the prevention and therapy of Alzheimer’s disease of oleuropein have been investigated. Our paper presents modifications of the method previously employed for noncovalent complex observation, namely, the amyloid beta (1–40) pretreatment, followed by an increase in the pH and replacement of the chemical environment from ammonium acetate to ammonium bicarbonate. The formation of noncovalent complexes with one or two molecules of oleuropein was detected in all chemical solutions used, and the amyloid beta (17–28) binding site was identified via proteolytic experiments using trypsin prior to and after noncovalent complex formation. Our results highlight the importance of further studies on the effect of oleuropein against amyloid beta aggregation.
Acne Vulgaris: The Majority of Patients Do Not Achieve Success According to FDA Guidance.

BACKGROUND The Food and Drug Administration (FDA) recommends grading Acne vulgaris via an Investigator’s Global Assessment (IGA) scale and assessing treatment as either success or failure, with success defined as clear (grade 0) or almost clear (grade 1) with at least a two-grade improvement in acne severity from baseline. OBJECTIVE To determine the likelihood of achieving real world treatment success in patients with acne according to FDA guidance. METHODS We calculated estimated appropriates to obtain the IGA 0/1 (clear or almost clear rate) for many of the oral and topical medications. We also used the National Ambulatory Medical Care Survey (NAMCS) data to determine the number of medications prescribed for outpatient visits when isotretinoin was prescribed or when isotretinoin was not prescribed and the one and only diagnosis was acne. RESULTS Isotretinoin had the highest IGA 0/1 at 87%. None of the other medications had an IGA 0/1 > 40%. Of all outpatient acne visits, only 6% receive isotretinoin. When excluding isotretinoin visits, 71% of patients received ≤ 2 medications. LIMITATIONS The majority of the acne medication studies lasted 12 weeks, however, it can take 6 months or longer to get the maximum effect. None of the studies combined topical and oral medications. CONCLUSIONS The majority of acne patients are not likely to achieve success according to FDA guidance. We propose that the FDA guidance may be too rigorous. An alternative hypothesis is that most acne patients are undertreated. J Drugs Dermatol. 2021;20(6):648-651. doi:10.36849/JDD.5727.
Crosstalk of Multi-Omics Platforms with Plants of Therapeutic Importance

From time immemorial, humans have exploited plants as a source of food and medicines. The World Health Organization (WHO) has recorded 21,000 plants with medicinal value out of 300,000 species available worldwide. The promising modern “multi-omics” platforms and tools have been proven as functional platforms able to endow us with comprehensive knowledge of the proteome, genome, transcriptome, and metabolome of medicinal plant systems so as to reveal the novel connected genetic (gene) pathways, proteins, regulator sequences and secondary metabolite (molecule) biosynthetic pathways of various drug and protein molecules from a variety of plants with therapeutic significance. This review paper endeavors to abridge the contemporary advancements in research areas of multi-omics and the information involved in decoding its prospective relevance to the utilization of plants with medicinal value in the present global scenario. The crosstalk of medicinal plants with genomics, transcriptomics, proteomics, and metabolomics approaches will be discussed.