Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic engineering of bread wheat improves grain iron concentration and bioavailability

Summary Bread wheat (Triticum aestivum L.) is cultivated on more land than any other crop and produces a fifth of the calories consumed by humans. Wheat endosperm is rich in starch yet contains low concentrations of dietary iron (Fe) and zinc (Zn). Biofortification is a micronutrient intervention aimed at increasing the density and bioavailability of essential vitamins and minerals in staple crops; Fe biofortification of wheat has proved challenging. In this study we employed constitutive expression (CE) of the rice (Oryza sativa L.) nicotianamine synthase 2 (OsNAS2) gene in bread wheat to up‐regulate biosynthesis of two low molecular weight metal chelators – nicotianamine (NA) and 2′‐deoxymugineic acid (DMA) – that play key roles in metal transport and nutrition. The CE‐OsNAS2 plants accumulated higher concentrations of grain Fe, Zn, NA and DMA and synchrotron X‐ray fluorescence microscopy (XFM) revealed enhanced localization of Fe and Zn in endosperm and crease tissues, respectively. Iron bioavailability was increased in white flour milled from field‐grown CE‐OsNAS2 grain and positively correlated with NA and DMA concentrations.
Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors

BACKGROUND Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blockade (ICB) in particular has shown improved survival compared with previous standards of care for several tumor types. Although proven to be successful in more immunogenic tumors, ICB is still largely ineffective in patients with tumors that are not infiltrated by immune cells, the so-called cold tumors. PATIENTS AND METHODS This review describes the effects of different chemotherapeutic agents on the immune system and the potential value of these different types of chemotherapy as combination partners with ICB in patients with solid tumors. Both preclinical data and currently ongoing clinical trials were evaluated. In addition, we reviewed findings regarding different dosing schedules, including the effects of an induction phase and applying metronomic doses of chemotherapy. RESULTS Combining ICB with other treatment modalities may lead to improved immunological conditions in the tumor microenvironment and could thereby enhance the antitumor immune response, even in tumor types that are so far unresponsive to ICB monotherapy. Chemotherapy, that was originally thought to be solely immunosuppressive, can exert immunomodulatory effects which may be beneficial in combination with immunotherapy. Each chemotherapeutic drug impacts the tumor microenvironment differently, and in order to determine the most suitable combination partners for ICB it is crucial to understand these mechanisms. CONCLUSION Preclinical studies demonstrate that the majority of chemotherapeutic drugs has been shown to exert immunostimulatory effects, either by inhibiting immunosuppressive cells and/or activating effector cells, or by increasing immunogenicity and increasing T-cell infiltration. However, for certain chemotherapeutic agents timing, dose and sequence of administration of chemotherapeutic agents and ICB is important. Further studies should focus on determining the optimal drug combinations, sequence effects and optimal concentration-time profiles in representative preclinical models.
Probabilistic learning of emotion categories.

Although the configurations of facial muscles that humans perceive vary continuously, we often represent emotions as categories. This suggests that, as in other domains of categorical perception such as speech and color perception, humans become attuned to features of emotion cues that map onto meaningful thresholds for these signals given their environments. However, little is known about the learning processes underlying the representation of these salient social signals. In Experiment 1 we test the role of statistical distributions of facial cues in the maintenance of an emotion category in both children (6-8 years old) and adults (18-22 years old). Children and adults learned the boundary between neutral and angry when provided with explicit feedback (supervised learning). However, after we exposed participants to different statistical distributions of facial cues, they rapidly shifted their category boundaries for each emotion during a testing phase. In Experiments 2 and 3, we replicated this finding and also tested the extent to which learners are able to track statistical distributions for multiple actors. Not only did participants form actor-specific categories, but the distributions of facial cues also influenced participants' trait judgments about the actors. Taken together, these data are consistent with the view that the way humans construe emotion (in this case, anger) is not only flexible, but reflects complex learning about the distributions of the myriad cues individuals experience in their social environments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Development of Lobular Panniculitis Long After Completing the Personalized Peptide Vaccine Therapy

Patient: Female, 64 Final Diagnosis: Lobular panniculitis Symptoms: Subcutaneous indurations Medication: — Clinical Procedure: Skin biopsy/Administration of prednisolone Specialty: Oncology Objective: Patient complains/malpractice Background: Personalized peptide vaccine therapy is regarded as a well-tolerated, safe and effective immunotherapy for patients with advanced cancers. Herein we report an exceptional case of a patient with advanced pancreatic cancer who developed delayed lobular panniculitis at sites corresponding to vaccine injections. Case Report: A 64-year-old Japanese female visited our clinic due to thirst and polydipsia; she was diagnosed as having type 2 diabetes. Simultaneously, she was diagnosed as having advanced pancreatic cancer; and a distal pancreatectomy and splenectomy were performed. Afterwards, she received adjuvant chemotherapy with titanium silicate-1 and personalized peptide vaccination using Montanide® ISA-51 by a subcutaneous injection to her abdomen over a total of 30 times. Thirteen months after the vaccine therapy had come to an end, lobular panniculitis appeared at the vaccination sites. At this point, corticosteroid was administered, resulting in significant improvement in the condition of the subcutaneous nodules. Conclusions: This case report highlights the importance of careful patient explanation before initiation of cancer vaccine therapy about the possibilities of lobular panniculitis as an adverse event. It also highlights that it is important that physicians have a greater awareness of the possibility of panniculitis in patients with concerns regarding subcutaneous indurations even long after the end of peptide vaccine therapy.
Alterations in cardiovascular function in an experimental model of lung fibrosis and pulmonary hypertension

What is the central question of this study? We have evaluated changes in cardiovascular physiology using echocardiography in an experimental model of lung fibrosis. What is the main finding and its importance? Remarkably, we report changes in cardiovascular function as early as day 7, concomitant with evidence of vascular remodelling. We also report that isolated pulmonary arteries were hypercontractile in response to a thromboxane A2 agonist. These findings are significant because the development of pulmonary hypertension is one of the most significant predictors of mortality in patients with lung fibrosis, where there are no available therapies and a lack of animal models.
Milk drinking and risk of hip fracture. The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Milk provides energy and nutrients considered protective for bone. Meta-analyses of cohort studies have found no clear association between milk drinking and risk of hip fracture, and results of recent studies are contradictory. We studied the association between milk drinking and hip fracture in Norway, which has a population characterised by high fracture incidence and a high Ca intake. Baseline data from two population-based cohorts were used: the third wave of the Norwegian Counties Study (1985–1988) and the Five Counties Study (2000–2002). Diet and lifestyle variables were self-reported through questionnaires. Height and weight were measured. Hip fractures were identified by linkage to hospital data with follow-up through 2013. Of the 35 114 participants in the Norwegian Counties Study, 1865 suffered a hip fracture during 613 018 person-years of follow-up. In multivariable Cox regression, hazard ratios (HR) per daily glass of milk were 0·97 (95 % CI 0·92, 1·03) in men and 1·02 (95 % CI 0·96, 1·07) in women. Of 23 259 participants in the Five Counties Study, 1466 suffered a hip fracture during 252 996 person-years of follow-up. HR for hip fractures per daily glass of milk in multivariable Cox regression was 0·99 (95 % CI 0·92, 1·07) in men and 1·02 (95 % CI 0·97, 1·08) in women. In conclusion, there was no overall association between milk intake and risk of hip fracture in Norwegian men and women.
Podocan affects C2C12 myogenic differentiation by enhancing Wnt/β‐catenin signaling

Podocan, a small leucine‐rich repeat protein, is a negative regulator of cell proliferation. In this study, we demonstrated that podocan is involved in the differentiation of C2C12 murine myoblasts. Podocan expression increased with the progression of C2C12 differentiation. As expect, siRNA‐mediated podocan knockdown inhibited C2C12 differentiation, as indicated by inhibition of MYOG, MYH2, and desmin expression, as well as reductions in the differentiation and fusion indices. Overexpression of podocan using dCas9 technology promoted C2C12 cell differentiation. In addition, supplementation of culture medium with podocan influenced C2C12 differentiation. Podocan knockdown reduced Wnt/β‐catenin signaling, characterized by a reduction in the nuclear translocation of β‐catenin, whereas podocan overexpression had the opposite effect. Furthermore, treatment with XAV939, an inhibitor of Wnt/β‐catenin, reduced the podocan‐mediated promotion of C2C12 differentiation. Induction of muscle injury in mice by bupivacaine administration suggested that podocan may play a role in muscle regeneration. In summary, our results suggest that podocan is required for normal C2C12 differentiation and that its role in myogenesis is mediated by the Wnt/β‐catenin pathway.
ReGNN: a ReRAM-based heterogeneous architecture for general graph neural networks

Graph Neural Networks (GNNs) have both graph processing and neural network computational features. Traditional graph accelerators and NN accelerators cannot meet these dual characteristics of GNN applications simultaneously. In this work, we propose a ReRAM-based processing-in-memory (PIM) architecture called ReGNN for GNN acceleration. ReGNN is composed of analog PIM (APIM) modules for accelerating matrix vector multiplication (MVM) operations, and digital PIM (DPIM) modules for accelerating non-MVM aggregation operations. To improve data parallelism, ReGNN maps data to aggregation sub-engines based on the degree of vertices and the dimension of feature vectors. Experimental results show that ReGNN speeds up GNN inference by 228x and 8.4x, and reduces energy consumption by 305.2x and 10.5x, compared with GPU and the ReRAM-based GNN accelerator ReGraphX, respectively.
Using semantic web technologies to build a semantic desktop

A paperboard carton having a large capacity pouring spout formed in a relatively narrow end wall, the pouring spout being fabricated as the carton is tubed into knocked-down flat-folded condition, the carton having an opposing pair of side walls and an opposing pair of relatively narrow end walls, with a glue flap hingedly connected to the side edge of one of the side walls, the glue flap being juxtaposed and adhesively secured to the inner surface of the adjacent end wall to form a tubular carton body; an outwardly displaceable pouring spout tab is formed in the end wall to which the glue flap is juxtaposed, the pouring spout tab being of generally rectangular configuration and having one of its side edges lying along the line of articulation between the end wall and the other of the side walls, the underlying glue flap being enlarged to extend across the full width of the end wall in the area of the pouring spout tab, the enlarged portion of the glue flap having an extension hingedly connected to its outermost side edge which is juxtaposed to the innersurface of the other of the carton side walls; a pouring spout being formed in the enlarged portion of the glue flap and its extension, the pouring spout having a generally rectangular center member secured to the inner surface of the pouring spout tab in the end wall, and a pair of wing members hingedly connected to the opposite sides of the center member, one of the wings being struck from the enlarged portion of the glue flap on one side of the center member, and the other wing being struck from the extension which lies along the inner surface of the other side wall, the outward displacement of the pouring spout tab causing the spout members to be displaced outwardly with the wings bearing against the opposite sides of the opening defined by the displaced pouring spout tab, the wings providing full depth side walls for the spout.
Expression of miR-520c in intestinal type gastric adenocarcinoma.

Background MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation in cells thereby playing active role in pathological conditions and have been nominated as new class of biomarkers in disease including cancer. miR-520c has been reported as potential oncogenic micro-RNA in several previous studies. Gastric cancer is the most common cancer of digestive tract and the fourth prevalent cancer worldwide with the intestinal-type gastric adenocarcinoma (IGA) the dominant type of gastric malignancies. This study aimed to explore miR-520c putative role, in IGA and patient's clinicopathological features. Methods Total RNA was first extracted from 42 pairs of IGA tissues and relevant non-tumorous adjacent tissues. cDNA was synthesized from extracted RNAs using specific primers for miR-520c. The level of miR-520c was quantified using SYBER Green Real-Time PCR master mix. The relationship between miR-520c expression and clinicopathological features were examined. Results Our study resulted in no differential expression of miR-520c in IGA. There was no significant correlation between miR-520c expression and clinicopathological features including tumor grade, genus and age groups. Conclusions To our knowledge, this is the first report about exploring miR-520c expression in IGA tissue samples. Our results do not verify miR-520c previously established oncogenic role in IGA.
The sinonasal mycobiota in chronic rhinosinusitis and control patients.

BACKGROUND While bacterial associations with chronic rhinosinusitis (CRS) are increasingly well described, fewer studies have examined the fungal component of the sinonasal microbiota. Here we present a study of the sinonasal mycobiota in a cohort of 144 patients (106 patients with CRS and 38 controls). METHODOLOGY Fungal communities were characterised by analysis of mucosal swab samples of the left and right middle meatuses via ITS2 marker amplicon sequencing on the Illumina MiSeq platform. Fungal associations with previously published bacterial community and inflammatory cytokine and cell data for this cohort (collected at the same intra-operative time point) were also investigated. RESULTS Malassezia spp. were ubiquitous and often highly predominant. Season of sampling explained more of the variability in the data than any of the clinical parameters. The predominant Malassezia sp. was distinct in patients with cystic fibrosis compared to those without. However, distinctions in the mycobiota were not evident between any other patient groupings assessed, and few fungal-bacterial or fungal-inflammatory associations were observed. CONCLUSIONS This study confirms the prominent place of Malassezia spp. within the upper respiratory tract. Overall, few distinctions between patient groups were evident, and these data lend further support to the hypothesis that fungal community types may have no direct causative association with idiopathic CRS. Additional studies incorporating a broader array of inflammatory markers are required to assess whether these ubiquitous fungi nonetheless play an exacerbating role in some sensitive individuals.
Intermittent Use of Portable NIV Increases Exercise Tolerance in COPD: A Randomised, Cross-Over Trial

During exercise, non-invasive ventilation (NIV) prolongs endurance in chronic obstructive pulmonary disease (COPD), but routine use is impractical. The VitaBreath device provides portable NIV (pNIV); however, it can only be used during recovery. We assessed the effect of pNIV compared to pursed lip breathing (PLB) on exercise tolerance. Twenty-four COPD patients were randomised to a high-intensity (HI: 2-min at 80% peak work rate (WRpeak) alternated with 2-min recovery; n = 13), or a moderate-intensity (MOD: 6-min at 60% WRpeak alternated with 2-min recovery; n = 11) protocol, and within these groups two tests were performed using pNIV and PLB during recovery in balanced order. Upon completion, patients were provided with pNIV; use over 12 weeks was assessed. Compared to PLB, pNIV increased exercise tolerance (HI: by 5.2 ± 6.0 min; MOD: by 5.8 ± 6.7 min) (p < 0.05). With pNIV, mean inspiratory capacity increased and breathlessness decreased by clinically meaningful margins during recovery compared to the end of exercise (HI: by 140 ± 110 mL and 1.2 ± 1.7; MOD: by 170 ± 80 mL and 1.0 ± 0.7). At 12 weeks, patients reported that pNIV reduced anxiety (median: 7.5/10 versus 4/10, p = 0.001) and recovery time from breathlessness (17/24 patients; p = 0.002); 23/24 used the device at least weekly. pNIV increased exercise tolerance by reducing dynamic hyperinflation and breathlessness in COPD patients.
Parameter Estimation Based on Sigmoid Transform in Wideband Bistatic MIMO Radar System under Impulsive Noise Environment

Since second-order statistics-based methods rely heavily on Gaussianity assumption and fractional lower-order statistics-based methods depend on a priori knowledge of non-Gaussian noise, there remains a void in wideband bistatic multiple-input/multiple-output (MIMO) radar systems under impulsive noise. In this paper, a novel method based on Sigmoid transform was used to estimate target parameters, which do not need a priori knowledge of the noise in an impulsive noise environment. Firstly, a novel wideband ambiguity function, termed Sigmoid wideband ambiguity function (Sigmoid-WBAF), is proposed to estimate the Doppler stretch and time delay by searching the peak of the Sigmoid-WBAF. A novel Sigmoid correlation function is proposed. Furthermore, a new MUSIC algorithm based on the Sigmoid correlation function (Sigmoid-MUSIC) is proposed to estimate the direction-of-departure (DOD) and direction-of-arrival (DOA). Then, the boundness of the Sigmoid-WBAF to the symmetric alpha stable (SαS) noise, the feasibility analysis of the Sigmoid-WBAF, and complexity analysis of the Sigmoid-WBAF and Sigmoid-MUSIC are presented to evaluate the performance of the proposed method. In addition, the Cramér–Rao bound for parameter estimation was derived and computed in closed form, which shows that better performance was achieved. Simulation results and theoretical analyses are presented to verify the effectiveness of the proposed method.
Genome-Wide Analysis of Watermelon HSP20s and Their Expression Profiles and Subcellular Locations under Stresses

Watermelon (Citrullus lanatus L.), which is an economically important cucurbit crop that is cultivated worldwide, is vulnerable to various adverse environmental conditions. Small heat shock protein 20s (HSP20s) are the most abundant plant HSPs and they play important roles in various biotic and abiotic stress responses. However, they have not been systematically investigated in watermelon. In this study, we identified 44 watermelon HSP20 genes and analyzed their gene structures, conserved domains, phylogenetic relationships, chromosomal distributions, and expression profiles. All of the watermelon HSP20 proteins have a conserved the α-crystallin (ACD) domain. Half of the ClHSP20s arose through gene duplication events. Plant HSP20s were grouped into 18 subfamiles and a new subfamily, nucleo-cytoplasmic XIII (CXIII), was identified in this study. Numerous stress- and hormone-responsive cis-elements were detected in the putative promoter regions of the watermelon HSP20 genes. Different from that in other species, half of the watermelon HSP20s were repressed by heat stress. Plant HSP20s displayed diverse responses to different virus infections and most of the ClHSP20s were generally repressed by Cucumber green mottle mosaic virus (CGMMV). Some ClHSP20s exhibited similar transcriptional responses to abscisic acid, melatonin, and CGMMV. Subcellular localization analyses of six selected HSP20- green fluorescence protein fusion proteins revealed diverse subcellular targeting. Some ClHSP20 proteins were affected by CGMMV, as reflected by changes in the size, number, and distribution of fluorescent granules. These systematic analyses provide a foundation for elucidating the physiological functions and biological roles of the watermelon HSP20 gene family.
Evaluation of a Novel Preference Assessment Tool for Patients with Multiple Sclerosis.

Background We developed a preference assessment tool to help assess patient goals, values, and preferences for multiple sclerosis (MS) management. All preference items in the tool were generated by people with MS. The aim of this study was to evaluate this tool in a national sample of people with MS. Methods English-speaking patients with MS aged 21 to 75 years with access to the internet were recruited. Participants completed the preference tool online, which included separate modules assessing three core preference areas: treatment goals, preferences for attributes of disease-modifying therapies, and factors influencing a change in treatment. The tool generated a summary of participants' treatment goals and preferences. Immediately after viewing the summary, participants were asked to evaluate the tool. Rankings of preference domains were compared with rankings obtained in another study. Results In 135 people with MS who completed the tool and evaluation, the highest ranked goal was brain health (memory, thinking, brain), followed by disability concerns (walking, strength, vision). Rankings were highly similar to those in the referent study. Nearly all participants reported that the tool helped them understand their goals and priorities regarding MS and that the summary appropriately reflected what is important to them. Most participants (87%) wanted to discuss their treatment goals and priorities with their clinician. Conclusions This preference assessment tool successfully captured patients' goals, values, and preferences for MS treatment and could potentially be used to help patients communicate their preferences to their clinician.