Miracle-dz/UniFAR-FTUs huggingface dataset:
VAMP724 and VAMP726 are involved in autophagosome formation in Arabidopsis thaliana

ABSTRACT Macroautophagy/autophagy, an evolutionarily conserved degradative process essential for cell homeostasis and development in eukaryotes, involves autophagosome formation and fusion with a lysosome/vacuole. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play important roles in regulating autophagy in mammals and yeast, but relatively little is known about SNARE function in plant autophagy. Here we identified and characterized two Arabidopsis SNAREs, AT4G15780/VAMP724 and AT1G04760/VAMP726, involved in plant autophagy. Phenotypic analysis showed that mutants of VAMP724 and VAMP726 are sensitive to nutrient-starved conditions. Live-cell imaging on mutants of VAMP724 and VAMP726 expressing YFP-ATG8e showed the formation of abnormal autophagic structures outside the vacuoles and compromised autophagic flux. Further immunogold transmission electron microscopy and electron tomography (ET) analysis demonstrated a direct connection between the tubular autophagic structures and the endoplasmic reticulum (ER) in vamp724-1 vamp726-1 double mutants. Further transient co-expression, co-immunoprecipitation and double immunogold TEM analysis showed that ATG9 (autophagy related 9) interacts and colocalizes with VAMP724 and VAMP726 in ATG9-positive vesicles during autophagosome formation. Taken together, VAMP724 and VAMP726 regulate autophagosome formation likely working together with ATG9 in Arabidopsis. Abbreviations: ATG, autophagy related; BTH, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester; Conc A, concanamycin A; EM, electron microscopy; ER, endoplasmic reticulum; FRET, Förster/fluorescence resonance energy transfer; MS, Murashige and Skoog; MVB, multivesicular body; PAS, phagophore assembly site; PM, plasma membrane; PVC, prevacuolar compartment; SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor; TEM, transmission electron microscopy; TGN, trans-Golgi network; WT, wild-type.
The borderland of multiple sclerosis and functional neurological disorder: A call for clinical research and vigilance

Functional neurological disorders (FNDs) have attracted much attention from the neurological medical community over the last decades as new developments in neurosciences have reduced stigma around these by showing brain network dysfunctions. An overlap with other neurological conditions such as multiple sclerosis (MS) is well known by clinicians but there is a lack of clinical and fundamental research in this field to better define diagnosis and therapeutic decisions, as well as a lack of deep understanding of the underlying pathophysiology.
Behavior analytic jargon does not seem to influence treatment acceptability ratings

Some have argued that behavior analysts have insulated themselves by eschewing the vernacular and adopting idiosyncratic and sometimes counterintuitive technical terms to describe their science and practice. Because of this, behavior analysis plays a minor role in psychology and related fields and effective behavior‐change interventions go unused. All told, findings about the effects of behavior‐analytic jargon are mixed. Studies that provided technical terms independent of context have produced unfavorable results, whereas studies that have provided context have produced positive or neutral results, overall. This study evaluated the effects of behavioral jargon on the acceptability ratings of several applied behavior analysis interventions described in terms of varying target behaviors, populations, and settings. We presented brief vignettes adapted from published research articles that were described in either jargon or nonjargon versions. There were no appreciable differences in the rated acceptability of interventions described with or without jargon.
Development of an Innovative Soft Piezoresistive Biomaterial Based on the Interconnection of Elastomeric PDMS Networks and Electrically-Conductive PEDOT:PSS Sponges

A deeply interconnected flexible transducer of polydimethylsiloxane (PDMS) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) was obtained as a material for the application of soft robotics. Firstly, transducers were developed by crosslinking PEDOT:PSS with 3-glycidyloxypropryl-trimethoxysilane (GPTMS) (1, 2 and 3% v/v) and using freeze-drying to obtain porous sponges. The PEDOT:PSS sponges were morphologically characterized, showing porosities mainly between 200 and 600 µm2; such surface area dimensions tend to decrease with increasing degrees of crosslinking. A stability test confirmed a good endurance for up to 28 days for the higher concentrations of the crosslinker tested. Consecutively, the sponges were electromechanically characterized, showing a repeatable and linear resistance variation by the pressure triggers within the limits of their working range (∆RR0 max = 80% for 1–2% v/v of GPTMS). The sponges containing 1% v/v of GPTMS were intertwined with a silicon elastomer to increase their elasticity and water stability. The flexible transducer obtained with this method exhibited moderately lower sensibility and repeatability than the PEDOT:PSS sponges, but the piezoresistive response remained stable under mechanical compression. Furthermore, the transducer displayed a linear behavior when stressed within the limits of its working range. Therefore, it is still valid for pressure sensing and contact detection applications. Lastly, the flexible transducer was submitted to preliminary biological tests that indicate a potential for safe, in vivo sensing applications.
Plasma MicroRNA Signature of Alcohol Consumption: The Rotterdam Study

ABSTRACT Background MicroRNAs (miRNAs) represent a class of noncoding RNAs that regulate gene expression and are implicated in the pathogenesis of different diseases. Alcohol consumption might affect the expression of miRNAs, which in turn could play a role in risk of diseases. Objectives We investigated whether plasma concentrations of miRNAs are altered by alcohol consumption. Given the existing evidence showing the link between alcohol and liver diseases, we further explored the extent to which these associations are mediated by miRNAs. Methods Profiling of plasma miRNAs was conducted using the HTG EdgeSeq miRNA Whole Transcriptome Assay in 1933 participants of the Rotterdam Study. Linear regression was implemented to explore the link between alcohol consumption (glasses/d) and miRNA concentrations, adjusted for age, sex, cohort, BMI, and smoking. Sensitivity analysis for alcohol categories (nondrinkers, light drinkers, and heavy drinkers) was performed, where light drinkers corresponded to 0–2 glasses/d in men and 0–1 glasses/d in women, and heavy drinkers to >2 glasses/d in men and >1 glass/d in women. Moreover, we utilized the alcohol-associated miRNAs to explore their potential mediatory role between alcohol consumption and liver-related traits. Finally, we retrieved putative target genes of identified miRNAs to gain an understanding of the molecular pathways concerning alcohol consumption. Results Plasma concentrations of miR-193b-3p, miR-122-5p, miR-3937, and miR-4507 were significantly associated with alcohol consumption surpassing the Bonferroni-corrected P < 8.46 × 10−5. The top significant association was observed for miR-193b-3p (β = 0.087, P = 2.90 × 10−5). Furthermore, a potential mediatory role of miR-3937 and miR-122-5p was observed between alcohol consumption and liver traits. Pathway analysis of putative target genes revealed involvement in biological regulation and cellular processes. Conclusions This study indicates that alcohol consumption is associated with plasma concentrations of 4 miRNAs. We outline a potential mediatory role of 2 alcohol-associated miRNAs (miR-3937 and miR-122-5p), laying the groundwork for further exploration of miRNAs as potential mediators between lifestyle factors and disease development.
Gorenstein derived functors

Over any associative ring R it is standard to derive Hom R (-,-) using projective resolutions in the first variable, or injective resolutions in the second variable, and doing this, one obtains Ext n R(-,-) in both cases. We examine the situation where projective and injective modules are replaced by Gorenstein projective and Gorenstein injective ones, respectively. Furthermore, we derive the tensor product - ⊗ R - using Gorenstein flat modules.
Long‐term anthropometric development of individuals with inherited metabolic diseases identified by newborn screening

Newborn screening (NBS) for inherited metabolic diseases (IMDs) substantially shortens a patient's journey. It enables the early start of metabolic treatment which might prevent potentially lethal neonatal disease manifestations, while promoting favorable development and long‐term clinical outcomes. This study aims to assess growth in screened individuals with IMDs under different dietary regimes. Anthropometric data (3585 prospective measures) of 350 screened individuals with IMDs born between 1999 and 2018 and participating in a German prospective multicenter observational study were evaluated. Overall, birth measures were within the reference ranges, suggesting unaffected prenatal growth, except for phenylketonuria (weight) and glutaric aciduria Type 1 (head circumference). After birth, longitudinal analysis of anthropometric measures revealed a loss of height standard deviation score (SDS; −0.5 SDS; p < 0.0001), head circumference SDS (−0.2 SDS; p = 0.0028), but not for weight SDS (0.1 SDS; p = 0.5097) until the age of 18 years, while BMI SDS increased (0.4 SDS; p < 0.0001). The significant interaction with age and diet groups was pronounced for the linear growth in individuals receiving diets being low in protein, long‐chain triglycerides, and galactose (p < 0.001). Identification by NBS and subsequent early (dietary) treatment cannot completely protect against alterations in growths. Disease‐specific (e.g., metabolic impairments, neurotoxins) and dietary‐specific (e.g., diets reduced in protein) factors may have an amplified impact on longitudinal growth. Therefore, alongside other important follow‐ups, the continuous observation of the anthropometric development of screened individuals with IMDs needs special attention to early identify and support individuals at risk.
Clinical Profile and Outcome of Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer With Brain Metastases: Real-World Experience

PURPOSE There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. METHODS This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. RESULTS A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. CONCLUSION There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.
A Spectrally-Dense Encoding Method for Designing a High-Speed SSVEP-BCI With 120 Stimuli

The practical functionality of a brain-computer interface (BCI) is critically affected by the number of stimuli, especially for steady-state visual evoked potential based BCI (SSVEP-BCI), which shows promise for the implementation of a multi-target system for real-world applications. Joint frequency-phase modulation (JFPM) is an effective and widely used method in modulating SSVEPs. However, the ability of JFPM to implement an SSVEP-BCI system with a large number of stimuli, e.g., over 100 stimuli, remains unclear. To address this issue, a spectrally-dense JPFM (sJFPM) method is proposed to encode a broad array of stimuli, which modulates the low- and medium-frequency SSVEPs with a frequency interval of 0.1 Hz and triples the number of stimuli in conventional SSVEP-BCI to 120. To validate the effectiveness of the proposed 120-target BCI system, an offline experiment and a subsequent online experiment testing 18 healthy subjects in total were conducted. The offline experiment verified the feasibility of using sJFPM in designing an SSVEP-BCI system with 120 stimuli. Furthermore, the online experiment demonstrated that the proposed system achieved an average performance of <inline-formula> <tex-math notation="LaTeX">${92.4}7\pm {1.83}\%$ </tex-math></inline-formula> in online accuracy and <inline-formula> <tex-math notation="LaTeX">${213.23}\pm {6.60}$ </tex-math></inline-formula> bits/min in online information transfer rate (ITR), where more than <inline-formula> <tex-math notation="LaTeX">${75}\%$ </tex-math></inline-formula> of the subjects attained the accuracy above <inline-formula> <tex-math notation="LaTeX">${90}\%$ </tex-math></inline-formula> and the ITR above 200 bits/min. This present study demonstrates the effectiveness of sJFPM in elevating the number of stimuli to more than 100 and extends our understanding of encoding a large number of stimuli by means of finer frequency division.
Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention

The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
SIRT1 inactivation switches reactive astrocytes to an antiinflammatory phenotype in CNS autoimmunity

Astrocytes are highly heterogeneous in their phenotype and function, which contributes to CNS disease, repair, and aging; however, the molecular mechanism of their functional states remains largely unknown. Here, we show that activation of sirtuin 1 (SIRT1), a protein deacetylase, played an important role in the detrimental actions of reactive astrocytes, whereas its inactivation conferred these cells with antiinflammatory functions that inhibited the production of proinflammatory mediators by myeloid cells and microglia and promoted the differentiation of oligodendrocyte progenitor cells. Mice with astrocyte-specific Sirt1 knockout (Sirt1–/–) had suppressed progression of experimental autoimmune encephalomyelitis (EAE), an animal model of CNS inflammatory demyelinating disease. Ongoing EAE was also suppressed when Sirt1 expression in astrocytes was diminished by a CRISPR/Cas vector, resulting in reduced demyelination, decreased numbers of T cells, and an increased rate of IL-10–producing macrophages and microglia in the CNS, whereas the peripheral immune response remained unaffected. Mechanistically, Sirt1–/– astrocytes expressed a range of nuclear factor erythroid–derived 2–like 2 (Nfe2l2) target genes, and Nfe2l2 deficiency shifted the beneficial action of Sirt1–/– astrocytes to a detrimental one. These findings identify an approach for switching the functional state of reactive astrocytes that will facilitate the development of astrocyte-targeting therapies for inflammatory neurodegenerative diseases such as multiple sclerosis.
What are the similarities and differences in lung cancer symptom appraisal and help‐seeking according to smoking status? A qualitative study with lung cancer patients

Lung cancer in never‐smokers represents a growing proportion of patients. The relationship between smoking status, symptom appraisal and help‐seeking behaviour is complex. Little is known about cancer symptom‐related health behaviours according to smoking status. The aim of the study was to explore lung cancer patients' experiences of a lung cancer diagnosis, identifying differences by smoking history.
PREVALENCE AND PATHOGEN LOAD OF EIMERIA IN WILD YELLOW-EYED PENGUINS (MEGADYPTES ANTIPODES) AND THE MORPHOLOGIC CHARACTERIZATION OF A NOVEL EIMERIA SPECIES

Abstract: Coccidia infections in wild birds rarely cause clinical signs; however, disease and mortality can occur with predisposing environmental and host conditions. The Yellow-eyed Penguin (Megadyptes antipodes) is an endangered species endemic to New Zealand that has seen significant ongoing population decline. The aim of this study was to examine the host–pathogen dynamics of coccidian parasites in two wild populations of Yellow-eyed Penguin: the mainland (South Island) population and the sub-Antarctic (Enderby Island) population. There was weak evidence for a difference in the prevalence of the Eimeria sp. in birds from Enderby Island (76.6%; 36/47; 95% confidence interval [CI] 62.78–86.4%) and the South Island of New Zealand (58.54%; 24/41; 95% CI 43.37–72.24%). The mean pathogen load in penguins on Enderby Island was 9,723 oocysts/g of feces (SE=5831 oocysts/g) and from the South Island of New Zealand was 1,050 oocysts/g (SE=398 oocysts/g). No evidence of an association was found between pathogen load and body weight in either study population. The morphology of the sporulated coccidial oocysts was consistent with a novel species of Eimeria. There was statistically significant variation between the oocysts collected from the two sites in all measurements apart from the oocyst wall thickness. However, the standard technique of assessing linear regressions of the length and width of oocysts from both sampling sites was 0.80, and therefore above the standard R2>0.5 used to indicate variation within a single population of oocysts, suggesting that only a single species of Eimeria was present at both sampling locations. The prevalence and pathogen load of Eimeria sp. was substantially higher than previous reports of coccidial oocysts in Yellow-eyed Penguins and free-living Sphenisciformes globally. This host–parasite relationship deserves further investigation, as the impact of this novel organism on the population remains unclear.
The Transmission of US Monetary Policy Shocks: The Role of Investment&Financial Heterogeneity

This paper studies the transmission of US monetary policy shocks into Emerging Markets emphasizing the role of investment and financial heterogeneity. First, we use a panel SVAR model to show that a US interest tightening leads to a persistent recession in Emerging Markets driven by a sharp reduction in aggregate investment. Second, we study the role of firms’ financial heterogeneity in the transmission of US interest rate shocks by exploiting detailed balance sheet dataset from Chile. We find that more indebted firms experience greater drops in investment in response to a US tightening shock than less indebted firms. This result is at odds with recent evidence from US firms, even when using the same identification strategy and econometric methods. Third, we rationalize this finding using a stylized model of heterogeneous firms subject to a tightening leverage constraint. Finally, we present evidence in support of this hypothesis as well as robustness checks to our main results. Overall, our results suggests that the transmission channel of US monetary policy shocks within and outside the US differ, a result novel to the literature.
One-Shot Federated Learning for Model Clustering and Learning in Heterogeneous Environments

The paper presents a communication eﬃcient approach for federated learning in heterogeneous environments in which users obtain data from one of K diﬀerent data distributions. In the proposed setup, the number K of data distributions and their underlying statistical properties as well as the user cluster structure (i.e., the grouping of users based on the data distributions they sample) are apriori unknown. A one-shot decentralized learning approach, based on a single round of communication between the users and the server, is proposed with the objective of learning the true model at each user. The proposed one-shot approach, based on local computations at the users and a convex clustering based aggregation step at the server is shown to provide strong learning guarantees in such heterogeneous environments. In particular, it is shown that for strongly convex learning setups, as long as the number of data points per user is above a threshold, the proposed approach achieves order-optimal mean-squared error (MSE) rates in terms of the sample size with respect to a hypothetical oracle that has access to all data points at all users and perfect information about the
Metamorphic Testing in Autonomous System Simulations

Metamorphic testing has proven to be effective for test case generation and fault detection in many domains. It is a software testing strategy that uses certain relations between input-output pairs of a program, referred to as metamorphic relations. This approach is relevant in the autonomous systems domain since it helps in cases where the outcome of a given test input may be difficult to determine. In this paper therefore, we provide an overview of metamorphic testing as well as an implementation in the autonomous systems domain. We implement an obstacle detection and avoidance task in autonomous drones utilising the GNC API alongside a simulation in Gazebo. Particularly, we describe properties and best practices that are crucial for the development of effective metamorphic relations. We also demonstrate two metamorphic relations for metamorphic testing of single and more than one drones, respectively. Our relations reveal several properties and some weak spots of both the implementation and the avoidance algorithm in the light of metamorphic testing. The results indicate that metamorphic testing has great potential in the autonomous systems domain and should be considered for quality assurance in this field.