Miracle-dz/UniFAR-FTUs huggingface dataset:
TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis

Purpose Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a glycoprotein involved in cell survival and tumorigenesis. There have been some promising results regarding the diagnostic value of TIMP-1 for patients with colorectal cancer (CRC). The aim of the present study was to assess the diagnostic accuracy and clinical utility of serum TIMP-1 in CRC patients through meta-analysis. Methods A systematic search of online databases was performed to collect eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operator characteristic (SROC) curve were generated from accuracy data using the random-effects model. Fagan’s nomogram and the likelihood matrix were applied to estimate the clinical utility of TIMP-1. Results A total of 9 eligible studies with 1886 patients were included. Among the patients, 819 were pathologically diagnosed with CRC, whereas 1067 did not have adenomas or other cancers. The overall sensitivity, specificity, and DOR of TIMP-1 for the diagnosis of CRC were 0.65 (95% confidence interval (CI): 0.57–0.72), 0.87 (95% CI: 0.76–0.94), and 12.73 (95% CI 5.71–28.38), respectively. The area under the SROC was 0.77 (95% CI, 0.73–0.81), suggesting the potential diagnostic value of TIMP-1 in CRC patients. Among patients with a pretest CRC probability of 20%, posttest probabilities were 56% and 9% for positive and negative TIMP-1 results, respectively. Conclusions TIMP-1 expression exhibits an upper moderate diagnostic value in CRC, and TIMP-1 assessment may be useful as a noninvasive screening tool for CRC in clinical practice.
Signatures of T and B Cell Development, Functional Responses and PD-1 Upregulation After HCMV Latent Infections and Reactivations in Nod.Rag.Gamma Mice Humanized With Cord Blood CD34+ Cells

Human cytomegalovirus (HCMV) latency is typically harmless but reactivation can be largely detrimental to immune compromised hosts. We modeled latency and reactivation using a traceable HCMV laboratory strain expressing the Gaussia luciferase reporter gene (HCMV/GLuc) in order to interrogate the viral modulatory effects on the human adaptive immunity. Humanized mice with long-term (more than 17 weeks) steady human T and B cell immune reconstitutions were infected with HCMV/GLuc and 7 weeks later were further treated with granulocyte-colony stimulating factor (G-CSF) to induce viral reactivations. Whole body bio-luminescence imaging analyses clearly differentiated mice with latent viral infections vs. reactivations. Foci of vigorous viral reactivations were detectable in liver, lymph nodes and salivary glands. The number of viral genome copies in various tissues increased upon reactivations and were detectable in sorted human CD14+, CD169+, and CD34+ cells. Compared with non-infected controls, mice after infections and reactivations showed higher thymopoiesis, systemic expansion of Th, CTL, Treg, and Tfh cells and functional antiviral T cell responses. Latent infections promoted vast development of memory CD4+ T cells while reactivations triggered a shift toward effector T cells expressing PD-1. Further, reactivations prompted a marked development of B cells, maturation of IgG+ plasma cells, and HCMV-specific antibody responses. Multivariate statistical methods were employed using T and B cell immune phenotypic profiles obtained with cells from several tissues of individual mice. The data was used to identify combinations of markers that could predict an HCMV infection vs. reactivation status. In spleen, but not in lymph nodes, higher frequencies of effector CD4+ T cells expressing PD-1 were among the factors most suited to distinguish HCMV reactivations from infections. These results suggest a shift from a T cell dominated immune response during latent infections toward an exhausted T cell phenotype and active humoral immune response upon reactivations. In sum, this novel in vivo humanized model combined with advanced analyses highlights a dynamic system clearly specifying the immunological spatial signatures of HCMV latency and reactivations. These signatures can be merged as predictive biomarker clusters that can be applied in the clinical translation of new therapies for the control of HCMV reactivation.
Impact of Nicotine and Other Stimulants on Sleep in Young Adults.

OBJECTIVES Sleep problems can have long-term negative consequences. This study explored the relationship of commonly used stimulant substances to poor sleep quality in young adults. METHODS We surveyed 498 participants, aged 18 to 25, who reported recent alcohol or marijuana use. Stimulant substances measured included coffee, energy drinks, nonmedical prescription stimulants (NPS), cocaine, and nicotine. Sleep outcomes were measured using the Pittsburgh Sleep Quality Index (PSQI) and its components. RESULTS Participants averaged 21.3 (±2.07) years of age, 47.8% male, 65.5% non-Latino white, 10.8% African-American, 12.3% Latino, and 11.5% other ethnic origins. In the past 30 days, 24.9% had used cigarettes, 48.1% energy drinks, 17.3% NPS, 79.3% coffee, and 7.9% cocaine. Mean PSQI global score was 6.21 (±3.66, median = 5). After adjusting for background characteristics, PSQI global scores were positively and significantly associated with number of cigarettes/day (b = 0.16, 95% confidence interval 0.07 to 0.25, P < 0.001) and days of NPS (b = 0.10, 95% confidence interval 0.01 to 0.18, P = 0.030). CONCLUSIONS NPS negatively affects sleep, but nicotine is particularly deleterious to sleep quality. Addressing smoking cessation to improve sleep may be a novel way to motivate young adult smokers to quit.
Effects of Salt Stress on Physiological Indexes of 'Ganmi 6' and 'Hayward' Kiwifruit Seedlings

Seedlings of two kiwifruit varieties, ‘Ganmi 6’ and ‘Hayward’, were used as experimental materials to study their tolerance to salt stress by comparing physiological indexes , The results showed that the contents of H2O2, MDA, chlorophyll and soluble protein in leaves of seedlings increased with the salt concentrations increase, accompanied with increased membrane permeability. At the same time, the activities of POD and SOD gradually increased. Furthermore, Hayward had significant higher than the Hair flower, indicating its more sensitive to salt stress.
Antimicrobial use in European long-term care facilities: results from the third point prevalence survey of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobials are commonly prescribed and contribute to the development of antimicrobial resistance in long-term care facilities (LTCFs). In 2010, the European Centre for Disease Prevention and Control initiated point prevalence surveys (PPS) of healthcare-associated infections and antimicrobial use in European LTCFs, performed by external contractors as the Healthcare-Associated infections in Long-Term care facilities (HALT) projects. Here, we investigated prevalence and characteristics of antimicrobial use and antimicrobial stewardship indicators in European LTCFs in 2016–17. Twenty-four European Union/European Economic Area (EU/EEA) countries, the former Yugoslav Republic of Macedonia and Serbia participated in the third PPS in European LTCFs. Overall, 4.9% (95% confidence interval: 4.8–5.1) of LTCF residents in the EU/EEA participating countries received at least one antimicrobial. The most commonly reported Anatomical Therapeutic Chemical (ATC) groups were beta-lactam antibacterials/penicillins (J01C), other antibacterials (J01X) (e.g. glycopeptide antibacterials, polymyxins), quinolones (J01M), sulfonamides and trimethoprim (J01E), and other beta-lactams (J01D). Urinary tract infections and respiratory tract infections were the main indications for antimicrobial prescription. This PPS provides updated and detailed information on antimicrobial use in LTCFs across the EU/EEA that can be used to identify targets for future interventions, follow-up of these interventions and promote prudent use of antimicrobials in European LTCFs.
Atypical presentation of pediatric BRAF RASopathy with acute encephalopathy

We report a 9‐year‐old girl with hypotonia, severe motor delay, absent speech, and facial dysmorphism who developed acute encephalopathy with severe neurological outcome. Trio‐based whole exome sequencing (WES) analysis detected a de novo heterozygous mutation in the BRAF gene leading to the diagnosis of an atypical presentation of cardiofaciocutaneous (CFC) syndrome. This is the second case of CFC syndrome complicated with acute encephalopathy reported in the literature and supports the hypothesis that acute encephalopathy might be one of the complications of the syndrome due to an intrinsic susceptibility to this acute event. The report furthermore highlights the role of WES in providing a fast diagnosis in patients in critical conditions with atypical presentation of rare genetic syndromes.
AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger. SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.
A New Role of OmpR in Acid and Osmotic Stress in Salmonella and E. coli

Bacteria survive and respond to diverse environmental conditions and during infection inside the host by systematic regulation of stress response genes. E. coli and S. Typhimurium can undergo large changes in intracellular osmolality (up to 1.8 Osmol/kg) and can tolerate cytoplasmic acidification to at least pHi 5.6. Recent analyses of single cells challenged a long held view that bacteria respond to extracellular acid stress by rapid acidification followed by a rapid recovery. It is now appreciated that both S. Typhimurium and E. coli maintain an acidic cytoplasm through the actions of the outer membrane protein regulator OmpR via its regulation of distinct signaling pathways. However, a comprehensive comparison of OmpR regulons between S. Typhimurium and E. coli is lacking. In this study, we examined the expression profiles of wild-type and ompR null strains of the intracellular pathogen S. Typhimurium and a commensal E. coli in response to acid and osmotic stress. Herein, we classify distinct OmpR regulons and also identify shared OmpR regulatory pathways between S. Typhimurium and E. coli in response to acid and osmotic stress. Our study establishes OmpR as a key regulator of bacterial virulence, growth and metabolism, in addition to its role in regulating outer membrane proteins.
Mobile Laser Scanned Point-Clouds for Road Object Detection and Extraction: A Review

The mobile laser scanning (MLS) technique has attracted considerable attention for providing high-density, high-accuracy, unstructured, three-dimensional (3D) geo-referenced point-cloud coverage of the road environment. Recently, there has been an increasing number of applications of MLS in the detection and extraction of urban objects. This paper presents a systematic review of existing MLS related literature. This paper consists of three parts. Part 1 presents a brief overview of the state-of-the-art commercial MLS systems. Part 2 provides a detailed analysis of on-road and off-road information inventory methods, including the detection and extraction of on-road objects (e.g., road surface, road markings, driving lines, and road crack) and off-road objects (e.g., pole-like objects and power lines). Part 3 presents a refined integrated analysis of challenges and future trends. Our review shows that MLS technology is well proven in urban object detection and extraction, since the improvement of hardware and software accelerate the efficiency and accuracy of data collection and processing. When compared to other review papers focusing on MLS applications, we review the state-of-the-art road object detection and extraction methods using MLS data and discuss their performance and applicability. The main contribution of this review demonstrates that the MLS systems are suitable for supporting road asset inventory, ITS-related applications, high-definition maps, and other highly accurate localization services.
A Faster Algorithm for Reducing the Computational Complexity of Convolutional Neural Networks

Convolutional neural networks have achieved remarkable improvements in image and video recognition but incur a heavy computational burden. To reduce the computational complexity of a convolutional neural network, this paper proposes an algorithm based on the Winograd minimal filtering algorithm and Strassen algorithm. Theoretical assessments of the proposed algorithm show that it can dramatically reduce computational complexity. Furthermore, the Visual Geometry Group (VGG) network is employed to evaluate the algorithm in practice. The results show that the proposed algorithm can provide the optimal performance by combining the savings of these two algorithms. It saves 75% of the runtime compared with the conventional algorithm.
A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti‐PD‐1 immune checkpoint antibody in a lung cancer patient

The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death‐ligand 2 (PD‐L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo‐responsive Th2 cells via the PD‐1/PD‐L2 inhibitory pathway in lung could be reawaken by PD‐1 blockade therapy.
Finely tuned conformational dynamics regulate the protective function of the lncRNA MALAT1 triple helix

Abstract Nucleic acid triplexes may regulate many important biological processes. Persistent accumulation of the oncogenic 7-kb long noncoding RNA MALAT1 is dependent on an unusually long intramolecular triple helix. This triplex structure is positioned within a conserved ENE (element for nuclear expression) motif at the lncRNA 3′ terminus and protects the entire transcript from degradation in a polyA-independent manner. A requisite 3′ maturation step leads to triplex formation though the precise mechanism of triplex folding remains unclear. Furthermore, the contributions of several peripheral structural elements to triplex formation and protective function have not been determined. We evaluated the stability, conformational fluctuations, and function of this MALAT1 ENE triple helix (M1TH) protective element using in vitro mutational analyses coupled with biochemical and biophysical characterizations. Using fluorescence and UV melts, FRET, and an exonucleolytic decay assay we define a concerted mechanism for triplex formation and uncover a metastable, dynamic triplex population under near-physiological conditions. Structural elements surrounding the triplex regulate the dynamic M1TH conformational variability, but increased triplex dynamics lead to M1TH degradation. Taken together, we suggest that finely tuned dynamics may be a general mechanism regulating triplex-mediated functions.
Mapping Fishing Activities and Suitable Fishing Grounds Using Nighttime Satellite Images and Maximum Entropy Modelling

Fisheries surveys over broad spatial areas are crucial in defining and delineating appropriate fisheries management areas. Yet accurate mapping and tracking of fishing activities remain largely restricted to developed countries with sufficient resources to use automated identification systems and vessel monitoring systems. For many countries, the spatial extent and boundaries of fishing grounds are not completely known. We used satellite images at night to detect fishing grounds in the Philippines for fishing gears that use powerful lights to attract coastal pelagic fishes. We used nightly boat detection data, extracted by U.S. NOAA from the Visible Infrared Imaging Radiometer Suite (VIIRS), for the Philippines from 2012 to 2016, covering 1713 nights, to examine spatio-temporal patterns of fishing activities in the country. Using density-based clustering, we identified 134 core fishing areas (CFAs) ranging in size from 6 to 23,215 km2 within the Philippines’ contiguous maritime zone. The CFAs had different seasonal patterns and range of intensities in total light output, possibly reflecting differences in multi-gear and multi-species signatures of fishing activities in each fishing ground. Using maximum entropy modeling, we identified bathymetry and chlorophyll as the main environmental predictors of spatial occurrence of these CFAs when analyzed together, highlighting the multi-gear nature of the CFAs. Applications of the model to specific CFAs identified different environmental drivers of fishing distribution, coinciding with known oceanographic associations for a CFA’s dominant target species. This case study highlights nighttime satellite images as a useful source of spatial fishing effort information for fisheries, especially in Southeast Asia.
Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions

The bloodstream forms of Trypanosoma brucei (BSF), the parasite protist causing sleeping sickness, primarily proliferate in the blood of their mammalian hosts. The skin and adipose tissues were recently identified as additional major sites for parasite development. Glucose was the only carbon source known to be used by bloodstream trypanosomes to feed their central carbon metabolism, however, the metabolic behaviour of extravascular tissue-adapted parasites has not been addressed yet. Since the production of glycerol is an important primary function of adipocytes, we have adapted BSF trypanosomes to a glucose-depleted but glycerol-rich culture medium (CMM_Glyc/GlcNAc) and compared their metabolism and proteome to those of parasites grown in standard glucose-rich conditions (CMM_Glc). BSF were shown to consume 2-folds more oxygen per consumed carbon unit in CMM_Glyc/GlcNAc and were 11.5-times more sensitive to SHAM, a specific inhibitor of the plant-like alternative oxidase (TAO), which is the only mitochondrial terminal oxidase expressed in BSF. This is consistent with (i) the absolute requirement of the mitochondrial respiratory activity to convert glycerol into dihydroxyacetone phosphate, as deduced from the updated metabolic scheme and (ii) with the 1.8-fold increase of the TAO expression level compared to the presence of glucose. Proton NMR analysis of excreted end products from glycerol and glucose metabolism showed that these two carbon sources are metabolised through the same pathways, although the contributions of the acetate and succinate branches are more important in the presence of glycerol than glucose (10.2% versus 3.4% of the excreted end products, respectively). In addition, metabolomic analyses by mass spectrometry showed that, in the absence of glucose, 13C-labelled glycerol was incorporated into hexose phosphates through gluconeogenesis. As expected, RNAi-mediated down-regulation of glycerol kinase expression abolished glycerol metabolism and was lethal for BSF grown in CMM_Glyc/GlcNAc. Interestingly, BSF have adapted their metabolism to grow in CMM_Glyc/GlcNAc by concomitantly increasing their rate of glycerol consumption and decreasing that of glucose. However, the glycerol kinase activity was 7.8-fold lower in CMM_Glyc/GlcNAc, as confirmed by both western blotting and proteomic analyses. This suggests that the huge excess in glycerol kinase that is not absolutely required for glycerol metabolism, might be used for another yet undetermined non-essential function in glucose rich-conditions. Altogether, these data demonstrate that BSF trypanosomes are well-adapted to glycerol-rich conditions that could be encountered by the parasite in extravascular niches, such as the skin and adipose tissues.
Chronic stroke: an oxymoron or a challenge for rehabilitation?

surprising that most attention is currently focused on efforts to improve acute care of the disease, and indeed recent years have seen a significant reduction in mortality. In the United States, for example, the relative rate of strokerelated mortality dropped by 35.8% between 2000 and 2010 (Mozaffarian et al., 2015; Powers et al., 2018). But the flip side of these improvements in acute stroke care, which are certainly to be welcomed, is that stroke continues to be a major cause of longer-term disability. In fact, even though stroke is generally considered, and managed, as a transient condition, it leaves most stroke survivors with persistent, critical limitations in activities of daily living (ADL). It has been estimated that 33 to 42% of stroke survivors still require assistance with ADL between 3 and 6 months after stroke, and 36% of these patients still report a disability after 5 years (Teasell et al., 2014). Moreover, although 50% of stroke survivors report unmet needs such as incontinence, emotional problems, mobility issues, pain and speaking problems, most of them do not receive rehabilitation follow-up or any additional therapeutic intervention (Murray et al., 2003). For patients and their caregivers, therefore, stroke is a devastating event, whose long-term impact is known but still poorly understood (Teasell et al., 2012).