Miracle-dz/UniFAR-FTUs huggingface dataset:
Thrombin-mediated activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease.

Vaso-occlusive crisis (VOC) is the primary cause of morbidity and hospitalization in sickle cell disease (SCD). However, only three therapies (hydroxyurea, L-glutamine, and crizanlizumab) are currently approved in SCD. These agents limit the duration, severity, and frequency of crises. Activation of coagulation is a hallmark of SCD. Studies in animal models of SCD have shown that coagulation contributes to the chronic inflammation and end-organ damage associated with the disease. However, it is unknown if coagulation directly contributes to the microvascular stasis that causes VOC. Herein, we demonstrate that inhibition of tissue factor (TF) and the downstream coagulation proteases, factor Xa and thrombin, significantly attenuates heme-induced microvascular stasis in mouse models of VOC. Pharmacologic inhibition of the principal thrombin receptor, protease activated receptor-1 (PAR-1) as well as deficiency of PAR-1 in all non-hematopoietic cells, also reduces stasis in sickle mice. PAR-1 deficiency was associated with reduced endothelial von Willebrand factor (vWF) expression, which has been shown to mediate microvascular stasis. In addition, TF inhibition reduces lung vaso-occlusion in sickle mice mediated by arteriolar neutrophil-platelet microemboli. In sum, these results suggest that prophylactic anticoagulation might attenuate the incidence of VOC.
Longitudinal Changes in Disability Rating Scale Scores: A Secondary Analysis Among Patients With Severe TBI Enrolled in the Epo Clinical Trial

Abstract Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)
Strategies to prevent adverse outcomes following Clostridioides difficile infection in the elderly

ABSTRACT Introduction Clostridioides difficile remains the most common cause of healthcare-associated infections in the US, and it disproportionately affects the elderly. Older patients are more susceptible and have a greater risk of adverse outcomes from C. difficile infection (CDI), despite advances in treatment and prevention. Areas covered The epidemiology and pathogenesis of CDI, as well as risk factors in the aging host, will be reviewed. The importance of antimicrobial stewardship and infection prevention in order to avoid acquisition and transmission will be discussed, as well as strategies to prevent adverse outcomes and recurrent CDI, through optimization of CDI treatment s,election. Expert opinion Appropriate CDI-prevention strategies to avoid adverse outcomes in this susceptible population involve antimicrobial stewardship and methods to prevent C. difficile transmission in healthcare settings. Management strategies to prevent adverse outcomes include initiation of supportive therapy and proper selection of CDI specific treatments. Many patients may also benefit from adjunctive therapies or additional procedures.
LouvainNE: Hierarchical Louvain Method for High Quality and Scalable Network Embedding

Network embedding, that aims to learn low-dimensional vector representation of nodes such that the network structure is preserved, has gained significant research attention in recent years. However, most state-of-the-art network embedding methods are computationally expensive and hence unsuitable for representing nodes in billion-scale networks. In this paper, we present LouvainNE, a hierarchical clustering approach to network embedding. Precisely, we employ Louvain, an extremely fast and accurate community detection method, to build a hierarchy of successively smaller subgraphs. We obtain representations of individual nodes in the original graph at different levels of the hierarchy, then we aggregate these representations to learn the final embedding vectors. Our theoretical analysis shows that our proposed algorithm has quasi-linear run-time and memory complexity. Our extensive experimental evaluation, carried out on multiple real-world networks of different scales, demonstrates both (i) the scalability of our proposed approach that can handle graphs containing tens of billions of edges, as well as (ii) its effectiveness in performing downstream network mining tasks such as network reconstruction and node classification.
The Ebola virus disease outbreak in Tonkolili district, Sierra Leone: a retrospective analysis of the Viral Haemorrhagic Fever surveillance system, July 2014–June 2015

Abstract In Sierra Leone, the Ebola virus disease (EVD) outbreak occurred with substantial differences between districts with someone even not affected. To monitor the epidemic, a community event-based surveillance system was set up, collecting data into the Viral Haemorrhagic Fever (VHF) database. We analysed the VHF database of Tonkolili district to describe the epidemiology of the EVD outbreak during July 2014–June 2015 (data availability). Multivariable analysis was used to identify risk factors for EVD, fatal EVD and barriers to healthcare access, by comparing EVD-positive vs. EVD-negative cases. Key-performance indicators for EVD response were also measured. Overall, 454 EVD-positive cases were reported. At multivariable analysis, the odds of EVD was higher among those reporting contacts with an EVD-positive/suspected case (odds ratio (OR) 2.47; 95% confidence interval (CI) 2.44–2.50; P < 0.01) and those attending funeral (OR 1.02; 95% CI 1.01–1.04; P < 0.01). EVD cases from Kunike chiefdom had a lower odds of death (OR 0.22; 95% CI 0.08–0.44; P < 0.01) and were also more likely to be hospitalised (OR 2.34; 95% CI 1.23–4.57; P < 0.05). Only 25.1% of alerts were generated within 1 day from symptom onset. EVD preparedness and response plans for Tonkolili should include social-mobilisation activities targeting Ebola/knowledge-attitudes-practice during funeral attendance, to avoid contact with suspected cases and to increase awareness on EVD symptoms, in order to reduce delays between symptom onset to alert generation and consequently improve the outbreak-response promptness.
Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration

Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and the retina leading to loss of central vision. Polymorphisms in genes involved in lipid metabolism, including the ATP-binding cassette transporter A1 (ABCA1), have been associated with AMD risk. However, the significance of retinal lipid handling for AMD pathogenesis remains elusive. Here, we study the contribution of lipid efflux in the RPE by generating a mouse model lacking ABCA1 and its partner ABCG1 specifically in this layer. Mutant mice show lipid accumulation in the RPE, reduced RPE and retinal function, retinal inflammation and RPE/photoreceptor degeneration. Data from human cell lines indicate that the ABCA1 AMD risk-conferring allele decreases ABCA1 expression, identifying the potential molecular cause that underlies the genetic risk for AMD. Our results highlight the essential homeostatic role for lipid efflux in the RPE and suggest a pathogenic contribution of reduced ABCA1 function to AMD.
Targets of olivocochlear collaterals in cochlear nucleus of rat and guinea pig

Descending auditory pathways can modify afferent auditory input en route to cortex. One component of these pathways is the olivocochlear system which originates in brainstem and terminates in cochlea. Medial olivocochlear (MOC) neurons also project collaterals to cochlear nucleus and make synaptic contacts with dendrites of multipolar neurons. Two broadly distinct populations of multipolar cells exist: T‐stellate and D‐stellate neurons, thought to project to inferior colliculus and contralateral cochlear nucleus, respectively. It is unclear which of these neurons receive direct MOC collateral input due to conflicting results between in vivo and in vitro studies. This study used anatomical techniques to identify which multipolar cell population receives synaptic innervation from MOC collaterals. The retrograde tracer Fluorogold was injected into inferior colliculus or cochlear nucleus to label T‐stellate and D‐stellate neurons, respectively. Axonal branches of MOC neurons were labeled by biocytin injections at the floor of the fourth ventricle. Fluorogold injections resulted in labeled cochlear nucleus multipolar neurons. Biocytin abundantly labeled MOC collaterals which entered cochlear nucleus. Microscopic analysis revealed that MOC collaterals made some putative synaptic contacts with the retrogradely labeled neurons but many more putative contacts were observed on unidentified neural targets. This suggest that both T‐ and D‐stellate neurons receive synaptic innervation from the MOC collaterals on their somata and proximal dendrites. The prevalence of these contacts cannot be stated with certainty because of technical limitations, but the possibility exists that the collaterals may also make contacts with neurons not projecting to inferior colliculus or the contralateral cochlear nucleus.
Low-Resource Syntactic Transfer with Unsupervised Source Reordering

We describe a cross-lingual transfer method for dependency parsing that takes into account the problem of word order differences between source and target languages. Our model only relies on the Bible, a considerably smaller parallel data than the commonly used parallel data in transfer methods. We use the concatenation of projected trees from the Bible corpus, and the gold-standard treebanks in multiple source languages along with cross-lingual word representations. We demonstrate that reordering the source treebanks before training on them for a target language improves the accuracy of languages outside the European language family. Our experiments on 68 treebanks (38 languages) in the Universal Dependencies corpus achieve a high accuracy for all languages. Among them, our experiments on 16 treebanks of 12 non-European languages achieve an average UAS absolute improvement of 3.3% over a state-of-the-art method.
Comparison of Biochemical, Anatomical, Morphological, and Physiological Responses to Salinity Stress in Wheat and Barley Genotypes Deferring in Salinity Tolerance

A greenhouse hydroponic experiment was performed using salt-tolerant (cv. Suntop) and -sensitive (Sunmate) wheat cultivars and a salt-tolerant barley cv. CM72 to evaluate how cultivar and species differ in response to salinity stress. Results showed that wheat cv. Suntop performed high tolerance to salinity, being similar tolerance to salinity with CM72, compared with cv. Sunmate. Similar to CM72, Suntop recorded less salinity induced increase in malondialdehyde (MDA) accumulation and less reduction in plant height, net photosynthetic rate (Pn), chlorophyll content, and biomass than in sensitive wheat cv. Sunmate. Significant time-course and cultivar-dependent changes were observed in the activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) in roots and leaves after salinity treatment. Higher activities were found in CM72 and Suntop compared to Sunmate. Furthermore, a clear modification was observed in leaf and root ultrastructure after NaCl treatment with more obvious changes in the sensitive wheat cv. Sunmate, rather than in CM72 and Suntop. Although differences were observed between CM72 and Suntop in the growth and biochemical traits assessed and modified by salt stress, the differences were negligible in comparison with the general response to the salt stress of sensitive wheat cv. Sunmate. In addition, salinity stress induced an increase in the Na+ and Na+/K+ ratio but a reduction in K+ concentrations, most prominently in Sunmate and followed by Suntop and CM72.
ScholarWorks @ UTRGV ScholarWorks @ UTRGV

Advances in technology have given us the ability to create and manipulate robots for numerous applications at the molecular scale. At this size, fabrication tool limitations motivate the use of simple robots. The individual control of these simple objects can be infeasible. We investigate a model of robot motion planning, based on global external signals, known as the tilt model. Given a board and initial placement of polyominoes, the board may be tilted in any of the 4 cardinal directions, causing all slidable polyominoes to move maximally in the speciﬁed direction until blocked.Wepropose a new hierarchy of shapes and design a single conﬁguration that is strongly universal for any w × h bounded shape within this hierarchy (it can be reconﬁgured to construct any w × h bounded shape in the hierarchy). This class of shapes constitutes the most general set of buildable shapes in the literature, with most previous work consisting of just the ﬁrst-level of our hierarchy. We accompany this result with a O ( n 4 log n )- time algorithm for deciding if a given hole-free shape is a member of the hierarchy. For our second result, we resolve a long-standing open problem within the ﬁeld: We show that deciding if a given position may be covered by a tile for a given initial board conﬁguration is PSPACE-complete, even when all movable pieces are 1 × 1 tiles with no glues. We achieve this result by a reduction from Non-deterministic Constraint Logic for a one-player unbounded game.
Behavioral effects of postnatal ketamine exposure in rhesus macaque infants are dependent on MAOA-LPR genotype.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles in prenatal and early postnatal neural development, and since previous work suggests ketamine can inhibit monoamine transporters, we hypothesized that there would be behavioral consequences of prenatal and early postnatal exposure to ketamine moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. From a large sample of animals (N = 408), we compared groups of rhesus monkeys that had experienced a single exposure to ketamine during prenatal development, an exposure during prenatal development and one postnatal exposure, a postnatal exposure with no prenatal exposure, and no exposures. Animals were classified by putative activity levels for the MAOA genotype and were tested between 3 and 4 months of age on a battery of behavioral tests. Results suggested that animals exposed to ketamine postnatally, at a dose typically used for sedative effects that also had the low-activity variant of MAOA performed poorly on a visual memory test compared to animals with the high-activity variant of the MAOA gene.
Louse-borne relapsing fever (Borrelia recurrentis infection)

Abstract Louse-borne relapsing fever (LBRF) is an epidemic disease with a fascinating history from Hippocrates’ times, through the 6th century ‘Yellow Plague’, to epidemics in Ireland, Scotland and England in the 19th century and two large Afro-Middle Eastern pandemics in the 20th century. An endemic focus persists in Ethiopia and adjacent territories in the Horn of Africa. Since 2015, awareness of LBRF in Europe, as a re-emerging disease, has been increased dramatically by the discovery of this infection in dozens of refugees arriving from Africa. The causative spirochaete, Borrelia recurrentis, has a genome so similar to B. duttonii and B. crocidurae (causes of East and West African tick-borne relapsing fever), that they are now regarded as merely ecotypes of a single genomospecies. Transmission is confined to the human body louse Pediculus humanus corporis, and, perhaps, the head louse P. humanus capitis, although the latter has not been proved. Infection is by inoculation of louse coelomic fluid or faeces by scratching. Nosocomial infections are possible from contamination by infected blood. Between blood meals, body lice live in clothing until the host's body temperature rises or falls, when they seek a new abode. The most distinctive feature of LBRF, the relapse phenomenon, is attributable to antigenic variation of borrelial outer-membrane lipoprotein. High fever, rigors, headache, pain and prostration start abruptly, 2–18 days after infection. Petechial rash, epistaxis, jaundice, hepatosplenomegaly and liver dysfunction are common. Severe features include hyperpyrexia, shock, myocarditis causing acute pulmonary oedema, acute respiratory distress syndrome, cerebral or gastrointestinal bleeding, ruptured spleen, hepatic failure, Jarisch–Herxheimer reactions (J-HR) and opportunistic typhoid or other complicating bacterial infections. Pregnant women are at high risk of aborting and perinatal mortality is high. Rapid diagnosis is by microscopy of blood films, but polymerase chain reaction is used increasingly for species diagnosis. Severe falciparum malaria and leptospirosis are urgent differential diagnoses in residents and travellers from appropriate geographical regions. High untreated case-fatality, exceeding 40% in some historic epidemics, can be reduced to less than 5% by antibiotic treatment, but elimination of spirochaetaemia is often accompanied by a severe J-HR. Epidemics are controlled by sterilising clothing to eliminate lice, using pediculicides and by improving personal hygiene.
SPORADIC POLYMER CRYSTALLIZATION IN THE n-DIMENSIONAL SPACE

In this manuscript, we investigate the spontaneous polymer crystallization by extending the classical Kolmogorov–Johnson–Mehl–Avrami theory to a multi-dimensional space. We obtained a generalized Avrami equation, described by two parameters, the Avrami index and the overall crystallization rate constant, as the classical theory does. Both parameters essentially depend on the space dimensionality, and we confirm the results by means of computer simulations. We also investigated the dependence of the overall crystallization rate constant on the growing velocity and on the nucleation rate, expressed as number of nuclei that appear per unit time on the crystallization space. The simulation results are in very good agreement with our theoretical results, both of them also being direct generalizations of the prediction of the classical Avrami equation.
Chapter 2 TRAIL-R 3 / R 4 and Inhibition of TRAIL Signalling in Cancer

The tumour necrosis factor (TNF) ligand family member TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis predominantly in tumour cells, but not in normal tissues, representing therefore an attractive candidate for cancer therapy. The human TRAIL/TRAIL receptor system is very complex, four different membrane receptors bind the ligand. Two of these receptors, TRAIL-R1 and TRAIL-R2, transmit apoptotic but also non-apoptotic signals, whereas the other two, TRAIL-R3 and TRAIL-R4, act as inhibitors. Most tumour cells co-express several TRAIL receptors, allowing receptor interference. Several molecular mechanisms have been proposed by which TRAIL-R3 and TRAIL-R4 may counteract proapoptotic TRAIL signalling at the plasma membrane level, but possibly also intracellularly. A detailed understanding of the role of the individual TRAIL receptors and their interplay will be advantageous for the development of new TRAIL receptor agonists for cancer therapy. In fact, new TRAIL formulations will be needed since first clinical studies with soluble TRAIL or receptor agonistic antibodies showed only limited success. This review summarizes the complex TRAIL/TRAIL receptor system and the mechanisms by which TRAIL-R3 and TRAIL-R4 may interfere with TRAIL-mediated apoptosis induction. In addition, we discuss the prognostic and predictive value of TRAIL receptor expression in patients’ tumour material.
Annual relative increased in inpatient mortality from antimicrobial resistant nosocomial infections in Thailand

Abstract Antimicrobial resistance is a major health threat worldwide as it brings about poorer treatment outcome and places economic burden to the society. This study aims to estimate the annual relative increased in inpatient mortality from antimicrobial resistant (AMR) nosocomial infections (NI) in Thailand. A retrospective cohort study was conducted at Ramathibodi Hospital, Bangkok, Thailand, over 2008–2012. Survival model was used to estimate the hazard ratio of mortality of AMR relative to those patients without resistance (non-AMR) after controlling for nine potential confounders. The majority of NI (73.80%) were caused by AMR bacteria over the study period. Patients in the AMR and non-AMR groups had similar baseline clinical characteristics. Relative to patients in the non-AMR group, the expected hazard ratios of mortality for patients in the AMR group with Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were 1.92 (95% CI 0.10–35.52), 1.25 (95% CI 0.08–20.29), 1.60 (95% CI 0.13–19.10) and 1.84 (95% CI 0.04–95.58), respectively. In the complete absence of AMR bacteria, this study estimated that annually, in Thailand, there would be 111 295 fewer AMR cases and 48 258 fewer deaths.
Learning Parallax Attention for Stereo Image Super-Resolution

Stereo image pairs can be used to improve the performance of super-resolution (SR) since additional information is provided from a second viewpoint. However, it is challenging to incorporate this information for SR since disparities between stereo images vary significantly. In this paper, we propose a parallax-attention stereo superresolution network (PASSRnet) to integrate the information from a stereo image pair for SR. Specifically, we introduce a parallax-attention mechanism with a global receptive field along the epipolar line to handle different stereo images with large disparity variations. We also propose a new and the largest dataset for stereo image SR (namely, Flickr1024). Extensive experiments demonstrate that the parallax-attention mechanism can capture correspondence between stereo images to improve SR performance with a small computational and memory cost. Comparative results show that our PASSRnet achieves the state-of-the-art performance on the Middlebury, KITTI 2012 and KITTI 2015 datasets.