Miracle-dz/UniFAR-FTUs huggingface dataset:
Together strong: cooperative Android app analysis

Recent years have seen the development of numerous tools for the analysis of taint flows in Android apps. Taint analyses aim at detecting data leaks, accidentally or by purpose programmed into apps. Often, such tools specialize in the treatment of specific features impeding precise taint analysis (like reflection or inter-app communication). This multitude of tools, their specific applicability and their various combination options complicate the selection of a tool (or multiple tools) when faced with an analysis instance, even for knowledgeable users, and hence hinders the successful adoption of taint analyses. In this work, we thus present CoDiDroid, a framework for cooperative Android app analysis. CoDiDroid (1) allows users to ask questions about flows in apps in varying degrees of detail, (2) automatically generates subtasks for answering such questions, (3) distributes tasks onto analysis tools (currently DroidRA, FlowDroid, HornDroid, IC3 and two novel tools) and (4) at the end merges tool answers on subtasks into an overall answer. Thereby, users are freed from having to learn about the use and functionality of all these tools while still being able to leverage their capabilities. Moreover, we experimentally show that cooperation among tools pays off with respect to effectiveness, precision and scalability.
The medical and mental health comorbidities of children with adhd in a sibling control design study

Ibilola O, Silva D Princess Margaret Hospital, Perth, WA, Australia; Telethon Kids Institute and Joondalup Health Campus, Perth, WA, Australia Objectives: Attention deficit hyperactivity disorder (ADHD) is a common disorder affecting 5% of the children. Although the morbidity of children with ADHD has been examined; most studies are curtailed and unable to control for genetic and parental factors and others are focused on singular comorbidities and their associations with ADHD. Our study investigates the general medical and mental health conditions present in children with ADHD compared to their non-ADHD sibling. Method: Data were collected from a cross-sectional community study of 130 children who met the DSM-IV diagnosis of ADHD and commenced on stimulant medication, compared with their siblings closest in age not diagnosed with ADHD. All parents received paired questionnaires to complete for both index case and sibling. Information on demographics, general paediatric conditions and doctor diagnosed mental health conditions and the need for early allied services were included. Results: There was no difference between the ADHD cases and controls for birthweight, gestation, mean age, but significantly more female non-ADHD siblings. The ADHD child was significantly more likely to be diagnosed with a neurodevelopmental condition including depression, anxiety, obsessive compulsive disorder, autism and learning difficulties when compared with their sibling controls, which corroborates findings from previous study. In their infancy, they were two and half times more likely to be described as a fussy eater (OR 2.68; CI 1.26–5.66); five times more likely to be hospitalised for irritability (OR 5.00; CI 1.10–22.82) and four times more likely to experience sleep issues (OR 4.29; CI 1.85–9.95) in comparison to their non-ADHD sibling. Children with ADHD were more likely to have had significant injury requiring admission, as supported by earlier study and be affected by preservatives and migraine. Children with ADHD were more likely to require allied services which included speech therapy, OT, physiotherapy and psychology support in primary school when compared to their non-ADHD sibling. Conclusion: Our findings suggest children affected with ADHD, from a very early age experience considerably more medical and mental health problems than their non-ADHD siblings despite their shared genetic and environmental factors; hence requiring significantly more services.
Model-based pose estimation for texture-less objects with differential evolution algorithm

This paper proposes a novel object-tracking method to estimate three dimensions position of texture-less objects using one camera system and 3D model. The system uses efficient chamfer matching method to calculated distances between 2D edge templates of pose hypotheses with edges from the Canny edge query image. Differential Evolution algorithm uses those distances as inputs to ensure the close optimum results and find the most suitable position of objects. For initialization the exhaustive searching is employed. With the good initialization, a smaller searching space is set to guaranty the online tracking ability. The first results showed the potential of the method in solving object tracking and detection problem.
Hyaluronan promotes TRPV4-induced chondrogenesis in ATDC5 cells

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan essential for the homeostasis of cartilage-related tissues. Intracellular adhesion molecule-1 (ICAM-1) and CD44 have been identified as receptors for HA. Recently, transient receptor potential vanilloid 4 (TRPV4) has emerged as a potential research target in several areas of physiology. TRPV4 is a Ca2+-permeable, non-selective cation channel that appears to have mechanosensory or osmosensory roles in several musculoskeletal tissues. HA and TRPV4 play key roles in chondrogenesis; however, it has remained unclear whether they have interactive effects on chondrogenesis and, if so, how do they interact with each other? This study investigated the relationship between HA, its receptors ICAM-1 and CD44, and TRPV4 in the chondrogenic pathway using the ATDC5 cell line. It was found that the presence of HA is required for TRPV4-induced chondrogenesis. Loss of HA suppressed TRPV4-induced expression of the chondrogenic markers, SOX9 and Aggrecan. Moreover, HA affects TRPV4-induced chondrogenic development via each of ICAM-1 and CD44 partially. In conclusion, for the first time, the existence of an interaction between HA, its receptor ICAM-1 and CD44, and TRPV4-activity in chondrogenesis in the ATDC5 cell line was reported. TRPV4 is known to function as a mechanosensory channel in several musculoskeletal tissues. Therefore, findings of this study may suggest the existence of a molecular mechanism that underlies the interactive effects of HA and mechanical loading on joint chondrogenesis.
Impact of Vascular Function on Maximum Power Output in Elite Handball Athletes

ABSTRACT Purpose: To evaluate vascular function and its relationship to cardiorespiratory fitness in professional handball athletes. Method: We examined 30 male professional handball athletes (age 27 ± 4 y) and 10 male sedentary controls (age 26 ± 5 y) at rest. The workup included exercise testing via ergometry. To assess vascular function, a validated electronic model of the arterial tree (vasc assist 2®) was used. It replicates noninvasively acquired pulse pressure waves by modulating the relevant functional parameters of compliance, resistance, inertia, pressure, and flow. The maximum oxygen uptake (VO2max) was estimated using the validated heart rate ratio method. Results: Athletes had a significantly lower systolic and diastolic central blood pressure (cBP) compared to controls (102 ± 9/60 ± 9 vs. 110 ± 8/74 ± 9 mmHg, p < .01), whereas aortic pulse wave velocity (PWV) (6.2 ± 0.8 vs. 6.3 ± 0.5 m/s, p = .45) and augmentation index at a heart rate of 75 (Aix@75) (−4 ± 12 vs. −13 ± 16%, p = .06) were not different. Resistance index (R) (15.9 ± 4.4 vs. 10.6 ± 0.6, p = .001) and maximum power output (MPO) (3.55 ± 0.54 vs. 2.46 ± 0.55 Watt/kg, p < .001) were significantly higher in athletes compared to controls. We found no relevant correlation between MPO, resting heart rate, PWV, Aix@75, and cBP. A higher VO2max (p = .02) and a lower R (p < .01) were significant predictors of a higher MPO in athletes. Conclusion: R had an independent and strong correlation to MPO in athletes, which might help to disentangle the contribution of aerobic capacity and arterial function to physical power.
Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes

Impaired wound healing is a major complication of diabetes, and despite the associated risks, treatment strategies for diabetic wounds remain limited. This is due, in part, to an incomplete understanding of the underlying pathological mechanisms, including the effects of hyperglycemia on components of the extracellular matrix (ECM). In the current study, we explored whether the expression of thrombospondin 2 (TSP2), a matricellular protein with a demonstrated role in response to injury, was associated with delayed healing in diabetes. First, we found that TSP2 expression was elevated in diabetic mice and skin from patients with diabetes. Then, to determine the contribution of TSP2 to impaired healing in diabetes, we developed a novel diabetic TSP2-deficient model. Though the TSP2-deficient mice developed obesity and hyperglycemia comparable with diabetic control mice, they exhibited significantly improved healing, characterized by accelerated reepithelialization and increased granulation tissue formation, fibroblast migration, and blood vessel maturation. We further found that hyperglycemia increased TSP2 expression in fibroblasts, the major cellular source of TSP2 in wounds. Mechanistically, high glucose increased activation of the hexosamine pathway and nuclear factor-κB signaling to elevate TSP2 expression. Our studies demonstrate that hyperglycemia-induced TSP2 expression contributes to impaired healing in diabetes.
Declining malformation rates with changed antiepileptic drug prescribing

Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.
Improving legibility in language without space between words

Background, purpose. The purpose of the present study was to determine what text format, in the absence of space between words, is the easiest to read – “First-Letter-Capitalized” (e.g., SetTextStyle), “Uppercase-Word-Lowercase-Word-Alternation” (e.g., SETtextSTYLE), or “All-Lowercase” (e.g., settextstyle). Material and methods. Forty-five graduate students read nine statements (six true and three false) shown in those three text formats in a LATIN SQUARE design with repeated measures. Results, conclusions. The results indicated that the average reading time for the First-Letter-Capitalized condition was significantly less than that of the Uppercase-WordLowercase-Word-Alternation condition (p < .01). The average reading time for the Uppercase-Word-Lowercase-Word-Alternation condition, in turn, was significantly less than that of the All-Lowercase condition (p < .01).
Expression of obesity-related adipokine genes during fasting in a naturally obese marine mammal.

Northern elephant seals (Mirounga angustirostris) are exceptional among fasting-adapted animals in coupling prolonged fasting with energetically costly activities, relying on oxidation of fat stores accrued during foraging to power metabolic demands of reproduction and molting. We hypothesized that high rates of energy expenditure, insulin resistance, and immune responses to colonial breeding in fasting seals are mediated by adipokines, or signaling molecules secreted by adipose tissue that are associated with obesity and inflammation in humans. We measured mRNA expression of 10 adipokine genes in blubber tissue of adult female elephant seals sampled early and late during their lactation and molting fasts and correlated gene expression with adiposity and circulating levels of corticosteroid and immune markers. Expression of adiponectin (ADIPOQ) and its receptor ADIPOR2, leptin receptor (LEPR), resistin (RETN), retinol binding protein 4 (RBP4), and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) was increased, whereas that of fat mass and obesity associated protein (FTO) was decreased in late-fasted compared to early-fasted groups. Abundance of adipokine transcripts that increased in late fasting was negatively associated with body mass and positively associated with cortisol, suggesting that they may mediate local metabolic effects of cortisol in blubber during fasting. Expression of several adipokines was correlated with the immune markers IL-6, haptoglobin, IgM, and IgE, suggesting a potential role in modulating immune responses to colonial breeding and molting. Since many of these adipokines have not been measured in other wild animals, this study provides preliminary insights into their local regulation in fat tissue and targeted assays for future studies.
The conserved histone chaperone LIN‐53 is required for normal lifespan and maintenance of muscle integrity in Caenorhabditis elegans

Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and aspects of healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN‐53 (RBBP4/7) associates with different chromatin‐regulating complexes to safeguard cell identities in Caenorhabditis elegans as well as mammals, and has a role in preventing memory loss and premature aging in humans. We show that LIN‐53 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in C. elegans muscles to ensure functional muscles during postembryonic development and in adults. While mutants for other NuRD members show a normal lifespan, animals lacking LIN‐53 die early because LIN‐53 depletion affects also the histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin‐53 and sin‐3 mutants die early, we performed transcriptome and metabolomic analysis revealing that levels of the disaccharide trehalose are significantly decreased in both mutants. As trehalose is required for normal lifespan in C. elegans, lin‐53 and sin‐3 mutants could be rescued by either feeding with trehalose or increasing trehalose levels via the insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN‐53 is required for maintaining lifespan and muscle integrity through discrete chromatin regulatory mechanisms. Since both LIN‐53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan regulation is also evolutionarily conserved.
Modulation of Agrin and RhoA Pathways Ameliorates Movement Defects and Synapse Morphology in MYO9A-Depleted Zebrafish

Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders characterised by impaired function of the neuromuscular junction (NMJ). This is due to defects in one of the many proteins associated with the NMJ. In three patients with CMS, missense mutations in a gene encoding an unconventional myosin protein, MYO9A, were identified as likely causing their disorder. Preliminary studies revealed a potential involvement of the RhoA/ROCK pathway and of a key NMJ protein, agrin, in the pathophysiology of MYO9A-depletion. In this study, a CRISPR/Cas9 approach was used to generate genetic mutants of MYO9A zebrafish orthologues, myo9aa/ab, to expand and refine the morphological analysis of the NMJ. Injection of NT1654, a synthetic agrin fragment compound, improved NMJ structure and zebrafish movement in the absence of Myo9aa/ab. In addition, treatment of zebrafish with fasudil, a ROCK inhibitor, also provided improvements to the morphology of NMJs in early development, as well as rescuing movement defects, but not to the same extent as NT1654 and not at later time points. Therefore, this study highlights a role for MYO9A at the NMJ, the first unconventional myosin motor protein associated with a neuromuscular disease, and provides a potential mechanism of action of MYO9A-pathophysiology.
Energetically optimized pharmacophore modeling to identify dual negative allosteric modulators against group I mGluRs in neurodegenerative diseases

Abstract Glutamate is the key neurotransmitter in human brain that regulates the important functions such as learning, memory and cognition. Abnormal regulation of glutamate leads to various neurodegenerative disorders. To regulate the glutamate signaling pathway we have employed a computational technique called energetically optimized pharmacophore model. We selected four-point pharmacophore (HRRR) based on the glide energy scores and screened the eMolecules database having more than 10 million compounds to find the potential dual negative allosteric modulators for both mGluR1 and mGluR5. The pharmacokinetic properties were calculated to filter out the unwanted molecules. Further, molecular docking, enrichment calculations and molecular dynamics simulations were executed. Finally, the top two compounds (1080734, 22696638) selected from the screened database could be potent dual negative allosteric modulators for the targeted proteins mGluR1 and mGluR5. AbbreviationsCNS central nervous systemGPCR G-protein coupled receptormGluR metabotropic glutamate receptorIFD induced fit dockingPOPC palmitoyloleoylphosphatidylcholineVFT Venus flytrap domainRMSD root mean square deviationRMSF root mean square fluctuation7TM seven transmembrane Communicated by Ramaswamy H. Sarma
From cortex to cord: motor circuit plasticity after spinal cord injury

Spinal cord injury is associated with chronic sensorimotor deficits due to the interruption of ascending and descending tracts between the brain and spinal cord. Functional recovery after anatomically complete spinal cord injury is limited due to the lack of long-distance axonal regeneration of severed fibers in the adult central nervous system. Most spinal cord injuries in humans, however, are anatomically incomplete. Although restorative treatment options for spinal cord injury remain currently limited, research from experimental models of spinal cord injury have revealed a tremendous capability for both spontaneous and treatment-induced plasticity of the corticospinal system that supports functional recovery. We review recent advances in the understanding of corticospinal circuit plasticity after spinal cord injury and concentrate mainly on the hindlimb motor cortex, its corticospinal projections, and the role of spinal mechanisms that support locomotor recovery. First, we discuss plasticity that occurs at the level of motor cortex and the reorganization of cortical movement representations. Next, we explore downstream plasticity in corticospinal projections. We then review the role of spinal mechanisms in locomotor recovery. We conclude with a perspective on harnessing neuroplasticity with therapeutic interventions to promote functional recovery.
Aggravation of Human Diseases and Climate Change Nexus

For decades, researchers have debated whether climate change has an adverse impact on diseases, especially infectious diseases. They have identified a strong relationship between climate variables and vector’s growth, mortality rate, reproduction, and spatiotemporal distribution. Epidemiological data further indicates the emergence and re-emergence of infectious diseases post every single extreme weather event. Based on studies conducted mostly between 1990-2018, three aspects that resemble the impact of climate change impact on diseases are: (a) emergence and re-emergence of vector-borne diseases, (b) impact of extreme weather events, and (c) social upliftment with education and adaptation. This review mainly examines and discusses the impact of climate change based on scientific evidences in published literature. Humans are highly vulnerable to diseases and other post-catastrophic effects of extreme events, as evidenced in literature. It is high time that human beings understand the adverse impacts of climate change and take proper and sustainable control measures. There is also the important requirement for allocation of effective technologies, maintenance of healthy lifestyles, and public education.
HtrA‐mediated selective degradation of DNA uptake apparatus accelerates termination of pneumococcal transformation

Natural transformation mediates horizontal gene transfer, and thereby promotes exchange of antibiotic resistance and virulence traits among bacteria. Streptococcus pneumoniae, the first known transformable bacterium, rapidly activates and then terminates the transformation state, but it is unclear how the bacterium accomplishes this rapid turn‐around at the protein level. This work determined the transcriptomic and proteomic dynamics during the window of pneumococcal transformation. RNA sequencing revealed a nearly uniform temporal pattern of rapid transcriptional activation and subsequent shutdown for the genes encoding transformation proteins. In contrast, mass spectrometry analysis showed that the majority of transformation proteins were substantially preserved beyond the window of transformation. However, ComEA and ComEC, major components of the DNA uptake apparatus for transformation, were completely degraded at the end of transformation. Further mutagenesis screening revealed that the membrane‐associated serine protease HtrA mediates selective degradation of ComEA and ComEC, strongly suggesting that breakdown of the DNA uptake apparatus by HtrA is an important mechanism for termination of pneumococcal transformation. Finally, our mutagenesis analysis showed that HtrA inhibits natural transformation of Streptococcus mitis and Streptococcus gordonii. Together, this work has revealed that HtrA regulates the level and duration of natural transformation in multiple streptococcal species.