Miracle-dz/UniFAR-FTUs huggingface dataset:
Thinging for Software Engineers

The aim of this paper is to promote the terms thing and thinging (which refers to the act of defining a boundary around some portion of reality and labeling it with a name) as valued notions that play an important role in software engineering modeling. Additionally, we attempt to furnish operational definitions for terms thing, object, process, and thinging. The substantive discussion is based on the conception of an (abstract) machine, named the Thinging Machine (TM), used in several research works. The TM creates, processes, receives, releases, and transfers things. Accordingly, a diagrammatic representation of the TM is used to model reality. In the discussion section, this paper clarifies interesting issues related to conceptual modeling in software engineering. The substance of this paper and its conclusion suggest that thinging should be more meaningfully emphasized as a valuable research and teaching topic, at least in the requirement analysis phase of the software development cycle.
The route to massive black hole formation via merger-driven direct collapse: a review

The direct collapse model for the formation of massive black holes has gained increased support as it provides a natural explanation for the appearance of bright quasars already less than a billion years from the Big Bang. In this paper we review a recent scenario for direct collapse that relies on multi-scale gas inflows initiated by the major merger of massive gas-rich galaxies at z > 6, where gas has already achieved solar composition. Hydrodynamical simulations undertaken to explore our scenario show that supermassive, gravitationally bound compact gaseous disks weighing a billion solar masses, only a few pc in size, form in the nuclei of merger remnants in less than 105 yr. These could later produce a supermassive protostar or supermassive star at their center via various mechanisms. Moreover, we present a new analytical model, based on angular momentum transport in mass-loaded gravitoturbulent disks. This naturally predicts that a nuclear disk accreting at rates exceeding yr−1, as seen in the simulations, is stable against fragmentation irrespective of its metallicity. This is at variance with conventional direct collapse scenarios, which require the suppression of gas cooling in metal-free protogalaxies for gas collapse to take place. Such high accretion rates reflect the high free-fall velocities in massive halos appearing only at z < 10, and occur naturally as a result of the efficient angular momentum loss provided by the merger dynamics. We discuss the implications of our scenario on the observed population of high-z quasars and on its evolution to lower redshifts using a semi-analytical galaxy formation model. Finally, we consider the intriguing possibility that the secondary gas inflows in the unstable disks might drive gas to collapse into a supermassive black hole directly via the General Relativistic radial instability. Such dark collapse route could generate gravitational wave emission detectable via the future Laser Interferometer Space Antenna (LISA).
Inhibition of tumor formation and metastasis by a monoclonal antibody against lymphatic vessel endothelial hyaluronan receptor 1

Although cancer metastasis is associated with poor prognosis, the mechanisms of this event, especially via lymphatic vessels, remain unclear. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE‐1) is expressed on lymphatic vessel endothelium and is considered to be a specific marker of lymphatic vessels, but it is unknown how LYVE‐1 is involved in the growth and metastasis of cancer cells. We produced rat monoclonal antibodies (mAb) recognizing the extracellular domain of mouse LYVE‐1, and investigated the roles of LYVE‐1 in tumor formation and metastasis. The mAb 38M and 64R were selected from hybridoma clones created by cell fusion between spleen cells of rats immunized with RH7777 rat hepatoma cells expressing green fluorescent protein (GFP)‐fused mouse LYVE‐1 proteins and mouse myeloma cells. Two mAb reacted with RH7777 and HEK293F human embryonic kidney cells expressing GFP‐fused mouse LYVE‐1 proteins in a GFP expression‐dependent manner, and each recognized a distinct epitope. On immunohistology, the 38M mAb specifically stained lymphatic vessels in several mouse tissues. In the wound healing assay, the 64R mAb inhibited cell migration of HEK293F cells expressing LYVE‐1 and mouse lymphatic endothelial cells (LEC), as well as tube formation by LEC. Furthermore, this mAb inhibited primary tumor formation and metastasis to lymph nodes in metastatic MDA‐MB‐231 xenograft models. This shows that LYVE‐1 is involved in primary tumor formation and metastasis, and it may be a promising molecular target for cancer therapy.
Projecting the Potential Effect of Using Paliperidone Palmitate Once-Monthly and Once-Every-3-Months Long-Acting Injections Among Medicaid Beneficiaries with Schizophrenia

BACKGROUND: Once-monthly and once-every-3-months long-acting injectable (LAI) formulations of paliperidone palmitate (PP1M and PP3M, respectively) are available for the treatment of patients with schizophrenia. However, information on the comparative effectiveness and costs of using these LAIs versus oral antipsychotics (OAs) is not available. The population effectiveness of using these treatments is also not known. OBJECTIVE: To project the effect of using PP1M and PP3M LAIs on psychiatric (Psych) and all-cause (AC) hospitalization rates over 18 months in patients with schizophrenia receiving Medicaid and treated with OAs. METHODS: A decision model, informed by data from 3 randomized controlled trials (PRIDE [NCT01157351], 3001 [NCT00111189], and 3012 [NCT01529515]), was developed to compare 3 strategies: (a) initiating OA and switching only to OA; (b) initiating with PP1M and continuing PP1M if the patient was stable at 6 months (or switching to OA if unstable; PP1M→PP1M); and (c) initiating with PP1M and switching to PP3M if the patient was stable at 6 months (or switching to OA if unstable; PP1M→PP3M). PRIDE data were used to inform the first 6-month outcomes; 3001 and 3012 data were used to inform outcomes in stable patients over the following 12 months. The primary outcome for this decision model study was Psych hospitalizations. AC hospitalizations and time to discontinuation were also assessed. Outcomes from each arm and time portions within an arm were reweighted to reflect the distribution of patient characteristics found in the real-world Medicaid sample with PRIDE trial inclusion/exclusion criteria applied. Several validation exercises were carried out to ensure that the reweighted results could reproduce observed outcomes in the Medicaid sample. RESULTS: Our final target real-world sample size was N=4,609. We found that in the Medicaid sample, compared with initiating treatments with OA, the PP1M→PP1M strategy was projected to produce a per patient decrease of 0.27 (95% CI = -0.43-0.97) and 0.28 (95% CI = -0.28-0.84) in Psych- and AC-related hospitalizations, respectively. Similarly, the PP1M→PP3M strategy was projected to produce a per patient decrease of 0.31 (95% CI = -0.27-0.87) in both Psych- and AC-related hospitalizations over OA. Validation exercises ensured that the reweighting methodology used could replicate observed outcomes in the Medicaid sample. These incremental reductions in hospitalization rates are worth about $3.4-$3.8 billion over an 18-month period in patients with schizophrenia receiving Medicaid. CONCLUSIONS: Our results suggest that using PP1M and PP3M treatment strategies for patients with schizophrenia receiving Medicaid could result in reduced hospitalizations. This finding, along with improvement to patients’ health, should be considered when assessing the value of these LAIs.
Antithyroid drug therapy in pregnancy: a review of guideline recommendations

ABSTRACT Introduction: The antithyroid drugs, Carbimazole, Methimazole, and Propylthiouracil remain the mainstay of Graves’ disease management in pregnancy. A series of Clinical Practice Guidelines aimed at optimising fetal and maternal outcomes in women with Graves’ disease have been published in recent years. Areas covered: This review examines existing guideline recommendations on antithyroid drug management of Graves’ disease in pregnancy. Expert commentary: Recent guidelines have been shaped by expanding knowledge of the adverse effect profiles of antithyroid drugs on the developing fetus. A core management strategy is to limit fetal exposure to excess thyroid hormones and to curtail adverse drug effects through effective preconception and peri-conception management. Propylthiouracil is the recommended treatment in the first trimester of pregnancy but there is uncertainty regarding antithyroid drug choices in women who continue to require treatment in later pregnancy. Further studies are needed to fully evaluate the risks of congenital anomalies following intrauterine thionamide exposure.
B-1a Cell Development in Splenectomized Neonatal Mice

B-1a cells are mainly generated from fetal liver progenitor cells, peri- and neonatally. The developmental steps and anatomical sites required for these cells to become mature B-1a cells remain elusive. We recently described a phenotypically distinct transitional B cell subset in the spleen of neonatal mice that generated B-1a cells when adoptively transferred. This, in combination with findings demonstrating that B-1a cells are lacking in congenitally asplenic mice, led us to hypothesize that the neonatal spleen is required for B-1a cell development. In accordance with previous reports, we found that B-1a cell numbers were reduced in adult mice that had undergone splenectomy compared to after sham surgery. In contrast, neonatal splenectomy led to peritoneal B-1a cell frequencies comparable to those observed in sham-operated mice until 6 weeks after surgery, suggesting that an intact spleen is required for B-1a cell maintenance rather than development. To study the role of the prenatal spleen in generating B-1a cells, we transferred fetal liver cells from pre-splenic embryos [embryonic age 11 (E11) days] into splenectomized recipient mice. B-1a cells were generated in the absence of the spleen, albeit at slightly reduced frequencies, and populated the peritoneal cavity and bone marrow. Lower bone marrow B-1a cell frequencies were also observed both after neonatal and adult splenectomy. These results demonstrated that B-1a cells could be generated in the complete absence of an intact spleen, but that asplenia led to a decline in these cells, suggesting a role of the spleen for maintaining the B-1a compartment.
The Time Course of Response Activation with Dangerous Objects

Abstract The action property of an object appears to function as an intrinsic part of its mental representation. This phenomenon has been demonstrated in cases where although the grasp response evoked by a visual object is irrelevant to a participant’s task it still appears to be encoded. This is an affordance effect. Recent findings have shown that dangerous objects can modulate the motor system by evoking aversive affordances. However, the way the time course of response activation generated by the dangerous object develops remains unclear. To investigate this process, we used a priming paradigm that varied the stimulus-onset asynchrony (SOA) between a prime and a target. Participants were asked to judge a symbol after presentation of a dangerous object. Results showed a significant congruency effect between the affordance of the ignored object and the requisite response when the SOA was 800 and 1,200 ms, (t(29) = 4.13, p < . 001; t(29) = 2.56, p < . 05, respectively). However, with briefer SOAs (0 and 400 ms), this congruency effect was not observed (ps > .10). Results indicate the time course of response activation with a dangerous object are relatively long-lasting.
Social and behavioural factors associated with risky sexual behaviours among university students in nine ASEAN countries: a multi-country cross-sectional study

ABSTRACT While university students are potential human resources, this population group is particularly involved in health risk behaviours. Preventing risky sexual behaviours among them would contribute to prevention of HIV, sexually transmitted infections (STIs), and unwanted pregnancies, which have posed a great burden on population health. This study was therefore conducted to identify social and behavioural factors associated with risky sexual behaviours among university students in nine ASEAN countries. A multi-country, cross-sectional study was conducted in 2015 among university students by a network of researchers in the selected countries. A convenient sampling method and stratified random sampling procedures were employed to select universities and students, respectively. A structured questionnaire was translated into national languages of the participating countries and used to collect data from the selected students in the classrooms. Using STATA, Chi-square test was used to test differences in proportions, and multinomial logistic regression analyses were performed to obtain relative risk ratios and 95% confidence intervals. Multivariate logistic regression analysis was performed with to identify independent social and behavioural factors associated with non-condom use at last sexual intercourse. In total, 8,836 students with a mean age of 20.6 (SD = 2.0) participated in the study. Most of them (98.5%) were unmarried. In all countries, male students were significantly more likely to have two or more sexual partners in the past 12 months compared to female students (4.8% vs. 1.1%, p < 0.001). Female students were significantly more likely to report unprotected sex compared to male students (50.5% vs. 58.8%, p = 0.01). Results of multivariable logistic regression analyses showed that students who reported having two or more partners in the past 12 months were significantly more likely to be male, be aged between 20–30, be current tobacco smokers, be binge drinkers, have severe depressive symptoms, and have been in a physical fight in the past 12 months, compared to students who reported having less than two sexual partners in the past 12 months. Health intervention programmes to prevent and control STIs, especially HIV infection, should focus on university students having the social and behavioural characteristics that are associated with risky sexual behaviours.
Evaluation of genotype by environment interactions on milk production traits of Holstein cows in southern Brazil

Objective This study assessed the possible existence of genotype by environment interactions for milk, fat and protein yields in Holstein cattle raised in one of the most important milk production basins in Brazil. Methods Changes in the genetic parameters and breeding values were evaluated for 57,967 animals from three distinct regions of southern Brazil, divided according to differences in climate. The genotype by environment interaction was determined by genetic correlations between regions, estimated by the restricted maximum likelihood, considering the animal model. Bull rankings were investigated to verify the ratio of coincident selected animals between regions for each trait. Results The estimates of heritability coefficients were similar between two regions, but were lower in the third evaluated area, for all traits. Genetic correlations between regions were high, ranging from 0.91 to 0.99 for milk, fat and protein yields, representing the absence of a genotype by environment interaction for productive traits. The percentage of selection error between regions for the top 10% of animals ranged from 0.88% to 2.07% for milk yield, 0.99% to 2.46% for fat yield and 0.59% to 3.15% for protein yield. Conclusion A slight change in genotype between areas was expected since no significant genotype by environment interactions were identified, facilitating the process of selecting Holstein cattle in southern Brazil.
Formulation, optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis

Abstract Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box–Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456 ± 11 nm, %EE of 84.12 ± 2.78%, and %DL of 15.68 ± 1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6 months does not revealed any significant change in characteristics of developed RIF-SLNs.
Surviving All the Way to College: Pathways Out of One of America’s Most Crime Ridden Cities

The purpose of this study is to better understand the factors and processes related to resilience of youth who are among the most at risk for academic failure and involvement in the criminal justice system. To address the research questions about resilience and risk, in-depth interviews were conducted with a racially and ethnically diverse sample (N = 146) from one of the “most dangerous” cities in America. To obtain an objective assessment of risk, crime data were disaggregated by the city’s census tracts. Respondents were recruited from a college campus that is located within the city limits of the research site. The retrospective interviews included questions related to family structure and dynamics, educational experiences and support, peers, mentors, extra-curricular activities, neighborhood attributes, inner traits of the respondent, and adverse childhood experiences (ACEs). Results suggest that this diverse sample of college students and recent graduates were not immune from the dangers and adversity known to exist within the northeastern city where they grew up. Crime rates and poverty indicators within the neighborhoods far exceeded national averages and findings indicate participants were exposed to serious forms and levels of community violence. Furthermore, outcome data suggest that participants also suffered from many traditional ACEs (e.g., high rates of parental separation, household substance abuse and mental illness, and family incarceration). The outcomes suggested a trifecta of protective factors in the respondent’s resilience: engaged parenting, self-selected high schools, and the interaction of an individual’s inner traits and local ecological supports. Community level suggestions include targeted parental programming, educational support, gang and crime resistance initiatives, and coping interventions for community violence exposure. Future resilience studies should consider an array of ecological factors that may help mediate the harms associated with exposure to community violence as well as data on household level stressors.
Risk factors for interpersonal violence: an umbrella review of meta-analyses

Background Interpersonal violence is a leading cause of morbidity and mortality. The strength and population effect of modifiable risk factors for interpersonal violence, and the quality of the research evidence is not known. Aims We aimed to examine the strength and population effect of modifiable risk factors for interpersonal violence, and the quality and reproducibility of the research evidence. Method We conducted an umbrella review of systematic reviews and meta-analyses of risk factors for interpersonal violence. A systematic search was conducted to identify systematic reviews and meta-analyses in general population samples. Effect sizes were extracted, converted into odds ratios and synthesised, and population attributable risk fractions (PAF) were calculated. Quality analyses were performed, including of small study effects, adjustment for confounders and heterogeneity. Secondary analyses for aggression, intimate partner violence and homicide were conducted, and systematic reviews (without meta-analyses) were summarised. Results We identified 22 meta-analyses reporting on risk factors for interpersonal violence. Neuropsychiatric disorders were among the strongest in relative and absolute terms. The neuropsychiatric risk factor that had the largest effect at a population level were substance use disorders, with a PAF of 14.8% (95% CI 9.0–21.6%), and the most important historical factor was witnessing or being a victim of violence in childhood (PAF = 12.2%, 95% CI 6.5–17.4%). There was evidence of small study effects and large heterogeneity. Conclusions National strategies for the prevention of interpersonal violence may need to review policies concerning the identification and treatment of modifiable risk factors. Declarations of interest J.R. G. is an NIHR Senior Investigator. The views expressed within this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.