Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic Correlates of the Effects of a Heroin Vaccine on Heroin Self-Administration in Rats

The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy.
Antibiotic resistance pattern of group-a beta-hemolytic streptococci isolated from north Indian children.

BACKGROUND The current resistance pattern of GABHS (group-A beta-hemolytic streptococci) in India has not been discussed. AIM To fill the above-mentioned void, we planned this study to determine the prevalence and degree of antibacterial resistance in GABHS isolates. SETTINGS AND DESIGN Children with acute pharyngo-tonsillitis who had not received antibiotic in the preceding week, attending the pediatric OPD, were prospectively enrolled over a period of 1 year. Throat swabs were collected from each child and transported to microbiology laboratory, as early as possible. MATERIALS AND METHODS A throat swab culture for GABHS was done. All GABHS were subjected to antibiotic susceptibility and minimum inhibitory concentration (MIC) test according to Clinical Laboratory Standard Institute (CLSI) guidelines. RESULTS In the present study, 12.6% (55/435) of the children with acute pharyngo-tonsillitis had throat swab culture positive for GABHS. The prevalence of macrolide resistance was 10.2%. The MIC50 for macrolide-resistant strain was 0.5 microg/mL (range, 0.125-8 microg/mL), and MIC90 was 8 microg/mL (range, 0.125-8 microg/mL). Tetracycline and co-trimoxazole resistances were 24.5% and 12.2% respectively. The values of MIC50 for tetracycline- and co-trimoxazole-resistant strains were 4 microg/mL (range, 0.125-32 microg/mL) and 2 microg/mL (range, 0.25-8 microg/mL) respectively. All isolates were sensitive to penicillin G and chloramphenicol on disc diffusion test. However, their MIC50 was 0.032 microg/mL (range, 0.012-0.125 microg/mL) and 2 microg/mL (range, 0.25-4 microg/mL) respectively. CONCLUSION High prevalence of antimicrobial resistance found among GABHS needs a longitudinal surveillance of isolates from different centers in India.
Historical Correlates of Social Trust

Much recent research suggests that social trust strongly affects economic and political behaviour, both at the individual and national level. This paper asks how deep the historical roots of social trust may be. Substantial evidence shows that trust has been persistent among American 2nd and 3rd generation immigrants. Other findings suggest that the roots of trust may be considerably deeper. Evidence using historical data indicates that present trust scores correlate well with even very old national characteristics. The paper concludes by discussing the importance of the findings for how societies develop.
CoDisasm: Medium Scale Concatic Disassembly of Self-Modifying Binaries with Overlapping Instructions

Fighting malware involves analyzing large numbers of suspicious binary files. In this context, disassembly is a crucial task in malware analysis and reverse engineering. It involves the recovery of assembly instructions from binary machine code. Correct disassembly of binaries is necessary to produce a higher level representation of the code and thus allow the analysis to develop high-level understanding of its behavior and purpose. Nonetheless, it can be problematic in the case of malicious code, as malware writers often employ techniques to thwart correct disassembly by standard tools. In this paper, we focus on the disassembly of x86 self-modifying binaries with overlapping instructions. Current state-of-the-art disassemblers fail to interpret these two common forms of obfuscation, causing an incorrect disassembly of large parts of the input. We introduce a novel disassembly method, called concatic disassembly, that combines CONCrete path execution with stATIC disassembly. We have developed a standalone disassembler called CoDisasm that implements this approach. Our approach substantially improves the success of disassembly when confronted with both self-modification and code overlap in analyzed binaries. To our knowledge, no other disassembler thwarts both of these obfuscations methods together.
Spatial modeling of leprosy in the state of Bahia and its social determinants: a study of health inequities*

Background: Leprosy is a neglected disease caused by Mycobacterium leprae. Brazil has the second largest number of cases in the world. Objectives: To analyze the spatial distribution of leprosy in the state of BAHIA, Brazil, and the association between his occurrence and the synthetic indicators of municipal socioeconomic performance, social vulnerability and income inequality. Methods: An ecological study with secondary data obtained from the National System of Notifiable Diseases. Dependent variables: coefficient of detection in the general population and in the population under 15 years old and the rate of grade II of physical disability. Independent variables: Synthetic indicators of socioeconomic performance, social vulnerability and income inequality. Results: The highest coefficients of detection of new cases in the general population and in children under 15 years old are concentrated in the north-west axis and in the southern region of the state. On the other hand, the highest rates of degree II of physical incapacity are concentrated in the north, northeast and south regions. Only the Index of Social and Economic Performance(IPESE)-Economy and Finance composed the final regression model of the general detection coefficients and in children under 15 years old. The municipalities with the highest indexes had the highest detection coefficients, reflecting the capacity to diagnose new cases. Study limitations: The use of synthetic indicators is a limitation of the study. Conclusions: Leprosy presents a heterogeneous spatial pattern in the state of BAHIA, and the IPESE-Economics and Finance indicator is the only one with explanatory potential of the disease.
Pattern of Cancer Deaths in a Saudi Tertiary Care Hospital

The medical records of deceased patients were reviewed to describe the pattern of cancer deaths in a newly established Saudi tertiary care hospital. During eleven months, 87 patients died of cancer. The majority (80 patients, 92%) died of incurable cancer; among which 53% did not receive any systemic anti-cancer therapy (SAT) and 43% received SAT with palliative intent. Younger age (< 65 years), relatively chemosensitive tumours and initial presentation in a potentially curable stage were associated with higher prevalence of palliative SAT administration (p = 0.009, 0.019 and 0.001, respectively). The last palliative SAT was administered during the last two months of life in 66% and during the last two weeks in 14%. During the last admission, 54% of patients were admitted through emergency room, 50% stayed >14 days and 14% died in intensive care unit or emergency room. The results demonstrate that palliative care is a realistic treatment for the majority of patients in our setting and that a significant proportion of these patients receive aggressive care at the end-of-life. There is a need to establish an integrative palliative care program to improve the quality-of-life of dying cancer patients in our region and to minimize the aggressiveness of end-of-life care.
Site of disease and opportunistic infection predict survival in HIV‐associated tuberculosis

Objective:Infection with HIV adversely affects survival in patients with tuberculosis (TB), even when TB is effectively treated. The aim of this study was to identify the determinants of survival in HIV-associated TB. Design:Retrospective cohort study. Setting:Four US academic medical centers. Patients:An inception cohort of 112 HIV-infected patients (mean age 41 years, 96% men, 46% African American) with their first episode of culture-proven TB. Outcome measures:Observed survival from the date of diagnosis of TB to the date of death or censoring. Independent variables included demographics, HIV-related conditions, risk behavior for HIV, absolute CD4+ counts, and site of disease with Mycobacterium tuberculosis. Results:Of the 112 patients, 54 (48%) had pulmonary TB alone, 36 (32%) had both pulmonary and extra-pulmonary TB and 22 (20%) had extrapulmonary TB alone. Median CD4+ count was 95 × 106/l (range, 2–767 × 106/l). During follow-up, 45 patients (40%) died. Median survival was shortest in patients with both pulmonary and extrapulmonary disease (8.4 months), followed by extrapulmonary disease alone (15.6 months), then pulmonary disease (30.4 months; P < 0.001, log-rank test). Median survival was also reduced in patients with previous opportunistic infection and in those with CD4+ < 200 × 106/l. In a proportional hazards regression analysis, which adjusted for CD4+ count, extrapulmonary disease and previous opportunistic infection were the only factors independently associated with shorter survival. Of the extrapulmonary sites of disease, TB meningitis was associated with the greatest risk of death. Conclusion:The site of culture-proven TB at presentation and the history of previous opportunistic infection are important predictors of survival in HIV-infected patients with TB.
Multi-keyframe abstraction from videos

This paper presents a method for abstracting multi-keyframe from video datasets. Existing video abstraction methods focused on simple view videos, and the results will be unacceptable if applied to overlapping views directly due to limitations like unavoidable redundancy and complicated inner correlations. We propose a correlation map to naturally model the correlations with various attributes among multi-keyframe, keyframe importance and weighted correlations are then computed to construct the map. The weighted correlations, unlike the unweighted ones, not only model probabilistic relationship among keyframes but also address the temporal and visual similarity. We facilitate the abstraction process via SVM classification and keyframes reduction using rough set. The multi-keyframe correlation map, which serially assembles event-centered keyframes in temporal order, is presented for displaying the abstraction, which shows the correlations and improves the browsability of video datasets.
A global risk assessment of primates under climate and land use/cover scenarios

Primates are facing an impending extinction crisis, driven by extensive habitat loss, land use change and hunting. Climate change is an additional threat, which alone or in combination with other drivers, may severely impact those taxa unable to track suitable environmental conditions. Here, we investigate the extent of climate and land use/cover (LUC) change‐related risks for primates. We employed an analytical approach to objectively select a subset of climate scenarios, for which we then calculated changes in climatic and LUC conditions for 2050 across primate ranges (N = 426 species) under a best‐case scenario and a worst‐case scenario. Generalized linear models were used to examine whether these changes varied according to region, conservation status, range extent and dominant habitat. Finally, we reclassified primate ranges based on different magnitudes of maximum temperature change, and quantified the proportion of ranges overall and of primate hotspots in particular that are likely to be exposed to extreme temperature increases. We found that, under the worst‐case scenario, 74% of Neotropical forest‐dwelling primates are likely to be exposed to maximum temperature increases up to 7°C. In contrast, 38% of Malagasy savanna primates will experience less pronounced warming of up to 3.5°C. About one quarter of Asian and African primates will face up to 50% crop expansion within their range. Primary land (undisturbed habitat) is expected to disappear across species' ranges, whereas secondary land (disturbed habitat) will increase by up to 98%. With 86% of primate ranges likely to be exposed to maximum temperature increases >3°C, primate hotspots in the Neotropics are expected to be particularly vulnerable. Our study highlights the fundamental exposure risk of a large percentage of primate ranges to predicted climate and LUC changes. Importantly, our findings underscore the urgency with which climate change mitigation measures need to be implemented to avert primate extinctions on an unprecedented scale.
The effect of threonine and vitamin A on intestinal histology of broiler chickens.

The aim of this was to find the intestinal histological alterations in chickens under the influence of threonine (Thr) and vitamin A treatment. A total 60 one day old birds were allotted to three treatments. Each treatment was further divided into four replicates of ten chickens each. They were fed 0.80% Thr and 1500 IU/kg vitamin A (control; NRC 1994 recommendation; T1), 0.87% Thr and 6250 IU/kg vitamin A (T2) and 0.94% thr and 11000 IU/kg vitamin A (T3) from the age of 1 to 14 days. Management and husbandry practices were in accordance with current standards. The villus height was significantly high (P<0.05) in T2 group with no significant effect on crypt depth. From the present study, it is clear that the higher level of Thr and vitamin A (T2) than the recommended level of NRC (1994) improved the villus height in growing broiler chicks.
Effective Messages in Vaccine Promotion: A Randomized Trial

OBJECTIVES: To test the effectiveness of messages designed to reduce vaccine misperceptions and increase vaccination rates for measles-mumps-rubella (MMR). METHODS: A Web-based nationally representative 2-wave survey experiment was conducted with 1759 parents age 18 years and older residing in the United States who have children in their household age 17 years or younger (conducted June–July 2011). Parents were randomly assigned to receive 1 of 4 interventions: (1) information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; (2) textual information about the dangers of the diseases prevented by MMR from the Vaccine Information Statement; (3) images of children who have diseases prevented by the MMR vaccine; (4) a dramatic narrative about an infant who almost died of measles from a Centers for Disease Control and Prevention fact sheet; or to a control group. RESULTS: None of the interventions increased parental intent to vaccinate a future child. Refuting claims of an MMR/autism link successfully reduced misperceptions that vaccines cause autism but nonetheless decreased intent to vaccinate among parents who had the least favorable vaccine attitudes. In addition, images of sick children increased expressed belief in a vaccine/autism link and a dramatic narrative about an infant in danger increased self-reported belief in serious vaccine side effects. CONCLUSIONS: Current public health communications about vaccines may not be effective. For some parents, they may actually increase misperceptions or reduce vaccination intention. Attempts to increase concerns about communicable diseases or correct false claims about vaccines may be especially likely to be counterproductive. More study of pro-vaccine messaging is needed.
Restriction fragment length polymorphisms among uropathogenic Escherichia coli isolates: pap-related sequences compared with rrn operons

Among the adhesin-encoding virulence operons associated with uropathogenic Escherichia coli, only pap (pyelonephritis-associated pilus)-related gene clusters typically exhibit variation in their structure and chromosomal copy number. To access further such variability, we compared pap restriction fragment length polymorphisms (RFLPs) with those detected among rRNA (rrn) operons, which encode an essential host function unrelated to virulence. To place such findings in a phylogenetic perspective, the E. coli isolates were also characterized by using multilocus enzyme electrophoresis. Variation in the rrn RFLP profiles correlated with evolutionary divergence resolved by multilocus enzyme electrophoresis; isolates with identical rrn profiles represented the same or closely related electrophoretic types. In contrast, such isolates frequently had different pap-related RFLPs, indicating that these genetic variations have developed recently relative to the changes associated with essential rrn operons or metabolic enzymes. Despite such fluctuations, two lines of evidence indicate conditions under which the pap-related RFLPs can be stably maintained. First, for each of 20 patients with urosepsis, both the primary urinary tract isolate and the concurrent blood isolate were identical. Second, although obtained from different patients, some isolates representing the same electrophoretic type also had identical pap-related RFLPs. Thus, the genotypic diversity of this virulence adhesin operon was not generated during the course of acute infection or during laboratory manipulations. Since fecal E. coli isolates frequently carry chromosomally encoded pap-related gene clusters, these findings suggest that the intra- and interchromosomal recombination events generating the polymorphisms associated with the pap-related sequences likely occur among the E. coli of the commensal reservoir.
ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells

The low-density lipoprotein receptor (LDLR) doesn’t directly bind AP-1B; however, it relies on this clathrin adaptor for basolateral exocytosis. Identification of the autosomal recessive hypercholesterolemia protein (ARH) as a link between LDLR and AP-1B explains this apparent discrepancy and provides a model for how other endocytic proteins may contribute to endosomal recycling.
Human mitochondrial transcription factors TFAM and TFB2M work synergistically in promoter melting during transcription initiation

Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has ‘post-recruitment’ roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from −4 to +1 in the open complex with all three proteins and from −4 to +3 with addition of ATP. Our equilibrium binding studies show that POLRMT forms stable complexes with TFB2M or TFAM on LSP with low-nanomolar Kd values, but these two-component complexes lack the mechanism to efficiently melt the promoter. This indicates that POLRMT needs both TFB2M and TFAM to melt the promoter. Additionally, POLRMT+TFB2M makes 2-mer abortives on LSP, but longer RNAs are observed only with TFAM. These results are explained by TFAM playing a role in promoter melting and/or stabilization of the open complex on LSP. Based on our results, we propose a refined model of transcription initiation by the human mitochondrial transcription machinery.
Mutation of Inositol 1,3,4-trisphosphate 5/6-kinase6 Impairs Plant Growth and Phytic Acid Synthesis in Rice

Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK) is encoded by six genes in rice (OsITPK1-6). A previous study had shown that nucleotide substitutions of OsITPK6 could significantly lower the phytic acid content in rice grains. In the present study, the possibility of establishing a genome editing-based method for breeding low-phytic acid cultivars in rice was explored, in conjunction with the functional determination of OsITPK6. Four OsITPK6 mutant lines were generated by targeted mutagenesis of the gene’s first exon using the CRISPR/Cas9 method, one (ositpk6_1) with a 6-bp in-frame deletion, and other three with frameshift mutations (ositpk6_2, _3, and _4). The frameshift mutations severely impaired plant growth and reproduction, while the effect of ositpk6_1 was relatively limited. The mutant lines ositpk6_1 and _2 had significantly lower levels (−10.1% and −32.1%) of phytic acid and higher levels (4.12- and 5.18-fold) of inorganic phosphorus compared with the wild-type (WT) line. The line ositpk6_1 also showed less tolerance to osmotic stresses. Our research demonstrates that mutations of OsITPK6, while effectively reducing phytic acid biosynthesis in rice grain, could significantly impair plant growth and reproduction.
Tracing CD34+ Stromal Fibroblasts in Palatal Mucosa and Periodontal Granulation Tissue as a Possible Cell Reservoir for Periodontal Regeneration

Abstract The aim of the present research was to trace CD34+ stromal fibroblastic cells (CD34+ SFCs) in the palatal connective tissue harvested for muco-gingival surgical procedures and in granulation tissues from periodontal pockets using immunohistochemical and transmission electron microscopy. Immunohistochemical analysis targeted the presence of three antigens: CD31, α-smooth muscle actin (α-SMA), and CD34. In the palate, CD31 staining revealed a colored inner ring of the vessels representing the endothelium, α-SMA+ was located in the medial layer of the vasculature, and CD34 was intensely expressed by endothelial cells and artery adventitial cells (considered to be CD34+ SFCs). Granulation tissue showed the same pattern for CD31+ and α-SMA, but a different staining pattern for CD34. Ultrastructural examination of the palatal tissue highlighted perivascular cells with fibroblast-like characteristics and pericytes in close spatial relationship to endothelial cells. The ultrastructural evaluation of granulation tissue sections confirmed the presence of neovasculature and the inflammatory nature of this tissue. The present study traced the presence of CD34+ SFCs and of pericytes in the palatal connective tissue thus highlighting once more its intrinsic regenerative capabilities. The clinical and systemic factors triggering mobilization and influencing the fate of local CD34+SCFs and other progenitors are issues to be further investigated.