Miracle-dz/UniFAR-FTUs huggingface dataset:
Managing Illicit Online Pharmacies: Web Analytics and Predictive Models Study

Background Online pharmacies have grown significantly in recent years, from US $29.35 billion in 2014 to an expected US $128 billion in 2023 worldwide. Although legitimate online pharmacies (LOPs) provide a channel of convenience and potentially lower costs for patients, illicit online pharmacies (IOPs) open the doors to unfettered access to prescription drugs, controlled substances (eg, opioids), and potentially counterfeits, posing a dramatic risk to the drug supply chain and the health of the patient. Unfortunately, we know little about IOPs, and even identifying and monitoring IOPs is challenging because of the large number of online pharmacies (at least 30,000-35,000) and the dynamic nature of the online channel (online pharmacies open and shut down easily). Objective This study aims to increase our understanding of IOPs through web data traffic analysis and propose a novel framework using referral links to predict and identify IOPs, the first step in fighting IOPs. Methods We first collected web traffic and engagement data to study and compare how consumers access and engage with LOPs and IOPs. We then proposed a simple but novel framework for predicting the status of online pharmacies (legitimate or illicit) through the referral links between websites. Under this framework, we developed 2 prediction models, the reference rating prediction method (RRPM) and the reference-based K-nearest neighbor. Results We found that direct (typing URL), search, and referral are the 3 major traffic sources, representing more than 95% traffic to both LOPs and IOPs. It is alarming to see that direct represents the second-highest traffic source (34.32%) to IOPs. When tested on a data set with 763 online pharmacies, both RRPM and R2NN performed well, achieving an accuracy above 95% in their predictions of the status for the online pharmacies. R2NN outperformed RRPM in full performance metrics (accuracy, kappa, specificity, and sensitivity). On implementing the 2 models on Google search results for popular drugs (Xanax [alprazolam], OxyContin, and opioids), they produced an error rate of only 7.96% (R2NN) and 6.20% (RRPM). Conclusions Our prediction models use what we know (referral links) to tackle the many unknown aspects of IOPs. They have many potential applications for patients, search engines, social media, payment companies, policy makers or government agencies, and drug manufacturers to help fight IOPs. With scarce work in this area, we hope to help address the current opioid crisis from this perspective and inspire future research in the critical area of drug safety.
Effect of Local Infiltration Analgesia on Functional Outcomes in Total Knee Arthroplasty: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial

Abstract Local infiltration analgesia (LIA) is a simple, surgeon-administered technique for the treatment of postoperative pain after total knee arthroplasty (TKA). The aim of the study was to investigate the efficacy of LIA and its effects on functional outcomes in TKA. A total of 135 patients with primary TKA were recruited and randomized either to receive LIA or to receive placebo injection (PI). Pain, active range of motion (ROM), knee function score, functional activities, and hospital length of stay (LOS) were assessed before surgery and from postoperative day (POD) 1 to at discharge. Lower pain scores at rest were recorded on POD1 and POD2 in the LIA group (p = 0.027 and p = 0.020, respectively). Lower pain score on walking was recorded on POD1 in the LIA group (p = 0.002). There was a statistically significant difference in active knee flexion between groups on POD1 (p = 0.038). There was a significant difference in LOS between LIA and PI groups. Shorter stay was seen in LIA group. There were no statistically significant differences between the groups in terms of knee function score and functional outcomes. LIA technique is effective for pain management in the early postoperative period. LIA added benefit for knee function in terms of active knee flexion ROM after TKA. A shorter hospital LOS was observed in LIA group. However, we did not find any differences in groups in terms of functional assessment such as ability to rise from a chair and walking capacity.The level of evidence is randomized controlled trial, level I.
How do Crocodylian embryos process yolk? Morphological evidence from the American alligator, Alligator mississippiensis

Recent studies have demonstrated a mechanism of embryonic yolk processing in lizards, snakes and turtles that differs markedly from that of birds. In the avian pattern, cells that line the inside of the yolk sac take up products of yolk digestion and deliver nutrients into the vitelline circulation. In contrast, in squamates and turtles, proliferating endodermal cells invade and fill the yolk sac cavity, forming elongated strands of yolk‐filled cells that surround small blood vessels. This arrangement provides a means by which yolk material becomes cellularized, digested, and transported for embryonic use. Ultrastructural observations on late‐stage Alligator mississippiensis eggs reveal elongated, vascular strands of endodermal cells within the yolk sac cavity. The strands of cells are intermixed with free yolk spheres and clumps of yolk‐filled endodermal cells, features that reflect early phases in the yolk‐processing pattern. These observations indicate that yolk processing in Alligator is more like the pattern of other reptiles than that of birds.
Interactive Graphics in Industry: The Early Days

Computer graphics has a long history. Industrial organizations and laboratories drove significant improvements as they adapted and assembled basic capabilities into complex interactive applications. Of particular concern in the early days was providing interactive 3-D applications for computer-aided design and engineering. This article describes the experience of two early industry practitioners who built successful 1970s interactive 3-D systems.
In Vitro Activation of Macrophages by an MHC Class II-restricted Trichomonas Vaginalis TvZIP8-derived Synthetic Peptide

ABSTRACT Background Macrophages play an important role in the inflammatory response towards pathogens and their effector functions depend on the mode of activation which is mediated by recognition of pathogen-associated molecular patterns, as peptides. Trichomonas vaginalis provokes an inflammatory response in the host in which macrophages are the first line of defense. This study aimed to analyze the effect of a specific peptide derived from the transporter TvZIP8 of T. vaginalis on the activation of macrophages. Methods An in silico approach based on computational prediction of epitopes was applied to detect potential murine MHC class II-restricted peptides from TvZIP8 that can activate macrophages and the immunomodulatory activity was evaluated by in vitro stimulation of murine macrophages. Results Based on binding scores, one peptide denominated TvZIP8-pep was selected for further analysis. In vitro stimulation with synthetic TvZIP8-pep triggered on murine macrophages the NO and H2O2 production and an overexpression of iNOS and NOX-2 genes. Also, a significant increase of pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, as well as, overexpression of the TLR4, MyD88, and NF-κB genes and NF-κB activation were observed on macrophages after stimulation with TvZIP8-pep in vitro. Moreover, higher levels of IFN-γ were detected in co-cultures using CD4 + T cells with TvZIP8-pep-stimulated macrophages Conclusion These results support the potential of TvZIP8 as a promising antigen to stimulates a specific macrophage response against T. vaginalis, but further analyses are required to evaluate their possible potential as a novel antigen for immunodiagnosis and/or vaccine against trichomoniasis.
Optimal P2Y12 inhibition in older adults with acute coronary syndromes: A network meta-analysis of randomized controlled trials.

AIMS Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischemic and bleeding endpoints in older adults with ACS. METHODS AND RESULTS Randomized clinical trials that reported separately the results of adults older >70 years for at least the primary endpoint (composite of death, myocardial infarction [MI] and stroke). Seven studies (14,485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischemic endpoint (composite of MI and stroke) and was most likely the best treatment (Surface Under the Cumulative Ranking curve Analysis [SUCRA] 54.5 and 59.8, respectively). With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%) while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA. CONCLUSION Among older subjects with ACS, DAPT should be balanced upon ischemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults.
Implant primary stability with an osteocondensation drilling protocol in different density polyurethane blocks

Abstract The implant primary stability is a fundamental condition for avoiding implant micro-motions that might result in fibrous encapsulation; its achievement is facilitated by macro- and micro-geometry of the implant, and by the bone density and architecture at the intended implant site. The aim was to evaluate an osteocondensing drilling protocol for dental implant positioning compared to standard protocol on polyurethane block. A total of 40 implants, 20 for each osteocondensing group (Test) and 20 for standard drilling group (Control), were positioned. Insertion torque (IT), removal torque (RT), and Periotest were measured. A IT, RT, and Periotest significant difference was present in favor of the implant osteocondensing protocol. The results suggested that osteocondensing protocol represents a useful technique for implant placement in poor density bone.
Culturally Responsive Health Promotion to Address Health Disparities in African American Men: A Program Impact Evaluation

African American (AA) men continue to experience worse health outcomes compared to men of other races/ethnicities. Community-based interventions are known to be effective in health promotion and disease prevention. The program objectives were to (a) increase knowledge and risk awareness of targeted conditions, (b) change health-care-seeking attitudes toward regular primary care among AA men, and (c) improve their lifestyle-related health behaviors by leveraging the influence of women in their lives. The community-engaged educational intervention targeted both men and women and included eight 90-min sessions per cohort. Topics included prostate cancer, cardiovascular disease, diabetes, mental health, health-care access, and healthy lifestyle. Sessions were both didactic and interactive. A pre-/post-intervention questionnaire assessed knowledge. Interviews were conducted with male participants and a focus group discussion (FGD) with women to assess program impact. Interview and FGD transcripts were analyzed for themes and recommendations. Major themes were—increased knowledge/awareness of risk associated with chronic conditions, change in health-care-seeking attitudes, increased self-efficacy to engage the health-care system, and lifestyle changes. Other impacts reported were building community/social support, a safe and enabling learning environment, and enhanced community health status overall. Recommendations included having extended, more in-depth sessions, targeting the younger generation, smaller cohort sizes, and more community-based health programming. Community-engaged health promotion using a cohort model as well as including women can be effective in increasing knowledge, enhancing self-efficacy, and providing the much-needed social support. These can influence health-related behaviors and thus contribute to improving health outcomes for AA men.
Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

Significance Genetic systems for controlling transmission of vector-borne diseases are moving from discovery-stage demonstrations of proofs-of-principle to the next phases of development. A successful transition requires meeting safety and efficacy criteria defined in target product profiles. We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance. This system is designed to achieve mosquito population modification when coupled with genes encoding antiparasite effector molecules and result in stable and sustainable blocking of malaria parasite transmission. A Cas9/guide RNA-based gene drive strain, AgNosCd-1, was developed to deliver antiparasite effector molecules to the malaria vector mosquito, Anopheles gambiae. The drive system targets the cardinal gene ortholog producing a red-eye phenotype. Drive can achieve 98 to 100% in both sexes and full introduction was observed in small cage trials within 6 to 10 generations following a single release of gene-drive males. No genetic load resulting from the integrated transgenes impaired drive performance in the trials. Potential drive-resistant target-site alleles arise at a frequency <0.1, and five of the most prevalent polymorphisms in the guide RNA target site in collections of colonized and wild-derived African mosquitoes do not prevent cleavage in vitro by the Cas9/guide RNA complex. Only one predicted off-target site is cleavable in vitro, with negligible deletions observed in vivo. AgNosCd-1 meets key performance criteria of a target product profile and can be a valuable component of a field-ready strain for mosquito population modification to control malaria transmission.
Using social robot PLEO to enhance the well-being of hospitalised children

Hospitalisation is stressful for children. Play material is often offered for distraction and comfort. We explored how contact with social robot PLEO could positively affect a child’s well-being. To this end, we performed a multiple case study on the paediatric ward of two hospitals. Child life specialists offered PLEO as a therapeutic activity to children in a personalised way for a well-being related purpose in three to five play like activity sessions during hospital visits/stay. Robot–child interaction was observed; care professionals, children and parents were interviewed. Applying direct content analysis revealed six categories of interest: interaction with PLEO, role of the adults, preferences for PLEO, PLEO as buddy, attainment of predetermined goal(s) and deployment of PLEO. Four girls and five boys, aged 4–13, had PLEO offered as a relief from stress or boredom or for physical stimulation. All but one started interacting with PLEO and showed behaviours like hugging, caring or technical exploration, promoting relaxation, activation and/or making contact. Interaction with PLEO contributed to achieving the well-being related purpose for six of them. PLEO was perceived as attractive to elicit play. Although data are limited, promising results emerge that the well-being of hospitalised children might be fostered by a personalised PLEO offer.
RNA–protein interaction mapping via MS2- or Cas13-based APEX targeting

Significance The biogenesis, processing, function, and degradation of cellular RNAs depend critically on their protein interaction partners. Systematic analysis of the protein interactome of specific RNAs of interest inside living cells can therefore enable a better understanding of many biological processes. We developed two complementary methods for tagging endogenous proteins in the vicinity of specific cellular RNAs, for subsequent identification by mass spectrometry. When applied to the human telomerase RNA, our methods recovered known interaction partners as well as unexpected hits, including an enzyme that catalyzes RNA posttranscriptional modification to influence telomerase activity. The technology introduced by our study should facilitate future investigations into RNA–protein interactions in living cells. RNA–protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA–protein interactions in living cells in an unbiased manner. We used two approaches to target the engineered peroxidase APEX2 to specific cellular RNAs for RNA-centered proximity biotinylation of protein interaction partners. Both an MS2-MCP system and an engineered CRISPR-Cas13 system were used to deliver APEX2 to the human telomerase RNA hTR with high specificity. One-minute proximity biotinylation captured candidate binding partners for hTR, including more than a dozen proteins not previously linked to hTR. We validated the interaction between hTR and the N6-methyladenosine (m6A) demethylase ALKBH5 and showed that ALKBH5 is able to erase the m6A modification on endogenous hTR. ALKBH5 also modulates telomerase complex assembly and activity. MS2- and Cas13-targeted APEX2 may facilitate the discovery of novel RNA–protein interactions in living cells.
Fracture Load of Different Zirconia Types: a Mastication Simulation Study.

PURPOSE To assess the effect of yttria mol% concentration and material thickness on the biaxial fracture load (N) of zirconia with and without mastication simulation. MATERIALS AND METHODS Disk-shaped specimens (N = 120) of 3 mol% yttria-partially stabilized zirconia, 3Y-PSZ (Katana High Translucent, Kuraray Noritake), 4 mol% yttria-partially stabilized zirconia, 4Y-PSZ (Katana Super Translucent Multi Layered) and 5 mol% Yttria-partially stabilized zirconia, 5Y-PSZ (Katana Ultra Translucent Multi Layered) were prepared to thicknesses of 0.7 and 1.2 mm. For each thickness, the biaxial fracture load (N) was measured with and without mastication simulation with 1.2 million cycles at a 110-N load and simultaneous thermal cycling at 5°C to 55°C. The data were analyzed by three-way Analysis of Variance (α = 0.05) and Tukey-Kramer adjusted multiple comparison test. RESULTS Yttria mol% concentration and material thickness had a statistically significant effect on the mean biaxial fracture load (F = 388.16, P < 0.001 and F = 714.33, P < 0.001 respectively). The mean biaxial fracture load ranged from the highest to the lowest; 3Y-PSZ, 4Y-PSZ, and 5Y-PSZ (P = 0.012). The mean biaxial fracture load of the 1.2 mm thickness groups was significantly higher than 0.7 mm thickness at any given condition (P = 0.002). Not all specimens survived the mastication simulation protocol. Fifty percent of the 0.7 mm thick 4Y-PSZ specimens, 70% of the 0.7 mm thick 5Y-PSZ specimens and 20% of 1.2 mm thick 5Y-PSZ specimens fractured during mastication simulation. Mastication simulation had no statistically significant effect on the biaxial fracture load (F = 1.24, P = 0.239) of the survived specimens. CONCLUSIONS Lowering yttria mol% concentration and increasing material thickness significantly increases the fracture load of zirconia. At 0.7 mm thickness, only 3Y-PSZ survived masticatory simulation. A minimum material thickness of 1.2 mm is required for 4Y-PSZ or 5Y-PSZ. This article is protected by copyright. All rights reserved.
Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors

Nocturnin (NOCT) is a eukaryotic enzyme that belongs to a superfamily of exoribonucleases, endonucleases, and phosphatases. In this study, we analyze the expression, processing, localization, and cellular functions of human NOCT. We find that NOCT protein is differentially expressed and processed in a cell and tissue type–specific manner to control its localization to the cytoplasm or mitochondrial exterior or interior. The N terminus of NOCT is necessary and sufficient to confer import and processing in the mitochondria. We measured the impact of cytoplasmic NOCT on the transcriptome and observed that it affects mRNA levels of hundreds of genes that are significantly enriched in osteoblast, neuronal, and mitochondrial functions. Recent biochemical data indicate that NOCT dephosphorylates NADP(H) metabolites, and thus we measured the effect of NOCT on these cofactors in cells. We find that NOCT increases NAD(H) and decreases NADP(H) levels in a manner dependent on its intracellular localization. Collectively, our data indicate that NOCT can regulate levels of both mRNAs and NADP(H) cofactors in a manner specified by its location in cells.
A Survey of Mid-Air Ultrasound Haptics and Its Applications

Ultrasound haptics is a contactless haptic technology that enables novel mid-air interactions with rich multisensory feedback. This article surveys recent advances in ultrasound haptic technology. We discuss the fundamentals of this haptic technology, how a variety of perceptible sensations are rendered, and how it is currently being used to enable novel interaction techniques. We summarize its strengths, weaknesses, and potential applications across various domains. We conclude with our perspective on key directions for this promising haptic technology.
Geotechnical/Geophysical Evaluation Of Karst Limestone Sites – A Case History

A collaborative effort between a geotechnical engineer and geophysicist in conducting subsurface evaluations of a karst limestone site is demonstrated with this case history. The example shown here from southwest Missouri, demonstrates how the traditional geotechnical approach to investigating karst limestone sites can be adapted to embrace the use of geophysics. The site was found to contain active sinkholes, which were of potential concern to the engineer. Terrain conductivity, 2-dimensional resistivity imaging, drilling and downhole logging were combined effectively on this fastmoving and resource-limited project on a large acreage site. In the case history presented, the geophysical results were used as a guide by the geotechnical engineer as he made decisions about recommendations for foundation design. The end result was the geophysical information gave the geotechnical engineer and his client what they wanted - greater assurance that they had exercised diligence in their efforts to define site conditions and avoid hazards.