Miracle-dz/UniFAR-FTUs huggingface dataset:
EGFR-Targeted Nanobody Functionalized Polymeric Micelles Loaded with mTHPC for Selective Photodynamic Therapy

meta-Tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second-generation photosensitizers, clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, improvements are still required concerning its present formulation (i.e., Foscan, a solution of mTHPC in ethanol/propylene glycol (40:60 w/w)), as mTHPC has the tendency to aggregate in aqueous media, e.g., biological fluids, and it has limited tumor specificity. In the present study, polymeric micelles with three different diameters (17, 24, and 45 nm) based on benzyl-poly(ε-caprolactone)-b-poly(ethylene glycol) (PCLn-PEG; n = 9, 15, or 23) were prepared with mTHPC loadings ranging from 0.5 to 10 wt % using a film-hydration method as advanced nanoformulations for this photosensitizer. To favor the uptake of the micelles by cancer cells that overexpress the epidermal growth factor receptor (EGFR), the micelles were decorated with an EGFR-targeted nanobody (named EGa1) through maleimide-thiol chemistry. The enhanced binding of the EGFR-targeted micelles at 4 °C to EGFR-overexpressing A431 cells, compared to low-EGFR-expressing HeLa cells, confirmed the specificity of the micelles. In addition, an enhanced uptake of mTHPC-loaded micelles by A431 cells was observed when these were decorated with the EGa1 nanobody, compared to nontargeted micelles. Both binding and uptake of targeted micelles were blocked by an excess of free EGa1 nanobody, demonstrating that these processes occur through EGFR. In line with this, mTHPC loaded in EGa1-conjugated PCL23-PEG (EGa1-P23) micelles demonstrated 4 times higher photocytotoxicity on A431 cells, compared to micelles lacking the nanobody. Importantly, EGa1-P23 micelles also showed selective PDT against A431 cells compared to the low-EGFR-expressing HeLa cells. Finally, an in vivo pharmacokinetic study shows that after intravenous injection, mTHPC incorporated in the P23 micelles displayed prolonged blood circulation kinetics, compared to free mTHPC, independently of the presence of EGa1. Thus, these results make these micelles a promising nanomedicine formulation for selective therapy.
A Review on the Development of Tunable Graphene Nanoantennas for Terahertz Optoelectronic and Plasmonic Applications

Exceptional advancement has been made in the development of graphene optical nanoantennas. They are incorporated with optoelectronic devices for plasmonics application and have been an active research area across the globe. The interest in graphene plasmonic devices is driven by the different applications they have empowered, such as ultrafast nanodevices, photodetection, energy harvesting, biosensing, biomedical imaging and high-speed terahertz communications. In this article, the aim is to provide a detailed review of the essential explanation behind graphene nanoantennas experimental proofs for the developments of graphene-based plasmonics antennas, achieving enhanced light–matter interaction by exploiting graphene material conductivity and optical properties. First, the fundamental graphene nanoantennas and their tunable resonant behavior over THz frequencies are summarized. Furthermore, incorporating graphene–metal hybrid antennas with optoelectronic devices can prompt the acknowledgment of multi-platforms for photonics. More interestingly, various technical methods are critically studied for frequency tuning and active modulation of optical characteristics, through in situ modulations by applying an external electric field. Second, the various methods for radiation beam scanning and beam reconfigurability are discussed through reflectarray and leaky-wave graphene antennas. In particular, numerous graphene antenna photodetectors and graphene rectennas for energy harvesting are studied by giving a critical evaluation of antenna performances, enhanced photodetection, energy conversion efficiency and the significant problems that remain to be addressed. Finally, the potential developments in the synthesis of graphene material and technological methods involved in the fabrication of graphene–metal nanoantennas are discussed.
COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission

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Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design. Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20–79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge. Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5–59.8]) than in the placebo phase (80.8 [interquartile range, 65.4–87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001). Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
Community gender systems and a daughter’s risk of female genital mutilation/cutting: Multilevel findings from Egypt

We tested a feminist social-ecological model to understand community influences on daughters’ experience of female genital mutilation/cutting (FGMC) in Egypt, where over 90% of women ages 15–49 are cut. FGMC has potential adverse effects on demographic and health outcomes and has been defined as a human-rights violation. However, an integrated multilevel-level framework is lacking. We theorized that a more favorable community-level gender system, including stronger gender norms opposing FGMC and expanded extra-familial opportunities for women in the village or neighborhood, would be associated with a daughter’s lower risk of FGMC and would strengthen the negative association of a mother’s opposition to FGMC with her daughter’s risk of cutting. Using a national sample of 14,171 mother-daughter dyads from the 2014 Egypt Demographic and Health Survey, we estimated multilevel discrete-time hazard models to test these relationships. Community gender norms opposing FGMC had significant direct, negative associations with the hazard that a daughter was cut, but women’s opportunities outside the family did not. Maternal opposition to FGMC was negatively associated with cutting a daughter, and these associations were stronger where community opposition to FGMC and opportunities for women were greater. Results provided good support for a gender-systems framework of the multilevel influences on FGMC. Integrated, multilevel interventions that address gender norms about FGMC and structural opportunities for women in the community, as well as beliefs about the practice among the mothers of at-risk daughters, may be needed for sustainable declines in the practice.
Central neurogenetic signatures of the visuomotor integration system

Significance Previous research has explored the association between behavioral disorders and dysfunction in corresponding neural networks. For example, autism spectrum disorder, Prader–Willi syndrome, and Dravet syndrome are characterized by behavioral deficits in the visuomotor integration system. To date, few investigations have combined brain connectomic–genetic data to investigate the biological basis of childhood neurodevelopment and clinical syndromes. The present study provides evidence of a link between expression of malfunctioning genes associated with these syndromes (i.e., TBR1, SCN1A, MAGEL2, and CACNB4) and cortical distribution across regions devoted to integrating visual and motor information (i.e., the lateral occipital cortex, OP4, and intraparietal sulcus). We suggest this altered gene expression may underlie brain network dysfunction which, in turn, leads to behavioral deficits. Visuomotor impairments characterize numerous neurological disorders and neurogenetic syndromes, such as autism spectrum disorder (ASD) and Dravet, Fragile X, Prader–Willi, Turner, and Williams syndromes. Despite recent advances in systems neuroscience, the biological basis underlying visuomotor functional impairments associated with these clinical conditions is poorly understood. In this study, we used neuroimaging connectomic approaches to map the visuomotor integration (VMI) system in the human brain and investigated the topology approximation of the VMI network to the Allen Human Brain Atlas, a whole-brain transcriptome-wide atlas of cortical genetic expression. We found the genetic expression of four genes—TBR1, SCN1A, MAGEL2, and CACNB4—to be prominently associated with visuomotor integrators in the human cortex. TBR1 gene transcripts, an ASD gene whose expression is related to neural development of the cortex and the hippocampus, showed a central spatial allocation within the VMI system. Our findings delineate gene expression traits underlying the VMI system in the human cortex, where specific genes, such as TBR1, are likely to play a central role in its neuronal organization, as well as on specific phenotypes of neurogenetic syndromes.
Energy needs in the treatment of uncomplicated severe acute malnutrition: Secondary analysis to optimize delivery of ready‐to‐use therapeutic foods

Abstract Outpatient therapeutic feeding protocols for the treatment of uncomplicated severe acute malnutrition in children were initially based on weight gain data from inpatient settings and expert knowledge of the physiological requirements during recovery. However, weight gain and energy requirements from historic inpatient settings may differ from modern outpatient settings and therefore may not be appropriate to guide current therapeutic feeding protocols. We calculated the weight gain and average estimated total daily energy requirement of children successfully treated for uncomplicated severe acute malnutrition as outpatients in Niger (n = 790). Mean energy provided by six therapeutic feeding protocols was calculated and compared with average estimated energy requirements in the study population. Overall weight gain was 5.5 g·kg−1·day−1 among recovered children. Average energy requirements ranged from 92 to 110 kcal·kg−1·day−1 depending on the estimation approach. Two current therapeutic feeding protocols were found to provide an excess of energy after the first week of treatment in our study population, whereas four research protocols tended to provide less energy than the estimated requirement after the first week of treatment. Alternative feeding protocols have the potential to simplify and lead to important savings for programmes but should be evaluated to show adequacy to meet the energy needs of children under treatment, as well as feasibility and cost efficiency. Our findings rely on theoretical calculations based on several assumptions and should be confirmed in field studies.
Trends and Outcomes with Kidney Failure from Antineoplastic Treatments and Urinary Tract Cancer in France.

BACKGROUND AND OBJECTIVES Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney transplantation access. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used the French Renal Epidemiology and Information Network registry to identify patients with kidney failure related to antineoplastic treatments or urinary tract cancer from 2003 to 2015. We identified 287 and 1157 cases with nephrotoxin- and urinary tract cancer-related kidney failure, respectively. The main study outcomes were death and kidney transplantation. After matching cases to two to ten controls (n=11,678) with other kidney failure causes for age, sex, year of dialysis initiation, and diabetes status, we estimated subdistribution hazard ratios (SHR) of each outcome separately for patients with and without active malignancy. RESULTS The mean age- and sex-adjusted incidence of nephrotoxin-related kidney failure was 0.43 (95% CI, 0.38 to 0.49) per million inhabitants and 1.80 (95% CI, 1.68 to 1.90) for urinary tract cancer-related kidney failure; they increased significantly by 5% and 2% annually, respectively, during 2006-2015. Compared with matched controls, age-, sex-, and comorbidity-adjusted SHRs for mortality in patients with nephrotoxin-related kidney failure were 4.2 (95% CI, 3.2 to 5.5) and 1.4 (95% CI, 1.0 to 2.0) for those with and without active malignancy, respectively; for those with urinary tract cancer, SHRs were 2.0 (95% CI, 1.7 to 2.2) and 1.1 (95% CI, 0.9 to 1.2). The corresponding SHRs for transplant wait-listing were 0.19 (95% CI, 0.11 to 0.32) and 0.62 (95% CI, 0.43 to 0.88) for nephrotoxin-related kidney failure cases and 0.28 (95% CI, 0.21 to 0.37) and 0.47 (95% CI, 0.36 to 0.60) for urinary tract cancer cases. Once on the waiting list, access to transplantation did not differ significantly between cases and controls. CONCLUSIONS Cancer-related kidney failure is slowly but steadily increasing. Mortality does not appear to be increased among patients without active malignancy at dialysis start, but their access to kidney transplant remains limited.
EXAMINING THE RELATIONSHIP BETWEEN THE GENOTYPE AND REDEFINED PHENOTYPE OF DENTAL CARIES

Dental caries is a multifactorial infectious disease and is a major public health problem estimated to affect 60 to 90 percent of school children as well as a vast number of adults. At this time, the best predictor of dental caries for a patient is whether or not they have had caries in the past. We have eight hundred seventy-six whole saliva samples collected from Norwegian patients from one of five primary care dental centers in Rogaland County. The University of Pittsburgh IRB under protocol #12110620 approved these study samples. dmft/DMFT scores were collected at ages 5, 12, 14, 16, 17, and 18 according to World Health Organization (WHO) Protocols. DNA was extracted from whole saliva using Oragene kits and an established protocol. Our objective was to use the dmft/DMFT scores over time to redefine the phenotype of caries and look for patterns of the disease in order to assist in the identification of individuals at risk for caries and aid in the development of new strategies of prevention. We aimed to categorize the patients according to characteristics such as more or less acute increases in their dmft/DMFT scores. We also aimed to compare our newly formed definitions with definitions based on dmft/DMFT cutoffs we have been using in our studies. We generated genotyping data using Taqman chemistry in SNPs involved in processes such as enamel formation and salivary contributions and test for association with caries defined using longitudinal caries experience scores. We compared dmft/DMFT data to diet data and dental erosion scores to determine the role of diet within our population and determine if dental caries and dental erosion scores are associated. Funding for this study came from NIH/NIDCR R01-DE18914 and graduate support from the University of Pittsburgh School of Dental Medicine.
Technology in the Lives of Educators and Early Childhood Programs

Age 8, as a response to increased public interest in and the ever-increasing market of digital media technology for early childhood. Since the statement's release, technology has continued to infiltrate the education sector at increasing rates. Given the dynamic and fast-paced nature of the educational technology sector, there is a need to keep up to date on trends in technology access in early childhood education , as well as to better understand how technology and digital media are being used, differential use based on student and teacher characteristics, and how use is related to support and professional development. As such, the current report provides a follow up to the 2012 report conducted by the Fred Rogers Center, Northwestern University, and NAEYC. This report draws on data from the 2012 cohort of 1,365 early childhood educators and new data from a 2014 cohort of 945 early childhood educators to understand trends and changes to the current early childhood technology environment that have occurred since the release of the NAEYC/Fred Rogers Center position statement. Since 2012, there has been a twofold increase in the percent of early childhood educators who are familiar with the NAEYC/Fred Rogers Center position statement regarding technology use in early childhood education. Whereas only 25 percent of educators knew about the statement six months following its release, now 52 percent of educators report knowing about it. Increased Access but Not Use Compared to educators in 2012, current early childhood educators reported more access to interactive whiteboards (26 percent vs. 22 percent) and tablet computers (55 percent vs. 29 percent). For tablets in particular, access increased across all program types and student income levels. However, there were no differences in the frequency with which educators used these devices. More educators in 2014 reported ever receiving professional development in educational technology compared to educators in 2012 (49 percent vs. 41 percent). However, there were no differences in the frequency with which schools provided such professional development across the two time points. Despite this, educators in 2014 did report higher levels of school support compared to 2012 educators, including financial support, access to hardware and software, and support for finding appropriate digital content. Decreased Attitudes Educators in 2014 had less positive attitudes toward the value of technology in early childhood education compared to 2012 educators. They were more likely to disagree or strongly disagree that technology could improve individualized learning, critical …
Characterizing the Quality of Insight by Interactions: A Case Study

Understanding the quality of insight has become increasingly important with the trend of allowing users to post comments during visual exploration, yet approaches for qualifying insight are rare. This article presents a case study to investigate the possibility of characterizing the quality of insight via the interactions performed. To do this, we devised the interaction of a visualization tool—MediSyn—for insight generation. MediSyn supports five types of interactions: selecting, connecting, elaborating, exploring, and sharing. We evaluated MediSyn with 14 participants by allowing them to freely explore the data and generate insights. We then extracted seven interaction patterns from their interaction logs and correlated the patterns to four aspects of insight quality. The results show the possibility of qualifying insights via interactions. Among other findings, exploration actions can lead to unexpected insights; the drill-down pattern tends to increase the domain values of insights. A qualitative analysis shows that using domain knowledge to guide exploration can positively affect the domain value of derived insights. We discuss the study’s implications, lessons learned, and future research opportunities.
Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation. RESEARCH DESIGN AND METHODS Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured. RESULTS Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 μU/mL; P < 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 μU/mL; P = 0.02) decreased, and plasma glucagon increased (all P < 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P < 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P < 0.001) was observed. CONCLUSIONS Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.