Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Multicenter comparison using two AI stroke CT perfusion software packages for determining thrombectomy eligibility.

BACKGROUND: Stroke AI platforms assess infarcted core and potentially salvageable tissue (penumbra) to identify patients suitable for mechanical thrombectomy. Few studies have compared outputs of these platforms, and none have been multicenter or considered NIHSS or scanner/protocol differences. Our objective was to compare volume estimates and thrombectomy eligibility from two widely used CT perfusion (CTP) packages, Viz.ai and RAPID.AI, in a large multicenter cohort. METHODS: We analyzed CTP data of acute stroke patients with large vessel occlusion (LVO) from four institutions. Core and penumbra volumes were estimated by each software and DEFUSE-3 thrombectomy eligibility assessed. Results between software packages were compared and categorized by NIHSS score, scanner manufacturer/model, and institution. RESULTS: Primary analysis of 362 cases found statistically significant differences in both software's volume estimations, with subgroup analysis showing these differences were driven by results from a single scanner model, the Canon Aquilion One. Viz.ai provided larger estimates with mean differences of 8cc and 18cc for core and penumbra, respectively (p<0.001). NIHSS subgroup analysis also showed systematically larger Viz.ai volumes (p<0.001). Despite volume differences, a significant difference in thrombectomy eligibility was not found. Additional subgroup analysis showed significant differences in penumbra volume for the Phillips Ingenuity scanner, and thrombectomy eligibility for the Canon Aquilion One scanner at one center (7 % increased eligibility with Viz.ai, p=0.03). CONCLUSIONS: Despite systematic differences in core and penumbra volume estimates between Viz.ai and RAPID.AI, DEFUSE-3 eligibility was not statistically different in primary or NIHSS subgroup analysis. A DEFUSE-3 eligibility difference, however, was seen on one scanner at one institution, suggesting scanner model and local CTP protocols can influence performance and cause discrepancies in thrombectomy eligibility. We thus recommend centers discuss optimal scanning protocols with software vendors and scanner manufacturers to maximize CTP accuracy.

The Impact of Palliative Care Consultation on Aggressive Medical Interventions in End-of-life Among Patients with Metastatic Breast Cancer: Insights from the U.S. National Patient Sample.

BACKGROUND: Advancement in treatment has led to prolonged survival and a rising number of women living with metastatic breast cancer (MBC) in the United States. Due to its high symptom burden, it is recommended that palliative care be integrated into the standard care to help improve quality of life. However, little is known about the use of palliative care among MBC patients in the nation. OBJECTIVES: To determine utilization of palliative care consult (PCC) after metastasis and the influence of PCC on healthcare utilization in the end of life among women living with MBC in the US. METHODS: This retrospective cohort study examined a national electronic health record database to quantify the PCC use after metastasis diagnosis until death and the associations of PCC with Emergency Department (ED), Intensive Care Unit (ICU), and chemotherapies in the end-of-life women (age ≥ 18 years) living with MBC. RESULTS: From a cohort of 2615 deceased MBC patients, 37% received PCC in the last 6 months of life. Patients who had received PCC in the end-of-life were more likely to be hospitalized, admitted to ED and ICU, and receive chemotherapies in the last 60 days before death. However, patients who had received end-of-life PCC had less hospital and ED visits and received less chemotherapies after PCC initiated. CONCLUSION: While PCC can reduce end-of-life aggressive interventions, it was underutilized among patients with MBC in the end-of-life. A myriad of clinical and patient factors may still challenge timely consultation. We urge for future endeavors in developing strategies to remove barriers in the implementation, especially earlier in the disease course, to assure timely PC treatments and reduce discomfort amid aggressive interventions for MBC.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Silk Industry Waste Protein-Derived Sericin Hybrid Nanoflowers for Antibiotics Remediation via Circular Economy.

Hybrid protein-copper nanoflowers have emerged as promising materials with diverse applications in biocatalysis, biosensing, and bioremediation. Sericin, a waste biopolymer from the textile industry, has shown potential for fabricating such nanoflowers. However, the influence of the molecular weight of sericin on nanoflower morphology and peroxidase-like activity remains unexplored. This work focused on the self-assembly of nanoflowers using high- and low-molecular-weight (HMW and LMW) silk sericin combined with copper(II) as an inorganic moiety. The peroxidase-like activity of the resulting nanoflowers was evaluated using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide (H2O2). The findings revealed that high-molecular-weight sericin hybrid nanoflowers (HMW-ShNFs) exhibited significantly higher peroxidase-like activity than low-molecular-weight sericin hybrid nanoflowers (LMW-ShNFs). Furthermore, HMW-ShNFs demonstrated superior reusability and storage stability, thereby enhancing their potential for practical use. This study also explored the application of HMW-ShNF for ciprofloxacin degradation to address the environmental and health hazards posed by this antibiotic in water. The results indicated that HMW-ShNFs facilitated the degradation of ciprofloxacin, achieving a maximum degradation of 33.2 ± 1% at pH 8 and 35 °C after 72 h. Overall, the enhanced peroxidase-like activity and successful application in ciprofloxacin degradation underscore the potential of HMW-ShNFs for a sustainable and ecofriendly remediation process. These findings open avenues for the further exploration and utilization of hybrid nanoflowers in various environmental applications.

Palliative Care and Mental Health among Pancreatic Cancer Patients in the United States: An Examination of Service Utilization and Health Outcomes.

INTRODUCTION: Palliative care (PC) utilization remains low among pancreatic cancer patients. This study explores the association of PC with mental health service and pharmacotherapy utilization among pancreatic cancer patients. METHODS: Retrospective analysis was conducted on a sample of patients in the United States with newly diagnosed pancreatic cancer using Electronic Health Record data from Optum's Integrated Claims-Clinical data set. Subsequent diagnoses of anxiety and depression and PC consultation encounters were determined using ICD-9/10 codes. Adjusted associations of mental health treatments with PC and patient characteristics were quantified using multiple logistic regression. RESULTS: Among newly diagnosed pancreatic cancer patients (n = 4029), those with PC consultations exhibited a higher prevalence of anxiety (33.9% vs. 22.8%) and depression (36.2% vs. 23.2%). Mental health service use and pharmacotherapy varied, with the highest utilization among patients having both anxiety and depression. Treatment pattern was also influenced by age (aOR 1.832 for age <55 vs. 65-70 years). Notably, PC consultations showed no significant effect on the likelihood of documented treatment. DISCUSSION: Our study emphasizes underutilization of PC and MH treatment for pancreatic cancer patients. These findings imply a crucial need for further investigation into palliative care's role in addressing mental health concerns among pancreatic cancer patients.

Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Purpose: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Methods: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. Results: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). Conclusions: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Bioengineering of Cu2O structured macro-biotemplate for the ultra-efficient and selective hand-retrieval of glyphosate from agro-farms.

Glyphosate (Gly) is a massively utilized toxic herbicide exceeding its statutory restrictions, causing adverse environmental and health impacts. Engineered nanomaterials, even though are integral to remediate Gly, their practical use is limited due to time and energy driven purifications, and negative environmental impacts. Here, a 3D wide area (~1.6 ± 0.4 cm2) Cu2O nanoparticle supported biotemplate is designed using fish-scale wastes as a sustainable approach for the ultra-efficient and selective hand-remediation of Gly from real-time samples from agro-farms. While the innate metal binding and reducing ability of collagenous scales aided self-synthesis cum grafting of Cu2O, the selective binding potential of Cu2O to Gly facilitated its hand-retrieval; as assessed using optical characterizations, Fourier transform infrared spectroscopy, thermogravimetric analysis and liquid chromatography mass spectrometry. Optimization studies revealed extractions of diverse pay-loads of Gly between 0.1 µg/mL to 40 µg/mL per 80 mg biotemplate grafted with ~6.354 µg of sub-5 nm Cu2O and was exponential to the number of Cu2O@biotemplates. Even though pH and surfactant didn't have any impact on the adsorption of Gly to the Cu2O@biotemplates, increase in the ionic strength led to a drastic increase in the adsorption. Density function theory simulations unveiled the involvement of phosphonic and carboxylic groups of Gly for interaction with Cu2O with a bond length of 1.826 Å and 1.833 Å, respectively. Overall, our sustainably generated, cost-efficient, hand-retrievable Cu2O supported biotemplate can be generalized to extract diverse organophosphorus toxins from agro-farms and other sewage embodiments. SYNOPSIS: Glyphosate is an excessively applied herbicide with potent health hazards and carcinogenicity. Thus, a hand removable Cu2O-supported biotemplate to selectively and efficiently remediate glyphosate from irrigation water is developed.

MEF2C Hypofunction in GABAergic Cells Alters Sociability and Prefrontal Cortex Inhibitory Synaptic Transmission in a Sex-Dependent Manner.

Background: Heterozygous mutations or deletions of MEF2C cause a neurodevelopmental disorder termed MEF2C haploinsufficiency syndrome (MCHS), characterized by autism spectrum disorder and neurological symptoms. In mice, global Mef2c heterozygosity has produced multiple MCHS-like phenotypes. MEF2C is highly expressed in multiple cell types of the developing brain, including GABAergic (gamma-aminobutyric acidergic) inhibitory neurons, but the influence of MEF2C hypofunction in GABAergic neurons on MCHS-like phenotypes remains unclear. Methods: We employed GABAergic cell type-specific manipulations to study mouse Mef2c heterozygosity in a battery of MCHS-like behaviors. We also performed electroencephalography, single-cell transcriptomics, and patch-clamp electrophysiology and optogenetics to assess the impact of Mef2c haploinsufficiency on gene expression and prefrontal cortex microcircuits. Results: Mef2c heterozygosity in developing GABAergic cells produced female-specific deficits in social preference and altered approach-avoidance behavior. In female, but not male, mice, we observed that Mef2c heterozygosity in developing GABAergic cells produced 1) differentially expressed genes in multiple cell types, including parvalbumin-expressing GABAergic neurons, 2) baseline and social-related frontocortical network activity alterations, and 3) reductions in parvalbumin cell intrinsic excitability and inhibitory synaptic transmission onto deep-layer pyramidal neurons. Conclusions: MEF2C hypofunction in female, but not male, developing GABAergic cells is important for typical sociability and approach-avoidance behaviors and normal parvalbumin inhibitory neuron function in the prefrontal cortex of mice. While there is no apparent sex bias in autism spectrum disorder symptoms of MCHS, our findings suggest that GABAergic cell-specific dysfunction in females with MCHS may contribute disproportionately to sociability symptoms.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

A mathematical model for velocity-selective arterial spin labeling.

PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

Comparative evaluation of pinhole surgical technique with and without A-PRF in the treatment of multiple adjacent recession defects: A clinico radiographic study.

BACKGROUND: To evaluate and compare efficacy of pinhole surgical technique (PST) alone and with advanced platelet rich fibrin (A-PRF) in the management of bilateral multiple adjacent gingival recession defects (MAGRD). METHODS: One hundred and sixty five MAGRD were randomly assigned to control group (treated with PST) and test group (PST with A-PRF). Clinical parameters of gingival recession depth (GRD), gingival recession width (GRW), width of keratinised gingiva (WKG), complete root coverage (CRC) and gingival thickness (GT) on ST-CBCT was measured at 2, 4 and 6 mm apically from the gingival margin. Also, root coverage aesthetic score and patient satisfaction ratings were recorded at baseline, 6 and 12 months postoperatively. RESULTS: Substantial reduction in GRD (Test: 1.29 ± 0.69 mm and Control 0.98 ± 0.30 mm) (p < 0.001) and GRW (Test: 2.03 ± 0.90 mm and control 1.73 ± 0.99 mm) (p < 0.05) with associated gain in WKG and GT was observed (p < 0.001). Mean GT values were increased in both the groups at 2, 4 and 6 mm from the crest. Comparison of Test and Control groups yielded significant reductions in GRD (-0.17 ± 0.56 mm) and WKG (0.73 ± 1.07 mm) favoring the Test group (p < 0.05). Similar increase in GT was observed with better results in Test than control group. (p < 0.001). CONCLUSION: Both groups exhibited sound clinical outcomes with test group offering better resolution of MAGRD in comparison to control group. Also, it enhances clinical and therapeutic end results in terms of attaining reduction in GRD and GRW along with greater gain in KTW and GT. CLINICAL SIGNIFICANCE: PST as a minimally invasive approach has numerous benefits, some of which include the absence of scarring and improved aesthetics linked to faster wound healing. The addition of A-PRF enhances the intended therapy outcomes, which is beneficial for both patients and professionals in the field of periodontics.

Human hnRNPA1 reorganizes telomere-bound Replication Protein A.

Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection. One Sentence Summary: At the single-stranded ends of human telomeres, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) binds to and modulates conformational dynamics of the ssDNA binding protein RPA forming a ternary complex which is controlled by telomeric repeat-containing RNA (TERRA).

Assessment of the Menstrual Problems among Teenage Girls: A Tertiary Care Center Study.

Introduction: Due to shame over discussing menstruation and fear of illness, many adolescent girls with monthly problems never visit their family doctor or gynecologist. The presentation can be delayed as a result. The current study's goal was to assess the sociodemographic characteristics of adolescent females experiencing menstruation issues and the nature of those problems, and how they were handled. Materials and Methods: The problems faced by the adolescent girls attending the Department of Obstetrics and Gynecology were analyzed retrospectively, and all their study characteristics and conditions were evaluated. The descriptive demographics are only represented in the current study. Results: Two hundred-two teenage girls with menstruation issues visited our hospital overall. 64% of them were late adolescents, 96% lived in cities, 89 were unmarried, and 50% belonged to the middle class socioeconomically. Amenorrhea, dysmenorrhea, and irregular menstrual periods affected 86 (61%) people, 38 (27%) people, and 17 (12%) people, respectively. Patients were treated with appropriate counseling and medicinal and/or surgical care. Conclusion: Most of the teenage girls in our study had anemia. Therefore, it is essential to educate people on the importance of nutrition, different menstrual disorders, normal physiology, and the prevention and management of anemia. Adolescent-friendly health care has been attempted and partially developed in India's governmental and private systems. As a result, counseling and management of adolescent menstrual difficulties must be offered in the current health and medical care systems.

Unveiling Spatial Associations between COVID-19 Severe Health Index, Racial/Ethnic Composition, and Community Factors in the United States.

There are limited efforts to incorporate different predisposing factors into prediction models that account for population racial/ethnic composition in exploring the burden of high COVID-19 Severe Health Risk Index (COVID-19 SHRI) scores. This index quantifies the risk of severe COVID-19 symptoms among a county's population depending on the presence of some chronic conditions. These conditions, as identified by the Centers for Disease Control and Prevention (CDC), include Chronic Obstructive Pulmonary Disease (COPD), heart disease, high blood pressure, diabetes, and obesity. Therefore, the objectives of this study were (1) to investigate potential population risk factors preceding the COVID-19 pandemic that are associated with the COVID-19 SHRI utilizing non-spatial regression models and (2) to evaluate the performance of spatial regression models in comparison to non-spatial regression models. The study used county-level data for 3107 United States counties, utilizing publicly available datasets. Analyses were carried out by constructing spatial and non-spatial regression models. Majority White and majority Hispanic counties showed lower COVID-19 SHRI scores when compared to majority Black counties. Counties with an older population, low income, high smoking, high reported insufficient sleep, and a high percentage of preventable hospitalizations had higher COVID-19 SHRI scores. Counties with better health access and internet coverage had lower COVID-19 SHRI scores. This study helped to identify the county-level characteristics of risk populations to help guide resource allocation efforts. Also, the study showed that the spatial regression models outperformed the non-spatial regression models. Racial/ethnic inequalities were associated with disparities in the burden of high COVID-19 SHRI scores. Therefore, addressing these factors is essential to decrease inequalities in health outcomes. This work provides the baseline typology to further explore many social, health, economic, and political factors that contribute to different health outcomes.

An Integrative Review of Response Rates in Nursing Research Utilizing Online Surveys.

BACKGROUND: Online surveys in nursing research have both advantages and disadvantages. Reaching a sample and attaining an appropriate response rate is an ongoing challenge and necessitates careful consideration when designing a nursing research study using an online survey approach. OBJECTIVE: In this study, we aimed to explore response rates and survey characteristics of studies by nurse researchers that used online methodologies to survey nurses, nursing students, and nursing faculty. METHODS: We conducted an integrative review of research studies that used online surveys for data collection published from 2011 to 2021. We examined response rates and survey characteristics such as recruitment method, use of incentives, question type, length of survey, time to complete the survey, and use of reminders. RESULTS: Our review included 51 studies published by nurses with target samples of nurses, nursing students, or nursing faculty. Study sample sizes ranged from 48 to 29,283, the number of respondents ranged from 29 to 3,607, and the response rates ranged from 3.4% to 98%, with an average of 42.46%. Few patterns emerged regarding recruitment or other factors to enhance response rates; only five studies used incentives. CONCLUSION: Response rates to online surveys are unlikely to reach the rates seen in older mailed surveys. Researchers need to design online survey studies to be easily accessible, concise, and appealing to participants.

Trends in Reasons for Human Papillomavirus Vaccine Hesitancy: 2010-2020.

OBJECTIVES: We sought to identify trends in the main reasons United States parents of unvaccinated children gave for not intending to vaccinate their adolescent children against HPV from 2010 to 2020. As interventions designed to increase vaccine uptake have been implemented across the United States, we predicted that reasons for hesitancy have changed over this period. METHODS: We analyzed data from the 2010 to 2020 National Immunization Survey-Teen, which included 119 695 adolescents aged 13 to 17 years. Joinpoint regression estimated yearly changes in the top five cited reasons for not intending to vaccinate using annual percentage changes. RESULTS: The five most frequently cited reasons for not intending to vaccinate included "not necessary," "safety concerns," "lack of recommendation," "lack of knowledge," and "not sexually active." Overall, parental HPV vaccine hesitancy decreased by 5.5% annually between 2010 and 2012 and then remained stable for the 9-year period of 2012 through 2020. The proportion of parents citing "safety or side effects" as a reason for vaccine hesitancy increased significantly by 15.6% annually from 2010 to 2018. The proportion of parents citing "not recommended," "lack of knowledge," or "child not sexually active" as reasons for vaccine hesitancy decreased significantly by 6.8%, 9.9%, and 5.9% respectively per year between 2013 and 2020. No significant changes were observed for parents citing "not necessary." CONCLUSIONS: Parents who cited vaccine safety as a reason for not intending to vaccinate their adolescent children against HPV increased over time. Findings support efforts to address parental safety concerns surrounding HPV vaccination.

Therapeutic disruption of RAD52-ssDNA complexation via novel drug-like inhibitors.

RAD52 protein is a coveted target for anticancer drug discovery. Similar to poly-ADP-ribose polymerase (PARP) inhibitors, pharmacological inhibition of RAD52 is synthetically lethal with defects in genome caretakers BRCA1 and BRCA2 (∼25% of breast and ovarian cancers). Emerging structure activity relationships for RAD52 are complex, making it challenging to transform previously identified disruptors of the RAD52-ssDNA interaction into drug-like leads using traditional medicinal chemistry approaches. Using pharmacophoric informatics on the RAD52 complexation by epigallocatechin (EGC), and the Enamine in silico REAL database, we identified six distinct chemical scaffolds that occupy the same physical space on RAD52 as EGC. All six were RAD52 inhibitors (IC50 ∼23-1200 µM) with two of the compounds (Z56 and Z99) selectively killing BRCA-mutant cells and inhibiting cellular activities of RAD52 at micromolar inhibitor concentrations. While Z56 had no effect on the ssDNA-binding protein RPA and was toxic to BRCA-mutant cells only, Z99 inhibited both proteins and displayed toxicity towards BRCA-complemented cells. Optimization of the Z99 scaffold resulted in a set of more powerful and selective inhibitors (IC50 ∼1.3-8 µM), which were only toxic to BRCA-mutant cells. RAD52 complexation by Z56, Z99 and its more specific derivatives provide a roadmap for next generation of cancer therapeutics.

Silver nanoparticles green synthesized with leaf extract of disease-resistant amaranthus genotypes effectively suppress leaf blight (Rhizoctonia solani Kühn) disease in a susceptible red amaranthus cultivar.

Silver nanoparticles (AgNPs) were green synthesized using leaf extract of the leaf blight disease (Rhizoctonia solani) susceptible red amaranthus (Amaranthus tricolor L.) and the disease-resistant green (A. dubius) and the wild amaranthus (A. viridis) genotypes, physically characterized, and assessed for their anti-fungal effects against R. solani. The green synthesized nanostructures showed an absorption maximum typical of silver nanoparticles in spectroscopy, and face-centered cubic structures in X-ray diffraction. Field Emission Scanning Electron Microscopic analysis and High-Resolution Transmission Electron Microscopy revealed the size range to be 35-45 nm for all the samples. In vitro mycelial growth inhibition of the pathogen occurred with 500 and 750 ppm concentrations of the nanoparticles in a poisoned-food assay. Further, detached leaves of red amaranthus variety were sprayed with the nanoparticles, and then challenged with the pathogen. There was significant difference in lesion development on leaves sprayed with Ad-AgNPs and Av-AgNPs compared to those treated with At-AgNPs. In the in vivo assay, challenging with the pathogen after spraying the foliage of the leaf blight susceptible red amaranthus variety with Ad-AgNPs at 750 ppm concentration recorded the lowest disease index (7.40) followed by that received Av-AgNPs spray at the same concentration (17.69), five days after inoculation. At-AgNPs treated plants had a disease index of 49.38. Our findings suggest that application of AgNPs green synthesized with leaf extract of disease-resistant genotypes of amaranthus effectively suppressed leaf blight disease incidence in a susceptible amaranthus genotype. To our knowledge, this is the first report on the improved plant pathogen-suppressive activity of any metal nanoparticle when biogenically synthesized using extracts from a disease-resistant plant genotype.