bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Evaluation of the Efficacy of Newer Irrigating Solutions in the Removal of Smear Layer Using SEM
Authors: Podili Srivalli , Prasad Parvataneni Krishna , Raju T. B. V. G. , Nadimpalli Mahendra Varma , Dondapati Gowtam Dev , Sowjanya Thangi
Published: January 2021

Aim: To compare the effect of EDTA, Phytic acid and Peracitic acid on smear layer removal by effective conventional irrigation.

Materials and Methodology: A total of 50 extracted mandibular premolars were selected. The canals were instrumented by rotary system up to F2 ProTaper and irrigated with 3% NaOCL simultaneously, teeth were divided into 4 groups according to the final irrigants: 17% EDTA; 2.25% PERACITIC ACID; 1% Phytic Acid; and saline. The canals were irrigated with 25 guage side vented needles for 5 minutes. Specimens were examined under scanning electron microscopy (SEM). Smear layer removal was evaluated at coronal, middle and apical thirds of the root canal. The data is analyzed using the Kruskal-Wallis and Mann-Whitney U tests.

Results: In this study, the control group that is normal saline (4.05 ± 1.06) showed very less amount of smear layer removal. The highest amount of smear layer removal was seen in the group with phytic acid followed by peracitic acid and sodium hypochlorite groups. The apical third showed significantly more smear layer than the coronal and middle thirds (p<0.05). No significant difference was found between the coronal and middle thirds in all experimental groups (p>0.05).

Conclusion: 1% phytic acid was the most effective in removing the smear layer at each level of the root canal followed by 2.5% peracitic and 17% EDTA.
Co‐purification of nitrate reductase 1 with components of the cytochrome bcc‐aa3 oxidase supercomplex from spores of Streptomyces coelicolor A3(2)
Authors: Falke Dörte , Fischer Marco , Ihling Christian , Hammerschmidt Claudia , Sinz Andrea , Sawers Gary
Published: January 2021

In order to reduce nitrate in vivo, the spore‐specific respiratory nitrate reductase, Nar1, of Streptomyces coelicolor relies on an active cytochrome bcc‐aa3 oxidase supercomplex (bcc‐aa3 supercomplex). This suggests that membrane‐associated Nar1, comprising NarG1, NarH1, and NarI1 subunits, might not act as a classical menaquinol oxidase but could either receive electrons from the bcc‐aa3 supercomplex, or require the supercomplex to stabilize the reductase in the membrane to allow it to function. To address the biochemical basis for this dependence on the bcc‐aa3 supercomplex, we purified two different Strep‐tagged variants of Nar1 and enriched the native enzyme complex from spore extracts using different chromatographic and electrophoretic procedures. Polypeptides associated with the isolated Nar1 complexes were identified using mass spectrometry and included components of the bcc‐aa3 supercomplex, along with an alternative, spore‐specific cytochrome b component, QcrB3. Surprisingly, we also co‐enriched the Nar3 enzyme with Nar1 from the wild‐type strain of S. coelicolor. Two differentially migrating active Nar1 complexes could be identified after clear native polyacrylamide gel electrophoresis; these had masses of approximately 450 and 250 kDa. The distribution of active Nar1 in these complexes was influenced by the presence of cytochrome bd oxidase and by QcrB3; the presence of the latter shifted Nar1 into the larger complex. Together, these data suggest that several respiratory complexes can associate in the spore membrane, including Nar1, Nar3, and the bcc‐aa3 supercomplex. Moreover, these findings provide initial support for the hypothesis that Nar1 and the bcc‐aa3 supercomplex physically associate.
Induction of M2‐Type Macrophage Differentiation for Bone Defect Repair via an Interpenetration Network Hydrogel with a GO‐Based Controlled Release System
Authors: Zou Min , Sun Jiachen , Xiang Zhou
Published: January 2021

Recently, biomaterials with immune‐regulating properties have emerged as crucial new platforms for bone tissue engineering. Inducing macrophages to differentiate into M2 subtype can reduce immune inflammatory response and accelerate tissue repair after implantation. An interpenetration network hydrogel is developed utilizing graphene oxide (GO)‐carboxymethyl chitosan (CMC)/poly(ethylene glycol) diacrylate (PEGDA), in which two bioactive molecules, interleukin‐4 (IL‐4) and bone morphogenetic protein‐2 (BMP‐2), are loaded and released in a controlled manner to induce macrophages to differentiate into M2 type and enhance bone formation. These two factors are initially loaded with GO and then embedded into the CMC/PEGDA hydrogel for sustained release. Results indicate that the hydrogel shows enhanced mechanical stiffness, strength, and stability. The hydrogel loaded with IL‐4 and BMP‐2 significantly promotes both macrophage M2‐type differentiation and bone marrow mesenchymal stem cell osteogenesis differentiation in vitro. Furthermore, in vivo studies show that the implantation of this hydrogel markedly reduces local inflammation while enhancing bone regeneration at 8 weeks post‐implantation. In all, the findings suggest that hydrogel loaded with IL‐4 and BMP‐2 has synergistic effects on bone regeneration. Such an induction and immunomodulation system offers a promising strategy for the development of future bone immune regulation and tissue engineering applications.
Medical student self‐assessment as emergency medicine residency applicants
Authors: Kukulski Paul , Ahn James , Babcock Christine , Cheema Navneet , Clayton Galeta C. , Olson Adriana S. , Olson Nathan , Tekwani Karis L. , Carter Keme
Published: January 2021

Background

Emergency medicine (EM) applicants are encouraged to consider their own “competitiveness” when deciding on the number of applications to submit. Program directors rank the Standardized Letter of Evaluation (SLOE) as the most important factor when reviewing an applicant. Accurate insight into how clinical performance is reflected on the SLOE could improve medical students’ ability to gauge their own competitiveness.

Objective

This study aims to determine the accuracy of students’ self‐assessment by SLOE evaluation measures when compared to the SLOE completed by faculty after their EM clerkship.

Methods

Participants of this multicenter study included fourth‐year medical students who had completed their EM clerkship and were applying to EM residency. Students completed a modified SLOE to reflect rankings they believed they would receive on their official SLOE. Additionally, students completed a survey assessing their knowledge of the SLOE, their perception of feedback during the clerkship, and their self‐perceived competitiveness as an EM applicant. Correlation between the rankings on the student‐completed SLOE and the official SLOE was analyzed using the Kendall correlation.

Results

Of the 49 eligible students, 42 (85.7%) completed the study. The correlation between scores on the student‐completed and official SLOE were significantly low (r < 0.68) for each item. The majority of students agreed that they were satisfied by the quantity and quality of feedback they received (31/42, 73.8%). Few students agreed that they knew how many applications to submit to ensure a match in EM (7/42, 16.7%).

Conclusion

This study demonstrates that students did not accurately predict their rankings on the official SLOE at the end of an EM rotation and had little insight into their competitiveness as an applicant. These findings highlight opportunities to mitigate the burden on students and programs caused by the increasing number of applications per applicant. Further research is needed as to whether strategies to increase insight into competitiveness are effective.
Prognostic impact of thoracic duct lymph node metastasis in esophageal squamous cell carcinoma
Authors: Matsuda Satoru , Kawakubo Hirofumi , Takeuchi Hiroya , Mayanagi Shuhei , Irino Tomoyuki , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Kitagawa Yuko
Published: January 2021

Aim

We have previously reported the existence of lymph nodes surrounding the thoracic duct ( TDLN) and transthoracic esophagectomy (TTE) with thoracic duct (TD) resection increased the number of lymph nodes (LNs) retrieved. The current study aims to evaluate the prognostic impact of TDLN metastasis in esophageal cancer patients subdivided by its location and comparing the patients’ survival with those with extra‐regional LN metastasis.

Methods

Patients who underwent TTE with TD resection for esophageal squamous cell carcinoma (ESCC) were reviewed. Patients were classified into those with or without TDLN metastasis, and clinicopathological factors were compared between groups. TDLN was further divided into TDLN‐Ut/Mt/Lt based on the location in the mediastinum. The relapse‐free survival (RFS) and overall survival (OS) were compared between groups.

Results

Of 232 patients, TDLN metastasis was observed in 17 (7%). RFS and OS were significantly worse in the TDLN metastasis group. TDLN metastasis was shown to be an independent prognostic factor for RFS and OS in the multivariate analysis. The negative prognostic impact of TDLN metastasis was evident in TDLN‐Mt/Lt. The RFS and OS of patients with TDLN metastasis were almost identical to those with positive LN metastasis in extra‐regional LNs.

Conclusion

TDLN metastasis was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be independently classified from the current regional LNs. Given that neoadjuvant therapy has been a standard, we might need to introduce adjuvant therapy when TDLN metastasis is observed.
Thorough overview of ubiquitin C‐terminal hydrolase‐L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury
Authors: Wang Kevin K.W. , Kobeissy Firas H. , Shakkour Zaynab , Tyndall J. Adrian
Published: January 2021

Traumatic brain injury (TBI) is a major cause of mortality and morbidity affecting all ages. It remains to be a diagnostic and therapeutic challenge, in which, to date, there is no Food and Drug Administration‐approved drug for treating patients suffering from TBI. The heterogeneity of the disease and the associated complex pathophysiology make it difficult to assess the level of the trauma and to predict the clinical outcome. Current injury severity assessment relies primarily on the Glasgow Coma Scale score or through neuroimaging, including magnetic resonance imaging and computed tomography scans. Nevertheless, such approaches have certain limitations when it comes to accuracy and cost efficiency, as well as exposing patients to unnecessary radiation. Consequently, extensive research work has been carried out to improve the diagnostic accuracy of TBI, especially in mild injuries, because they are often difficult to diagnose. The need for accurate and objective diagnostic measures led to the discovery of biomarkers significantly associated with TBI. Among the most well‐characterized biomarkers are ubiquitin C‐terminal hydrolase‐L1 and glial fibrillary acidic protein. The current review presents an overview regarding the structure and function of these distinctive protein biomarkers, along with their clinical significance that led to their approval by the US Food and Drug Administration to evaluate mild TBI in patients.
Bioinspired oil‐soluble polymers based on catecholamine chemistry for reduced friction
Authors: He Mingrui , Sun Yulong , Tan Xiaolong , Luo Jing , Zhang Hongyu
Published: January 2021

Reduction of friction and wear contributes significantly to energy saving for mechanical system as considerable energy has been consumed in various forms of friction worldwide. In the present study, two kinds of dopamine‐based oil‐soluble polymers were synthesized by atom transfer radical polymerization (DOPA‐BiBB‐pLMA) and photopolymerization (DOPA‐I2959‐pLMA), and modified onto the Ti6Al4V sheet by the “grafting to” method. The characterizations of nuclear magnetic resonance, Fourier transform infrared spectrum, water contact angle, and X‐ray photoelectron spectroscopy confirmed that the polymers were successfully grafted onto the Ti6Al4V surface. Additionally, a series of tribological tests were performed in oil environment using a universal materials tester under different experimental conditions. It was shown that the coefficient of friction using the Ti6Al4V sheets grafted by the dopamine‐based polymers was reduced by 23.5–46.2% compared with bare Ti6Al4V sheet. Furthermore, the wear depth and wear volume were also greatly decreased with the introduction of the dopamine‐based polymers. DOPA‐I2959‐pLMA showed slightly better lubrication enhancement than that of DOPA‐BiBB‐pLMA, which may be attributed to the relatively higher polymerization degree. In summary, a universal “grafting to” surface modification approach was proposed bioinspired by catecholamine chemistry, which remarkably reduced friction and wear of the tribopairs with the introduction of oil‐soluble polymers.
The preparation of Al2O3 based organic/inorganic composite films and the application in agricultural greenhouse
Authors: Zhang Lu , Chen Junjia , Lai Jinqing , Zhao Yang , Sun Xiaoyan , Xie Dong , Li Yuan
Published: January 2021

The work presented herein focuses on developing the Al2O3 based organic/inorganic multifunctional composite films via an internal addition method in the presence of dripping agent, antifogging agent, light stabilizer and insulation barrier agent. The resulting composite films were systematically characterized using scanning electron microscope, FTIR, differential scanning calorimetry, UV, and tensile testing machine. The morphology changed obviously after introducing the inorganic fillers. In addition, the results indicated that the contact angle of the activated Al2O3–10 film had the best stability and the film with ultrafine Al2O3 possessed the best anti‐dripping performance. The time of the first water drop of the film containing 10 g activated Al2O3 (the activated Al2O3–10) was 7 min and 18 s, and the time of each ten‐drops was less than 120 s. The simulated anti‐aging period of the films with anti‐aging agent was up to 423 days, which is superior to many other reported organic/inorganic composite films and can be applied to those extreme climate areas (such as Xinjiang, China).
Identity interplay: The importance and challenges of consumer research on multiple identities
Authors: Forehand Mark , Reed Americus , Saint Clair Julian K.
Published: January 2021

Although it is well accepted that the self‐concept includes numerous identities, the preponderance of past consumer identity research has explored one identity at a time and this focus has limited new insights into the interplay between identities. We integrate across research streams to propose a Multiple‐Identity Network as a unifying framework to help inform and direct future research on multiple identities. This framework identifies three important areas of opportunity for research on multiple identities: (a) Identity Structure, (b) Identity Management, and (c) Identity Change processes that drive both structure and management.
Saving Water With a Landscape Water Conservation Rebate Program
Authors: Bijoor Neeta S.
Published: January 2021

Key Takeaways

In response to severe drought in the state of California, local, regional, and state water agencies implemented rebate programs to encourage reductions in water use.

The Valley Water Landscape Rebate Program encourages residents and businesses to convert high‐water‐use landscape to approved low‐water‐use landscape, and to retrofit existing irrigation equipment with approved high‐efficiency irrigation equipment.

Significant and ongoing water savings can be achieved by rebate programs for turf removal, weather‐based irrigation controllers, and high‐efficiency sprinkler nozzles.
Building Trust in Your Utility: When Not to Apologize
Authors: Goetz Melanie K.
Published: January 2021

Key Takeaways

When a utility makes a mistake that affects its customers, an apology is warranted from the utility's management, not from its customer service staff.

Customer service representatives should not immediately apologize when a customer issues a complaint if the event facts are unknown or as a response to a given, such as rates.

Knowing when to apologize, and when not to, is important for engendering customer trust in a utility.
Social discounting: The effects of manipulating construal level and distance to socially closer person
Authors: Osiński Jerzy T. , Karbowski Adam , Rusek Jan , Reinholz Anna
Published: January 2021

In temporal discounting, when a smaller and sooner reward is selected over a larger and more delayed reward, the addition of a constant delay to both outcomes results in preference reversals. The present experimental study investigates preference reversals in social discounting, that is, allocating rewards based on social distance. The experiment was carried out on 140 participants asked to make hypothetical choices between a smaller reward for a socially closer person and a larger reward for a more distant person. The results showed that shifting both rewards by a constant and relatively large social distance caused a decrease of the discounting rate but only when concrete thinking about the recipients was not primed by the instructions. Shifting the rewards by a constant and relatively small distance caused steeper discounting, regardless of the type of instructions. Similarities and differences between temporal and social discounting are discussed in the context of these findings.
Olfactory function and viral recovery in COVID‐19
Authors: Mazzoli Marco , Molinari Maria Angela , Tondelli Manuela , Giovannini Giada , Ricceri Riccardo , Ciolli Ludovico , Picchetto Livio , Meletti Stefano
Published: January 2021

Background

Olfactory and taste disorders were reported in up to 30%–80% of COVID‐19 patients. The purpose of our study was to objectively assess smell impairment in COVID‐19 patients and to correlate olfactory function with viral recovery.

Methods

Between 15 and 30 April 2020, hospitalized patients with confirmed SARS‐CoV‐2 infection underwent an objective assessment of olfactory function with the Smell Identification subtest of the Sniffin’ Sticks Test (SI‐SST). Association between viral recovery and SI‐SST performance was evaluated.

Results

51 patients were enrolled (49% males, mean age 66.2 ± 14.6 years). At the time of test administration, 45% were clinically recovered and 39% were virus‐free. Objective hyposmia/anosmia was found in 45% of the patients. Subjective olfactory disorders showed no association with the clinical or viral recovery status of the patients. On the contrary, none of the patients with anosmia and the 5% of hyposmic patients at test had viral recovery. The relative risk for hyposmic patients to be still positive at swab test was 10.323 (95% CI 1.483–71.869, p < .0001). Logistic regression analysis showed an independent and significant correlation between viral clearance and SI‐SST scores (OR = 2.242; 95% CI 1.322–3.802, p < .003). ROC curve analysis confirmed that a SI‐SST > 10.5 predicts viral clearance with 79% sensitivity and 87% specificity (AUC = 0.883).

Conclusion

Hyposmia is part of COVID‐19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery. SI‐SST is an easy and safe instrument, and further large multicentric studies should assess its value to predict infection and recovery.
Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis
Authors: Geng Yichao , Zhang Qiuning , Feng Shuangwu , Li Chengcheng , Wang Lina , Zhao Xueshan , Yang Zhen , Li Zheng , Luo Hongtao , Liu Ruifeng , Lu Bing , Wang Xiaohu
Published: January 2021

Background

A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research.

Methods

We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis.

Results

The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC.

Conclusion

Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.
Supporting capital punishment for rape offenders as a collective retaliation against honour threat
Authors: Uysal Mete Sefa , Üzümçeker Emir , Boyacıoğlu İnci
Published: January 2021

Ambivalent sexism and related issues such as rape myths and gendered social norms serve to maintain structural gender inequalities. Exploring the implications of benevolent and hostile sexism separately in social practice, such as retaliatory acts in honour cultures, is essential for understanding gender‐based violence and inequalities. Although a vast majority of research focused on direct and interpersonal aggressive response or retaliatory acts against the honour threat in honour cultures, little is known about subtler collective social processes in honour‐damaging situations. To address the gap in our understanding of how retaliatory responses are carried out against honour threat in a subtler and collective way, we focused on the rising demands for reinstatement of the death penalty to stop the increased rates of sexual violence in Turkey as a collective retaliatory response against honour‐threat. To test this argument, we conducted a survey study with 450 participants to examine the role of ambivalent sexism, the gendered norms of honour culture, and rape myths in supporting the death penalty for rape offenders in Turkey. The results indicate that ambivalent sexism and honour culture's gendered norms predicted support for capital punishment. Furthermore, hostile sexism moderated the relationship between rape myth acceptance and support for death penalty. We find that individuals who have high hostile sexism and strong rape myth acceptance do not support capital punishment. These findings contribute to our understanding of the social mechanisms related to hostile and benevolent sexism which results in support for the death penalty in Turkey.
Confinement Effect on Heterogeneous Electron Transfer in Aqueous Solutions inside Conducting Nanotubes
Authors: Shermukhamedov Shokirbek A. , Nazmutdinov Renat R. , Bronshtein Michael D. , Probst Michael
Published: January 2021

An Fe3+/2+ redox couple in conducting single wall carbon nanotubes filled with water molecules is investigated in the framework of the electron transfer theory and with classical molecular dynamics simulations. The diameter of the nanotubes ranges from 0.8 nm to 3.5 nm. It can be concluded, qualitatively, that the electron transfer rate significantly increases with decreasing nanotube diameter. This effect is explained basically in terms of the solvent reorganization energy. Other factors that can affect the reaction rate are discussed as well.
Electrochemical Activity of Cytochrome P450 1A2: The Relevance of O2 Control and the Natural Electron Donor
Authors: Silveira Célia M. , Rodrigues Patrícia R. , Ghach Wissam , Pereira Sofia A. , Esteves Francisco , Kranendonk Michel , Etienne Mathieu , Almeida M. Gabriela
Published: January 2021

Invited for this month's cover picture is the Group of Biomarkers and Biosensors – GB2 (https://gb29.webnode.pt) at Universidade NOVA de Lisboa (Portugal) and CiiEM (Portugal). The cover picture shows the electrochemical response of the human monooxygenase enzyme, cytochrome P450 1A2 (CYP1A2), in the presence of its natural electron donor partner, cytochrome P450 oxidoreductase (CPR), highlighting the role of the interaction with the latter in the stabilization of CYP1A2 and attaining the electrochemically driven activity towards O2. The picture also emphasizes the protein entrapment matrix, a biocompatible sol‐gel film, which proved to be crucial for the achievement of interfacial electron transfer. Read the full text of the Article at 10.1002/celc.202001255.
Phase equilibria in the system sulphur dioxide‐water from 25–300°c
Authors: Spall B. C.
Published: January 2021

The liquid‐vapor phase relationships in the system sulphur dioxide‐water have been investigated by the dew and bubble point method. Measurements were made in the pressure range 4 to 250 atm. and the temperature range 25 to 350°C. At the higher temperatures and pressures the mixture in the tube reacted to give sulphuric acid and sulphur and the data in this region are inaccurate.

Below the consolute temperature of 127.5°C. two liquid phases can be formed and the system becomes invariant when a vapor phase is also present. At higher temperatures the phase diagrams are of simple shape, and above the critical point of sulphur dioxide the liquid‐vapor inhomogeneous regions become progressively smaller, eventually disappearing at the critical point of water.
Sex‐gender disparities in nonagenarians with acute coronary syndrome
Authors: Cepas‐Guillen Pedro L. , Echarte‐Morales Julio , Flores‐Umanzor Eduardo , Fernandez‐Valledor Andrea , Caldentey Guillem , Viana‐Tejedor Ana , Martinez Gomez Eduardo , Tundidor‐Sanz Elena , Borrego‐Rodriguez Javier , Vidal Pablo , Llagostera Marc , Quiroga Xavier , Freixa Xavier , Fernández‐Vázquez Felipe , Sabate Manel
Published: January 2021

Background

Acute coronary syndrome (ACS) remains one of the leading causes of mortality for women, increasing with age. There is an unmet need regarding this condition in a fast‐growing and predominantly female population, such as nonagenarians.

Hypothesis

Our aim is to compare sex‐based differences in ACS management and long‐term clinical outcomes between women and men in a cohort of nonagenarians.

Methods

We included consecutive nonagenarian patients with ACS admitted at four academic centers between 2005 and 2018. The study was approved by the Ethics Committee of each center.

Results

A total of 680 nonagenarians were included (59% females). Of them, 373 (55%) patients presented with non‐ST‐segment elevation ACS and 307 (45%) with ST‐segment elevation myocardial infarction (STEMI). Men presented a higher disease burden compared to women. Conversely, women were frailer with higher disability and severe cognitive impairment. In the STEMI group, women were less likely than men to undergo percutaneous coronary intervention (PCI) (60% vs. 45%; p = .01). Overall mortality rates were similar in both groups but PCI survival benefit at 1‐year was greater in women compared to their male counterparts (82% vs. 68%; p = .008), persisting after sensitivity analyses using propensity‐score matching (80% vs. 64%; p = .03).

Conclusion

Sex‐gender disparities have been observed in nonagenarians. Despite receiving less often invasive approaches, women showed better clinical outcomes. Our finding may help increase awareness and reduce the current gender gap in ACS management at any age.
Expenditures among young adults with acute lymphoblastic leukemia by site of care
Authors: Wolfson Julie A. , Bhatia Smita , Ginsberg Jill , Becker Laura K. , Bernstein David , Henk Henry J. , Lyman Gary H. , Nathan Paul C. , Puccetti Diane , Wilkes Jennifer J. , Winestone Lena E. , Kenzik Kelly M.
Published: January 2021

Background

Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute–designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures.

Methods

Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer‐related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log‐link modeled average monthly health‐plan–paid (HPP) expenditures and amount owed by the patient (out‐of‐pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non‐CCC). Incidence rate ratios (IRRs) compared CCC and non‐CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled.

Results

Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non‐CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non‐CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable.

Conclusions

Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long‐term cost savings.

Lay Summary

Health care expenditures in young adults (aged 22‐39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute‐designated Comprehensive Cancer Centers (CCC) than those at non‐CCCs.

The CCC/non‐CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs.

Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care.

Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events.
Isogeometric finite element‐based simulation of the aortic heart valve: Integration of neural network structural material model and structural tensor fiber architecture representations
Authors: Zhang Wenbo , Rossini Giovanni , Kamensky David , Bui‐Thanh Tan , Sacks Michael S.
Published: January 2021

The functional complexity of native and replacement aortic heart valves (AVs) is well known, incorporating such physical phenomenons as time‐varying non‐linear anisotropic soft tissue mechanical behavior, geometric non‐linearity, complex multi‐surface time varying contact, and fluid–structure interactions to name a few. It is thus clear that computational simulations are critical in understanding AV function and for the rational basis for design of their replacements. However, such approaches continued to be limited by ad‐hoc approaches for incorporating tissue fibrous structure, high‐fidelity material models, and valve geometry. To this end, we developed an integrated tri‐leaflet valve pipeline built upon an isogeometric analysis framework. A high‐order structural tensor (HOST)‐based method was developed for efficient storage and mapping the two‐dimensional fiber structural data onto the valvular 3D geometry. We then developed a neural network (NN) material model that learned the responses of a detailed meso‐structural model for exogenously cross‐linked planar soft tissues. The NN material model not only reproduced the full anisotropic mechanical responses but also demonstrated a considerable efficiency improvement, as it was trained over a range of realizable fibrous structures. Results of parametric simulations were then performed, as well as population‐based bicuspid AV fiber structure, that demonstrated the efficiency and robustness of the present approach. In summary, the present approach that integrates HOST and NN material model provides an efficient computational analysis framework with increased physical and functional realism for the simulation of native and replacement tri‐leaflet heart valves.
Vaccine‐related major cutaneous reaction size correlates with cellular‐mediated immune responses after tularaemia immunisation
Authors: Salerno‐Gonçalves Rosangela , Chen Wilbur H , Mulligan Mark J , Frey Sharon E , Stapleton Jack T , Keitel Wendy A , Bailey Jason , Sendra Eli , Hill Heather , Johnson Robert A , Sztein Marcelo B
Published: January 2021

Objectives

Francisella tularensis, the causative agent of tularaemia, is an exceptionally infectious bacterium, potentially fatal for humans if left untreated and with the potential to be developed as a bioweapon. Both natural infection and live‐attenuated vaccine strain (LVS) confer good protection against tularaemia. LVS vaccination is traditionally administered by scarification, and the formation of a cutaneous reaction or take at the vaccination site is recognised as a clinical correlate of protection. Although previous studies have suggested that high antibody titres following vaccination might serve as a useful surrogate marker, the immunological correlates of protection remain unknown.

Methods

We investigated the host T‐cell‐mediated immune (T‐CMI) responses elicited following immunisation with LVS vaccine formulated by the DynPort Vaccine Company (DVC‐LVS) or the United States Army Medical Research Institute of Infectious Diseases (USAMRIID‐LVS). We compared T‐CMI responses prompted by these vaccines and correlated them with take size.

Results

We found that both LVS vaccines elicited similar T‐CMI responses. Interestingly, take size associated with the T cells’ ability to proliferate, secrete IFN‐γ and mobilise degranulation, suggesting that these responses play an essential role in tularaemia protection.

Conclusions

These results renew the appreciation for vaccination through the scarification as a prime route of inoculation to target pathogens driving specific T‐CMI responses and provide further evidence that T‐CMI plays a role in protection from tularaemia.
Neural mechanisms of reward processing in adolescent irritability
Authors: Kryza‐Lacombe Maria , Hernandez Brianna , Owen Cassidy , Reynolds Richard C. , Wakschlag Lauren S. , Dougherty Lea R. , Wiggins Jillian L.
Published: January 2021

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward‐related brain function as a candidate neural mechanism. Adolescents from intervention‐seeking families in the community (N = 52; mean age = 13.80, SD = 1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole‐brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent‐ and youth‐reported Affective Reactivity Index. Irritability was associated with altered reward processing‐related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex‐mediated top‐down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism‐based interventions.
Mud Dauber Nests as Sources of Spiders in Mercury Monitoring Studies
Authors: Hannappel Madeline P. , Chumchal Matthew M. , Drenner Ray W. , Kennedy Jim , Barst Benjamin D. , Castellini J. Margaret
Published: January 2021

Identifying ecosystems where biota may be contaminated with hazardous levels of methylmercury (MeHg) is a challenge. One widely used approach for determining site-specific MeHg contamination is to monitor MeHg contamination in sentinel species. Terrestrial shoreline spiders that consume emergent aquatic insects (e.g., midges and mayflies) have been proposed as sentinels of MeHg contamination of aquatic ecosystems. The purpose of the present study was to determine whether a novel sampling technique, collection of spiders from nests of mud dauber wasps (Sphecidae), would be an efficient method for capturing MeHg-contaminated shoreline spiders for use as sentinels in ecological risk assessments. Mud dauber nests were collected near the Clear Fork of the Trinity River in Fort Worth, Texas (USA) on 3 dates from 4 human-made structures. Nests contained 627 unconsumed spiders from 5 families: Araneidae, Salticidae, Thomisidae, Oxyopidae, and Theridiidae. Methylmercury concentrations ranged from 12.2 to 56.3 ng/g wet weight in Thomisidae and Araenidae, respectively. Methylmercury concentrations of the spiders were generally low relative to risk thresholds for adult birds, but a few families of spiders could pose a risk to nestlings. Although mud dauber nests have been recognized as a source of spiders for biodiversity studies, the present study is the first to demonstrate the potential use of spiders collected from mud dauber nests for ecotoxicology studies. Environ Toxicol Chem 2021;40:1335–1340. © 2021 SETAC
Grassroots reserves rescue a river food web from cascading impacts of overharvest
Authors: Koning Aaron A , McIntyre Peter B
Published: January 2021

Intensive fishing is altering the functioning of aquatic ecosystems worldwide, threatening both biodiversity and food security. No‐fishing reserves have proven effective at restoring food‐web structure and enhancing fisheries in marine ecosystems, but remain virtually untested in freshwater systems. Using experiments inside and outside of community‐created riverine reserves in Thailand, we describe a trophic cascade across six trophic levels, from humans to algal responses to nutrient availability. Protection from fishing profoundly reconfigures fish communities – greatly increasing biodiversity, biomass, and body size – yet mean trophic position was unaffected. Cascade dynamics from fish to algae were observed regardless of protection status, although fishing intensified trophic interactions through strong effects on grazing insect behavior. The marked effectiveness of these small, grassroots reserves offers an important conservation‐planning model for protecting food webs and augmenting fishery yields in biodiverse tropical rivers.
Urban evolution of invasive species
Authors: Borden Jesse B , Flory S Luke
Published: January 2021

Urban areas can drive rapid evolution of species and are hotspots for entry and establishment of invasive species, but it is unclear how urban evolution is impacting the process and risk of invasion by non‐native species. Using a synthesis of current research as a basis, we contend that urban evolution of non‐native species can enhance invader establishment, spread, and ecological impact, which can facilitate invader success under future global change conditions. In addition, we highlight that ecological opportunity in urban areas is a potentially important but unexplored mechanism that could accelerate invader evolution. Urban evolution of invaders is a critical new area of research that could reveal novel pathways and mechanisms in the invasion process, and improve predictions and management of invasive species around the world.
OK, Boomer, MD: The Rights of Aging Physicians and the Health of Our Communities
Authors: Powell Tia
Published: January 2021

How do we balance the rights of aging physicians against the right of the public to competent health care? This version of a classic public health ethics dilemma is here now and likely to increase as the population ages. Peer review has long been the standard mechanism for assessing physician competence, but it is subjective and too easily subverted. New options are needed, both in medicine and throughout the professions, but they are challenging to implement. Physicians have an ethical obligation to protect the health of the public by acknowledging, assessing, and addressing the cognitive effects of aging on medical competence.
Realizing Present and Future Promise of DIY Biology and Medicine through a Trust Architecture
Authors: Rasmussen Lisa M. , Guerrini Christi J. , Kuiken Todd , Nebeker Camille , Pearlman Alex , Ware Sarah B. , Wexler Anna , Zettler Patricia J.
Published: January 2021

The speed and scale of the COVID‐19 pandemic has highlighted the limits of current health systems and the potential promise of non‐establishment research such as “DIY” research. We consider one example of how DIY research is responding to the pandemic, discuss the challenges faced by DIY research more generally, and suggest that a “trust architecture” should be developed now to contribute to successful future DIY efforts.
Multiparametric and multilevel characterization of morphological alterations in patients with transient ischemic attack
Authors: Lv Yating , Wei Wei , Han Xiujie , Song Yulin , Han Yu , Zhou Chengshu , Zhou Dan , Zhang Fuding , Wu Xiaoyan , Liu Jinling , Zhao Lijuan , Zhang Cairong , Wang Ningkai , Wang Jinhui
Published: January 2021

Transient ischemic attack (TIA), an important risk factor for stroke, is associated with widespread disruptions of functional brain architecture. However, TIA‐related structural alterations are not well established. By analyzing structural MRI data from 50 TIA patients versus 40 healthy controls (HCs), here we systematically investigated TIA‐related morphological alterations in multiple cortical surface‐based indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]) at multiple levels (local topography, interregional connectivity and whole‐brain network topology). For the observed alterations, their associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers were further examined. We found that compared with the HCs, the TIA patients showed widespread morphological alterations and the alterations depended on choices of morphological index and analytical level. Specifically, the patients exhibited: (a) regional CT decreases in the transverse temporal gyrus and lateral sulcus; (b) impaired FD‐ and GI‐based connectivity mainly involving visual, somatomotor and ventral attention networks and interhemispheric connections; and (c) altered GI‐based whole‐brain network efficiency and decreased FD‐based nodal centrality in the middle frontal gyrus. Moreover, the impaired morphological connectivity showed high sensitivities and specificities for distinguishing the patients from HCs. Altogether, these findings demonstrate the emergence of morphological index‐dependent and analytical level‐specific alterations in TIA, which provide novel insights into neurobiological mechanisms underlying TIA and may serve as potential biomarkers to help diagnosis of the disease. Meanwhile, our findings highlight the necessity of using multiparametric and multilevel approaches for a complete mapping of cerebral morphology in health and disease.
Mutational Signature Analysis Reveals Widespread Contribution of Pyrrolizidine Alkaloid Exposure to Human Liver Cancer
Authors: He Yisheng , Shi Mai , Wu Xu , Ma Jiang , Ng Kevin Tak‐Pan , Xia Qingsu , Zhu Lin , Fu Peter Pi‐Cheng , Man Kwan , Tsui Stephen Kwok‐Wing , Lin Ge
Published: January 2021

Background and Aims

Mutational signature analyses are an effective tool in identifying cancer etiology. Humans are frequently exposed to pyrrolizidine alkaloids (PAs), the most common carcinogenic phytotoxins widely distributed in herbal remedies and foods. However, due to the lack of human epidemiological data, PAs are classified as group II hepatocarcinogens by the World Health Organization. This study identified a PA mutational signature as the biomarker to investigate the association of PA exposure with human liver cancer.

Approach and Results

Pyrrole‐protein adducts (PPAs), the PA exposure biomarker, were measured and found in 32% of surgically resected specimens from 34 patients with liver cancer in Hong Kong. Next, we delineated the mode of mutagenic and tumorigenic actions of retrorsine, a representative PA, in mice and human hepatocytes (HepaRG). Retrorsine induced DNA adduction, DNA damage, and activation of tumorigenic hepatic progenitor cells, which initiated hepatocarcinogenesis. PA mutational signature, as the unique molecular fingerprint of PA‐induced mutation, was derived from exome mutations in retrorsine‐exposed mice and HepaRG cells. Notably, PA mutational signature was validated in genomes of patients with PPA‐positive liver cancer but not patients with PPA‐negative liver cancer, confirming the specificity of this biomarker in revealing PA‐associated liver cancers. Furthermore, we examined the established PA mutational signature in 1,513 liver cancer genomes and found that PA‐associated liver cancers were potentially prevalent in Asia (Mainland China [48%], Hong Kong [44%], Japan [22%], South Korea [6%], Southeast Asia [25%]) but minor in Western countries (North America [3%] and Europe [5%]).

Conclusions

This study provides a clinical indication of PA‐associated liver cancer. We discovered an unexpectedly extensive implication of PA exposure in patients with liver cancer, laying the scientific basis for precautionary approaches and prevention of PA‐associated human liver cancers.