bluuebunny/crossref_metadata_2025 huggingface dataset:
The art and science of developmental and advocacy evaluation
Authors: Taddy‐Sandino Sonia , Saltzman Anna , Spilker Shayla
Published: September 2021

Over the past 15 years, the field of advocacy and policy change (APC) evaluation has evolved considerably in terms of refining the purpose and methods of this type of evaluation. At the same time, the dynamic nature of APC work requires evaluators to draw upon a range of evaluation approaches, including systems thinking, developmental evaluation, and participatory evaluation, among others. Developmental evaluation is particularly well‐suited for an APC context given its focus on documenting complexity and establishing frequent feedback loops. Previous research has highlighted the value of APC and developmental evaluation approaches and the methods that can be used for each one (i.e., the science of these types of evaluations). However, less guidance exists on how evaluators can navigate the dance between APC and developmental evaluation methods and the mindset needed to simultaneously draw upon the strengths of each one (i.e., the art of doing APC and developmental evaluations simultaneously). This chapter fills that gap by exploring the interplay between APC and developmental evaluation through the lens of one case study. In 2017, Engage R+D embarked on an evaluation of an initiative—funded by The California Endowment—to defend and protect the health and well‐being of Californians, particularly immigrants and other vulnerable populations. The chapter includes an overview of this case example; a description of how we applied developmental evaluation principles; considerations for methods, data collection, and analysis; and a description of how we approached utilization of evaluative information. It concludes with considerations for the field.
A learning agenda for the advocacy evaluation field's future
Authors: Coffman Julia , Stachowiak Sarah , Raynor Jared
Published: September 2021

This volume set out to document, illustrate, and critique the progress and innovation that has occurred during the advocacy evaluation field's first phase of development. This final chapter identifies how the context in which advocacy evaluation plays out is shifting. It describes how these shifts impact how advocates, advocacy funders, and advocacy evaluators think about what works, and what has value. Given this context, and lifting up the ideas of other chapter authors, the chapter concludes with a learning agenda for the field's next phase of development—four questions to help guide future field innovation and collective learning.
River reversal of the Parlung River at Songzong Town in the eastern Himalayan Syntaxis, Tibetan Plateau
Authors: Wang Hu , Deng Lin , Li Kaijin
Published: September 2021

Revealing reorganization patterns of major rivers and their drainage basins have great implications for understanding evolution of mountainous landforms. Drainage reversal, as an important river process, has been widely considered to be directly associated with stream capture highlighting river erosion. As such, few study reported any other mechanisms for explaining formation of drainage reversal. However, its mechanism still remains open due to infrequent occurrence or lacking clear field evidence. Here, we first show that glacial damming highlighting river aggradation can also induce river reversal. Based on geomorphic analysis, measurements of terrace cobbles, and dating results, we suggest that two river reversals occurred at Songzong along the Parlung River in the south‐eastern region of the Tibetan Plateau. Specifically, the river reversed eastward due to a glacier damming event prior to ~23.7 ± 2.0 ka BP and then reversed to flow westward at 20.4 ± 2.7 ka BP due to the break of the glacier dam. Moreover, all the reaches upstream of the glacier deposits along the two rivers at Songzong have smaller channel steepness compared with the corresponding segments downstream, indicating that glacier deposits significantly influenced river incision process of the Parlung River. Combined with previous studies, our results may indicate that glaciers might be an important factor to influence river evolution and fluvial landform of the Eastern Himalayan Syntaxis of the Tibetan Plateau.
Tumor necrosis factor receptor‐1 is selectively sequestered into Schwann cell extracellular vesicles where it functions as a TNFα decoy
Authors: Sadri Mahrou , Hirosawa Naoya , Le Jasmine , Romero Haylie , Martellucci Stefano , Kwon Hyo Jun , Pizzo Donald , Ohtori Seiji , Gonias Steven L. , Campana Wendy M.
Published: September 2021

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell–cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor‐1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Although TNFR2 was robustly expressed by SCs in culture, TNFR2 was excluded from SC EVs. SC EV TNFR1 bound TNFα, decreasing the concentration of free TNFα available to bind to cells and thus served as a TNFα decoy. SC EV TNFR1 significantly inhibited TNFα‐induced p38 MAPK phosphorylation in cultured SCs. When TNFR1 was proteolytically removed from SC EVs using tumor necrosis factor‐α converting enzyme (TACE) or neutralized with antibody, the ability of TNFα to activate p38 MAPK in the presence of these EVs was restored. As further evidence of its decoy activity, SC EV TNFR1 modified TNFα activities in vitro including: (1) regulation of expression of other cytokines; (2) effects on SC morphology; and (3) effects on SC viability. SC EVs also modified the effects of TNFα on sciatic nerve morphology and neuropathic pain‐related behavior in vivo. By sequestering TNFR1 in EVs, SCs may buffer against the potentially toxic effects of TNFα. SC EVs provide a novel mechanism for the spatial and temporal regulation of neuro‐inflammation.
Immediate and informative feedback during a pandemic: Using stated preference analysis to predict vaccine uptake rates
Authors: Vásquez William F. , Trudeau Jennifer M. , Alicea‐Planas Jessica
Published: September 2021

In response to an emerging pandemic, there is urgent need for information regarding individual evaluation of risk and preferences toward mitigation strategies such as vaccinations. However, with social distancing policies and financial stress during an outbreak, traditional robust survey methodologies of face‐to‐face, probabilistic sampling, may not be feasible to deploy quickly, especially in developing countries. We recommend a protocol that calls for a sensitive survey design, acceptance of a web‐based approach and adjustments for uncertainty of respondents, to deliver urgently needed information to policymakers as the public health crisis unfolds, rather than in its aftermath. This information is critical to tailor comprehensive vaccination campaigns that reach critical immunity thresholds. We apply our recommendations in a regional study of 16 Latin American countries in the month following index cases of COVID‐19. We use a split‐sample, contingent valuation approach to evaluate the effects of cost, duration of immunity and effectiveness of the vaccine. Our results show that cost and duration of immunity are significant factors in the decision to vaccinate, while the degree of effectiveness is insignificant, unless the vaccine is 100% effective. Income as well as perceived risk and severity of the virus are important determinants also.
HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta
Authors: Sandmann Lisa , Yurdaydin Cihan , Deterding Katja , Heidrich Benjamin , Hardtke Svenja , Lehmann Patrick , Bremer Birgit , Manns Michael P. , Cornberg Markus , Wedemeyer Heiner , Maasoumy Benjamin ,   for the HIDIT‐II Study Group
Published: September 2021

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated‐interferon alfa (peg‐IFNα) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core‐related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN‐based treatment of hepatitis B virus (HBV) mono‐infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co‐infection undergoing peg‐IFNα treatment. The Hep‐Net‐International‐Delta‐Hepatitis‐Intervention Trial‐2 study included 120 patients co‐infected with HBV/HDV. Patients were treated for 96 weeks with peg‐IFNα and either tenofovir or placebo. Ninety‐nine patients with HDV‐RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg‐IFNα in patients with HBV/HDV co‐infection and could be a promising marker to determine treatment futility.
Quantifying the impact of landscape changes on hydrological variables in the alpine and cold region using hydrological model and remote sensing data
Authors: Jin Zizhen , Zhao Qiudong , Qin Xiang , Zhang Jingtian , Zhang Hui , Qin Jia , Qin Yu , Li Hongyuan , Chen Jizu , Liu Yushuo , Li Yanzhao , Wang Lihui
Published: September 2021

Quantifying the impact of landscape on hydrological variables is essential for the sustainable development of water resources. Understanding how landscape changes influence hydrological variables will greatly enhance the understanding of hydrological processes. Important vegetation parameters are considered in this study by using remote sensing data and VIC‐CAS model to analyse the impact of landscape changes on hydrology in upper reaches of the Shule River Basin (URSLB). The results show there are differences in the runoff generation of landscape both in space and time. With increasing altitude, the runoff yields increased, with approximately 79.9% of the total runoff generated in the high mountains (4200–5900 m), and mainly consumed in the mid‐low mountain region. Glacier landscape produced the largest runoff yields (24.9% of the total runoff), followed by low‐coverage grassland (LG; 22.5%), alpine cold desert (AL; 19.6%), mid‐coverage grassland (MG; 15.6%), bare land (12.5%), high‐coverage grassland (HG; 4.5%) and shrubbery (0.4%). The relative capacity of runoff generation by landscapes, from high to low, was the glaciers, AL, LG, HG, MG, shrubbery and bare land. Furthermore, changes in landscapes cause hydrological variables changes, including evapotranspiration, runoff and baseflow. The study revealed that HG, MG, and bare land have a positive impact on evapotranspiration and a negative impact on runoff and baseflow, whereas AL and LG have a positive impact on runoff and baseflow and a negative impact on evapotranspiration. In contrast, glaciers have a positive impact on runoff. After the simulation in four vegetation scenarios, we concluded that the runoff regulation ability of grassland is greater than that of bare land. The grassland landscape is essential since it reduced the flood peak and conserved the soil and water.
Clinical performance of methylation as a biomarker for cervical carcinoma in situ and cancer diagnosis: A worldwide study
Authors: Banila Cristiana , Lorincz Attila T. , Scibior‐Bentkowska Dorota , Clifford Gary M. , Kumbi Birhanu , Beyene Dereje , Wheeler Cosette M. , Cuschieri Kate , Cuzick Jack , Nedjai Belinda
Published: September 2021

The shift towards primary human papillomavirus (HPV)‐based screening has necessitated the search for a secondary triage test that provides sufficient sensitivity to detect high‐grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals. We evaluated the performance of the previously described DNA‐methylation test (S5) in detecting CIN3 and cancers from diverse geographic settings in high‐, medium‐ and low‐income countries, using the cut‐off of 0.80 and exploratory cut‐offs of 2.62 and 3.70. Assays were performed using exfoliated cervical specimens (n = 808) and formalin‐fixed biopsies (n = 166) from women diagnosed with cytology‐negative results (n = 220), CIN3 (n = 204) and cancer stages I (n = 245), II (n = 249), III (n = 28) and IV (n = 22). Methylation increased proportionally with disease severity (Cuzick test for trend, P < .0001). S5 accurately separated women with negative‐histology from CIN3 or cancer (P < .0001). At the 0.80 cut‐off, 543/544 cancers were correctly identified as S5 positive (99.81%). At cut‐off 3.70, S5 showed a sensitivity of 95.77% with improved specificity. The S5 odds ratios of women negative for cervical disease vs CIN3+ were significantly higher than for HPV16/18 genotyping at all cut‐offs (all P < .0001). At S5 cut‐off 0.80, 96.15% of consistently high‐risk human papillomavirus (hrHPV)‐negative cancers (tested with multiple hrHPV‐genotyping assay) were positive by S5. These cancers may have been missed in current primary hrHPV‐screening programmes. The S5 test can accurately detect CIN3 and malignancy irrespective of geographic context and setting. The test can be used as a screening and triage tool. Adjustment of the S5 cut‐off can be performed considering the relative importance given to sensitivity vs specificity.
Oncologic safety of laparoscopic surgery for women with apparent early‐stage uterine serous carcinoma: A multi‐institutional retrospective cohort study
Authors: Xu Yu , Shen Juan , Zhang Qianwen , He Yuedong , Chen Cheng , Tian Yong
Published: September 2021

Objective

To compare the long‐term survival outcomes of patients with apparent early‐stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging.

Methods

A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease‐free survival (DFS) were estimated and compared using the Kaplan‐Meier method and the log‐rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors.

Results

For patients with apparent early‐stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15–2.93, P = 0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99–3.08, P = 0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63–2.12, P = 0.636) and OS (adjusted HR 1.11, 95% CI 0.52–2.38, P = 0.794) in apparent early‐stage USC.

Conclusion

For apparent early‐stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.
Association of vaginal dysbiosis and gestational diabetes mellitus with adverse perinatal outcomes
Authors: Rafat Dalia , Singh Sunita , Nawab Tabassum , Khan Fatima , Khan Asad U. , Khalid Shamsi
Published: September 2021

Objective

Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes and is an independent risk factor for vaginal dysbiosis. Understanding the vaginal microbiota in health and disease is essential to screen, detect, and manage complications of pregnancy. Therefore, the aims of the present study were to assess and compare vaginal dysbiosis in pregnancy in women with and without GDM and examine its impact on perinatal outcomes in our population.

Methods

The present study was a prospective cohort study recruiting pregnant women. The subjects were divided into two groups (GDM and non‐GDM) and were followed until delivery to assess fetomaternal outcomes. Vaginal samples were collected at 24–28 weeks and 34–38 weeks for Nugent scoring and determination of bacterial and fungal species.

Results

The study recruited 502 pregnant women, with a final assessment of 320 mother–infant pairs (GDM n = 134; non‐GDM n = 186). We found a significant association of vaginal dysbiosis with GDM and adverse perinatal outcomes. Significant differences were also seen in status of infection and its trimester‐wise changes in relation to hyperglycemia.

Conclusion

By defining an association of vaginal dysbiosis with GDM and its correlation with perinatal outcomes, the present study calls for exploitation of this potential association as a new target in the prevention and treatment of GDM and in alleviating their undesired maternal and infant outcomes.
Prediction of vaginal birth after cesarean for labor dystocia by sonographic estimated fetal weight
Authors: Levin Gabriel , Tsur Abraham , Tenenbaum Lee , Mor Nizan , Zamir Michal , Meyer Raanan
Published: September 2021

Objective

To estimate the association of the weight difference between the index trial of labor after cesarean (TOLAC) sonographic estimated fetal weight (sEFW) and prior delivery birth weight with TOLAC success rate among women with previous labor dystocia and no prior vaginal delivery.

Methods

A retrospective cohort study including all women with prior cesarean for labor dystocia and no prior vaginal delivery undergoing TOLAC during between March 2011 and June 2020 with a sEFW within 1 week from delivery.

Results

Overall, 168 women were included, of those 107 (63.7%) successfully delivered vaginally. The mean sEFW and mean birth weight were lower in the TOLAC success group (P = 0.010 and P = 0.013, respectively). The rate of higher sEFW in the current delivery compared with the previous delivery did not differ between study groups. The rate of higher TOLAC birth weight was lower in the TOLAC success group (odds ratio 0.30; 95% confidence interval 0.15–0.58). In multivariable regression analysis, maternal age older than 30 years, induction of labor, and higher birth weight were independently negatively associated with TOLAC success (adjusted odds ratio [95% confidence interval]: 0.27 [0.10–0.70], 0.27 [0.08–0.90], and 0.43 [0.19–0.94]; P = 0.008, P = 0.034, and P = 0.035, respectively).

Conclusions

sEFW characteristics did not predict the success or failure of TOLAC among women with prior labor dystocia and no previous vaginal delivery.
Facial structure and perception of sexual orientation: Research with face models based on photographs of real people
Authors: González‐Alvarez Julio , Sos‐Peña Rosa
Published: September 2021

Some evidence suggests that lay persons are able to perceive sexual orientation from face stimuli above the chance level. A morphometric study of 390 heterosexual and homosexual Canadian people of both sexes reported that facial structure differed depending on the sexual orientation. Gay and heterosexual men differed on three metrics as the most robust multivariate predictors, and lesbian and heterosexual women differed on four metrics. A later study verified the perceptual validity of these multivariate predictors using artificial three‐dimensional face models created by manipulating the key parameters. Nevertheless, there is evidence of important processing differences between the perception of real faces and the perception of artificial computer‐generated faces. The present study which composed of two experiments tested the robustness of the previous findings and extended the research by experimentally manipulating the facial features in face models created from photographs of real people. Participants of the Experiment 1 achieved an overall accuracy (0.67) significantly above the chance level (0.50) in a binary hetero/homosexual judgement task, with some important differences between male and female judgements. On the other hand, results of the Experiment 2 showed that participants rated the apparent sexual orientation of series of face models created from natural photographs as a continuous linear function of the multivariate predictors. Theoretical implications are discussed.
Mucin‐producing urothelial‐type adenocarcinoma of the prostate diagnosed after robot‐assisted radical prostatectomy
Authors: Shimizu Kosuke , Inoue Ryo , Tomochika Shinobu , Isoyama Naohito , Yamamoto Yoshiaki , Matsumoto Hiroaki , Shiraishi Koji , Yoshino Shigefumi , Tsuzuki Toyonori , Matsuyama Hideyasu
Published: September 2021

Introduction

Mucin‐producing adenocarcinoma of the prostate is a rare disease that includes prostate adenocarcinoma with mucus production, secondary adenocarcinoma from the bladder or colorectum, and adenocarcinoma from the urothelium of the prostatic urethra. We describe prostate‐specific antigen‐negative mucin‐producing urothelial‐type adenocarcinoma of the prostate.

Case presentation

The patient had urinary retention and a serum prostate‐specific antigen level of 0.74 ng/mL. Computed tomography and magnetic resonance imaging revealed a prostate tumor with a mucous component. We diagnosed adenocarcinoma by prostate biopsy and subsequently performed robot‐assisted radical prostatectomy. Mucin‐producing urothelial‐type adenocarcinoma of the prostate was diagnosed by pathological examinations. Lung metastasis, developing within 3 months after surgery, was treated using chemotherapy.

Conclusion

Endocrine therapy is ineffective for mucin‐producing urothelial‐type adenocarcinoma of the prostate. Mucin‐producing urothelial‐type adenocarcinoma of the prostate diagnosis requires pathological and immunohistochemical analyses. It is important to surgically remove the primary lesion, and robot‐assisted radical prostatectomy may provide an effective approach. Multimodal therapy is essential to treat for mucin‐producing urothelial‐type adenocarcinoma of the prostate.
An efficient multiclass classifier for classification of Alzheimer's disease/mild cognitive impairment/Normal subjects
Authors: Dora Lingraj , Agrawal Sanjay , Panda Rutuparna , Abraham Ajith
Published: September 2021

Typically, in sparse representation‐based classifiers, the weight associated with each training sample is ignored, resulting in reduced accuracy. Moreover, individual binary classifiers solved a multiclass problem. It requires more time as multiple runs are needed to compute the accuracy. In this paper, we propose a novel optimal sparse representation‐based classifier. It solves the ternary classification problem with improved accuracy in a single run. The ternary classification considers Alzheimer's disease versus mild cognitive impairment versus normal control in a single run. A two‐stage sparse representation model is used to design the proposed classifier. To update the weight coefficients, we suggest a regularized Levenberg–Marquardt learning. It allows selecting a subset of significant training samples. To determine the appropriate subset size, we investigate an objective function in terms of classification accuracy. For optimization, we suggest a hybrid particle swarm optimization–squirrel search technique. The experiment conducted on the Alzheimer's Disease Neuroimaging Initiative database shows our method outperforms other state‐of‐the‐art methods in terms of computation time and accuracy. The use of different training–testing partition ratios makes the proposed method immune to biased results, overfitting, and underfitting difficulties. Moreover, results are obtained from 100 iterations to confirm its stability. The suggested model may be helpful for further research in medical image analysis.
Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering
Authors: Sakr Mahmoud A. , Sakthivel Kabilan , Hossain Towsif , Shin Su Ryon , Siddiqua Sumi , Kim Jaehwan , Kim Keekyoung
Published: September 2021

Gelatin methacryloyl (GelMA), a photocrosslinkable gelatin‐based hydrogel, has been immensely used for diverse applications in tissue engineering and drug delivery. Apart from its excellent functionality and versatile mechanical properties, it is also suitable for a wide range of fabrication methodologies to generate tissue constructs of desired shapes and sizes. Despite its exceptional characteristics, it is predominantly limited by its weak mechanical strength, as some tissue types naturally possess high mechanical stiffness. The use of high GelMA concentrations yields high mechanical strength, but not without the compromise in its porosity, degradability, and three‐dimensional (3D) cell attachment. Recently, GelMA has been blended with various natural and synthetic biomaterials to reinforce its physical properties to match with the tissue to be engineered. Among these, nanomaterials have been extensively used to form a composite with GelMA, as they increase its biological and physicochemical properties without affecting the unique characteristics of GelMA and also introduce electrical and magnetic properties. This review article presents the recent advances in the formation of hybrid GelMA nanocomposites using a variety of nanomaterials (carbon, metal, polymer, and mineral‐based). We give an overview of each nanomaterial's characteristics followed by a discussion of the enhancement in GelMA's physical properties after its incorporation. Finally, we also highlight the use of each GelMA nanocomposite for different applications, such as cardiac, bone, and neural regeneration.
Probability of survival and stress distribution of narrow diameter implants with different implant–abutment taper angles
Authors: Freitas Mariana I. M. , Gomes Rafael S. , Ruggiero Mirelle M. , Bergamo Edmara T. P. , Bonfante Estevam A. , Marcello‐Machado Raissa M. , Del Bel Cury Altair A.
Published: September 2021

This study evaluated the probability of survival, failure mode, and stress distribution of narrow diameter implants (NDIs) with internal implant–abutment conical connection comprised of different taper angles and thread designs. Sixty‐three NDIs (Ø 3.5 × 8.5 mm) were divided according to the taper angle (TA), internal diameter (ID), and trapezoidal thread design (TD) (n = 21/group), as follows: (a) 11.5°U (11.5° TA; ID: 2.5 mm; TD: dual threaded); (b) 11.5°S (11.5° TA; ID: 2.5 mm; TD: single threaded); (c) 16°S (16° TA; ID: 2.72 mm; TD: single threaded). They were subjected to step‐stress accelerated life testing. The reliability and use‐level probability Weibull curves were calculated at 50, 100, and 150 N for a mission of 100,000 cycles and the failure mode was analyzed using a scanning electron microscope. For finite element analysis the von‐Mises stress (σvM) was calculated for the abutment and implant. All groups showed high reliability (above 84%) and failures occurred predominantly in the abutment. In the FEA, 11.5°U showed higher σvM for the implant. All NDIs showed high reliability at clinically challenging loads. The system with greater taper angle showed lower σVm in the implant, and dual threaded implants showed a higher stress concentration in the implant and cortical bone.
Free energy of micellization of dodecyl phosphocholine (DPC) from molecular simulation: Hybrid PEACH‐BAR method
Authors: Zhang Xiaokun , Kindt James T.
Published: September 2021

A new method to extract the free energy of aggregation versus aggregate size from molecular simulation data is proposed and applied to a united atom model of the zwitterionic surfactant dodecyl phosphocholine in water. This system's slow dissociation rate and low critical micelle concentration (CMC of approximately 1–2 mM) make extraction of cluster free energies directly from simulation results using the “partition‐enabled analysis of cluster histogram” (PEACH) method impractical. The new approach applies PEACH to a model with weakened attractions between aggregants, which allows sampling of a continuous range of cluster sizes, then recovers the free energy of aggregation under the original fully‐attractive force field using the BAR free energy difference method. PEACH‐BAR results are compared with free energy differences calculated via umbrella sampling, and are used to make predictions of CMC, average cluster size, and SAXS scattering profiles that are in fair agreement with experiment.
Tumor necrosis factor alpha—an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?
Authors: Mirna Moritz , Holnthoner Mario , Topf Albert , Jirak Peter , Fejzic Dzeneta , Paar Vera , Kellermair Jörg , Blessberger Hermann , Reiter Christian , Kammler Jürgen , Motloch Lukas J. , Jung Christian , Kretzschmar Daniel , Franz Marcus , Alushi Brunilda , Lauten Alexander , Hoppe Uta C. , Steinwender Clemens , Lichtenauer Michael
Published: September 2021

Background

Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre‐interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF‐α in TAVR.

Methods

A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post‐intervention, 4, 5, and 7 days post‐intervention, and 1, 3, and 6 months post‐TAVR.

Results

In a univariate Cox proportional hazard analysis, plasma concentrations of TNF‐α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000–1.004), p = 0.028; after 5d: HR 1.003 (1.001–1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut‐offs were calculated. Patients above the cut‐off for TNF‐α after 5d had a significantly worse 12‐month mortality than patients below the cut‐off (18.8% vs. 2.8%, p = 0.046).

Conclusion

Plasma levels of TNF‐α after 24 h and 5 days were independently associated with 12‐month mortality in patients undergoing TAVR. Thus, TNF‐α could represent a novel biomarker for enhanced risk stratification in these patients.
Dysfunction of miR‐802 in tumors
Authors: Gao Tong , Zou Mengsha , Shen Tiancheng , Duan Shiwei
Published: September 2021

Recent studies have shown that miR‐802 is abnormally expressed in many tumors. miR‐802 is expressed at low levels in tissues and cells of gastric cancer, colorectal cancer, breast cancer, cervical cancer, epithelial ovarian cancer, tongue squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, and melanoma. In contrast, miR‐802 is overexpressed in hepatocellular carcinoma, bladder urothelial cancer, osteosarcoma, and cholesteatoma tissue cells. It should be noted that the results of studies on the expression of miR‐802 in pancreatic cancer, prostate cancer, and lung cancer are inconsistent. Current studies have found that miR‐802 can target and regulate genes in different tumors, and affect the regulation of the Wnt signaling pathway, EMT signaling pathway, PI3K/AKT signaling pathway, ERK signaling pathway, and Hedgehog signaling pathway. At the same time, miR‐802 is regulated by the endogenous competition of four ceRNAs, including circDONSON, IGFL2‐AS1, MIR155HG, and MIR4435‐2HG. This article reviews the abnormal expression of miR‐802 in a variety of tumors, expounds the mechanism by which miR‐802 affects tumor progression by regulating different target genes, and elaborates the network of miR‐802‐related ceRNAs. We also summarized the limitations of miR‐802 research and looked forward to the potential application of miR‐802 in the diagnosis and prognosis of tumors.
A case of CADASIL caused by NOTCH3 c.512_605delinsA heterozygous mutation
Authors: Liu Jiahui , Zhang Qiaoyu , Wang Qi , Luan Siyu , Dong Xiang , Cao Hua , Tao Dingbo , Dong Huijie , Ji Xiaofei
Published: September 2021

Background

Autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebrovascular disease closely related to the NOTCH3 gene. More than 200 mutations in this gene have been reported to be associated with this disease.

Methods

The NOTCH3 gene from CADASIL patient was screened for mutations by whole‐exome sequencing (WES). PCR amplification and direct Sanger sequencing were used to verify the suspicious gene mutation sites detected by WES.

Results

We performed second‐generation sequencing on a sample of the patient's genome and found a heterozygous deletion‐insertion mutation c.512_605delinsA in exon 4 of NOTCH3, which resulted in amino acid changes p.G171_A202delinsE. This variation was confirmed by the direct Sanger sequencing. It may be rated as a CADASIL clinical variation.

Conclusion

Discovery of this mutation site provides an important theoretical basis for specific gene‐based diagnosis and treatment of CADASIL.
Impact of the COVID‐19 pandemic on the psychological health of individuals with mental health conditions: A mixed methods study
Authors: Miller Alexia E. , Mehak Adrienne , Trolio Vittoria , Racine Sarah E.
Published: September 2021

Objectives

This study explored how the coronavirus disease 2019 (COVID‐19) pandemic has affected individuals with mental health conditions.

Methods

Participants were 477 adults (82% female) who reported a past‐year mental health condition. They completed an online survey that included an open‐ended question. Mixed methods analysis was conducted.

Results

While all mental health conditions were moderately impacted by the COVID‐19 pandemic, self‐reported impact on anxiety disorder and obsessive‐compulsive disorder symptoms was greater than for all other mental health symptoms. Thematic analysis revealed five themes: (1) the contribution of the pandemic to worsening mental health; (2) life interruptions due to the pandemic; (3) increased loneliness/isolation; (4) upsides of the pandemic; and (5) normalization of the anxieties previously experienced by those with mental health conditions.

Conclusion

Individuals with pre‐existing mental health conditions reported a worsening of symptoms during the COVID‐19 pandemic. Governments and organizations must focus on supporting and increasing access to treatment for this population.
The relative contribution of health cognitions and metacognitions about health anxiety to cyberchondria: A prospective study
Authors: Airoldi Sofia , Kolubinski Daniel C. , Nikčević Ana V. , Spada Marcantonio M.
Published: September 2021

Objectives

Cyberchondria involves the excessive and compulsive use of the Internet to search for health information. The present study investigated the relative contribution of health cognitions and metacognitions about health anxiety to prospective cyberchondria scores, controlling for health anxiety and hours spent online per day.

Methods

A convenience sample of 221 participants was recruited for the purpose of this study with a final sample totaling 125 participants (58.4% females, Mage = 34.51 years) who completed the full survey at baseline (T0) and a measure of cyberchondria after 30 days (T1).

Results

The results of the study showed that metacognition about health anxiety relating to beliefs about the uncontrollability of thoughts was the only significant predictor of prospective cyberchondria scores when controlling for health anxiety.

Conclusions

These results offer further support to the role of beliefs about the uncontrollability of thoughts in cyberchondria. The implications of the findings are discussed.
Treatment components in behavioral versus nondirective telephone‐assisted self‐help interventions for parents of children with externalizing behavior problems
Authors: Treier Anne‐Katrin , Hautmann Christopher , Katzmann Josepha , Nordmann Lisa , Pinior Julia , Scholz Kristin‐Katharina , Döpfner Manfred
Published: September 2021

Background

The aim of this study was to analyze treatment differentiation in a behavioral and a nondirective telephone‐assisted self‐help intervention for parents of children with externalizing behavior problems, including the development and evaluation of a rating scale.

Methods

In a randomized controlled trial, 149 parents of children aged 4–11 years with externalizing behavior problems were allocated to a behavioral or a nondirective guided self‐help intervention. Parents in both conditions received eight self‐help booklets and ten telephone consultations. To analyze the content of the interventions, we developed the Therapist Intervention Scale (TIS). In order to evaluate the scale and analyze treatment differentiation, parent booklets and recorded telephone consultations were rated.

Results

Item selection and scale development were based on predefined psychometric criteria. The subscales Guidance & Structures and Relationship & Emotions were developed based on exploratory factor analyses. Interrater reliability and internal consistency were found to be acceptable to excellent. Analyses of construct validity demonstrated positive correlations for corresponding and negative correlations for non‐corresponding subscales of therapist ratings. Therapists and booklets in the behavioral intervention showed higher scores on the subscale Guidance & Structures, while therapists and booklets in the nondirective intervention showed higher scores on the subscale Relationship & Emotions.

Conclusion

The analyses of the TIS support its reliability and validity. The subscale Guidance & Structures contains mainly cognitive‐behavioral treatment components, while the subscale Relationship & Emotions contains mainly nondirective treatment components. The implemented telephone‐assisted self‐help interventions demonstrated distinct treatment profiles which match their intended therapeutic approaches.
Pediatric Drug Development Studies for Familial Hypercholesterolemia Submitted to the US Food and Drug Administration Between 2007 and 2020
Authors: Park Kyunghun , Vishnevetskaya Kristina , Vaidyanathan Jayabharathi , Burckart Gilbert J. , Green Dionna J.
Published: September 2021

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism that leads to an increased risk of developing atherosclerosis and coronary artery disease. Hypercholesterolemia in pediatric patients is typically due to FH. Treatment of pediatric FH is achieved through lifestyle modifications, lipid‐modifying pharmacotherapy, and/or apheresis. The primary objective of this review is to describe the characteristics of clinical trials conducted in pediatric patients with FH with data submitted to the US Food and Drug Administration from 2007 to 2020. Of 10 trials with 8 products in pediatric FH submitted to the Food and Drug Administration, 1 product was studied in both the heterozygous and the homozygous phenotypes, 5 were studied for heterozygous hypercholesterolemia only, and 2 were studied for homozygous familial hypercholesterolemia only. Most of the trials included pediatric patients ≥10 years of age and older. Clinical trial characteristics including the primary efficacy end points between pediatric and adult trials were mostly identical. Many lipid‐lowering drugs with novel mechanisms of action have been recently approved or are currently being studied. In summary, the drug treatment of hypercholesterolemia in pediatric patients is expanding beyond the use of statins, and now involves multiple mechanisms of action involving cholesterol metabolism. As younger pediatric patients are diagnosed and treated for heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia, optimizing the doses of these agents and safety studies specific to younger pediatric patients will be necessary.
Engineered asparaginase from Erwinia chrysanthemi enhances asparagine hydrolase activity and diminishes enzyme immunoreactivity ‐ a new promise to treat acute lymphoblastic leukemia
Authors: Munhoz Costa Iris , Custódio Moura Débora , Meira Lima Guilherme , Pessoa Adalberto , Oresco dos Santos Camila , de Oliveira Marcos A , Monteiro Gisele
Published: September 2021

BACKGROUND

The treatment of acute lymphoblastic leukemia (ALL) uses the biopharmaceutical l‐asparaginase (ASNase) as the main medication. This drug, from bacterial origin (Escherichia coli or Erwinia chrysanthemi), depletes l‐asparagine (Asn) and secondarily l‐glutamine (Gln – GLNase activity) from the bloodstream, leading leukemic cells to die by deprivation of Asn. The use of ASNase is limited by the high incidence of adverse effects, which collectively can specifically impair quality of life of patients. Its high toxicity caused by the product of the hydrolysis of amino acids and the formation of anti‐ASNase antibodies often required treatment interruption, thus reducing the chances of cure and increasing the rates of disease relapse.

RESULTS

In order to improve enzymatic activity, while reducing toxicity, we developed through directed evolution a double‐mutant ASNase from Erwinia chrysanthemi (Erw_DM), which has specific activity for Asn 46% higher than the wild‐type enzyme (Erw_WT). This makes it possible to reduce the amount of protein necessary for depletion of this amino acid and, consequently, the reduction of GLNase activity, considered toxic. In silico analysis showed that a lower number of epitopes was exposed, resulting in reduced recognition of the recombinant protein by antibody anti‐ASNase observed in vitro assay. Furthermore, we observed the same cytotoxic profile for the MOLT‐4 and REH ALL cell lines using 40% lower protein mass of Erw_DM to achieve the minimum enzyme activity required in the bloodstream during treatment.

CONCLUSION

Altogether, our findings describe a potent and less immunogenic ASNase, an improvement that may alleviate treatment adverse effects developed in anti‐ALL therapy. © 2021 Society of Chemical Industry (SCI).
Differential barcoding of opioid receptors trafficking
Authors: Degrandmaison Jade , Grisé Olivier , Parent Jean‐Luc , Gendron Louis
Published: September 2021

Over the past several years, studies have highlighted the δ‐opioid receptor (DOPr) as a promising therapeutic target for chronic pain management. While exhibiting milder undesired effects than most currently prescribed opioids, its specific agonists elicit effective analgesic responses in numerous animal models of chronic pain, including inflammatory, neuropathic, diabetic, and cancer‐related pain. However, as compared with the extensively studied μ‐opioid receptor, the molecular mechanisms governing its trafficking remain elusive. Recent advances have denoted several significant particularities in the regulation of DOPr intracellular routing, setting it apart from the other members of the opioid receptor family. Although they share high homology, each opioid receptor subtype displays specific amino acid patterns potentially involved in the regulation of its trafficking. These precise motifs or “barcodes” are selectively recognized by regulatory proteins and therefore dictate several aspects of the itinerary of a receptor, including its anterograde transport, internalization, recycling, and degradation. With a specific focus on the regulation of DOPr trafficking, this review will discuss previously reported, as well as potential novel trafficking barcodes within the opioid and nociceptin/orphanin FQ opioid peptide receptors, and their impact in determining distinct interactomes and physiological responses.
Making the case for librarian expertise to support evidence synthesis for the sustainable development goals
Authors: Ghezzi‐Kopel Kate , Ault Jessica , Chimwaza Gracian , Diekmann Florian , Eldermire Erin , Gathoni Nasra , Kelly Julie , Kinengyere Alison Annet , Kocher Megan , Lwoga Edda Tandi , Page Jessica , Young Sarah , Porciello Jaron
Published: September 2021

Evidence syntheses that engage librarians as co‐authors produce higher‐quality results than those that do not. Trained as teachers, researchers, and information managers, librarians possess expert knowledge on research methodologies and information retrieval approaches that are critical for evidence synthesis. Researchers are under increasing pressure to produce evidence syntheses to inform practice and policymaking. Many fields outside of health science and medicine, however, do not have established guidelines, processes, or methodologies. This article describes how librarians led the creation of an interdisciplinary toolkit for researchers new to evidence synthesis. The implementation of the tools, including a protocol, supported eight evidence syntheses focused on effective agricultural interventions published in a special collection in Nature Research in October 2020. This article is a step‐by‐step overview of the tools and process. We advocate that librarian collaboration in evidence synthesis must become the norm, not the exception. Evidence synthesis project leads without access to a qualified librarian may use this toolkit as a point of entry for production of transparent, reproducible reviews.
Green molecularly imprinted polymers for sustainable sample preparation
Authors: Martín‐Esteban Antonio
Published: September 2021

The use of molecularly imprinted polymers in sample preparation as selective sorbent materials has received great attention during the last years leading to analytical methods with unprecedented selectivity. However, with the progressive implementation of Green Analytical Chemistry principles, it is necessary to critically review the greenness of synthesis and further use of molecularly imprinted polymers in sample preparation. Accordingly, in the present review, the different steps and strategies for the preparation of molecularly imprinted polymers, the used reagents, as well as their incorporation to microextraction techniques are reviewed from a green perspective and recent alternatives to make the use of molecularly imprinted polymers more sustainable are provided.
Ultrasound Evaluation for Extremity Deep Vein Thrombus in COVID‐19‐Positive Patients: Exam Positivity Rate and Association With D‐Dimer Level
Authors: Bello Hernan R. , Heilbrun Marta E. , Kallas Omar N. , Thongkham Dean W. , Powell Cindy D. , Moreno Courtney C.
Published: September 2021

Objectives

Determine the rate of positive extremity ultrasound exams for DVT in patients with COVID‐19 and assess for differences in laboratory values in patients with and without DVT, which could be used as a surrogate to decide the need for further evaluation with ultrasound.

Methods

Retrospective case control study with 1:2 matching of cases (COVID‐19+ patients) to controls (COVID‐19− patients) based on age, gender, and race. Laboratory values assessed were serum D‐dimer, fibrinogen, prothrombin time, international normalized ratio, and C‐reactive protein. Demographic variables, comorbidities, and clinical variables including final disposition were also evaluated. P‐values for categorical variables were calculated with the chi‐square test or Fisher's exact test. P‐values for continuous variables were compared with the use of a two‐tailed unpaired t‐test.

Results

The rate of extremity ultrasound exams positive for DVT were similar in patients with (14.7%) and without (19.3%) COVID‐19 (P = .423). No significant difference was observed in laboratory values including the D‐dimer level in COVID‐19 patients without (mean 9523.9 ng/mL (range 339 to >60,000)) or with DVT (mean 13,663.7 ng/mL (range 1193–>60,000)) (P = .475). No differences were found in demographic variabilities or co‐morbidities among COVID‐19 patients with and without extremity DVT.

Conclusions

We found no statistically significant difference in rate of positive DVT studies between COVID‐19+ and COVID‐19− patients. D‐dimer levels are elevated, in some cases markedly, in COVID‐19 patients with and without DVTs and therefore these data do not support their use as a surrogate when assessing the need for ultrasound evaluation.