bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient DNA interrogation of SpCas9 governed by its electrostatic interaction with DNA beyond the PAM and protospacer
Authors: Zhang Qian , Chen Ziting , Wang Fangzhu , Zhang Siqi , Chen Hongyu , Gu Xueying , Wen Fengcai , Jin Jiachuan , Zhang Xia , Huang Xingxu , Shen Bin , Sun Bo 
Published: October 2021

Abstract
Streptococcus pyogenes Cas9 (SpCas9), a programmable RNA-guided DNA endonuclease, has been widely repurposed for biological and medical applications. Critical interactions between SpCas9 and DNA confer the high specificity of the enzyme in genome engineering. Here, we unveil that an essential SpCas9–DNA interaction located beyond the protospacer adjacent motif (PAM) is realized through electrostatic forces between four positively charged lysines among SpCas9 residues 1151–1156 and the negatively charged DNA backbone. Modulating this interaction by substituting lysines with amino acids that have distinct charges revealed a strong dependence of DNA target binding and cleavage activities of SpCas9 on the charge. Moreover, the SpCas9 mutants show markedly distinguishable DNA interaction sites beyond the PAM compared with wild-type SpCas9. Functionally, this interaction governs DNA sampling and participates in protospacer DNA unwinding during DNA interrogation. Overall, a mechanistic and functional understanding of this vital interaction explains how SpCas9 carries out efficient DNA interrogation.
The Racial and Economic Foundations of Municipal Redistricting
Authors: Vargas Robert , Cano Christina , Del Toro Paola , Fenaughty Brian 
Published: October 2021

Abstract
How do local governments resist internal pressure for social change? This study explores this question by examining the role of redistricting. Using digitized ward maps from Chicago, Milwaukee, and St Louis from the 1800s to the present, this study applied mixed methods to systematically explore and understand the movement of districts over time. We discovered that local governments used redistricting for racially and economically motivated social control. Specifically, findings illuminated four practices aimed at regulating or resisting elected officials advocating for racial justice or equity: 1) suppressive redistricting, 2) disciplinary redistricting, 3) remunerative redistricting, and 4) transactional redistricting. These findings advance theories of racialized space and the racialized state by uncovering additional ways that governments regulate or suppress movements for racial equity or justice from within.
Factors Associated with the Development, Progression, and Outcome of Dupuytren Disease Treatment: A Systematic Review
Authors: Geoghegan Luke , Man Julian , Jain Abhilash , Price Andrew , Gibbons Elizabeth , Jerosch-Herold Christina , Sidey-Gibbons Chris , Rodrigues Jeremy N. 
Published: October 2021

Background:
The factors typically considered to be associated with Dupuytren disease have been described, such as those in the “Dupuytren diathesis.” However, the quality of studies describing them has not been appraised. This systematic review aimed to analyze the evidence for all factors investigated for potential association with the development, progression, outcome of treatment, or recurrence of Dupuytren disease.

Methods:
A systematic review of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature databases was conducted using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses–compliant methodology up to September of 2019. Articles were screened in duplicate. Prognostic studies were quality assessed using the Quality in Prognosis Study tool.

Results:
This study identified 2301 records; 51 met full inclusion criteria reporting data related to 54,491 patients with Dupuytren disease. In total, 46 candidate factors associated with the development of Dupuytren disease were identified. There was inconsistent evidence between the association of Dupuytren disease and the presence of “classic” diathesis factors. The quality of included studies varied, and the generalizability of studies was low. There was little evidence describing the factors associated with functional outcome.

Conclusions:
This systematic review challenges conventional notions of diathesis factors. Traditional diathesis factors are associated with disease development and recurrence, although they are not significantly associated with poor outcome following intervention based on the current evidence.
Successful Double DIEP Syngeneic Transplantation across Monozygotic Twins for Total Back Reconstruction
Authors: Selber Jesse C. , Kameni Lionel , Torres Keila , Mericli Alex , Chu Carrie , Schaverien Mark , Largo Rene , Butler Charles , Gaber Osama 
Published: October 2021

Background:
A 56-year-old woman presented with an extensive sarcoma requiring nearly total back resection. She had limited donor sites for reconstruction because of a previous laparotomy, but presented with a significantly larger, identical twin. Cancer has traditionally been considered a contraindication for vascularized composite allotransplantation; however, immunosuppression is potentially avoidable between monozygotic twins.

Methods:
A preoperative genetic workup revealed 10/10 human leukocyte antigen homozygosity. Despite substantial phenotypic divergence in size and facial features, the sisters were genotypically identical. A two-stage, double deep inferior epigastric perforator transplant was planned for delayed reconstruction. At the first stage following the resection, an arteriovenous loop was performed to provide recipient vasculature to the back. At a second stage, the transplantation was performed. In addition, bilateral lumbar artery perforator flaps were created to reduce the length of the defect. Intraoperative steroid bolus and a short taper alone were used for immunosuppression.

Results:
The resection resulted in a 22 × 29-cm specimen down to the spine. After a 4-day interval for permanent pathologic evaluation, the transplant was successfully transferred between twins. Two arteries and six veins were anastomosed to establish perfusion. Postoperatively, there have been no episodes of rejection or flap compromise at last follow-up (>36 months).

Conclusions:
This case represents one of the few vascularized composite allotransplantations between monozygotic twins, and the only reported successful vascularized composite allotransplantation for a recurrent cancer diagnosis. Oncologic safety depended on 100 percent histocompatibility to avoid immunosuppression. Limited patient donor sites precluded total autologous coverage, and a substantial size discrepancy between the twins favored a transplant.
Novel Strategies for Evaluating and Improving Plastic Surgery Applicant Selection
Authors: Graziano Francis D. , Mavrommatis Maria , Shay Paul L. , Ingargiola Michael J. , Sanati-Mehrizy Paymon , Henderson Peter W. , Fang Frank , Taub Peter J. 
Published: October 2021

Summary:
Residency applicant evaluation and selection is a critical part of developing and maintaining a high-quality plastic surgery residency program. Currently, many programs rely on objective measures such as the United States Medical Licensing Exam scores, number of research publications, grade point average, Alpha Omega Alpha Honor Medical Society status, or a combination of these objective metrics. However, there is a growing body of literature suggesting that the current means of residency applicant evaluation and selection may not be the best predictive factors of future resident success. The aim of this study was to identify nontraditional means of evaluating plastic surgery residency candidates and discuss how these means have been implemented at the authors’ institution. After reviewing industry hiring practices, the authors propose that standardized interviewing and personality testing can help evaluate some of the previously intangible parts of an applicant that may play a role in teamwork, commitment, and dedication to patient care.
HIV-1 envelope glycoproteins proteolytic cleavage protects infected cells from ADCC mediated by plasma from infected individuals
Authors: Prévost Jérémie , Medjahed Halima , Vézina Dani , Chen Hung-Ching , Hahn Beatrice H , Smith Amos B. , Finzi Andrés 
Published: October 2021

ABSTRACTThe HIV-1 envelope glycoprotein (Env) is synthesized in the endoplasmic reticulum as a trimeric gp160 precursor, which requires proteolytic cleavage by a cellular furin protease to mediate virus-cell fusion. Env is conformationally flexible, but controls its transition from the unbound “closed” conformation (State 1) to downstream CD4-bound conformations (States 2/3), which are required for fusion. In particular, HIV-1 has evolved several mechanisms that reduce the premature “opening” of Env which exposes highly conserved epitopes recognized by non-neutralizing antibodies (nnAbs) capable of mediating antibody-dependent cellular cytotoxicity (ADCC). Env cleavage decreases its conformational transitions favoring the adoption of the “closed” conformation. Here we altered the gp160 furin cleavage site to impair Env cleavage and to examine its impact on ADCC responses mediated by plasma from HIV-1-infected individuals. We found that infected primary CD4+ T cells expressing uncleaved, but not wildtype, Env are efficiently recognized by nnAbs and become highly susceptible to ADCC responses mediated by plasma from HIV-1-infected individuals. Thus, HIV-1 limits the exposure of uncleaved Env at the surface of HIV-1-infected cells at least in part to escape ADCC responses.
Predictor for local government social media use in Indonesia
Authors: Purbokusumo Yuyun , Santoso Anang Dwi 
Published: October 2021

Purpose
This study aims to test the impact of technological acceptance and trust toward e-government (TTEG), as well as perceived risk (PR) on the attitude toward using (AT) and the actual use (AU) of social media. This study also intends to examine the theoretical extension of the technology acceptance model by adding two variables, namely, TTEG and PR.

Design/methodology/approach
A total of 125 social media officers (SMO) were asked to fill out the questionnaire. To analyze the data, the researcher used the partial least square method using WarpPLS 6.0.

Findings
The findings of this study indicated that perceived ease of use (PEOU) has a positive and significant impact on perceived usefulness (PU). In addition, while PEOU, PU and TTEG influence AT significantly and positively, this research found that PR has no impact on AT. Furthermore, the authors also confirmed the positive and significant influence on AT, TTEG and AU. Meanwhile, PR has a significant and negative effect on AU.

Research limitations/implications
This study first used non-probability sampling and as a consequence, that result could not be generalized. Another limitation is that this study used self-perceptual measures.

Practical implications
The study found that PR and TTEG are essential factors for increasing the use of social media by local government. Therefore, policymakers must create regional regulations to reduce risk and increase the trust of SMO. In addition, this study found that technology acceptance also had an effect on increasing activity on social media. For this reason, training in the use of social media is needed for SMO to increase the quality of content produced and citizen engagement.

Originality/value
Previous research has tried to look at the population’s characteristics, education levels, internet penetration and economic potential. Unfortunately, these studies did not highlight the capabilities of human resources, which in this case were the SMO.
A novel system-level modeling and design approach for high performance single-loop sigma-delta (∑Δ) modulators
Authors: Vamsee Krishna S. , Sudhakara Reddy P. , Chandra Mohan Reddy S. 
Published: October 2021

PurposeThis paper attempted a novel approach for system-level modeling and simulation of sigma-delta modulator for low-frequency CMOS integrated analog to digital interfaces. Comparative analysis of various architectures topologies, circuit implementation techniques are described with analytical procedure for effective selection of topologies for targeted specifications.Design/methodology/approachVirtual instruments are presented in labview environment to analyze the correlation of circuit-level non-ideal effects with key design parameters over sampling ratio, coarse quantizer bits and loop filter order. A fourth-order single-loop sigma-delta modulator is designed and verified in MATLAB simulink environment with careful selection of integrator weights to meet stable desired performance.FindingsThe proposed designed achieved SNDR of 122 dB and 20 bit resolution satisfying high-resolution requirements of low-frequency biomedical signal processing applications. Even though the simulation performed at behavioral level, the results obtained are considered as accurate, by including all non-ideal and non-linear circuit errors in simulation process.Originality/valueVirtual instruments using labview environment used to analyze the correlation of circuit-level non-ideal effects with key design parameters over sampling ratio, coarse quantizer bits and loop filter order for accurate design.
“Pints or half‐pints”: Gender, functional democratization, and the consumption of drink in Ireland
Authors: Connolly John 
Published: October 2021

AbstractThis paper examines the relationship between the gender power balance, changes in the consumption of alcohol and changing social interdependences. The empirical setting is Ireland circa 1900 up to the present. Drawing from the works of Norbert Elias, I explain how a lessening of the power inequality between men and women was more moderate and limited up to the 1960s. The effect of this was that emancipatory changes around drinking were mainly confined to women from specific social cohorts. As the reduction in gender power inequality accelerated post 1960 it initially increased tensions between the genders, reflected in new power struggles over the social spaces in which drinking occurred and in the type of glass one should drink from. Despite the emergence of less unequal power relations, men continued to have a model setting function in relation to alcohol consumption. A central contention of the paper is the need to give greater consideration to the nature of social interdependences for they can generate a lessening of power inequalities for some social cohorts while failing to generate such a dynamic for other similar social groups.
Overall dynamic body acceleration measures activity differently on large versus small aquatic animals
Authors: Martín López Lucía Martina , Aguilar de Soto Natacha , Madsen Peter T. , Johnson Mark 
Published: October 2021

Abstract

Acceleration‐based proxies for activity and energy expenditure are widely used in bio‐logging studies of animal movement and locomotion to explore biomechanical strategies, energetic costs of behaviour, habitat use and the impact of anthropogenic disturbance. The foremost such proxy is overall dynamic body acceleration (ODBA) along with variants VeDBA and PDBA. This technique, which involves summing the magnitude of high‐pass‐filtered acceleration signals (the so‐called dynamic acceleration) over a reference interval, has been applied to animals as diverse as shags, lobsters, humans and whales. The relationship between ODBA and energy use has been tested empirically on animals small enough to house in laboratory facilities and arguments have been offered for why the method should be generally applicable; however, validations on larger animals are scant.

Here, we examine how body size impacts ODBA and its variants under steady locomotion in large aquatic animals, using cetaceans as model species. To do this, we first develop a simplified mathematical model for the acceleration signals that would be measured by a tag on a swimming animal. We then test this model with empirical data gathered using bio‐logging tags on whale species spanning 1.3 m harbour porpoises to 12‐m sperm whales.

We show that the motions measured by ODBA can be fundamentally different in small versus large aquatic animals. Whereas dynamic acceleration in small animals is predominantly due to specific acceleration (i.e. actual accelerative motions generated by muscle action), in larger aquatic animals, body rotations (i.e. cyclical angular displacements associated with swimming) can dominate the measured acceleration.

As body rotations do not necessarily increase in magnitude as swimming speed increases, ODBA may underestimate the relative cost of behaviours or responses to disturbance in large aquatic animals. This does not lessen the value of ODBA for small animals, but it raises a caution against uncritical use on larger animals. For large aquatic animals, activity proxies that specifically remove body rotations using gyroscopes or magnetometers may provide more consistent estimates of energy use although these methods are yet to be validated.
Stringent immigration enforcement and responses of the immigrant‐intensive sector: Evidence from E‐Verify adoption in Arizona
Authors: Luo Tianyuan , Kostandini Genti 
Published: October 2021

AbstractThis article examines the impact of the 2008 Legal Arizona Workers Act on farm wage, production mix, farm capital use, and agricultural innovation using the synthetic control method. The findings indicate that the law significantly reduced farm worker population in Arizona. Farm wage is not affected by the decreased supply of farm labor because farms in Arizona reduced labor‐intensive crop production. The agricultural sector does not increase the use of farm capital and experiences a decrease in profits. Moreover, this study finds no impact on agricultural patents and research funding in Arizona.
Joint modelling and simulation of M‐protein dynamics and progression‐free survival for alternative isatuximab dosing with pomalidomide/dexamethasone
Authors: Thai Hoai‐Thu , Gaudel Nadia , Cerou Marc , Ayral Geraldine , Fau Jean‐Baptiste , Sebastien Bernard , van de Velde Helgi , Semiond Dorothée , Veyrat‐Follet Christine 
Published: October 2021

AimsAddition of isatuximab (Isa) to pomalidomide/dexamethasone (Pd) significantly improved progression‐free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). We aimed to characterize the relationship between serum M‐protein kinetics and PFS in the phase 3 ICARIA‐MM trial (NCT02990338), and to evaluate an alternative dosing regimen of Isa by simulation.MethodsData from the ICARIA‐MM trial comparing Isa 10 mg/kg weekly for 4 weeks then every 2 weeks (QW‐Q2W) in combination with Pd versus Pd in 256 evaluable RRMM patients were used. A joint model of serum M‐protein dynamics and PFS was developed. Trial simulations were then performed to evaluate whether efficacy is maintained after switching to a monthly dosing regimen.ResultsThe model identified instantaneous changes (slope) in serum M‐protein as the best on‐treatment predictor for PFS and baseline patient characteristics impacting serum M‐protein kinetics (albumin and β2‐microglobulin on baseline levels, non‐IgG type on growth rate) and PFS (presence of plasmacytomas). Trial simulations demonstrated that switching to a monthly Isa regimen at 6 months would shorten median PFS by 2.3 weeks and induce 42.3% patients to progress earlier.ConclusionsTrial simulations supported selection of the approved Isa 10 mg/kg QW‐Q2W regimen and showed that switching to a monthly regimen after 6 months may reduce clinical benefit in the overall population. However, patients with good prognostic characteristics and with a stable, very good partial response may switch to a monthly regimen after 6 months without compromising the risk of disease progression. This hypothesis will be tested in a prospective clinical trial.
Transfer of chemicals to a secondary container, from the introduction of new labelling regulation to COVID‐19 lockdown: A retrospective analysis of exposure calls to the Poison Control Centre of Rome, Italy, 2017–2020
Authors: Milella Michele Stanislaw , Grassi Maria Caterina , Gasbarri Alessia , Mezzanotte Valeria , Pugliese Francesco , Vivino Gabriella 
Published: October 2021

AbstractThe transfer of a chemical product from its original container to an unlabelled secondary container by consumers is a potential health hazard that may result in unintentional exposures and intoxications. The aim of this study was to describe the pattern of prevalence of exposures to transferred products in Italy from year 2017, when the new European labelling regulation for chemicals became fully operative, to 2020, year of the coronavirus 19 disease first outbreak. Calls to the Poison Control Centre (PCC) of Policlinico Umberto I Hospital ‐ Sapienza University of Rome were analysed retrospectively for characteristics, clinical presentation and circumstances related to the event. We registered 198 cases of interest. There was a reduction in cases from 2017 (4.9%) to 2019 (2.2%), followed by an increased prevalence in 2020 (4.2%) mainly due to the months “post‐lockdown.” The transferred product was very frequently diluted, and an empty drinking bottle was usually used as secondary container. Exposures were mostly of minor severity, and no deaths occurred. The study highlights the importance of PCCs data in the evaluation of the hazard communication to users through labels and advises for public campaigns to promote safe behaviours during future lockdowns to prevent exposures at a later period.
High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma
Authors: Carreras Joaquim , Kikuti Yara Yukie , Hiraiwa Shinichiro , Miyaoka Masashi , Tomita Sakura , Ikoma Haruka , Ito Atsushi , Kondo Yusuke , Itoh Johbu , Roncador Giovanna , Martinez Antonio , Colomo Lluis , Hamoudi Rifat , Ando Kiyoshi , Nakamura Naoya 
Published: October 2021

AbstractTumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.