bluuebunny/crossref_metadata_2025 huggingface dataset:
Charge-neutral nonlocal response in superconductor-InAs nanowire hybrid devices
Authors: Denisov A O , Bubis A V , Piatrusha S U , Titova N A , Nasibulin A G , Becker J , Treu J , Ruhstorfer D , Koblmüller G , Tikhonov E S , Khrapai V S
Published: July 2021

Nonlocal quasiparticle transport in normal-superconductor-normal (NSN) hybrid structures probes sub-gap states in the proximity region and is especially attractive in the context of Majorana research. Conductance measurement provides only partial information about nonlocal response composed from both electron-like and hole-like quasiparticle excitations. In this work, we show how a nonlocal shot noise measurement delivers a missing puzzle piece in NSN InAs nanowire-based devices. We demonstrate that in a trivial superconducting phase quasiparticle response is practically charge-neutral, dominated by the heat transport component with a thermal conductance being on the order of conductance quantum. This is qualitatively explained by numerous Andreev reflections of a diffusing quasiparticle, that makes its charge completely uncertain. Consistently, strong fluctuations and sign reversal are observed in the sub-gap nonlocal conductance, including occasional Andreev rectification signals. Our results prove conductance and noise as complementary measurements to characterize quasiparticle transport in superconducting proximity devices.
Broad photoluminescence in ternary Ag-In-S and quaternary Ag-In-Zn-S nanoparticles: the role of Zn incorporation
Authors: Liu Xiangming , Peng Xiaoshi , Xu Tao , Li Yulong , Wei Huiyue , Guan Zanyang , Wang Feng
Published: July 2021

Ternary Ag-In-S and quaternary Ag-In-Zn-S nanoparticles with different ratio of Ag/In/Zn/S are synthesized. The incorporation of Zn into Ag-In-S nanoparticles leads to the increase in the optical bandgap and the blue shift of photoluminescence (PL). The optical properties of these nanoparticles are significantly dependent on the chemical composition of nanoparticles. Time-resolved PL spectroscopy in nanosecond time regime is used to study the recombination processes of carriers, which involve the surface states and intrinsic crystallographic defects. These measurements support the donor-acceptor model, in which the PL is achieved by radiative recombination of the localized electron and hole.
p53 induces a survival transcriptional response after nucleolar stress
Authors: Liao Han , Gaur Anushri , Mauvais Claire , Denicourt Catherine
Published: July 2021

Inhibition of ribosome biogenesis induces nucleolar stress characterized by p53-dependent cell cycle arrest. Here we find that during nucleolar stress p53 activates a transcriptional program involved in promoting cell cycle arrest, autophagy, metabolic remodeling, and clearance of reactive oxygen species.
Reduced Clostridioides difficile infections in hospitalised older people through multiple quality improvement strategies
Authors: Dohrendorf Carla Maria , Unkel Steffen , Scheithauer Simone , Kaase Martin , Meier Volker , Fenz Diana , Sasse Jürgen , Wappler Manfred , Schweer-Herzig Jutta , Friede Tim , Reichard Utz , Eiffert Helmut , Nau Roland , Seele Jana
Published: July 2021

Objectives

To reduce infections with Clostridioides difficile (CDI) in geriatric patients by interventions easily implementable in standard clinical care.

Methods

Prevalence and incidence of CDI between January 2015 and February 2020 were analysed (n = 25,311 patients). Pre-intervention status was assessed from April 2016 to March 2017 (n = 4,922). Between May 2017 and August 2019, a monocentric interventional crossover study (n = 4,655) was conducted including standard care and three interventions: (A) sporicidal cleaning of hospital wards, (B) probiotics and (C) improvement in personal hygiene for CDI patients. This was followed by a multicentric comparison of the interventional bundle (A + B + C) between September 2019 and February 2020 (n = 2,593) with the pre-intervention phase. In 98 CDI cases and matched controls individual risk factors for the development of CDI were compared.

Results

Time series analyses of CDI cases revealed a reduction in the prevalence of CDI in all three participating centres prior to the multicentric intervention phase. In the monocentric phase, no effect of individual interventions on CDI prevalence was identified. However, an aggregated analysis of CDI cases comparing the pre-intervention and the multicentric phase revealed a significant reduction in CDI prevalence. Risk factors for the development of CDI included use of antibiotics, anticoagulants, previous stay in long-term care facilities, prior hospital admissions, cardiac and renal failure, malnutrition and anaemia.

Conclusions

The observed reduction in CDI may be attributed to heightened awareness of the study objectives and specific staff training. Individual interventions did not appear to reduce CDI prevalence. A further randomised trial would be necessary to confirm whether the bundle of interventions is truly effective.
UCSCXenaShiny: an R/CRAN package for interactive analysis of UCSC Xena data
Authors: Wang Shixiang , Xiong Yi , Zhao Longfei , Gu Kai , Li Yin , Zhao Fei , Li Jianfeng , Wang Mingjie , Wang Haitao , Tao Ziyu , Wu Tao , Zheng Yichao , Li Xuejun , Liu Xue-Song
Published: July 2021

UCSC Xena platform provides huge amounts of processed cancer omics data from large cancer research projects (e.g. TCGA, CCLE and PCAWG) or individual research groups and enables unprecedented research opportunities. However, a graphical user interface-based tool for interactively analyzing UCSC Xena data and generating elegant plots is still lacking, especially for cancer researchers and clinicians with limited programming experience. Here, we present UCSCXenaShiny, an R Shiny package for quickly searching, downloading, exploring, analyzing and visualizing data from UCSC Xena data hubs. This tool could effectively promote the practical use of public data, and can serve as an important complement to the current Xena genomics explorer.

Availability and implementation

UCSCXenaShiny is an open source R package under GPLv3 license and it is freely available at https://github.com/openbiox/UCSCXenaShiny or https://cran.r-project.org/package=UCSCXenaShiny. The docker image is available at https://hub.docker.com/r/shixiangwang/ucscxenashiny.

Supplementary information

Supplementary data are available at Bioinformatics online.
Relation between preoperative aerobic fitness estimated by steep ramp test performance and postoperative morbidity in colorectal cancer surgery: prospective observational study
Authors: Cuijpers A. C. M. , Heldens A. F. J. M. , Bours M. J. L. , van Meeteren N. L. U. , Stassen L. P. S. , Lubbers T. , Bongers B. C.
Published: July 2021

Steep ramp test (SRT) performance provides an estimation of preoperative aerobic fitness that is associated with postoperative outcomes. Patients with a better SRT-estimated aerobic fitness are less likely to develop postoperative complications and more likely to experience a shorter time to recovery. The SRT might be a useful and clinically accessible tool in preoperative risk assessment to identify patients at risk of postoperative morbidity and who might benefit from preoperative exercise interventions.
Esophagectomy versus definitive chemoradiotherapy as initial treatment for clinical stage I esophageal cancer: a systematic review and meta-analysis
Authors: Mei Li-Xiang , Mo Jun-Xian , Chen Yong , Dai Lei , Wang Yong-Yong , Chen Ming-Wu
Published: July 2021

Background

Esophagectomy and definitive chemoradiotherapy are commonly used in the treatment of stage I esophageal cancer (EC). The present study aims to compare the efficacy and safety of esophagectomy and definitive chemoradiotherapy as the initial treatment for clinical stage I EC.

Methods

This study was registered with the International Prospective Register of Systematic Reviews (CRD42020197203). Relevant studies were identified through PubMed, Web of Science, EMBASE, and Cochrane Library from database inception to June 30, 2020. Hazard ratio (HR) with 95% confidence intervals (CI) was employed to compare overall survival (OS) and progression-free survival (PFS). Odds ratio (OR) with 95% CI was employed to compare treatment-related death, complications, and tumor recurrence.

Results

A total of 13 non-randomized controlled studies involving 3,346 patients were included. Compared with definitive chemoradiotherapy, esophagectomy showed an improved OS (HR 0.69, 95% CI 0.55–0.86; P < 0.001), PFS (HR 0.47, 95% CI 0.33–0.67; P < 0.001), and a lower risk of tumor recurrence (OR 0.43, 95% CI 0.30–0.61; P < 0.001). There was no significant difference in the incidence of complications (OR 1.11, 95% CI 0.75–1.65; P = 0.60) and treatment-related death (OR 1.15, 95% CI 0.31–4.30; P = 0.84) between the two treatments.

Conclusions

Current evidence shows esophagectomy has superior survival benefits as the initial treatment for clinical stage I EC. It is still the preferred choice for patients with clinical stage I EC. However, future high-quality randomized controlled trials are needed to validate this conclusion.
1. Introduction
Authors: Lowe N V , Douglas G
Published: July 2021

This introductory chapter begins with a discussion of the nature and scope of family law, covering the meaning of ‘family’ and the functions of family law. It then describes trends in family law; the family justice system; and the internationalisation of family law.
3. Determining the Validity of a Marriage or Civil Partnership
Authors: Lowe N V , Douglas G
Published: July 2021

This chapter discusses the law and procedures for determining the validity of a marriage or civil partnership. It covers declaration as to marital status; decree of nullity; grounds on which a marriage will be void; voidable marriages; effect of decree on voidable marriage; and establishing the validity of a civil partnership.
9. The Legal Position of Children
Authors: Lowe N V , Douglas G
Published: July 2021

This chapter discusses the legal position of children. It first considers the relatively simple issues of who the law regards as a child and the meaning of ‘child of the family’. It then discusses the child's legal status; the changing nature of the parent-child relationship; and the still developing notion of the child's independent or autonomy rights.
19. Adoption and Special Guardianship
Authors: Lowe N V , Douglas G
Published: July 2021

This chapter discusses the law on adoption. It covers the nature of adoption and background to the legislation; comparison of adoption with other legal relationships and orders; adoption and human rights; the changing pattern of adoption; responsibility for placing children for adoption; general principles when reaching decisions about adoption; adoption service under the Adoption and Children Act 2002; placement for adoption; the procedure for the making of adoption orders; contact considerations; registration of adoption and the adoption contact register; the effects of an adoption order; transfer of parentage; offences; and special guardianship.
20. The High Court’s Inherent Powers in Respect of Children
Authors: Lowe N V , Douglas G
Published: July 2021

This chapter discusses the High Court's inherent powers in respect of children. The development of these powers, principally under the aegis of the wardship jurisdiction, was highly influential in the modern development of law and practice concerning children, and the Children Act 1989 incorporates many of its features. The chapter covers the High Court's exercise of inherent jurisdiction; the court's powers; local authority use of the jurisdiction; and private law use of the jurisdiction.
26. International Aspects of Child Law
Authors: Lowe N V , Douglas G
Published: July 2021

This chapter begins by discussing the revised Brussels II Regulation, which has become the preeminent instrument within the EU and provides the basic rules of jurisdiction for hearing cases concerning children. It then examines the international aspects of adoption and, in that context, the 1993 Hague Convention on Intercountry Adoption. Next, it turns to the most developed area of international child law, namely international parental child abduction, and in respect of which a number of international instruments come into play. Finally, it discusses the international protection of children as governed by the 1996 Hague Convention on the Protection of Children which the UK ratified in 2012.
Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ+) Communities and the Coronavirus Disease 2019 Pandemic: A Call to Break the Cycle of Structural Barriers
Authors: Gil Raul Macias , Freeman Tracey L , Mathew Trini , Kullar Ravina , Fekete Thomas , Ovalle Anais , Nguyen Don , Kottkamp Angélica , Poon Jin , Marcelin Jasmine R , Swartz Talia H
Published: July 2021

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities. Many disparities mirror those of the human immunodeficiency virus (HIV)/AIDS epidemic. These health inequities have repeated throughout history due to the structural oppression of LGBTQ+ people. We aim to demonstrate that the familiar patterns of LGBTQ+ health disparities reflect a perpetuating, deeply rooted cycle of injustice imposed on LGBTQ+ people. Here, we contextualize COVID-19 inequities through the history of the HIV/AIDS crisis, describe manifestations of LGBTQ+ structural oppression exacerbated by the pandemic, and provide recommendations for medical professionals and institutions seeking to reduce health inequities.
Introduction
Authors: Wesselhoeft Kirsten , Moodie Deonnie
Published: July 2021

Although studies on the entwining of religious and economic forms in the discipline of religious studies have typically centered on Euro-American contexts, this roundtable offers multiple points of departure for analyzing religion and economy in four national contexts outside the West. Debates about the relationships between morality, sacred histories, market governance, and financial cultures have different terms and stakes outside of Western concentrations of capital. The ideologies of freedom and personal autonomy that underpin neoliberalism are inflected quite differently in contexts and intellectual traditions with both colonial and socialist histories. This is true not only for trenchant critics of neoliberalism but also for those actors who provocatively assert freedom through the market. By de-centering the West as the starting point for understanding neoliberal capitalism, we are better able to see the ways that colonial and imperial power is experienced across the globe and how it bears out in diverse neoliberal cultural formations.
Unified Multifactorial Model of Parental Factors in Community-Based Pediatric Chronic Pain
Authors: Brown Donnamay T , Claus Benedikt B , Könning Anna , Wager Julia
Published: July 2021

Objective

The combination of parental chronic pain and internalizing characteristics are relevant to chronic pain experiences in their children. A promising unified multifactorial intergenerational model of chronic pain was published in 2019; however, this model was only generalizable to children with severe chronic pain and some factors had limitations. This study aimed to determine validity of an adapted multifactorial model, including parent and child chronic pain status, pain characteristics, pain-related functioning, and internalizing symptoms, in a community setting. Subgroup analyses based on presence of chronic pain in parents and children were explored to determine whether effects were stronger in certain subsamples.

Methods

Adolescents (N = 1,450, Mage=12.7 years, 50% female), and their parents (82% mothers), were recruited from five schools to complete online surveys. Structural equation modeling was used to investigate interrelated pain-related experiences between parents and their offspring.

Results

The adapted unified multifactorial model had good model fit in the community sample. Significant weak associations were found between all parent and child factors. The strongest associations were found in the subsample of parents and children with chronic pain. In all subgroups, internalizing factors were the most strongly linked intergenerational constructs.

Conclusions

Our results support the validity of the unified multifactorial model of parental factors in pediatric chronic pain, although associations were weaker in the community sample than those previously reported in a clinical sample. In children who develop chronic pain, it is important to consider their parent’s chronic pain and internalizing symptoms to best manage intergenerational effects.
Identification of a gene responsible for seedpod spine formation and other phenotypic alterations using whole-genome sequencing analysis in Medicago truncatula
Authors: Zhao Zhili , Chai Maofeng , Sun Liang , Cong Lili , Jiang Qingzheng , Zhang Zhifei , Wang Zeng-Yu
Published: July 2021

In nature, some plant species produce seedpods with spines, which is an adaptive biological trait for protecting the seed and helping seed dispersal. However, the molecular mechanism of spine formation is still unclear. While conducting routine tissue culture and transformation in the model legume Medicago truncatula, we identified a smooth seedpod (ssp1) mutant with a suite of other phenotypic changes. Preliminary analysis showed that the mutation was derived from the tissue culture process. Genetic segregation analysis suggested that ssp1 is a recessive mutant. By combining whole-genome sequencing and bioinformatics analysis, we found that the mutant phenotype was caused by a single nucleotide polymorphism and a 30 bp deletion in the gene locus Medtr4g039430, named SSP1. Complementation of the M. truncatula ssp1 and Arabidopsis twd1 mutants showed complete restoration, indicating that SSP1 is an ortholog of Arabidopsis TWD1 which encodes an immunophilin-like FK506-binding protein 42. The formation of spines on seedpods is associated with auxin transport. The method used in this study offers an effective way for detecting genes responsible for somaclonal variations. The results demonstrate, for the first time, that SSP1 plays a crucial role in the determination of spine formation on seedpods.
Visuomotor Synchronization: Military Normative Performance
Authors: Maruta Jun , Spielman Lisa A , Ghajar Jamshid
Published: July 2021

Introduction

Cognitive processes such as perception and reasoning are preceded and dependent on attention. Because of the close overlap between neural circuits of attention and eye movement, attention may be objectively quantified with recording of eye movements during an attention-dependent task. Our previous work demonstrated that performance scores on a circular visual tracking task that requires dynamic synchronization of the gaze with the target motion can be impacted by concussion, sleep deprivation, and attention deficit/hyperactivity disorder. The current study examined the characteristics of performance on a standardized predictive visual tracking task in a large sample from a U.S. Military population to provide military normative data.

Materials and Methods

The sample consisted of 1,594 active duty military service members of either sex aged 18-29 years old who were stationed at Fort Hood Army Base. The protocol was reviewed and approved by the U.S. Army Medical Research and Materiel Command Institutional Review Board. Demographic, medical, and military history data were collected using questionnaires, and performance-based data were collected using a circular visual tracking test and Trail Making Test. Differences in visual tracking performance by demographic characteristics were examined with a multivariate analysis of variance, as well as a Kolmogorov-Smirnov test and a rank-sum test. Associations with other measures were examined with a rank-sum test or Spearman correlations.

Results

Robust sex differences in visual tracking performance were found across the various statistical models, as well as age differences in several isolated comparisons. Accordingly, norms of performance scores, described in terms of percentile standings, were developed adjusting for age and sex. The effects of other measures on visual tracking performance were small or statistically non-significant. An examination of the score distributions of various metrics suggested that strategies preferred by men and women may optimize different aspects of visual tracking performance.

Conclusion

This large-scale quantification of attention, using dynamic visuomotor synchronization performance, provides rigorously characterized age- and sex-based military population norms. This study establishes analytics for assessing normal and impaired attention and detecting changes within individuals over time. Practical applications for combat readiness and surveillance of attention impairment from sleep insufficiency, concussion, medication, or attention disorders will be enhanced with portable, easily accessible, fast, and reliable dynamic eye-tracking technologies.
Simulations of globular clusters within their parent galaxies: Metallicity spreads and anomalous precursor populations
Authors: McKenzie Madeleine , Bekki Kenji
Published: July 2021

Recent observations of globular clusters (GCs) suggest that elemental abundance variations may exist between first-generation (1G) stars. We propose that metal abundance (‘metallicity’) spreads within GC forming giant molecular clouds (GMCs) can influence the iron abundances of future cluster members. To investigate this, we use original hydrodynamical simulations to model GMC formation in a high redshift dwarf galaxy. Our simulations self-consistently model physical processes such as stellar feedback, dust formation and destruction, and molecular gas formation on dust grains, making them well suited to the study of GMC formation. We conclude that iron abundance variations in GMCs are due to the merging of gas clumps and self-enrichment processes. The metallicity dispersions of GC forming clumps is ∼0.1 dex, reflecting a growing number of studies that claim a non-zero dispersion within GCs. The galactic gas fraction is a key parameter for the formation of clumps and the metallicity ‘floor’ observed for both Galactic and extragalactic GCs are associated with the parent galaxy’s capacity to form massive GMCs. Finally, we argue that GMCs have the potential to trap surrounding metal-poor galactic disc stars, which we interpret as a precursor population (0G). These low metallicity stars are representative of the [Fe/H] value of the host dwarf and thus the chemistry of this 0G may be a fossilized record of the parent galaxy. These results depend on the initial metallicity and radial gradient of the galaxy, the threshold gas density for star formation, and the star formation prescription.
Dust grain growth at high redshift: starburst-driven CMB-dark supershells
Authors: Martínez-González Sergio , Silich Sergiy , Tenorio-Tagle Guillermo
Published: July 2021

We present a novel scenario for the growth of dust grains in galaxies at high redshift (z ∼ 6). In our model, the mechanical feedback from massive star clusters evolving within high-density pre-enriched media allows to pile up a large amount of matter into massive supershells. If the gas metallicity (≥Z⊙), number density (≥106 cm−3), and dust-to-gas mass ratio (∼1/150 × Z) within the supershell are sufficiently large, such supershells may become optically thick to the starlight emerging from their host star clusters and even to radiation from the cosmic microwave background (CMB). Based on semi-analytic models, we argue that this mechanism, occurring in the case of massive (${\ge} 10^7\, {\rm M}_{\odot }$) molecular clouds hosting ${\ge} 10^6\, {\rm M}_{\odot }$ star clusters, allows a large mass of gas and dust to acquire a temperature below that of the CMB, whereupon dust grain growth may occur with ease. In galaxies with total stellar mass M*, grain growth within supershells may increase the dust mass by ${\sim} 10^6\, {\rm M}_{\odot } (M_{*}/10^{8}\, {\rm M}_{\odot })$.
A HARPS-N mass for the elusive Kepler-37d: a case study in disentangling stellar activity and planetary signals
Authors: Rajpaul V M , Buchhave L A , Lacedelli G , Rice K , Mortier A , Malavolta L , Aigrain S , Borsato L , Mayo A W , Charbonneau D , Damasso M , Dumusque X , Ghedina A , Latham D W , López-Morales M , Magazzù A , Micela G , Molinari E , Pepe F , Piotto G , Poretti E , Rowther S , Sozzetti A , Udry S , Watson C A
Published: July 2021

To date, only 18 exoplanets with radial velocity (RV) semi-amplitude <2 m s−1 have had their masses directly constrained. The biggest obstacle to RV detection of such exoplanets is variability intrinsic to stars themselves, e.g. nuisance signals arising from surface magnetic activity such as rotating spots and plages, which can drown out or even mimic planetary RV signals. We use Kepler-37 – known to host three transiting planets, one of which, Kepler-37d, should be on the cusp of RV detectability with modern spectrographs – as a case study in disentangling planetary and stellar activity signals. We show how two different statistical techniques – one seeking to identify activity signals in stellar spectra, and another to model activity signals in extracted RVs and activity indicators – can each enable a detection of the hitherto elusive Kepler-37d. Moreover, we show that these two approaches can be complementary, and in combination, facilitate a definitive detection and precise characterization of Kepler-37d. Its RV semi-amplitude of 1.22 ± 0.31 m s−1 (mass 5.4 ± 1.4 M⊕) is formally consistent with TOI-178b’s $1.05^{+0.25}_{-0.30}$ m s−1, the latter being the smallest detected RV signal of any transiting planet to date, though dynamical simulations suggest Kepler-37d’s mass may be on the lower end of our 1σ credible interval. Its consequent density is consistent with either a water-world or that of a gaseous envelope ($\sim 0.4{{\ \rm per\ cent}}$ by mass) surrounding a rocky core. Based on RV modelling and a re-analysis of Kepler-37 TTVs, we also suggest that the putative (non-transiting) planet Kepler-37e should be stripped of its ‘confirmed’ status.
The H i intensity mapping bispectrum including observational effects
Authors: Cunnington Steven , Watkinson Catherine , Pourtsidou Alkistis
Published: July 2021

The bispectrum is a three-point statistic with the potential to provide additional information beyond power spectra analyses of survey data sets. Radio telescopes that broadly survey the 21-cm emission from neutral hydrogen (H i) are a promising way to probe LSS and in this work we present an investigation into the H i intensity mapping (IM) bispectrum using simulations. We present a model of the redshift space H i IM bispectrum including observational effects from the radio telescope beam and 21-cm foreground contamination. We validate our modelling prescriptions with measurements from robust IM simulations, inclusive of these observational effects. Our foreground simulations include polarization leakage, on which we use a principal component analysis cleaning method. We also investigate the effects from a non-Gaussian beam including side-lobes. For a MeerKAT-like single-dish IM survey at z = 0.39, we find that foreground removal causes an $8{{\ \rm per\ cent}}$ reduction in the equilateral bispectrum’s signal-to-noise ratio, whereas the beam reduces it by $62{{\ \rm per\ cent}}$. We find our models perform well, generally providing $\chi ^2_\text{dof}\sim 1$, indicating a good fit to the data. Whilst our focus is on post-reionization, single-dish IM, our modelling of observational effects, especially foreground removal, can also be relevant to interferometers and reionization studies.
A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum
Authors: Shang Xiaomin , Shen Shijun , Tang Jianxia , He Xiaoqin , Zhao Yuemeng , Wang Changhong , He Xiaohui , Guo Gangqiang , Liu Meng , Wang Liping , Zhu Qianshu , Yang Guang , Jiang Cizhong , Zhang Meihua , Yu Xinyu , Han Jiping , Culleton Richard , Jiang Lubin , Cao Jun , Gu Liang , Zhang Qingfeng
Published: July 2021

Gametocytogenesis, the process by which malaria parasites produce sexual forms that can infect mosquitoes, is essential for the transmission of malaria. A transcriptional switch of the pfap2-g gene triggers sexual commitment, but how the complex multi-step process is precisely programed remains largely unknown. Here, by systematic functional screening of a panel of ApiAP2 transcription factors, we identify six new ApiAP2 members associated with gametocytogenesis in Plasmodium falciparum. Among these, PfAP2-G5 (PF3D7_1139300) was found to be indispensable for gametocytogenesis. This factor suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, the latter is linked to the maintenance of local heterochromatin structure, thereby preventing initiation of sexual commitment. Removal of this repressive effect through pfap2-g5 knockout disrupts the asexual replication cycle and promotes sexual commitment accompanied by upregulation of pfap2-g expression. However, the gametocytes produced fail to mature fully. Further analyses show that PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development. Collectively, our findings reveal a regulation cascade of gametocyte production in malaria parasites, and provide a new target for transmission blocking interventions.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Perioperative Spine: Preoperative Pulmonary Evaluation and Optimization
Authors: Mohamed Basma , Wang Marjorie C , Bisson Erica F , Dimar John , Harrop James S , Hoh Daniel J , Mummaneni Praveen V , Dhall Sanjay
Published: July 2021

BACKGROUND

There are no current recommendations for preoperative pulmonary evaluation and management of patients undergoing elective spine surgery.

OBJECTIVE

The aim of this guideline is to determine preoperative risk factors for perioperative and postoperative pulmonary adverse events and to determine the optimal preoperative evaluation and management of at-risk patients.

METHODS

A systematic review of the literature was performed using the National Library of Medicine PubMed database and the Cochrane Library for studies relevant to postoperative pulmonary adverse events in patients undergoing spine surgery. Clinical studies evaluating preoperative patient risk factors and preoperative diagnostic and treatment interventions were selected for review.

RESULTS

The literature search yielded 152 abstracts relevant to the PICO (patient/population, intervention, comparison, and outcomes) questions included in this chapter. The task force selected 65 articles for full-text review, and 24 were selected for inclusion in this systematic review. Twenty-three articles addressed preoperative patient risk factors. One article addressed preoperative diagnostic studies of pulmonary function. There were no studies meeting the inclusion criteria for preoperative pulmonary treatment.

CONCLUSION

There is substantial evidence for multiple preoperative patient factors that predict an increased risk of a postoperative pulmonary adverse event. Individuals with these risk factors (functional dependence, advanced age [≥65 yr], chronic obstructive pulmonary disease, congestive heart failure, weight loss, and obstructive sleep apnea) who are undergoing spine surgery should be counseled regarding the potential increased risk of a perioperative and postoperative pulmonary adverse events. There is insufficient evidence to support any specific preoperative diagnostic test for predicting the risk of postoperative pulmonary adverse events or any treatment intervention that reduces risk. It is suggested, however, to consider appropriate preoperative pulmonary diagnostic testing and treatment to address active pulmonary symptoms of existing or suspected disease.

The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/5-preoperative-pulmonary-evaluation-optimization.
Short-term Mortality Outcomes of HIV-Associated Cryptococcal Meningitis in Antiretroviral Therapy–Naïve and –Experienced Patients in Sub-Saharan Africa
Authors: Kalata Newton , Ellis Jayne , Kanyama Cecilia , Kuoanfank Charles , Temfack Elvis , Mfinanga Sayoki , Lesikari Sokoine , Chanda Duncan , Lakhi Shabir , Nyazika Tinashe , Chan Adrienne K , van Oosterhout Joep J , Chen Tao , Hosseinipour Mina C , Lortholary Olivier , Wang Duolao , Jaffar Shabbar , Loyse Angela , Heyderman Robert S , Harrison Thomas S , Molloy Síle F
Published: July 2021

Background

An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for <14 days compared with those on ART for >14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described.

Methods

Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation.

Results

Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.

Conclusions

In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.
The Politics of Higher Police Education: An International Comparative Perspective
Authors: Terpstra Jan , Schaap Dorian
Published: July 2021

Several countries have introduced mandatory higher education for all police officers. However, we have scant empirical knowledge about the arguments and debates underlying these systems. This contribution unpacks the ‘politics of higher police education’ in Norway, Finland, and North Rhine-Westphalia. We discuss the circumstances and dominant actors’ views, expectations, and arguments involved in the introduction and evolution of higher police education, and how to understand similarities and differences between these three countries. We find that similar arguments recurred in each case: helping the police adapt to a changing society, making the police profession more attractive, preventing police education from lagging behind similar professions, and improving police–citizen relationships. Specific historical or political contexts and organizational arrangements also played important roles in the introduction and shaping of higher police education. The higher police education systems as such are seen as legitimate, but there are fierce ongoing debates on both substance and form.
Small-interfering RNA for c-Jun attenuates cell death by preventing JNK-dependent PARP1 cleavage and DNA fragmentation in nitrogen mustard-injured immortalized human bronchial epithelial cells
Authors: Ye Feng , Dan Guorong , Zhao Yuanpeng , Yu Wenpei , Cheng Jin , Chen Mingliang , Sai Yan , Zou Zhongmin
Published: July 2021

Sulfur mustard (a type of vesicant) can directly damage lung bronchial epithelium via aerosol inhalation, and prevalent cell death is an early event that obstructs the respiratory tract. JNK/c-Jun is a stress response pathway, but its role in cell death of the injured cells is not clear. Here, we report that JNK/c-Jun was activated in immortalized human bronchial epithelial (HBE) cells exposed to a lethal dose (20 μM) of nitrogen mustard (NM, a sulfur mustard analog). c-Jun silencing using small-interfering RNA (siRNA) rendered the cells resistant to NM-mediated cell death by blocking poly(ADP-ribose) polymerase 1 (PARP1) cleavage and DNA fragmentation. In addition, the transduction of upstream extrinsic (Fasl-Fas-caspase-8) and intrinsic (loss of Bcl-2 and mitochondrial membrane potential, ΔΨm) apoptosis pathways, as well as phosphorylated (p)-H2AX (Ser139), an epigenetic marker contributing to DNA fragmentation and PARP1 activity, was partially suppressed. To mimic the detachment of cells by NM, HBE cells were trypsinized and seeded on culture plates that were pre-coated with poly-HEMA to prevent cell adhesion. The JNK/c-Jun pathway was found to be activated in the detached cells. In conclusion, our results indicate that JNK/c-Jun pathway activation is necessary for NM-caused HBE cell death and further suggest that c-Jun silencing may be a potential approach to protect HBE cells from vesicant damage.
A National Study of Progression Policies and Course Repetition in Prelicensure Registered Nursing Programs
Authors: Lewis Lisa S. , Willingham Tonya L. , Milner Ann Marie T.
Published: July 2021

BACKGROUND

The literature lacks description of the incidence of nursing students failing and repeating courses. Nursing student repeaters delay graduation and entry into the workforce; they are also at risk for attrition.

AIM

The aim of the study was to describe the incidence of nursing student repeaters and progression policies in the United States.

METHOD

A national survey of prelicensure nursing program deans and directors was conducted.

RESULTS

Invitations were sent to 2,055 nursing programs; the response rate was 32 percent. The annual incidence of nursing student course repetition was found to be 11.5 percent. Progression policies varied widely.

CONCLUSION

Nursing student repeaters are a significant population, and examination of progression policies is warranted.
Clinical Evaluation in Prelicensure Baccalaureate Nursing Programs: A Qualitative Descriptive Study
Authors: Butts Patsy J.
Published: July 2021

AIM

The aim of the study was to understand and describe how clinical nurse educators evaluate prelicensure baccalaureate nursing students in clinical practicums.

BACKGROUND

Clinical evaluation is used to determine nursing students’ competency. There is no consensus about how competency is defined, which may lead to inconsistent clinical evaluation of students.

METHOD

Clinical nurse educators who evaluate baccalaureate nursing students in clinical practicums participated in semistructured interviews via a web-conferencing platform.

RESULTS

Three categories emerged from the data: decision-making about practicum grades, making final determinations of clinical competency, and clinical nurse educator training in the clinical evaluation process. Five subcategories emerged: determinants in process, relevance of time, issues with practices, deeming students competent, and relevance of course structure.

CONCLUSION

Implications for nursing education are offered related to the need for standardization in clinical evaluation.
Positive effects of roflumilast on behavior, neuroinflammation, and white matter injury in mice with global cerebral ischemia
Authors: Vilhena Emanuella R. , Bonato Jéssica M. , Schepers Melissa , Kunieda Juliana K.C. , Milani Humberto , Vanmierlo Tim , Prickaerts Jos , de Oliveira Rúbia M.W.
Published: July 2021

Inhibition of phosphodiesterase 4 (PDE4) is a promising pharmacological strategy for the treatment of cerebral ischemic conditions. To increase the relevance and increase the translational value of preclinical studies, it is important to conduct experiments using different animal species and strains, different animal models, and to evaluate long-term functional outcomes after cerebral ischemia. In the present study, the effects of the selective PDE4 inhibitor roflumilast were evaluated in vivo and in vitro. Balb/c mice were subjected to bilateral common carotid artery occlusion (BCCAO) and tested during 21 days in multiple behavioral tasks to investigate the long-term effects of roflumilast on functional recovery. The effects of roflumilast were also investigated on hippocampal cell loss, white matter injury, and expression of neuroinflammatory markers. Roflumilast prevented cognitive and emotional deficits induced by BCCAO in mice. Roflumilast also prevented neurodegeneration and reduced the white matter damage in the brain of ischemic animals. Besides, roflumilast decreased Iba-1 (microglia marker) levels and increased Arginase-1 (Arg-1; microglia M2 phenotype marker) levels in the hippocampus of these mice. Likewise, roflumilast suppressed inducible nitric oxide synthase (microglia M1 phenotype marker) expression and increased Arg-1 levels in a primary mouse microglia culture. These findings support evidence that PDE4 inhibition by roflumilast might be beneficial in cerebral ischemic conditions. The neuroprotective effects of roflumilast appear to be mediated by a decrease in neuroinflammation.
Histone acetylation at the sulfotransferase 1a1 gene is associated with its hepatic expression in normal aging
Authors: Kronfol Mohamad M. , Abudahab Sara , Dozmorov Mikhail G. , Jahr Fay M. , Halquist Matthew S. , McRae MaryPeace , Wijesinghe Dayanjan S. , Price Elvin T. , Slattum Patricia W. , McClay Joseph L.
Published: July 2021

Objectives

Phase II drug metabolism is poorly studied in advanced age and older adults may exhibit significant variability in their expression of phase II enzymes. We hypothesized that age-related changes to epigenetic regulation of genes involved in phase II drug metabolism may contribute to these effects.

Methods

We examined published epigenome-wide studies of human blood and identified the SULT1A1 and UGT1A6 genes as the top loci showing epigenetic changes with age. To assess possible functional alterations with age in the liver, we assayed DNA methylation (5mC) and histone acetylation changes around the mouse homologs Sult1a1 and Ugt1a6 in liver tissue from mice aged 4–32 months.

Results

Our sample shows a significant loss of 5mC at Sult1a1 (β = −1.08, 95% CI [−1.8, −0.2], SE = 0.38, P = 0.011), mirroring the loss of 5mC with age observed in human blood DNA at the same locus. We also detected increased histone 3 lysine 9 acetylation (H3K9ac) with age at Sult1a1 (β = 0.11, 95% CI [0.002, 0.22], SE = 0.05, P = 0.04), but no change to histone 3 lysine 27 acetylation (H3K27ac). Sult1a1 gene expression is significantly positively associated with H3K9ac levels, accounting for 23% of the variation in expression. We did not detect any significant effects at Ugt1a6.

Conclusions

Sult1a1 expression is under epigenetic influence in normal aging and this influence is more pronounced for H3K9ac than DNA methylation or H3K27ac in this study. More generally, our findings support the relevance of epigenetics in regulating key drug-metabolizing pathways. In the future, epigenetic biomarkers could prove useful to inform dosing in older adults.
Feasibility and Outcomes of Corneal Transplantation Performed at Rural Centers: An Extension of the Pyramidal Model of Enhanced Eye Care at Rural Outreach
Authors: Rathi Varsha M. , Murthy Somasheila I. , Vaddavalli Pravin K. , Khanna Rohit C.
Published: July 2021

Purpose:

The aim of this study was to report on the feasibility of setting up a system of corneal transplants at rural outreach centers and report the outcomes of the first 111 cases.

Methods:

Retrospective analysis of the outcomes of corneal transplantation performed on patients with optical indications between March 2016 and September 2019 at 4 secondary (rural) centers. The centers are a part of a network in the pyramidal model developed by L V Prasad Eye Institute. The graft clarity and best-corrected visual acuity (BCVA) at 1-year follow-up were analyzed.

Results:

Of the 111 patients, 34.23% underwent penetrating keratoplasty and 65.77% endothelial keratoplasty. The mean age was 59.4 ± 15.0 (range-17–86 years); 47.75% were men and 52.25% were women. The indications for surgery were bullous keratopathy (54.05%), corneal scar/adherent leukoma (23.42%), and repeat grafts (13.51%). At the end of 1 year, 69.37% grafts remained clear. Factors associated with graft failure included poor socioeconomic status and graft infiltrate in both univariate and multivariate analyses. Surgical technique of endothelial keratoplasty was associated with failure on multivariate analysis only. Of the 77 eyes with clear corneal grafts at 1 year, the preoperative mean logMAR BCVA was 1.91 ± 0.06, which improved to 0.90 ± 0.08 postoperatively. Overall, 84.4% had preoperative BCVA of <3/60. Postoperatively, 40% had BCVA of 6/18 or better.

Conclusions:

Our study showed that close to 70% grafts remained clear at 1 year. Graft failure was associated with poor socioeconomic status and graft infiltrates. This study established a viable model for delivery of corneal transplant surgery and care in a rural setup.
Intraocular Pressure Monitoring Using an Intraocular Sensor Before and After Glaucoma Surgery
Authors: Saxby Edward , Mansouri Kaweh , Tatham Andrew J.
Published: July 2021

Purpose:

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, with evidence from landmark randomized controlled trials demonstrating visual field preservation with IOP reduction. Over recent years, the use of remote sensors has formed an increasingly important component of the management of chronic diseases. During the coronavirus disease 2019 pandemic, the ability to remotely monitor IOP proved particularly useful when public stay at home orders have been in place.

Patients and Methods:

This report describes the first case of glaucoma surgery in a patient who had previously received an EYEMATE-IO implant. The EYEMATE-IO is an implant for IOP monitoring placed in the ciliary sulcus during cataract surgery.

Results:

Remote IOP monitoring enabled the clinician to identify sustained high IOP readings and the need for glaucoma surgery. Postoperatively, response to treatment could be monitored to ensure sufficient long-term IOP control.

Conclusion:

The EYEMATE-IO implanted during cataract surgery in this patient provided valuable remote continuous IOP information that guided timely glaucoma surgical interventions for poorly controlled IOP.