bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of vacuoles with gas–liquid inclusions on the thermobaric destruction conditions of natural quartz under dynamic heating in an RF-TICP torch system
Authors: MIAO Long , NIE Mingqing , GRISHIN Yuri Mihailovich , WANG Xiaoyu , ZHU Zhengxi , SONG Jiahui , LIANG Fuwen , HE Zihao , TIAN Feng , WANG Ningfei
Published: November 2022

In the present work, the turbulent mixing process of a polydisperse quartz particle flow with a plasma stream generated by a radio-frequency (RF) inductively coupled plasma torch was numerically studied. The thermobaric stress in the quartz particles under dynamic heating in a heterogeneous plasma flow was determined by a two-stage approximation approach. The effect of the presence of vacuoles in natural quartz on the particle thermobaric destruction conditions was studied. It was found that the equivalent thermal and baric stresses in quartz particles may significantly increase in the presence of vacuoles within a small gas volume fraction. The influence of the regime and energetic working conditions of an RF inductively coupled plasma torch system on the particle thermobaric destruction conditions was examined, and a recommendation was given to promote the degree of thermobaric destruction of quartz particles, which is of substantial importance for improving the overall enrichment efficiency of quartz concentrates.
A unified secondary electron cut-off presentation and common mistakes in photoelectron spectroscopy
Authors: Schultz Thorsten
Published: November 2022

Photoelectron spectroscopy is a powerful surface analysis technique that can differentiate different bonding environments and directly determine the absolute work function of a sample. Despite its ever-easier accessibility—or perhaps precisely because of it—some common mistakes or bad habits are often found in the literature when it comes to the evaluation or presentation of photoelectron spectroscopy data. Here we address some of these issues and give suggestions for best practice, i.e., a proper presentation of the secondary electron cut-off used for work function determination, correct binding energy referencing and some tips for appropriate peak fitting, as well as valuable literature references to more detailed tutorials. Finally, we present a concise step-by-step guide on how to conduct a complete x-ray photoelectron spectroscopy analysis of an unknown sample.
Assessing polygenic risk score models for applications in populations with under-represented genomics data: an example of Vietnam
Authors: Pham Duy , Truong Buu , Tran Khai , Ni Guiyan , Nguyen Dat , Tran Trang T H , Tran Mai H , Nguyen Thuy Duong , Vo Nam S , Nguyen Quan
Published: November 2022

Most polygenic risk score (PRS)models have been based on data from populations of European origins (accounting for the majority of the large genomics datasets, e.g. >78% in the UK Biobank and >85% in the GTEx project). Although several large-scale Asian biobanks were initiated (e.g. Japanese, Korean, Han Chinese biobanks), most other Asian countries have little or near-zero genomics data. To implement PRS models for under-represented populations, we explored transfer learning approaches, assuming that information from existing large datasets can compensate for the small sample size that can be feasibly obtained in developing countries, like Vietnam. Here, we benchmark 13 common PRS methods in meta-population strategy (combining individual genotype data from multiple populations) and multi-population strategy (combining summary statistics from multiple populations). Our results highlight the complementarity of different populations and the choice of methods should depend on the target population. Based on these results, we discussed a set of guidelines to help users select the best method for their datasets. We developed a robust and comprehensive software to allow for benchmarking comparisons between methods and proposed a computational framework for improving PRS performance in a dataset with a small sample size. This work is expected to inform the development of genomics applications in under-represented populations. PRSUP framework is available at: https://github.com/BiomedicalMachineLearning/VGP
Intrinsic brain functional connectivity patterns in alcohol use disorder
Authors: Maleki Nasim , Sawyer Kayle S , Levy Sarah , Harris Gordon J , Oscar-Berman Marlene
Published: November 2022

Alcohol use disorder is associated with damaging effects to the brain. This study aimed to examine differences in static and dynamic intrinsic functional connectivity patterns in individuals with a history of alcohol use disorder in comparison to those with no history of alcohol abuse. A total of 55 participants consisting of 23 patients and 32 control individuals underwent neuropsychological assessments and resting-state functional magnetic resonance imaging on a 3 Tesla MRI scanner. Differences in functional connectivity between the two groups were determined using static and dynamic independent component analysis. Differences in static functional connectivity between the two groups were identified in the default mode network, attention network, frontoparietal network, frontal cortical network and cerebellar network. Furthermore, the analyses revealed specific differences in the dynamic temporal characteristics of functional connectivity between the two groups of participants, in a cluster involving key regions in reward, sensorimotor and frontal cortical functional networks, with some connections correlating with the length of sobriety and some others with the severity of drinking. The findings altogether suggest dysregulation in the intrinsic connectivity of cortico-basal ganglia-thalamo-cortical loops that may reflect persistent alcohol use disorder-related network abnormalities, compensatory recovery-related processes whereby additional neural resources are recruited to achieve normal levels of performance, or a predisposition toward developing alcohol use disorder.
The Use and Efficacy of Biological Therapies for Inflammatory Bowel Disease in a Danish Tertiary Centre 2010–2020
Authors: Wewer Mads Damsgaard , Arp Laura , Sarikaya Melek , Felding Oluf Krautwald , Vind Ida , Pedersen Gitte , Mertz-Nielsen Anette , Kiszka-Kanowitz Marianne , Boysen Trine , Theede Klaus , Petersen Andreas Munk , Nordgaard-Lassen Inge , Bendtsen Flemming , Burisch Johan
Published: November 2022

Background

Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center.

Methods

We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed.

Results

The population consisted of 327 Crohn’s disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2–5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559–0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736–1.349).

Conclusions

The annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.
Zebrafish models of COVID-19
Authors: Tyrkalska Sylwia D , Candel Sergio , Pedoto Annamaria , García-Moreno Diana , Alcaraz-Pérez Francisca , Sánchez-Ferrer Álvaro , Cayuela María L , Mulero Victoriano
Published: November 2022

Although COVID-19 has only recently appeared, research studies have already developed and implemented many animal models for deciphering the secrets of the disease and provided insights into the biology of SARS-CoV-2. However, there are several major factors that complicate the study of this virus in model organisms, such as the poor infectivity of clinical isolates of SARS-CoV-2 in some model species, and the absence of persistent infection, immunopathology, severe acute respiratory distress syndrome, and, in general, all the systemic complications which characterize COVID-19 clinically. Another important limitation is that SARS-CoV-2 mainly causes severe COVID-19 in older people with comorbidities, which represents a serious problem when attempting to use young and immunologically naïve laboratory animals in COVID-19 testing. We review here the main animal models developed so far to study COVID-19 and the unique advantages of the zebrafish model that may help to contribute to understand this disease, in particular to the identification and repurposing of drugs to treat COVID-19, to reveal the mechanism of action and side-effects of Spike-based vaccines, and to decipher the high susceptibility of aged people to COVID-19.
Regulatory and metabolic adaptations in the nitrogen assimilation of marine picocyanobacteria
Authors: Díez J , López-Lozano A , Domínguez-Martín M A , Gómez-Baena G , Muñoz-Marín M C , Melero-Rubio Y , García-Fernández J M
Published: November 2022

Prochlorococcus and Synechococcus are the two most abundant photosynthetic organisms on Earth, with a strong influence on the biogeochemical carbon and nitrogen cycles. Early reports demonstrated the streamlining of regulatory mechanisms in nitrogen metabolism and the removal of genes not strictly essential. The availability of a large series of genomes, and the utilization of latest generation molecular techniques have allowed elucidating the main mechanisms developed by marine picocyanobacteria to adapt to the environments where they thrive, with a particular interest in the strains inhabiting oligotrophic oceans. Given that nitrogen is often limited in those environments, a series of studies have explored the strategies utilized by Prochlorococcus and Synechococcus to exploit the low concentrations of nitrogen-containing molecules available in large areas of the oceans. These strategies include the reduction in the GC and the cellular protein contents; the utilization of truncated proteins; a reduced average amount of N in the proteome; the development of metabolic mechanisms to perceive and utilize nanomolar nitrate concentrations; and the reduced responsiveness of key molecular regulatory systems such as NtcA to 2-oxoglutarate. These findings are in sharp contrast with the large body of knowledge obtained in freshwater cyanobacteria. We will outline the main discoveries, stressing their relevance to the ecological success of these important microorganisms.
Identification of genetic interactions with priB links the PriA/PriB DNA replication restart pathway to double-strand DNA break repair in Escherichia coli
Authors: McKenzie Aidan M , Henry Camille , Myers Kevin S , Place Michael M , Keck James L
Published: November 2022

Collisions between DNA replication complexes (replisomes) and impediments such as damaged DNA or proteins tightly bound to the chromosome lead to premature dissociation of replisomes at least once per cell cycle in Escherichia coli. Left unrepaired, these events produce incompletely replicated chromosomes that cannot be properly partitioned into daughter cells. DNA replication restart, the process that reloads replisomes at prematurely terminated sites, is therefore essential in E. coli and other bacteria. Three replication restart pathways have been identified in E. coli: PriA/PriB, PriA/PriC, and PriC/Rep. A limited number of genetic interactions between replication restart and other genome maintenance pathways have been defined, but a systematic study placing replication restart reactions in a broader cellular context has not been performed. We have utilized transposon-insertion sequencing to identify new genetic interactions between DNA replication restart pathways and other cellular systems. Known genetic interactors with the priB replication restart gene (uniquely involved in the PriA/PriB pathway) were confirmed and several novel priB interactions were discovered. Targeted genetic and imaging-based experiments with priB and its genetic partners revealed significant double-strand DNA break accumulation in strains with mutations in dam, rep, rdgC, lexA, or polA. Modulating the activity of the RecA recombinase partially suppressed the detrimental effects of rdgC or lexA mutations in ΔpriB cells. Taken together, our results highlight roles for several genes in double-strand DNA break homeostasis and define a genetic network that facilitates DNA repair/processing upstream of PriA/PriB-mediated DNA replication restart in E. coli.
Lesbian, Gay, and Bisexual Widows’ Experiences of Grief, Identity, and Support: A Qualitative Study of Relationships Following the Loss of a Spouse or Partner
Authors: Valenti Korijna G , Hahn Sarah , Enguidanos Susan , Quinn Gwendolyn , de Medeiros Kate
Published: November 2022

Objectives

Research with lesbian, gay, and bisexual (LGB) older widows rarely focuses on familial relationships. Studies on heterosexual spousal bereavement indicate older widows face issues influencing identity but show resilience by maintaining close relationships with adult children and extended family. Though research with older LGB widows suggests similarities around loss and resilience, grief and family engagement are markedly different.

Methods

Guided by Relational Cultural Theory, which illuminates how LGB women cope through connection/disconnection, this qualitative descriptive study employed semistructured, open-ended interviews with 16 LGB women, 60–85 years of age from across the United States who had lost a spouse or partner within the past 5 years. We conducted interviews regarding the perception of self as bereaved LGB women and sustained or altered relationships with biological and chosen families following the loss of their spouses/partners.

Results

Findings are illustrated in three themes around acceptance, support, and identity. Participants: (a) experienced differing levels of acceptance, tolerance, and inclusion from biological families; (b) experienced family or friends “disappearing” or providing critical support following a spouse/partner’s death; and (c) negotiated challenges by creating or seeking out families of choice, new communities, and a better understanding of themselves.

Discussion

While LGB widows share some grief experiences with heterosexual widows, they also experience varying biological family acceptance and support, as well as the need for friends and families of choice as advocates. It is important to recognize the unique consequences of spousal loss for this population and be cognizant of the differences in normative grief.
Definition and Contextual Factors of Nursing Home Residents’ Mobility in a Holistic View: A Delphi Study
Authors: Vogel Oliver , Otto Ann-Kathrin , Zimmel Hanna , Hinrichs Timo , Giannouli Eleftheria , Wollesen Bettina
Published: November 2022

Background and Objectives

Current definitions of older adults’ mobility do not cover the full range of influencing factors and do not consider nursing home residents. The present study reports expert ratings from a Delphi study regarding factors influencing the mobility of long-term nursing home residents.

Research Design and Methods

We invited 129 professionals with expertise in a field relevant to research on mobility in older adults such as health care, medicine, or human movement science to participate in a Delphi study comprising 3 rounds of online questionnaires. Up to 40 experts participated in each round. In the first round, we used open-ended questions to solicit possible definitions, contextual factors, and assessment tools. In the second round, the participants used Likert scales (1–10) to rate their suitability. In the final round, we presented a definition based on consensus as well as the top-rated contextual factors and assessment tools from the first 2 rounds for a final rating of agreement.

Results

The experts showed broad agreement on the final version of the mobility definition, with 8.9 ± 1.4 (mean ± standard deviation) out of 10 points. The experts also showed broad consensus on the selected contextual factors, with 8.4 ± 1.8 points to 8.9 ± 1.2 points (out of 10 points). This was also the case for the top 3 assessment tools selected from results of previous rounds, which showed an agreement of 7 or more points (out of 10 points) by 81.6% to 100% of all experts in the different categories.

Discussion and Implications

Given that an interdisciplinary group of experts considered various hitherto neglected contextual factors as relevant, the Delphi survey and its results imply the need for an updated interdisciplinary and holistic understanding of mobility in nursing home residents and can provide a basis for putting it into practice.
Counting stars: contribution of early career scientists to marine and fisheries sciences
Authors: Smoliński Szymon , Ottmann Daniel , Outinen Okko , Schadeberg Amanda , Melli Valentina , Funk Lara , Denechaud Côme , Wieczorek Alina , Orio Alessandro , Mussgnug Robert , Morkūnė Rasa , Vereide Emilie Hernes , Zdulska Maja , Phillips Genevieve , Lishchenko Fedor , Srėbalienė Greta
Published: November 2022

Scientific careers and publishing have radically changed in recent decades creating an increasingly competitive environment for early career scientists (ECS). The lack of quantitative data available on ECS in marine and fisheries sciences prevents direct assessment of the consequences of increased competitiveness. We assessed the contributions of ECS (up to 6 years post first publication) to the field using an indirect approach by investigating the authorships of peer-reviewed articles. We analysed 118461 papers published by 184561 authors in the top 20 marine and fisheries sciences journals over the years 1991–2020. We identified a positive long-term trend in the proportion of scientific articles (co-)authored by ECS. This suggests a growing contribution by ECS to publications in the field. However, the mean proportion of ECS (co-)authors within one publication declined significantly over the study period. Subsequent tests demonstrated that articles with ECS (co-)authors receive fewer citations and that the proportion of ECS (co-)authors on an article has a significant negative effect on the number of citations. We discuss the potential causes of these inequalities and urge systematic support to ECS to achieve more balanced opportunities for funding and publishing between ECS and senior scientists.
Who Joins and Who Fights? Explaining Tacit Coalition Behavior among Civil War Actors
Authors: Steinwand Martin C , Metternich Nils W
Published: November 2022

Which armed organizations form coalitions despite the inherent difficulties of cooperation in civil wars? We introduce the concept of tacit coalitions, which pertains to strategic and informal coalition behavior between civil war actors to address this puzzle. Our theoretical model of coalition behavior takes in theater-wide conflict behavior to allow for predictions that coalitions are more likely to form. It provides novel insights into the way military synergies within potential coalitions affect the trade-off between pooling resources and worrying about the division of gains. The empirical section finds considerable support for our theoretical argument that actors are more likely to engage in tacit coalition behavior (1) if potential coalitions are power balanced, (2) if joint capability of potential coalitions is not too high, and (3) when coalitions can unlock synergies. In addition, it produces evidence for the important role of geography and ethnic ties in generating military synergies.
Fast and New Microbiological Method for Evaluating the Potency of Marbofloxacin-Based Tablets
Authors: Ferreira Raissa Gabrielle Lima , Da Silva Júnior João Roberto , Torres Ieda Maria Sapateiro , Kogawa Ana Carolina
Published: November 2022

Background

Marbofloxacin (MAR) is an antimicrobial belonging to the fluoroquinolone class and is marketed in the form of tablets. There is no microbiological monograph in official compendia to evaluate the potency of the final product. Furthermore, the literature is scarce in this context.

Objective

The objective is to develop and validate a microbiological method by turbidimetry to evaluate the potency of MAR-based tablets, based on the principles of green analytical chemistry.

Methods

Purified water–ethanol (9 + 1, v/v) was used as diluent to prepare the MAR solutions at concentrations of 0.25, 0.8, and 2.56 µg/mL, brain heart infusion (BHI) broth as culture media, E. coli American Type Culture Collection (ATCC) 25922 at 10% and incubation in a shaker at 37°C for 4 h were used in the method.

Results

The method was: linear in the range of 0.25 to 2.56 µg/mL; selective against the sample adjuvants; precise (intra-day RSD 2.26%, inter-day RSD 3.49%, and inter-analyst RSD 3.59%); accurate with a recovery of 100.20%; and robust against changes in culture medium volume in the tube, shaker rotation, and incubation temperature in the shaker. The potency of MAR tablets was 96.98% using the proposed method.

Conclusion

The turbidimetric method developed is a new, fast, and optimized option to the routine QC of MAR in tablets, since it allows the evaluation of the drug's potency in the final product and can be used to complement the results of the physicochemical analysis, in addition to being a green and sustainable alternative.

Highlights

The work shows an ecological and green alternative to the routine microbiological pharmaceutical analysis of MAR tablets.
Castration alters the cecal microbiota and inhibits growth in Holstein cattle
Authors: Li Zemin , Shi Jinping , Lei Yu , Wu Jianping , Zhang Rui , Zhang Xiao , Jia Li , Wang Ying , Ma Yue , He Pengjia , Ma Yannan , Cheng Qiang , Zhang Zhao , Zhang Ke , Lei Zhaomin
Published: November 2022

To determine the effects of castration on growth performance, serum hormone levels, cecal microbiota composition, and metabolites in cattle. A total of 18 Holstein bulls and steers were divided into bull and steer groups and randomly assigned to 3 pens (3 cattle per pen, and each cattle were separated by a fence) to determine the average daily gain (ADG), daily dry matter intake (DMI), and feed efficiency (G/F). After the finishing trial, six cattle per group were randomly slaughtered. Serum was collected to measure the hormone concentration, and the cecal content was collected to measure the pH, short-chain fatty acids, and digestive enzyme activities. Metagenome sequencing and untargeted metabolomics were used to investigate the microbiota composition, functional profiles, and differential metabolites of the cecal contents. We found that castration significantly decreased ADG, DMI, and G/F in cattle (P < 0.05). The serum testosterone, thyroxine, growth hormone (P < 0.05), and triiodothyronine (P < 0.01) concentrations significantly decreased in the steer group when compared to those of the bull group. The activities of cellulase, xylanase, pectinase, and β-glucosidase (P < 0.05) significantly decreased in the steer group, whereas the activities of lipase and α-amylase significantly increased. Moreover, castration significantly decreased the relative abundance of Ruminococcaceae_bacterium, Treponema_porcinum, Oscillibacter_sp. (P < 0.05), and Alistipes_senegalensis (P < 0.01), whereas the relative abundance of Phocaeicola_plebeius (P < 0.05) was significantly increased. Also, the relative abundance of Phocaeicola_plebeius was negatively correlated with testosterone levels, and the function of the cecal microbiota was enriched in the GH29 and GH97 families in the steer group. Metabolomic analysis indicated that castration increased the levels of L-valine, L-phenylalanine, L-aspartic acid, L-isoleucine, L-lysine, methionine, L-glutamic acid, and L-leucine, while decreasing the levels of α-ketoglutaric acid through the 2-oxocarboxylic acid metabolism pathway. In addition, α-ketoglutaric acid was negatively correlated with Oscillibacter_sp. (P < 0.01). Overall, castration can inhibit cattle growth by altering the composition of the cecal microbiota. Therefore, this study provides a theoretical and practical basis for improving the growth performance of steers.
Race, Locality, and Representative Bureaucracy: Does Community Bias Matter?
Authors: Park Joohyung , Favero Nathan
Published: November 2022

Despite burgeoning research on representative bureaucracy theory, there is limited examination of how environmental contexts shape the manner in which the demographic makeup of a bureaucracy is linked to distributional bureaucratic outcomes. Scholars in the field of social psychology, however, have suggested that community-level variation in the pervasiveness of biases against particular social groups helps to explain inequitable outcomes in such diverse settings as education, policing, and health care. Incorporating social psychology research into representative bureaucracy theory, this article examines how community racial biases shape the association between the demographic makeup of an organization’s personnel and its bureaucratic outcomes. Using county-level implicit and explicit bias measures that are estimated by multilevel regression and poststratification (MRP) based on a dataset containing more than 1.2 million respondents, we find that more inequitable educational outcomes occur for black students in counties where white residents hold stronger anti-black biases. Our findings also suggest that while black teachers are associated with more favorable outcomes for black students in the zero-sum context of assignment to gifted classes, the association of outcomes with passive representation is more limited in counties with strong racial biases. By accounting for the racial biases exhibited in the communities where both clients and bureaucrats are socially and culturally embedded, this article extends our understanding of how contextual factors shape the nature of bureaucratic representation.
Hidden Religious Identities Online
Authors: Tsuria Ruth
Published: November 2022

This chapter provides an overview of the study of LGBTQIA+ religious identities online. Reviewing the limited scholarship on the intersection of queer studies, sexuality, gender, and religion, three key themes from the broader digital religion field were identified: community, authority, and identity. Each theme further highlighted a specific tension: offline-online community interactions, resisting-strengthening religious authority, and validation-discreditation of LGBT+ religious identity. While these themes and tensions are also found in digital religion, because LGBTQIA+ issues are usually a contentious topic in religious contexts, this interaction uniquely stresses the ways that digital media are used anonymously or for advocacy and activism.
Past, Present, and Potential Futures of Digital Hinduism Research
Authors: Zeiler Xenia
Published: November 2022

This chapter provides an overview of the varied scope of past, present, and potential future research on digital Hinduism, highlighting central themes, approaches, and perspectives. It proceeds chronologically and begins with prevailing thematic foci and lines of inquiry in the early days, considering how these lay a groundwork for current studies. The early days saw a particular academic interest in Hindu online practices. In the more recent past and the present, and with ongoing recognition and diversifying of the field, the ways of studying the increasingly important intersection of Hinduism and digital media encompass increasing numbers of frameworks and methodologies. To exemplify currently prominent and important themes and theoretical and methodical approaches, the chapter specifically discusses mediatization, actor-centered research, and an exemplary novel digital space, video games. Finally, the conclusion provides an outlook on the potential future(s) of digital Hinduism research.
New Religious Movements and the Internet
Authors: Guillory Margarita Simon
Published: November 2022

This chapter provides an overview of scholarship on new religious movements (NRMs) and the Internet. A brief snapshot of NRM studies provides a meaningful context in discussing past, present, and future works committed to the exploration of new religions in digital religion studies. As will be shown, thematic concerns that characterized the former subfield are also present in past and present research that focuses on the intersections between NRMs and computer-mediated communication. What follows is a historical tracing of this scholarship, with special attention given to studies that occupy the liminal spaces between NRM studies and digital religion studies.
Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor
Authors: Wei Yinghui , Zhang Meiling , Hu Jing , Zhou Yingsi , Xue Mingxing , Yin Jianhang , Liu Yuanhua , Feng Hu , Zhou Ling , Li Zhifang , Wang Dongshuang , Zhang Zhiguo , Zhou Yin , Liu Hongbin , Yao Ning , Zuo Erwei , Hu Jiazhi , Du Yanzhi , Li Wen , Xu Chunlong , Yang Hui
Published: November 2022

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and non-carriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus (SLE) and familial hypercholesterolemia (FH). Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
The next generation Birmingham Solar Oscillations Network (BiSON) spectrophotometer: a new miniaturized instrument for helioseismology
Authors: Hale S J , Chaplin W J , Davies G R , Elsworth Y P , Howe R
Published: November 2022

We describe a new spectrophotometer for the Birmingham Solar Oscillations Network (BiSON), based on a next generation observation platform, BiSON:NG, a significantly miniaturized system making use of inexpensive consumer-grade hardware and off-the-shelf components, where possible. We show through system modelling and simulation, along with a summer observing campaign, that the prototype instrument produces data on the Sun’s low-degree acoustic (p-mode) oscillations that are of equal quality and can be seamlessly integrated into the existing network. Refreshing the existing ageing hardware, and the extended observational network potential of BiSON:NG, will secure our ongoing programme of high-quality synoptic observations of the Sun’s low-degree oscillations (e.g. for seismic monitoring of the solar cycle at a ‘whole Sun’ level).
From “Civilian Clergy to Officer”: Hiring and Training Chaplains for Federal Government Positions
Authors: Tien Grace , Cadge Wendy
Published: November 2022

This article asks how people hired into federal chaplaincy positions are trained on the job. We find that unlike those hired into positions based on education, knowledge, and skills to date, chaplains are hired—by design—without some of the skills required for the job. Employers do not expect hired chaplains to understand organizational norms and practices, and so we identify strategies like inculcation and embodiment that employers use to help chaplains integrate their religious identity with their new professional identity. Drawing on interviews and archival data, we examine the process of hiring and training for federal chaplains as a case study of religious professionals in secular and pluralistic organizational contexts. This article contributes to and bridges work between scholars of religion and scholars of work and organizations who are interested in processes of hiring and training but do not often consider the role of religion in relation to such processes.
Intramuscular administration of glyoxylate rescues swine from lethal cyanide poisoning and ameliorates the biochemical sequalae of cyanide intoxication
Authors: Bebarta Vik S , Shi Xu , Zheng Shunning , Hendry-Hofer Tara B , Severance Carter C , Behymer Matthew M , Boss Gerry R , Mahon Sari , Brenner Matthew , Knipp Gregory T , Davisson Vincent Jo , Peterson Randall T , MacRae Calum A , Rutter Jared , Gerszten Robert E , Nath Anjali K
Published: November 2022

Cyanide—a fast-acting poison—is easy to obtain given its widespread use in manufacturing industries. It is a high-threat chemical agent that poses a risk of occupational exposure in addition to being a terrorist agent. FDA-approved cyanide antidotes must be given intravenously, which is not practical in a mass casualty setting due to the time and skill required to obtain intravenous access. Glyoxylate is an endogenous metabolite that binds cyanide and reverses cyanide-induced redox imbalances independent of chelation. Efficacy and biochemical mechanistic studies in an FDA-approved preclinical animal model have not been reported. Therefore, in a swine model of cyanide poisoning, we evaluated the efficacy of intramuscular glyoxylate on clinical, metabolic, and biochemical endpoints. Animals were instrumented for continuous hemodynamic monitoring and infused with potassium cyanide. Following cyanide-induced apnea, saline control or glyoxylate was administered intramuscularly. Throughout the study, serial blood samples were collected for pharmacokinetic, metabolite, and biochemical studies, in addition, vital signs, hemodynamic parameters, and laboratory values were measured. Survival in glyoxylate-treated animals was 83% compared with 12% in saline-treated control animals (p < .01). Glyoxylate treatment improved physiological parameters including pulse oximetry, arterial oxygenation, respiration, and pH. In addition, levels of citric acid cycle metabolites returned to baseline levels by the end of the study. Moreover, glyoxylate exerted distinct effects on redox balance as compared with a cyanide-chelating countermeasure. In our preclinical swine model of lethal cyanide poisoning, intramuscular administration of the endogenous metabolite glyoxylate improved survival and clinical outcomes, and ameliorated the biochemical effects of cyanide.
Normative Team Age Prototypes: Exploring Follower, Leader, and Team Characteristics
Authors: Weidner Nathan , Thrasher Gregory R , Rudolph Cort W
Published: November 2022

The concept of implicit organizational timetables suggests that leaders are expected to be older than their followers. However, increased age diversity in the workforce has led to situations in which this is not the case. Expanding on the core tenets of leader categorization theory, the present study establishes the concept of an age-prototypical team characterized by the age of the leader relative to their followers and explores how team age prototypicality influences subsequent observer evaluations of the team. Moreover, this study examines possible boundary conditions and intermediary mechanisms that further explain bias in the evaluation of age-diverse teams. To establish and explore the nature and effect of age-based team prototypes, we conducted 3 independent experimental vignette studies. In Study 1 (n = 590), we establish evidence for age-based team prototypes, by demonstrating a “leaders are older, followers are younger” prototype and further considering the diversity of follower age as a boundary condition for the effects of leader age on ratings of attraction to the team, anticipated team behaviors, and expectations for future success. Then, in Study 2 (n = 686) and Study 3 (n = 782), we extend these results by examining how the perception of team (Study 2) and leader (Study 3) performance cues are influenced by team age composition prototypes. In Study 3, we also consider intermediary attributional mechanisms that explain associations between performance and perceived qualities of the team. Results suggest that prototype inconsistent teams (i.e., teams with younger leaders and older followers) are viewed more harshly in the face of negative performance cues as a function of team composition rather than because of leader or follower attributes individually.
Neither leg nor jaw—nor always the same: a critical revision of the eumalacostracan maxilliped
Authors: Grams Markus , Klinger Michael , Richter Stefan
Published: November 2022

Within Malacostraca, legs are diversified variously throughout the groups. Most conspicuous is the transformation of anterior thoracopods, especially the first, into maxillipeds involved in feeding. However, the concept of a maxilliped is not precise, because it relates to a vague combination of morphological and functional deviation from a locomotory limb. Although general homology of the first thoracopod (maxilliped or not) is beyond doubt, special homology (synapomorphy) of the anteriormost maxillipeds remains uncertain. For better insights, we studied the musculature and exoskeletal structures of the first thoracopods in Anaspidacea, Euphausiacea, Lophogastrida, Mysida and Stygiomysida, using three-dimesional reconstruction of laser scanning microscopy and micro-computed tomography data. Our analysis shows high muscular and skeletal complexity of the first thoracopods. We herein reject the term ‘maxilliped’ for Anaspidacea and Euphausiacea, because their first thoracopods differ little from the posterior limbs, although specific correspondences between these taxa might represent synapomorphies. The ‘mysidacean maxilliped’ is morphologically well derived from the posterior thoracopods and appears synapomorphic for the mysidacean subtaxa. A comparison with other Peracarida additionally shows correspondences indicating a homologous ‘peracaridan maxilliped’. In contrast, we consider the peracaridan maxilliped not to be homologous to the decapodan maxilliped. As a distinction, we propose the term ‘unguiped’ for the peracaridan first thoracopod.
Effects of Exogenous Nitric Oxide Treatment on Grape Berries Against Botrytis cinerea and Alternaria alternata Related Enzymes and Metabolites
Authors: Shi Jinxin , Huang Dandan , Du Yejuan , Zhu Shuhua , Hussain Zahoor , Haider Muhammad Salman , Anwar Raheel
Published: November 2022

Postharvest losses of grape berries caused by the pathogenic fungi Botrytis cinerea and Alternaria alternata have been widely reported, and nitric oxide (NO) as a plant signaling molecule to control postharvest diseases has recently become an active research topic. This study aimed to investigate the regulatory effect of NO on the interaction between grape berries and fungi. During interactions between grape berries and pathogenic fungi, treatment with 10 mM sodium nitroprusside (SNP, an NO donor) delayed the decline of the physiological quality of the grape berries and had positive effects on the weight loss rate, firmness, and respiration intensity. SNP treatment increased the activities of superoxide dismutase (SOD) and polyphenol oxidase (PPO) and inhibited the activities of peroxidase (POD) and catalase (CAT) of grape berries during the resistance to fungal pathogen infection. In addition, the increase in browning degree and the accumulation of hydrogen peroxide were inhibited by SNP treatment. In the phenylpropane metabolic pathway, the activities of phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumaric acid coenzyme A ligase (4CL) were increased during the activation of grape berries during the resistance to pathogen infection by SNP, and the intermediate metabolites lignin, flavonoids, and total phenols were accumulated. In addition, SNP treatment had a regulatory effect on the gene expression levels of SOD, POD, PPO, PAL, and 4CL. These results suggested that SNP treatment was effective for the preservation and disease reduction of grape berries.
Species Identification and Fungicide Sensitivity of Fungi Causing Alternaria Leaf Blight and Head Rot in Cole Crops in the Eastern United States
Authors: Nieto-Lopez Edgar H. , Cerritos-Garcia Daniel G. , Koch Bach Rachel A. , Petkar Aparna , Smart Christine D. , Hoepting Christy , Langston David , Rideout Steven , Dutta Bhabesh , Everhart Sydney E.
Published: November 2022

Alternaria leaf blight and head rot is an important disease of broccoli and other cole crops. With no resistant host varieties, fungicides are utilized to manage this disease. However, anecdotal evidence suggests that, in southeastern U.S. broccoli-producing states, there is a loss of disease control through the use of quinone outside inhibitor (QoI) fungicides. To understand why there is a reduced sensitivity to QoI fungicides in these states, we isolated Alternaria spp. from symptomatic lesions on cole crops from Georgia and Virginia (two states with observations of loss of fungicide sensitivity) as well as New York (a state with no observations of loss of fungicide sensitivity). Using multilocus sequencing and phylogenetic analysis, we identified two species, Alternaria brassicicola and A. japonica. Whereas A. brassicicola was isolated in all states, A. japonica was only isolated in Georgia. Next, we wanted to determine the sensitivity of these isolates to azoxystrobin—an active ingredient in some QoI fungicides—by estimating the effective concentration at which only 50% of spores germinate (EC50). The EC50of A. brassicicola ranged from 0.01 to 0.17 ppm, whereas that of A. japonica was 8.1 to 28.1 ppm. None of the known target-site mutations that confer resistance to QoI fungicides were identified during screening of either species. A. japonica was first reported on the east coast of the United States in 2020 in South Carolina. The substantially higher EC50value suggests that its emergence in the southeastern United States may play at least a part in the observed loss of disease control. However, further in planta and field studies are needed to thoroughly test this hypothesis.
Key Advances in the New Era of Genomics-Assisted Disease Resistance Improvement ofBrassicaSpecies
Authors: Amas Junrey C. , Thomas William J. W. , Zhang Yueqi , Edwards David , Batley Jacqueline
Published: November 2022

Disease resistance improvement remains a major focus in breeding programs as diseases continue to devastate Brassica production systems due to intensive cultivation and climate change. Genomics has paved the way to understand the complex genomes of Brassicas, which has been pivotal in the dissection of the genetic underpinnings of agronomic traits driving the development of superior cultivars. The new era of genomics-assisted disease resistance breeding has been marked by the development of high-quality genome references, accelerating the identification of disease resistance genes controlling both qualitative (major) gene and quantitative resistance. This facilitates the development of molecular markers for marker assisted selection and enables genome editing approaches for targeted gene manipulation to enhance the genetic value of disease resistance traits. This review summarizes the key advances in the development of genomic resources for Brassica species, focusing on improved genome references, based on long-read sequencing technologies and pangenome assemblies. This is further supported by the advances in pathogen genomics, which have resulted in the discovery of pathogenicity factors, complementing the mining of disease resistance genes in the host. Recognizing the co-evolutionary arms race between the host and pathogen, it is critical to identify novel resistance genes using crop wild relatives and synthetic cultivars or through genetic manipulation via genome-editing to sustain the development of superior cultivars. Integrating these key advances with new breeding techniques and improved phenotyping using advanced data analysis platforms will make disease resistance improvement in Brassica species more efficient and responsive to current and future demands.
Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms*
Authors: Cox Christopher E. , Gu Jessie , Ashana Deepshikha Charan , Pratt Elias H. , Haines Krista , Ma Jessica , Olsen Maren K. , Parish Alice , Casarett David , Al-Hegelan Mashael S. , Naglee Colleen , Katz Jason N. , O’Keefe Yasmin Ali , Harrison Robert W. , Riley Isaretta L. , Bermejo Santos , Dempsey Katelyn , Johnson Kimberly S. , Docherty Sharron L.
Published: November 2022

OBJECTIVES:

While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months.

DESIGN:

Prospective cohort study.

SETTING:

Six adult medical and surgical ICUs.

PARTICIPANTS:

Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0–130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0–63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12–40) at baseline and 19 (IQR, 9–37) at 7 days (change, –2.0; IQR, –11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15).

CONCLUSIONS:

Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.