bluuebunny/crossref_metadata_2025 huggingface dataset:
8Media Theory
Authors: Enns Anthony
Published: May 2022

Most countries experienced an extended period of lockdown during 2021 due to the rapid increase in the number of Covid-19 cases and the comparatively slow process of developing and distributing effective vaccines. It is therefore no surprise that the pandemic was often mentioned in the introductions to books on media theory, although these projects were clearly conceived and written long before the pandemic began, and many of them were directly responding to the social crisis that preceded our current one—namely, the rapid rise in participation in social media and the accompanying rise in online extremism, which had devastating political consequences in the US and around the world. While these books were released after the 6 January attack on the US Capitol and the end of Donald Trump’s term as president, many of them were attempting to examine how media technologies had contributed to the rise of authoritarianism and the decline of democratic values during his administration, and they often addressed similar concerns, such as the oppressive structures of digital media platforms, the potential threat that they pose to democracy, and how they might be used for political activism. The following review is divided into three sections that focus on each of these concerns: 1. Digital Media and Neoliberal Capitalism discusses how digital media introduced new forms of labour that were inherently linked to neoliberal capitalism; 2. Digital Media and Disinformation discusses the potential causes of and solutions to the problem of online disinformation; and 3. Digital Media and Political Change discusses the potential benefits and limitations of using digital media to promote positive political change, followed by 4. Conclusion. These books thus provide an insightful analysis of our current social, political, and economic situation, and they offer a wide range of suggestions on how our media technologies could be reconfigured in order to facilitate a more promising future.
Virulence Survey of Puccinia striiformis in Israel Revealed Considerable Changes in the Pathogen Population During the Period 2001 to 2019
Authors: Kosman Evsey , Ben-Yehuda Pnina , Manisterski Jacob , Anikster Yehoshua , Sela Hanan
Published: May 2022

A total of 353 urediniospore isolates of Puccinia striiformis f. sp. tritici (Pst) collected in Israel during 2001 to 2019 were analyzed. Pst pathogenicity was studied with a set of 20 differentials (17 Avocet and 3 other lines). Three periods were compared: 2001 to 2007, 2009 to 2016, and 2017 to 2019. No virulence to Yr5 or Yr15 was detected. Virulence frequencies on Yr4, Yr10, Yr24, and YrSp genes rose to the moderate level (0.28 to 0.44) in 2017 to 2019. Virulence frequencies to Yr2 and Yr9 decreased. One Pst phenotype was identified in all three periods, but its frequency drastically decreased from 0.74 in 2001 to 2016 to 0.21 in 2017 to 2019. The most probable scenario of emergence of wheat yellow rust in Israel is wind dissemination of Pst urediniospores from the Horn of Africa. Variability of the Pst population increased amid considerable evolution with two major transformations in 2009 and 2017. The first modification can be attributed to changes in wheat genetic background in Israel due to deployment of new cultivars resistant to yellow rust since 2004. The second shift in 2017 can be primarily explained by intensive deployment of wheat cultivars resistant to the stem rust race Ug99 in the 2010s in the Horn of Africa. This led to changing genetic backgrounds of the cultivated wheats in the donor region and development and long-distance spread of new Pst phenotypes to Israel. Two singular multivirulent Pst phenotypes were identified in 2019, one of them being closely related to the aggressive Warrior race. Such phenotypes may potentially defeat existing resistances.
Ralstonia Strains from Potato-Growing Regions of Kenya Reveal Two Phylotypes and Epidemic Clonality of Phylotype II Sequevar 1 Strains
Authors: Sharma Kalpana , Iruegas-Bocardo Fernanda , Abdurahman Abdulwahab , Alcalá-Briseño Ricardo I. , Garrett Karen A. , Goss Erica M. , Ngundo George , Kreuze Jan , Atieno Elly , Munguti Florence
Published: May 2022

Bacterial wilt, caused by the Ralstonia solanacearum species complex (RSSC), is the most destructive potato disease in Kenya. Studies were conducted to (i) determine the molecular diversity of RSSC strains associated with bacterial wilt of potato in Kenya, (ii) generate an RSSC distribution map for epidemiological inference, and (iii) determine whether phylotype II sequevar 1 strains exhibit epidemic clonality. Surveys were conducted in 2018 and 2019, in which tubers from wilting potato plants and stem samples of potential alternative hosts were collected for pathogen isolation. The pathogen was phylotyped by multiplex PCR and 536 RSSC strains typed at a sequevar level. Two RSSC phylotypes were identified, phylotype II (98.4%, n = 506 [sequevar 1 ( n = 505) and sequevar 2 ( n = 1)]) and phylotype I (1.6%, n = 30 [sequevar 13 ( n = 9) and a new sequevar ( n = 21)]). The phylotype II sequevar 1 strains were haplotyped using multilocus tandem repeat sequence typing (TRST) schemes. The TRST scheme identified 51 TRST profiles within the phylotype II sequevar 1 strains with a modest diversity index (HGDI = 0.87), confirming the epidemic clonality of RSSC phylotype II sequevar 1 strains in Kenya. A minimum spanning tree and mapping of the TRST profiles revealed that TRST27 ‘8-5-12-7-5’ is the primary founder of the clonal complex of RSSC phylotype II sequevar 1 and is widely distributed via latently infected seed tubers.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Implicit Racial Bias in Pediatric Orthopaedic Surgery
Authors: Guzek Ryan , Goodbody Christine M. , Jia Lori , Sabatini Coleen S. , Sankar Wudbhav N. , Williams Brendan A. , Shah Apurva S.
Published: May 2022

Introduction:

Racial and ethnic minority patients continue to experience disparities in health care. It is important to understand provider-level factors that may contribute to these inequities. This study aims to evaluate the presence of implicit racial bias among pediatric orthopaedic surgeons and determine the relationship between bias and clinical decision making.

Methods:

A web-based survey was distributed to 415 pediatric orthopaedic surgeons. One section measured for potential implicit racial bias using a child-race implicit association test (IAT). IAT scores were compared with US physicians and the US general population using publicly available data. Another section consisted of clinical vignettes with associated questions. For each vignette, surgeons were randomly assigned a single race-version, White or Black. Vignette questions were grouped into an opioid recommendation, management decision, or patient perception category for analysis based on subject tested. Vignette answers from surgeons with IAT scores that were concordant with their randomized vignette race-version (ie, surgeon with pro-White score assigned White vignette version) were compared with those that were discordant.

Results:

IAT results were obtained from 119 surveyed surgeons (29% response rate). Overall, respondents showed a minor pro-White implicit bias (P<0.001). Implicit bias of any strength toward either race was present among 103/119 (87%) surgeons. The proportion of pediatric orthopaedic surgeons with a strong pro-White implicit bias (29%) was greater than that of US physicians overall (21%, P=0.032) and the US general population (19%, P=0.004). No differences were found in overall opioid recommendations, management decisions, or patient perceptions between concordant and discordant groups.

Conclusion:

Most of the pediatric orthopaedic surgeons surveyed demonstrated implicit racial bias on IAT testing, with a large proportion demonstrating strong pro-White bias. Despite an association between implicit bias and clinical decision making in the literature, this study observed no evidence that implicit racial bias affected the management of pediatric fractures.

Level of Evidence:

Level IV.
Normative Values for Adolescent Quality of Life in Plastic Surgery: A Longitudinal, Cohort Study
Authors: Nuzzi Laura C. , Firriolo Joseph M. , McNamara Catherine T. , Malloy Shannon M. , Massey Gabrielle G. , DiVasta Amy D. , Labow Brian I.
Published: May 2022

Background:

Adolescence is a challenging time, and an increasing number of young people are seeking plastic surgery. With the rise of health-related quality of life studies in plastic surgery, it is critical to understand the natural variation and changes in health-related quality of life for this population.

Methods:

In this longitudinal, cohort study validated surveys were administered to cisgender participants aged 12–21 years: Short-Form 36v2, Rosenberg Self-Esteem Scale, Breast-Related Symptoms Questionnaire, and Eating-Attitudes Test-26. Surveys were administered at baseline and up to 9 years follow-up. At the time of enrollment, participants were in a current state of good health with no considerable past or current medical, surgical, or psychological history.

Results:

A total of 149 female and 75 male participants were included, with a median (interquartile range) baseline age of 16.0 (4.4) years and follow-up time of 3.3 (4.1) years. Over the study period, girls who were not overweight or obese experienced significant declines in five SF-36 domains (general health, vitality, social functioning, role-emotional, and mental health) and on the Rosenberg Self-Esteem Scale, Breast-Related Symptoms Questionnaire, and Eating-Attitudes Test-26 (P < 0.05). In contrast, boys’ and overweight/obese girls’ health-related quality of life largely remained stable (P > 0.05).

Conclusions:

Adolescence is a challenging time, on which plastic surgery-related concerns are superimposed. Our findings suggest that girls may be more at risk for developing psychosocial deficits that worsen over adolescence and young adulthood. This observation is critical for the interpretation and contextualization of health-related quality of life in adolescent plastic surgery patients.
A Cost-Benefit Analysis of Osseointegrated Prostheses for Lower Limb Amputees in the US Health Care System
Authors: Black Grant G. , Jung Wooram , Wu Xian , Rozbruch S. Robert , Otterburn David M.
Published: May 2022

Background

Patients with transfemoral and transtibial amputations generally rely on socket-suspended (SS) prostheses for ambulation. The use of these aids can be complicated by poor fit, leading to tissue damage, pain at the socket-limb interface, and inability to ambulate. Osseointegrated implants (OIs) directly anchor a prosthesis to the patient’s residual limb, eliminating these issues. However, they require customized components and additional surgeries. The purpose of this study was to conduct the first cost–benefit analysis of OI prostheses compared to SS prostheses for lower limb amputees in the United States.

Methods

A retrospective chart review was performed on all patients who received unilateral lower limb OI prostheses at our institution. Costs were calculated in a bottom-up approach using Current Procedural Terminology codes. Utilities and SS prosthesis costs were derived from previous studies. A Monte Carlo model was used to project costs and lifetime quality-adjusted life years for OI and SS prostheses, and the incremental cost-effectiveness ratio (ICER) of OI compared SS prostheses was determined.

Results

Twenty-five patients (12 female) were included in the study. The mean follow-up was 17 months postimplantation. The average cost of OI surgery was $54,463. Twenty percent of patients required preimplantation soft tissue revision surgery ($49,191). Complication rates per year and average costs were as follows: soft tissue infection (29%, $435), bone/implant infection (11%, $11,721), neuroma development (14%, $14,659), and mechanical failure (17%, $46,513). The ICER was $44,660. A cost-effectiveness acceptability curve demonstrated that OI was favored over SS in 78% of cases at a willingness-to-pay of $100,000 per quality-adjusted life year. In a 1-way sensitivity analysis, the ICER was most sensitive to the mechanical failure rate, mechanical failure cost, and prior SS prosthesis costs.

Conclusions

The model shows that OI prostheses provide a higher quality of life at affordable costs when compared to poorly tolerated SS prostheses in patients with lower limb amputations in the United States. The cost-effectiveness is largely determined by the patient's previous SS prosthesis costs and is limited by the frequency and costs of OI mechanical failure. More research must be done to understand the long-term benefits and risks of OI prostheses.
Committee on Surgical Combat Casualty Care position statement on the use of single surgeon teams and invited commentaries
Authors: Gurney Jennifer M. , Jensen Shane D. , Gavitt Brian J. , Edson Theodore D. , Brown Shaun R. , Cunningham Cord W. , Drew Brendon G. , Eckert Matthew J. , Hall Andrew B. , Holcomb John B. , Knipp Brian S. , Lesperance Richard N. , Polk Travis M. , Schreiber Martin A. , Tadlock Matthew D. , Shackelford Stacy A.
Published: May 2022

BACKGROUND

Over the last 20 years of war, there has been an operational need for far forward surgical teams near the point of injury. Over time, the medical footprint of these teams has decreased and the utilization of mobile single surgeon teams (SSTs) by the Services has increased. The increased use of SSTs is because of a tactical mobility requirement and not because of proven noninferiority of clinical outcomes. Through an iterative process, the Committee on Surgical Combat Casualty Care (CoSCCC) reviewed the utilization of SSTs and developed an expert-opinion consensus statement addressing the risks of SST utilization and proposed mitigation strategies.

METHODS

A small triservice working group of surgeons with deployment experience, to include SST deployments, developed a statement regarding the risks and benefits of SST utilization. The draft statement was reviewed by a working group at the CoSCCC meeting November 2021 and further refined. This was followed by an extensive iterative review process, which was conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. The final draft was voted on by the entire CoSCCC membership. To inform the civilian trauma community, commentaries were solicited from civilian trauma leaders to help put this practice into context and to further the discussion in both military and civilian trauma communities.

RESULTS

After multiple revisions, the SST statement was finalized in January 2022 and distributed to the CoSCCC membership for a vote. Of 42 voting members, there were three nonconcur votes. The SST statement underwent further revisions to address CoSCCC voting membership comments. Statement commentaries from the President of the American Association for the Surgery for Trauma, the chair of the Committee on Trauma, the Medical Director of the Military Health System Strategic Partnership with the American College of Surgeons and a recently retired military surgeon we included to put this military relevant statement into a civilian context and further delineate the risks and benefits of including the trauma care paradigm in the Department of Defense (DoD) deployed trauma system.

CONCLUSION

The use of SSTs has a role in the operational environment; however, operational commanders must understand the tradeoff between tactical mobility and clinical capabilities. As SST tactical mobility increases, the ability of teams to care for multiple casualty incidents or provide sustained clinical operations decreases. The SST position statement is a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields.
Lentilactobacillus rapi subsp. dabitei subsp. nov., a lactic acid bacterium isolated from naturally fermented dairy product
Authors: Li Yu , Li Weicheng , Luo Rui , Sakandar Hafiz Arbab , Zhang Heping , Liu Wenjun
Published: May 2022

Two lactic acid bacterial strains (IMAU80584T and IMAU92037) were isolated from naturally fermented dairy products (kurut and yoghurt) in China and Russia. Based on sequence analysis of the 16S rRNA gene it was revealed that these strains belonged to

Lentilactobacillus rapi

. However, phylogenetic tree analyses of two housekeeping genes, rpoA (encoding RNA polymerase alpha subunit) and pheS (encoding phenylalanyl-tRNA synthase alpha subunit), and 88 core genes, indicated the two strains were separated into an independent monophyletic branch from

L. rapi

DSM 19907T, forming an infra-specific subgroup. The average nucleotide identity and digital DNA–DNA hybridization values between IMAU80584T and

L. rapi

DSM 19907T were 93.1 and 52.8 %, respectively. Strains IMAU80584T and IMAU92037 are distinguished from

L. rapi

DSM 19907T because they have different polar lipids and fatty acids. The novel subgroup strains could not ferment gluconate potassium. The DNA G+C content of strain IMAU80584T was 42.3 mol%. The major cellular fatty acids were C16 : 0, C18 : 1
 ω9t and summed feature 5 (C18 : 0 ante and/or C18 : 2
 ω6c and/or C18 : 2
 ω9c). Therefore, based on the results of polyphasic taxonomic analysis, IMAU80584T and IMAU92037 could be considered as a novel subspecies in the species

L. rapi

with the proposed name

Lentilactobacillus rapi

subsp. dabitei subsp. nov. The type strain is IMAU80584T (=GDMCC 1.2566T=JCM 34647T).
Predicting Oncogene Mutations of Lung Cancer Using Deep Learning and Histopathologic Features on Whole-Slide Images
Authors: Tomita Naofumi , Tafe Laura J. , Suriawinata Arief A. , Tsongalis Gregory J. , Nasir-Moin Mustafa , Dragnev Konstantin , Hassanpour Saeed
Published: May 2022

Lung cancer is a leading cause of death in both men and women globally. The recent development of tumor molecular profiling has opened opportunities for targeted therapies for lung adenocarcinoma (LUAD) patients. However, the lack of access to molecular profiling or cost and turnaround time associated with it could hinder oncologists’ willingness to order frequent molecular tests, limiting potential benefits from precision medicine. In this study, we developed a weakly supervised deep learning model for predicting somatic mutations of LUAD patients based on formalin-fixed paraffin-embedded (FFPE) whole-slide images (WSIs) using LUAD subtypes-related histological features and recent advances in computer vision. Our study was performed on a total of 747 hematoxylin and eosin (H&E) stained FFPE LUAD WSIs and the genetic mutation data of 232 patients who were treated at Dartmouth-Hitchcock Medical Center (DHMC). We developed our convolutional neural network-based models on 172 training cases and tested on 60 independent cases to analyze whole slides and predict five major genetic mutations, i.e., BRAF, EGFR, KRAS, STK11, and TP53. We additionally used 111 cases from the LUAD dataset of the CPTAC-3 study for external validation. Our model achieved an AUROC of 0.799 (95% CI: 0.686-0.904) and 0.686 (95% CI: 0.620-0.752) for predicting EGFR genetic mutations on the DHMC and CPTAC-3 test sets, respectively. Predicting TP53 genetic mutations also showed promising outcomes. Our results demonstrated that H&E stained FFPE LUAD whole slides could be utilized to predict oncogene mutations, such as EGFR, indicating that somatic mutations could present subtle morphological characteristics in histology slides, where deep learning-based feature extractors can learn such latent information.
Development and Validation of Audio-based Guided Imagery and Progressive Muscle Relaxation Tools for Functional Bloating
Authors: Tee Vincent , Kuan Garry , Kueh Yee Cheng , Abdullah Nurzulaikha , Sabran Kamal , Tagiling Nashrulhaq , Sahran Nur-Fazimah , Alang Tengku Ahmad Iskandar Tengku , Lee Yeong Yeh
Published: May 2022

Mind-body techniques, including Guided Imagery (GI) or Progressive Muscle Relaxation (PMR), may effectively manage bloating. The current study aimed to develop and validate (psychometric and psychological responses) audio-based GI and PMR techniques for bloating. Audio scripts were first developed from literature reviews and in-depth interviews of participants with bloating diagnosed based on the Rome IV criteria. Scripts were validated using psychometric (content & face validity index) and physiological approaches (brain event-related potentials & heart rate variability). 45/63 participants completed the in-depth interview, and ‘balloon’ emerged as the synonymous imagery description for bloating, of which inflation correlated with a painful sensation. The final tools consisted of narrated audio scripts in the background of a validated choice of music. Overall, content and face validity index for PMR and GI ranged from 0.92 - 1.00. For ERP and HRV, 17/20 participants were analysed. For ERP, there was significant difference between GI and PMR for alpha waves (p=0.029), delta waves (p=0.029) and between PMR and control for delta waves (p=0.014). For HRV, both GI and PMR exhibited similar autonomic responses over controls (overall p<0.05). The newly developed GI and PMR audio-based tools have been validated using psychometric and physiological approaches.
Pregnant women’s knowledge of obstetrical danger signs: A cross-sectional survey in Kigali, Rwanda
Authors: Uwiringiyimana Emmanuel , Manirambona Emery , Byiringiro Samuel , Nsanzimana Albert , Uhawenayo Neophyte , Ufitinema Pacifique , bayizere Janviere , Moreland Patricia J. , Meharry Pamela , Ntasumbumuyange Diomede
Published: May 2022

BACKGROUND

Maternal mortality remains critically high worldwide, particularly in sub-Saharan Africa. The leading causes of maternal death in Rwanda include postpartum hemorrhage and obstructed labor. Maternal recognition of obstetrical danger signs is critical for timely access to emergency care, in order to reduce maternal mortality.

OBJECTIVE

To assess the knowledge of obstetrical danger signs among pregnant women attending antenatal care in Kigali, Rwanda.

METHODS

A cross-sectional study was conducted between September and December 2018 at five health centers and one district hospital in Kigali, Rwanda. Pregnant women attending antenatal care (ANC) services completed a structured questionnaire. Data were analyzed using descriptive statistics.

RESULTS

A total of 382 pregnant women were included in the study. The majority of women (67.8%) were aged 23-35 years, and 44.5% had completed secondary education. Almost half (43.2%) reported traveling more than 30 minutes to reach the health facility; only 23.3% were within 15 minutes of the health facility. Over half (57%) reported attending three or more ANC visits during pregnancy. The majority (85.6%) knew at least one obstetrical danger sign, with nearly half (46.1%) obtaining knowledge of danger signs from midwives and nurses.

CONCLUSION

Knowledgeability was significantly associated with the parity and number of ANC visits, though CHW was also a good source of information for pregnant women. We encourage a systematically designed curriculum to teach mothers during their follow-up visits for ANC.
Generating variability from motor primitives during infant locomotor development
Authors: Hinnekens Elodie , Barbu-Roth Marianne , Do Manh-Cuong , Berret Bastien , Teulier Caroline
Published: May 2022

Motor variability is a fundamental feature of developing systems allowing motor exploration and learning. In human infants, leg movements involve a small number of basic coordination patterns called locomotor primitives, but whether and when motor variability could emerge from these primitives remains unknown. Here we longitudinally followed 10 neonates (∼4 days old) until walking onset (∼14 months old) and recorded the activity of their leg muscles during locomotor or rhythmic movements. Using unsupervised machine learning, we show that the structure of trial-to-trial variability changes during early development. In the neonatal period, infants own a minimal number of motor primitives but generate a maximal motor variability across trials thanks to variable activations of these primitives. A few months later, toddlers generate significantly less variability despite the existence of more primitives, due to more regularity within their activation. These results suggest that human neonates initiate motor exploration as soon as birth by variably activating a few basic locomotor primitives that later fraction and become more consistently activated by the motor system.
Soil microbe-induced plant resistance alters aphid inter-genotypic competition leading to rapid evolution with consequences for plant growth and aphid abundance
Authors: Xi Xinqiang , Zytynska Sharon E.
Published: May 2022

Plants and insect herbivores are two of the most diverse multicellular groups in the world, and both are strongly influenced by interactions with the belowground soil microbiome. Effects of reciprocal rapid evolution on ecological interactions between herbivores and plants have been repeatedly demonstrated, but it is unknown if (and how) the soil microbiome could mediate these eco-evolutionary processes.

We tested the role of a plant-beneficial soil bacterium (Acidovorax radicis) in altering eco-evolutionary interactions between sap-feeding aphid herbivores (Sitobion avenae) feeding on barley (Hordeum vulgare). We reared two aphid genotypes separately or together on three barley varieties that were inoculated with or without A. radicis bacteria. In the first experiment we counted the aphid number and plant biomass after 7, 14 and 21 days of aphid growth, while in a second experiment we counted and removed offspring every 1-2 days to assess aphid longevity and fecundity.

Results showed that A. radicis increased plant growth and suppressed aphids of both genotypes. The strength of effect was dependent on aphid genotype and barley variety, while the direction of effect was altered by aphid population mixture. Fescue aphids experienced increased growth when they were sharing the plant with Sickte aphids on inoculated plants; this increase was not seen in the control plants without A. radicis and was only apparent after 14 days of aphid population growth.

Plant inoculation with A. radicis reduced aphid survival (reduced number of reproductive days) and fecundity (reduced daily reproductive output for surviving aphids). In the second experiment, when density was controlled, Fescue aphids did not experience increased reproduction in mixed populations, suggesting this is a density-dependent effect. Using Lotka-Volterra modelling, we demonstrated that A. radicis inoculation decreased aphid population stability as it increased inter-genotype competition but decreased the intra-genotype competition (likely through reduced population density).

Our work demonstrates the important role that plant-associated microbiomes can have in mediating eco-evolutionary interactions between herbivores and host plants.
Identification of viral dose and administration time in simulated phage therapy occurrences
Authors: Plunder Steffen , Lauer Ulrich M. , Helling Thomas , Venturelli Sascha , Marongiu Luigi
Published: May 2022

The rise in multidrug-resistant bacteria has sprung a renewed interest in applying phages as antibacterial, a procedure Western practitioners eventually abandoned due to several downfalls, including poor understanding of the dynamics between phages and bacteria. A successful phage therapy needs to account for the loss of infective virions and the multiplication of the hosts. The parameters critical inoculation size (VF) and failure threshold time (TF) have been introduced to assure that the viral dose (vϕ) and administration time (tϕ) would lead to an effective treatment. The problem with the definition of VF and TF is that they are non-linear equations with two unknowns; thus, their solution is cumbersome and not unique. The current study used machine learning in the form of a decision tree algorithm to determine ranges for the viral dose and administration times required to achieve an effective phage therapy. Within these ranges, a Pareto optimal solution of a multi-criterial optimization problem (MCOP) provides values leading to effective treatment. The algorithm was tested on a series of microbial consortia that described allochthonous invasions (the outgrowing of a species at high cell density by another species initially present at low concentration) to inhibit the growth of the invading species. The present study also introduced the concept of ‘mediated phage therapy’, where targeting a booster bacteria might decrease the virulence of a pathogen immune to phagial infection. The results demonstrated that the MCOP could provide pairs of vϕ and tϕ that could effectively wipe out the bacterial target from the considered micro-environment. In summary, the present work introduced a novel method for investigating the phage/bacteria interaction that could help increase the effectiveness of phage therapy.

Author summary

Phage therapy is a treatment that can help fight infections with bacteria resistant to antibiotics. However, several phage therapy application have failed, possibly because phages were administered at the wrong time or in insufficient amounts. The present study implemented a machine learning protocol to correctly calculate the administration time and viral load to obtain effective phage therapy. Four simulated microbial consortia, including one case where the pathogen was not directly a phage’s host, were employed to prove the procedure’s concept. The results demonstrated that the procedure is suitable to help the microbiologists to instantiate an effective phage therapy and clear infections.
Acoustic cues and season affect mobbing responses in a bird community
Authors: Salis Ambre , Léna Jean-Paul , Lengagne Thierry
Published: May 2022

Heterospecific communication is common for birds when mobbing a predator. However, joining the mob should depend on the number of callers already enrolled, as larger mobs imply lower individual risks for the newcomer. In addition, some ‘community informant’ species seem more reliable regarding the information transferred in mobbing calls. Birds should therefore rely on both the number of callers and the species identity of the caller(s) when mobbing. In the present study, we tested the potential interaction between two acoustic cues. In a playback experiment, we modified the number of callers (through an increased number of calling individuals correlated to an increased duty cycle) and the emitter species (crested tits versus coal tits). Overall, we found that soundtracks with three callers triggered more mobbing than soundtracks with one caller and that soundtracks with coal tits’ calls triggered more mobbing than soundtracks with crested tits’ calls. Our results therefore support the hypothesis that birds consider both the species and the number of callers when joining a mobbing chorus in winter. Finally, we replicated the experiment in spring and did not record the same responses from the bird community. Indeed, only soundtracks with three coal tits triggered a mobbing response, suggesting therefore that the seasonal context can affect the results of studies on heterospecific communication. The potential mechanisms implicated in the varying responses to different acoustic cues and different seasons are discussed and should deserve further investigations.
Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism
Authors: Khanh Le-Trilling Vu Thuy , Banchenko Sofia , Paydar Darius , Leipe Pia Madeleine , Binting Lukas , Lauer Simon , Graziadei Andrea , Gotthold Christine , Bürger Jörg , Bracht Thilo , Sitek Barbara , Lebbink Robert Jan , Malyshkina Anna , Mielke Thorsten , Rappsilber Juri , Spahn Christian M. T. , Voigt Sebastian , Trilling Mirko , Schwefel David
Published: May 2022

Human cytomegalovirus (CMV) is a highly relevant and ubiquitously distributed human pathogen. Its rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted the first global proteome profiling of rat CMV-infected cells and uncovered a pronounced loss of the transcription factor STAT2, which is crucial for interferon signalling. Deletion mutagenesis documented that STAT2 is targeted by the viral protein E27. Cellular and in vitro analyses showed that E27 exploits host-derived Cullin4-RING ubiquitin ligases (CRL4) to induce poly-ubiquitylation and proteasomal degradation of STAT2. A cryo-electron microscopic structure determination revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors called DDB1- and Cullin4-associated factors (DCAFs) to displace them from the catalytic core of CRL4. Moreover, structural analyses elucidated the mechanism of STAT2 recruitment and indicate that E27-binding additionally disturbs STAT2-dependent interferon signalling by occupying its IRF9 binding interface. For the first time, these data provide structural insights into cytomegalovirus-encoded interferon antagonism and establish an atomic model for STAT2 counteraction by CRL4 misappropriation with important implications for viral immune evasion.
The modulation of acute stress on Model-Free and Model-Based reinforcement learning in Gambling Disorder
Authors: Wyckmans Florent , Banerjee Nilosmita , Saeremans Mélanie , Ross Otto , Kornreich Charles , Vanderijst Laetitia , Gruson Damien , Carbone Vincenzo , Bechara Antoine , Buchanan Tony , Noël Xavier
Published: May 2022

Background and aims

Experiencing acute stress is common in behavioral addictions such as gambling disorder. Additionally, like most substance-induced addictions, aberrant decision-making wherein a reactive habit-induced response (conceptualized as a Model-free [MF] in reinforcement learning) suppresses a flexible goal-directed response (conceptualized as a Model-based [MB]) is also common in gambling disorder. In the current study we investigated the influence of acute stress on the balance between habitual response and the goal-directed system.

Methods

A sample of N = 116 pathological gamblers (PG) and healthy controls (HC) performed an acute stress task – the Socially Evaluated Cold pressure task (SECPT) – or a control task. Self-reported stress and salivary cortisol were collected as measures of acute stress. Following the SECPT, participants performed the Two-Step Markov Task to account for the relative contribution of MB and MF strategies. Additionally, verbal working-memory and IQ measures were collected to account for their mediating effects on the orchestration between MB/MF and the impact of stress.

Results

Both groups had comparable baseline and stress-induced cortisol response to the SECPT. Non-stressed PG displayed lower MB learning than HC. MANOVA and regression analyses showed a deleterious effect of stress-induced cortisol response on the orchestration between MB and MF learning in HC but not in PG. Neither working memory nor IQ mediated these effects.

Discussion and Conclusions

Despite normal cortisol response to stress, we found an abnormal pattern of modulation of stress on the orchestration between MB and MF learning among PG.
Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
Authors: Zhou Jeff Jiajing , Cho Jin Sun , Han Han , Blitz Ira L. , Wang Wenqi , Cho Ken W.Y.
Published: May 2022

Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.
GliaMorph: A modular image analysis toolkit to quantify Müller glial cell morphology
Authors: Kugler Elisabeth , Bravo Isabel , Durmishi Xhuljana , Marcotti Stefania , Beqiri Sara , Carrington Alicia , Stramer Brian M. , Mattar Pierre , MacDonald Ryan B.
Published: May 2022

Cell morphology is critical for all cell functions. This is particularly true for glial cells as they rely on their complex shape to contact and support neurons. However, methods to quantify complex glial cell shape accurately and reproducibly are lacking. To address this gap in quantification approaches, we developed an analysis pipeline called “GliaMorph”. GliaMorph is a modular image analysis toolkit developed to perform (i) image pre-processing, (ii) semi-automatic region-of-interest (ROI) selection, (iii) apicobasal texture analysis, (iv) glia segmentation, and (v) cell feature quantification. Müller Glia (MG) are the principal retinal glial cell type with a stereotypic shape linked to their maturation and physiological status. We here characterized MG on three levels, including (a) global image-level, (b) apicobasal texture, and (c) apicobasal vertical-to-horizontal alignment. Using GliaMorph, we show structural changes occurring in the developing retina. Additionally, we study the loss of cadherin2 in the zebrafish retina, as well as a glaucoma mouse disease model. The GliaMorph toolkit enables an in-depth understanding of MG morphology in the developing and diseased retina.

Graphical Abstract

Highlights

Glial morphology is complex, making it challenging to accurately quantify 3D cell shape.

We developed the GliaMorph toolkit for image pre-processing, glial segmentation, and quantification of Müller glial cells.

Müller glia elaborate their morphology and rearrange subcellular features during embryonic development.

GliaMorph accurately identifies subcellular changes in models with disrupted glia cells, including zebrafish cadherin2 loss of function and a mouse glaucoma model.
Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
Authors: Mello Ashley , Ngodup Tenzin , Lee Yusoo , Donahue Katelyn L. , Li Jinju , Rao Arvind , Carpenter Eileen S. , Crawford Howard C. , di Magliano Marina Pasca , Lee Kyoung Eun
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibroinflammatory stroma and often experiences conditions of insufficient oxygen availability, or hypoxia. Cancer-associated fibroblasts (CAF) are a predominant and heterogeneous population of stromal cells within the pancreatic tumor microenvironment. Here, we uncover a previously unrecognized role for hypoxia in driving an inflammatory phenotype in PDAC CAFs. We identify hypoxia as a strong inducer of tumor IL1α expression, which is required for inflammatory CAF (iCAF) formation. Notably, iCAFs preferentially reside in hypoxic regions of PDAC. Our data implicate hypoxia as a critical regulator of CAF heterogeneity in PDAC.
The microtubule minus end-binding protein CAMSAP2 does not regulate microtubule dynamics in primary pancreatic β-cells but facilitates insulin secretion
Authors: Ho Kung-Hsien , Osipovich Anna B. , Jayathilake Anissa , Magnuson Mark A. , Gu Guoqiang , Kaverina Irina
Published: May 2022

Glucose stimulation induces the remodeling of microtubules in Islet β-cells to potentiate glucose-stimulated insulin secretion. CAMSAP2 is a microtubule minus-end binding protein and is reported to stabilize and position microtubules in several non-β-cells, such as human retinal pigment epithelium cells. In immortalized insulinoma MIN6 cells, CAMSAP2 binds to and forms short stretches at microtubule minus ends in the cytoplasm, which is consistent with the reported subcellular localization and functions of CAMSAP2 in non-β-cells. Surprisingly, we found that CAMSAP2 expressed in primary islet β-cells does not form short stretches in the cytoplasm, but instead is localized to the Golgi apparatus. This novel localization is specific to β-but not α-cells in islets and it is independent of MT-binding. Knockdown of CAMSAP2 by shRNA impairs Golgi-ER trafficking, reduces total insulin content, and attenuates GSIS without affecting the MT dynamics or releasability of insulin granules in islet β-cells. Corresponding to these results, we found that primary islets and MIN6 cells express different CAMSAP2 isoforms. We propose that primary islet β cells use a novel CAMSAP2 isoform for a MT-independent non-canonical function, which is to promote Golgi-ER trafficking that supports efficient production of insulin secretory granules.
Novel ACE2 nanoparticles universally block SARS-CoV-2 variants in the human respiratory tract
Authors: Sauvanet Cécile , Lemos Moara , Bezault Armel , de Francisco Borja Rodríguez , Chan Michael CW , Hui Kenrie PY , Ng Ka-chun , Nicholls John M , Volkmann Niels , Hanein Dorit
Published: May 2022

The continual evolution of SARS-CoV-2 has challenged the efficacy of many COVID19 vaccines and treatment options. One strategy that evades viral escape is using the entry receptor, human Angiotensin-Converting Enzyme 2 (hACE2). Soluble hACE2 receptor domains show potential as decoys but genetic modifications are necessary to provide sufficient efficacy. However, these engineered constructs are potentially susceptible to viral escape. We combined native hACE2 with viral vectors to form nanoparticles presenting hACE2 analogous to human cells. Cell-based viral infection assays and cryogenic in-situ tomography show that hACE2 nanoparticles sequester viruses through aggregation, efficiently blocking entry of SARS-CoV-2 and its variants in model cell systems and human respiratory tract explants using native hACE2. Thus, we show that hACE2 nanoparticles have high potential as pan-variant COVID19 therapeutics.
Differential regulation of mRNA stability modulates transcriptional memory and facilitates environmental adaptation
Authors: Li Bingnan , Zeis Patrice , Alekseenko Alisa , Lin Gen , Tekkedil Manu M , Steinmetz Lars M. , Pelechano Vicent
Published: May 2022

Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Factors related to chromatin organization and activation of transcription have been shown to play a role in the faster response of those cells previously exposed to a stimulus (primed). However, the contribution of post-transcriptional regulation is not yet explored. Here, combining flow cytometry and high throughput sequencing, we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose nutrition sources. In addition to the well-known chromatin factors modulating transcriptional memory, we find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. We perform a genome-wide characterisation of this process and show that changes in nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that in addition to nuclear mRNA degradation, differences in cytoplasmic mRNA decay also modulate transcriptional memory and contribute to faster gene expression remodelling in primed cells. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.
Probabilistic Tracking of U-fibers on the Superficial White Matter Surface
Authors: Nie Xinyu , Shi Yonggang
Published: May 2022

The short association fibers or U-fibers connect two neighboring gyri and travel in the superficial white matter (SWM) beneath the cortical layer. These U-fibers are essential for the understanding of neurodevelopment and neurodegeneration. However, the complex structures and the high curvature of the U-fibers lead to erroneous streamlines reconstruction of the traditional tractography since the volume-based tractography cannot use the biological characteristic of U-fibers that they tightly beneath the cortical layer. In this work, we proposed a surface-based framework for probabilistic tracking of the U-fibers on the triangular mesh of the SWM. We develop a novel approach to project the fiber orientation distributions (FODs) data onto the tangent space of the SWM surface. With the projected FODs, an advanced probabilistic tracking technique, which regularizes the streamlines based on the intrinsic geometry of the surface, is developed to reconstruct the highly bent U-fibers on the SWM surface. In the experiment, we demonstrate our method based on the high-resolution diffusion imaging data from the Human Connectome Project (HCP). We quantitatively compare the proposed method with state-of-the-art volume-based tractography from MRTrix and another surface-based tractography on the U-fibers of the central sulcus. Moreover, we show the reconstructed U-fibers on the parietal lobe and frontal lobe. The results show that our method outperforms the other two methods and successfully reconstructs the U-fibers on the cortical regions with high intersubject variability.
Promiscuous feeding across multiple honey bee hosts amplifies the vectorial capacity ofVarroa destructor
Authors: Lamas Zachary S. , Solmaz Serhat , Ryabov Eugene V. , Mowery Joseph , Heermann Matthew , Sonenshine Daniel , Evans Jay D. , Hawthorne David J.
Published: May 2022

Varroadestructor is a cosmopolitan pest and leading cause of colony loss of the European honey bee. Historically described as a competent vector of honey bee viruses, this arthropod vector is cause for the global pandemic of Deformed wing virus, now endemic in honeybee populations. Our work shows viral spread is driven byVarroaactively switching from one adult bee to another as they feed. Assays using fluorescent microspheres were used to show the movement of fluids in both directions between host and vector whenVarroafeed. Therefore,Varroacould be in either an infectious or naïve state dependent upon the disease status of their host. We tested this and confirm that the relative risk of aVarroafeeding was dependent on the infectiousness of their previous host.Varroaexhibit remarkable heterogeneity in their host switching behavior, with someVarroaswitching infrequently while others switch at least daily. As a result, relatively few of the most activeVarroaparasitize the majority of bees. This multiple feeding behavior has analogs in vectorial capacity models of other systems, where promiscuous feeding by individual vectors is a leading driver of vectorial capacity. We propose that the honeybee-Varroarelationship offers a unique opportunity to apply principles of vectorial capacity to a social organism, as virus transmission is both vectored and occurs through multiple host-to-host routes common to a crowded society.