bluuebunny/crossref_metadata_2025 huggingface dataset:
Unearthing New Learning Opportunities: Adapting and Innovating through the “Antibiotics Under Our Feet” Citizen Science Project in Scotland during COVID-19
Authors: Cornwell Rebecca Mary , Ross Kirsty , Gibeily Caius , Guthrie Isobel , Li Pak Hei , Seeley Laurence Taylor , Kong Yaxuan , True Ava , Barnes Arun , Nimmo Emma , Len Gloriya , Oprea Ioana , Lin Boyang , Sasi Aswin , Chu Vicky , Davidson Chloe , Ulasavets Daniil , Renouf-Bilanski Grace , Dmitrieva Maria , Leung Yana , Ye Ziying , Brown Sasha , Vaidya Meghna , Hynes Jenna , Mullner Catherine , Agarwal Priyansha , Johnston Paul , Thorley Charlotte , Melo Czekster Clarissa
Published: March 2024

“Antibiotics under our feet” is a Scottish citizen science project that aimed to raise science capital in primary school learners and their teachers through measurement of microbial diversity in urban soil samples in the search for novel antimicrobial compounds. Resistance to antibiotics is rising, posing a global threat to human health. Furthermore, science, technology, engineering and mathematics (STEM) skills are in crisis, jeopardising our capacity to mobilise as a society to fight antimicrobial resistance (AMR). Originally conceived as a response to the AMR and STEM emergencies, our project was hit by the unprecedented challenge of engaging with schools during the COVID-19 pandemic. We describe how we adapted our project to enable remote participation from primary schools and youth groups, utilising COVID-19 response initiatives as opportunities for multi-level co-creation of resources with learners in primary, secondary, and higher education. We produced portable kit boxes for soil sample collection with learning activities and videos linked to the Scottish Curriculum for Excellence. We also addressed glaring project specific content gaps relating to microbiology on English and Simple English Wikipedia. Our hybrid model of working extended our geographical reach and broadened inclusion. We present here the inception, implementation, digital resource outputs, and evaluation of pedagogical aspects of “Antibiotics under our feet”. Our strategies and insights are applicable post-pandemic for educators to develop STEM skills using soil, microbes, and antibiotics as a theme.
Phylometagenomics of cycad coralloid roots reveals shared symbiotic signals
Authors: Bustos-Diaz Edder D. , Cruz-Perez Arely , Garfias-Gallegos Diego , D'Agostino Paul M. , Gehringer Michelle M. , Cibrian-Jaramillo Angelica , Barona-Gomez Francisco
Published: March 2024

Cycads are known to host symbiotic cyanobacteria, including Nostocales species, as well as other sympatric bacterial taxa within their specialized coralloid roots. Yet, it is unknown if these bacteria share a phylogenetic origin and/or common genomic functions that allow them to engage in facultative symbiosis with cycad roots. To address this, we obtained metagenomic sequences from 39 coralloid roots sampled from diverse cycad species and origins in Australia and Mexico. Culture-independent shotgun metagenomic sequencing was used to validate sub-community co-cultures as an efficient approach for functional and taxonomic analysis. Our metanalysis shows a host-independent microbiome core consisting of seven bacterial orders with high species diversity within the identified taxa. Moreover, we recovered 43 cyanobacterial metagenome-assembled genomes, and in addition to Nostoc spp., symbiotic cyanobacteria of the genus Aulosira were identified for the first time. Using this robust dataset, we used phylometagenomic analysis to reveal three monophyletic cyanobiont clades, two host-generalist and one cycad-specific that includes Aulosira spp. Although the symbiotic clades have independently arisen, they are enriched in certain functional genes, such as those related to secondary metabolism. Furthermore, the taxonomic composition of associated sympatric bacterial taxa remained constant. Our research quadruples the number of cycad cyanobiont genomes and provides a robust framework to decipher cyanobacterial symbioses, with the potential of improving our understanding of symbiotic communities. This study lays a solid foundation to harness cyanobionts for agriculture and bioprospection, and assist in conservation of critically endangered cycads.
Investigation of diffusion time dependence of apparent diffusion coefficient and intravoxel incoherent motion parameters in the human kidney
Authors: Stabinska Julia , Thiel Thomas Andreas , Zöllner Helge Jörn , Benkert Thomas , Wittsack Hans-Jörg , Ljimani Alexandra
Published: March 2024

Purpose

To characterize the diffusion time (Δeff) dependence of apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-related parameters in the human kidney at 3T.

Methods

Sixteen healthy volunteers underwent an MRI examination at 3T including DWI at different Δeffranging from 24.1 ms to 104.1 ms. The extended mono-exponential ADC, and IVIM models were fitted to the data for each Δeff, and medullary and cortical ADC, (pseudo-) diffusion coefficients (D* and D) and flow-related signal fraction (f) were calculated.

Results

When all the data was used for fitting, a trend toward higher ADC with increasing Δeffwas observed between 24.1 and 104.1 ms ([median and interquartile range]: 2.10 [1.94 2.26] to 2.36 [2.09 2.69] x10−3mm2/s for cortex, and 2.24 [2.10 2.36] to 2.64 [2.49 2.78] x10−3mm2/s for medulla). In contrast, no significant differences in ADC were found when only the data acquired at b-values higher than 200 s/mm2was used for fitting. When the IVIM model was applied, cortical and medullary f increased significantly (cortex: 0.24 [0.22 0.30] to 0.54 [0.43 0.63] x10−3mm2/s; medulla: 0.26 [0.23 0.38] to 0.50 [0.39 0.62] x10−3mm2/s) and cortical D (cortex: 1.66 [1.59 1.71] to 1.24 [1.10 1.47] x10−3mm2/s) and cortical D* (cortex: 9.10 [5.50 12.9] to 4.19 [3.84 5.73] x10−3mm2/s) decreased significantly between 24.1 and 104.1 ms.

Conclusion

Renal perfusion and tubular flow substantially contribute to the observed increase in ADC over a wide range of Δeffbetween 24 and 104 ms.
SRNT Health Equity Network Survey on Authentic Health Disparity/Equity Research
Authors: Addicott Merideth , Hinds Josephine , Mithi Vita , Kypriotakis George , Jacobs Wura , Martinez Sydney A. , Denlinger-Apte Rachel , Phan Lilianna , Levy Douglas E. , Osibogun Olatokunbo , Mosalpuria Kavita , Kumar Danusha Selva , Czaplicki Lauren , Tan Andy
Published: March 2024

The Society for Research on Nicotine and Tobacco (SRNT) Health Equity Network (HEN) Evaluation Subcommittee members conducted an open-ended survey regarding what should be considered “authentic” health disparity/equity (HD/E) research and how the SRNT community defines this term. Anonymous surveys were emailed to over 300 SRNT HEN members, and invitees were asked to complete the survey if they conducted HD/E research or engaged in HD/E research in some other way. A total of 26 usable survey responses were collected and qualitatively coded. Respondents were asked to describe “authentic HD/E research”, challenges in their field, and indicators of good and poor quality HD/E research. Respondents expressed that authentic HD/E research investigates disparities/inequalities in health outcomes or access to healthcare services that are specific to communities defined by a social or demographic characteristic. Challenges included lack of funding, a slow rate of recruiting minority populations, and an under-valuation of HD/E research among funders and scientific journals. Indicators of good quality HD/E research were community involvement and a social justice context. Respondents also expressed concerns that poor quality HD/E research could inadvertently harm minoritized communities. As this field grows, we feel it is necessary for experts to set standards for the appropriate conduct of HD/E research, set benchmarks for success, and voice their concerns about the potentially negative impacts of poorly conducted HD/E research.
Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance
Authors: Harrison Daniel M. , Allette Yohance M. , Zeng Yuxin , Cohen Amanda , Dahal Shishir , Choi Seongjin , Zhuo Jiachen , Hua Jun
Published: March 2024

Background/Purpose

Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE).

Methods

This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR).

Results

LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non- significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008).

Conclusion

7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.
Gender Biases In Sports Concussions: A Differential Item Functioning Analysis into NCAA Female Athlete Symptom Presentation and Validity of the SCAT3 Checklist
Authors: Edelstein Rachel , Cushing Sydney , Schmidt Karen M. , Horn John Darrell Van
Published: March 2024

Background

As a consequence of sports-related concussions, female athletes have been documented as reporting more symptoms than their male counterparts, in addition to incurring longer periods of recovery. However, the role of gender and its potential influence on symptom reporting and recovery outcomes in concussion management has not been completely explored.

Study Design

This study investigates potential differential item functioning (DIF) related to gender biases within the SCAT3 symptom severity checklist. The data was obtained from the Federal Interagency of Traumatic Brain Injury Research (FITBIR), which included information from the 2014-2017 NCAA and DoD CARE Consortium. A total of 1,258 NCAA athletes (n=473 females andn=785 males) SCAT3 Symptom Severity sub-scores were analyzed across five time points post-concussion: less than six hours post-injury, 24-48 hours post-injury, asymptomatic, unrestricted return to play, and at 6 months.

Results

During the recovery phase, women experienced more headaches, pressure in the head, and fatigue than male athletes. Overall, both male and female athletes had equivalent knowledge of concussions, and there was no significant difference in symptom-reporting ability for most items, including emotional-related symptoms. Only during the unrestricted return to play phase were group-level differences detected, with females being more likely to report more severe symptoms than males. However, upon further analysis, it was discovered females exhibit a relatively high difficulty level reporting symptom severity beyond ‘Mild’, therefore the group-level DIF may result from gender biases within the checklist.

Conclusion

The present analysis posits that Differential Item Functioning (DIF) in specific symptoms may lead to gender bias. The findings of this study reveal that female athletes tend to exhibit symptomatic behavior upon returning to play, a phenomenon consistent with prior research. However, the possible DIF may provoke biases due to unreliable reporting measures within the SCAT3 symptom severity checklist. Furthermore, explaining why recent literature reports that female athletes do not present as symptomatic upon return to play. Additional research is warranted to determine whether females genuinely experience more symptoms or whether the presence of these potential assessment gender biases obstructs the manifestation of asymptomatic recoveries.
An integrative multi-context Mendelian randomization method for identifying risk genes across human tissues
Authors: Lu Yihao , Xu Ke , Kang Bowei , Pierce Brandon L. , Yang Fan , Chen Lin S.
Published: March 2024

Mendelian randomization (MR) provides valuable assessments of the causal effect of exposure on outcome, yet the application of conventional MR methods for mapping risk genes encounters new challenges. One of the issues is the limited availability of expression quantitative trait loci (eQTLs) as instrumental variables (IVs), hampering the estimation of sparse causal effects. Additionally, the often context/tissue-specific eQTL effects challenge the MR assumption of consistent IV effects across eQTL and GWAS data. To address these challenges, we propose a multi-context multivariable integrative MR framework, mintMR, for mapping expression and molecular traits as joint exposures. It models the effects of molecular exposures across multiple tissues in each gene region, while simultaneously estimating across multiple gene regions. It uses eQTLs with consistent effects across more than one tissue type as IVs, improving IV consistency. A major innovation of mintMR involves employing multi-view learning methods to collectively model latent indicators of disease relevance across multiple tissues, molecular traits, and gene regions. The multi-view learning captures the major patterns of disease-relevance and uses these patterns to update the estimated tissue relevance probabilities. The proposed mintMR iterates between performing a multi-tissue MR for each gene region and joint learning the disease-relevant tissue probabilities across gene regions, improving the estimation of sparse effects across genes. We apply mintMR to evaluate the causal effects of gene expression and DNA methylation for 35 complex traits using multi-tissue QTLs as IVs. The proposed mintMR controls genome-wide inflation and offers new insights into disease mechanisms.
The performance of AlphaMissense to identify genes causing disease
Authors: Chen Yiheng , Butler-Laporte Guillaume , Liang Kevin Y. H. , Ilboudo Yann , Yasmeen Summaira , Sasako Takayoshi , Langenberg Claudia , Greenwood Celia M.T. , Richards J Brent
Published: March 2024

A novel algorithm, AlphaMissense, has been shown to have an improved ability to predict the pathogenicity of rare missense genetic variants. However, it is not known whether AlphaMissense improves the ability of gene-based testing to identify disease-causing genes. Using whole-exome sequencing data from the UK Biobank, we compared gene-based association analysis strategies including sets of deleterious variants: predicted loss-of-function (pLoF) variants only, pLoF plus AlphaMissense pathogenic variants, pLoF with missense variants predicted to be deleterious by any of five commonly utilized annotation methods (Missense (1/5)) or only variants predicted to be deleterious by all five methods (Missense (5/5)). We measured performance to identify 519 previously identified positive control genes, which can cause Mendelian diseases, or are the targets of successfully developed medicines. These strategies identified 850k pLoF variants and 5 million deleterious missense variants, including 22k likely pathogenic missense variants identified exclusively by AlphaMissense. The gene-based association tests found 608 significant gene associations (atP<1.25×10−7) across 24 common traits and diseases. Compared to pLOFs plus Missense (5/5), tests using pLoFs and AlphaMissense variants found slightly more significant gene-disease and gene-trait associations, albeit with a marginally lower proportion of positive control genes. Nevertheless, their overall performance was similar. Merging AlphaMissense with Missense (5/5), whether through their intersection or union, did not yield any further enhancement in performance. In summary, employing AlphaMissense to select deleterious variants for gene-based testing did not improve the ability to identify genes that are known to cause disease.
Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity
Authors: Roederer Alex L. , Cao Yi , St. Denis Kerri , Sheehan Maegan L. , Li Chia Jung , Lam Evan C. , Gregory David J. , Poznansky Mark C. , Iafrate A. John , Canaday David H. , Gravenstein Stefan , Garcia-Beltran Wilfredo F. , Balazs Alejandro B.
Published: March 2024

Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.
Predictors of mortality among COVID-19 patients at Kilimanjaro Christian Medical Centre in Northern Tanzania: A hospital-based retrospective cohort study
Authors: Waria Gilbert G. , Muro Florida J. , Jonas Norman , Sakita Francis , Shirima Laura , Mlay Henry L. , Ngowi Michael , Meela Elvis B. , Mboya Innocent B. , Kilonzo Kajiru G.
Published: March 2024

Background

COVID-19 disease is a global public health disaster causing a range of social, economic, and healthcare difficulties, border restrictions, high human loss, lockdown, and transportation challenges. Despite it being a global pandemic, there are few studies conducted in Tanzania to examine the predictors of mortality. This disease has caused a significant number of mortalities worldwide but literature shows low mortality and better survival in Africa than in other WHO regions. Therefore, this study aimed to determine the predictors of mortality among COVID-19 patients at KCMC Hospital in Northern Tanzania.

Methodology

This was the hospital-based retrospective cohort study, conducted at KCMC Hospital in Northern Tanzania among all admitted patients with confirmed COVID-19, from 10thMarch 2020 to 26thJanuary 2022. The main study event was COVID-19 mortality. The predictors of mortality were determined by using the Weibull survival regression model and the statistically significant results were declared at a p-value of <0.05.

Results

A total of 547 confirmed COVID-19 patient records were included in the study. Their median age was 63 (IQR; 53-83), about 60% were aged 60 years and above, and 56.7% were males. The most common clinical features were; fever (60.8%), a severe form of the disease (44.4%), difficulty in breathing (73.3%), chest pain (46.1%), and generalized body weakness (71.3%). Of all participants, over one-third (34.6%) died (95%CI; 0.31-0.39). The median survival time was 7 days (IQR; 3-12). The overall mortality rate was 32.33 per 1000 person-days while the independent predictors of higher mortality risk were age ≥60 years (AHR=2.01; 95%CI 1.41-2.87; P<0.001), disease severity (AHR=4.44; 95%CI 2.56-7.73; P<0.001) and male sex (AHR=1.28; 95%CI; 0.93-1.73; P=0.128).

Conclusion

Mortality was higher in elderly male patients, with a severe form of the disease and those with any comorbidities. Therefore, more attention should be provided to older patients including uptake of the current vaccine and ensuring standard and supportive care at primary health facilities is available.
Roles of TYRO3 Family Receptors in Germ Cell Development During Mouse Testis Formation
Authors: Ming Zhenhua , Bagheri-Fam Stefan , Frost Emily R , Ryan Janelle M , Binder Michele D , Harley Vincent R
Published: March 2024

Structured Abstract

Objective

To investigate the role of a potential SOX9 target gene,Tyro3, along with its family members,AxlandMertk(TAM family) in mouse testis development.

Design

Experimental laboratory study.

Setting

Research institute units.

Subject(s)

Embryonic day (E)11.5 Swiss mouse gonads forex vivogonad culture;Tyro3knockout mouse embryos.

Intervention(s)

E11.5 Swiss mouse gonads were cultured in hanging droplets of 30 µL DMEM medium supplemented with 10% FBS and 1% antibiotic-antimycotic. A pair of gonads were treated with 20 μM of BMS-777607 or 30 μM of LDC1267 and an equivalent volume of the vehicle control DMSO.

Main Outcome Measure(s)

Immunofluorescence to measure morphological changes ofex vivocultured gonads andin vivo Tyro3mouse testes; qRT-PCR to measure gene expressions.

Result(s)

Inhibition of the TAM family in E11.5ex vivocultured male mouse gonads led to reduced germ cell numbers caused by reduced proliferation and increased apoptosis of the germ cells.Tyro3knockout mice exhibited reduced expression levels of the germ cell genesDdx4,DazlandPou5f1and increased expression levels of the Sertoli cell genesSox9andAmhat E12.5. However, by E14.5, the expression ofDdx4,Dazl,Sox9andAmhhad returned to normal levels inTyro3knockout testes.Tyro3knockout testes displayed normal morphology and structures during fetal testis development.

Conclusion(s)

TAM family members have redundant roles in regulating germ cell development during early testis development.

Attestation Statement

Data regarding any of the subjects in the study has not been previously published unless specified.

Data will be made available to the editors of the journal for review or query upon request.

Data Sharing Statement

N/A

Capsule

Inhibition of the TAM family led to loss of germ cells in fetal gonads and deletion ofTyro3alone disturbed gene expressions of germ cells and Sertoli cells.
The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation
Authors: Bjerke Ingvild E. , Carey Harry , Bjaalie Jan G. , Leergaard Trygve B. , Kim Jee Hyun
Published: March 2024

The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages. Our findings show a cortico-subcortical shift in D1/D2 balance, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.
The costs and cost-effectiveness of different service models of palliative care, focusing on end of life care: A rapid review
Authors: Spencer Llinos Haf , Anthony Bethany Fern , Davies Jacob , Pisavadia Kalpa , Gillen Liz , Noyes Jayne , Fitzsimmons Deborah , Lewis Ruth , Cooper Alison , Hughes Dyfrig , Edwards Rhiannon Tudor , Edwards Adrian
Published: March 2024

Some people receive palliative or end of life care at home, others in hospitals or hospices, or a combination of home and hospice/home and hospital models. This rapid review aims to determine the costs and cost-effectiveness of different service models of palliative care or end of life care. These studies are mostly conducted from the perspective of the healthcare system, disregarding costs related to patients/caregivers economic burden (Perea-Bello et al., 2023).

Research Implications and Evidence Gaps

More UK research is needed on cost impacts of new services such as Enhanced Supported Care (ESC). Future research should consider which methods are most appropriate to evaluate palliative care models. Standard methodology, such as the calculation of quality-adjusted life years (QALYs), may not be most appropriate for this end of life population.

Improving QALYs may not be the intended aim of palliative care or end of life interventions, and prolonging death may be inconsistent with patient preferences and wishes. The quality and applicability of the evidence we found in our rapid review were variable, and therefore, uncertainty remains, especially when the perspective of analysis was not stated clearly.

Therefore, it was difficult to ascertain whether all relevant costs were considered. Assumptions on costs were not varied in many studies, and most studies had different time horizons.

Policy and Practice Implications

This rapid review has shown thathospital-based palliative care costs are higher than hospice or home-basedpalliative care. This suggests thathome-based palliative care should be available to allpatients in a recognisable end of life phase who desire to remain and die at home. Healthcare planners shouldaim to reduce hospitalisation at the end of lifebutonly if access to quality home careat the end of life is guaranteed.Patients should have a choiceabout where they prefer to die without moving the costs from the healthcare system to the home caregivers, rendering the costs invisible.

Funding Statement

The Bangor Institute for Medical and Health Research, was funded for this work by the Health and Care Research Wales Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Low-frequency hearing thresholds improve as high-frequency hearing sensitivity deteriorates between young adulthood and middle age in normally hearing people
Authors: Izmaylova Tatiana , Undurraga Jaime A. , Sowman Paul F.
Published: March 2024

Hearing sensitivity changes throughout a person’s lifetime. This work aimed to describe changes in pure-tone audiometric (PTA) thresholds that occur in the transition from young adulthood to middle age in 121 adults with normal or nearly normal hearing. Results showed that older people had worse high-frequency (4000-8000 Hz) thresholds and better low-frequency (125-500 Hz) thresholds than younger individuals, suggesting that hearing sensitivity in the low-frequency range may improve with age. The improvement of low-frequency thresholds may be part of a central compensation for age-related deterioration of high-frequency hearing sensitivity. Further investigation of age-related changes in low-frequency hearing sensitivity is needed to confirm our findings.
Molecular mechanism of α-latrotoxin action
Authors: Klink BU , Alavizargar A , Subramaniam KK , Chen M , Heuer A , Gatsogiannis C
Published: March 2024

The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report the first high resolution structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles synchronously rearrange to progressively form a highly stable 15 nm cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data unveil a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.
A maternal-effectPadi6variant causes nuclear and cytoplasmic abnormalities in oocytes, as well as failure of epigenetic reprogramming and zygotic genome activation in embryos
Authors: Giaccari Carlo , Cecere Francesco , Argenziano Lucia , Pagano Angela , Galvao Antonio , Acampora Dario , Rossi Gianna , Hay Mele Bruno , Acurzio Basilia , Coonrod Scott , Cubellis Maria Vittoria , Cerrato Flavia , Andrews Simon , Cecconi Sandra , Kelsey Gavin , Riccio Andrea
Published: March 2024

Maternal inactivation of genes encoding components of the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multilocus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying aPadi6missense variant that was identified in a family with Beckwith–Wiedemann syndrome and MLID. If homozygous in female mice, this variant resulted in interruption of embryo development at the two-cell stage. Single-cell multiomic analyses demonstrated defective maturation ofPadi6mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes, and developmental delay in two-cell embryos developing fromPadi6mutant oocytes but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced levels of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for preimplantation epigenetic reprogramming and ZGA.
Unconditional Wigner-negative mechanical entanglement with linear-and-quadratic optomechanical interactions
Authors: McConnell Peter , Houhou Oussama , Brunelli Matteo , Ferraro Alessandro
Published: March 2024

The generation of entangled states that display negative values of the Wigner function in the quantum phase space is a challenging task, particularly elusive for massive, and possibly macroscopic, systems such as mechanical resonators. In this work, we propose two schemes based on reservoir engineering for generating Wigner-negative entangled states unconditionally. We consider two noninteracting mechanical resonators that are radiation-pressure coupled to either one or two common cavity fields; the optomechanical coupling with the field(s) features both a linear and quadratic part in the mechanical displacement and the cavity is driven at multiple frequencies. We show analytically that both schemes stabilize a Wigner-negative entangled state that combines the entanglement of a two-mode squeezed vacuum with a cubic nonlinearity, which we dub cubic-phase entangled (CPE) state. We then perform extensive numerical simulations to test the robustness of Wigner-negative entanglement attained by approximate CPE states stabilized in the presence of thermal decoherence.

Published by the American Physical Society
2024
Efficient microwave spin control of negatively charged group-IV color centers in diamond
Authors: Pieplow Gregor , Belhassen Mohamed , Schröder Tim
Published: March 2024

In this paper, we provide a comprehensive overview of the microwave-induced manipulation of electronic spin states in negatively charged group-IV color centers in diamond with a particular emphasis on the influence of strain. Central to our investigation is the consideration of the full vectorial attributes of the magnetic fields involved, which are a dc field for lifting the degeneracy of the spin levels and an ac field for microwave control between two spin levels. We observe an intricate interdependence between their spatial orientations, the externally applied strain, and the resultant efficacy in spin-state control. In most studies to date the ac and dc magnetic field orientations have been insufficiently addressed, which has led to the conclusion that strain is indispensable for the effective microwave control of heavier group-IV vacancies, such as tin- and lead-vacancy color centers. In contrast, we find that the alignment of the dc magnetic field orthogonal to the symmetry axis and the ac field parallel to it can make the application of strain obsolete for effective spin manipulation. Furthermore, we explore the implications of this field configuration on the spin's optical initialization, readout, and gate fidelities.

Published by the American Physical Society
2024
Prospects for exotic
h→4τ
decays in single and di-Higgs boson production at the LHC and future hadron colliders
Authors: Adhikary Amit , Banerjee Shankha , Barman Rahool Kumar , Batell Brian , Bhattacherjee Biplob , Bose Camellia , Qian Zhuoni , Spannowsky Michael
Published: March 2024

We study the prospects for observing exotic decays of the Standard Model Higgs boson h into light beyond the Standard Model scalars a with mass ma≲mh/2 in the single Higgs and Higgs pair production channels at the high luminosity run of the Large Hadron Collider (HL-LHC). Discovery prospects for single Higgs production in the gluon-gluon fusion and vector boson fusion modes with the Higgs boson decaying via the exotic mode h→aa→4τ are analyzed at the HL-LHC. The projected sensitivity for exotic Higgs decays in the nonresonant Higgs pair production channel pp→hh→(h→bb¯)(h→aa→4τ)→2b4τ at the HL-LHC and a future s=100  TeV hadron collider (FCC-hh) are also estimated. Furthermore, we study HL-LHC’s potential reach for the Higgs-strahlung process in the 2b4τ channel, taking into account the contamination from nonresonant Higgs pair production. Finally, the potential reach for resonant Higgs pair production in the 2b4τ channel at the HL-LHC is also explored for several choices of {mH,ma}. Our studies suggest that significant improvements over existing bounds are achievable in several production channels, motivating new dedicated searches for h→aa→4τ at the HL-LHC and future colliders.

Published by the American Physical Society
2024
Doped semiconductor devices for sub-MeV dark matter detection
Authors: Du Peizhi , Egaña-Ugrinovic Daniel , Essig Rouven , Sholapurkar Mukul
Published: March 2024

Dopant atoms in semiconductors can be ionized with ∼10  meV energy depositions, allowing for the design of low-threshold detectors. We propose using doped semiconductor targets to search for sub-MeV dark matter scattering or sub-eV dark matter absorption on electrons. Currently unconstrained cross sections could be tested with a 1 g-day exposure in a doped detector with backgrounds at the level of existing pure semiconductor detectors, but improvements would be needed to probe the freeze-in target. We discuss the corresponding technological requirements and lay out a possible detector design.

Published by the American Physical Society
2024
Exploring magnetic fluctuation effects in QED gauge fields: Implications for mass generation
Authors: Castaño-Yepes Jorge David , Muñoz Enrique
Published: March 2024

In this work, we calculate the one-loop contribution to the polarization tensor for photons (and gluons) in the presence of a classical background magnetic field with white-noise stochastic fluctuations. The magnetic field fluctuations are incorporated into the fermion propagator in a quasiparticle picture, which we developed in previous works using the . By focusing on the strong-field limit, here we explicitly calculate the polarization tensor. Our results reveal that it does not satisfy the transversality conditions outlined by the Ward identity, thus breaking the U(1) symmetry. As a consequence, in the limit of vanishing photon four-momenta, the tensor coefficients indicate the emergence of an effective magnetic mass induced on photons (and gluons) by these stochastic fluctuations, leading to the interpretation of a dispersive medium with a noise-dependent index of refraction.

Published by the American Physical Society
2024
UV massive resonance from IR double copy consistency
Authors: Carrasco John Joseph M. , Pavao Nicolas H.
Published: March 2024

From the perspective of effective field theory (EFT), Wilson coefficients of the low energy theory are determined by integrating out modes of the full ultraviolet (UV) theory. The spectrum can be in principle resummed if one has access to all available infrared (IR) coefficients at low energies. In this work we show that there exists a general class of consistent massive resonance double-copy (CMRDC) models where UV massive residues are reconstructed through double-copy consistency conditions between the IR Wilson coefficients of the full EFT expansion. Through a color-dual bootstrap, we find surprisingly that double-copy consistency alone introduces the kinematic factors of CMRDC models that soften high energy behavior by exponentiating color-dual contacts. This bootstrap suggests that our massive resonance paradigm is an inevitable consequence of the duality between color and kinematics, thereby providing a path towards emergent UV structure directly from the IR. We then demonstrate how CMRDC models can capture a spectrum of massive modes compatible with general multiplicity, and use Padé extrapolation to solve the inverse problem of identifying massive UV resonance from a small number of IR Wilson coefficients.

Published by the American Physical Society
2024
Bulk reconstruction using timelike entanglement in (A)dS
Authors: Das Avijit , Sachdeva Shivrat , Sarkar Debajyoti
Published: March 2024

It is well known that the entanglement entropies for spacelike subregions, and the associated modular Hamiltonians play a crucial role in the bulk reconstruction program within anti–de Sitter (AdS) holography. Explicit examples of the Hamilton-Kabat-Lifschytz-Lowe (HKLL) map exist mostly for the cases where the emergent bulk region is the so-called entanglement wedge of the given boundary subregion. However, motivated from the complex pseudoentropy in Euclidean conformal field theories (CFT), one can talk about a “timelike entanglement” in Lorentzian CFTs dual to AdS spacetimes. One can then utilize this boundary timelike entanglement to define a boundary “timelike modular Hamiltonian.” We use constraints involving these Hamiltonians in a manner similar to how it was used for spacelike cases, and write down bulk operators in regions which are not probed by an RT surface corresponding to a single CFT. In the context of two-dimensional CFT, we rederive the HKLL formulas for free bulk scalar fields in three examples: in AdS Poincaré patch, inside and outside of the AdS black hole, and for de Sitter flat slicings. In this method, one no longer requires the knowledge of bulk dynamics for subhorizon holography.

Published by the American Physical Society
2024
Incompatibility as a Resource for Programmable Quantum Instruments
Authors: Ji Kaiyuan , Chitambar Eric
Published: March 2024

Quantum instruments represent the most general type of quantum measurement, as they incorporate processes with both classical and quantum outputs. In many scenarios, it may be desirable to have some “on-demand” device that is capable of implementing one of many possible instruments whenever the experimenter desires. We refer to such objects as programmable instrument devices (PIDs), and this paper studies PIDs from a resource-theoretic perspective. A physically important class of PIDs are those that do not require quantum memories to implement, and these are naturally “free” in this resource theory. Additionally, these free objects correspond precisely to the class of unsteerable channel assemblages in the study of channel steering. The traditional notion of measurement incompatibility emerges as a resource in this theory since any PID controlling an incompatible family of instruments requires a quantum memory to build. We identify an incompatibility preorder between PIDs based on whether one can be transformed into another using processes that do not require additional quantum memories. Necessary and sufficient conditions are derived for when such transformations are possible based on how well certain guessing games can be played using a given PID. Ultimately our results provide an operational characterization of incompatibility, and they offer semi-device-independent tests for incompatibility in the most general types of quantum instruments.

Published by the American Physical Society
2024
A human-centered perspective on individual risks for digital innovation management: an integrative conceptual review
Authors: Du Plooy Hilda , Tommasi Francesco , Furlan Andrea , Nenna Federica , Gamberini Luciano , Ceschi Andrea , Sartori Riccardo
Published: March 2024

Purpose

Following the imperative for human-centric digital innovation brought by the paradigm of Industry 5.0, the article aims to integrate the dispersed and multi-disciplinary literature on individual risks for workers to define, explain and predict individual risks related to Industry 4.0 technologies.

Design/methodology/approach

The paper follows the question, “What is the current knowledge and evidence base concerning risks related to Industry 4.0 technologies, and how can this inform digital innovation management in the manufacturing sector through the lens of the Industry 5.0 paradigm?” and uses the method of systematic literature review to identify and discuss potential risks for individuals associated with digital innovation. N = 51 contributions met the inclusion criteria.

Findings

The literature review indicates dominant trends and significant gaps in understanding risks from a human-centric perspective. The paper identifies individual risks, their interplay with different technologies and their antecedents at the social, organizational and individual levels. Despite this, the paper shows how the literature concentrates in studying risks on only a limited number of categories and/or concepts. Moreover, there is a lack of consensus in the theoretical and conceptual frameworks. The paper concludes by illustrating an initial understanding of digital innovation via a human-centered perspective on psychological risks.

Practical implications

Findings yield practical implications. In investing in the adoption, generation or recombination of new digital technologies in organizations, the paper recommends managers ensure to prevent risks at the individual level. Accordingly, the study’s findings can be used as a common starting point for extending the repertoire of managerial practices and interventions and realizing human-centric innovation.

Originality/value

Following the paradigm of Industry 5.0, the paper offers a holistic view of risks that incorporates the central role of the worker as crucial to the success of digital innovation. This human-centric perspective serves to inform the managerial field about important factors in risk management that can result in more effective targeted interventions in risk mitigation approaches. Lastly, it can serve to reinterpret digital innovation management and propose future avenues of research on risk.
Business model innovation and Industry 5.0: a possible integration in GLAM institutions
Authors: Botti Antonio , Baldi Giovanni
Published: March 2024

Purpose

This research delves into the realm of Business Model Innovation (BMI), integrating it with the human-centric, sustainable, and resilient principles of Industry 5.0, proposing a new theoretical framework.

Design/methodology/approach

An abductive approach has been chosen to expand existing knowledge developing new ideas based on emerging phenomena. Data were gathered via semi-structured interviews with directors, managers and curators of public institutions in Italy, Switzerland, Germany and Spain encompassing Galleries, Libraries, Archives, and Museums (GLAM). These data were subsequently subjected to thematic analysis.

Findings

The findings indicate that the main enablers for Business Model Innovation (BMI) in combination with Industry 5.0 encompassed stakeholder, customer and organizational engagement, collaborative environment, knowledge and innovation management, and sustainability. These drivers were effectively leveraged through three pivotal facilitators-inhibitors: technology, resources, and leadership.

Research limitations/implications

The principal constraints are rooted in the narrow contextual focus and the limited participants number. However, upcoming research efforts may broaden the horizons of this multifaceted and extensive investigation.

Originality/value

This study is groundbreaking as it fills a significant gap in the existing literature by integrating Business Model Innovation (BMI) with the Industry 5.0 paradigm, a novel approach that has not been explored previously. Additionally, the inclusion of GLAM institutions in this research adds a unique dimension, as they have been largely overlooked in both research domains.
Consumer and brand value formation, value creation and co-creation in social media brand communities
Authors: Marchowska-Raza Magdalena , Rowley Jennifer
Published: March 2024

Purpose

Social media has significantly impacted the value creation processes within the consumer–brand relationship. This study aims to examine value formation processes within a cosmetics social media brand community and to establish the types of value formation associated with different categories of interactions within a social media brand community.

Design/methodology/approach

The research adopted a netnographic approach and followed the operational protocols of netnography. Conversations in one large cosmetics social media brand community were observed and downloaded for analysis over a two-month period. Examples of value-creation and formation processes were identified using netnographic interpretative procedures to develop higher-order themes.

Findings

The findings supported the creation of a “Consumer and brand value creation and co-creation framework” highlighting disparate value types within the following interactions: consumer-to-consumer; brand-to-consumer; and consumer-to-brand. The identified value types were specific to the actors (i.e. consumers and brands) involved in value formation processes. The analysis also revealed consumers’ ability to independently generate value through direct interaction with a social media brand community and the brands’ role in supporting consumers in value formation through value facilitation.

Originality/value

The pivotal role of disparate actors’ interactions in value formation processes is highlighted, alongside the autonomous ability to form value with the aid of resources stored and shared within the social media brand community. The network of interactions and value-creation processes contribute to a holistic understanding of the interactions in a social media brand community. Furthermore, the research explores and highlights the emerging role of social media brand communities as “value vestiges”.