bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Capabilities Associated With Behavioral Health Integration Within Emergency Departments
Authors: Bui Linh N. , Knox Margae , Miller-Rosales Chris , Meara Ellen , Rodriguez Hector P.
Published: January 2024

Objectives:

To identify hospital capabilities associated with behavioral health (BH) processes in emergency departments (EDs).

Research Design:

Six hundred two hospital responses to the 2017/2018 National Survey of Healthcare Organizations and Systems were linked to 2017 American Hospital Association Annual Survey data. Separate multivariable regressions estimated how hospital capabilities (the use of quality improvement methods, approaches to disseminate best patient-care practices, barriers to using care delivery innovations, and inpatient beds for psychiatric or substance use) were associated with each of 4 ED-based BH processes: mental health and substance use disorder screening, team-based approaches to BH, telepsychiatry, and direct referrals to community-based BH clinicians. Models controlled for hospital structural characteristics and area-level socioeconomic factors.

Results:

Most hospitals screened for BH conditions and provided direct referrals to community-based BH clinicians. Approximately half of the hospitals used a team approach to BH. A minority had implemented telepsychiatry. Each additional process used to disseminate best patient-care practices was associated with more screening for BH conditions (an increase of 4.07 points on the screening index, P<0.01) and greater likelihood of using a team approach to BH [4.41 percentage point (P<0.01) increase]. Hospitals reporting more barriers to the use of care delivery innovations reported less screening and use of a team approach [a decrease of 0.15 points on the screening index (P<0.01) and 0.28 percentage points reduction in likelihood of team approach use (P<0.001) for 1-point increase in the barrier index].

Conclusions:

Research and interventions focused on removing innovation barriers or adding processes to disseminate best practices offer a path to accelerate BH integration in hospital EDs.
Effect of family-centered care on the anxiety levels among family members of patients undergoing cardiac surgery: a randomized controlled trial
Authors: Lotfalipoor Roja , Jafaraghaee Fateme , Kazemnejad Leyli Ehsan , Ghorbani Vajargah Pooyan , Karkhah Samad , Javadi-Pashaki Nazila
Published: January 2024

Background:

The present study aims to determine the effect of family-centered care on anxiety levels among family members of patients undergoing cardiac surgery.

Materials and methods:

This study was a randomized clinical trial study that was conducted on the families of Iranian cardiac surgery patients. In the intervention group, family-centered care was implemented, and the content of the intervention included providing informational and emotional support to the family member and the family member’s participation in patient care according to the set framework.

Results:

A total of 144 family members of patients undergoing cardiac surgery were included in this study. Among the 144 family members, 71 were in the intervention group, and 73 were in the control group. The changes in the state anxiety score before and after the intervention were significant between the two groups, and the changes were higher in the control group (P=0.043). Also, there was no significant difference in the changes in trait anxiety before and after the intervention between the two groups (P>0.05).

Conclusion:

In general, the high prevalence of anxiety in patients’ families has negative functional consequences on both patients and their families. To reduce the level of anxiety, special attention should be paid to knowing the effective factors and appropriate coping methods. Nevertheless, it is important to note that additional research is warranted to delve deeper into this matter in future studies.
Recurrent Tolosa-Hunt syndrome: a case report
Authors: Neupane Shashank , Pudasaini Prasamsa , Dhakal Bishal , Sherpa Pasang , Rokaya Pooja , Subedi Anukul
Published: January 2024

Introduction and importance:

Tolosa-Hunt syndrome is a rare condition with unknown aetiology that manifests clinically as unilateral orbital pain and ophthalmoplegia. It is a diagnosis of exclusion that resolves spontaneously but can recur and respond dramatically to systemic steroids.

Case presentation:

The authors herein report a case of a 38-year-old male who presented with horizontal diplopia, limited outward movement of the right eye, and blurry vision for two days which was managed with oral Prednisolone. The patient visited 3 months later with progressive ptosis and vertical diplopia with periorbital pain over the right eye. It was eventually diagnosed via magnetic imaging resonance studies and successfully treated for Tolosa-Hunt syndrome with IV methylprednisolone followed by oral prednisolone.

Clinical discussion:

Hence, the typical clinical presentation of the case with significant response to steroids, exclusion of other conditions from investigation and imaging, and subsequent recurrence of similar symptoms were crucial for making the diagnosis of Tolosa-Hunt syndrome.

Conclusion:

Tolosa-Hunt syndrome is a syndrome of painful ophthalmoplegia which responds well to steroid therapy but has a tendency to recur. Hence, patients must be adequately informed about the reoccurrence and kept under follow-up.
Serum Levels of Vitamin C and Thiamin in Children With Suspected Sepsis: A Prospective Observational Cohort Study
Authors: McWhinney Brett , Ungerer Jacobus , LeMarsey Renate , Phillips Natalie , Raman Sainath , Gibbons Kristen , Schlapbach Luregn J. ,   on behalf of the Rapid Acute Paediatric Infection Diagnosis in Suspected Sepsis (RAPIDS) Study Investigators
Published: January 2024

OBJECTIVES:

Vitamin C and thiamin have been trialed as adjunctive therapies in adults with septic shock but their role in critically ill children is unclear. We assessed serum levels of vitamin C and thiamin in children evaluated for sepsis.

DESIGN:

Single-center prospective observational study. Serum levels of vitamin C and thiamin were measured on admission and association with multiple organ dysfunction syndrome (MODS) was explored using logistic regression.

SETTING:

Emergency department and PICU in a tertiary children’s hospital, Queensland, Australia.

PATIENTS:

Children greater than 1 month and less than 17 years evaluated for sepsis.

INTERVENTIONS:

Not applicable.

MEASUREMENTS AND MAIN RESULTS:

Vitamin levels were determined in 221 children with a median age of 3.5 (interquartile range [IQR] 1.6, 8.3) years. Vitamin C levels were inversely correlated with severity as measured by pediatric Sequential Organ Failure Assessment (Spearman’s rho = –0.16, p = 0.018). Median (IQR) vitamin C levels on admission were 35.7 (17.9, 54.1) µmol/L, 36.1 (21.4, 53.7) µmol/L, and 17.9 (6.6, 43.0) µmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.017). In multivariable analyses, low levels of vitamin C at the time of sampling were associated with greater odds of MODS (adjusted odds ratio [aOR] 3.04; 95% CI, 1.51–6.12), and vitamin C deficiency was associated with greater odds of MODS at 24 hours after sampling (aOR 3.38; 95% CI, 1.53–7.47). Median (IQR) thiamin levels were 162 (138, 192) nmol/L, 185 (143, 200) nmol/L, and 136 (110, 179) nmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.061). We failed to identify an association between thiamin deficiency and either MODS at sampling (OR 2.52; 95% CI, 0.15–40.86) or MODS at 24 hours (OR 2.96; 95% CI, 0.18–48.18).

CONCLUSIONS:

Critically ill children evaluated for sepsis frequently manifest decreased levels of vitamin C, with lower levels associated with higher severity.
Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial
Authors: Harley Amanda , George Shane , Phillips Natalie , King Megan , Long Debbie , Keijzers Gerben , Lister Paula , Raman Sainath , Bellomo Rinaldo , Gibbons Kristen , Schlapbach Luregn J ,   on behalf of the Resuscitation in Paediatric Sepsis Randomized Controlled Pilot Platform Study in the Emergency Department (RESPOND ED) Study Group
Published: January 2024

OBJECTIVES:

In children with septic shock, guidelines recommend resuscitation with 40–60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock.

DESIGN:

Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days.

SETTING:

Four pediatric Emergency Departments in Queensland, Australia.

PATIENTS:

Children between 28 days and 18 years old with septic shock.

INTERVENTIONS:

Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n= 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n= 23).

MEASUREMENTS AND MAIN RESULTS:

Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9–12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12–26 min) in the intervention group, and 49 minutes (IQR, 29–63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0–10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6–28.6 mL/kg) in the standard group (difference, –20.0; 95% CI, –28.0 to –12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26–27 d) versus 26 days (IQR, 25–27 d). There were no adverse events reported associated with the intervention.

CONCLUSIONS:

In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.
The Importance of Physical Therapy in the Evaluation of Fall Prevention Programs in Older Adults
Authors: Santos Luis Eduardo , de Sá Ferreira Arthur , Vilella Renato Carvalho , Lunkes Luciana Crepaldi
Published: January 2024

The rapidly growing population of elderly individuals worldwide poses a significant public health concern due to the increased risk of falls and their associated consequences. Falls affect up to 30% of those older than 60 years and are the leading cause of injuries in this age group, with the oldest old being the most vulnerable. This review summarizes fall risk assessment methods and fall prevention programs for elderly individuals. This scoping review aims to identify exercise protocols aimed at reducing the risk of falling in elderly individuals. The authors used the PRISMA-ScR recommendation for scoping reviews and searched several databases for studies published between 2010 and 2020. Twelve studies met the inclusion criteria and were assessed for methodological quality and risk of bias using the PEDro scale. All selected articles presented strong data for the reduction and prevention of falls in the elderly individuals by using specific training programs based on strength and muscle balance exercises. The best results were those protocols lasting more than 18 weeks, performed 2 to 3 times a week, with 60 minutes' duration. Physiotherapeutic exercise protocols are, therefore, an excellent option for reducing the risk of falls in elderly individuals, in addition to promoting a better quality of life.
MEK1/2-PKM2 Pathway Modulates the Immunometabolic Reprogramming of Proinflammatory Allograft-Infiltrating Macrophages During Heart Transplant Rejection
Authors: Chen Zhang , Li Yuan , Niu Yuqing , Zhang Xi , Yu Jizhang , Cui Jikai , Ran Shuan , Wang Song , Ye Weicong , Xia Jiahong , Wu Jie
Published: January 2024

Background.

Emerging evidence has highlighted the role of macrophages in heart transplant rejection (HTR). However, the molecular signals modulating the immunometabolic phenotype of allograft-infiltrating macrophages (AIMs) during HTR remain unknown.

Methods.

We analyzed single-cell RNA sequencing data from cardiac graft-infiltrating immunocytes to characterize the activation patterns and metabolic features of AIMs. We used flow cytometry to determine iNOS and PKM2 expression and MEK/ERK signaling activation levels in AIMs. We then generated macrophage-specific Mek1/2 knockout mice to determine the role of the MEK1/2-PKM2 pathway in the proinflammatory phenotype and glycolytic capacity of AIMs during HTR.

Results.

Single-cell RNA sequencing analysis showed that AIMs had a significantly elevated proinflammatory and glycolytic phenotype. Flow cytometry analysis verified that iNOS and PKM2 expressions were significantly upregulated in AIMs. Moreover, MEK/ERK signaling was activated in AIMs and positively correlated with proinflammatory and glycolytic signatures. Macrophage-specific Mek1/2 deletion significantly protected chronic cardiac allograft rejection and inhibited the proinflammatory phenotype and glycolytic capacity of AIMs. Mek1/2 ablation also reduced the proinflammatory phenotype and glycolytic capacity of lipopolysaccharides + interferon-γ–stimulated macrophages. Mek1/2 ablation impaired nuclear translocation and PKM2 expression in macrophages. PKM2 overexpression partially restored the proinflammatory phenotype and glycolytic capacity of Mek1/2-deficient macrophages. Moreover, trametinib, an Food and Drug Administration–approved MEK1/2 inhibitor, ameliorated chronic cardiac allograft rejection.

Conclusions.

These findings suggest that the MEK1/2-PKM2 pathway is essential for immunometabolic reprogramming of proinflammatory AIMs, implying that it may be a promising therapeutic target in clinical heart transplantation.
The pharmacogenomic assessment of molecular epithelial-mesenchymal transition signatures reveals drug susceptibilities in cancer cell lines
Authors: Ohnmacht Alexander J. , Avar Göksu , Schübel Marisa K. , O’Neill Thomas J. , Krappmann Daniel , Menden Michael P.
Published: January 2024

The epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-cell adhesion and cell polarity, which is often exploited by cancer cells to adopt a motile, invasive and metastatic phenotype. Whilst EMT is often linked with cancer progression and therapy resistance, strategies for its selective targeting remain limited. In order to address this, we infer EMT states of cancer cell lines from their molecular signatures and use predictive and causal modelling to estimate the effect of EMT on drug susceptibility in high-throughput drug screens. For example, we show that EMT signatures in melanoma cells can predict favourable responses to the HSP90 inhibitor luminespib and demonstrate that epithelial-like melanoma cells can be sensitised to luminespib upon stimulation of EMT by TGF-β. Thus, we provide an analysis that systematically yields a set of potent drugs by exploiting vulnerabilities of cancer cells undergoing EMT, which may pave the way for therapies to target these cells.
Genome assembly of the edible jelly fungusDacryopinax spathularia(Dacrymycetaceae)
Authors:   Hong Kong Biodiversity Genomics Consortium,   Project Coordinator and Co-Principal Investigators, Hui Jerome H.L. , Chan Ting Fung , Chan Leo L. , Cheung Siu Gin , Cheang Chi Chiu , Fang James K.H. , Gaitan-Espitia Juan Diego , Lau Stanley C.K. , Sung Yik Hei , Wong Chris K.C. , Yip Kevin Y.L. , Wei Yingying ,   DNA extraction, library preparation and sequencing, Chong Tze Kiu , Law Sean T.S. ,   Genome assembly and gene model prediction, Nong Wenyan ,   Genome analysis and quality control, Nong Wenyan ,   Sample collector and logistics, Chong Tze Kiu , Law Sean T.S. , Yip Ho Yin
Published: January 2024

The edible jelly fungusDacryopinax spathularia(Dacrymycetaceae) is wood-decaying and can be commonly found worldwide. It has also been used in food additives given its ability to synthesize long-chain glycolipids. In this study, we present the genome assembly ofD. spathulariausing a combination of PacBio HiFi reads and Omni-C data. The genome size ofD. spathulariais 29.2 Mb and in high sequence contiguity and completeness, including scaffold N50 of 1.925 Mb and 92.0% BUSCO score, respectively. A total of 11,510 protein-coding genes, and 474.7 kb repeats accounting for 1.62% of the genome, were also predicted. TheD. spathulariagenome assembly generated in this study provides a valuable resource for understanding their ecology such as wood decaying capability, evolutionary relationships with other fungus, as well as their unique biology and applications in the food industry.
Grouping cells in primate visual cortex
Authors: Franken Tom P. , Reynolds John H.
Published: January 2024

Our perception of how objects are laid out in visual scenes is remarkably stable, despite rapid shifts in the patterns of light that fall on the retina with each saccade. One mechanism that may help establish perceptual stability is border ownership assignment. Studies in macaque area V2 have identified border ownership neurons that signal which side of a border belongs to a foreground surface. This signal persists for hundreds of milliseconds after border ownership has been rendered ambiguous by deleting the stimulus features that distinguish foreground from background. Remarkably, this signal survives eye movements: border ownership neurons also exhibit border ownership signalsde novowhen an eye movement places the newly ambiguous border within their receptive field. The grouping cell hypothesis proposes the existence of hypothetical grouping cells in a downstream brain area. These cells would compute persistent proto-object representations and therefore have the properties to endow cells in upstream brain areas with selectivity for border ownership. Such grouping cells have been predicted to show a centripetal and persistent pattern of preferred side of ownership for a border placed parallel to the perimeter of their classical receptive field, and such a centripetal ownership preference pattern should also occurde novoin these same cells if an ambiguous border lands in their receptive field after a saccade. It is unknown if grouping cells exist. Here we used laminar multielectrodes in area V4 – the main source of feedback to V2 – of behaving macaques to determine whether such grouping cells exist. Consistent with the model prediction we find a substantial population of neurons with these properties, in all laminar compartments, and they exhibit a response latency that is short enough to act as the source that endows neurons in V2 with selectivity for border ownership. While grouping cell activity provides information about the location of foreground surfaces, these neurons are, counterintuitively, not as strongly tuned for luminance contrast polarity, a feature of those surfaces, as are border ownership cells. Our data suggest a division of labor in which these newly discovered grouping cells provide spatiotemporal continuity of segmented surfaces whereas border ownership cells link this location information with surface features such as luminance contrast.
Cutting through host autofluorescence: fluorescence lifetime imaging microscopy for visualising intracellular bacteria in Symbiodiniaceae
Authors: Deore Pranali , Tsang Min Ching Sarah Jane , Brumley Douglas R. , van Oppen Madeleine J.H. , Hinde Elizabeth , Blackall Linda L.
Published: January 2024

Photoperiodicity is key to the synchronization of life stages in Symbiodiniaceae,Breviolum minutumwhich harbors taxonomically diverse epi- and endosymbiotic bacteria. We examined influence of a light dark regime on the spatial association betweenB. minutumand bacteria.

We employed a novel approach using combination of fluorescence lifetime imaging microscopy with fluorescencein situhybridisation approach to clearly distinguish labelled intracellular bacteria from broad spectrum (450–800 nm) background autofluorescence ofB. minutum.

Bacteria were observed inside, tethered to and burrowing into the cell exterior, and at the furrow of dividing cells inB. minutum. Significant changes in the abundance of intracellular bacteria relative to autofluorescence inB. minutumcells were observed at initiation of light and dark conditions.

We suggest that the onset of bacterial endosymbiosis is linked to the photoperiod driven changes inB. minutumlife stages. The re-organisation of thecal plates during cell division ofB.minutumin dark is likely to result in internalisation of bacteria.
Early evolution of the ecdysozoan body plan
Authors: Wang Deng , Qiang Yaqin , Guo Junfeng , Vannier Jean , Song Zuchen , Peng Jiaxin , Zhang Boyao , Sun Jie , Yu Yilun , Zhang Yiheng , Zhang Tao , Yang Xiaoguang , Han Jian
Published: January 2024

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e., elongated and tubular) of their ancestral body plan. We describe hereBeretella spinosagen et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament.Beretellahas no equivalent among animals, exceptSaccorhytus, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.
Knowledge Innovation Ecosystem for the Promotion of User-Centre Health Innovations: Living Lab Methodology and Lessons Learned Through the Proposal of Standard Good Practices
Authors: Rosa Natacha , Leite Sofia , Alves Juliana , Carvalho Angela , Oliveira Diana , Santos Flavia , Macedo Barbara , Prazeres Hugo
Published: January 2024

Living Labs, experiencing a global surge in popularity over the past years, demands standardized guidance through the development of widely accepted good practices. While challenging due to the complex and evolving nature of Living Labs, this task remains essential. These knowledge innovation ecosystems facilitate a diverse array of interconnected and interacting end-users and stakeholder partners who engage collaboratively to co-create, embed, and/or leverage end-user-centric breakthroughs at one or more innovation phases within a real-world context. Based on the development of six Living Labs in the health domain, this study proposes a more general yet critical set of Living Labs’ good practices, emphasizing the importance of strong initial marketing and promotion strategies for Living Labs’ open calls, enforcing gender equality, carefully selecting stakeholders, devising and implementing effective framework strategies for end-user engagement and value creation, ensuring value creation for all Living Labs partners, prolonging the long-term viability of the Living Lab project, promoting and disseminating impactful actions and results, fostering environmental sustainability, and processing results data for Living Lab performance evaluation.
Muscle-controlled physics simulations of the emu (a large running bird) resolve grounded running paradox
Authors: van Bijlert Pasha A. , van Soest A.J. “Knoek” , Schulp Anne S. , Bates Karl T.
Published: January 2024

Humans and birds utilize very different running styles. Unlike humans, birds adopt “grounded running” at intermediate speeds – a running gait where at least one foot is always in contact with the ground. Avian grounded running is paradoxical: animals tend to minimize locomotor energy expenditure, but birds prefer grounded running despite incurring higher energy costs. Using predictive gait simulations of the emu (Dromaius novaehollandiae), we resolve this paradox by demonstrating that grounded running represents an energetic optimum for birds. Our virtual experiments decoupled biomechanically relevant anatomical features that cannot be isolated in a real bird. The avian body plan prevents (near) vertical leg postures while running, making the running style used by humans impossible. Under this anatomical constraint, grounded running is optimal if the muscles produce the highest forces in crouched postures, as is true in most birds. Anatomical similarities between birds and non-avian dinosaurs suggest that, as a behavior, avian grounded running first evolved within non-avian theropods.
Examining the influence of environmental factors onAcanthamoeba castellaniiandPseudomonas aeruginosain co-culture
Authors: Cecil Rhiannon E. , Yoder-Himes Deborah R.
Published: January 2024

Exploration of interspecies interactions between microorganisms can have taxonomic, ecological, evolutionary, or medical applications. To better explore interactions between microorganisms it is important to establish the ideal conditions that ensure survival of all species involved. In this study, we sought to identify the ideal biotic and abiotic factors that would result in high co-culture viability of two interkingdom species,Pseudomonas aeruginosaandAcanthamoeba castellanii, two soil dwelling microbes. Long-term co-culture of these two organisms has traditionally been unsuccessful and usually results in high mortality for one or both organisms suggesting a predator-predator interaction may exist between them. In this study, we identified biotic and abiotic conditions that resulted in a high viability for both organisms in long-term co-culture, including optimizing temperature, nutrient concentration, choice of bacterial strains, and the initial ratio of interacting partners. These two species represent ideal partners for studying microbial interactions because amoebae act similarly to mammalian immune cells in many respects, and this can allow researchers to study host-pathogen interactionsin vitro. Therefore, long-term interaction studies between these microbes might reveal the evolutionary steps that occur in bacteria when subjected to intense predation, like what occurs when pathogens enter the human body. The culture conditions characterized here resulted in high viability for both organisms for at least 14-days in co-culture suggesting that long-term experimental studies between these species can be achieved using these culture conditions.
Helicases DDX5 and DDX17 promote Hepatitis B Virus transcription termination heterogeneity in infected human hepatocytes
Authors: Chapus Fleur , Giraud Guillaume , Huchon Pélagie , Charre Caroline , Goldsmith Chloé , Rodà Mélanie , Martinez Maria-Guadalupe , Fresquet Judith , Diederichs Audrey , Locatelli Maëlle , Polvèche Hélène , Grand Xavier , Scholtès Caroline , Chemin Isabelle , Vargas Hector Hernandez , Rivoire Michel , Bourgeois Cyril F. , Zoulim Fabien , Testoni Barbara
Published: January 2024

Background & Aims

Transcription termination fine tunes gene expression and contributes to specify the function of RNAs in eukaryotic cells. Transcription termination of hepatitis B virus (HBV) is subjected to the recognition of the canonical polyadenylation signal (cPAS) common to all viral transcripts. The regulation of the usage of this cPAS and its impact on viral gene expression and replication is currently unknown.

Approach & Results

To unravel the regulation of HBV transcript termination, we implemented a 3’ RACE-PCR assay coupled to single molecule sequencing both inin vitroinfected hepatocytes and in chronically infected patients. The detection of a previously unidentified transcriptional readthrough indicated that the cPAS was not systematically recognized during HBV replicationin vitroandin vivo. Gene expression downregulation experiments demonstrated a role for the RNA helicases DDX5 and DDX17 in promoting viral transcriptional readthrough, which was, in turn, associated to HBV RNA destabilization and decreased HBx protein expression. RNA and chromatin immunoprecipitation, together with mutation of cPAS sequence suggested a direct role of DDX5 and DDX17 in functionally linking cPAS recognition to transcriptional readthrough, HBV RNA stability and replication.

Conclusions

Our findings identify DDX5 and DDX17 as crucial determinants for HBV transcriptional fidelity and as host restriction factors for HBV replication.
Seasonal Metabolic Dynamics of Microeukaryotic Plankton: A Year-long Metatranscriptomic Study in a Temperate Sea
Authors: Perneel Michiel , Lagaisse Rune , Mortelmans Jonas , Maere Steven , Hablützel Pascal I.
Published: January 2024

Seasonal fluctuations profoundly affect marine microeukaryotic plankton composition and metabolism, but accurately tracking these changes has been a longstanding challenge. In this study, we present a year-long metatranscriptomic dataset from the Southern Bight of the North Sea, shedding light on the seasonal dynamics in temperate plankton ecosystems. We observe distinct shifts in active plankton species and their metabolic processes in response to seasonal changes. We characterised the metabolic signatures of different seasonal phases in detail, thereby revealing the metabolic versatility of dinoflagellates, the heterotrophic dietary strategy ofPhaeocystisduring its late-stage blooms, and diatoms being most abundant and metabolically active in autumn. Our data illuminates the varied contributions of microeukaryotic taxa to biomass production and nutrient cycling at different times of the year and allows to delineate their ecological niches. These findings underscore the use of metatranscriptomics for continuous marine ecosystem monitoring to enhance our ecological understanding of the ocean’s eukaryotic microbiome.
Characterisation of anhydro-sialic acid transporters from mucosa-associated bacteria
Authors: Wu Yunhan , Bell Andrew , Thomas Gavin H. , Bolam David N. , Sargent Frank , Juge Nathalie , Palmer Tracy , Severi Emmanuele
Published: January 2024

Sialic acid (Sia) transporters are critical to the capacity of host-associated bacteria to utilise sialic acid for growth and/or cell-surface modification. While N-acetyl-neuraminic acid (Neu5Ac)-specific transporters have been studied extensively, little is known on transporters dedicated to anhydro-sialic acid forms such as 2,7-anhydro-Neu5Ac (2,7-AN) or 2,3-dehydro-2-deoxy-Neu5Ac (Neu5Ac2en). Here, we used a Sia-transport-null strain ofEscherichia colito investigate the function of members of anhydro-Sia transporter families previously identified by computational studies. First, we showed that the transporter NanG, from the Glycoside-Pentoside-Hexuronide:cation symporter family, is a specific 2,7-AN transporter, and identified by mutagenesis a crucial functional residue within the putative substrate-binding site. We then demonstrated that NanX transporters, of the Major Facilitator Superfamily, also only transport 2,7-AN and not Neu5Ac2en nor Neu5Ac. Finally, we provided evidence that SiaX transporters, of the Sodium-Solute Symporter superfamily, are promiscuous Neu5Ac/Neu5Ac2en transporters able to acquire either substrate equally well. The characterisation of anhydro-Sia transporters expands our current understanding of prokaryotic Sia metabolism within host-associated microbial communities.
Glycan-costumed virus-like particles promote type 1 anti-tumor immunity
Authors: Lensch Valerie , Gabba Adele , Hincapie Robert , Bhagchandani Sachin H. , Basak Ankit , Alam Mohammad Murshid , Irvine Darrell J. , Shalek Alex K. , Johnson Jeremiah A. , Finn M. G. , Kiessling Laura L.
Published: January 2024

Cancer vaccine development is inhibited by a lack of strategies for directing dendritic cell (DC) induction of effective tumor-specific cellular immunity. Pathogen engagement of DC lectins and toll-like receptors (TLRs) shapes immunity by directing T cell function. Strategies to activate specific DC signaling pathways via targeted receptor engagement are crucial to unlocking type 1 cellular immunity. Here, we engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunityin vivo. VLPs encapsulating TLR7 agonists and decorated with a selective mannose-derived ligand for the lectin DC-SIGN induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand failed to promote DC-mediated immunity. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4+and CD8+T cells that infiltrated solid tumors, inhibiting tumor growth in a murine melanoma model. Thus, VLPs employing lectin-driven immune reprogramming provide a framework for advancing cancer immunotherapies.
Architecture of genome-wide transcriptional regulatory network reveals dynamic functions and evolutionary trajectories inPseudomonas syringae
Authors: Sun Yue , Li Jingwei , Huang Jiadai , Li Shumin , Li Youyue , Lu Beifang , Deng Xin
Published: January 2024

The model Gram-negative plant pathogenPseudomonas syringaeutilises hundreds of transcription factors (TFs) to regulate its functional processes, including virulence and metabolic pathways that control its ability to infect host plants. Although the molecular mechanisms of regulators have been studied for decades, a comprehensive understanding of genome-wide TFs inPsph1448A remains limited. Here, we investigated the binding characteristics of 170 of 301 annotated TFs through ChIP-seq. Fifty-four TFs, 62 TFs and 147 TFs were identified in top-level, middle-level and bottom-level, reflecting multiple higher-order network structures and direction of information-flow. More than forty thousand TF-pairs were classified into 13 three-node submodules which revealed the regulatory diversity of TFs inPsph1448A regulatory network. We found that bottom-level TFs performed high co-associated scores to their target genes. Functional categories of TFs at three levels encompassed various regulatory pathways. Three and 25 master TFs were identified to involve in virulence and metabolic regulation, respectively. Evolutionary analysis and topological modularity network revealed functional variability and various conservation of TFs inP. syringae(Psph1448A,PstDC3000,PssB728a andPsaC48). Overall, our findings demonstrated the global transcriptional regulatory network of genome-wide TFs inPsph1448A. This knowledge can advance the development of effective treatment and prevention strategies for related infectious diseases.
EmergingMycobacterium bovisin Lebanon: a snapshot based on whole-genome sequencing
Authors: El Jouaid Israa , Sobh Ghena , Araj George F , Achache Wafaa , Grine Ghiles , Tokajian Sima , Al Khoury Charbel , Abdel-Sater Fadi , Drancourt Michel , Saad Jamal
Published: January 2024

Background

Tuberculosis is a pressing public health issue in Lebanon, a country of approximately five million people, including around 1.5 million refugees from Palestine and Syria. Prior research has revealed uncontrolled animal sources ofMycobacterium bovis, emphasizing the necessity for a comprehensive approach to combat tuberculosis in the region.

Methods

48 clinicalMycobacterium tuberculosiscomplex isolates were identified through whole genome sequence. Also, 43 animal fecal samples were collected from various farms across Lebanon to investigate the presence of theM. tuberculosiscomplex using CRISPR-csm4 PCR.

Results

Genomic analysis revealed that 39/48 (81.25%) of isolates wereM. tuberculosisand 9/48 (18.75%) wereM. bovis. M. tuberculosiswas distributed over four lineages, Indo-Oceanic L1 (n = 3/39)(7.6%), East-Asian L2 (n = 1/39)(2.5%), East-African Indian L3 (n = 5/39)(12.8%) and Euro-American L4 (n = 30/39)(76.9%). Sub-lineage L4.8 (Euro-American (mainly T), comprising 8/39 of the isolates (20.5%) was predominant, followed by sub-lineages L3 (East-African Indian, n = 5/39 isolates)(12.8%), L4.2.2.2 (Euro-American (Ural), n= 4/39 isolates)(10.2%) and L4.6.5 (Euro American, n=4/39 isolates)(10.2%). NineM. boviswere classified into two clades, designated as unknown2 (n=2/9; 22.2%) and unknown3 (n=7/9; 77.8%). Interestingly, none of the clades or others were detected in the 48 faecal samples using CRISPR standard PCR and qPCR.

Conclusions

This study offers insights into human and bovine tuberculosis in Lebanon, emphasizingM. tuberculosislineages prevalence andM. bovisdistribution into two clades, aiding the fight against tuberculosis, especially bovine tuberculosis, and renewing our understanding of tuberculosis dynamics in Lebanon.
Bridging Viruses and Prokaryotic Host through Miniature Inverted-repeat Transposable Elements (MITEs)
Authors: Nadal-Molero Francisco , Roselli Riccardo , Garcia-Juan Silvia , Campos-Lopez Alicia , Martin-Cuadrado Ana-Belen
Published: January 2024

Transposable elements (TEs) have a pivotal role in the evolution of genomes across all life domains. “Miniature Inverted-repeat Transposable-Elements” (MITEs) are non-autonomous TEs mainly located in intergenic regions, relying on external transposases for mobilization. The boundaries of MITEs’ mobilome were explored across nearly 1700 prokaryotic genera, 183232 genomes, revealing a widespread distribution. MITEs were identified in 56.5% of genomes, totaling over 1.4 million cMITEs (cellular). Cluster analysis revealed that a significant 97.4% of cMITEs were conserved within genera boundaries, with up to 23% being species-specific. Subsequently, this genus-specificity was evaluated as a tool to link microbial host to their viruses. A total of 51655 cMITEs had counterparts in viral sequences, termed vMITE (viral), resulting in the identification of 2798 viral sequences with vMITEs. Among these, 1501 sequences were positively assigned to a previously known host (41.8% were isolated virus, and 12.3% were assigned through CRISPR data), while 379 new host-virus associations were predicted. Deeper analysis in Neisseria and Bacteroidetes groups allowed the association of 242 and 530 new additional viral sequences, respectively. Given the abundance of non-culturable virus sequences accumulated in databases lacking affiliations with their microbial targets, MITEs are proposed as a novel approach to establishing valid virus-host relationships.

GRAPHICAL ABSTRACT
Fluoride export is required for competitive fitness of pathogenic microorganisms in dental biofilm models
Authors: Banerjee Aditya , Kang Chia-Yu , An Minjun , Koff B. Ben , Sunder Sham , Kumar Anuj , Tenuta Livia M. A. , Stockbridge Randy B.
Published: January 2024

Microorganisms resist fluoride toxicity using fluoride export proteins from one of several different molecular families. Cariogenic speciesStreptococcus mutansandCandida albicansextrude intracellular fluoride using a CLCFF−/H+antiporter and FEX fluoride channel, respectively, whereas commensal eubacteria, such asStreptococcus gordonii,export fluoride using a Fluc fluoride channel. In this work, we examine how genetic knockout of fluoride export impacts pathogen fitness in single-species and three-species dental biofilm models. For biofilms generated usingS. mutanswith genetic knockout of the CLCFtransporter, exposure to low fluoride concentrations decreasedS. mutanscounts, synergistically reduced the populations ofC. albicans, increased the relative proportion of commensalS. gordonii, and reduced properties associated with biofilm pathogenicity, including acid production and hydroxyapatite dissolution. Biofilms prepared withC. albicanswith genetic knockout of the FEX channel also exhibited reduced fitness in the presence of fluoride, but to a lesser degree. Imaging studies indicate thatS. mutansis highly sensitive to fluoride, with the knockout strain undergoing complete lysis when exposed to low fluoride for a moderate amount of time, and biochemical purification theS. mutansCLCFtransporter and functional reconstitution establishes that the functional protein is a dimer encoded by a single gene. Together, these findings suggest that fluoride export by oral pathogens can be targeted by specific inhibitors to restore biofilm symbiosis in dental biofilms, and thatS. mutansis especially susceptible to fluoride toxicity.

Importance

Dental caries is a globally prevalent condition that occurs when pathogenic species, includingStreptococcus mutansandCandida albicans, outcompete beneficial species, such asStreptococcus gordonii,in the dental biofilm. Fluoride is routinely used in oral hygiene to prevent dental caries. Fluoride also has antimicrobial properties, although most microbes possess fluoride exporters to resist its toxicity. This work shows that sensitization of cariogenic speciesStreptococcus mutansandCandida albicansto fluoride by genetic knockout of fluoride exporters alters the microbial composition and pathogenic properties of dental biofilms. These results suggest that the development of drugs that inhibit fluoride exporters could potentiate the anticaries effect of fluoride in over-the-counter products like toothpastes and mouth rinses. This is a novel strategy to treat dental caries.
C-di-AMP accumulation disrupts glutathione metabolism and inhibits virulence program expression inListeria monocytogenes
Authors: Siletti Cheta , Freeman Matthew , Tu Zepeng , Stevenson David M. , Amador-Noguez Daniel , Sauer John-Demian , Huynh TuAnh N.
Published: January 2024

C-di-AMP is an essential second messenger in many bacteria but its levels must be regulated. Unregulated c-di-AMP accumulation attenuates the virulence of many bacterial pathogens, including those that do not require c-di-AMP for growth. However, the mechanisms by which c-di-AMP regulates bacterial pathogenesis remain poorly understood. InListeria monocytogenes, a mutant lacking both c-di-AMP phosphodiesterases, denoted as the ΔPDE mutant, accumulates a high c-di-AMP level and is significantly attenuated in the mouse model of systemic infection. All keyL. monocytogenesvirulence genes are transcriptionally upregulated by the master transcription factor PrfA, which is activated by reduced glutathione (GSH) during infection. Our transcriptomic analysis revealed that the ΔPDE mutant is significantly impaired for the expression of virulence genes within the PrfA core regulon. Subsequent quantitative gene expression analyses validated this phenotype both at the basal level and upon PrfA activation by GSH. A constitutively active PrfA*variant, PrfA G145S, which mimics the GSH-bound conformation, restores virulence gene expression in ΔPDE but only partially rescues virulence defect. Through GSH quantification and uptake assays, we found that the ΔPDE strain is significantly depleted for GSH, and that c-di-AMP inhibits GSH uptake. Constitutive expression ofgshF(encoding a GSH synthetase) does not restore GSH levels in the ΔPDE strain, suggesting that c-di-AMP inhibits GSH synthesis activity or promotes GSH catabolism. Taken together, our data reveals GSH metabolism as another pathway that is regulated by c-di-AMP. C-di-AMP accumulation depletes cytoplasmic GSH levels withinL. monocytogenesthat leads to impaired virulence program expression.

IMPORTANCE

C-di-AMP regulates both bacterial pathogenesis and interactions with the host. Although c-di-AMP is essential in many bacteria, its accumulation also attenuates the virulence of many bacterial pathogens. Therefore, disrupting c-di-AMP homeostasis is a promising antibacterial treatment strategy, and has inspired several studies that screened for chemical inhibitors of c-di-AMP phosphodiesterases. However, the mechanisms by which c-di-AMP accumulation diminishes bacterial pathogenesis are poorly understood. Such understanding will reveal the molecular function of c-di-AMP, and inform therapeutic development strategies. Here, we identify GSH metabolism as a pathway regulated by c-di-AMP that is pertinent toL. monocytogenesreplication in the host. Given the role of GSH as a virulence signal, nutrient, and antioxidant, GSH depletion impairs virulence program expression and likely diminishes host adaptation.
Phase Diagram of the Two-Flavor Schwinger Model at Zero Temperature
Authors: Dempsey Ross , Klebanov Igor R. , Pufu Silviu S. , Søgaard Benjamin T. , Zan Bernardo
Published: January 2024

We examine the phase structure of the two-flavor Schwinger model as a function of the θ angle and the two masses, m1 and m2. In particular, we find interesting effects at θ=π: along the SU(2)-invariant line m1=m2=m, in the regime where m is much smaller than the charge g, the theory undergoes logarithmic renormalization group flow of the Berezinskii-Kosterlitz-Thouless type. As a result, dimensional transmutation takes place, leading to a nonperturbatively small mass gap ∼e−Ag2/m2. The SU(2)-invariant line lies within a region of the phase diagram where the charge conjugation symmetry is spontaneously broken and whose boundaries we determine numerically. Our numerical results are obtained using the Hamiltonian lattice gauge formulation that includes the mass shift mlat=m−g2a/4 dictated by the discrete chiral symmetry.

Published by the American Physical Society
2024
Exploring the neighborhood of 1-layer QAOA with instantaneous quantum polynomial circuits
Authors: Leontica Sebastian , Amaro David
Published: January 2024

We embed 1-layer QAOA circuits into the larger class of parametrized instantaneous quantum polynomial circuits to produce an improved variational quantum algorithm for solving combinatorial optimization problems. The use of analytic expressions to find optimal parameters classically makes our protocol robust against barren plateaus and hardware noise. The average overlap with the ground state scales as 2−0.31(2)N with the number of qubits N for random Sherrington-Kirkpatrick (SK) Hamiltonians of up to 29 qubits, a polynomial improvement over 1-layer QAOA. Additionally, we observe that performing variational imaginary time evolution on the manifold approximates low-temperature pseudo-Boltzmann states. Our protocol outperforms 1-layer QAOA on the recently released Quantinuum H2 trapped-ion quantum hardware and emulator, where we obtain an average approximation ratio of 0.985 across 312 random SK instances of 7 to 32 qubits, from which almost 44% are solved optimally using only 4 to 1208 shots per instance.

Published by the American Physical Society
2024
Synthesis and structure of trans-bis(4-amino-3-nitrobenzoato-κO)bis(4-amino-3-nitrobenzoic acid-κO)diaquamanganese(II) dihydrate
Authors: Narmanova Feruza S. , Turaev Khayit Kh. , Ibragimov Aziz B. , Ashurov Jamshid M.
Published: January 2024

The manganese title complex, [Mn(C7H5N2O4)2(C7H6N2O4)2(H2O)2]·2H2O, is one of the first 4-amino 3-nitrobenzoic acid (4 A3NBA) monoligand metal complexes to be synthesized. It crystallizes in the centrosymmetric monoclinic space group P21/n with the complex molecules located on inversion centers. Four 4 A3NBA ligand molecules are monodentately coordinated by the Mn2+ ion through the carboxylic oxygen atoms while the other two positions of the inner coordination sphere are occupied by water molecules, giving rise to a distorted octahedron, and two water molecules are in the outer coordination sphere. There are two intramolecular hydrogen bonds in the complex molecule. The first is of the common N—H...O=N type, while the second is a rarely occurring very strong hydrogen bond in which a common proton is shared by two uncoordinated oxygen atoms of neighboring carboxylate groups. In the crystal, an intricate system of intermolecular hydrogen bonds links the complex molecules into a three-dimensional-network.
Crystal structure of Ti4Ni2C
Authors: Liu Huizi , Liang Xinyu , Liu Yibo , Fan Changzeng , Wen Bin , Zhang Lifeng
Published: January 2024

Single crystals of the intermetallic phase with composition Ti4Ni2C were serendipitously obtained by high-pressure sintering of a mixture with initial chemical composition Ti2Ni. The Ti4Ni2C phase crystallizes in the Fd\overline{3}m space group and can be considered as a partially filled Ti2Ni structure with the C atom occupying an octahedral void. Ti4Ni2C is isotypic with Ti4Ni2O, Nb4Ni2C and Ta4Ni2C, all of which were studied previously by means of powder diffraction.