bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Use of Emapalumab With Ruxolitinib and Dexamethasone as an Effective Treatment for Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis Complicated With Multiorgan Damage and Severe Infection
Authors: Liang Juan , Xu Xiaojun , Chen Zhenjie , Yu Jia , Tang Yongmin
Published: May 2024

Anti–interferon-γ monoclonal antibody emapalumab and JAK1/2 inhibitors ruxolitinib have been widely reported for the treatment of hemophagocytic lymphohistiocytosis (HLH) recently. These targeted drugs have fewer side effects and may provide new options for patients with HLH who are refractory to previous treatment or intolerant to chemotherapy. Herein, we reported a case of Epstein-Barr virus–related HLH, which did not respond well to HLH-94 plus ruxolitinib and developed severe fungal infection. The disease was successfully controlled after a combination therapy of emapalumab, ruxolitinib, and dexamethasone.
Crowdsourced Partner Services Among Men Who Have Sex With Men Living With HIV: A Pilot Randomized Controlled Trial in China
Authors: Yan Xumeng , Tucker Joseph D. , Miller William C. , Xu Huifang , Zhou Yi , Gu Yuzhou , Chen Meichun , Liang Meiqing , Lu Jie , Zhan Lishan , Tang Weiming
Published: May 2024

Background

This study aimed to assess the acceptability, feasibility, and preliminary effectiveness of a crowdsourced HIV partner services (PS) intervention among men who have sex with men living with HIV (MLWH) in China.

Methods

A pilot 2-arm randomized controlled trial was conducted in 3 HIV testing clinics in China. The control arm received conventional HIV PS, whereas the intervention arm received a crowdsourced intervention, including HIV self-testing kits for secondary distribution (HIVST-SD), digital education materials, and assisted PS. The intervention was developed through 2-phase crowdsourcing events including an open call and a Designathon. The primary outcomes were measured by the 3-month follow-up rate (i.e., the proportion of participants who completed the follow-up survey to report HIV PS outcomes 3 months after enrollment) and the frequency of using intervention components (feasibility), index evaluation of intervention components (acceptability), and the proportion of partners getting HIV testing (preliminary effectiveness).

Results

The study enrolled 121 newly diagnosed MLWH between July 2021 and May 2022. The 3-month follow-up rates were 93% (75 of 81) and 83% (33 of 40) in the intervention and control arms, respectively. Crowdsourced intervention components demonstrated feasibility, with all indexes using digital educational materials, 23 successfully using HIVST-SD, and 6 employing provider-referral to notify 9 sexual partners. Acceptability was high, with HIVST-SD and digital educational materials rated 4.4 and 4.1 out of 5. The proportion of partners receiving HIV testing was 11% higher in the intervention arm than in the control arm (marginal significance with 95% confidence interval, −2% to 24%; 38% vs. 27%).

Conclusions

The crowdsourced HIV PS intervention was acceptable and feasible, suggesting the potential to facilitate partner HIV testing among Chinese MLWH. Further implementation research is recommended to expand HIV PS among key populations in low- and middle-income countries.

Clinical Trial Registration ID

NCT04971967 (Protocol ID: 19-0496).
Distinct anal microbiome is correlated with anal cancer precursors in MSM with HIV
Authors: Brickman Cristina E. , Agnello Melissa , Imam Nabeel , Camejo Pamela , Pino Rodolfo , Carroll Lauren N. , Chein Aung , Palefsky Joel M.
Published: May 2024

Objectives:

Anal cancer risk is elevated in MSM with HIV (MSMWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMWH.

Design:

Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMWH and cross-sectional comparison of the anal microbiome of MSMWH with anal HSIL with the anal microbiome of MSMWH without anal HSIL.

Methods:

Sterile swabs were used to sample the anus of MSMWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity, and differential abundance analysis were used to compare samples.

Results:

One hundred sixty-six anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia, and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMWH/hr-HPV/HSIL.

Conclusion:

The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL.
Does delayed operation increase morbidity and mortality? An analysis of emergency general surgery procedures
Authors: Franklin Kelsey N. , Nishtala Madhuri , McCracken Ana , Berian Julia R. , Zarzaur Ben
Published: May 2024

BACKGROUND

Early operation is assumed to improve outcomes after emergency general surgery (EGS) procedures; however, few data exist to inform this opinion. We aimed to (1) characterize time-to-operation patterns among EGS procedures and (2) test the association between timing and patient outcomes. We hypothesize that patients receiving later operations are at greater risk for mortality and morbidity.

METHODS

We performed a retrospective cohort study of the American College of Surgeons National Surgical Quality Improvement Program data for adults aged 18 to 89 years who underwent nonelective intra-abdominal operations (appendectomy, cholecystectomy, small bowel resection, lysis of adhesions, and colectomy) from 2015 to 2020. The primary outcome was 30-day postoperative mortality. Secondary outcomes were serious morbidity and all morbidity. Admission-to-operation timing was calculated and classified as early (≤48 hours) or late (>48 hours). A multivariable logistic regression model adjusted risk estimates for age, comorbidities, frailty (Modified Frailty Index, 5-item score), and other confounders.

RESULTS

Of 269,959 patients (mean age, 47.0 years; 48.0% male, 61.6% White), 88.7% underwent early operation, ranging from 70.36% (lysis of adhesions) to 98.67% (appendectomy). Unadjusted 30-day mortality was higher for late versus early operation (6.73% vs. 1.96%;p< 0.0001). After risk adjustment, late operation significantly increased risk for 30-day mortality (odds ratio [OR], 1.545; 95% confidence interval [CI], 1.451–1.644), serious morbidity (OR, 1.464; 95% CI, 1.416–1.514), and all morbidity (OR, 1.468; 95% CI, 1.417–1.520). This mortality risk persisted for all EGS procedures; risk of serious and any morbidity persisted for all procedures except cholecystectomy.

CONCLUSION

Late operation significantly increased risk for 30-day mortality, serious morbidity, and all morbidity across a variety of EGS procedures. We believe that these findings will inform decisions regarding timing of EGS operations and allocation of surgical resources.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Research priorities in tranexamic acid after trauma: Secondary analysis of the National Trauma Research Action Plan
Authors: Brito Alexandra MP , Meizoso Jonathan P. , Costantini Todd W.
Published: May 2024

INTRODUCTION

Tranexamic acid (TXA) is an antifibrinolytic drug that is used in traumatic hemorrhage and traumatic brain injury. Although TXA is considered relatively safe and inexpensive and is widely available, data regarding its mechanisms, optimal dosing, and timing, as well as relative risks and benefits for different patient populations, are inconsistent. In this study, we aim to identify and summarize consensus research questions related to TXA across all National Trauma Research Action Plan (NTRAP) Delphi expert panels to identify priorities for future research on TXA in trauma.

METHODS

A secondary analysis was performed using consensus-based research priorities collected by 11 NTRAP topic panels using a Delphi methodology. The database of questions was queried for the keywords “tranexamic” and “TXA.” The identified questions were sorted by subject matter and summarized.

RESULTS

Seven panels included a total of 73 TXA-related questions. Forty-six questions reached consensus. The most addressed topic was outcomes (discussed in 64% of questions) followed by indications (49%) and specific patient populations (38%). Because of overlap across panels, questions were summarized and sorted by topic resulting in 21 priority research questions.

CONCLUSION

Seventy-three total questions and 46 questions reaching consensus were identified by NTRAP panelists. The key topics identified in these questions should be prioritized in future funded research on TXA in trauma.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level V.
Removing the barriers to prehospital blood: A roadmap to success
Authors: Schaefer Randall M. , Bank Eric A. , Krohmer Jon R. , Haskell Andrew , Taylor Audra L. , Jenkins Donald H. , Holcomb John B.
Published: May 2024

This review describes the necessity, evolution, and current state of prehospital blood programs in the United States. Less than 1% of 9-1-1 ground emergency medical service agencies have been able to successfully implement prehospital blood transfusions as part of a resuscitation strategy for patients in hemorrhagic shock despite estimates that annually between 54,000 and 900,000 patients may benefit from its use. The use of prehospital blood transfusions as a tool for managing hemorrhagic shock has barriers to overcome to ensure it becomes widely available to patients throughout the United States. Barriers include (1) current state Emergency Medical Services clinicians' scope of practice limitations; (2) program costs and reimbursement of blood products; (3) no centralized data collection process for prehospital hemorrhagic shock and patient outcomes; (4) collaboration between prehospital agencies, blood suppliers, and hospital clinicians and transfusion service activities. The following article identifies barriers and a proposed roadmap to reduce death due to prehospital hemorrhage.
Myocardial function, mechanics and work by echocardiography in adolescents with severe obesity
Authors: Larios Guillermo , Uribe Sergio , Trincado Claudia , Arancibia-Galilea Francisca , Valderrama Paulo , Espejo Juan Pablo , Amezquita María Virginia , Barja Salesa
Published: May 2024

Introduction

Obesity and its metabolic complications can impact the heart’s structure and function in childhood, although demonstrating this impact has been challenging. New echocardiographic parameters such as left atrial strain (LAε) and left ventricular strain (LVε), as well as myocardial work (MW), could reveal subclinical alterations in cardiac function.

Objective

The aim is to evaluate the feasibility of these parameters in adolescents with severe obesity and explore their associations with body fat, metabolic comorbidities, and physical capacity.

Methods

This is a cross-sectional study in adolescents with obesity who underwent echocardiography with analysis of LAε, LVε and MW using speckle tracking. Feasibility and association with anthropometry, body fat percentage, comorbidities and cardiopulmonary test were analyzed.

Results

Twenty adolescents were recruited, 13 (65%) were males, median age 14.2 (interquartile range: 12.9–14.9) years old. The median Z-score for BMI (zBMI) was +3.03 (2.87–3.14), 14 (70%) had severe obesity (zBMI ≥+3), 12 (60%) body fat ≥95th percentile, 9 (45%) high blood pressure (HBP) and 8 (40%) metabolic syndrome. The analysis of the echocardiographic parameters was feasible in 95% (LAε) and 100% (LVε and MW). LVε was lower in adolescents with vs. without metabolic syndrome: 17.8% (17.5–19.3%) vs. 19.3% (18.3–20.3%), P = 0.046; and with vs. without HBP 17.8% (17.5–18.6%) vs. 19.7% (18.4–20.3%), P = 0.02. Those with body fat ≥95th percentile had lower LAε and MW parameters, without association with cardiopulmonary test.

Conclusion

Echocardiographic evaluation of LAε, LVε and MW is feasible in adolescents with severe obesity. A higher proportion of body fat and the presence of comorbidities are associated with alterations in these new echocardiographic functional parameters suggesting myocardial impact of higher metabolic compromise.
A robotic falcon induces similar collective escape responses in different bird species
Authors: Storms Rolf F. , Carere Claudio , Musters Robert , Hulst Ronja , Verhulst Simon , Hemelrijk Charlotte K.
Published: May 2024

Patterns of collective escape of a bird flock from a predator are fascinating, but difficult to study under natural conditions because neither prey nor predator is under experimental control. We resolved this problem by using an artificial predator (RobotFalcon) resembling a peregrine falcon in morphology and behaviour. We imitated hunts by chasing flocks of corvids, gulls, starlings and lapwings with the RobotFalcon, and compared their patterns of collective escape to those when chased by a conventional drone and, in case of starlings, hunted by wild peregrine falcons. Active pursuit of flocks, rather than only flying nearby by either the RobotFalcon or the drone, made flocks collectively escape more often. The RobotFalcon elicited patterns of collective escape in flocks of all species more often than the drone. Attack altitude did not affect the frequency of collective escape. Starlings escaped collectively equally often when chased by the RobotFalcon or a wild peregrine falcon. Flocks of all species reacted most often by collective turns, second most often by compacting and third by splitting into subflocks. This study demonstrates the potential of an artificial aerial predator for studying the collective escape behaviour of free-living birds, opening exciting avenues in the empirical study of prey–predator interactions.
Essential roles of the nucleolus during early embryonic development: a regulatory hub for chromatin organization
Authors: Fu Bo , Ma Hong , Liu Di
Published: May 2024

The nucleolus is the most prominent liquid droplet-like membrane-less organelle in mammalian cells. Unlike the nucleolus in terminally differentiated somatic cells, those in totipotent cells, such as murine zygotes or two-cell embryos, have a unique nucleolar structure known as nucleolus precursor bodies (NPBs). Previously, it was widely accepted that NPBs in zygotes are simply passive repositories of materials that will be gradually used to construct a fully functional nucleolus after zygotic genome activation (ZGA). However, recent research studies have challenged this simplistic view and demonstrated that functions of the NPBs go beyond ribosome biogenesis. In this review, we provide a snapshot of the functions of NPBs in zygotes and early two-cell embryos in mice. We propose that these membrane-less organelles function as a regulatory hub for chromatin organization. On the one hand, NPBs provide the structural platform for centric and pericentric chromatin remodelling. On the other hand, the dynamic changes in nucleolar structure control the release of the pioneer factors (i.e. double homeobox (Dux)). It appears that during transition from totipotency to pluripotency, decline of totipotency and initiation of fully functional nucleolus formation are not independent events but are interconnected. Consequently, it is reasonable to hypothesize that dissecting more unknown functions of NPBs may shed more light on the enigmas of early embryonic development and may ultimately provide novel approaches to improve reprogramming efficiency.
Exploring new technologies for the future generation: exploration–exploitation trade-off in an intergenerational framework
Authors: Nakawake Yo , Kobayashi Yutaka
Published: May 2024

Decision making on exploring or exploiting technology was studied by means of a laboratory experiment with a two-generation framework. In this framework, the design of a virtual tool is transmitted from the first to second generation, and hence, the former can help the latter by frequently exploring better tool designs but at the cost of reduced opportunities to exploit the existing tool to increase its own benefits. We set two experimental conditions (‘repaid’ and ‘unrepaid’) as well as a control condition (asocial), in which the second generation is absent. In the ‘repaid’ experimental condition, participants received an extra payment proportional to the score gained by the second generation, such that they were monetarily incentivized to help the second generation. Such an incentive was not given in the ‘unrepaid’ condition. An analysis of a formal model and computer simulations predicted that rational participants should increase investment in exploration only in the repaid condition when compared with the asocial control. The prediction was confirmed by the results of the experiment. These findings together suggest that humans may not have a propensity to invest in costly exploration of new technologies solely to help future generations.
Evidence for socially influenced and potentially actively coordinated cooperation by bumblebees
Authors: Loukola Olli J. , Antinoja Anna , Mäkelä Kaarle , Arppi Janette , Peng Fei , Solvi Cwyn
Published: May 2024

Cooperation is common in animals, yet the specific mechanisms driving collaborative behaviour in different species remain unclear. We investigated the proximate mechanisms underlying the cooperative behaviour of bumblebees in two different tasks, where bees had to simultaneously push a block in an arena or a door at the end of a tunnel for access to reward. In both tasks, when their partner’s entry into the arena/tunnel was delayed, bees took longer to first push the block/door compared with control bees that learned to push alone. In the tunnel task, just before gaining access to reward, bees were more likely to face towards their partner than expected by chance or compared with controls. These results show that bumblebees’ cooperative behaviour is not simply a by-product of individual efforts but is socially influenced. We discuss how bees’ turning behaviours, e.g. turning around before first reaching the door when their partner was delayed and turning back towards the door in response to seeing their partner heading towards the door, suggest the potential for active coordination. However, because these behaviours could also be interpreted as combined responses to social and secondary reinforcement cues, future studies are needed to help clarify whether bumblebees truly use active coordination.
A hydrocele revealing epididymal tuberculosis
Authors: Ben Lahlou Yassine , Laanibi Zakaria , Malihy Zakaria , Benaissa Elmostapha , Maleb Adil , Elktaibi Abderrahim , Chadli Mariama , Elouennass Mostapha
Published: May 2024

Abstract:

Urogenital tuberculosis is a severe form of extrapulmonary tuberculosis. The organs most commonly affected are the epididymis and the testis. Clinical manifestations may include epididymitis, orchi-epididymitis, hydrocele, associated with leukocyturia, and significant hematuria.
We report a case of a patient with a hydrocele that revealed epididymal tuberculosis.
Whole-Genome Sequencing assisted outbreak investigation of Salmonella Enteritidis, at a hospital in South Africa, September 2022
Authors: Brummer Brian , Smith Anthony Marius , Modise Motshabi , Thomas Juno , Mdose Hetani , Mokoena Ramasedi , Baleni Dikeledi
Published: May 2024

Introduction Health authorities were notified of a suspected outbreak of foodborne disease in a hospital in South Africa. Staff and patients reported acute onset of abdominal cramps, diarrhoea, fever and rigors after eating a chicken pasta meal.
Aim To report on the use whole-genome sequencing (WGS) analysis of bacterial isolates to support an epidemiological investigation.
Methodology Epidemiological investigation of the outbreak was led by the Infection Control Manager of the hospital and supported by an outbreak response team. Standard microbiological procedures were used to process stool samples and culture/identify diarrhoeal pathogens. Bacterial cultures were investigated using WGS performed using Illumina NextSeq technology. WGS data were analyzed using multiple bioinformatics tools, including those available at the Center for Genomic Epidemiology and EnteroBase. Core-genome multilocus sequence typing (cgMLST) was used to investigate the phylogeny of isolates.
Results Forty-nine cases were identified. Stool samples were collected from 21 cases and nontyphoidal Salmonella was isolated from 19/21 (90%) of the samples. All isolates were identified as Salmonella enterica serovar Enteritidis. All isolates differed from each other by  allele differences on cgMLST, indicating that isolates are highly genetically related. Delays in testing of food retention samples rendered the negative test results of limited value. A case control study was conducted; eating chicken pasta was strongly associated with developing gastroenteritis (Haldane-Anscombe Adjusted Odds Ratio, 15.398)
Conclusion The epidemiological evidence suggests that the chicken pasta was the likely vehicle of transmission in this outbreak. The source of Salmonella enterica serovar Enteritidis remains unknown.
Most human DNA replication initiation is dispersed throughout the genome with only a minority within previously identified initiation zones
Authors: Carrington Jamie T. , Wilson Rosemary H C , Thiyagarajan Sathish , Barker Tom , Catchpole Leah , Durrant Alex , Knitlhoffer Vanda , Watkins Chris , Gharbi Karim , Nieduszynski Conrad A.
Published: May 2024

The identification of sites of DNA replication initiation in mammalian cells has been challenging. Here, we present unbiased detection of replication initiation events in human cells using BrdU incorporation and single-molecule nanopore sequencing. Increases in BrdU incorporation allow us to measure DNA replication dynamics, including identification of replication initiation, fork direction and termination on individual nanopore sequencing reads. Importantly, initiation and termination events are identified on single-molecules with high resolution, throughout S-phase and across the human genome. We find a significant enrichment of initiation sites within the broad initiation zones identified by population level studies. However, these focussed initiation sites only account for ∼20% of all identified replication initiation events. Most initiation events are dispersed throughout the genome and are missed by cell population approaches. This indicates that most initiation occurs at sites that, individually, are rarely used. These dispersed initiation sites contrast with the focused sites identified by population studies, in that they do not show a strong relationship to transcription or a particular epigenetic signature. Therefore, single-molecule sequencing enables unbiased detection and characterisation of DNA replication initiation events, including the numerous dispersed initiation events that replicate most of the human genome.
Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain
Authors: Pattison Luke A. , Rickman Rebecca H. , Hilton Helen , Wijesinghe Susanne N. , Ladds Graham , Yang Li , Jones Simon W. , Smith Ewan St. John
Published: May 2024

Inflammation is associated with localised acidosis, however, attributing physiological and pathological roles to proton-sensitive receptors is challenging due to their diversity and widespread expression. Here, agonists of the proton-sensing GPCR, GPR65, were systematically characterised. The synthetic agonist BTB09089 (BTB) recapitulated many proton-induced signalling events and demonstrated selectivity for GPR65. BTB was used to show that GPR65 activation on fibroblast-like synoviocytes (FLS), cells that line synovial joints, results in the secretion of pro-inflammatory mediators capable of recruiting immune cells and sensitising sensory neurons. Intra-articular injection of BTB resulted in GPR65-dependent sensitisation of knee-innervating neurons and nocifensive behaviours in mice. Stimulation of GPR65 on human FLS also triggered the release of inflammatory mediators and synovial fluid samples from human osteoarthritis patients were shown to activate GPR65. These results suggest a role of GPR65 in mediating cell-cell interactions that drive inflammatory joint pain in both mice and humans.
Cell rearrangement progression along the apical-basal axis is linked with 3D epithelial tissue structure
Authors: Kusaka Erika M. , Ostvar Sassan , Wang Xun , Liu Xiaoyun , Kasza Karen E.
Published: May 2024

Epithelial tissues undergo extensive structural remodeling during embryonic development. Tissue remodeling is often enabled by oriented cell rearrangements that are linked with patterns of mechanical stress in the tissue and with tissue mechanical properties. Cell rearrangements and their links to tissue structure have largely been studied at the apical side of tissues at the level of adherens junctions. Less is known about the involvement of basolateral domains in cell rearrangements. Here we use live confocal imaging to quantify cell rearrangements, cell packing structure, and cell morphology in 3D in the converging and extendingDrosophilagermband epithelium. We report gradients in cell shapes and tissue structure along the apical-basal axis of the germband, suggesting that the apical and basolateral domains display distinct behaviors. Cell rearrangements initiate at apical as well as basolateral positions, with initiation frequencies also displaying a gradient along the apical-basal axis. Following initiation, rearrangements propagate across the apical-basal axis and lateral cell contacts remodel; these events involve scutoids and other complex 3D cell shapes as intermediate states. These findings uncover novel aspects of the cell rearrangements that drive dynamic remodeling of epithelia and reveal links between rearrangements and gradients in tissue structure along the apical-basal axis.
Exploring the Transcriptomic Profile of Human Monkeypox Virus via CAGE and Native RNA Sequencing Approaches
Authors: Nagy Gergely Ármin , Tombácz Dóra , Prazsák István , Csabai Zsolt , Dörmő Ákos , Gulyás Gábor , Kemenesi Gábor , Tóth Gábor E. , Holoubek Jiří , Růžek Daniel , Kakuk Balázs , Boldogkői Zsolt
Published: May 2024

In this study, we employed short- and long-read sequencing technologies to delineate the transcriptional architecture of the human monkeypox virus and to identify key regulatory elements that govern its gene expression. Specifically, we conducted a transcriptomic analysis to annotate the transcription start sites (TSSs) and transcription end sites (TESs) of the virus by utilizing cap analysis of gene expression sequencing on the Illumina platform and direct RNA sequencing on the Oxford Nanopore technology device. Our investigations uncovered significant complexity in the use of alternative TSSs and TESs in viral genes. In this research, we also detected the promoter elements and poly(A) signals associated with the viral genes. Additionally, we identified novel genes in both the left and right variable regions of the viral genome.

Importance

Generally, gaining insight into how the transcription of a virus is regulated offers insights into the key mechanisms that control its life cycle. The recent outbreak of the human monkeypox virus has underscored the necessity of understanding the basic biology of its causative agent. Our results are pivotal for constructing a comprehensive transcriptomic atlas of the human monkeypox virus, providing valuable resources for future studies.
Performance of the BD Phoenix CPO detect assay for the detection and classification of OXA-48 producing-Escherichia colithat do not coproduce ESBL/pAmpC
Authors: Galán-Sánchez Fátima , Portillo-Calderón Inés , Rodriguez-Iglesias Manuel , Pascual Álvaro , López-Cerero Lorena
Published: May 2024

Reliable detection of OXA-48-like enzymes in routine antimicrobial susceptibility testing is difficult, especially if the isolate does not coproduce other beta-lactamases. The BD Phoenix™ Emerge panel includes the CPO Detect Test (CPO-T), which allows simultaneous antimicrobial susceptibility testing and carbapenemase detection and characterization. We evaluated the accuracy of detection and classification of carbapenemases determined by CPO-T against a characterized set of OXA-48-producingEscherichia coliisolates that do not co-produce ESBL/pAmpC, and BD Phoenix™ for rapid antimicrobial susceptibility testing. A total of 51E. coliisolates were included All the isolates were sequenced using Illumina and analyzed using Resfinder and CARD for resistance determinants, MLSTfinder for typing and Clermont Phylotyper for phylotypes. CPO-T was performed within the BD Phoenix™ NMIC-502 panel. Disk diffusion, with readings at 4, 6, 8 and 24 hours, was performed as reference method (RDD). The CPO-T detected carbapenemase activity in 100% of the isolates within 7 hours of incubation and 42 (82.4%) isolates were correctly assigned to the class D Ambler. For all isolates and antibiotics, BD Phoenix™ provided definitive susceptibility results in less than 8 hours in 64.6% of cases compared to 58.2% with RDD. Overall categorical agreement was 90.7% and 5.9% very major, 6.2% major and 3.2% minor errors were observed. Our results demonstrate that CPO-T is a reliable tool for the detection of OXA-48 inE. coliisolates that do not co-produce ESBL/pAmpCwithout the need for additional testing, and that BD Phoenix™ provides rapid results for the antibiotics most commonly used in empirical treatment.

IMPORTANCE

Detection of OXA-48-like enzymes in isolates that do not co-produce other beta-lactamases in routine antimicrobial susceptibility testing is difficult, and studies on these types of isolates are scarce. Our study analyzes the performance of the BD Phoenix™ Emerge panel, which includes the CPO detection test (CPO-T), in a characterized set of OXA-48-producingEscherichia coliisolates that do not co-produce ESBL/pAmpC, and also provide information about time to results of this system.
The Streptococcus pneumoniae transcriptome in patient cerebrospinal fluid identifies novel virulence factors required for meningitis
Authors: Wall Emma C , Guerra-Assuncao Jose-Afonso , Yang Marie , Konig Rutger , Audshasai Teerawit , Proust Alize , Aprianto Rieza , Ramos-Sevillano Elisa , Ercoli Giuseppe , Bordin Nicola , Agostinho-Terra Vanessa S , Veening Jan-Willem , Lalloo David G , Wren Brendan W , Wilkinson Robert J , Brouwer Matthijs C , van de Beek Diederik , Kadiloglu Aras , Heyderman Robert S , Brown Jeremy S
Published: May 2024

To better understand Streptococcus pneumoniae pathogenesis we performed RNA sequencing on cerebrospinal fluid (CSF) from meningitis patients to identify bacterial genes expressed during invasion of the central nervous system. Comparison to transcriptome data for serotype 1 S. pneumoniae cultured in ex vivo human CSF defined a subset of 57 genes with high expression during human meningitis. Deletion of two of the most highly expressed genetic loci, bgaA (encodes for a beta-galactosidase) or the SP_1801-5 putative stress response operon, resulted in S. pneumoniae strains still able to transmigrate the blood brain barrier but which were more susceptible to complement opsonisation and unable to maintain brain infection in a murine meningitis model. In 1144 meningitis patients, infection with bgaA containing S. pneumoniae strains was associated with a higher mortality (22% versus 14% p=0.02). These data demonstrate that direct bacterial RNAseq from CSF can identify previously undescribed S. pneumoniae virulence factors required for meningitis pathogenesis.
How light at night sets the circalunar clock in the marine midgeClunio marinus
Authors: Peralta Carolina M. , Feunteun Eric , Guillaudeau Julien , Briševac Dušica , Kaiser Tobias S.
Published: May 2024

Many organisms inhabiting the interface between land and sea have evolved biological clocks corresponding to the period of the semilunar (14.77d) or the lunar (29.53d) cycle. Since tidal amplitude is modulated across the lunar cycle, these circasemilunar or circalunar clocks allow organisms to adapt to the tides. Biological clocks are synchronized to external cycles via environmental cues calledzeitgebers. Here, we explore how light at night sets the circalunar and circasemilunar clocks ofClunio marinus, a marine insect that relies on these clocks to control timing of emergence. We first characterized how moonlight intensity is modulated by the tides by measuring light intensity in the natural habitat ofC. marinus. In laboratory experiments, we then explored how different moonlight treatments set the phase of the clocks of twoC. marinusstrains, one with a lunar rhythm and one with a semilunar rhythm. Light intensity alone does not affect the phase or strength of the lunar rhythm. Presenting moonlight during different 2-hour or 4-hour windows during the subjective night shows that (1) the required duration of moonlight is strain-specific, (2) there are strain-specific moonlight sensitivity windows and (3) timing of moonlight can shift the phase of the lunar rhythm to stay synchronized with the lowest low tides. Experiments simulating natural moonlight patterns with moonrise and moonset confirm that the phase is set by the timing of moonlight. Light intensity within the ranges observed in the field leads to the best synchronization. Taken together, we show that there is a complex and strain-specific integration of intensity, duration and timing of light at night to precisely entrain the lunar and semilunar rhythms. The observed fine-tuning of the rhythms under the most natural moonlight regimes lays the foundation for a better chronobiological and genetic dissection of the circa(semi)lunar clock inC. marinus.
WITHDRAWN: Revealing Mechanism of Allostery in RIPK2 kinase
Authors: Bhakat Soumendranath , Siokas Ioannis , Covitz Rachel Mei-Lian , Degterev Alexei
Published: May 2024

Withdrawal Statement

The authors have withdrawn their manuscript owing to a conflict of interest. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author, Soumendranath Bhakat.
Convergent evolution of noncoding elements associated with short tarsus length in birds
Authors: Shakya Subir B. , Edwards Scott V. , Sackton Timothy B.
Published: May 2024

Convergent evolution is the independent evolution of similar traits in unrelated lineages across the Tree of Life. Various factors underlie convergent evolution including convergent rate changes through consistent shifts in substitution rate in the same genes or gene networks. In this study, we use comprehensive phenotypic data to identify seven bird clades with independent shortening in tarsus length and use both comparative genomic and population genetic data to identify convergent evolutionary changes among four target clades with shifts to shorter optimal tarsus length. Using a newly generated, comprehensive set of avian conserved non-exonic elements (CNEEs), we find strong evidence for convergent acceleration in short-tarsi clades among CNEEs, but not protein-coding genes. Accelerated CNEEs in short-tarsi clades are preferentially located near genes with functions in development, with the strongest enrichment associated with skeletal system development. Further analysis of gene networks highlighted this larger role of changes in regulation of broadly homologous developmental genes and pathways as being an integral aspect of limb size variability in birds.
Flexibility in the face of climate change? A rapid and dramatic shift toward later spring migration in Hudsonian Godwits (Limosa haemastica)
Authors: Puleo Lauren , Huang Feipeng , Stager Maria , Senner Nathan R.
Published: May 2024

With rapid environmental change, shifts in migration timing are vitally important for maintaining population stability and have been widely documented. However, little remains known abouthowmigrants are driving these shifts and what factors may influence the effective utilization of these strategies, limiting our ability to accurately assess species- and population-level vulnerability to climate change. The Hudsonian godwit (Limosa haemastica) is an extreme long-distance migratory shorebird that has (1) previously shifted its population-level migration timing and (2) exhibits sex-specific morphological differences. Therefore, we combined over a decade of light-level geolocator tracking data from a single breeding population with a historical predictive model to assess on-going shifts in migration timing while determining the time-shifting strategies utilized by each sex. Surprisingly, we found that godwit departure and arrival timing rapidly shifted 6 days later from 2010-2023 with no differences in timing between the sexes. Despite this change in migration timing, the population has maintained an average migratory duration of 24 days, suggesting that godwits are driving shifts in arrival timing entirely by shifting their nonbreeding ground departure, something rarely documented in long-distance migrants. Yet, we also found that godwits are not shifting their migration timing in the direction predicted by our model, providing evidence that this response may not be adaptive. These results emphasize the urgent need for a more holistic approach to assessing the relative vulnerability of migratory species and the adaptiveness of changes in migration timing.
Ballistic to diffusive crossover in a weakly interacting Fermi gas
Authors: Lloyd Jerome , Rakovszky Tibor , Pollmann Frank , von Keyserlingk Curt
Published: May 2024

In the absence of disorder and interactions, fermions move coherently and their associated charge and energy exhibit ballistic spreading, even at finite energy density. In the presence of weak interactions and a finite energy density, fermion-fermion scattering leads to a crossover between early-time ballistic and late-time diffusive transport. The relevant crossover timescales and the transport coefficients are both functions of interaction strength, but the question of determining the precise functional dependence is likely impossible to answer exactly. In this work we develop a numerical method (fDAOE) which is powerful enough to provide an approximate answer to this question, and which is consistent with perturbative arguments in the limit of very weak interactions. Our algorithm, which adapts the existing dissipation-assisted operator evolution (DAOE) to fermions, is applicable to systems of interacting fermions at high temperatures. The algorithm approximates the exact dynamics by systematically discarding information from high n-point functions, and is tailored to capture noninteracting dynamics exactly. Applying our method to a microscopic model of interacting fermions, we numerically determine crossover timescales and diffusion constants for a wide range of interaction strengths. In the limit of weak interaction strength (Δ), we demonstrate that the crossover from ballistic to diffusive transport happens at a time tD∼1/Δ2 and that the diffusion constant similarly scales as D∼1/Δ2. We confirm that these scalings are consistent with a perturbative Fermi's golden rule calculation, and we provide a heuristic operator-spreading picture for the crossover between ballistic and diffusive transport.

Published by the American Physical Society
2024
Role of electromagnetic interactions in the
X(3872)
and its analogs
Authors: Chen Ping , Liu Zhan-Wei , Zhang Zi-Le , Luo Si-Qiang , Wang Fu-Lai , Wang Jun-Zhang , Liu Xiang
Published: May 2024

We investigate the role of the electromagnetic interaction in the formation and decay of the X(3872). The binding properties of the X(3872) are studied by assuming the molecular nature and considering the S−D wave mixing, isospin breaking, and coupled channel effects, and in particular the correction from the electromagnetic interaction. The radiative decays can better reflect the difference between the charged and neutral DD¯* components, since the electromagnetic interaction explicitly breaks the isospin symmetry. We further study the radiative decay widths with the obtained wave functions for different DD¯* channels. We also explore other similar hidden-charm molecular states. The electromagnetic interaction can make the molecule tighter. Our result of the radiative decay width for X(3872)→γJ/ψ is in agreement with the experiment. The branching ratio Rγψ is less than 1 in our framework, which supports the Belle and BESIII measurements.

Published by the American Physical Society
2024
New physics interpretations for nonstandard values of
h→Zγ
Authors: Boto Rafael , Das Dipankar , Romão Jorge C. , Saha Ipsita , Silva Joao P.
Published: May 2024

Current measurements of the h→Zγ signal strength invite us to speculate about possible new physics interactions that exclusively affect μZγ without altering the other signal strengths. Additional consideration of tree unitarity enables us to correlate the nonstandard values of μZγ with an upper limit on the scale of new physics. We find that even when μZγ deviates from the Standard Model value by only 20%, the scale of new physics should be well within the reach of the LHC.

Published by the American Physical Society
2024
Hunting for hypercharge anapole dark matter in all spin scenarios
Authors: Choi Seong Youl , Jeong Jaehoon , Kang Dong Woo , Shin Seodong
Published: May 2024

We conduct a combined analysis to investigate dark matter (DM) with hypercharge anapole moments, focusing on scenarios where Majorana DM particles with spin 1/2, 1, 3/2, and 2 interact exclusively with Standard Model particles through U(1)Y hypercharge anapole terms for the first time. For completeness, we construct general effective U(1) gauge-invariant three-point vertices. These enable the generation of hypercharge gauge-invariant interaction vertices for both a virtual photon γ and a virtual Z boson with two identical massive Majorana particles of any nonzero spin s, after the spontaneous breaking of electroweak gauge symmetry. For complementarity, we adopt effective operators tailored to each dark matter spin allowing crossing symmetry. We calculate the relic abundance, analyze current constraints and future sensitivities from dark matter direct detection and collider experiments, and apply the conceptual naive perturbativity bound. Our estimations based on a generalized vertex calculation demonstrate that the scenario with a higher-spin DM is more stringently constrained than a lower-spin DM, primarily due to the reduced annihilation cross section and/or the enhanced rate of LHC monojet events. As a remarkable outcome, the spin-2 anapole DM scenario is almost entirely excluded, while the high-luminosity LHC exhibits high sensitivities in probing spin-1 and -

3

/

2

scenarios, except for a tiny parameter range of DM mass around 1 TeV. A significant portion of the remaining parameter space in the spin-1/2 DM scenario can be explored through upcoming Xenon experiments, with more than 20 ton-yr exposure equivalent to approximately 5 years of running the XENONnT experiment.

Published by the American Physical Society
2024
Hydrodynamical dual of the gravitational axial anomaly and the cosmological constant
Authors: Khakimov R. V. , Prokhorov G. Yu. , Teryaev O. V. , Zakharov V. I.
Published: May 2024

We construct the hydrodynamic expansion for a rotating and accelerated medium in a curved space-time, and establish the relationship between the currents generated by the cosmological constant and the acceleration. Then we consider the more general case with a nonzero Weyl tensor, and show the duality between the current in flat space-time and the gravitational axial anomaly. This generalizes the previous derivation to the case with a nonzero Ricci tensor.

Published by the American Physical Society
2024
Searching for axion resonances in vacuum birefringence with three-beam collisions
Authors: Evans Stefan , Schützhold Ralf
Published: May 2024

We consider birefringent (i.e., polarization changing) scattering of x-ray photons at the superposition of two optical laser beams of ultrahigh intensity and study the resonant contributions of axions or axionlike particles, which could also be short lived. Applying the specifications of the Helmholtz International Beamline for Extreme Fields (HIBEF), we find that this setup can be more sensitive than previous light-by-light scattering (birefringence) or light-shining-through-wall experiments in a certain domain of parameter space. By changing the pump and probe laser orientations and frequencies, one can even scan different axion masses, i.e., chart the axion propagator.

Published by the American Physical Society
2024
Reverse design of the ideal pulse for hollow capillary fiber post-compression schemes
Authors: Galán Marina Fernández , Conejero Jarque Enrique , San Roman Julio
Published: May 2024

The countless applications of ultrashort laser pulses in very different scientific areas explain the ongoing efforts to develop new strategies for the generation of light pulses with increasingly better characteristics. In this work, we theoretically study the application of the nonlinear reverse propagation method to produce few-cycle pulses with clean temporal profiles from standard post-compression setups based in hollow capillary fibers. By numerically solving the propagation of a desired goal pulse in the backward direction, we are able to predict the structure of the ideal input pulse that could be perfectly compressed in a given setup. Although the goal pulse cannot be chosen in a simple manner due to the fundamental symmetries of the nonlinear propagation equation, our analysis shows that the ideal pulse presents a recurring form and that, in general, both its intensity profile and phase must be shaped to recover the optimized goal output.

Published by the American Physical Society
2024
Supervisor incivility and service employee creativity: a moderated mediation model of negative affect state and core self-evaluation
Authors: A. Anjaly , S. Nemat Sheereen
Published: May 2024

Purpose

The present study examines the effect of supervisor incivility on service employee creativity and the mediating mechanism of negative affect state on the said relationship with the aid of Affective Events Theory (AET) and Social Power Theory. Additionally, the study explores the mitigating role of core self-evaluation in the dual stage of the moderated mediation model.

Design/methodology/approach

Survey data were collected from 420 frontline employees working in four-star and five-star hotels across India and PROCESS macro in SPSS 23.0 was employed to test the hypotheses proposed in the study.

Findings

The study findings observe that frontline employees experiencing supervisor incivility face a negative affect state and it further diminishes service employee creativity. Also, the indirect effect gets attenuated at dual stages when frontline employees are equipped with a high level of core self-evaluation.

Practical implications

The study findings provide various insights to the managers to understand the deleterious effect of supervisor incivility at work and to develop interventions to manage supervisor incivility and the negative affect state among frontline hotel employees.

Originality/value

The present study is the first and unique attempt to investigate the role of supervisor incivility experienced by frontline hotel employees in India with reference to their creativity towards customers and mediating mechanism of negative affect state. The study adds value to the literature by establishing the role of core self-evaluation in the moderated mediation model. Further, the study also provides a unique contribution to the management of frontline hospitality employees.