bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing the Implementing Readiness of Shared Medical Appointments in China’s Primary Healthcare Institutions: A Mixed-Method Study Utilizing Qualitative Comparative Analysis
Authors: Yang Wei , Liu Lingrui , Chen Jiajia , Mao Run , Yang Tao , Linghu Lang , Huang Lieyu , Xu Dong (Roman) , Cai Yiyuan
Published: June 2024

Background and ObjectiveDiabetes mellitus (DM) is a mounting public health concern in China, home to the largest number of patients with diabetes globally. A primary challenge has been the integration of high-quality chronic disease services, with poor outcomes and inefficient health management intensifying the disease burden. Shared Medical Appointments (SMAs) offer a promising solution, yet evidence of their practical application in resource-limited settings like China’s primary healthcare institutions is scant. This study aims to evaluate the organizational readiness for change (ORC) in implementing SMA services in Guizhou province’s primary healthcare institutions and to identify determinants of high-level ORC to foster implementation success.

MethodsThis study employed a mixed-method approach. The validated Chinese version of the Workplace Readiness Questionnaire (WRQ-CN) was used to assess the ORC status across 12 institutions participating in the SMART pilot trial. A Normalization Process Theory (NPT) -guided qualitative interview and quantitative survey were used to collect the conditions. Data analysis encompassed standardized descriptive statistics, Spearman correlation analysis, and qualitative comparative analysis (QCA) to discern condition variables and configurations that are favorable to high-level ORC.

ResultsThe study engaged 70 institutional participants, including administrators, clinicians, and public health workers. The median ORC score was 105.20 (101.23-107.33). We identified 12 condition variables through the interview and survey. The Spearman correlation analysis highlighted a moderate correlation between Specific tasks and responsibilities (r=0.393, p=0.206) and Key participants (r=0.316, p=0.317) with ORC. QCA also revealed these condition configurations and pathways that collectively align with heightened ORC, accentuating the pivotal role of key participants.

ConclusionsThis study unveiled a spectrum of dynamic conditions and pathways affecting ORC, which are consistent with the NPT-based theoretical steps. They were essential for attaining high-level ORC in rolling out health service innovations like the SMART study, especially in resource-limited settings.
Pulmonary hypertension misdiagnosis due to preventable errors in echocardiography and right heart catheterization
Authors: Saunders Alexandra , Bainey Kevin R , Varughese Rhea , Michelakis Evangelos D
Published: June 2024

Objectives

We hypothesized that preventable human errors in performance and reporting of transthoracic echocardiograms (TTEs) and right RHCs are common and may lead to misdiagnosis of pulmonary hypertension (PH) subgroups.

Background

PH is a common disease, however PH subgroups have vastly different mortality and treatment. This is particularly the case for pulmonary arterial hypertension (PAH) versus PH secondary to heart failure with preserved ejection fraction (HFpEF). TTE) and RHC are needed to differentiate these two diseases. Diagnosis requires specific cut-offs for mean pulmonary artery pressure (mPAP) and pulmonary artery wedge pressure (PAWP), which can only be measured by RHC. However, TTE first identifies PH, triggering referral to specialized PH centres.

Methods

We re-analyzed TTEs and RHCs of 252 PH program referrals over 5 years. We also compared the inferred diagnosis from the original reports to the diagnosis made after error correction.

Results

We identified numerous preventable errors in the performance and reporting of both tests, and subsequently there was a poor correlation between the parameters measured by both tests. The referral TTE reports missed or overcalled PH in 44 patients. The RHC, mostly by PAWP mistakes, led to misdiagnosis in 41 patients.

Conclusion

TTE errors may delay referrals, while RHC errors may lead to misdiagnosis and applying wrong therapies to patients. As PAH therapies are extremely expensive, this also impacts the health care system. Primary care physicians need to be on alert for such errors and referral centres need to promote quality improvement programs to mitigate these errors.
Telomerase RNA component knockout exacerbatesS. aureuspneumonia by extensive inflammation and dysfunction of T cells
Authors: Reisser Yasmina , Hornung Franziska , Häder Antje , Lauf Thurid , Nietzsche Sandor , Löffler Bettina , Deinhardt-Emmer Stefanie
Published: June 2024

The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation.

Our study unveils heightened susceptibility to pneumonia caused byStaphylococcus aureus (S. aureus)inTercknockout (Tercko/ko) mice compared to both young and old infected counterparts. The exacerbated infection in Tercko/komice correlates with heightened inflammation, manifested by elevated interleukin-1β (IL-1β) levels and activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome within the lung.

Employing mRNA sequencing methods alongsidein vitroanalysis of alveolar macrophages (AMs) and T cells, our study elucidates a compelling correlation between Tercko/ko, inflammation, and impaired T cell functionality.Tercdeletion results in compromised T cell function, characterized by dysregulation of the T cell receptor and absence of CD247, potentially compromising the host’s capacity to mount an effective immune response againstS. aureus.

This investigation provides insights into the intricate mechanisms governing increased vulnerability to severe pneumonia in the context of Terc deficiency, which might also contribute to aging-related pathologies, while also revealing for the first time the influence of Terc on T cell function.

Graphical abstract
Interdisciplinarity through internationality: results from a US-Mexico graduate course bridging computational and plant science
Authors: Chitwood Daniel H. , Rougon-Cardoso Alejandra , VanBuren Robert
Published: June 2024

Interdisciplinarity is used to integrate and synthesize new research directions between scientific domains, but it is not the only means by which to generate novelty by bringing diverse perspectives together. Internationality draws upon cultural and linguistic diversity that can potentially impact interdisciplinarity as well. We created an interdisciplinary class originally intended to bridge computational and plant science that eventually became international in scope, including students from the US and Mexico. We administered a survey over four years designed to evaluate student expertise. The first year of the survey included only US students and demonstrated that biology and computational student groups have distinct expertise but can learn the skills of the other group over the course of a semester. Modeling of survey responses shows that biological and computational science expertise is equally distributed between US and Mexico student groups, but that nonetheless these groups can be predicted based on survey responses due to sub-specialization within each domain. Unlike interdisciplinarity, differences arising from internationality are mostly static and do not change with educational intervention and include unique skills such as working across languages. We end by discussing a distinct form of interdisciplinarity that arises through internationality and the implications of globalizing research and education efforts.
Head-to-head comparison of diagnostic accuracy of TB screening tests: Chest-X-ray, Xpert TB host response, and C-reactive protein
Authors: Crowder Rebecca , Thangakunam Balamugesh , Andama Alfred , Christopher Devasahayam J , Dalay Victoria , Dube-Nwamba Welile , Kik Sandra V. , Van Nguyen Dong , Nhung Nguyen Viet , Phillips Patrick PJ , Ruhwald Morten , Theron Grant , Worodria William , Yu Charles , Nahid Payam , Cattamanchi Adithya , Gupta-Wright Ankur , Denkinger Claudia M. ,   R2D2 TB Network
Published: June 2024

Background

Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. We compared the diagnostic accuracy of available TB triage tests.

Methods

We prospectively screened consecutive adults with ≥2 weeks of cough presenting to primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. All participants received the index tests: chest-X-ray (CXR), venous or capillary Cepheid Xpert TB Host Response (HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech iChroma II). CXR images were processed using computer-aided detection (CAD) algorithms. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to achieve sensitivity ≥90% and maximize specificity. Two-test screening algorithms were considered, using two approaches: 1) sequential negative serial screening in which the second screening test is conducted only if the first is negative and positive is defined as positive on either test and 2) sequential positive serial screening, in which the second screening test is conducted only if the first is positive and positive is defined as positive on both tests.

Results

Between July 2021 and August 2022, 1,392 participants with presumptive TB had valid results on index tests and the reference standard, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity when using a cut-point that achieves 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Among the possible two-test screening algorithms, three met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive].

Conclusions

CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. Cost and feasibility of two-test screening algorithms should be explored.

Registration

NCT04923958
segcsvdWMH: A convolutional neural network-based tool for quantifying white matter hyperintensities in heterogeneous patient cohorts
Authors: Gibson Erin , Ramirez Joel , Woods Lauren Abby , Ottoy Julie , Berberian Stephanie , Scott Christopher J.M. , Yhap Vanessa , Gao Fuqiang , Coello Roberto Duarte , Valdes Hernandez Maria , Lang Anthony E. , Tartaglia Carmela M. , Kumar Sanjeev , Binns Malcolm A. , Bartha Robert , Symons Sean , Swartz Richard H. , Masellis Mario , Singh Navneet , Moody Alan , MacIntosh Bradley J. , Wardlaw Joanna M. , Black Sandra E. ,   ONDRI Investigators, ADNI, CAIN Investigators, colleagues from the Foundation Leducq Transatlantic Network of Excellence, Lim Andrew SP , Goubran Maged
Published: June 2024

White matter hyperintensities (WMH) of presumed vascular origin are an MRI-based biomarker of cerebral small vessel disease (CSVD). WMH are associated with accelerated cognitive decline and increased risk of stroke and dementia, and are commonly observed in aging, vascular cognitive impairment, Alzheimer’s and Parkinson’s disease, and related dementias. The accurate, reliable, and rapid measurement of WMH in large-scale multi-site clinical studies with heterogeneous patient populations remains challenging. The diversity of MRI protocols and image characteristics across different studies as well as the diverse nature of WMH, in terms of their highly variable shape, size, distribution, and underlying pathology, adds additional complexity to this task. Here, we present segcsvdWMH, a novel convolutional neural network-based tool for quantifying WMH. segcsvdWMHis specifically designed for accurate and robust performance when applied to diverse clinical patient datasets. Central to the development of this tool is the curation of a large patient dataset (>700 scans) sourced from seven multi-site studies, encompassing a wide range of clinical populations, WMH burden, and imaging parameters. The performance of segcsvdWMHis evaluated against three widely used WMH segmentation tools, where we demonstrate significantly enhanced accuracy and robustness across a range of challenging conditions and datasets.
The association between NfL and Cognitive Functioning in older adults diagnosed diabetes: a cross-sectional analysis from NHANES
Authors: LiLi  , Li Cheng-Bo , Zhu Li , Zhu Jiang
Published: June 2024

Objective

This research aimed to explore the correlation between serum Neurofilament Light Chain (NfL) levels and Cognitive Function in diabetic participants.

Methods

Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2014, 173 individuals aged 60 years and above with diabetes were included in the analysis. Cognitive function was measured using the Animal Fluency exercise. Weighted multivariate linear regression analysis and a restricted cubic spline model were employed to assess the association between serum NfL levels and Animal Fluency Score (CFDAST) in diabetic patients.

Results

Serum NfL was categorized into weighted tertiles, with participants divided into groups Q1, Q2, and Q3. Significant differences in serum NfL were observed among the groups (P < 0.01). Participants in group Q3 exhibited higher levels of hemoglobin A1c and were older compared to groups Q1 and Q2 (P < 0.01). Furthermore, when serum NfL was treated as a continuous variable, it was found to have a negative correlation with CFDAST score (P < 0.01). Group Q1 had a higher CFDAST score than group Q3, as well as group Q2 (p for trend = 0.0021). A nonlinear relationship was observed between serum NfL and CFDAST score, displaying an inverted ‘U-shaped’ curve (P-overall = 0.01, P-for-non-linear = 0.0026).

Conclusions

Serum NfL has the potential to serve as a clinical biomarker for early detection of cognitive impairment in diabetic individuals aged over 60 years.

Highlights

Study about biomarkers for diabetes-associated cognitive decline is limited.

We found that there is an inverted U-shaped association between serum NfL and cognitive score.

Serum NfL may be a biomarker for early detection of cognitive decline in elderly diabetics.
WITHDRAWN: Deep Learning Solutions for Pneumonia Detection: Performance Comparison of Custom and Transfer Learning Models
Authors: Zhong Yihao , Liu Yanan , Gao Erdi , Wei Changsong , Wang Zhuoyue , Yan Chao
Published: June 2024

Withdrawal Statement

The authors have withdrawn this manuscript because of the following reasons:

Significant Methodological Errors: Upon further review of our work, we discovered critical methodological errors in the data preprocessing stage that affect the reliability and reproducibility of the results. These errors could mislead other researchers if left unaddressed.

Inaccurate Data Interpretation: In addition, we have found that some of the interpretations of the results, especially concerning model performance, were not adequately supported by the data. This misinterpretation has led to conclusions that do not align with our current understanding of the study.

Ethical Considerations: After further reflection, we have recognized the need to clarify certain ethical aspects of our data collection process, especially regarding the dataset used. This issue needs to be addressed in compliance with ethical guidelines before the findings can be deemed credible and citable.

New Research Developments: Finally, new developments in related research have emerged, which contradict some of the conclusions presented in our manuscript. As we plan to pursue a different direction that incorporates these new findings, we feel that it is necessary to retract the current manuscript.

After careful reconsideration, my co-authors and I have identified several issues that we believe warrant the withdrawal of the manuscript. 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.
Implementation of a “people-like-me” tool for personalized rehabilitation after total knee arthroplasty: A mixed methods pilot study
Authors: Graber Jeremy , Hinrichs-Kinney Lauren , Churchill Laura , Matlock Daniel D , Kittelson Andrew , Lutz Adam , Bade Michael , Stevens-Lapsley Jennifer
Published: June 2024

Rationale

While there are numerous tools available to inform if and when to use total knee arthroplasty (TKA), very few tools exist to help guide the recovery period after surgery.

Aims and Objectives

We piloted a decision support tool that promotes a “people-like-me” (PLM) approach to rehabilitation after total knee arthroplasty (TKA). The PLM approach encourages person-centered care by “using historical outcomes data from similar (past) patients as a template of what to expect for a new patient”. In this study, we evaluated how successfully the PLM tool was implemented and examined contextual factors that may have influenced its implementation.

Methods

Two outpatient physical therapy clinics (Clinics A and B) piloted the PLM tool from September 2020 – December 2022. We gathered data related to its implementation from multiple sources including the electronic health record, the tool itself, and surveys and interviews with patients and clinicians. We used an explanatory sequential mixed methods design to analyze the data overall and separately by each clinic.

Results

Overall, the clinics met most pre-specified implementation targets, but did not use the tool as frequently as intended. Both clinics identified time, technology, and scheduling barriers to using the tool, but Clinic A scored higher in nearly every implementation outcome. Clinic A’s success may have been related to its clinicians’ higher level of experience, more positive attitudes towards the tool, and more active approach to implementation compared to Clinic B.

Conclusions

The clinics met most of our implementation targets, but Clinic A experienced more success than Clinic B. Future efforts to implement this PLM tool should (1) engage clinicians as active participants in the implementation process, (2) explore whether incorporating treatment recommendations into the PLM tool and/or using alternative training strategies can enhance its ability to alter clinician behavior, (3) integrate the tool within the EHR to complement existing workflows and mitigate implementation barriers, and (4) include randomized controlled trials that evaluate the tool’s effectiveness and scalability across diverse clinical settings.
Advances in methods for characterizing dietary patterns: A scoping review
Authors: Hutchinson Joy M. , Raffoul Amanda , Pepetone Alexandra , Andrade Lesley , Williams Tabitha E. , McNaughton Sarah A. , Leech Rebecca M. , Reedy Jill , Shams-White Marissa M. , Vena Jennifer E. , Dodd Kevin W. , Bodnar Lisa M. , Lamarche Benoît , Wallace Michael P. , Deitchler Megan , Hussain Sanaa , Kirkpatrick Sharon I.
Published: June 2024

There is a growing focus on better understanding the complexity of dietary patterns and how they relate to health and other factors. Approaches that have not traditionally been applied to characterize dietary patterns, such as machine learning algorithms and latent class analysis methods, may offer opportunities to measure and characterize dietary patterns in greater depth than previously considered. However, there has not been a formal examination of how this wide range of approaches has been applied to characterize dietary patterns. This scoping review synthesized literature from 2005-2022 applying methods not traditionally used to characterize dietary patterns, referred to as novel methods. MEDLINE, CINAHL, and Scopus were searched using keywords including machine learning, latent class analysis, and least absolute shrinkage and selection operator (LASSO). Of 5274 records identified, 24 met the inclusion criteria. Twelve of 24 articles were published since 2020. Studies were conducted across 17 countries. Nine studies used approaches that have applications in machine learning to identify dietary patterns. Fourteen studies assessed associations between dietary patterns that were characterized using novel methods and health outcomes, including cancer, cardiovascular disease, and asthma. There was wide variation in the methods applied to characterize dietary patterns and in how these methods were described. The extension of reporting guidelines and quality appraisal tools relevant to nutrition research to consider specific features of novel methods may facilitate complete and consistent reporting and enable evidence synthesis to inform policies and programs aimed at supporting healthy dietary patterns.
Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway inTrichoderma reesei
Authors: Burger Isabella , Schmal Matthias , Peikert Kathrin , Fourtis Lukas , Suster Christoph , Stanetty Christian , Schnalzer Dominik , Birner-Gruenberger Ruth , Mach Robert L , Mach-Aigner Astrid R. , Schittmayer Matthias , Zimmermann Christian
Published: June 2024

In the quest to discover novel antifungal agents and new antifungal production processes, we investigated the biosynthetic gene cluster (BGC) for ilicicolin H in the fungusTrichoderma reesei. While the BGC is silent under standard cultivation conditions, we achieved to activate it by over-expressing its transcription factor TriliR. Successful BGC activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. Metabolomic profiling upon BGC expression revealed high-yield production of the supposed main product ilicicolin H. To elucidate the functionality of this BGC, we employed a combination of overexpression and deletions of individual biosynthetic gene cluster constituents. Deletion oftriliA, encoding for the core polyketide synthase TriliA, completely ceased product formation, as expected. In contrast to previous heterologous expression experiments, we could demonstrate that the epimerase TriliE is necessary for the formation of ilicicolin H in the native host. While we hardly observed any of the previously reported side- or shunt products associated with heterologous ilicicolin H expression, we discovered a novel member of the ilicicolin family using a metabolomic molecular networking approach. This new compound, which we termed ilicicolin K, is expressed in substantial amounts in the genetically engineeredTrichoderma reesei, enabling us to elucidate its structure by NMR. The structure of ilicicolin K is similar to that of ilicicolin H but differs by an additional hydroxylation and an intramolecular etherification of the hydroxyl group at the pyridone towards the tyrosine moiety of the molecule. Initial tests of ilicicolin K showed antifungal activity againstSaccharomyces cerevisiaeandAspergillus nidulanswith a similar minimum inhibitory concentration as ilicicolin H.
Genetic diversity and cross-species transmissibility of bat-associated picornaviruses from Spain
Authors: Carrascosa-Sàez Marc , Buigues Jaime , Viñals Adrià , Andreu-Moreno Iván , Martínez-Recio Raquel , Soriano-Tordera Clàudia , Monrós Juan S. , Cuevas José M. , Sanjuán Rafael
Published: June 2024

Background

Emerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families.

Methods

We set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition.

Results

We found five complete or nearly complete genomes belonging to the familyPicornaviridae, including a new species of the subfamilyEnsavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the orderPicornavirales, and for which genome composition analysis suggested a plant host.

Conclusions

Our findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.
The amniote-conserved DNA-binding domain of CGGBP1 restricts cytosine methylation of transcription factor binding sites in proximal promoters to regulate gene expression
Authors: Morbia Ishani , Kumar Praveen , Satish Aditi Lakshmi , Mudgal Akanksha , Datta Subhamoy , Singh Umashankar
Published: June 2024

CGGBP1 is a GC-rich DNA-binding protein which is important for genomic integrity, gene expression and epigenome maintenance through regulation of CTCF occupancy and cytosine methylation. It has remained unclear how CGGBP1 integrates multiple diverse functions with its simple architecture of only a DNA-binding domain tethered to a C-terminal tail with low structural rigidity. We have used truncated forms of CGGBP1 with or without the DNA-binding domain (DBD) to assay cytosine methylation and global gene expression. Proximal promoters of CGGBP1-repressed genes, although significantly GC-poor, contain GC-rich transcription factor binding motifs and exhibit base compositions indicative of low C-T transition rates due to prevention of cytosine methylation. Genome-wide analyses of cytosine methylation and binding of CGGBP1 DBD show that CGGBP1 restricts cytosine methylation in a manner that depends on its DBD and its DNA-binding. The CGGBP1-repressed genes show an increase in promoter cytosine methylation alongside a decrease in transcript abundance when the DBD-deficient CGGBP1 is expressed. Our findings suggest that CGGBP1 protects transcription factor binding sites (TFBS) from cytosine methylation-associated loss and thereby regulates gene expression. By analysing orthologous promoter sequences we show that restriction of cytosine methylation is a function of CGGBP1 progressively acquired during vertebrate evolution. A superimposition of our results and evolution of CGGBP1 suggests that mitigation of cytosine methylation is majorly achieved by its N-terminal DBD. Our results position CGGBP1 DNA-binding as a major evolutionarily acquired mechanism through which it keeps cytosine methylation under check and regulates TFBS retention and gene activity.
Sex Differences in Human Brain Structure at Birth
Authors: Khan Yumnah T. , Tsompanidis Alex , Radecki Marcin A. , Dorfschmidt Lena ,   APEX Consortium, Austin Topun , Suckling John , Allison Carrie , Lai Meng-Chuan , Bethlehem Richard A. I. , Baron-Cohen Simon
Published: June 2024

Sex differences in human brain anatomy have been well-documented; however, their underlying causes remain controversial. Neonatal research offers a pivotal opportunity to address this long-standing debate. Given that postnatal environmental influences (e.g., gender socialisation) are minimal at birth, any sex differences observed at this stage can be more readily attributed to prenatal influences. Here, we assessed on-average sex differences in global and regional brain volumes in 514 newborns (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. On average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed higher total cortical gray matter volumes, whilst males showed higher total white matter volumes. After controlling for total brain volume in regional comparisons, females had increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. While postnatal experiences likely amplify sex differences in the brain, our findings demonstrate that several global and regional on-average sex differences are already present at birth.
High resolution profiling of cell cycle-dependent protein and phosphorylation abundance changes in non-transformed cells
Authors: Rega Camilla , Tsitsa Ifigenia , Roumeliotis Theodoros I. , Krystkowiak Izabella , Portillo Maria , Yu Lu , Vorhauser Julia , Pines Jonathon , Mansfeld Joerg , Choudhary Jyoti , Davey Norman E.
Published: June 2024

The cell cycle governs a precise series of molecular events, regulated by coordinated changes in protein and phosphorylation abundance, that culminates in the generation of two daughter cells. Here, we present a proteomic and phosphoproteomic analysis of the human cell cycle in hTERT-RPE-1 cells using deep quantitative mass spectrometry by isobaric labelling. Through analysing non-transformed cells, and improving the temporal resolution and coverage of key cell cycle regulators, we present a dataset of cell cycle-dependent protein and phosphorylation site oscillation that offers a foundational reference for investigating cell cycle regulation. These data reveal uncharacterised regulatory intricacies including proteins and phosphorylation sites exhibiting previously unreported cell cycle-dependent oscillation, and novel proteins targeted for degradation during mitotic exit. Integrated with complementary resources, our data link cycle-dependent abundance dynamics to functional changes and are accessible through the Cell Cycle database (CCdb), an interactive web-based resource for the cell cycle community.
A granular view of the traits controlling soil bacterial community reconstruction following a prescribed burn
Authors: Uppal Siddharth , Woolet Jamie , Venkateshwaran Muthusubramanian , Baxer Christopher , Johnson Yari , Tung Ashley , Yu Charlie S , Whitman Thea , Kwan Jason C
Published: June 2024

Prescribed burns and wildfires both cause transient reduction of soil microbiome diversity, which has wide-ranging functions in soil and plant health. However, a genetic basis for understanding the mechanisms behind post-fire microbiome recovery is not well-established. Here, we conducted prescribed burns in multiple plots with paired unburned controls, at two prairie locations, sampling each over 5 months. We assembled >300 bacterial genomes that were conserved in both time and space, then identified genomes that were either enriched or depleted post-fire compared to timepoint controls. On a metagenome level, burned and unburned samples were functionally equivalent, but on a species level we determined that post-fire survival is more nuanced than possession of previously hypothesized pyrophilous traits. Our study therefore advances the understanding of how both function and taxonomy contribute to success during the reconstruction of a complex soil microbiome.
HARMONY (HARM reduction for Opiates, Nicotine and You) Trial: Protocol of a Randomised Controlled Trial of the Effectiveness of Vaporised Nicotine Products for Tobacco Smoking Cessation amongst NSW Opiate Agonist Treatment Clients
Authors: Bonevski B , Jackson M , Austin E , Lintzeris N , Ezard N , Gartner C , Oldmeadow C , Haber P , Hallinan R , Rodgers C , Ho T , Nean M , Harrod M , Dunlop A
Published: June 2024

Introduction

Tobacco smoking is a major cause of preventable disease in Australia. Individuals receiving opiate agonist treatment (OAT) are a group who experience high tobacco-related morbidity and mortality rates. Despite reporting a desire to stop, relapse rates in OAT clients are high and cessation attempts supported by pharmacotherapy are less effective than in general populations. New and innovative ways of addressing smoking amongst this group are needed.

Vaporised nicotine products (VNPs), or e-cigarettes, may reduce a person’s exposure to toxicants and carcinogens when compared to tobacco cigarettes. High quality evidence indicates that VNPs can increase rates of smoking cessation compared to nicotine replacement therapy. Pilot results of VNPs as a smoking cessation aid in OAT clients suggests their use is feasible and acceptable but effectiveness in this group has not been explored.

This protocol details the rationale and methodology for a randomised controlled trial to examine the effectiveness of VNPs for tobacco smoking cessation amongst OAT clients in New South Wales, Australia.

Methods and Analysis

This will be a randomised single-blinded parallel group trial comparing 12-weeks of 12mg/mL vaporised nicotine to best-practice NRT. Participants must be 18 years or older, accessing opiate treatment at a participating health site, and a current daily tobacco smoker seeking to quit or reduce their smoking.

The primary outcome will be self-reported 7-day point prevalence abstinence from tobacco after 12-weeks of treatment. Secondary outcomes include biochemically verified abstinence, self-reported 30-day abstinence, number of cigarettes smoked each day, craving and withdrawal symptoms, and VNP safety. Between-group comparisons will be conducted at end of treatment, and at 12-weeks post-treatment.

Discussion

This study examines new ways of reducing tobacco related harm in individuals receiving OAT. Outcomes may be enhanced by leveraging participants interactions with health care provides who can facilitate the required support. Study findings have the potential to significantly impact tobacco smoking prevalence in priority populations.

Ethics and Dissemination

Protocol approval was granted by Hunter New England Human Research Ethics Committee (Reference 2020/ETH01866). Findings will be disseminated via academic conferences, peer-reviewed publications and social media.

Registration

The study was registered in the Australian New Zealand Clinical Trials Registry (Reference ACTRN12621000148875).
Effect of intravenous lidocaine dose on pain upon awakening in pediatric tonsillectomy: A randomized trial
Authors: Hu Yang , Du Ming-Cheng , Chen Yi , Long Xiang , Jiang Jing-Jing , Gong Yuan
Published: June 2024

We investigated the potential of intravenous lidocaine to reduce pain on awakening in a dose- dependent manner and aimed to determine the median effective dose of lidocaine in 200 children aged 3–12 years (American Society of Anesthesiologists physical status I–II) who underwent elective tonsillectomy with or without adenoidectomy at Yichang Central People’s Hospital. The patients were randomized into four dose groups (A–D: 0.0, 1.0, 1.5, and 2.0 mg/kg, respectively), and they underwent the same anesthetic induction and maintenance protocols. The primary outcome was pain on awakening, while secondary outcomes included pain scores at 1, 4, 12, and 24 h after awakening; incidences of laryngospasm, bronchospasm, or perioperative stridor; and time to extubation. Intraoperative cardiac events were classified as safety events. Our findings indicated that intravenous lidocaine dose-dependently reduced pain on awakening, with the median effective dose being 1.75 mg/kg. Significant differences were observed between groups A and D (P ≤ 0.001). No incidents of laryngospasm, bronchospasm, or perioperative stridor were observed. Furthermore, there were significant between-group differences in time to extubation (P ≤ 0.05). In conclusion, our study demonstrated that lidocaine dose-dependently reduced pain on awakening in children undergoing tonsillectomy with or without adenoidectomy, with no severe adverse events.
Evolution of the Umbilical Cord Blood Proteome Across Gestational Development
Authors: Mithal Leena B. , Lancki Nicola , Ling-Hu Ted , Goo Young Ah , Otero Sebastian , Rhodes Nathaniel J. , Cho Byoung-Kyu , Grobman William A. , Hultquist Judd F. , Scholtens Denise , Mestan Karen G. , Seed Patrick C.
Published: June 2024

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 24 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. Furthermore, these data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions.
Prevalence and determinants of food insecurity among households headed by mothers who are female sex workers in three African Countries: Validation and application of food insecurity experience scale
Authors: Weerasinghe Swarna D.S. , Jackson Jennifer A. , Stadler Diane D. , Macias-Konstantopoulos Wendy L. , Wills Brian
Published: June 2024

Reduction in prevalence of food insecurity, a key factor in reaching the United Nations Sustainable Development Goal 2.2, was challenged by COVID-19 lockdowns in low- and middle-income countries, which impacted the affordability and accessibility of food. Prevalence and determinants of food insecurity among female sex workers who are mothers (FSWM) and heads of households (FSWM-HH) in the African region have not been previously assessed. This study validated the food insecurity experience scale (FIES) using data collected from 852 FSWM-HH living in the Democratic Republic of the Congo (DRC), Kenya, or Nigeria. Results were calibrated on the global metric to compare with the country-level prevalence of household severe food insecurity (HSFI). Associated individual and household determinants and their intersections were examined to identify vulnerable sub-groups. The FIES reliably assessed (fit index=0.75) household food insecurity among FSWM-HH using a 7-item scale, omitting the item of being worried about not having enough food to eat. The prevalence of HSFI was 59.6% in the DRC, 77.8% in Kenya, and 89.0% in Nigeria and compared to FAO 2016-2018 country levels, 1.5, 3.0, and 4.5 times higher, respectively, than previous estimates. Determinants of HSFI among FSWM-HH were similar to the African region, except FSWM-HH composition of children, but the magnitudes of odds were higher. Multiple logistic regression revealed important ecological relationships. FSWM-HH with 0-3 children living with them (AOR=1.63,95% CI:1.13-2.37, reference>4 children) and mothers having no schooling or primary education (AOR=1.92,95% CI:1.33-2.78, reference with higher education) significantly determined HSFI. Prevalence of HSFI was highest among two subgroups of FSWM-HH: those>30 years of age, without partners (93.7%, p=0.002) and those with low levels of education with 0-3 children living with them (85%, p=0.03). Food programs and welfare policies may be effective strategies to reduce HSFI among this high-risk group of mothers with children.
Tripartite entanglement in
H→ZZ,WW
decays
Authors: Aguilar-Saavedra J. A.
Published: June 2024

The decays of the Higgs boson produce a state in which the spins of the decay products and the orbital angular momentum (L) are highly entangled. We obtain the tripartite density operator, as well as reduced operators, for the decay into two weak bosons. For H→ZZ in the four-lepton final state we also estimate the statistical sensitivity at the Large Hadron Collider and future upgrades, using a binned method to reconstruct the density operators from distributions. With the expected Run 3 data, establishing genuine tripartite entanglement would be possible beyond the 5σ level. The violation of Bell inequalities involving the spins of the two weak bosons could also be established beyond the 5σ level.

Published by the American Physical Society
2024
Fireball antinucleosynthesis
Authors: Fedderke Michael A. , Kaplan David E. , Mathur Anubhav , Rajendran Surjeet , Tanin Erwin H.
Published: June 2024

The tentative identification of approximately ten relativistic antihelium (He¯) cosmic-ray events at AMS-02 would, if confirmed, challenge our understanding of the astrophysical synthesis of heavy antinuclei. We propose a novel scenario for the enhanced production of such antinuclei that is triggered by isolated, catastrophic injections of large quantities of energetic Standard Model (SM) antiquarks in our galaxy by physics beyond the Standard Model (BSM). We demonstrate that SM antinucleosynthetic processes that occur in the resulting rapidly expanding, thermalized fireballs of SM plasma can, for a reasonable range of parameters, produce the reported tentative ∼2:1 ratio of He¯3 to He¯4 events at AMS-02, as well as their relativistic boosts. Moreover, we show that this can be achieved without violating antideuterium or antiproton flux constraints for the appropriate antihelium fluxes. A plausible BSM paradigm for the catastrophic injections is the collision of macroscopic composite dark-matter objects carrying large net antibaryon number. Such a scenario would require these objects to be cosmologically stable, but to destabilize upon collision, promptly releasing a fraction of their mass energy into SM antiparticles within a tiny volume. We show that, in principle, the injection rate needed to attain the necessary antihelium fluxes and the energetic conditions required to seed the fireballs appear possible to obtain in such a paradigm. We leave open the question of constructing a BSM particle physics model to realize this, but we suggest two concrete scenarios as promising targets for further investigation.

Published by the American Physical Society
2024
New mechanism for primordial black hole formation from the QCD axion
Authors: Ge Shuailiang , Guo Jinhui , Liu Jia
Published: June 2024

We present a new mechanism for the primordial black hole (PBH) production within the QCD axion framework. We take the case where the Peccei-Quinn symmetry breaks during inflation, resulting in a NDW=1 string-wall network that reenters the horizon sufficiently late. Therefore, closed axion domain walls naturally arising in the network are sufficiently large to collapse into PBHs. Our numerical simulation shows that ∼0.3% of the total wall area is in the form of closed walls. In addition, the relic abundance of dark matter is dominantly accounted for by free axions from the collapse of open walls bounded by strings. In this framework, the abundance of PBH within dark matter is calculated to be ∼0.9%. This fraction remains unaffected by axion parameters or the reentering horizon temperature, as it is determined by the fixed proportion of closed walls in the network, governed by the principles of percolation theory. The resultant PBHs uniformly share the same mass, which spans from about 10−9 to 1 solar mass, corresponding to the classical QCD axion mass window 10−5–10−2  eV and the reentering horizon temperature 300−1  MeV. Intriguingly, PBHs in this mechanism can naturally account for the ultrashort-timescale gravitational microlensing events observed by the OGLE collaboration.

Published by the American Physical Society
2024
Gravitational waveforms: A tale of two formalisms
Authors: Bini Donato , Damour Thibault , De Angelis Stefano , Geralico Andrea , Herderschee Aidan , Roiban Radu , Teng Fei
Published: June 2024

We revisit the quantum-amplitude-based derivation of the gravitational waveform emitted by the scattering of two spinless massive bodies at the third order in Newton’s constant, h∼G+G2+G3 (one-loop level), and correspondingly update its comparison with its classically derived multipolar-post-Minkowskian counterpart. A spurious-pole-free reorganization of the one-loop five-point amplitude substantially simplifies the post-Newtonian expansion. We find complete agreement between the two results up to the fifth order in the small velocity expansion after taking into account three subtle aspects of the amplitude derivation: (1) in agreement with [A. Georgoudis , ], the term quadratic in the amplitude in the observable-based formalism [D. A. Kosower , ] generates a frame rotation by half the classical scattering angle; (2) the dimensional regularization of the infrared divergences of the amplitude introduces an additional (d−4)/(d−4) finite term; and (3) zero-frequency gravitons are found to contribute additional terms both at order h∼G1 and at order h∼G3 when including disconnected diagrams in the observable-based formalism.

Published by the American Physical Society
2024
Higgs branch RG flows via decay and fission
Authors: Bourget Antoine , Sperling Marcus , Zhong Zhenghao
Published: June 2024

Magnetic quivers have been an instrumental technique for advancing our understanding of Higgs branches of supersymmetric theories with eight supercharges. In this work, we present the “decay and fission” algorithm for unitary magnetic quivers. It enables the derivation of the complete phase (Hasse) diagram and is characterized by the following key attributes: First and foremost, the algorithm is inherently simple, just relying on convex linear algebra. Second, any magnetic quiver can only undergo decay or fission processes; these reflect the possible Higgs branch RG flows (Higgsings), and the quivers thereby generated are the magnetic quivers of the new RG fixed points. Third, the geometry of the decay or fission transition (i.e., the transverse slice) is simply read off. As a consequence, the algorithm does not rely on a complete list of minimal transitions, but rather outputs the transverse slice geometry automatically. As a proof of concept, its efficacy is showcased across various scenarios, encompassing superconformal field theories from dimensions 3 to 6, instanton moduli spaces, and little string theories.

Published by the American Physical Society
2024
Circular terahertz ratchets in a two-dimensionally modulated Dirac system
Authors: Hild M. , Yahniuk I. , Golub L. E. , Amann J. , Eroms J. , Weiss D. , Watanabe K. , Taniguchi T. , Ganichev S. D.
Published: June 2024

We report on the observation of the circular ratchet effect excited by terahertz laser radiation in a specially designed two-dimensional metamaterial consisting of a graphene monolayer deposited on a few-layer graphene gate patterned with an array of triangular antidots. We show that a periodically driven Dirac fermion system with spatial asymmetry converts the a.c. power into a d.c. current, whose direction reverses when the radiation helicity is switched. The circular ratchet effect is demonstrated for room temperature and a radiation frequency of 2.54 THz. It is shown that the ratchet current magnitude can be controllably tuned by the patterned and uniform back gate voltages. The results are analyzed in the light of the developed microscopic theory considering electronic and plasmonic mechanisms of the ratchet current formation.

Published by the American Physical Society
2024