bluuebunny/crossref_metadata_2025 huggingface dataset:
The what and when of word retrieval in spoken language
production
Authors: Mahon Bradford Z. , Navarrete Eduardo
Published: December 2024

Semantically driven lexical access in spoken
language production is the process of transposing a communicative
intention into phono-articulatory codes. At each stage of
processing, from lexical-semantic retrieval through to
phono-articulatory processing, more representations are active than
are minimally necessary to produce the target word. In recognition
of that fact, research over the past three decades has been driven
by a (putative) need to answer a core question: How is conflict
resolved at the lexical level? The ‘standard view’ involves some
form of the idea that selection of the target word is governed by a
stochastic process implemented via a biased competition mechanism,
with the nature of the ‘bias’ differing quite widely across
proposals. Here we argue that the standard view is out of synchrony
with a range of findings; interestingly, and as a matter of historical
precedent, a number of those findings pre-date the earliest
formulations of the standard view. Stepping back, we argue for a new
approach to framing the question of word retrieval: no mechanism is
needed to resolve conflict at the lexical level, because there is no
conflict at the lexical level. Selection occurs at
the semantic/message level. After selection of the intended meaning
representation, the next opportunity in the processing pathway to
re-evaluate which word to produce is at the level
of the pre-articulatory response monitor. We refer to this as a
‘ballistic’ model of word retrieval to emphasize there is no
uncertainty about the identity of the target
word at the lexical level, and that retrieval of
the correct representation at that level can be sped up, but not
slowed down.
Can learning explain cognate effects in bilingual comprehension
and production?
Authors: Winther Irene E. , Matusevych Yevgen , Pickering Martin J.
Published: December 2024

Most theories of bilingual word recognition and
production assume parallel, on-line activation of both languages,
even in one-language contexts. A considerable amount of the evidence
for parallel activation comes from the study of translation
equivalents with similar form and meaning across two languages
(cognates), which bilinguals process differently to translation
equivalents with no form similarity across languages (non-cognates).
The on-line account has been queried by Costa et al. (2017), who suggest that the
cognate effect can be explained by learning: on-line cross-talk
during second language acquisition would lead to different
representations for cognates compared to non-cognates in the
bilingual mental lexicon. In this chapter, we focus on these two
hypothesised origins of the cognate effect and consider the extent
to which cognate effects can be explained by learning and on-line
activation.
1683 and All That: The Habsburgs and the Prospects of a War on Two Fronts
Authors: Höbelt Lothar
Published: December 2024

The danger of a war on two fronts presented the late seventeenth-century Habsburg court in Vienna with a strategic choice, epitomised by the two factions of ‘Easterners’ versus ‘Westerners’. As long as Leopold I wanted to keep his hopes of claiming the Spanish inheritance alive, the priority of western issues was hardly ever in doubt. There was little evidence of an Austrian Drang nach Osten at the time, perhaps surprisingly. But there was a predictable tug-of-war between ‘hawks’ and ‘doves’ (or ‘appeasers’) in Vienna. The issue that concerned imperial decision makers in 1681–2 was less the French ‘réunions’ and the ‘rape of Strasbourg’ than the far less strident but potentially far more dangerous moves of Louis XIV to secure footholds in Italy. Above all, turning their back on the nascent anti-French coalition would have entailed huge opportunity costs for the Habsburgs. That is why the Emperor was willing to risk a war on two fronts. What was regarded as a desperate gamble before the battle of the Kahlenberg developed into a subtle attempt to let others bear the brunt of fighting for the Austrians on both fronts after the relief of Vienna. Leopold signed the armistice of Ratisbon in August 1684, but only when he could be fairly certain that it would not allow Louis XIV to play off the allies one against the other. His brinkmanship in 1683 laid the groundwork for the Grand Alliances of 1689 and 1702.
Reduction of amylose–amylopectin ratio in low-protein diets: impacts on growth performance and intestinal health in weaned pigs
Authors: Correa Federico , Luise Diana , Virdis Sara , Negrini Clara , Polimeni Barbara , Amarie Roxana Elena , Serra Andrea , Biagi Giacomo , Trevisi Paolo
Published: December 2024

Improving the synchrony between amino acids (AAs) and glucose appearance in the blood can support the growth performance of weaned pigs fed a low crude protein (CP) diet. This can be achieved using a diet with a low amylose-to-amylopectin ratio (AM/AP). The aim of this experiment was to evaluate whether reducing the AM/AP by using a corn variety characterized by a high amylopectin content, in the weaning diet can sustain growth performance and improve the intestinal health of pigs fed a low-CP diet. At weaning (25 ± 2 d), 90 pigs were assigned to 3 treatment groups: 1) control group (CTR), fed a standard diet with a medium-high CP content and high AM/AP (days 0 to 13: 18.0% CP, 0.13 AM/AP; days 14 to 27: 16.6% CP, 0.30 AM/AP; days 28 to 49: 16.7% CP, 0.15 AM/AP); 2) a group fed a low-CP diet with a high AM/AP (LP) (days 0 to 13: 16.0% CP, 0.17 AM/AP; days 13 to 27: 14.7% CP, 0.17 AM/AP; days 28 to 49: 14.5% CP, 0.25 AM/AP); 3) a group fed a low CP and a low AM/AP diet (LPLA) (days 0 to 13: 16.0% CP, 0.09 AM/AP; days 14 to 27: 14.7% CP, 0.05 AM/AP; days 28 to 49: 14.5% CP, 0.09 AM/AP). Pigs were weighted weakly until day 49. Fecal samples were collected on days 10 and 42 (12 samples/group/timepoint) for ammonia and calprotectin content and microbiota profile characterization. Until day 28, body weight (BW) of pigs from CTR was not different from pigs of the LPLA group, whereas it was higher from pigs of the LP group (P < 0.05). Thereafter, CTR group had greater BW compared with LP and LPLA groups for all the other timepoints considered (P < 0.05). From days 0 to 7 LPLA group had a lower incidence of diarrhea than the LP group (P = 0.04). On day 10, LPLA group had a greater alpha diversity (Shannon and InvSimpson indices), than the CTR (P = 0.03) and LP (P = 0.04) groups. On day 42, LPLA group had significantly greater InvSimpson diversity than LP group (P = 0.028). On day 10, LP group was characterized by greater abundance of Lactobacillus (LDA score = 5.15, P = 0.02), Clostridium-sensu-stricto-1 (LDA score = 4.90, P = 0.02) and Oscillospiraceae NK4A214-group (LDA score = 4.87, P = 0.004), whereas LPLA group was characterized by greater abundance of Prevotella (LDA score = 5.04, P = 0.003) and Agathobacter (LDA score = 4.77, P = 0.05). In conclusion, while reducing CP levels may negatively impact growth performance, when combined with higher amylopectin levels, it can reduce the incidence of diarrhea and increase fecal microbial diversity.
Contested Burial Grounds: African Religious Communities, Urban Displacement, and the Spatial Politics of Difference in Colonial Lagos, Nigeria
Authors: Somotan Titilola Halimat
Published: December 2024

This article uncovers how Black interfaith communities agitated to preserve public cemeteries on Lagos Island from the nineteenth century until the 1930s. As burial grounds became full during the 1920s, the British administration proposed closing Muslim and Christian cemeteries. The Black residents would be expected to bury the dead on Lagos mainland, which was connected to the island by the Carter Bridge. News of the cemetery closure galvanized Africans to successfully campaign for the expansion rather than the closing of public graveyards. Historians of mortuary politics and colonial planning have studied how European rulers mandated cemeteries and how Africans developed new burial rites in public burial grounds. This article demonstrates that the cemeteries were more than colonial instruments of dispossession. Interfaith practitioners developed new meanings for burial grounds that later motivated their struggles to ensure cemeteries’ accessibility. Despite their varying attitudes to burial grounds, as the traditional rulers maintained the precolonial practice of home burial, Lagosians claimed the right to inter their loved ones in the same area that they considered home. I argue that Black residents agitated against cemetery closure to challenge colonial residential segregation and maintain belonging to Lagos Island. The campaigns for burial grounds offer insight into Lagosians’ intervention in the built environment and resistance to colonial planning schemes.
Formal Thought Disorder in Schizophrenia: A Problematic History
Authors: Barrera Alvaro
Published: December 2024

Background and Hypothesis

Formal thought disorder (FTD), studied even before the inception of the concept of schizophrenia, remains a deeply isolating experience for patients as well as a difficult one for their interlocutors, including clinicians.

Study Design

The views on language, paralinguistic, and extralinguistic features exhibited by patients with severe mental ill health are reviewed, including the contributions from 19th-century European authors to the last third of the 20th century.

Study Results

Stages in the construction of FTD are described, including its merging with Dementia Praecox, and its subsequently being shaped by notions such as primitive archaic thinking, paralogical or autistic thinking, concretism, overinclusive thinking, and the return of the efforts to describing it with increased reliability.

Conclusions

It appears that some features of communication in schizophrenia, but not others, have been selected at different points in time for clinical and research use without realizing that by carrying out that selection, the phenomenon under study itself is changed. Remarkably, some theories of FTD remained in use, despite being empirically disproved (eg, word association disorder, concrete thinking, paralogical thinking) or despite its highly problematic and discriminatory nature. We would suggest that studies of FTD should explicitly consider which and why some of its features are included or excluded when assessing it. Furthermore, we would suggest that the study of FTD should incorporate the complexity of human communication, including the pragmatic, paralinguistic, non-verbal, and cognitive dimensions of the localized and unique situation where it takes place.
From community as data providers to community as data users: developing a community-led research platform using program data in HIV/STI Program Science in Kenya
Authors: Tahmo Nancy , Noah Anthony , Odhiambo Byron , Kyalo Charles , Ondiek Elly , Ligare Fortune , Asuri Gilbert , Wanjiku Jedidah , Njenga John Alex , Maina John , Mwendwa Kennedy , Olango Kennedy , Ouma Kennedy , Nekesa Loice , Macharia Pascal , Tabbu Silvano , Yiu Kristy CY , Lorway Robert , Bhattacharjee Parinita , Ma Huiting , Lazarus Lisa , Mishra Sharmistha , Walimbwa Jeffrey
Published: December 2024

Background

Community-based organizations (CBOs) are critical in providing trusted and targeted HIV/STI services to gay, bisexual, and other men who have sex with men (GBMSM). Despite significant strides in CBOs’ involvement in HIV/STI research, there remain gaps in meaningful engagement, especially in quantitative research. This paper explores the development of HEKA, a community-led research platform where community-based organizations build capacity and leverage routinely collected program data to design research that aims to improve HIV/STI programs. We share a collective reflection on the lessons learned in the process, the challenges that emerged, and recommendations for facilitating community-based program science.

Methodology

Through a collaborative process, seven CBOs serving GBMSM in Kenya created the HEKA Research Initiative and designed a framework of collaboration, through which we assessed the technical gaps in quantitative research among staff, applied for funding, co-designed capacity-building workshops with academic partners, and developed a research agenda. We established a monthly meeting frequency and through collective reflection, documented the lessons and challenges in the process.

Outcomes

With our successful grant, we organized an in-person workshop on quantitative research methods and R programming. The team identified research questions and completed data cleaning/harmonization of program data. HEKA was successful because we emphasized a co-leadership framework (research direction evolved through shared/delegated leadership), and peer-to-peer mentorship. Major challenges included: obtaining sustained funding for engagement; ensuring the learning pace allows all individuals to be on the same page; confronting the socio-political climate; long commutes between counties for in-person meetings; and the limitation in using Excel files as primary tools for data capture.

Conclusions

HEKA demonstrates the potential for community-based and led research in the HIV/STI field. The model we present can serve as a blueprint for other community-based organizations aiming to lead collaborative or independent research and build capacity.
IGFs regulate cancer cell immune evasion in prostate cancer
Authors: Nandakumar Ashwin M. , Barberis Alessandro , Kim Jinseon , Lang Cameron R. , Mills Jack V. , Rieunier Guillaume , Doultsinos Dimitrios , Taylor Avigail , Jainarayanan Ashwin , Phyu Su M. , Campo Leticia , Easton Alistair , Parkes Eileen , James Timothy , Hamdy Freddie C. , Verrill Clare , Mills Ian G. , Macaulay Valentine M.
Published: December 2024

Insulin-like growth factor-1 (IGF-1) promotes prostate cancer (PCa) development and lethality, with immunosuppressive properties in other disease models. These studies investigated the tumor-intrinsic immune effects of IGF-1 in PCa to understand mechanisms underlying its poor immunotherapy response. Transcriptional profiling of human (DU145, 22Rv1) and murine (Myc-CaP) PCa cells revealed, through pathway enrichment, that cytokine signalling, antigen processing and presentation, and other immune regulatory pathways, were most suppressed by IGF-1. We went on to investigate changes in the expression of components of two key pathways responsible for cancer cell recognition by immune cells and immune evasion: antigen processing and presentation, and PD-L1 checkpoint expression. These pathways are crucial for determining immunotherapy response. IGF-1 downregulated transporters associated with antigen processing (TAPs), endoplasmic reticulum aminopeptidase-1 (ERAP-1), and Class I component β2-microglobulin, without major changes in Class I allele expression. These effects were associated with reduced presentation of Class I complexes on the Myc-CaP cell surface suggesting altered peptide transport, processing, and/or presentation. In contrast, IGF-1 upregulated immune checkpointCD274(PD-L1) via IGF receptor/AKT/ERK-dependent signaling. Analysis of public data (TCGA Firehose Legacy PCa) revealed increasedCD274expression in PCa with high endogenousIGF1andIGFBP5, markers of high IGF axis activity. Additionally, in primary PCa (n=32), multiplex immunofluorescence revealed higher PD-L1 expression in the central tumor of men with high serum IGF-1 promoting cancer cell immune evasion in PCa. These findings indicate a novel mechanism by which IGF-1 mediates immunosuppressive effects in malignant prostate epithelium, potentially explaining the poor responsiveness of PCa to immunotherapy and highlighting the complex interplay between IGF signaling and immune evasion.
Assessing Behavioral and Neural Correlates of Change Detection in Spatialized Acoustic Scenes
Authors: Poole Katarina C. , Cappotto Drew , Martin Vincent , Sztandera Jakub , Chait Maria , Picinali Lorenzo , Shiell Martha
Published: December 2024

The ability to detect changes in complex auditory scenes is crucial for human survival, yet the neural mechanisms underlying this process remain elusive. This study investigates how the presence and location of sound sources impacts active auditory change detection as well as neural correlates of passive change detection. We employed stimuli designed to minimize semantic associations while preserving naturalistic temporal envelopes and broadband spectra, presented in a spatial loudspeaker array. Behavioral change detection experiments tasked participants with detecting new sources added to spatialized and non-spatialized multi-source auditory scenes. In a passive listening experiment, participants were given a visual decoy task while neural data were collected via electroencephalography (EEG) during exposure to unattended spatialized scenes and added sources.

Our behavioral experiments (N = 21 and 21) demonstrated that spatializing sounds facilitated change detection compared to non-spatialized presentation, but that performance declined with increasing number of sound sources and higher hearing thresholds at high frequencies, exclusively in spatialized conditions. Slower reaction times were also observed when changes occurred from above or behind the listener, exacerbated by a higher number of sources. EEG experiments (N = 32 and 30), using the same stimuli, showed robust change-evoked responses. However, no significant differences were detected in our analysis as a function of spatial location of the appearing source.
Association between virtual visits and health outcomes of people living with HIV: A cross-sectional study
Authors: Rehman Nadia , Mbuagbaw Lawrence , Mertz Dominik , Muraca Giulia M. , Jones Aaron
Published: December 2024

Background

Virtual care has been integrated as a modality of care in Ontario, yet its effectiveness for people living with HIV remains largely unexplored.

Objectives

We aimed to determine the association of visit modality (virtual, in-person, or both) on adherence to antiretroviral therapy (ART), viral load, and quality of life (QOL) in people living with HIV in Ontario, Canada.

Methods

We conducted a cross-sectional study using data from the 2022 Ontario HIV Treatment Network Cohort Study (OCS), collected during the COVID-19 pandemic when virtual visits were first introduced. Participants were grouped into three categories based on the mode of care: virtual, in-person, or a combination of both. Data were collected through self-reported questionnaires and medical records, with viral load data linked to Public Health Ontario Laboratories (PHOL). Logistic regression was used to examine the outcomes of optimal ART adherence and viral load suppression, and linear regression was used for quality of life (mental and physical) outcomes.

Results

In 2022, 1930 participants accessed HIV care in the OCS. Among them, 19.0% received virtual care, 45.6% received in-person care, and 34.3% received care through virtual and in-person modalities. The median age of the participants was 55 years (IQR: 45-62). In the multivariable logistic regression model, virtual care was associated with an increased likelihood of optimal adherence to antiretroviral therapy (Adjusted Odds Ratio (AOR) 1.30, 95% confidence interval (CI): 1.00-1.70) and an increased likelihood of achieving viral load suppression (AOR 1.67, 95% CI:1.03-2.63). Moreover, combined virtual and in-person care is associated with an improved mental quality of life compared to in-person care (Adjusted Mean difference (MD) - 0.960, 95% CI 0.052,1.869).

Conclusion

This study suggests virtual care is positively associated with adherence to antiretroviral therapy (ART) and viral suppression within this context. However, future research is necessary to establish causality and to assess the long-term effects of virtual care.
Using genomic epidemiology and geographic activity spaces to investigate tuberculosis outbreaks in Botswana
Authors: Baker Chelsea R. , Barilar Ivan , de Araujo Leonardo S. , Parker Daniel M. , Fornace Kimberly , Moonan Patrick K. , Oeltmann John E. , Tobias James L. , Minin Volodymyr M. , Modongo Chawangwa , Zetola Nicola M. , Niemann Stefan , Shin Sanghyuk S.
Published: December 2024

Background

The integration of genomic and geospatial data into infectious disease transmission analyses typically includes residential locations and excludes other activity spaces where transmission may occur (e.g. work, school, or social venues). The objective of this analysis was to explore residential as well as other activity spaces of tuberculosis (TB) outbreaks to identify potential geospatial ‘hotspots’ of transmission.

Methods

We analyzed data that included geospatial coordinates for residence and other activity spaces collected during 2012–2016 for the Kopanyo Study, a population-based study of TB transmission in Botswana. We included participants with results from whole genome sequencing conducted on archived samples from the original study. We used a spatial log-Gaussian Cox process model to detect core areas of increased activity spaces of individuals belonging to TB outbreaks (genotypic groups with ≤5 single-nucleotide polymorphisms), which we compared to ungrouped participants (those not in a genotypic group of any size).

Findings

We analyzed data collected from 636 participants, including 70 participants belonging to six outbreak groups with a combined total of 293 locations, and 566 ungrouped participants with a combined total of 2289 locations. Core areas of activity space for each outbreak group were geographically distinct, and we found evidence of localized transmission in four of six outbreaks. For most of the outbreaks, including activity space data led to the detection of larger areas of higher spatial intensity and more focal points compared to residential location alone.

Interpretation

Geospatial analysis using activity space data (social gathering places as well as residence) may lead to improved understanding of areas of infectious disease transmission compared to using residential data alone.

Funding

This work was supported by funding from the National Institute of Allergy and Infectious Diseases R01AI097045, R01AI147336, and R01AI170204.
Synergistic generation of cardiac resident-like macrophages and cardiomyocyte maturation in tissue engineered platforms
Authors: Suku Meenakshi , Murphy Jack F. , Corbezzolo Sara , Biggs Manus , Forte Giancarlo , Turnbull Irene C. , Costa Kevin D. , Forrester Lesley , Monaghan Michael G
Published: December 2024

Cardiovascular disease stands as the leading cause of death globally, claiming approximately 19million lives in 2020. On the contrary, the development of cardiovascular drugs is experiencing a decline, largely due to the bottleneck in understanding the pathophysiology of various heart diseases and assessing the effects of drugs on healthy human hearts. The development of induced pluripotent stem cell (iPSC) technology and the availability of cardiac cell typesin vitro, has resulted in a surge in efforts to fabricate human cardiac models for disease modelling and drug discovery applications. Although numerous attempts evidence successful fabrication of 3 dimensional (3D) engineered heart tissues, the innate immune cell population of the myocardium – particularly cardiac macrophages, was until recently, overlooke. With increasing appreciation of the interactions between cardiomyocytes and macrophages in the myocardium, in this work, isogenic populations of cardiac resident-like macrophages and cardiomyocytes were generated using iPSCs, to understand the interactions between the two cell types in both 2D and 3D settings, and subjected to electric stimulation. After characterizing iPSC-derived macrophages (iMacs) and iPSC-derived cardiomyocytes (iCMs) in depth, the conditioning of iMacs to align to a cardiac resident macrophage-like phenotype in the presence of iCMs in 2D culture was explored. In co-culture with iCMs, iMacs upregulated known genes expressed by cardiac resident macrophages. Additionally, in co-culture with iMacs, iCMs displayed an elongated morphology, improved calcium function and an increase in known maturation genes such as the ratio between MYH7 and MYH6 as well as SERCA2. In a 2D setting, iMacs showed the ability to electrically couple with iCMs and facilitate synchronous beating in iCM cultures. The 2D characterisation was translated into an engineered cardiac tissue model, wherein, improvement in tissue characteristics in the presence of iMacs was demonstrated in terms of increased cell alignment, enhanced cardiomyocyte elongation, physiologically relevant beat rates and improved tissue compaction. Taken together, these findings may open new avenues to use iMacs in engineered cardiac tissue models, not only as an innate immune cell source, but also as a support cell type to improve cardiomyocyte function and maturation.
Drug Response Modeling across Cancers: Proteomics vs. Transcriptomics
Authors: Zheng Zetian , Huang Lei , Wang Fuzhou , Liu Linjing , Yu Jixiang , Xie Weidun , Chen Xingjian , Li Xiangtao , Wong Ka-Chun
Published: December 2024

Cancer cell lines are the most commonin-vitromodels for the evaluation of anti-cancer drug sensitivities. Past studies have been conducted to decipher and characterize the pharmacogenomic feature of cell lines based on other omics data, such as genomic mutation data and whole-genome RNA sequencing (RNA-seq) profiles. In particular, proteomic data is also an essential component for the characterization of tumours. However, different from RNA-seq datasets rich in numerous transcriptome profiles of cancer cell lines and cell viability assay of drug responses, the pharmacogenomic protein quantifications are relatively scarce. With the availability of the recently enriched proteomic dataset ProCan-DepMapSanger, we systematically evaluated the interplays among genomic mutations, transcription, and protein expressions across cancer cell lines. In general, blood cancers have higher RNA-protein correlations than those in solid cancers. The differential expression analysis on protein data helped identify more expressional and functional impact of genomic mutations of cancer genes. We also integrated the proteomic map with drug molecular chemical features to construct a bi-modal machine learning model to infer the drug sensitivities of cancer cell lines. Our results demonstrated that protein quantifications can lead to better drug response prediction performance than the model trained on transcriptome profiles. In addition, integrating protein data with drug chemical features, represented as molecular graphs and learned by Graph Neural Network, outperformed the state-of-the-art model DeepOmicNet for drug response prediction in proteomics.
The evolution of pectate lyase-like genes across land plants, and their roles in haustorium formation in parasitic plants
Authors: Zhang Huiting , Wafula Eric , Kelly Elizabeth , Ko Itsuhiro , Yocca Alan , Gunathilake Pradeepa , Yang Zhenzhen , Yoder John , Honaas Loren , dePamphilis Claude
Published: December 2024

Parasitic plants in the Orobanchaceae family are noxious agricultural pests that severely impact crops worldwide. These plants acquire water and nutrients from their hosts through a specialized organ called the haustorium. A critical process in the formation and function of the haustorium involves cell wall modification. In this study, we identified and analyzed the evolutionary relationships ofpectate lyase-like(PLL) genes in parasitic plants and other major land plant lineages. One particularPLLgene, denoted asPLL1in parasitic Orobanchaceae, which our previous research identified as a potential key parasitism gene, belongs to the largest sub-clade of this gene family. To explore the role ofPLL1gene in parasitic Orobanchaceae further, we manipulated its transcript abundance during haustorium development inTriphysaria versicolor, a model species in parasitic Orobanchaceae, using both direct transformation of the parasite and host-induced-gene-silencing (HIGS). For HIGS, we generated transgenic hosts (Medicago truncatulaandArabidopsis thaliana) carrying hairpin RNAs targeting thePLLgene inT. versicolor. Our results demonstrated that both methods effectively reduced thePLL1expression in the haustorium ofT. versicolor, leading to an increase in poorly adhered parasites. These findings highlightPLL1’s crucial role in haustorium development in Orobanchaceae and may inform novel strategies towards parasitic weed management.
Fluctuations and the limit of predictability in protein evolution
Authors: Rossi Saverio , Di Bari Leonardo , Weigt Martin , Zamponi Francesco
Published: December 2024

Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct sites and times. To quantify these correlations, we examine the role of various fluctuation sources in protein evolution, simulated using a data-driven energy landscape, used as a proxy for protein fitness. By applying spatio-temporal correlation functions developed in the context of disordered physical systems, we disentangle fluctuations originating from the initial condition, i.e. the ancestral sequence from which the evolutionary process originated, from those driven by stochastic mutations along independent evolutionary paths. Our analysis shows that, in diverse protein families, fluctuations from the ancestral sequence predominate at shorter time scales. This allows us to identify a time scale over which ancestral sequence information persists, enabling its reconstruction. We link this persistence to the strength of epistatic interactions: ancestral sequences with stronger epistatic signatures impact evolutionary trajectories over extended periods. At longer time scales, however, ancestral influence fades as epistatically constrained sites evolve collectively. To confirm this idea, we apply a standard ancestral sequence reconstruction algorithm and verify that the time-dependent recovery error is influenced by the properties of the ancestor itself.
A randomized controlled trial comparing epinephrine and dexamethasone to placebo in the treatment of infants with bronchiolitis: the Bronchiolitis in Infants Placebo versus Epinephrine and Dexamethasone (BIPED) study protocol
Authors: Plint Amy C. , Heath Anna , Rowe Tremaine , Vogel Kristina I. , Wills-Ibarra Natasha , O’Brien Sharon , Borland Meredith L. , Johnson David W. , Zorc Joseph J. , Pechlivanoglou Petros , Schuh Suzanne , Rao Medhawani , Bonisch Megan , Craig Simon S. , Gouin Serge , Kochar Amit , Thompson Graham C. , Lash Chris , Dixon Andrew , Sawyer Scott , Joubert Gary , Oakley Ed , Offringa Martin , Klassen Terry P. , Dalziel Stuart R.
Published: December 2024

Background

Bronchiolitis exerts a significant burden of illness on infants worldwide predominantly due to need for hospitalization. Currently only supportive care is advised by national guidelines for infants with bronchiolitis. There is evidence that treating infants with bronchiolitis with a combination of inhaled epinephrine and dexamethasone may reduce hospital admissions. Synergy between beta-agonists and corticosteroids is recognized in asthma management and basic science literature demonstrates that co-administration of these medications enhances each other’s effectiveness.

Objective

To determine if infants with bronchiolitis treated with inhaled epinephrine (delivered by metered dose inhaler with spacer or nebulizer) in the emergency department and a 2-day course of oral dexamethasone have fewer hospitalizations (due to bronchiolitis) over 7 days compared to infants treated with placebo.

Design

The BIPED study (Bronchiolitis in Infants Epinephrine versus Dexamethasone and Placebo) is a randomized, placebo-controlled, observer, investigator, clinician, and patient blinded superiority clinical trial being conducted in 12 emergency departments across three countries (Canada, New Zealand, and Australia). We will recruit 864 infants between 60 days and 12 months of age with bronchiolitis to receive either (1) two inhaled epinephrine treatments (3 mg via nebulizer or 625 mcg via metered dose inhaler with spacer) 30 minutes apart and a simultaneous dose of oral dexamethasone (0.6 mg/kg, maximum 10 mg) in the emergency department with the dexamethasone repeated at 24 hours or (2) inhaled placebo and oral placebo. The primary outcome is hospital admission for bronchiolitis within 7 days (168 hours) of enrolment. Secondary outcomes include hospital admission during enrolment, and all cause hospital admissions and healthcare provider visits within 21 days of enrolment. We will use a Bayesian approach for data analysis and inference.

Discussion

Given the healthcare burden of bronchiolitis, there is urgent need for a trial to confirm if combination therapy with epinephrine and dexamethasone is effective.

Trial registration

ClinicalTrials.gov:NCT03567473. Registered on 2018-06-13.

Protocol version

CTO 1423, dated 20 January 2023

Sponsor-Investigator

Dr. Amy C Plint, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada

Secondary Sponsor

Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
Transparency in epidemiological analyses of cohort data A case study of the Norwegian Mother, Father, and Child cohort study (MoBa)
Authors: Roettger Timo , Askelund Adrian Dahl , Birkenæs Viktoria , Bjørndal Ludvig Daae , Bochynska Agata , Glaser Bernt Damian , Kalandadze Tamara , Korbmacher Max , Malovic Ivana , Mayor Julien , Parekh Pravesh , Quintana Daniel S. , Hannigan Laurie J.
Published: December 2024

Background

Epidemiological research is central to our understanding of health and disease. Secondary analysis of cohort data is an important tool in epidemiological research, but is vulnerable to practices that can reduce the validity and robustness of results. As such, adopting measures to increase the transparency and reproducibility of secondary data analysis is paramount to ensuring the robustness and usefulness of findings. The uptake of such practices has not yet been systematically assessed.

Methods

Using the Norwegian Mother, Father and Child Cohort study (MoBa; Magnus et al., 2006, 2016) as a case study, we assessed the prevalence of the following reproducible practices in publications between 2007-2023: preregistering secondary analyses, sharing of synthetic data, additional materials, and analysis scripts, conducting robustness checks, directly replicating previously published studies, declaring conflicts of interest and publishing publicly available versions of the paper.

Results

Preregistering secondary data analysis was only found in 0.4% of articles. No articles used synthetic data sets. Sharing practices of additional data (2.3%), additional materials (3.4%) and analysis scripts (4.2%) were rare. Several practices, including data and analysis sharing, preregistration and robustness checks became more frequent over time. Based on these assessments, we present a practical example for how researchers might improve transparency and reproducibility of their research.

Conclusions

The present assessment demonstrates that some reproducible practices are more common than others, with some practices being virtually absent. In line with a broader shift towards open science, we observed an increasing use of reproducible research practices in recent years. Nonetheless, the large amount of analytical flexibility offered by cohorts such as MoBa places additional responsibility on researchers to adopt such practices with urgency, to both ensure the robustness of their findings and earn the confidence of those using them. A particular focus in future efforts should be put on practices that help mitigating bias due to researcher degrees of freedom – namely, preregistration, transparent sharing of analysis scripts, and robustness checks. We demonstrate by example that challenges in implementing reproducible research practices in analysis of secondary cohort data - even including those associated with data sharing - can be meaningfully overcome.
Virtual Care and Medical Cannabis Access: A Geospatial Study of Telemedicine’s Role in Reducing Socioeconomic Disparities
Authors: Doucette Mitchell L. , Fisher Emily , Hemraj Dipak , Kasabuski Mark , Chin Junella
Published: December 2024

Introduction

Telemedicine has the potential to improve healthcare access and reduce disparities. We examined whether the incidence rate of medical cannabis patients (MC) was associated with concentrated disadvantage in Pennsylvania in 2022, accounting for a population of patients approved through telemedicine.

Methods

This zip code-level analysis examined associations between the Concentrated Disadvantage Index (CDI) and two outcomes: (1) the number of telemedicine-approved MC patients, as obtained from a specific telemedicine provider, and (2) the number of all other MC patients, calculated by subtracting the number of telemedicine-approved patients from the total number of MC patients at the zip code-level. Total counts of MC patients and in-office MC providers for Pennsylvania were sourced from the Pennsylvania Department of Health, while CDI data were derived from the 2022 American Community Survey. We used multivariate negative binomial regression models with population offsets and robust standard errors, adjusting for spatial autocorrelation through spatial lag adjustments.

Results

The CDI was not associated with the incidence rate of telemedicine-approved MC patients (IRR = 0.962;p= 0.355), but it was significantly negatively associated with the incidence rate of all other MC patients (IRR = 0.904;p= 0.000). The density of in-office MC providers was significantly associated with the incidence rate of all other MC patients but not with telemedicine-approved patients. Spatial factors, including autocorrelation, significantly influenced the distribution of both groups of patients.

Discussion

These findings suggest that telemedicine plays a crucial role in improving access to MC for socioeconomically disadvantaged areas. The lack of a significant association between the CDI and telemedicine-approved MC patients highlights the ability of telemedicine to bypass barriers such as provider scarcity and transportation challenges. By facilitating remote consultations and approvals, telemedicine ensures access for patients who might otherwise face difficulties obtaining MC.
Carbapenem Stewardship Program in a Cardiovascular Hospital in Tehran, Iran and Literature Review
Authors: Nazari Elham , Roumi Azin , Kamali Monireh , Sabooteh Toomaj
Published: December 2024

Introduction

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are critical global challenges. Antimicrobial Stewardship Programs (ASPs) aim to optimize antibiotic use and reduce resistance. This study evaluates carbapenem stewardship compliance in open-heart surgery patients at Shaheed Rajaie Cardiovascular Medical and Research Center, Tehran, emphasizing improved infection control and antibiotic management.

Methodology

This descriptive, cross-sectional study assessed carbapenem antibiotic use compliance with national guidelines in open-heart surgery patients at Shaheed Rajaie Cardiovascular Medical Center, Tehran. Seventy patients were selected, and data on demographics, clinical factors, microbiology, and antibiotic use were analyzed using SPSS 26 to evaluate compliance rates and prescribing factors.

Results

This study analyzed data from 70 patients undergoing open-heart surgery at a cardiovascular hospital in Tehran. The cohort had an equal gender distribution and a mean age of 59.15 years (SD: 12.0). Of the procedures, 51.43% were elective, while 48.57% were emergencies. The most common surgeries included CABG (45.71%) and valvular procedures (30%). Meropenem was the most prescribed antibiotic (92.9%), with prophylactic use noted in 78.57% intraoperatively. Positive cultures identified Candida albicans (32.7%), Klebsiella pneumoniae (29.8%), and Staphylococcus aureus (22.6%) as predominant pathogens. Serum creatinine levels exceeded the normal range in 55.7% of patients, necessitating dosage adjustments. Antibiotic side effects led to treatment discontinuation in 15.7% of cases.

Conclusion

This study highlights a high level of rational carbapenem use in a specialized cardiac surgery ICU, with prescribing guided by infectious disease consultations and adherence to guidelines. Implementing antibiotic stewardship programs can further optimize carbapenem use, reduce antibiotic resistance, and improve treatment outcomes, emphasizing the importance of individualized infection management and monitoring in cardiac surgery patients.
Increased risk of asthma in female night shift workers
Authors: Maidstone Robert J. , Ray David W. , Liu Junxi , Bowden Jack , Rutter Martin K. , Durrington Hannah J.
Published: December 2024

Background

Asthma is more common in females and more common in night shift workers. Since increasing numbers of females are becoming shift workers it is important to determine if shift work-associated asthma risk is higher in females.

Research Question

Is increasing frequency of night shift work more strongly related to prevalent asthma in females than in males?

Study Design and Methods

We used cross-sectional data from >280,000 UK Biobank participants and logistic regression models adjusted for demographic and lifestyle factors to describe sex differences in prevalent asthma related to shift work frequency. To obtain mechanistic insights, we explored associations with chronotype, sex hormones and menopause.

Results

Compared to female day workers, female permanent night shift workers had higher covariate-adjusted odds of moderate-severe asthma (OR: 1.50 (95% CI 1.18 – 1.91)) but there was no corresponding relationship in males (OR 0.95 (95% CI 0.72 – 1.26); sex interaction p-value = 0.01). Similar relationships were observed for ‘all asthma’ and for ‘wheeze or whistling in the chest’ outcomes. Female shift work-related asthma was driven by relationships in postmenopausal women not using HRT (e.g., adjusted OR: 1.89 (1.24-2.87) for moderate-severe asthma; sex interaction p-value = 0.02 in permanent nightshift workers compared to dayworkers) but these relationships attenuated to the null in postmenopausal women using HRT.

Interpretation

Our finding that increasing shift work frequency is more strongly related to asthma in females than in males could have Public Health implications. Intervention studies should determine if modifying shift work schedules or HRT can reduce asthma risk in females.
The diagnostic value of hyperlipidemia and lipophagy-related genes, PLAUR, IVNS1ABP, and QKI, in acute myocardial infarction
Authors: Zou Jun-Hua , Wang Hua-Wei , Long Jia-Zhi , Yang Xiao-Na , Yang Li-Hong , Li Long-Jun , Chen Li-Xing , Dong Ling , Chen Jing , Meng Zhao-Hui , Wan Wen
Published: December 2024

Background

Hyperlipidemia (HLP) may intensify myocardial cell damage by disrupting lipophagy, a pivotal lipid metabolism pathway, thereby heightening the risk of acute myocardial infarction (AMI). This study aims to identify HLP- and lipophagy-associated biomarkers for AMI through a combined transcriptomic and mendelian randomization (MR) approach.

Methods

The mRNA expression data for AMI, along with HLP-related genes (HRGs) and lipophagy-related genes (LRGs), were sourced from public databases. Biomarkers were identified by conducting differential expression analysis, weighted gene co-expression network analysis (WGCNA), MR analysis, and receiver operating characteristic (ROC) analysis, complemented by two machine learning algorithms and expression validation. These biomarkers facilitated an investigation into the role of platelet activation-related genes (PARGs) in AMI, with enrichment analysis providing insights into their underlying mechanisms. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to validate biomarker expression in clinical samples.

Results

Three biomarkers exhibited a consistently significant upregulation trend in AMI samples, corroborated by RT-qPCR findings. Notably, PLAUR [Odds ratio (OR) = 1.115, 95% confidence interval (CI): 1.006–1.237,P= 0.038] and IVNS1ABP (OR = 1.047, 95% CI: 1.000–1.096,P= 0.048) emerged as AMI risk factors, while QKI (OR = 0.946, 95% CI: 0.903– 0.991,P= 0.020) was identified as a protective factor. Additionally, PLAUR, QKI, and IVNS1ABP demonstrated robust diagnostic efficacy with area under the curve (AUC) values of 0.773, 0.933, and 0.807, respectively; when integrated into a nomogram, the combined AUC reached 0.924. These genes were enriched in pathways linked to cardiovascular diseases, inflammatory responses, and cellular metabolic processes and appeared actively involved in platelet activation, as indicated by their strong associations with PARGs.

Conclusion

In summary, the biomarkers PLAUR, QKI, and IVNS1ABP, connected to HLP and lipophagy, showed a causal relationship with AMI and marked diagnostic potential for predicting AMI risk, offering valuable support for clinical diagnostics and AMI research.
Occupational Exposures to Blood and other Body Fluids among Healthcare Workers in Cameroon: A Systematic Review and Meta-analysis
Authors: Cheuyem Fabrice Zobel Lekeumo , Mouangue Christian , Ajong Brian Ngongheh , Edzamba Michel Franck , Hamadama Dilane Christian Maidey , Achangwa Chabeja , Mohamadou Adama , Sonfack Pamela , Amani Adidja
Published: December 2024

Background

Occupational exposure to blood and body fluids has become a serious public health problem for healthcare workers and is a major risk for the transmission of bloodborne infections such as human immune-deficiency, hepatitis B, and hepatitis C viruses. It has been identified as one of the most serious issues affecting the health and well-being of health workers in most health systems especially in developing countries. The present systematic review and meta-analysis was conducted to estimate the pooled prevalence of blood and other body fluids exposures among healthcare workers in Cameroon.

Methods

Online platform including PubMed, Google Scholar, Cochrane Library, and Science Direct were systematically searched to collect relevant research reports. Unpublished studies in a national library were also consulted. TheI2tests were used to assess the heterogeneity of the included studies. A fixed and random-effects meta-analysis model was used to estimate the lifetime and 12-month prevalence of occupational exposure to blood and other body fluids among healthcare workers in Cameroon.

Results

Of the 539 records identified through the database search, 15 study reports were included in the final analysis. The random-effects model showed that the estimated overall pooled prevalence of 12-month and lifetime exposure to blood and other body fluids among healthcare workers in Cameroon was 55.44% (95% Confidence Interval (CI): 41.20-69.68); (I2=97.5%;p<0.001) and 57.27% (95% CI: 42.43-72.10); (I2=97.7%;p<0.001) respectively. The highest 12-month pooled prevalence was observed in intermediate level health facilities (84.73%; 95% CI: 85.55-88.50), in Regions other than the Centre (70.87%; 95% CI: 37.26-95.13) and for studies conducted from 2017 to 2023 (65.63%; 95% CI: 45.73-83.06). The lifetime prevalence of blood and other body fluids exposures was the highest for Regions namely the North-west and South-west Regions (77.96%; 95% CI: 57.39-93.19).

Conclusion

Healthcare workers in Cameroon face a significant risk of occupational exposure to blood and body fluids (BBFs), with a high prevalence of exposure over their lifetime and in the past 12 months. This highlights the urgent need to enhance and implement effective occupational safety and health policies to protect healthcare workers in Cameroon.