bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth patterns by birth size of preterm children born at 24–29 gestational weeks for the first 3 years
Authors: Fenton Tanis R. , Samycia Lauren , Elmrayed Seham , Nasser Roseann , Alshaikh Belal
Published: May 2024

Background

Concerns are prevalent about preterm infant long‐term growth regarding plotting low on growth charts at discharge, stunting, underweight, high body fat and subsequent cardiometabolic morbidities.

Objectives

To examine (a) longitudinal growth patterns of extremely and very preterm infants to 3 years corrected age (CA) (outcome), categorised by their birthweight for gestational age: small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) (exposure); and (b) the ability of growth faltering (<−2 z‐scores) to predict suboptimal cognitive scores at 3 years CA.

Methods

Post‐discharge head, length, weight and weight‐4‐length growth patterns of the PreM Growth cohort study infants born <30 weeks and < 1500 g, who had dietitian and multi‐disciplinary support before and after discharge, were plotted against the World Health Organization growth standard. Infants with brain injuries, necrotising enterocolitis and bronchopulmonary dysplasia were excluded.

Results

Of the included 405 infants, the proportions of infants with anthropometric measures > − 2 z‐scores improved with age. The highest proportions <−2 z‐scores for length (24.2%) and weight (24.0%) were at 36 gestational weeks. The proportion with small heads was low by 0 months CA (1.8%). By 3 years CA, only a few children plotted lower than −2 z‐scores for length, weight‐4‐length and weight (<6%). After zero months CA, high weight‐4‐length and body mass index > + 2 z‐scores were rare (2.1% at 3 years CA). Those born SGA had higher proportions with shorter heights (16.7% vs. 5.2%) and lower weights (27.8% vs. 3.5%) at 3 years CA compared to those born AGA. The ability of growth faltering to predict cognitive scores was limited (AUROC 0.42, 95% CI 0.39, 0.45 to 0.52, 95% CI 0.41, 0.63).

Conclusions

Although children born <30 weeks gestation without major neonatal morbidities plot low on growth charts at 36 weeks CA most catch up to growth chart curves by 3 years CA.
Sympathetic arousal among depressed college students: Examining the interplay between psychopathology and social activity
Authors: Jelsma Elizabeth , Zhang Amy , Goosby Bridget J. , Cheadle Jacob E.
Published: May 2024

Depressed individuals exhibit altered sensitivity to both positive and negative social contact, and may not reap the same psychological and emotional benefits to socializing as non‐depressed individuals. Although depressive symptoms and loneliness predict social withdrawal and decreased pleasure, little is currently understood about immediate affective arousal dynamics during real‐time socializing. Using a novel ambulatory protocol that tracked both objective features of affective arousal (electrodermal activity) and subjective valence (self‐reported) during college students' social interactions, we evaluated the moderating role of depression and loneliness symptoms on the associations between socializing with others (specifically, with a romantic partner, a close friend, or a group of friends) and the arousal and valence dimensions of affect. Among a racially and ethnically diverse sample of 118 college students (64% African American/Black/Continental African, 20% Latinx, 8% Asian, and 8% White) recruited from a large, predominantly White Midwestern university, those lower in depression and loneliness symptomatology evinced decreased average arousal (Β = −0.10, SE = 0.04, p < .01) when in relaxed and intimate socializing contexts (e.g., with a romantic partner and a close friend), consistent with the idea that these contexts facilitate important opportunities for psychological rest and recovery. Those lower in depression and loneliness symptoms also showed higher average arousal when socializing in the energizing context of being with a group of friends. Overall, the results suggest psychopathology is reflected in patterns of sympathetic arousal when socializing, with more depressed and lonely individuals generally feeling worse while receiving fewer psychophysiological rewards in multiple socializing contexts.
The Balancing Exercise and the Resolution of Rhetorical Antinomies in Judicial Decision‐Making
Authors: Soboleva Anita
Published: May 2024

The “balancing exercise” engaged in by judges in cases involving conflicts of rights can be analysed in rhetorical terms as a process for resolving rhetorical antinomies, where an antinomy is understood as a contradiction between two equally justifiable conclusions drawn from two or more equally applicable rules or principles. By investigating the possible responses to antinomies and identifying their types, we can better understand the process of judicial decision‐making and the ways which international and national courts justify their decisions.
Causal effects of genetically determined metabolites on androgenetic alopecia: A two‐sample Mendelian randomization analysis
Authors: Du Yimei , Lu Changpei , Bi Lingbo , Wang Chaofan , Zhao Min , Ding Yunbu , Fan Weixin
Published: May 2024

Background

Androgenic alopecia (AGA) is the most common non‐scarring alopecia disorder. Given its increasing incidence and onset during adolescence, AGA significantly impacts both the physical and psychological well‐being of affected individuals. Emerging evidence suggests a pivotal role of metabolites in AGA. This study aims to elucidate the causal relationship between metabolites and AGA using Mendelian randomization (MR) analysis.

Methods

We conducted a two‐sample Mendelian randomization (TSMR) analysis based on a genome‐wide association study (GWAS) to assess the causality of 452 metabolites on AGA. The main approach employed for inferring causal effects was inverse variance weighted (IVW), which was complemented by MR‐Egger regression, weighted median, as well as MR pleiotropy residual sum and outlier (MR‐PRESSO) approaches. Additionally, sensitivity analyses were performed to ensure result robustness. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) in GWAS dataset comprising 452 metabolites.

Results

Notably, we identified Scyllo‐inositol and Alpha‐ketoglutarate as the most potent protective factors against AGA, while Heme* and 2‐palmitoylglycerophosphocholine* emerged as significant risk factors for AGA. Furthermore, sensitivity analysis revealed no heterogeneity in these findings.

Conclusions

Overall, our research suggests a potential causal link between metabolites and AGA, offering a more comprehensive insight into the pathogenesis of AGA and present additional strategies for prevention and treatment.
On a lower bound of Hausdorff dimension of weighted singular vectors
Authors: Kim Taehyeong , Park Jaemin
Published: May 2024

Let be a ‐tuple of positive real numbers such that and . A ‐dimensional vector is said to be ‐singular if for every , there exists such that for all , the system of inequalities
has an integer solution . We prove that the Hausdorff dimension of the set of ‐singular vectors in is bounded below by . Our result partially extends the previous result of Liao et al. [Hausdorff dimension of weighted singular vectors in , J. Eur. Math. Soc. 22 (2020), 833–875].
Political economy analysis of health: a scoping review protocol
Authors: Karuveettil Vineetha , Janakiram Chandrashekar , John Denny , Mathur Manu , Varma Balagopal , Green Heidi
Published: May 2024

Objective:

The objective of this scoping review is to identify and map the literature on concepts, definitions, frameworks, outcomes, and applications of political economic analysis of health.

Introduction:

The political economy of health approach seeks to understand how political and economic domains interact and shape individual and population health outcomes. A political economic analysis can provide insights into health problems and inequalities; however, there needs to be more clarity on how the political economy framework is defined and the methods adopted for conducting political economy analysis concerning health.

Inclusion criteria:

Studies focusing on the political economy analysis addressing specific health problems will be included. The study population is not limited to any sociodemographic characteristics, and there will be no restrictions on language or the source of evidence (primary studies or secondary data studies). Both qualitative and quantitative methodologies will included, but narrative and systematic reviews will be excluded, as will conference abstracts and editorials. Studies involving sector- or country-level analysis will be included.

Methods:

The review will follow the JBI methodology for scoping reviews. Databases to be searched include MEDLINE, Scopus, Web of Science, Cochrane CENTRAL, CINAHL, Embase, ProQuest, DynaMed, and gray literature via Google Scholar and OAIster. Two reviewers will perform study screening and data extraction using a customized data extraction form. The concepts, definitions, frameworks, outcomes, and applications of the political economy of health will be summarized and discussed. The health problems addressed using political economy analysis will be enumerated. Stakeholder engagement will guide all steps of the study. Results will be presented in tabular and graphical formats accompanied by a narrative summary.

Review registration:

Open Science Framework https://osf.io/4qaxr/
Age‐related changes in reticulospinal contributions to anticipatory postural adjustments between back extensors and abdominal muscles
Authors: Chiou Shin‐Yi , Unwin Catherine , Lilley Alice
Published: May 2024

Anticipatory postural adjustments (APAs) give feedforward postural control of the trunk, but they are delayed with ageing, affecting balance and mobility in older individuals. The reticulospinal tract contributes to postural control of the trunk; however, the extent to which age‐related changes affect the reticulospinal contributions to APAs of the trunk remains unknown in humans. Here, we tested the hypothesis that a startling acoustic sound, which activates the reticulospinal tract, improves delayed APAs in older individuals. Twenty‐two old (75 ± 6 years) and 20 healthy young adults (21 ± 4 years) performed a self‐initiated fast bilateral shoulder flexion or shoulder extension task in response to visual, visual and auditory (80 dB), or visual and startling (115 dB) cues. Electromyography (EMG) was recorded from bilateral anterior deltoid (AD) and erector spinae (ES) during shoulder flexion and from bilateral posterior deltoid (PD) and rectus abdominis (RA) during shoulder extension. EMG onset of all muscles shortened during the startling cue in both age groups, suggesting a non‐specific modulation of the reticulospinal tract on prime movers (AD or PD) and non‐prime movers (ES or RA). Interestingly, APAs of the ES were accelerated in older participants to a similar degree as in younger participants during the startling cue. Conversely, APAs of the RA were not influenced by the startling cue in older participants. Our results suggest differential effects of ageing on functional contributions of the reticulospinal tract to APAs between back extensors and abdominal muscles.
Oncogene
EVI1
drives acute myeloid leukemia via a targetable interaction with CTBP2
Authors: Pastoors Dorien , Havermans Marije , Mulet-Lazaro Roger , Brian Duncan , Noort Willy , Grasel Julius , Hoogenboezem Remco , Smeenk Leonie , Demmers Jeroen A. A. , Milsom Michael D. , Enver Tariq , Groen Richard W. J. , Bindels Eric , Delwel Ruud
Published: May 2024

Acute myeloid leukemia (AML) driven by the activation of
EVI1
due to chromosome 3q26/
MECOM
rearrangements is incurable. Because transcription factors such as EVI1 are notoriously hard to target, insight into the mechanism by which EVI1 drives myeloid transformation could provide alternative avenues for therapy. Applying protein folding predictions combined with proteomics technologies, we demonstrate that interaction of EVI1 with CTBP1 and CTBP2 via a single PLDLS motif is indispensable for leukemic transformation. A 4× PLDLS repeat construct outcompetes binding of EVI1 to CTBP1 and CTBP2 and inhibits proliferation of 3q26/
MECOM
rearranged AML in vitro and in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML with specific EVI1-CTBP inhibitors. This has important implications for other tumor types with aberrant expression of EVI1 and for cancers transformed by different CTBP-dependent oncogenic transcription factors.
RACER-m leverages structural features for sparse T cell specificity prediction
Authors: Wang Ailun , Lin Xingcheng , Chau Kevin Ng , Onuchic José N. , Levine Herbert , George Jason T.
Published: May 2024

Reliable prediction of T cell specificity against antigenic signatures is a formidable task, complicated by the immense diversity of T cell receptor and antigen sequence space and the resulting limited availability of training sets for inferential models. Recent modeling efforts have demonstrated the advantage of incorporating structural information to overcome the need for extensive training sequence data, yet disentangling the heterogeneous TCR-antigen interface to accurately predict MHC-allele-restricted TCR-peptide interactions has remained challenging. Here, we present RACER-m, a coarse-grained structural model leveraging key biophysical information from the diversity of publicly available TCR-antigen crystal structures. Explicit inclusion of structural content substantially reduces the required number of training examples and maintains reliable predictions of TCR-recognition specificity and sensitivity across diverse biological contexts. Our model capably identifies biophysically meaningful point-mutant peptides that affect binding affinity, distinguishing its ability in predicting TCR specificity of point-mutants from alternative sequence-based methods. Its application is broadly applicable to studies involving both closely related and structurally diverse TCR-peptide pairs.
egr3
is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis
Authors: da Silva Agatha Ribeiro , Gunawan Felix , Boezio Giulia L. M. , Faure Emilie , Théron Alexis , Avierinos Jean-François , Lim SoEun , Jha Shivam Govind , Ramadass Radhan , Guenther Stefan , Looso Mario , Zaffran Stéphane , Juan Thomas , Stainier Didier Y. R.
Published: May 2024

Biomechanical forces, and their molecular transducers, including key mechanosensitive transcription factor genes, such as
KLF2
, are required for cardiac valve morphogenesis. However,
klf2
mutants fail to completely recapitulate the valveless phenotype observed under no-flow conditions. Here, we identify the transcription factor EGR3 as a conserved biomechanical force transducer critical for cardiac valve formation. We first show that
egr3
null zebrafish display a complete and highly penetrant loss of valve leaflets, leading to severe blood regurgitation. Using tissue-specific loss- and gain-of-function tools, we find that during cardiac valve formation, Egr3 functions cell-autonomously in endothelial cells, and identify one of its effectors, the nuclear receptor Nr4a2b. We further find that mechanical forces up-regulate
egr3
/
EGR3
expression in the developing zebrafish heart and in porcine valvular endothelial cells, as well as during human aortic valve remodeling. Altogether, these findings reveal that EGR3 is necessary to transduce the biomechanical cues required for zebrafish cardiac valve morphogenesis, and potentially for pathological aortic valve remodeling in humans.
Valence can control the nonexponential viscoelastic relaxation of multivalent reversible gels
Authors: Le Roy Hugo , Song Jake , Lundberg David , Zhukhovitskiy Aleksandr V. , Johnson Jeremiah A. , McKinley Gareth H. , Holten-Andersen Niels , Lenz Martin
Published: May 2024

Gels made of telechelic polymers connected by reversible cross-linkers are a versatile design platform for biocompatible viscoelastic materials. Their linear response to a step strain displays a fast, near-exponential relaxation when using low-valence cross-linkers, while larger supramolecular cross-linkers bring about much slower dynamics involving a wide distribution of timescales whose physical origin is still debated. Here, we propose a model where the relaxation of polymer gels in the dilute regime originates from elementary events in which the bonds connecting two neighboring cross-linkers all disconnect. Larger cross-linkers allow for a greater average number of bonds connecting them but also generate more heterogeneity. We characterize the resulting distribution of relaxation timescales analytically and accurately reproduce stress relaxation measurements on metal-coordinated hydrogels with a variety of cross-linker sizes including ions, metal-organic cages, and nanoparticles. Our approach is simple enough to be extended to any cross-linker size and could thus be harnessed for the rational design of complex viscoelastic materials.
Globally, songs and instrumental melodies are slower and higher and use more stable pitches than speech: A Registered Report
Authors: Ozaki Yuto , Tierney Adam , Pfordresher Peter Q. , McBride John M. , Benetos Emmanouil , Proutskova Polina , Chiba Gakuto , Liu Fang , Jacoby Nori , Purdy Suzanne C. , Opondo Patricia , Fitch W. Tecumseh , Hegde Shantala , Rocamora Martín , Thorne Rob , Nweke Florence , Sadaphal Dhwani P. , Sadaphal Parimal M. , Hadavi Shafagh , Fujii Shinya , Choo Sangbuem , Naruse Marin , Ehara Utae , Sy Latyr , Parselelo Mark Lenini , Anglada-Tort Manuel , Hansen Niels Chr. , Haiduk Felix , Færøvik Ulvhild , Magalhães Violeta , Krzyżanowski Wojciech , Shcherbakova Olena , Hereld Diana , Barbosa Brenda Suyanne , Varella Marco Antonio Correa , van Tongeren Mark , Dessiatnitchenko Polina , Zar Su Zar , El Kahla Iyadh , Muslu Olcay , Troy Jakelin , Lomsadze Teona , Kurdova Dilyana , Tsope Cristiano , Fredriksson Daniel , Arabadjiev Aleksandar , Sarbah Jehoshaphat Philip , Arhine Adwoa , Meachair Tadhg Ó , Silva-Zurita Javier , Soto-Silva Ignacio , Millalonco Neddiel Elcie Muñoz , Ambrazevičius Rytis , Loui Psyche , Ravignani Andrea , Jadoul Yannick , Larrouy-Maestri Pauline , Bruder Camila , Teyxokawa Tutushamum Puri , Kuikuro Urise , Natsitsabui Rogerdison , Sagarzazu Nerea Bello , Raviv Limor , Zeng Minyu , Varnosfaderani Shahaboddin Dabaghi , Gómez-Cañón Juan Sebastián , Kolff Kayla , der Nederlanden Christina Vanden Bosch , Chhatwal Meyha , David Ryan Mark , Setiawan I. Putu Gede , Lekakul Great , Borsan Vanessa Nina , Nguqu Nozuko , Savage Patrick E.
Published: May 2024

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech.
Nature and human well-being: The olfactory pathway
Authors: Bratman Gregory N. , Bembibre Cecilia , Daily Gretchen C. , Doty Richard L. , Hummel Thomas , Jacobs Lucia F. , Kahn Peter H. , Lashus Connor , Majid Asifa , Miller John D. , Oleszkiewicz Anna , Olvera-Alvarez Hector , Parma Valentina , Riederer Anne M. , Sieber Nancy Long , Williams Jonathan , Xiao Jieling , Yu Chia-Pin , Spengler John D.
Published: May 2024

The world is undergoing massive atmospheric and ecological change, driving unprecedented challenges to human well-being. Olfaction is a key sensory system through which these impacts occur. The sense of smell influences quality of and satisfaction with life, emotion, emotion regulation, cognitive function, social interactions, dietary choices, stress, and depressive symptoms. Exposures via the olfactory pathway can also lead to (anti-)inflammatory outcomes. Increased understanding is needed regarding the ways in which odorants generated by nature (i.e., natural olfactory environments) affect human well-being. With perspectives from a range of health, social, and natural sciences, we provide an overview of this unique sensory system, four consensus statements regarding olfaction and the environment, and a conceptual framework that integrates the olfactory pathway into an understanding of the effects of natural environments on human well-being. We then discuss how this framework can contribute to better accounting of the impacts of policy and land-use decision-making on natural olfactory environments and, in turn, on planetary health.
Substrate uptake patterns shape niche separation in marine prokaryotic microbiome
Authors: Zhao Zihao , Amano Chie , Reinthaler Thomas , Orellana Mónica V. , Herndl Gerhard J.
Published: May 2024

Marine heterotrophic prokaryotes primarily take up ambient substrates using transporters. The patterns of transporters targeting particular substrates shape the ecological role of heterotrophic prokaryotes in marine organic matter cycles. Here, we report a size-fractionated pattern in the expression of prokaryotic transporters throughout the oceanic water column due to taxonomic variations, revealed by a multi-“omics” approach targeting ATP-binding cassette (ABC) transporters and TonB-dependent transporters (TBDTs). Substrate specificity analyses showed that marine SAR11, Rhodobacterales, and Oceanospirillales use ABC transporters to take up organic nitrogenous compounds in the free-living fraction, while Alteromonadales, Bacteroidetes, and Sphingomonadales use TBDTs for carbon-rich organic matter and metal chelates on particles. The expression of transporter proteins also supports distinct lifestyles of deep-sea prokaryotes. Our results suggest that transporter divergency in organic matter assimilation reflects a pronounced niche separation in the prokaryote-mediated organic matter cycles.
Stereoscopic artificial compound eyes for spatiotemporal perception in three-dimensional space
Authors: Bae Byungjoon , Lee Doeon , Park Minseong , Mu Yujia , Baek Yongmin , Sim Inbo , Shen Cong , Lee Kyusang
Published: May 2024

Arthropods’ eyes are effective biological vision systems for object tracking and wide field of view because of their structural uniqueness; however, unlike mammalian eyes, they can hardly acquire the depth information of a static object because of their monocular cues. Therefore, most arthropods rely on motion parallax to track the object in three-dimensional (3D) space. Uniquely, the praying mantis (Mantodea) uses both compound structured eyes and a form of stereopsis and is capable of achieving object recognition in 3D space. Here, by mimicking the vision system of the praying mantis using stereoscopically coupled artificial compound eyes, we demonstrated spatiotemporal object sensing and tracking in 3D space with a wide field of view. Furthermore, to achieve a fast response with minimal latency, data storage/transportation, and power consumption, we processed the visual information at the edge of the system using a synaptic device and a federated split learning algorithm. The designed and fabricated stereoscopic artificial compound eye provides energy-efficient and accurate spatiotemporal object sensing and optical flow tracking. It exhibits a root mean square error of 0.3 centimeter, consuming only approximately 4 millijoules for sensing and tracking. These results are more than 400 times lower than conventional complementary metal-oxide semiconductor–based imaging systems. Our biomimetic imager shows the potential of integrating nature’s unique design using hardware and software codesigned technology toward capabilities of edge computing and sensing.
Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays
Authors: Mühlemann Barbara , Wilks Samuel H. , Baracco Lauren , Bekliz Meriem , Carreño Juan Manuel , Corman Victor M. , Davis-Gardner Meredith E. , Dejnirattisai Wanwisa , Diamond Michael S. , Douek Daniel C. , Drosten Christian , Eckerle Isabella , Edara Venkata-Viswanadh , Ellis Madison , Fouchier Ron A. M. , Frieman Matthew , Godbole Sucheta , Haagmans Bart , Halfmann Peter J. , Henry Amy R. , Jones Terry C. , Katzelnick Leah C. , Kawaoka Yoshihiro , Kimpel Janine , Krammer Florian , Lai Lilin , Liu Chang , Lusvarghi Sabrina , Meyer Benjamin , Mongkolsapaya Juthathip , Montefiori David C. , Mykytyn Anna , Netzl Antonia , Pollett Simon , Rössler Annika , Screaton Gavin R. , Shen Xiaoying , Sigal Alex , Simon Viviana , Subramanian Rahul , Supasa Piyada , Suthar Mehul S. , Türeli Sina , Wang Wei , Weiss Carol D. , Smith Derek J.
Published: May 2024

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models.
mRNA cap-binding protein eIF4E1 is a novel regulator of
Toxoplasma gondii
latency
Authors: Holmes Michael J. , Bastos Matheus S. , Dey Vishakha , Severo Vanessa , Wek Ronald C. , Sullivan William J.
Published: May 2024

The protozoan parasite
Toxoplasma gondii
causes serious opportunistic disease due to its ability to persist in patients as latent tissue cysts. The molecular mechanisms coordinating conversion between proliferative parasites (tachyzoites) and latent cysts (bradyzoites) are not fully understood. We previously showed that phosphorylation of eIF2α accompanies bradyzoite formation, suggesting that this clinically relevant process involves regulation of mRNA translation. In this study, we investigated the composition and role of eIF4F multi-subunit complexes in translational control. Using CLIPseq, we find that the cap-binding subunit, eIF4E1, localizes to the 5′-end of all tachyzoite mRNAs, many of which show evidence of stemming from heterogeneous transcriptional start sites. We further show that eIF4E1 operates as the predominant cap-binding protein in two distinct eIF4F complexes. Using genetic and pharmacological approaches, we found that eIF4E1 deficiency triggers efficient spontaneous formation of bradyzoites without stress induction. Consistent with this result, we also show that stress-induced bradyzoites exhibit reduced eIF4E1 expression. Overall, our findings establish a novel role for eIF4F in translational control required for parasite latency and microbial persistence.

IMPORTANCE

Toxoplasma gondii
is an opportunistic pathogen important to global human and animal health. There are currently no chemotherapies targeting the encysted form of the parasite. Consequently, a better understanding of the mechanisms controlling encystation is required. Here we show that the mRNA cap-binding protein, eIF4E1, regulates the encystation process. Encysted parasites reduce eIF4E1 levels, and depletion of eIF4E1 decreases the translation of ribosome-associated machinery and drives
Toxoplasma
encystation. Together, these data reveal a new layer of mRNA translational control that regulates parasite encystation and latency.
TurboID mapping reveals the exportome of secreted intrinsically disordered proteins in the transforming parasite
Theileria annulata
Authors: Brühlmann Francis , Perry Carmen , Griessen Charlotte , Gunasekera Kapila , Reymond Jean-Louis , Naguleswaran Arunasalam , Rottenberg Sven , Woods Kerry , Olias Philipp
Published: May 2024

Theileria annulata
is a tick-transmitted apicomplexan parasite that gained the unique ability among parasitic eukaryotes to transform its host cell, inducing a fatal cancer-like disease in cattle. Understanding the mechanistic interplay between the host cell and malignant
Theileria
species that drives this transformation requires the identification of responsible parasite effector proteins. In this study, we used TurboID-based proximity labeling, which unbiasedly identified secreted parasite proteins within host cell compartments. By fusing TurboID to nuclear export or localization signals, we biotinylated proteins in the vicinity of the ligase enzyme in the nucleus or cytoplasm of infected macrophages, followed by mass spectrometry analysis. Our approach revealed with high confidence nine nuclear and four cytosolic candidate parasite proteins within the host cell compartments, eight of which had no orthologs in non-transforming
T. orientalis
. Strikingly, all eight of these proteins are predicted to be highly intrinsically disordered proteins. We discovered a novel tandem arrayed protein family, nuclear intrinsically disordered proteins (NIDP) 1–4, featuring diverse functions predicted by conserved protein domains. Particularly, NIDP2 exhibited a biphasic host cell-cycle-dependent localization, interacting with the EB1/CD2AP/CLASP1 parasite membrane complex at the schizont surface and the tumor suppressor stromal antigen 2 (STAG2), a cohesion complex subunit, in the host nucleus. In addition to STAG2, numerous NIDP2-associated host nuclear proteins implicated in various cancers were identified, shedding light on the potential role of the
T. annulata
exported protein family NIDP in host cell transformation and cancer-related pathways.

IMPORTANCE

TurboID proximity labeling was used to identify secreted proteins of
Theileria annulata
, an apicomplexan parasite responsible for a fatal, proliferative disorder in cattle that represents a significant socio-economic burden in North Africa, central Asia, and India. Our investigation has provided important insights into the unique host-parasite interaction, revealing secreted parasite proteins characterized by intrinsically disordered protein structures. Remarkably, these proteins are conspicuously absent in non-transforming
Theileria
species, strongly suggesting their central role in the transformative processes within host cells. Our study identified a novel tandem arrayed protein family, with nuclear intrinsically disordered protein 2 emerging as a central player interacting with established tumor genes. Significantly, this work represents the first unbiased screening for exported proteins in
Theileria
and contributes essential insights into the molecular intricacies behind the malignant transformation of immune cells.
SoxY
gene family expansion underpins adaptation to diverse hosts and environments in symbiotic sulfide oxidizers
Authors: Sudo Marta , Osvatic Jay , Taylor John D. , Dufour Suzanne C. , Prathep Anchana , Wilkins Laetitia G. E. , Rattei Thomas , Yuen Benedict , Petersen Jillian M.
Published: May 2024

Sulfur-oxidizing bacteria (SOB) have developed distinct ecological strategies to obtain reduced sulfur compounds for growth. These range from specialists that can only use a limited range of reduced sulfur compounds to generalists that can use many different forms as electron donors. Forming intimate symbioses with animal hosts is another highly successful ecological strategy for SOB, as animals, through their behavior and physiology, can enable access to sulfur compounds. Symbioses have evolved multiple times in a range of animal hosts and from several lineages of SOB. They have successfully colonized a wide range of habitats, from seagrass beds to hydrothermal vents, with varying availability of symbiont energy sources. Our extensive analyses of sulfur transformation pathways in 234 genomes of symbiotic and free-living SOB revealed widespread conservation in metabolic pathways for sulfur oxidation in symbionts from different host species and environments, raising the question of how they have adapted to such a wide range of distinct habitats. We discovered a gene family expansion of
soxY
in these genomes, with up to five distinct copies per genome. Symbionts harboring only the “canonical”
soxY
were typically ecological “specialists” that are associated with specific host subfamilies or environments (e.g., hydrothermal vents, mangroves). Conversely, symbionts with multiple divergent
soxY
genes formed versatile associations across diverse hosts in various marine environments. We hypothesize that expansion and diversification of the
soxY
gene family could be one genomic mechanism supporting the metabolic flexibility of symbiotic SOB enabling them and their hosts to thrive in a range of different and dynamic environments.

IMPORTANCE

Sulfur metabolism is thought to be one of the most ancient mechanisms for energy generation in microorganisms. A diverse range of microorganisms today rely on sulfur oxidation for their metabolism. They can be free-living, or they can live in symbiosis with animal hosts, where they power entire ecosystems in the absence of light, such as in the deep sea. In the millions of years since they evolved, sulfur-oxidizing bacteria have adopted several highly successful strategies; some are ecological “specialists,” and some are “generalists,” but which genetic features underpin these ecological strategies are not well understood. We discovered a gene family that has become expanded in those species that also seem to be “generalists,” revealing that duplication, repurposing, and reshuffling existing genes can be a powerful mechanism driving ecological lifestyle shifts.
Replacement of unsatisfactory ceramic veneers with the aid of a digital workflow
Authors: Sanchez Renato Lardin Sartori , dos Santos Giulia Gonçalves , Fukuoka Gisele Lie , Reis Isabella Neme Ribeiro dos
Published: May 2024

This case report focuses on the replacement of ceramic laminate veneers with suboptimal marginal fit and design, employing a digital workflow and CAD–CAM technology. The patient, a woman in her 30s, expressed concerns about the appearance and hygiene challenges of her existing veneers. A comprehensive assessment, including clinical examination, facial photographs and intraoral scanning, was conducted. Utilising CAD software, facial photographs and 3D models merged to create a digital wax-up, crucial in designing suitable veneers and addressing issues like overcontouring and a poor emergence profile. Following the removal of old veneers, a mock-up was performed and approved. Preparations ensured space for restorations with well-defined margins. The final restorations, milled with Leucite-reinforced vitreous ceramic, were cemented. At the 1 year follow-up, improved aesthetics, gingival health and functional restorations were observed. This report highlights the efficacy of digital workflows in achieving consistent and aesthetically pleasing outcomes in ceramic laminate veneer replacement.
Effectiveness of exercise-based sports injury prevention programmes in reducing injury rates in adolescents and their implementation in the community: a mixed-methods systematic review
Authors: Zhang Zhe Xin , Lai Joseph , Shen Liang , Krishna Lingaraj
Published: May 2024

Objective

Despite evidence supporting the efficacy of sport injury prevention programmes (SIPPs) in adolescents, implementation of SIPPs in community settings is low. This review aims to synthesise and integrate evidence on the efficacy of exercise-based SIPPs in reducing injury rates in adolescents with implementation strategies for such programmes in the community.

Design

A systematic review with meta-analysis, narrative synthesis and meta-aggregation was conducted, followed by a convergent segregated approach to integrate the findings. Sensitivity and subgroup analyses were conducted. Study appraisal was performed using Joanna Briggs Institute Critical Appraisal Checklists and Mixed Methods Appraisal Tool.

Data sources

Literature search of nine databases was carried out to identify studies in English from January 2012 to December 2022.

Eligibility criteria

Included were randomised controlled trials (RCTs), qualitative or mixed-methods studies. Population included adolescents (10–19 years). Interventions included SIPPs. Outcomes were injury rate and rate ratio (IRR). Phenomena of interest were facilitators and barriers to the implementation of SIPPs.

Results

23 studies were included for analysis. Meta-analysis for 16 RCTs showed a protective effect of SIPP (IRR 0.63, 95% CI 0.53 to 0.74, p<0.00001) in adolescents. Meta-aggregation of seven qualitative/mixed-method studies revealed four sets of synthesised findings that impact implementation namely players’ perceptions and beliefs, coaches as key facilitators, organisational support and characteristics of the SIPP.

Conclusion

Implementation of SIPPs provides a 37% risk reduction in adolescents but requires targeting key stakeholders through a top-down multifaceted approach for its efficacy to be translated. Future research should investigate the effectiveness of SIPPs and implementation strategies in adolescents in community settings.
Clinical perspectives on the frequency of hypoglycemia in treat-to-target randomized controlled trials comparing basal insulin analogs in type 2 diabetes: a narrative review
Authors: Rosenstock Julio , Bajaj Harpreet S , Lingvay Ildiko , Heller Simon R
Published: May 2024

The objective of this review was to comprehensively present and summarize trends in reported rates of hypoglycemia with one or two times per day basal insulin analogs in individuals with type 2 diabetes to help address and contextualize the emerging theoretical concern of increased hypoglycemic risk with once-weekly basal insulins.

Hypoglycemia data were extracted from treat-to-target randomized clinical trials conducted during 2000–2022. Published articles were identified on PubMed or within the US Food and Drug Administration submission documents. Overall, 57 articles were identified: 44 assessed hypoglycemic outcomes in participants receiving basal-only therapy (33 in insulin-naive participants; 11 in insulin-experienced participants), 4 in a mixed population (insulin-naive and insulin-experienced participants) and 9 in participants receiving basal-bolus therapy. For the analysis, emphasis was placed on level 2 (blood glucose <3.0 mmol/L (<54 mg/dL)) and level 3 (or severe) hypoglycemia.

Overall, event rates for level 2 or level 3 hypoglycemia across most studies ranged from 0.06 to 7.10 events/person-year of exposure (PYE) for participants receiving a basal-only insulin regimen; the rate for basal-bolus regimens ranged from 2.4 to 13.6 events/PYE. Rates were generally lower with second-generation basal insulins (insulin degludec or insulin glargine U300) than with neutral protamine Hagedorn insulin or first-generation basal insulins (insulin detemir or insulin glargine U100). Subgroup categorization by sulfonylurea usage, end-of-treatment insulin dose or glycated hemoglobin reduction did not show consistent trends on overall hypoglycemia rates. Hypoglycemia rates reported so far for once-weekly basal insulins are consistent with or lower than those reported for daily-administered basal insulin analogs.
Predictors of mortality within 1 year after primary ovarian cancer surgery: a nationwide cohort study
Authors: Ørskov Mette , Iachina Maria , Guldberg Rikke , Mogensen Ole , Mertz Nørgård Bente
Published: May 2024

Objectives

To identify predictors of mortality within 1 year after primary surgery for ovarian cancer.

Design

Prospective nationwide cohort study from 1 January 2005 to 31 December 2012.

Setting

Evaluation of data from the Danish Gynaecology Cancer Database and the Danish Civil Registration System.

Participants

2654 women who underwent surgery due to a diagnosis of primary ovarian cancer.

Outcome measures

Overall survival and predictors of mortality within 0–180 and 181–360 days after the primary surgery. Examined predictors were age, preoperative American Society of Anesthesiologists (ASA) score, body mass index (BMI), International Federation of Gynaecology and Obstetrics (FIGO) stage, residual tumour tissue after surgery, perioperative blood transfusion and calendar year of surgery.

Results

The overall 1-year survival was 84%. Within 0–180 days after surgery, the 3 most important predictors of mortality from the multivariable model were residual tumour tissue >2 cm versus no residual tumour (HR=4.58 (95% CI 3.20 to 6.59)), residual tumour tissue ≤2 cm versus no residual tumour (HR=2.50 (95% CI 1.63 to 3.82)) and age >64 years versus age ≤64 years (HR=2.33 (95% CI 1.69 to 3.21)). Within 181–360 days after surgery, FIGO stages III–IV versus I–II (HR=2.81 (95% CI 1.75 to 4.50)), BMI<18.5 vs 18.5–25 kg/m2(HR=2.08 (95% CI 1.18 to 3.66)) and residual tumour tissue >2 cm versus no residual tumour (HR=1.84 (95% CI 1.25 to 2.70)) were the 3 most important predictors.

Conclusions

The most important predictors of mortality within 1 year after surgery were residual tumour tissue (0–180 days after surgery) and advanced FIGO stage (181–360 days after surgery). However, our results suggest that the surgeon should not just aim at radical surgery, but also pay special attention to comorbidity, nutritional state, age >64 years and the need for perioperative blood transfusion.
Facilitators and barriers to self-management in Iranian men with chronic obstructive pulmonary disease: a qualitative study
Authors: Rafii Forough , Alinejad-Naeini Mona , Soleymani Babadi Akbar , Shahriari Elahe , Heidari Beni Farshad
Published: May 2024

Introduction

Self-management, as the most common method of chronic obstructive pulmonary disease (COPD) management, is not an isolated behaviour, but a set of physical, social, cultural, psychological and existential factors affecting it.

Aim

This study aimed to explore the facilitators and barriers to self-management in men with COPD in the unique social, cultural, political and economic context of Iran.

Methods

This paper reports part of the findings of a qualitative grounded theory study aimed at exploring the process of self-management in Iranian men with COPD, which was conducted in Iran from January 2019 to July 2023. Participants included men with COPD, their family members and pulmonologists. The selection of participants in this research began with the purposeful sampling method. Data was collected using semistructured interviews. Data collection continued until the data saturation was achieved. A total of 15 interviews were conducted with nine patients, three family members of patients and three pulmonologists. The data was analysed using the constant comparative analysis method.

Results

The findings of this study showed that knowledge, education, experience, family involvement and financial support are the factors that facilitate self-management. Factors related to deficits include lack of education, lack of treatment support, family cooperation deficit, financial problems, medication obtaining problems and factors related to disease impacts include specific nature of the disease, residual effect, comorbidity and factors related to negative patients characteristics include false beliefs, poor self-efficacy, feeling shame and non-adherence are barriers to self-management in men with COPD.

Conclusion

Based on results of this study, healthcare providers and health planners can strengthen the factors that facilitate self-management and weaken or remove the barriers to self-management, so that these patients use self-management strategies with maximum capacity to control the disease.
Examining the hospital costs of children born into relative deprivation in England
Authors: Dale Veronica , Gutacker Nils , Bradshaw Jonathan , Bloor Karen
Published: May 2024

Objective

To examine the association between being born into relative deprivation and hospital costs during childhood.

Design

Retrospective cohort study.

Methods

We created a birth cohort using Hospital Episode Statistics for children born in NHS hospitals in 2003/2004. The Index of Multiple Deprivation (IMD) rank at birth was missing from 75% of the baby records, so we linked mother and baby records to obtain the IMD decile from the mother’s record. We aggregated and costed each child’s hospital inpatient admissions, and outpatient and emergency department (ED) attendances up to 15 years of age. We used 2019/2020 NHS tariffs to assign costs. We constructed an additional cohort, all children born in 2013/2014, to explore any changes over time, comparing the utilisation and costs up to 5 years of age.

Results

Our main cohort comprised 567 347 babies born in 2003/2004, of which we could include 91%. Up to the age of 15 years, children born into the most deprived areas used more hospital services than those born in the least deprived, reflected in higher costs of inpatient, outpatient and ED care. The highest costs and greatest differences are in the year following birth. Comparing this with the later cohort (up to age 5 years), the average cost per child increased across all deprivation deciles, but differences between the most and least deprived deciles appeared to narrow slightly.

Conclusions

Healthcare utilisation and costs are consistently higher for children who are born into the most deprived areas compared with the least.
Association of postabsorptive glucose and acetate metabolism with feed intake, growth, and efficiency in finishing beef heifers
Authors: Foote Andrew P. , Rathert-Williams Abigail R. , Salisbury Carlee M. , McConnell Hunter , Lalman David
Published: May 2024

The objective of this experiment was to determine whether acetate and glucose metabolism and insulin response to glucose are associated with the growth, feed intake, and feed efficiency of finishing heifers. Charolais heifers ( n = 18; initial body weight = 415.7 ± 45.17 kg) were acclimated to restraint with a halter and fed a finishing diet ad libitum using an Insentec feeding system. Following a 12 h fast, a jugular catheter was inserted, and an acetate clearance test was performed followed by a glucose clearance test. Four days after the metabolic tests, heifers began an 84-day DMI and ADG test period. Heifers gained 1.69 ± 0.03 kg/day and consumed 10.4 ± 0.19 kg/day. Acetate and glucose clearance rates were not associated with any production trait ( P ≥ 0.40). Insulin time to peak concentration after the glucose challenge was associated ( r = 0.69; P = 0.003) with G:F, but not peak concentration ( P = 0.45). The increased time to insulin peak could indicate that efficient heifers have pancreatic β-cell dysfunction, which is a contributor to insulin resistance. These data indicate that insulin resistance early in the finishing period could be related to improved feed efficiency in finishing heifers.