bluuebunny/crossref_metadata_2025 huggingface dataset:
Opposing effects of thyroid hormones on hypothalamic subunits and limbic structures in hyperthyroidism patients: A comprehensive volumetric study
Authors: Genç Barış , Aslan Kerim , Avcı Uğur , İncesu Lütfi , Günbey Hediye Pınar
Published: February 2024

Thyroid hormones play a critical role in brain development, but paradoxically, patients with hyperthyroidism often exhibit cognitive decline and irritability. This study aims to explore the pattern of atrophy in hyperthyroid patients, changes in specific areas of the brain, including hypothalamic subfields and limbic structures, and their relationships with hormonal levels and psychometric tests. This prospective cross‐sectional study involves 19 newly diagnosed, untreated hyperthyroid patients, and 15 age and gender‐matched control subjects. The participants underwent psychometric and cognitive tests and volumetric MRI. The hypothalamic subfield (anterior‐inferior, anterior‐superior, superior‐tubular, inferior‐tubular, and posterior hypothalamus) and limbic structures (fornix, basal forebrain, nucleus accumbens, and septal nucleus) were segmented using voxel‐based morphometry, surface‐based morphometry, and deep learning algorithms. The groups were compared using the t‐test, and correlation analyses were performed between clinical parameters and volumetric measurements. The correlation between hormonal parameters and volumetric measurements in patient and control groups was assessed with the Meng test. Hyperthyroid patients displayed widespread grey matter loss and sulcal shallowing in the left hemisphere. However, no local gyrification index changes or cortical thickness variations were detected. The limbic structures and hypothalamic subunits did not show any volume discrepancies. Free thyroxine in the patient group negatively correlated with bilateral anterior‐inferior and right septal nucleus, but positively correlated with left anterior‐inferior in the control group. Thyroid stimulating hormone in the patient group showed a positive correlation with bilateral fornix volume, a correlation absent in the control group. Disease duration negatively correlated with right anterior‐inferior, right tubular inferior, and right septal nucleus. Changes in cognitive and psychometric test scores in the patient group correlated with the bilateral septal nucleus volume. Hyperthyroidism primarily leads to a reduction in grey matter volume and sulcal shallowing. Thyroid hormones have differing volumetric effects in limbic structures and hypothalamic subunits under physiological and hyperthyroid conditions.
Parent‐proxy pediatric CMT quality of life outcome measure: Validation of the Italian version
Authors: Danti Federica Rachele , Pagliano Emanuela , Pareyson Davide , Foscan Maria , Marchi Alessia , Feoli Alessia , Bruschi Fabio , Piscosquito Giuseppe , Shy Micheal E. , Ramchandren Sindhu , Moroni Isabella , Wu Tong Tong
Published: February 2024

Background and Aims

The parent‐proxy reports can offer complementary informations or be the only source of Quality of Life measurement in young children. The aim of this study was to provide and validate the Italian version of the recently published parent‐proxy pCMT‐QOL for patients aged 8–18 years old, making it available for possible trials in Italian speaking children.

Methods

The English‐language instrument was translated and adapted into the Italian language using standard procedures: translation, transcultural adaptation, and back‐translation. Parent‐proxy pCMT‐QOL was administered to parents of patients with a genetic diagnosis of CMT, aged 8–18 years old. All parents were retested 2 weeks later to assess reliability.

Results

A total of 21 parents of CMT patients (18 CMT1A, 2 CMT2A, 1 CMT2K) were assessed during their children clinical appointments. The Italian‐pCMT‐QOL showed a high test–retest reliability; none of the parents had any difficulties with the completion of the questionnaire and no further revisions were necessary after completion.

Interpretation

The Italian parent‐proxy pCMT‐QOL is a reliable, culturally adapted, and comparable version of the original English instrument. This questionnaire will improve the quality of the follow‐up and will make it possible to monitor more accurately the severity of the disease in Italian‐speaking families.
Skin necrosis after intradermal injection of lyophilized exosome: A case report and a review of the literature
Authors: Tawanwongsri Weeratian , Vachiramon Vasanop
Published: February 2024

Background

Exosomes have gained attention for their potential in skin rejuvenation. Currently, most exosome products are available for topical administration, and the use of subdermal injection as a route of administration has not been approved.

Aims

The purpose of this case report is to describe a case of skin necrosis that occurred following an intradermal injection of lyophilized exosomes.

Materials and Methods

We hereby report a case of a middle‐aged man who experienced adverse effects after receiving an intradermal injection of lyophilized exosomes. Multiple injections of an exosome product were administered to treat enlarged facial pores. Shortly after the injection, the patient felt pain and noticed several dark red bumps. Three days after injection, the lesions transformed into palpable, painful, non‐blanchable purplish papules and nodules, accompanied by central, tiny crusted erosions. The residual product was injected into the upper arm using an intradermal method. Similar lesions also appeared, and a skin biopsy showed necrotic keratinocytes, leukocytoclastic vasculitis, and eccrine necrosis.

Results

There are few reports available regarding complications, especially those related to intradermal exosomes. These complications include multiple foreign‐body granulomatous reactions at the injection sites. In our case, oral prednisolone was administered for a duration of 7 days. After the treatment, the lesions exhibited notable improvement, eventually leaving post‐inflammatory hyperpigmentation.

Conclusion

Utilizing exosomes through unapproved methods should be avoided due to the possibility of adverse reactions that could cause aesthetic issues.
Associations of menopausal status and eating behaviour with subjective measures of sleep
Authors: Lankila Hannamari , Kuutti Mari A. , Kekäläinen Tiia , Hietavala Enni‐Maria , Laakkonen Eija K.
Published: February 2024

Eating and sleeping behaviour are known to interact with each other, yet research is limited in the context of menopausal women. The aim of this study was to examine whether menopausal status is associated with perceived problems in sleeping. Furthermore, we studied different aspects of eating behaviour as potential risk factors for poor sleep in menopausal women. The present study is exploratory in nature, thus the results should be interpreted as hypothesis‐generating. We analysed the sleeping and eating behaviour of 1098 women aged 47–55 years and represented different menopausal statuses with regression analyses. Over 20% of them reported fairly poor or poor perceived sleep quality. A higher number of postmenopausal women reported experiencing at least fairly poor sleep quality compared with the other menopausal groups. However, in regression models controlled for several confounding factors menopausal status was not associated with measures of sleep. Women who reported more snacking‐type eating behaviour were more likely to report shorter sleep duration, and more daytime tiredness. Externally cued eating was associated with shorter sleep duration and emotional eating was associated with experiencing daytime tiredness. However, after adjusting for multiple testing, it appears that eating behaviour is associated only with daytime tiredness. Menopausal women with sleeping problems may benefit from nutritional interventions targeting eating behaviour.
Comparison of D‐dimer concentration and thromboelastography for diagnosis of cerebrovascular accidents in dogs: A retrospective study
Authors: DiPaola Elizabeth , Cameron Starr , Rylander Helena , Zidan Natalia , Hetzel Scott
Published: February 2024

Background

Cerebrovascular accidents (CVAs) in dogs are diagnosed using magnetic resonance imaging (MRI). This modality is sometimes unavailable, and CVAs can resemble other lesions on MRI. D‐dimer concentration and thromboelastography (TEG) are utilized in human medicine in addition to diagnostic imaging to support diagnosis of CVAs, but their use in veterinary patients has not been assessed.

Objective

Assess utility of blood D‐dimer concentration and TEG in supporting the imaging diagnosis of CVAs in dogs.

Animals

Sixty‐eight client‐owned dogs with neurologic signs that had brain MRI and D‐dimer concentration or TEG performed.

Methods

Multicenter, retrospective study. The incidence of abnormal D‐dimer concentration or TEG was compared between patients with MRI evidence of CVA and a control population. Analysis methods included Fisher's exact test or Chi‐squared test for association and comparison of independent proportions.

Results

Neither D‐dimer concentration nor TEG was significantly associated with a CVA (P = .38 and .2, respectively). D‐dimer testing was performed in a low‐risk population and showed low sensitivity (30.8%; 95% confidence interval [CI], 10%‐61%) and high specificity (86.4%; 95% CI, 64%‐96%) for CVA diagnosis. Thromboelastography was performed in a high‐risk population and showed moderate sensitivity (64.3%; 95% CI, 44%‐81%) and specificity (66.7%; 95% CI, 24%‐94%) for CVA diagnosis. Abnormal D‐dimer concentration or TEG were not helpful in differentiating hemorrhagic from ischemic stroke (P = .43 and .41, respectively).

Conclusions

Although blood D‐dimer concentration or TEG alone are not diagnostic of CVAs in dogs, a positive D‐dimer result supports additional testing for CVA.
Asymmetries in Potential for Partisan Gerrymandering
Authors: Goedert Nicholas , Hildebrand Robert , Travis Laurel , Pierson Matt
Published: February 2024

This article investigates the effectiveness of potential partisan gerrymandering of the US House of Representatives across a range of states. We use a heuristic algorithm to generate district maps that optimize for multiple objectives, including compactness, partisan benefit, and competitiveness. While partisan gerrymandering is highly effective for both sides, we find that the majority of states are moderately biased toward Republicans when optimized for either compactness or partisan benefit, meaning that Republican gerrymanders have the potential to be more effective. However, we also find that more densely populated and more heavily Hispanic states show less Republican bias or even Democratic bias. Additionally, we find that in almost all cases we can generate reasonably compact maps with very little sacrifice to partisan objectives through a mixed‐objective function. This suggests that there is a strong potential for stealth partisan gerrymanders that are both compact and beneficial to one party. Nationwide, partisan gerrymandering is capable of swinging over 100 seats in the US House, even when compact districts are simultaneously sought.
Scaffolding comprehension with reading while listening and the role of reading speed and text complexity
Authors: Hui Bronson
Published: February 2024

Audiobooks allow language learners to read and listen to the same text simultaneously; yet the effects of this bimodal input (written and spoken) on learners’ comprehension have been inconsistent, suggesting that the conditions under which audiobooks can help comprehension are not well understood. As such, I explored silent reading speed and text complexity as two potential variables that moderate reading‐while‐listening (RWL) comprehension. In a within‐participant design, 46 English learners in an American university read, listened to, and simultaneously read and listened to two complexity versions of a fictional text. Mixed‐effects regression modeling revealed that participants comprehended better in the RWL conditions than in the listening‐only conditions, echoing findings from the captions literature. This effect was moderated by neither silent reading speed nor text complexity. There were also no main effects between RWL and reading‐only conditions, indicating limitations in the use of audiobooks in language classrooms to promote written text comprehension.
Phenazine biosynthesis protein MoPhzF regulates appressorium formation and host infection through canonical metabolic and noncanonical signaling function in Magnaporthe oryzae
Authors: Ma Danying , Xu Jiayun , Wu Miao , Zhang Ruiming , Hu Zhao , Ji Chang‐an , Wang Yifan , Zhang Ziqi , Yu Rui , Liu Xinyu , Yang Leiyun , Li Gang , Shen Danyu , Liu Muxing , Yang Zhixiang , Zhang Haifeng , Wang Ping , Zhang Zhengguang
Published: February 2024

Microbe‐produced secondary metabolite phenazine‐1‐carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection.

However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence.

MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host‐derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G‐protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity.

Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.
The effect of c‐Fos on the prognosis, proliferation, and invasion of oral squamous cell carcinoma
Authors: Peng Lu , Sun Ercan , Zhang Jinfang , Cai Lanyu , Zheng Jun , Zeng Yan
Published: February 2024

Objective

This study aimed to determine the role of c‐Fos in growth and invasion of oral squamous cell carcinoma (OSCC).

Methods

Immunohistochemistry was used to assess c‐Fos expression in 94 OSCC tissues and 30 adjacent normal tissues, the correlation between c‐Fos expression and clinicopathological characteristics was examined, and Kaplan–Meier and Cox analysis were used to investigate the role of c‐Fos in predicting the prognosis of OSCC patients. The effects of c‐Fos on the growth and invasion of OSCC were disclosed by overexpression and knockdown of c‐Fos. Furthermore, based on bioinformatics prediction, the effect of miR‐155‐5p on c‐Fos expression was examined, and dual‐luciferase reporter assay system was used to determine whether miR‐155‐5p regulated the transcriptional activity of c‐Fos in OSCC.

Results

c‐Fos was markedly increased in OSCC tissues and cells. c‐Fos upregulation indicates a poor prognosis in OSCC patients, and c‐Fos promotes cell proliferation, migration, and invasion in OSCC. miR‐155‐5p could regulate the expression and the transcriptional activity of c‐Fos by directly targeting the c‐Fos 3′‐UTR.

Conclusion

This study demonstrated that c‐Fos contributed to the progression of OSCC and may act as a potential target for OSCC therapy, and a potential prognostic biomarker of OSCC.
Dermatologic manifestations in pediatric patients with inflammatory bowel disease
Authors: Afarideh Mohsen , Bartoletta Katherine , Tollefson Megha M.
Published: February 2024

Background

Despite studies of dermatologic manifestations in adults with inflammatory bowel disease (IBD), little is known about the prevalence of IBD‐associated skin lesions and their correlation with IBD severity in children. We aimed to address these knowledge gaps in our single‐center cohort of children with IBD.

Methods

Retrospective chart review of 528 children and adolescents (≤18 years old) with IBD and seen at Mayo Clinic (Rochester, MN) between 1999 and 2017 was conducted. The Chi‐Square/Fischer's exact test (with p ≤ .05 to signify statistical significance) was applied to compare categorical outcomes between Crohn's disease (CD) and ulcerative colitis (UC) patients.

Results

In total, 425 IBD patients (64.9% CD, 53% males) and ≥1 dermatologic diagnosis were included. Presence of ≥1 cutaneous infection was recorded in 42.8% of participants. Acne was the most common non‐infectious dermatologic condition (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%). Angular cheilitis (p = .024), keratosis pilaris (KP, p = .003), and perianal skin complications (i.e., skin tags, fistula, and abscesses; all p < .001) were more frequently diagnosed among children with CD, while fungal skin infections (p = .017) were more frequently diagnosed in UC patients. Severity of IBD correlated with higher prevalence of perianal fistula (p = .003), perianal abscess (p = .041), psoriasis (p < .001), and pyoderma gangrenosum (PG, p = .003).

Conclusions

Both IBD‐specific and IBD‐nonspecific dermatologic conditions are very prevalent in childhood IBD, the most common being infectious. Children with CD are more likely to experience angular cheilitis, KP, and perianal skin findings than those with UC. Perianal disease, psoriasis, and PG are associated with more severe IBD.
Thyroid hormone may predict treatment failure in Kawasaki disease
Authors: Hashida Yuichiro , Mino Yoichi , Okuno Keisuke , Uemasu Hitoshi , Sakata Shinji , Fujimoto Masanobu , Namba Noriyuki
Published: February 2024

Background

In systemic inflammatory conditions, inflammatory cytokines can cause low thyroid hormone levels. There are no reports discussing the relation between thyroid hormone levels and response to treatment for Kawasaki disease.

Methods

We investigated 67 patients who underwent treatment in the acute phase of Kawasaki disease. We divided patients into two groups based on their response to initial intravenous immunoglobulin (IVIG) treatment: the responder group (n = 40), and the non‐responder group (n = 27). The serum levels of the thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4), and thyroid‐stimulating hormone (TSH) were compared before and after treatment in all patients, and between responder and non‐responder groups.

Results

The FT3, FT4, and TSH levels were low before the initial treatment and increased significantly after treatment (p < 0.05). The FT3, FT4, and TSH levels before treatment were significantly lower in the non‐responder group than in the responder group (p < 0.05). Logistic regression analysis suggested that the addition of pre‐treatment FT4 values to Gunma score was useful in predicting treatment failure.

Conclusions

Thyroid hormone and TSH levels were lower in the non‐responder group than in the responder group in the initial IVIG treatment for Kawasaki disease. This study suggests that Kawasaki disease in the acute phase is associated with low thyroid hormone levels and TSH. It is possible that these hormone levels predict response to the initial IVIG.
Shyness, social engagement, and conversational response times in children's dyadic interactions with an unfamiliar peer
Authors: Wilson McLennon , Powell Adrienne Richter , Hernandez Linda Sosa , Green Emma , Labahn Claudia , Henderson Heather
Published: February 2024

To be a desirable social partner and develop healthy relationships with peers, a child must be able to engage with peers across a variety of contexts. Understanding the factors supporting high levels of social engagement with peers is thereby essential, requiring the development of nuanced and ecologically valid indices of social engagement. Building on recent adult work, the current study explores conversational response time as a novel index of children's social engagement with peers in a dyadic context. This study further explores relationship between conversational response time and children's shyness. Fifty‐six 9‐ to 11‐year‐old children interacted with an unfamiliar peer in an unstructured setting and completed a self‐report measure of shyness. Children's behaviour was coded for their conversational RTs and overall social engagement. Faster conversational RTs were significantly related to children's own social engagement and marginally related to their partners' engagement. Moreover, higher shyness in children's partners predicted faster conversational RTs in children themselves. New directions for using conversational RT as an index of children's social engagement and implications for accounts children's social development are discussed.
Monitoring performance of clinical artificial intelligence: a scoping review protocol
Authors: Andersen Eline Sandvig , Birk-Korch Johan Baden , Röttger Richard , Brasen Claus Lohman , Brandslund Ivan , Madsen Jonna Skov
Published: February 2024

Objective:

The objective of this scoping review is to describe the scope and nature of research on the monitoring of clinical artificial intelligence (AI) systems. The review will identify the various methodologies used to monitor clinical AI, while also mapping the factors that influence the selection of monitoring approaches.

Introduction:

AI is being used in clinical decision-making at an increasing rate. While much attention has been directed toward the development and validation of AI for clinical applications, the practical implementation aspects, notably the establishment of rational monitoring/quality assurance systems, has received comparatively limited scientific interest. Given the scarcity of evidence and the heterogeneity of methodologies used in this domain, there is a compelling rationale for conducting a scoping review on this subject.

Inclusion criteria:

This scoping review will include any publications that describe systematic, continuous, or repeated initiatives that evaluate or predict clinical performance of AI models with direct implications for the management of patients in any segment of the health care system.

Methods:

Publications will be identified through searches of the MEDLINE (Ovid), Embase (Ovid), and Scopus databases. Additionally, backward and forward citation searches, as well as a thorough investigation of gray literature, will be conducted. Title and abstract screening, full-text evaluation, and data extraction will be performed by 2 or more independent reviewers. Data will be extracted using a tool developed by the authors. The results will be presented graphically and narratively.

Review registration:

Open Science Framework https://osf.io/afkrn
Green's Function for Laminar Flow in Channels With Porous Walls in the Presence of a Transverse Magnetic Field
Authors: Tisdell Christopher C.
Published: February 2024

Despite the significant and ongoing interest in Green's functions from scientists, engineers, and mathematicians, the area remains underdeveloped with respect to understanding problems from laminar fluid flow and magnetohydrodynamics (MHD) in porous media. The purpose of this paper is to partially address this gap by constructing a new and explicit representation of the Green's function for a boundary value problem that is derived from laminar flow in channels with porous walls in the presence of a transverse magnetic field. We discuss some interesting consequences of our constructed Green's function, including: the establishment of an equivalent integral equation; and the generation of new information regarding solutions to our boundary value problem. We discover that, for any given transverse magnetic field, our laminar flow problem has a unique solution in a particular location provided the Reynolds number is sufficiently small, and that the solution may be approximated by Picard iterations.
The usage of subgenera in taxonomy of the genus Raphignathus Dugès: a reaction to Khan et al. (2023), with the revised checklist of Raphignathidae

Authors: Doğan Salih , Doğan Sibel , Fan Qing-Hai , Uğurlu Şifanur
Published: February 2024

The reaction paper provides a brief response and critique Khan et al.’s (2023) proposal categorisation about dividing four subgenera of the genus Raphignathus Dugès. The present work contains following nomenclatural recommendation in Raphignathus: (1) Raphignathus bengalensis Modak, 1991 and R. sayedi Gomaa and Hassan, 1986 are considered here as nomina nuda due to no formally publishing. (2) Raphignathus curtipilus Berlese, 1888 is transferred to the genus Eustigmaeus Berlese. (3) Raphignathus striatus Trägardh, 1904 is moved to the genus Prostigmaeus? Kuznetsov in Stigmaeidae based on their original descriptions and illustrations. This paper also presents a current species list for the family Raphignathidae Kramer, with a new country (Türkiye) recorded species and a case of numerical variation in its external suranal setae.
Plants distinguish different photoperiods to independently control seasonal flowering and growth
Authors: Wang Qingqing , Liu Wei , Leung Chun Chung , Tarté Daniel A. , Gendron Joshua M.
Published: February 2024

Plants measure daylength (photoperiod) to regulate seasonal growth and flowering. Photoperiodic flowering has been well studied, but less is known about photoperiodic growth. By using a mutant with defects in photoperiodic growth, we identified a seasonal growth regulation pathway that functions in long days in parallel to the canonical long-day photoperiod flowering mechanism. This is achieved by using distinct mechanisms to detect different photoperiods: The flowering pathway measures photoperiod as the duration of light intensity, whereas the growth pathway measures photoperiod as the duration of photosynthetic activity (photosynthetic period). Plants can then independently control expression of genes required for flowering or growth. This demonstrates that seasonal flowering and growth are dissociable, allowing them to be coordinated independently across seasons.
A deep reservoir for hydrogen drives intense degassing in the Bulqizë ophiolite
Authors: Truche Laurent , Donzé Frédéric-Victor , Goskolli Edmond , Muceku Bardhyl , Loisy Corinne , Monnin Christophe , Dutoit Hugo , Cerepi Adrian
Published: February 2024

Deep crustal production of hydrogen (H
2
) is a potential source of primary energy if recoverable accumulations in geological formations are sufficiently large. We report direct measurements of an elevated outgassing rate of 84% (by volume) of H
2
from the deep underground Bulqizë chromite mine in Albania. A minimum of 200 tons of H
2
is vented annually from the mine’s galleries, making it one of the largest recorded H
2
flow rates to date. We cannot attribute the flux solely to the release of paleo-fluids trapped within the rocks or to present-day active and pervasive serpentinization of ultramafic rocks; rather, our results demonstrate the presence of a faulted reservoir deeply rooted in the Jurassic ophiolite massif. This discovery suggests that certain ophiolites may host economically useful accumulations of H
2
gas.
Fracturing and tectonic stress drive ultrarapid magma flow into dikes
Authors: Sigmundsson Freysteinn , Parks Michelle , Geirsson Halldór , Hooper Andrew , Drouin Vincent , Vogfjörd Kristín S. , Ófeigsson Benedikt G. , Greiner Sonja H. M. , Yang Yilin , Lanzi Chiara , De Pascale Gregory P. , Jónsdóttir Kristín , Hreinsdóttir Sigrún , Tolpekin Valentyn , Friðriksdóttir Hildur María , Einarsson Páll , Barsotti Sara
Published: February 2024

Many examples of exposed giant dike swarms can be found where lateral magma flow has exceeded hundreds of kilometers. We show that massive magma flow into dikes can be established with only modest overpressure in a magma body if a large enough pathway opens at its boundary and gradual buildup of high tensile stress has occurred along the dike pathway prior to the onset of diking. This explains rapid initial magma flow rates, modeled up to about 7400 cubic meters per second into a dike ~15-kilometers long, which propagated under the town of Grindavík, Southwest Iceland, in November 2023. Such high flow rates provide insight into the formation of major dikes and imply a serious hazard potential for high–flow rate intrusions that propagate to the surface and transition into eruptions.
Bipartite viral RNA genome heterodimerization influences genome packaging and virion thermostability
Authors: Zhou Yiyang , Routh Andrew L.
Published: February 2024

Multi-segmented viruses often multimerize their genomic segments to ensure efficient and stoichiometric packaging of the correct genetic cargo. In the bipartite Nodaviridae family, genome heterodimerization is also observed and conserved among different species. However, the nucleotide composition and biological function for this heterodimer remain unclear. Using Flock House virus as a model system, we developed a next-generation sequencing approach (“XL-ClickSeq”) to probe heterodimer site sequences. We identified an intermolecular base-pairing site which contributed to heterodimerization in both wild-type and defective virus particles. Mutagenic disruption of this heterodimer site exhibited significant deficiencies in genome packaging and encapsidation specificity to viral genomic RNAs. Furthermore, the disruption of this intermolecular interaction directly impacts the thermostability of the mature virions. These results demonstrate that the intermolecular RNA-RNA interactions within the encapsidated genome of an RNA virus have an important role on virus particle integrity and thus may impact its transmission to a new host.

IMPORTANCE

Flock House virus is a member of Nodaviridae family of viruses, which provides a well-studied model virus for non-enveloped RNA virus assembly, cell entry, and replication. The Flock House virus genome consists of two separate RNA molecules, which can form a heterodimer upon heating of virus particles. Although similar RNA dimerization is utilized by other viruses (such as retroviruses) as a packaging mechanism and is conserved among Nodaviruses, the role of heterodimerization in the Nodavirus replication cycle is unclear. In this research, we identified the RNA sequences contributing to Flock House virus genome heterodimerization and discovered that such RNA-RNA interaction plays an essential role in virus packaging efficiency and particle integrity. This provides significant insight into how the interaction of packaged viral RNA may have a broader impact on the structural and functional properties of virus particles.
HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s
Authors: Lewitus Eric , Li Yifan , Bai Hongjun , Pham Phuc , Rolland Morgane
Published: February 2024

Knowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against HIV-1 infection. We developed the Hervé platform to analyze and visualize trends in HIV-1 diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, and 3,002 Pol publicly available independent sequences corresponding to subtypes A1, A6, B, C, D, F1, and G and circulating recombinant forms (CRFs) 01_AE, 02_AG, and 07_BC; sequences were sampled between 1980 and 2020 from 82 countries. HIV-1 diversified with a median of 1.82 amino acid substitutions per year in Env, 0.297 in Gag, and 0.779 in Pol. Yet, Env subtype B diversification plateaued post-2000. Pairwise diversity within subtypes and CRFs increased by 41.82% (range = 24.85%–54.41%) in Env, 56.93% (15.38%–89.16%) in Gag, and 46.12% (11.70%–70.57%) in Pol. Consensus sequences based on sequences sampled in each decade remained relatively stable over time. Similarly, at antibody epitope sites, only 0–8 residues that were minority variants became consensus over time in any subtype/CRF and only one known drug resistance mutation site differed from the reference (subtype G). The apparent contradiction between the fast diversification of HIV-1 and its limited adaptation illustrates that HIV-1 evolution is not directional and its consensus is at the intersection of millions of within-host selective processes occurring in a star-like manner. While a consensus sequence is a better representation of HIV-1 diversity than any individual sequence, consensus sequences have progressively become more distant from the circulating sequences they represent.

IMPORTANCE

Global surveillance of HIV-1 sequences is critical for designing relevant prophylactic and therapeutic interventions to infection. We designed an open-source platform, Hervé, for analyzing and visualizing the diversification dynamics of HIV-1 protein sequences. We characterized the evolution of over 12,000 HIV-1 Env, Gag, and Pol protein sequences from 1980–2020 and found that, despite a steady increase in intra-subtype and circulating recombinant form diversity, the most frequent residue at each site, i.e., the consensus, has varied only moderately.
Whole community shotgun metagenomes of two biological soil crust types from the Mojave Desert
Authors: Nguyen Thuy M. , Pombubpa Nuttapon , Huntemann Marcel , Clum Alicia , Foster Brian , Foster Bryce , Roux Simon , Palaniappan Krishnaveni , Varghese Neha , Mukherjee Supratim , Reddy T. B. K. , Daum Chris , Copeland Alex , Chen I-Min A. , Ivanova Natalia N. , Kyrpides Nikos C. , Harmon-Smith Miranda , Eloe-Fadrosh Emiley A. , Pietrasiak Nicole , Stajich Jason E. , Hom Erik F. Y.
Published: February 2024

We present six whole community shotgun metagenomic sequencing data sets of two types of biological soil crusts sampled at the ecotone of the Mojave Desert and Colorado Desert in California. These data will help us understand the diversity and function of biocrust microbial communities, which are essential for desert ecosystems.
Erratum to: Design of a Nonlinear Model of a Pseudomorphic 0.15 µm рHEMT AlGaAs/InGaAs/GaAs Transistor
Authors: Tsunvaza D. , Ryzhuk R. V. , Vasil’evskii I. S. , Kargin N. I. , Klokov V. A.
Published: February 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1063739723900043
Utero-cutaneous fistula following caesarean section
Authors: Coumary Senthil , Galidevara Indira , Naga Daliya Venna , Ghose Seetesh
Published: February 2024

A multiparous woman in her 20s, presented to the clinic with bleeding from caesarean scar site. After clinical examination and radiological evaluation with ultrasound and MR fistulogram, the diagnosis was utero-cutaneous fistula. Complete resection of fistulous tract with uterine defect closure and supportive omental patch placement was done after an intraoperative demonstration of the utero-cutaneous fistula by injecting methylene blue dye. Utero-cutaneous fistula is a rare complication after caesarean section. Cyclical bleeding from an abnormal opening in previous caesarean scar site is the classical presentation of this condition.
Linezolid-induced lactic acidosis
Authors: Ramesh Venkat , Gattu Santosh , Maqsood Maryam , Rao Vishnu
Published: February 2024

Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged administration of linezolid, lactic acidosis is a rare adverse drug reaction. We present the case of a patient on linezolid for disseminated multidrug-resistant tuberculosis who presented with vomiting, dyspnoea, hypotension and high anion gap metabolic acidosis. The initial presentation mimicked sepsis syndrome. Ketoacidosis and renal dysfunction were ruled out. There was no history of ingestion of toxins/toxic alcohols. Sepsis was unlikely because extensive radiological and microbiological testing could not identify an infection. Given the possibility of linezolid-induced lactic acidosis (LILA), linezolid was discontinued on admission. The patient’s lactic acidosis resolved, and his overall condition improved. A retrospective diagnosis of LILA was thus established. LILA should be considered when patients on linezolid present with lactic acidosis and other causes for the lactic acidosis have been ruled out.
Multiple modes of data sharing can facilitate secondary use of sensitive health data for research
Authors: Tamuhla Tsaone , Lulamba Eddie T , Mutemaringa Themba , Tiffin Nicki
Published: February 2024

Evidence-based healthcare relies on health data from diverse sources to inform decision-making across different domains, including disease prevention, aetiology, diagnostics, therapeutics and prognosis. Increasing volumes of highly granular data provide opportunities to leverage the evidence base, with growing recognition that health data are highly sensitive and onward research use may create privacy issues for individuals providing data. Concerns are heightened for data without explicit informed consent for secondary research use. Additionally, researchers—especially from under-resourced environments and the global South—may wish to participate in onward analysis of resources they collected or retain oversight of onward use to ensure ethical constraints are respected. Different data-sharing approaches may be adopted according to data sensitivity and secondary use restrictions, moving beyond the traditional Open Access model of unidirectional data transfer from generator to secondary user. We describe collaborative data sharing, facilitating research by combining datasets and undertaking meta-analysis involving collaborating partners; federated data analysis, where partners undertake synchronous, harmonised analyses on their independent datasets and then combine their results in a coauthored report, and trusted research environments where data are analysed in a controlled environment and only aggregate results are exported. We review how deidentification and anonymisation methods, including data perturbation, can reduce risks specifically associated with health data secondary use. In addition, we present an innovative modularised approach for building data sharing agreements incorporating a more nuanced approach to data sharing to protect privacy, and provide a framework for building the agreements for each of these data-sharing scenarios.
Randomised controlled trial of exercise training during lactation on breast milk composition in breastfeeding people with overweight/obesity: a study protocol for the MILKSHAKE trial
Authors: Moholdt Trine , Ashby Emily Rose , Tømmerdal Karina Hammer , Lemoine Maëliss Cynthia Chloé , Holm Rebecca Lyng , Sætrom Pål , Iversen Ann-Charlotte , Ravi Anuradha , Simpson Melanie Rae , Giskeødegård Guro F
Published: February 2024

Breast milk from people with overweight/obesity may differ in composition compared with that from normal-weight people. Exercise training can modify breast milk composition in rodent models, with a beneficial impact demonstrated on the offspring’s metabolism, but whether these findings translate to humans is unclear. This trial aims to determine the effect of an exercise intervention on breast milk composition and whether an exercise-induced modification of breast milk impacts the infants’ growth and body composition. Effect of Exercise Training on Breastmilk Composition is a randomised, controlled trial with two parallel groups, one exercise group and one control group, with a 1:1 allocation. We will include a minimum of 62 exclusively breastfeeding participants, 6 weeks postpartum. The exercise intervention lasts 8 weeks and comprises 25 supervised endurance exercise sessions with moderate or high intensity. The primary outcome measure is the change in the relative concentration of the human milk oligosaccharide 3′sialyllactose in breast milk from baseline at 6 weeks postpartum to the end of the intervention period. Secondary outcomes include breast milk concentrations of other metabolites, cytokines, hormones and microRNA, maternal health outcomes, infant growth, infant gut microbiome and infant circulating microRNA. Maternal and infant outcomes will be measured before, during and after the intervention period, with a follow-up of the infants until they are 24 months old. Trial registration numberNCT05488964.
Lifetime non-fatal overdose experiences among at-risk adolescents and young adults in the emergency department with past-year opioid use in the USA
Authors: Seewald Laura , Bonar Erin , Bohnert Amy S B , Carter Patrick M , King Cheryl A , Losman Eve D , Bacon Linnea , Wheeler Tiffany , Walton Maureen
Published: February 2024

Background

Adolescents and young adults with risk factors for opioid misuse and opioid use disorder are at elevated risk for overdose. We examined prior non-fatal overdose experiences among at-risk adolescents/young adults to inform prevention efforts.

Methods

Adolescents/young adults (ages 16–30) in two US emergency departments self-reporting past year opioid misuse or opioid use plus a misuse risk factor completed a baseline survey as part of an ongoing randomised controlled trial. We describe baseline factors associated with (a) overall non-fatal overdose experiences and (b) groups based on substance(s) used during the worst overdose experience.

Results

Among 771 participants (27.9% male), 40.7% reported a non-fatal overdose experience. Compared with those without a prior overdose experience, those with prior overdose experience(s) were less likely to be heterosexual, and more likely to report a prior suicide attempt and greater peer substance misuse. Regarding the worst overdose experience, substance(s) included: 36.6% alcohol only, 28.0% alcohol and cannabis, 22.6% alcohol with other substance(s) and 12.7% other substance(s) only (eg, opioids). Compared with the alcohol only group, the alcohol and cannabis group were younger and less likely to be heterosexual; the alcohol with other substance(s) group were older and had greater peer substance misuse; and the other substance(s) only group were more likely to be male, receive public assistance, screen positive for anxiety and less likely to be heterosexual.

Conclusions

Among at-risk adolescents/young adults, findings support the need for tailored overdose prevention efforts based on substance(s) used, with consideration of sexuality, mental health and peer substance use.

Trial registration number

NCT04550715.
How socio-political change is associated with the number of individually reported negative life events: a population-based study using the German reunification 1989/1990 as an example
Authors: Hahm Stefanie , Altweck Laura , Schmidt Silke , Fleischer Toni , Helmert Claudia , Ulke Christine , Speerforck Sven , Schomerus Georg , Klinger-König Johanna , Grabe Hans J , Schmidt Carsten Oliver , Beutel Manfred E , Brähler Elmar , Muehlan Holger
Published: February 2024

Background

Socio-political change often leads to disruptions in employment and social networks, which can exacerbate health issues and increase mortality rates. These consequences are likely observed as an increase in negative life events (NLEs), serving as indicators of the broader social and health impacts. Using the German reunification in 1989/1990 as an example, this study investigates changes in reported numbers of NLEs and differences regarding sociodemographic characteristics.

Methods

We used data from the population-based Study of Health in Pomerania (SHIP-START-0, SHIP-Life-Events and Gene-Environment Interaction in Depression; N=1932). Numbers of NLEs in different categories (work/financial, social/interpersonal, illness (own) and illness/death (others)) were measured retrospectively in 5-year intervals (1980–2004) using a semistructured interview. Pre-reunification and post-reunification changes were modelled using piecewise mixed-effects Poisson regressions with the 1990–1994 interval (reunification) as change point. Interactions with age, sex and education were examined.

Results

The number of most NLE categories, except social/interpersonal NLEs, increased at reunification. Whereas work/financial NLEs slightly decreased post-reunification, illness-related NLEs continued to increase. Higher numbers of social/interpersonal NLEs were found with younger age. More illness-related NLEs were reported with older age, lower education (illness (own)) and by women (illness/death (others)). However, the majority reported no NLEs at reunification (68.2%–80.7%, varying by category).

Conclusion

Our findings suggest that although some individuals experience a marked increase in NLEs due to socio-political changes, many remain unaffected, emphasising the need for a differentiated understanding of these effects. This increase in NLEs may partly account for ongoing health and well-being disparities among countries with differing transformation histories.
Association of same-sex criminalisation laws and national HIV policies with HIV testing in African MSM: an ecological single-level and multilevel cross-sectional study of sub-Saharan African countries
Authors: Kalu Ngozi , Ross Michael W , Taegtmeyer Miriam , Lamontagne Erik , Howell Sean , Neuman Melissa
Published: February 2024

Background

HIV incidence among men who have sex with men (MSM) in sub-Saharan Africa (SSA) remains high compared with the general population. Many countries in the region still criminalise consensual homosexual relationships, and some are yet to adopt WHO-recommended interventions for MSM into national HIV policies. This study examines how HIV testing of adult MSM in SSA varies according to the legal climate and presence of targeted HIV policy using data from the cross-sectional 2019 Global LGBTI Internet Survey study.

Methods

Using data from 3191 MSM in 44 SSA countries, we assessed associations of legal climate and HIV policy with ever and recent HIV testing using linear ecological and logistic multilevel analyses. From the single-level analysis, we can compare our findings to previously reported data, then, extending to a two-level multilevel analysis, we account for the hierarchical structure of the population and simultaneously adjust for differences in context and composition in each country. We then test the sensitivity of our analyses to excluding countries from the model.

Results

We find evidence that legalised same-sex relationships were associated with increased odds of ever testing (OR=2.00, 95% CI 1.04, 3.82) in multilevel analyses. We also find evidence of an association of targeted HIV policies with increased odds of ever testing (OR=2.49, 95% CI 1.12, 5.52). We did not find evidence of an association of the legal climate (OR=1.01, 95% CI 0.69, 1.46) and targeted HIV policies (OR=1.26, 95% CI 0.78, 2.04) with recent testing.

Conclusions

This study suggests elimination of discriminatory laws and policies might be important for increasing HIV status awareness of MSM, an important first step in epidemic control. Additionally, we highlight heterogeneity between South Africa and other SSA countries, which has implications for studying SSA countries as a homogeneous group.