bluuebunny/crossref_metadata_2025 huggingface dataset:
CrossIsoFun: predicting isoform functions using the integration of multi-omics data
Authors: Liu Yiwei , Li Hong-Dong , Wang Jianxin
Published: December 2024

Motivation

Isoforms spliced from the same gene may carry distinct biological functions. Therefore, annotating functions at the isoform level provides valuable insights into the functional diversity of genomes. Since experimental approaches for determining isoform functions are time- and cost-demanding, computational methods have been proposed. In this case, multi-omics data integration helps enhance the model performance, providing complementary insights for isoform functions. However, current methods underperform in leveraging diverse omics data, primarily due to the limited power to integrate the heterogeneous feature domains. Besides, among the multi-omics data, isoform-isoform interactions (IIIs) are a key data source, as isoforms interact with each other to perform functions. Unfortunately, IIIs remain largely underutilized in isoform function predictions until now.

Results

We introduce CrossIsoFun, a multi-omics data analysis framework for isoform function prediction. CrossIsoFun combines omics-specific and cross-omics learning for data integration and function prediction. In detail, CrossIsoFun uses a graph convolutional network (GCN) as the omics-specific classifier for each data source. The initial label predictions from GCNs are forwarded to the View Correlation Discovery Network (VCDN) and processed as a cross-omics integrative representation. The representation is then used to produce final predictions of isoform functions. In addition, an antoencoder within a cycle-consistency generative adversarial network (cycleGAN) is designed to generate IIIs from PPIs and thereby enrich the interactomics data. Our method outperforms the state-of-the-art methods on three tissue-naive datasets and 15 tissue-specific datasets with mRNA expression, sequence, and PPI data. The prediction of CrossIsoFun is further validated by its consistency with subcellular localization and isoform-level annotations with literature support.

Availability and implementation

CrossIsoFun is freely available at https://github.com/genemine/CrossIsoFun.
Matching the general or the specific child with a foster home?
Authors: Järkestig Berggren Ulrika , Engwall Kristina , Bask Miia , Bergman Ann-Sofie
Published: December 2024

Matching a child with a foster home is a professional practice with considerable room for discretion since there are no specific guidelines in Sweden. The aim is to describe what knowledge do social workers’ assessments build upon in the matching process. The material consists of matching investigation files of 116 children from 6 municipalities in Sweden. A data form was used to assemble excerpts of descriptions of the child’s needs and how the family would be expected to meet the child’s needs. The findings show that social workers describe the child’s basic needs in line with the theory of Maslow and the ability of foster parents to form attachment and take a child perspective. Specific needs of the child are motioned regarding medical diagnoses and challenging behaviour of the child. This focus on basic needs is due to several circumstances, a shortage of available foster homes and that the matching social worker seldom meets the child, hence the child’s interests and wishes are seldom known. Implications for practice concern the right for children to be involved in the decision-making process and for the social worker to take in to account the specific needs of the child.
Increased cell-free DNA in CSF and serum of hip fracture patients with delirium
Authors: Bratseth Vibeke , Watne Leiv Otto , Neerland Bjørn Erik , Halaas Nathalie Bodd , Pollmann Christian Thomas , Karabeg Adi , Odegaard Olav Tobias , Sydnes Kristian , Zetterberg Henrik , Seljeflot Ingebjørg , Helseth Ragnhild
Published: December 2024

Delirium is a neuropsychiatric syndrome commonly presenting during acute illness. The pathophysiology of delirium is unknown, but neuroinflammation is suggested to play a role. In this cross-sectional study, we aimed to investigate whether cell-free DNA and markers of neutrophil extracellular traps in serum and CSF were associated with delirium and neuronal damage, assessed by neurofilament light chain. Hip fracture patients (n = 491) with a median (25, 75 percentiles) age of 83 (74, 88) years and 69% females were enrolled at Oslo University Hospital, Diakonhjemmet Hospital, Akershus University Hospital and Bærum Hospital. Delirium was assessed daily, pre- and postoperatively. Cognitively healthy adults (n = 32) with a median (25, 75 percentiles) age of 75 (70, 77) years and 53% females were included as controls. Cell-free DNA was measured by using the fluorescent nucleic acid stain Quant-iT PicoGreen® in serum and CSF. Myeloperoxidase-DNA and citrullinated histone H3 were analysed by enzyme-linked immunosorbent assay in serum. Hip fracture patients have significantly higher levels of cell-free DNA and neutrophil extracellular traps in blood than cognitively healthy controls. In hip fracture patients without dementia, cell-free DNA in CSF and serum was significantly higher in patients with (n = 68) versus without (n = 221) delirium after adjusting for age and sex (70 (59, 84) versus 62 (53, 77) ng/ml, P = 0.037) and 601 (504, 684) versus 508 (458, 572) ng/ml, P = 0.007, respectively). In the total hip fracture cohort, CSF levels of cell-free DNA and neurofilament light chain were significantly correlated after adjusting for age and sex (r = 0.441, P < 0.001). The correlation was stronger in those with delirium (r = 0.468, P < 0.001) and strongest in delirious patients without dementia (r = 0.765, P = 0.045). In delirious patients without dementia, significantly higher levels of cell-free DNA in CSF and serum were shown. The association between cell-free DNA and neurofilament light chain suggest simultaneous release of cell-free DNA and neuronal damage during delirium.
Bibliometric analysis of studies investigating the association between isotretinoin use and depression and suicide
Authors: Ünlü Açıkel Sezin , Sadettin Burak Açıkel
Published: December 2024

Background

Acne vulgaris has significant effects on the emotional and social wellbeing of an affected individual, leading to conditions like anxiety, depression and social isolation. Oral isotretinoin has been associated with various side-effects, including psychiatric concerns like depression and suicidal ideation. However, the connection between isotretinoin and these mental health issues remains controversial.

Objectives

To provide an overview of the literature on the subject by investigating data such as the effects of articles in the field on the literature as a whole, coauthorship and citation analysis.

Methods

A bibliometric analysis was conducted using the Web of Science database to search for studies from 1986 to 2024 with keywords related to isotretinoin, suicide and depression. Data were analysed using VOSviewer software to visualize the bibliometric networks and trends.

Results

For the study, 380 publications were identified, with a peak in 2018. The most common article types were original articles (60.3%), reviews (13.9%) and letters (12.1%). English is the predominant language of publication (93.4%). The h-index of these articles was 49, with an average of 23.0 citations per article. The top research areas included dermatology, pharmacology and psychiatry. The analysis highlights key authors and their contributions to the field.

Conclusions

The bibliometric analysis has revealed an evolving research landscape. The number of studies has increased since 2004, following the Food and Drug Administration’s black box warning in 2005. While early studies linked isotretinoin to psychiatric issues, recent data have shown a stronger association between acne and these conditions rather than the medication itself. This analysis underscores the importance of continuous research and re-evaluation of clinical guidelines based on emerging evidence.
Exit Interviews Exploring Patients’ Experience of Change in Crohn’s Disease Symptoms During the Mirikizumab Phase 3 Clinical Trial In Adult Patients With Moderately-to-Severely Crohn’s Disease
Authors: Hunter Gibble Theresa , Macey Jake , Makin Harriet , Rosu Rodica , Mellor Katie , Kitchen Helen , Hon Emily , Dubinsky Marla
Published: December 2024

Background

Exit interviews with patients who completed the Phase 3 VIVID-1 mirikizumab clinical trial for moderately-to-severely active Crohn’s disease explored the content validity of bowel urgency, stool frequency, and abdominal pain patient-reported outcome measures and perceptions of meaningful within-patient change and remission in these key Crohn’s disease symptoms.

Methodology

Cognitive debriefing explored patient understanding of the bowel urgency numeric rating scale (Urgency NRS), Crohn’s Disease Activity Index: Stool Frequency (CDAI-SF) and Abdominal Pain (CDAI-AP), and patient global rating/impression of severity/change (PGRS/PGIC). Perceptions of meaningful change and remission were explored qualitatively. Transcripts were analyzed using directed content and framework analysis.

Results

Interviewed participants (N = 62; mean age 44.8 years, 55% female, mean 12.0 years since Crohn’s disease diagnosis) were from the United States (n = 29), Czech Republic (n = 10), Poland (n = 8), Germany (n = 7), Canada (n = 4), Australia (n = 3), and the United Kingdom (n = 1). Participants understood the Urgency NRS, CDAI-SF, and CDAI-AP and could use them to rate their bowel urgency, stool frequency, and abdominal pain. Participants considered these symptoms when responding to the PGRS/PGIC. Meaningful change was described as symptom relief resulting in the ability to live daily life without pain or fear/need of rushing to the toilet. Most participants agreed with a proposed remission definition of ≤3 type 6/7 bowel movements and None/Mild abdominal pain.

Discussion

The Urgency NRS, CDAI-SF, and CDAI-AP are content-valid patient-reported outcome measures in Crohn’s disease. The PGRS/PGIC are conceptually related global assessments of bowel urgency, stool frequency, and abdominal pain. Patients considered reduction in these symptoms as meaningful and remission.
Multiple Ileal and Colonic Stenoses: Is It Always Crohn’s Disease?
Authors: Bencardino Sarah , Allocca Mariangela , Furfaro Federica , D’Amico Ferdinando , Parigi Tommaso Lorenzo , Danese Silvio , Zilli Alessandra
Published: December 2024

A 62-year-old woman presented with multiple ileal and colonic stenoses, initially suspected to be Crohn’s disease. Despite unremarkable endoscopic biopsies, surgery was performed due to clinical deterioration, and histological analysis confirmed the presence of metastatic breast cancer. This case highlights the importance of considering metastatic disease in the differential diagnosis of gastrointestinal (GI) strictures, particularly when inflammatory bowel disease markers are inconclusive or marginal. Clinicians should be aware of the potential for breast cancer to metastasize to the GI tract, which may present with symptoms mimicking primary GI diseases.
Catheter ablation of atrial flutter in an adult with a univentricular heart, common atrium, and single atrioventricular valve: a case report—‘complex things don’t always require a complex solution’
Authors: Ortíz-Avalos Martín , Galindo-Garza Silvia Melissa , Chavez-Collazos Chris Keith , Andrade-Cuellar Elias Noel , Rodríguez-Diez Gerardo
Published: December 2024

Background

The ‘univentricular’ heart encompasses a variety of congenital cardiac defects characterized by a single functional ventricle and an underdeveloped ventricular chamber. Surgical intervention, typically in infancy or childhood, aims to regulate pulmonary blood flow volume. In adulthood, untreated patients may experience limitations in physical activity and elevated morbidity due to persistent cyanosis and arrhythmias, notably after the Fontan procedure.

Case summary

A 38-year-old Mexican man with an unrepaired morphologically right single ventricle and a common atrium presented with palpitations. Diagnostic imaging revealed a hypertrophic systemic single ventricle with severe atrioventricular valve regurgitation and pulmonary stenosis. Despite ongoing anticoagulant and beta-blocker therapy, persistent symptoms prompted catheter ablation guided by CARTO-Merge®, a function that overlays computed tomography or magnetic resonance imaging onto a CARTO® electroanatomical map. Ablation along the cavo-annular isthmus was successfully performed, achieving arrhythmia termination. Post-ablation, the patient developed sinus rhythm and second-degree atrioventricular block, necessitating the implantation of an epicardial pacemaker.

Discussion

Atrial flutter ablation in univentricular hearts without prior surgery is rare. Such patients are predisposed to post-Fontan arrhythmias, often requiring intervention due to increased morbidity. Atrial flutter arises from scarred post-surgery regions, necessitating careful assessment and management. Our case demonstrates successful ablation in a complex congenital heart condition, highlighting the importance of comprehensive imaging, understanding arrhythmia mechanisms, and meticulous procedural techniques for optimal outcomes.
Aberration correction—impact on image quality and chamber quantification in transthoracic echocardiography
Authors: Berg Erik Andreas Rye , Espeland Torvald , Dalen Håvard , Grenne Bjørnar , Bjåstad Tore Grüner , Holte Espen , Måsøy Svein-Erik
Published: December 2024

Aims

To improve image quality (IQ) in echocardiography, an aberration correction (AC) algorithm has recently been implemented in commercial scanners. We aimed to study (i) the correlation of a subjective IQ-score and an objective IQ-metric [global image coherence (GIC)], (ii) if AC improved IQ; (iii) if AC affected average values and interobserver agreement of left ventricular (LV) size, LV longitudinal strain, and left atrial (LA) volume.

Methods and results

From 50 adult patients, where 45 (90%) had cardiovascular disease, unprocessed image data (channel data) were acquired from six standard transthoracic views. The data were processed with and without AC, resulting in 300 pairs of cine-loops. The cine-loops were randomly presented one-by-one to two blinded raters experienced in echocardiography. Both raters scored IQ subjectively from 1 (poor) to 4 (very good) and quantified LV dimensions, volumes and longitudinal strain, and LA volume. IQ-score correlated with GIC, Spearman rho 0.72, P < 0.001. AC improved median IQ-score from 2.5 to 3.0 (Wilcoxon signed rank: P < 0.001). The differences in average values of LV size, LV longitudinal strain, or LA volume with and without AC were not statistically significant and numerically minimal. Measured by intraclass correlation, interobserver agreement of these values was not significantly affected by AC.

Conclusion

Image quality-score strongly correlated with GIC. Aberration correction improved IQ. However, AC did not lead to statistically significant changes in average values or interobserver agreement of LV size, LV longitudinal strain or LA volume quantification. Likely, the major benefit of AC is enhanced visualization of anatomical details.
Sex-specific immunocompetence: resistance and tolerance can both be futile but not under the same circumstances
Authors: Brenninger Franziska A , Kovalov Viktor , Kokko Hanna
Published: December 2024

Immunocompetence evolution can involve a “resistance is futile” scenario if parasite encounter rates are so high that high investment in resistance only marginally delays infection. Here, we investigate two understudied aspects of “futility”: the mode of immunocompetence and sexual selection. First, immunocompetence is usefully categorized as reducing the rate of becoming infected (resistance) or reducing the negative fitness consequences of infection once it happened (tolerance). We compare the prospects of futility for resistance, tolerance, and their joint occurrence, showing that resistance futility arises with respect to parasite encounter rates, while tolerance futility arises with respect to parasite virulence. However, if the same host trait improves pleiotropically both resistance and tolerance, futility disappears altogether and immunity investment remains profitable when increasing parasite encounter rates, virulence, or both. Second, we examine how sexual selection strength impacts these findings. If one sex (typically males) is near the faster end of a fast-slow continuum of life histories, then life history patterns reflecting futility can evolve sex-specificity. The solutions often feature sexual dimorphism in immunocompetence, but not always in the direction of strong sexual selection yielding low immunity: sexual selection can select for faster and “sicker” lives, but if sexual selection also favors traits that impact parasite encounter rates, the results are strongly dependent on whether futility (along any axis) plays a role.
Meanings and Roles of Great-Grandparenthood: A Scoping Review
Authors: Talašová Zuzana , Souralová Adéla
Published: December 2024

Background and Objectives

Great-grandparenthood brings a new internal dynamic to intergenerational relationships in which contact between four generations is now the norm. In this scoping review, we sought to identify the roles of great-grandparents and what those roles entail.

Research Design and Methods

We performed a review using PRISMA-ScR to identify peer-reviewed studies investigating the roles of great-grandparents. The reviewed articles were selected from four databases. The article selection conditions were met by 23 studies that used quantitative or qualitative methods. The studies had to be published in English; the selected publications spanned eight countries.

Results

The scoping review covers a collection qualitative and quantitative research with different types of respondents (great-grandchild, grandparents, great-grandparents, etc.). An important element was a statement on great-grandparenting from at least one of the four generations. We selected 23 articles from an initial selection of 176 studies. The studies were heterogeneous in conceptual frameworks, collection methods, and interview conduct, with qualitative methods predominating over quantitative methods.

Discussion and Implications

Based on research on great-grandparenting, the roles of great-grandparents can be categorized as continuing, insignificant, or significant. Each role category has a specific function and each represents a different meaning for the great-grandparents within the family. Several factors and constraints frame the great-grandparent roles. Based on the research results, some characteristics are shared by all role categories despite the dividing elements.
Opaque ontology: neuroimaging classification of ICD-10 diagnostic groups in the UK Biobank
Authors: Easley Ty , Luo Xiaoke , Hannon Kayla , Lenzini Petra , Bijsterbosch Janine
Published: December 2024

Background

The use of machine learning to classify diagnostic cases versus controls defined based on diagnostic ontologies such as the International Classification of Diseases, Tenth Revision (ICD-10) from neuroimaging features is now commonplace across a wide range of diagnostic fields. However, transdiagnostic comparisons of such classifications are lacking. Such transdiagnostic comparisons are important to establish the specificity of classification models, set benchmarks, and assess the value of diagnostic ontologies.

Results

We investigated case-control classification accuracy in 17 different ICD-10 diagnostic groups from Chapter V (mental and behavioral disorders) and Chapter VI (diseases of the nervous system) using data from the UK Biobank. Classification models were trained using either neuroimaging (structural or functional brain magnetic resonance imaging feature sets) or sociodemographic features. Random forest classification models were adopted using rigorous shuffle-splits to estimate stability as well as accuracy of case-control classifications. Diagnostic classification accuracies were benchmarked against age classification (oldest vs. youngest) from the same feature sets and against additional classifier types (k-nearest neighbors and linear support vector machine). In contrast to age classification accuracy, which was high for all feature sets, few ICD-10 diagnostic groups were classified significantly above chance (namely, demyelinating diseases based on structural neuroimaging features and depression based on sociodemographic and functional neuroimaging features).

Conclusion

These findings highlight challenges with the current disease classification system, leading us to recommend caution with the use of ICD-10 diagnostic groups as target labels in brain-based disease prediction studies.
‘The Strength Even to Comprehend the Incomprehensible’: Rereading Adorno in the Age of Authoritarian Resurgence
Authors: Bakiner Onur
Published: December 2024

ABSTRACT∞

This article reappraises Theodor W. Adorno’s call for ‘working through the past’ as an ethical practice in the wake of Auschwitz, and as a prescriptive model for rebuilding the collective, by situating Adorno’s 1959 lecture ‘What Does Coming to Terms with the Past Mean?’ and 1966 lecture ‘Education after Auschwitz’ in the totality of his corpus. Adorno’s reflections reveal the effort to build a positive political project in the wake of catastrophe, but its ethical demands on present generations complicate any practical proposal to address the past. Heralding contemporary transitional justice theory and practice in important ways, fruitful tensions in his lectures reveal the inherent difficulty of reckoning with past wrongs: rebuilding ethical life in the wake of Auschwitz presupposes the impossibility of a foundational metaphysics; understanding and overcoming past wrongs runs the risk of trivializing and relativizing them; and history should be understood as the unfolding of constellations of given conditions.
Evolutionary history of soil-feeding Neotropical termites reveals recent divergences linked to geologic-climatic influences
Authors: Gergonne Damien , Roy Virginie , Poteaux Chantal , Hellemans Simon , Bourguignon Thomas , Fougeyrollas Romain , Hanus Robert , Roisin Yves , Vecco-Giove Carlos Daniel , Cerna-Mendoza Agustín , Armbrecht Inge , Valladares Romero Cynthia Stefania , Vieira de Oliveira Couto Alane Ayana , Šobotnik Jan , Sillam-Dussès David
Published: December 2024

The Neotropics harbor a diverse array of flora and fauna shaped by a complex geological and climatic history. It includes marine invasions, pulses of Andean uplift, glaciations, and the uplift of the Panama Isthmus. These events have shaped organism distribution, which can be described by methods of historical phylogeography. However, the evolutionary history of nonvertebrate organisms in the Neotropics is still largely unknown. This applies to termites, which are particularly diverse and ecologically important. The phylogeography of the soil-feeding termites Embiratermes neotenicus and Embiratermes chagresi (Termitidae: Syntermitinae) was studied across their whole distribution range, using samples of 243 colonies from eight countries. Analyses based on mitochondrial DNA fragments, microsatellite loci, and complete mitochondrial genomes revealed 4 major mitochondrial haplogroups (H1–H4). The H4 haplogroup occurs in northeastern Brazil and diverged first. The other groups appear to be associated with the Pebas System and marine invasions during the Miocene, which may have contributed to the separation of the ancestral population along a north–south axis. The H1 haplogroup was affiliated with E. chagresi. The phylogenomic analysis estimated the divergence of E. chagresi from the other groups to 5 million years ago, aligning with the northern cordillera uplift during the Miocene. Microsatellite data highlighted the isolation of E. neotenicus populations in Suriname and French Guiana, possibly linked to Pleistocene climatic fluctuations. Our study provides insights into the evolutionary history of these species, contributing to a better understanding of how geological and climatic events have influenced species evolution in the Neotropics.
Difficulties faced by three hospitals evacuated from the urgent protective action planning zone after the 2011 Fukushima Daiichi Nuclear power plant accident
Authors: Nonaka Saori , Sawano Toyoaki , Oikawa Tomoyoshi , Murakami Michio , Ozaki Akihiko , Zhao Tianchen , Yoshida Makoto , Yamamoto Chika , Tsubokura Masaharu
Published: December 2024

In radiological disasters, evacuating institutionalized individuals such as hospitalized patients and nursing home residents presents complex challenges. The Fukushima Daiichi Nuclear power plant (FDNPP) accident, triggered by the Great East Japan Earthquake (GEJE), exposed critical issues in evacuation planning. This case series investigates the evacuation difficulties encountered by three hospitals situated 20 to 30 km from the FDNPP following the GEJE and FDNPP accident. Data collection involved reviewing records, stakeholder interviews and analyzing publicly available resources. Six key challenges emerged: acute phase influx—hospitals faced an abrupt surge in patients, including trauma victims and vulnerable individuals; initial discharge and transfers—coordinating patient discharges and transfers during the chaotic aftermath proved daunting; staff shortages—evacuation and personal factors lead to reduced staffing levels and strained hospital capabilities; infrastructure damage and logistics suspension—infrastructure issues, such as burst water pipes, halted gas supplies, and heavy oil shortage disrupted hospital operations; unclear evacuation criteria—ad hoc evacuation decisions underscored the lack of clear criteria; and limited preparation time—minimal preparation time hindered communication and planning. These findings underscore the need for robust disaster planning, resource management, and communication strategies to ensure the safety of patients and staff during radiological emergencies. Government interventions, early patient discharge, and improved medical record communication may alleviate the burden of evacuation. The lessons learned emphasize the importance of maintaining hospital functions in disaster-prone areas, particularly for vulnerable populations, and highlight the necessity for comprehensive community-wide disaster prevention planning.
Detection of genome instability by 53BP1 expression as a long-lasting health effect in human epidermis surrounding radiation-induced skin cancers
Authors: Matsuda Katsuya , Kurohama Hirokazu , Kuwatsuka Yutaka , Iwanaga Akira , Murota Hiroyuki , Nakashima Masahiro
Published: December 2024

We previously reported endogenous activation of the DNA damage response (DDR) in the epidermis surrounding basal cell carcinoma resected from Nagasaki atomic bomb survivors, suggesting the presence of genomic instability (GIN) in the survivors as a late effect of radiation. Dual-color immunofluorescence (IF) analysis of TP53-binding protein-1 (53BP1) and a proliferative indicator, Ki-67, to elucidate GIN in tumor tissues revealed that abnormal 53BP1 expression is closely associated with carcinogenesis in several organs. The present study aimed to confirm the presence of radiation-induced GIN in the non-neoplastic epidermis of patients with radiation-induced skin cancer. Formalin-fixed paraffin-embedded tissues were obtained from all participants between 2008 and 2019 at the Nagasaki University Hospital. 53BP1 nuclear expression was examined using dual-color IF analysis with Ki-67 expression to assess the extent and integrity of the DDR. Expressions of gamma-H2AX, p53 and p21 were also analyzed using the dual-color IF analysis for their association with 53BP1. The results of this study provide evidence for sporadic activation of the DDR in medically irradiated and ultraviolet-exposed epidermis as a long-lasting radiation effect, which is a predisposition to skin cancer. Furthermore, the incidence of abnormal 53BP1 expression in cancer cells was higher than in non-neoplastic epidermal cells surrounding cancer, suggesting a correlation between the type of 53BP1 and the malignant potential of skin tumors. This study highlights the usefulness of dual-color IF for 53BP1 (and Ki-67) as an indicator to estimate the level of GIN as a long-lasting health effect of radiation exposure.
Mutagenesis studies suggest a mechanism for influenza polymerase stalling during polyadenylation
Authors: Li Minke , Wu Yixi , Li Huanhuan , Song Wenjun , Chen Zhenxing , Peng Yuzhou , Yang Boyao , Xu Chang , Zhang Jihua , Xing Lei , Weng Zhuangfeng , Liu Yingfang , Liang Huanhuan
Published: December 2024

Influenza polymerase (FluPol) carries out both viral transcription and replication using the same viral genome segment as a template to yield distinct end products. However, it remains largely unclear how FluPol synthesizes transcripts containing poly (A) tails during transcription termination, while producing fully complementary products during replication termination. In this study, through structural analysis combined with cell-based and biochemical assays, we identified that the PB1 Leu675/Asn676 and PB2 Arg38 residues of FluPol are critical for transcription termination and polyadenylation. During transcription termination, these three residues adopt the PB1 Leu675/Asn676down and PB2 Arg38out conformations, with their side chains positioned against the G12 and G14 residues of the RNA template at the 5′ end. These steric hindrances block template translocation and facilitate FluPol ‘stuttering’ at U17, which is required for viral messenger RNA polyadenylation. Importantly, both structural analysis and mutational studies suggest that this specific conformation of these residues is unique to the transcription termination state. Overall, our findings provide novel insights into the mechanisms by which FluPol generates distinct 3′ end products during transcription and replication termination.
The hexose transporters CsHT3 and CsHT16 regulate postphloem transport and fruit development in cucumber
Authors: Cheng Jintao , Wen Suying , Li Kexin , Zhou Yixuan , Zhu Mengtian , Neuhaus H Ekkehard , Bie Zhilong
Published: December 2024

Hexoses are essential for plant growth and fruit development. However, the precise roles of hexose/H+ symporters in postphloem sugar transport and cellular sugar homeostasis in rapidly growing fruits remain elusive. To elucidate the functions of hexose/H+ symporters in cucumber (Cucumis sativus L.) fruits, we conducted comprehensive analyses of their tissue-specific expression, localization, transport characteristics, and physiological functions. Our results demonstrate that CsHT3 (C. sativus hexose transporter), CsHT12, and CsHT16 are the primary hexose/H+ symporters expressed in cucumber fruits. CsHT3 and CsHT16 are localized in the sieve element–companion cell during the ovary and early fruit development stages. As the fruit develops and expands, the expression of both symporters shifts to phloem parenchyma cells. The CsHT16 knockout mutant produces shorter fruits with a larger circumference, likely due to impaired sugar and phytohormone homeostasis. Concurrent reduction of CsHT3, CsHT12, and CsHT16 expression leads to decreased fruit size. Conversely, CsHT3 overexpression results in increased fruit size and higher fruit sugar levels. These findings suggest that CsHT16 plays an important role in maintaining sugar homeostasis, which shapes the fruit, while CsHT3, CsHT12, and CsHT16 collectively regulate the supply of carbohydrates required for cucumber fruit enlargement.
A syndemic approach to the study of Covid-19-related death: a cohort study using UK Biobank data
Authors: Fonseca de Freitas Daniela , Bhui Kamaldeep , Clesse Christophe , Zahid Uzma , Mooney Roisin , Joury Easter , Hayes Richard D , Khondoker Mizanur
Published: December 2024

Background

The Covid-19 pandemic showed higher infection, severity and death rates among those living in poorer socioeconomic conditions. We use syndemic theory to guide the analyses to investigate the impact of social adversity and multiple long-term conditions (MLTC) on Covid-19 mortality.

Methods

The study sample comprised 154 725 UK Biobank participants. Structural equation modeling was used to investigate pathways between traumatic events, economic deprivation, unhealthy behaviors, MLTC, for Covid-19 mortality. Cox regression analysis was used to investigate MLTC and Covid-19 mortality. We also tested effect modification by traumatic events, economic deprivation and unhealthy behaviors.

Results

Covid-19 mortality (n = 186) was directly explained by overall level of MLTC. Economic deprivation and unhealthy behaviors contributed to Covid-19 death indirectly via their negative impact on MLTC. The risk for Covid-19 mortality grew exponentially for every quintile of predicted scores of MLTC. The presence of traumatic events, economic deprivation or unhealthy behaviors did not modify the impact of MLTC on Covid-19 mortality.

Conclusions

Results suggest a serially causal pathway between economic deprivation and unhealthy behaviors leading to MLTC, which increased the risk of Covid-19 mortality. Policies to tackle the social determinants of health and to mitigate the negative impact of multimorbidity are needed.
Do trees use stemflow water? A manipulative experiment on Singleleaf piñon and Utah juniper in Great Basin woodlands
Authors: Snyder Keirith A , Morrow Amira C , Stringham Tamzen K , Allen Scott T
Published: December 2024

It has been postulated that stemflow, precipitation that flows from plant crowns down along branches and stems to soils, benefits plants that generate it because it increases plant-available soil water near the base of the plant; however, little direct evidence supports this postulation. Were plants’ crowns to preferentially route water to their roots, woody plants with large canopies could benefit. For example, piñon and juniper tree encroachment into sagebrush steppe ecosystems could be facilitated by intercepted precipitation routed to tree roots as stemflow, hypothetically reducing water available for shrubs and grasses. We tested whether Great Basin piñon and juniper trees use and benefit from stemflow. In a drier-than-average and wetter-than-average water year, isotopically labeled water was applied to tree stems to simulate stemflow. Both species took up stemflow, with label signals peaking and receding over 2–4 days. Despite this uptake, no alleviation of water stress was detected in the drier year. The stemflow uptake resulted in some water stress alleviation in the wetter year, specifically for piñons, which took up water from deeper in the soil profile than did junipers. Mixing model analyses suggested that stemflow was a small fraction of the water in stems (⁓0–2%), but an order-of-magnitude larger fraction of the stemflow was transpired in those few days after addition. These findings represent a novel demonstration of the rapid uptake and use of stemflow that infiltrates the rhizosphere, but they also prompt questions about the remaining stemflow’s fate and why alleviation of water stress was so minor.
Correction of Ankle Malalignment in Severe Fibular Hemimelia
Authors: Shadi Milud , Janusz Piotr , Kotwicki Tomasz
Published: December 2024

Background:

Management of ankle joint deformity and instability are challenging issues in congenital fibular hemimelia (FH). This study aims to assess how much the SUPERankle procedure improves ankle alignment and provides durable ankle stability in patients with severe FH.

Methods:

Seventeen children aged 53.4±44.1 months with severe form of FH, equinovalgus foot deformation, ankle instability, and tibial curvature (Paley type IIIC), affecting 19 limbs, underwent the SUPERankle procedure. Foot and ankle position was evaluated clinically and radiologically before surgery, immediately after, and at follow-up of 63.0±19.7 months. Mechanical lateral distal tibial angle (mLDTA), tibiocalcaneal angle (mTCA), and tibiocalcaneal distance (mTCD) were measured on the AP radiograms, while the anterior distal tibial angle (mADTA) and lateral tibiocalcaneal angle (mLTCA) were measured on the lateral radiograms. Recurrences, additional procedures, and complications were documented based on medical records. Quality of life was evaluated with Limb Deformity-SRS questionnaire.

Results:

On clinical examination, the normal tibia and ankle alignment, along with a plantigrade foot were achieved in all limbs after the first surgery. In 11 limbs (58%) this result was maintained at follow-up. Due to recurrence, additional procedures were necessary to provide durable ankle alignment in 7 limbs (37%), while in 1 limb (5%) the ankle joint remained in equinus at the last follow-up. Significant improvement of radiologic alignment was found in all parameters (preoperative vs. postoperative vs. FU) as follows—mLDTA: 71.4±11.2 versus 88.7±5.6 versus 88.1±2.7 degrees, P=0.0001; mTCA: 41.4±14.9 versus 8.7±8.4 versus 11.6±8.9 degrees, P=0.0001; mTCD: 22.3±7.9 versus 4.0±3.6 versus 7.7±6.5 mm, P=0.0001; mADTA: 99.5±19.4 versus 82.3±4.2 versus 81.5±5.9 degrees, P=0.0002; mLTCA: 116.7±23.9 versus 95.8±11.7 versus 93.5±15.1 degrees, P=0.0002. The mean follow-up LD-SRS score was 4.03.

Conclusion:

In children with severe fibular hemimelia, the SUPERankle procedure provided clinically and radiologically fully corrected ankle joint and plantigrade foot, suitable for further lengthening procedure. The 40% rate of deformity recurrence was managed with additional surgical intervention to achieve a good clinical, radiologic, and functional outcome in 95% of children at 5-year follow-up.

Level of Evidence:

Level IV.
Efficacy of Nonablative Bipolar Radiofrequency in the Treatment of Fingernail Psoriasis
Authors: El-Basiony Mohamed Ahmed Salem , El-Komy Mohamed Hussein Medhat , Samy Nevien Ahmed , Aly Dalia Gamal , El-Gendy Hala , Soliman Mohamed Mohsen , Abdel Salam Hassan Mohamed Fouad , El Sayed Hagar
Published: December 2024

BACKGROUND

Psoriasis is a common chronic systemic disease affecting the skin, nails, and joints. Nails are commonly associated with a greater severity of the disease. Radiofrequency (RF) is a nonionizing radiation that provides energy originating from electric current to generate heat inside the dermis with anti-inflammatory effects.

OBJECTIVE

To assess the efficacy of nonablative bipolar radiofrequency in treating fingernail psoriasis.

METHODS

Forty-three affected fingernails were treated with nonablative bipolar RF. Sessions were performed every 2 weeks for 2 months, with a maximum of 5 sessions. The 32-point target nail psoriasis severity index (tNAPSI), ultrasonography, and the physicians' global assessment were used for assessment at baseline, 1 month, and 3 months from the last treatment session.

RESULTS

One month after the last RF session, a significant reduction in median tNAPSI score from baseline was recorded (p = .002), with a 58.33% reduction in pit count. The median thickness of subungual hyperkeratosis decreased significantly from baseline (p = .024), and the median score of onycholysis was also significantly reduced (p = .005). Ultrasonography revealed a significant reduction in the median nail matrix, bed thickness, and nail vascularity (p = .020, p < .001, and p = .013, respectively).

CONCLUSION

Radiofrequency may offer a safe and effective treatment modality for fingernail psoriasis.
Diagnostic efficacy of cytologic smear and pathologic histology in the differential diagnosis of distal biliary stricture via EUS-guided fine-needle aspiration
Authors: Liang Zheng , Li Peng , Han Xiao , Zhang Shutian , Wei Yongqiu
Published: December 2024

Background and Objectives

Distal biliary strictures (DBSs) can be caused by various malignancies, making accurate and early diagnosis crucial. Histopathology is the gold standard for diagnosis, with several methods available for tissue sampling. This study evaluates the performance of EUS-guided fine-needle aspiration (EUS-FNA) cytologic smears and histopathology in diagnosing suspected malignant DBSs.

Methods

A retrospective cohort study was conducted on patients who underwent EUS-FNA between January 2017 and January 2023 for DBSs. Demographic, imaging, procedural, and clinical data were collected. The diagnostic performance of EUS-FNA cytology, histology, and their combination was assessed in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Subgroup analyses were conducted based on imaging and endoscopy characteristics.

Results

EUS-FNA for cytology had a sensitivity of 69.1% and specificity of 97.5%. EUS-FNA histology had a sensitivity of 76.4% and specificity of 99.1%. There was no difference in diagnostic efficacy between the two above (P > 0.05). Combining cytology and histology improved sensitivity to 82%. When 20 cases (6.8%) with histological slide failures were considered as negative, histologic sensitivity was 69.1%, completely consistent with cytology alone (P = 1). The presence of a mass shadow on computed tomography or magnetic resonance imaging was associated with higher cytologic diagnostic sensitivity compared with simple stenosis without a mass shadow (57.4% vs. 75.9%, P = 0.011). The larger the mass, the higher the cytologic diagnostic sensitivity. The radiologist’s diagnostic imaging tendencies, that is, malignant, benign, and indeterminate, also affected cytologic diagnostic sensitivity (78.2% vs. 63.9% vs. 51.9%, P = 0.002). Furthermore, among our cohort of 118 patients diagnosed with benign DBSs, a notable subset of 33 individuals (28%) received a diagnosis of IgG4-related disease.

Conclusion

EUS-FNA histology combined with cytology was a reliable diagnostic method. There is no difference in diagnostic efficacy between EUS-FNA cytology and histology, irrespective of considering instances of histological slide failure. The presence of a mass shadow on computed tomography or magnetic resonance imaging and the size of the mass influenced the diagnostic efficacy of cytology. Additionally, IgG4-related diseases, accounting for a significant proportion of cases, were important in the differential diagnosis of these strictures.
CATALYZE: a deep learning approach for cataract assessment and grading on SS-OCT images
Authors: Panthier Christophe , Zeboulon Pierre , Rouger Helene , Bijon Jacques , Gatinel Damien
Published: December 2024

Purpose:

To assess a new objective deep learning model cataract grading method based on swept-source optical coherence tomography (SS-OCT) scans provided by the Anterion.

Setting:

Single-center study at the Rothschild Foundation, Paris, France.

Design:

Prospective cross-sectional study.

Methods:

All patients consulting for cataract evaluation and consenting to study participation were included. History of previous ocular surgery, cornea or retina disorders, and ocular dryness were exclusion criteria. Our CATALYZE pipeline was applied to Anterion image providing layerwise cataract metrics and an overall clinical significance index (CSI) of cataract. Ocular scatter index (OSI) was also measured with a double-pass aberrometer (OQAS) and compared with our CSI.

Results:

548 eyes were included, 331 in the development set (48 with cataract and 283 controls) and 217 in the validation set (85 with cataract and 132 controls) of 315 patients aged 19 to 85 years (mean ± SD: 50 ± 21 years). The CSI correlated with the OSI (r
2 = 0.87, P < .01). CSI area under the receiver operating characteristic curve (AUROC) was comparable with OSI AUROC (0.985 vs 0.981 respectively, P > .05) with 95% sensitivity and 95% specificity.

Conclusions:

The deep learning pipeline CATALYZE based on Anterion SS-OCT may be a reliable and comprehensive objective cataract grading method.
Transmission rates of UV-A and green light in an ex vivo corneal crosslinking model for infectious keratitis
Authors: Lu Nan-Ji , Meier Philipp , Reina Giacomo , Aydemir M. Enes , Eitner Stephanie , Koliwer-Brandl Hendrik , Egli Adrian , Kissling Vera , Wick Peter , Hafezi Farhad
Published: December 2024

Purpose:

To investigate the light transmission (LT) of UV-A and green light through infected corneas saturated with riboflavin or rose bengal in an ex vivo porcine model for infectious keratitis.

Setting:

University of Zurich, Zurich, Switzerland, and Empa, St. Gallen, Switzerland.

Design:

Laboratory study.

Methods:

Ex vivo porcine eyes (n = 162) were divided into 3 groups: control eyes, eyes infected with Staphylococcus aureus, and eyes infected with Pseudomonas aeruginosa. Corneas remained either uninfected or were infected with S. aureus and P. aeruginosa and were either left untreated or were instilled with 0.1% riboflavin or 0.1% rose bengal. Corneal buttons were prepared, and corneal LT was measured at 365 nm and 522 nm using a spectrophotometer. LT values were calculated and compared. Transmission electron microscopy (TEM) was used to visualize structural damage and bacteria within infected corneas.

Results:

Riboflavin-saturated corneas infected by S. aureus or P. aeruginosa (LT = 0.77% [0.41-1.87] and 0.81% [0.23, 1.46]) exhibited 3.18-fold and 3.02-fold lower LT values, respectively, than uninfected corneas (LT = 2.45% [2.15, 5.89]) (both P-values < 0.001). No LT difference was found between rose bengal–saturated corneas infected by S. aureus or P. aeruginosa and uninfected corneas (all LT values = 0.01% [0.01-0.01]; both P-values = 0.08). TEM showed bacteria on corneal stroma borders and occasionally inside the stroma.

Conclusions:

The results indicate that the amount of light arriving at the corneal endothelium is substantially reduced in infected corneas. The total fluence of clinical photoactivated chromophore for keratitis corneal crosslinking protocols can be safely increased substantially while maintaining a low risk of corneal endothelial damage.
The association of serum manganese concentrations with all-cause, cardiovascular disease and cancer mortality: A cohort study based on the 2011–2014 National Health and Nutrition Examination Survey (NHANES)
Authors: Tang Jie , Zhu Li-Qun , Chen Xiao-Feng , Jin Ke , Shu Yong-Qian
Published: December 2024

Objectives

There is a debate on the association between the circulating manganese (Mn) levels and mortality. The aim of this study was to explore the nonlinear association between the serum Mn levels and all-cause or cause-specific mortality.

Methods

We included 8,145 adults from the United States (US) and their serum Mn concentrations obtained from the National Health and Nutrition Examination Survey (NHANES 2011–2014). We retrieved their survival information from baseline until 2019 using the national death index. Multivariable Cox proportional hazards models were used to show the risk of all-cause or cause-specific mortality according to the baseline serum Mn concentrations. Smooth curve fitting and threshold effect analyses were used to clarify the potential nonlinearity.

Results

During a median follow-up of 6.2 years, there were 716 deaths from all causes, 224 of which were due to cardiovascular disease (CVD) and 165 due to cancer. The serum Mn levels exhibited a U-shaped relationship with all-cause or CVD-associated mortality. Serum Mn levels lower than the threshold value (7.32 μg/L) were negatively associated with all-cause (fully adjusted HR: 0.86, 95% CI: 0.80–0.94) and CVD (fully adjusted HR: 0.82, 95% CI: 0.71–0.94) mortality. In contrast, serum Mn levels higher than the threshold value (7.32 μg/L) were positively associated with all-cause (fully adjusted HR: 1.04, 95% CI: 1.02–1.06) and CVD (fully adjusted HR: 1.05, 95% CI: 1.02–1.08) mortality.

Conclusions

The serum Mn concentrations showed a U-shaped relationship with all-cause and CVD-associated mortality among NHANES participants.