bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Efficacy of Selection on a Young Z Chromosome Region of Schistosoma japonicum
Authors: Mrnjavac Andrea , Vicoso Beatriz
Published: February 2025

Sex-linked and autosomal loci experience different selective pressures and evolutionary dynamics. X (or Z) chromosomes are often hemizygous in males (or females), as Y (or W) chromosomes often degenerate. Such hemizygous regions can be under greater efficacy of selection, as recessive mutations are immediately exposed to selection in the heterogametic sex leading to faster adaptation and faster divergence on the X chromosome (the so-called Faster-X or Faster-Z effect). However, in young nonrecombining regions, Y/W chromosomes often have many functional genes, and many X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on the X/Z by the Y/W homolog is expected to drive slower adaptation for diploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect has been studied extensively, much less is known empirically about the evolutionary dynamics of diploid X or Z chromosomes. Here, we took advantage of published population genomic data in the female-heterogametic human parasite Schistosoma japonicum to characterize the gene content and diversity levels of the diploid and hemizygous regions of the Z chromosome. We used different metrics of selective pressures acting on genes to test for differences in the efficacy of selection in hemizygous and diploid Z regions, relative to autosomes. We found consistent patterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both hemizygous and diploid Z regions. Moreover, relaxed selection was particularly pronounced for female-biased genes on the diploid Z, as predicted by recent theoretical work.
Stratifying and predicting progression to acute liver failure during the early phase of acute liver injury
Authors: Yoshimura Raiki , Tanaka Masatake , Kurokawa Miho , Nakamura Naotoshi , Goya Takeshi , Imoto Koji , Kohjima Motoyuki , Fujiu Katsuhito , Iwami Shingo , Ogawa Yoshihiro
Published: February 2025

Acute liver failure (ALF) is a serious disease that progresses from acute liver injury (ALI) and that often leads to multiorgan failure and ultimately death. Currently, effective treatment strategies for ALF, aside from transplantation, remain elusive, partly because ALI is highly heterogeneous. Furthermore, clinicians lack a quantitative indicator that they can use to predict which patients hospitalized with ALI will progress to ALF and the need for liver transplantation. In our study, we retrospectively analyzed data from 319 patients admitted to the hospital with ALI. By applying a machine-learning approach and by using the SHapley Additive exPlanations (SHAP) algorithm to analyze time-course blood test data, we identified prothrombin time activity percentage (PT%) as a biomarker reflecting individual ALI status. Unlike previous studies predicting the need for liver transplantation in patients with ALF, our study focused on PT% dynamics. Use of this variable allowed us to stratify the patients with highly heterogeneous ALI into six groups with distinct clinical courses and prognoses, i.e. self-limited, intensive care–responsive, or intensive care–refractory patterns. Notably, these groups were well predicted by clinical data collected at the time of admission. Additionally, utilizing mathematical modeling and machine learning, we assessed the predictability of individual PT% dynamics during the early phase of ALI. Our findings may allow for optimizing medical resource allocation and early introduction of tailored individualized treatment, which may result in improving ALF prognosis.
Glycosyltransferase-Like Toxin of Burkholderia gladioli Strain NGJ1 Is a Potent Antifungal Protein with Potential for Control of Sheath Blight Disease in Rice
Authors: Pradhan Amrita , Yadav Sunil K. , Jha Gopaljee
Published: February 2025

Sheath blight disease caused by the fungal pathogen Rhizoctonia solani poses a great challenge for sustainable rice cultivation. It is important to develop environment-friendly measures for its control. Previously, a rice-associated Burkholderia gladioli strain NGJ1 has been shown to exhibit mycophagous and antifungal activity on R. solani. Here we report that a glucosyltransferase-like (BGT1) protein with a canonical DxD motif that is homologous to glycosyltransferase (GT) toxin of different bacteria is encoded in the antibacterial type VI secretion system (T6SS) encoding gene cluster of NGJ1. The recombinant BGT1 protein purified from Escherichia coli exhibits antifungal activity on R. solani, Magnaporthe oryzae, Fusarium oxysporum, Saccharomyces cerevisiae, and Candida albicans, under laboratory conditions. Using a variant of BGT1 protein (BGT1D168L/D170L), we demonstrate that DxD motif is important for its antifungal activity. The heterologous expression of native BGT1 but not BGT1D168L/D170L protein prevents the growth of yeast cells. Moreover, treatment with BGT1 but not BGT1D168L/D170L significantly reduces sheath blight disease severity in rice. BGT1 treatment does not elicit adverse effects on plants. In conclusion, we emphasize that BGT1 protein-based or transgene-based biotechnological interventions can be exploited for effective control of sheath blight disease in rice.
Hybrid Epithelioid Schwannoma/Neurofibroma: A Report of 3 Cases
Authors: Mitsui Yasuhiro , Ishida Eiwa , Ogawa Kohei , Fukumoto Takaya , Asada Hideo
Published: February 2025

Peripheral nerve sheath tumors can include neurofibroma, schwannoma, and perineurioma, with hybrid nerve sheath tumor (HNST) being rare. We describe 3 HNST cases with epithelioid schwannoma and neurofibroma features, an uncommon manifestation of hybrid schwannoma/neurofibroma. The 3 cases involved the upper back, forearm, and thigh. Histopathologically, the tumors were located in the subcutis or dermis and subcutis. The epithelioid schwannoma component showed nests/cords of epithelioid cells with round nuclei and abundant cytoplasm. In contrast, the neurofibroma component showed spindle cell proliferation within myxoid stroma. The 3 cases showed variable proportions of both components. Immunohistochemically, the epithelioid schwannoma components were positive for S100 protein and negative for CD34, whereas the neurofibroma component showed partial S100 immunoreactivity and contained abundant CD34-positive cells with a fingerprint pattern. Epithelial membrane antigen and GLUT1 revealed the perineurial capsules. In conclusion, our cases expand the morphologic spectrum of HNST and underscore the importance of recognizing this variant.
“CONCURRENT INTRACRANIAL TUBERCULOMAS AND SPINAL TUBERCULOSIS WITH MULTIFOCAL ABSCESSES: A RARE CASE REPORT”
Authors: Thakur Alok Chandra , Sedain Gopal , Chhantyal Sangit , Mishra Amit Kumar , Gajurel Bikram Prasad
Published: February 2025

Introduction:

Neurotuberculosis is a severe form of tuberculosis affecting the central nervous system, manifesting as tuberculomas or abscesses. Simultaneous intracranial and spinal tuberculomas with abscesses are exceptionally rare, presenting unique diagnostic and therapeutic challenges.

Case presentation:

A 40-year-old female presented with headaches, seizures, and lower limb weakness. MRI revealed multiple intracranial and spinal tuberculomas with abscesses. She was treated with antitubercular therapy and corticosteroids, along with surgical drainage, leading to significant improvement.

Discussion:

Neurotuberculosis can present without evident pulmonary involvement, making early diagnosis crucial. MRI plays a key role in identifying tuberculomas, which must be differentiated from other lesions such as neurocysticercosis or gliomas. Conservative management with ATT and steroids is often effective, particularly in resource-limited settings. Surgical intervention is reserved for cases with severe neurological deficits or diagnostic uncertainty.

Conclusion:

This case highlights the need to consider neurotuberculosis in patients with neurological symptoms, especially in endemic areas. The rarity of concurrent intracranial and spinal tuberculomas with abscesses requires a multidisciplinary approach for early diagnosis and effective management.
Insomnia remission and improvement of bodily pain in older adults: a randomized clinical trial
Authors: Bjurstrom Martin F. , Olmstead Richard , Irwin Michael R.
Published: February 2025

Introduction:

Older adults with insomnia frequently report bothersome pain. Whether insomnia treatment reduces bodily pain in older adults without chronic pain conditions is not known.

Objectives:

This randomized controlled trial aimed to determine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I), as compared with sleep education therapy (SET), yields durable remission of insomnia and reduces moderate pain symptoms over 36 months in older adults with insomnia disorder.

Methods:

A community-based sample of 291 adults ages 60 years and older (mean age, 70.1 years; 57.7% female) with insomnia disorder, but no chronic pain condition, were randomized to 2 months of intervention with either CBT-I (n = 156) or SET (n = 135). The primary outcome was change in bodily pain as measured by the short form 36 (SF-36) health survey. Secondary outcome was remission of insomnia continuously sustained over 36 months of follow-up.

Results:

Improvements in bodily pain, as indexed by increases in SF-36 scores, were found in CBT-I with insomnia remission (adjusted β = 0.18; 95% CI, 0.004–0.360; P = 0.045) and in SET with insomnia remission (adjusted β = 0.25; 95% CI, 0.035–0.457; P = 0.023) but not in treatment groups without insomnia remission. As compared with those without insomnia remission, insomnia remission was associated with improvements in pain (adjusted β = 0.19; 95% CI, 0.047–0.325; P = 0.009) and with increases in the proportion of participants who achieved a minimal clinically important difference (likelihood ratio χ2
1,16 = 264.04; P < 0.001).

Conclusions:

Sustained remission of insomnia disorder leads to improvements in bodily pain, with the potential to prevent chronic pain disorders in older adults with insomnia.

Trial Registration:

ClinicalTrials.gov NCT01641263.
Neighborhood deprivation is a risk factor for severe child physical abuse: A multicenter cohort investigation
Authors: Wilson Nicole A. , Ruffolo Luis , Juviler Peter , Fabiano Tiffany , Kelly William , Lillvis Denise , Edwards Mary , Vu Natalie , Chiou Ryan , Wallenstein Kim , Craven Amanda , Klein-Cloud Rafael , Bullaro Francesca , Philipose Jency , Salik Irim , Fisher John , Wakeman Derek S.
Published: February 2025

BACKGROUND

Our purpose was to investigate whether neighborhood deprivation is associated with outcomes in a multicenter population of children with suspected or confirmed child physical abuse. We hypothesized that community level social determinants of health are associated with worse outcomes following child physical abuse.

METHODS

This multicenter retrospective review included children (18 years or younger) admitted with suspected or confirmed physical abuse at six pediatric trauma centers. A national Area Deprivation Index (ADI) score was assigned to each patient based on home address. Area Deprivation Index was divided into quartiles using the distribution of our dataset. Exclusion of a caregiver at discharge was used as a proxy for confirmed physical abuse. Descriptive statistics and stepwise logistic regression were used to identify covariates. Multiple logistic regression was used to test for associations between ADI and caregiver exclusion.

RESULTS

Of 1,105 included patients, 512 had confirmed abuse. These patients were younger (median [interquartile range], 0.50 [1.50] vs. 0.83 [1.67]; p = 0.002), more likely to be Black or African American (28.3% vs. 19.5%, p < 0.001), and had higher ADI scores (81.0 [35.0] vs. 66.0 [60.0], p < 0.001). A dose-dependent relationship between ADI and caregiver exclusion was identified. Compared with those from the least vulnerable neighborhoods (ADI first quartile), patients from the most vulnerable neighborhoods (ADI fourth quartile) had 2.65 (95% confidence interval, 1.73–4.08; p < 0.001) times higher odds of confirmed abuse. Despite no differences in Injury Severity Scores (8.0 [6.0] vs. 9.0 [10.0], p = 0.163), they also had longer lengths of hospital stay (1.0 [2.0] vs. 3.0 [2.8], p = 0.002) and higher mortality (1.5% vs. 5.0%, p = 0.028).

CONCLUSION

This large multicenter experience demonstrates a dose-dependent relationship between socioeconomic disadvantage and child physical abuse. We further demonstrate that disadvantage is associated with worse outcomes, including increased mortality, in child physical abuse. These findings provide objective data and lead to suggestions for interdisciplinary and multiscale approaches to primary prevention of child physical abuse.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
CiFi: Accurate long-read chromatin conformation capture with low-input requirements
Authors: McGinty Sean P. , Kaya Gulhan , Sim Sheina B. , Corpuz Renée L. , Quail Michael A. , Lawniczak Mara K. N. , Geib Scott M. , Korlach Jonas , Dennis Megan Y.
Published: February 2025

By coupling chromatin conformation capture (3C) with PacBio HiFilong-read sequencing, we have developed a new method (CiFi) that enables analysis of genome interactions across repetitive genomic regions with low-input requirements. CiFi produces multiple interacting concatemer segments per read, facilitating genome assembly and scaffolding. Together, the approach enables genomic analysis of previously recalcitrant low-complexity loci, and of small organisms such as single insect individuals.
Higher throughput assays for understanding the pathogenicity of variants of unknown significance (VUS) in the RPE65 gene
Authors: Pormehr Leila Azizzadeh , Manian Kannan Vrindavan , Cho Ha Eun , Comander Jason
Published: February 2025

Purpose

RPE65is a key enzyme in the visual cycle that regenerates 11-cis retinal. Mutations inRPE65cause a retinal dystrophy that is treatable with an FDA-approved gene therapy. Variants of unknown significance (VUS) on genetic testing can prevent patients from obtaining a firm genetic diagnosis and accessing gene therapy. Since mostRPE65mutations have a low protein expression level, this study developed and validated multiple methods for assessing the expression level ofRPE65variants. This functional evidence is expected to aid in reclassifyingRPE65VUS as pathogenic, which in turn can broaden the application of gene therapy forRPE65patients.

Methods

30 different variants ofRPE65(12 pathogenic, 13 VUS, 5 benign) were cloned into lentiviral expression vectors. Protein expression levels were measured after transient transfection or in stable cell lines, using Western blots and immunostaining with flow cytometry. Then, a pooled, high throughput, fluorescence-activated cell sorting (FACS) assay with an NGS-based sequencing readout was used to assay pools ofRPE65variants.

Results

There was a high correlation between protein levels measured by Western blot, flow cytometry, and the pooled FACS assay. Using these assays, we confirm and extendRPE65variant data, including that Pro111Ser has a low, pathogenic expression level. There was a high correlation between RPE65 expression and previously reported enzyme activity levels; further development of a high throughput enzymatic activity assay would complement this expression data.

Conclusion

This scalable approach can be used to solve patient pedigrees with VUS inRPE65, facilitating treatment and providingRPE65structure-function information.
A CDE-based data structure for radiotherapeutic decision-making in breast cancer
Authors: Dennstädt Fabio , Schmalfuss Maximilian , Zink Johannes , Hastings Janna , Gaio Roberto , Schmerder Max , Putora Paul Martin , Cihoric Nikola
Published: February 2025

Background

The increasing complexity and data-driven nature of oncology and radiation therapy necessitates structured and precise data management strategies. The National Institutes of Health (NIH) has introduced Common Data Elements (CDEs) as a uniform approach to facilitate consistent data collection. However, there is currently a lack of a comprehensive set of CDEs for describing situations for and within radiation oncology. Aim of this study was to create a CDE-based data structure for radiotherapeutic decision-making in breast cancer to promote structured data collection on the level of a local hospital.

Methods

Local Standard Operating Procedures (SOPs) were analyzed to identify relevant decision-making criteria used in clinical practice. Corresponding CDEs were identified and a structured data framework based on these CDEs was created. The framework was translated into machine-readable JSON format. Six clinical practice guidelines of the American Society for Radiation Oncology (ASTRO) were analyzed as full-text to investigate how many guideline recommendations and corresponding decision-making criteria could be presented using the data structure.

Results

The study identified 31 decision-making criteria mentioned in the SOPs, leading to the establishment of 46 CDEs. A hierarchical structure within an object-oriented data framework was created and converted into JSON format. 94 recommendations with mentioning of decision-making criteria in 216 cases were identified across the six ASTRO guidelines. In 151 cases (70.0%) the mentioned criterion could be presented with the data framework.

Conclusions

The CDE-based data structure represents a clear framework for structuring medical data for radiotherapeutic decision-making in breast cancer patients. The approach facilitates detailed description of individual breast cancer cases and aids in the integration of information technology. Furthermore, it promotes sharing of standardized data among healthcare providers.
Impact of climatic variations on the global distribution and prevalence of Mpox disease: Analysis of data from 52 countries using linear regression and time forecasting analyses.
Authors: Ojo Iyanuloluwa Samuel , Badero Olurotimi John , Rahman Muhammad Aziz , Aderinto Nicholas , Oral Onur , Robin Rishad Choudhury , Dansu Emmanuel Jesuyon , Ogunjimi Temitope , Ibidun Faridat
Published: February 2025

MPOX infection has become a global health concern. Despite this global concern, the disease has shown epidemiological variations across different countries. This study examines the impact of climatic variations on MPOX prevalence and mortality using quantitative, cross-sectional approach. We analyzed daily confirmed MPOX cases from 52 countries using linear regression and Prophet models, focusing on average mean surface air temperature, precipitation, and climate types based on the Köppen classification.Globally, no significant relationship was found between temperature, precipitation, and MPOX prevalence (p-values 0.99 and 0.82); no significance was also noted for mortality globally (p-values 0.45 and 0.54). However, temperature had a more substantial impact on MPOX prevalence in Europe and South America (p-values of 0.049 and 0.0036, respectively). Precipitation was also significant in South America (p-value 0.044). The Prophet model, accounting for seasonality, revealed fluctuating influences of temperature and precipitation on MPOX prevalence, with their effects diminishing over time. Tropical and temperate climate types were most strongly associated with increased MPOX transmission. Monitoring these climatic factors, particularly in affected regions, is crucial for understanding and mitigating MPOX spread and its associated mortality.
Network-aware self-supervised learning enables high-content phenotypic screening for genetic modifiers of neuronal activity dynamics
Authors: Grosjean Parker , Shevade Kaivalya , Nguyen Cuong , Ancheta Sarah , Mader Karl , Franco Ivan , Heo Seok-Jin , Lewis Greyson , Boggess Steven , Di Domenico Angelique , Ullian Erik , Shafer Shawn , Litterman Adam , Przybyla Laralynne , Keiser Michael J. , Ifkovits Jamie , Yala Adam , Kampmann Martin
Published: February 2025

High-throughput phenotypic screening has historically relied on manually selected features, limiting our ability to capture complex cellular processes, particularly neuronal activity dynamics. While recent advances in self-supervised learning have revolutionized the ability to study cellular morphology and transcriptomics, dynamic cellular processes have remained challenging to phenotypically profile. To address this limitation, we developed Plexus, a novel self-supervised model specifically designed to capture and quantify network-level neuronal activity dynamics. Unlike existing phenotyping tools that focus on static readouts, Plexus leverages a novel network-level cell encoding method, which enables it to efficiently encode dynamic neuronal activity data into rich representational embeddings. In turn, Plexus achieves state of the art performance in detecting phenotypic changes in neuronal activity. We validated Plexus using a comprehensive GCaMP6m simulation framework and demonstrated its enhanced ability to classify distinct neuronal activity phenotypes compared to traditional signal-processing approaches. To enable practical application, we integrated Plexus with a scalable experimental system utilizing human iPSC-derived neurons equipped with the GCaMP6m calcium indicator and CRISPR interference machinery. This integrated platform successfully identified nearly twice as many distinct phenotypic changes in response to genetic perturbations compared to conventional methods, as demonstrated in a 52-gene CRISPRi screen across multiple iPSC lines. Using this framework, we identified potential genetic modifiers of aberrant neuronal activity in frontotemporal dementia, illustrating its utility for understanding complex neurological disorders.
EPHA2 and scavenger receptor-directed trafficking enhances endosomal leakiness and antisense therapy delivery
Authors: Marco Sergi , Walsh Peter J. , Revenko Alexey S. , Thomason Peter A. , McGarry Lynn , MacLeod A. Robert , Ansell Sonam , Tataran Dina , Bushell Martin , Braconi Chiara , Norman Jim C.
Published: February 2025

The potential for using therapeutic antisense oligonucleotides (ASOs) has been hampered by lack of understanding of how they enter cells and subsequently access their targets. Endocytosis contributes to ASO uptake, but the machinery mediating subsequent ASO trafficking to permit suppression of their target mRNAs has not been described. Here, we show that ASO engagement with a scavenger receptor (CD44) activates the ERK-RSK axis to promote serine phosphorylation of a receptor tyrosine kinase (EPHA2). Serine phosphorylation of EPHA2 permits endocytosis, trafficking, and accumulation of ASOs in nuclear-adjacent endosomes. These endosomes then become leaky, allowing ASOs to escape and effectively suppress target mRNA expression. Inhibition of stress granule-mediated repair of leaky endosomes further enhances ASO effectiveness. These data identify an endocytic route to the nucleus which may be exploited to maximise effectiveness of ASO-mediated therapies.
Mechanism of counterattack against eIF2α kinase immune signalling by viral pseudo-kinase PK2
Authors: Takeshita Daijiro , Takagi Yuko
Published: February 2025

Viral infection triggers the activation of host innate immune responses, including the integrated stress response (ISR). The antiviral response is mediated by the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) catalyzed by host eIF2α kinase, resulting in suppression of global protein synthesis and induction of selected genes in the cell. To evade and/or subvert the host antiviral signalling pathway, viruses have evolved and harnessed elaborate counter-attack mechanisms to repress the activation of host eIF2α kinase. In insects, eIF2α kinase-mimic protein PK2 encoded in baculovirus directly binds to and inhibits host eIF2α kinase for viral propagation. However, the mechanism underlying how viral PK2 recognizes host eIF2α kinase and interrupts its activity has remained unclear. Here we present a series of crystal structures of apo PK2 and its complex with eIF2α kinase, revealing a conformational transition mechanism of PK2 for eIF2α kinase inhibition. PK2 alone, comprised of an N-terminal extension (NTE) and eIF2α kinase C-lobe mimic (EKCM), adopted a two-fold symmetric homotetramer assembled mainly by the NTE region. Pull-down assay identified a region ofBombyx moriHRI-like kinase (BmHRI) that binds to PK2, and its complex structure revealed that the PK2-binding region of BmHRI, subdomain III-IV, is entrapped in a newly formed groove between the NTE region and EKCM of PK2. The structural data, together with biochemical analyses, indicated that PK2 suppresses eIF2α kinase activity by the pullout and subsequent blockade of the subdomain III-IV, a regulatory element essential for its kinase activity. These results not only provide the molecular mechanisms for the inhibition of host eIF2α kinase by viral pseudo-kinase, but also unveil the viral evolutionary strategy to shut-off host immunity via horizontal gene transfer from host to virus.
Cognitive maps for hierarchical spaces in the human brain
Authors: Peer Michael , Epstein Russell A.
Published: February 2025

Many of the environments that we navigate through every day are hierarchically organized—they consist of spaces nested within other spaces. How do our mind/brains represent such environments? To address this question, we familiarized participants with a virtual environment consisting of a building within a courtyard, with objects distributed throughout the courtyard and building interior. We then scanned them with fMRI while they performed a memory task that required them to think about spatial relationships within and across the subspaces. Behavioral responses were less accurate and response times were longer on trials requiring integration across the subspaces compared to trials not requiring integration. fMRI response differences between integration and non-integration trials were observed in scene-responsive and medial temporal lobe brain regions, which were correlated the behavioral integration effects in retrosplenial complex, occipital place area, and hippocampus. Multivoxel pattern analyses provided additional evidence for representations in these brain regions that reflected the hierarchical organization of the environment. These results indicate that people form cognitive maps of nested spaces by dividing them into subspaces and using an active cognitive process to integrate the subspaces. Similar mechanisms might be used to support hierarchical coding in memory more broadly.
Copper-controlled gene expression via transmembrane-induced ribosomal stalling
Authors: Öztürk Yavuz , Shen Kai-Wei , Emmanuel Philip , Daldal Fevzi , Koch Hans-Georg
Published: February 2025

Regulated gene expression in response to metabolite sensing is a fundamental process for cellular adaptation and survival. Cells have developed diverse strategies to detect and respond to various metabolites in their environment. Here, we have identified a post-transcriptional mechanism inRhodobacter capsulatusthat integrates the periplasmic Cu concentration into the translational control of the copper detoxifying enzyme CutO. This is achieved through Cu-induced stalling of the nascent CutF protein inside the ribosomal peptide tunnel during co-translational secretion. Stalling at a C-terminal proline-rich motif overrides the function of elongation factor P (EF-P) and allows melting of an mRNA stem-loop that shields thecutOribosome-binding site. Thus, CutF acts as a transmembrane Cu sensor that controls CutO production via ribosomal stalling. Considering that CutF is a member of the widely distributed bacterial DUF2946 protein family, the mechanism identified here likely represents a conserved bacterial strategy for adapting to toxic heavy metals.
Systemic Factors Affect Bone Health in SMA Type II Patients and a Mouse Model of SMA
Authors: Grandi Fiorella Carla , Pezet Sonia , Arnould Alice , Mazzucchi Sabrina , Gidaja Elèna , Astord Stéphanie , Chapart Maud , Vasseur Stéphane , Ricupero Alessandra , Ernu Matteo , Sampaio Yasmim , Cohen-Tannoudji Mathilde , Meunier Pierre , Benkhelifa-Ziyyat Sofia , Miladi Lofti , Vialle Raphael , Smeriglio Piera
Published: February 2025

Spinal muscular atrophy (SMA) is a rare developmental disorder affecting multiple tissues. Among the non-central nervous system tissues implicated in SMA is the skeletal system, including bone and cartilage. Low bone mineral density, increased numbers of fractures of the long bones and vertebra, hip pain, and scoliosis have been reported across the spectrum of SMA patients. While lack of ambulation likely contributes significantly to bone pathology, SMA patients have markedly lower bone density compared to other non-ambulatory patients with debilitating diseases such as Duchenne muscular dystrophy, suggesting that there is a cell-intrinsic contribution of SMN to bone homeostasis and function. Mouse models of SMA have also confirmed the presence of bone and cartilage phenotypes. These alterations frequently persist post-treatment. Recent advancements in therapeutic strategies, approved by both the FDA and the EMA, have represented a leap forward in the management of SMA. However, treatment gaps remain. Post-treatment, patients frequently face continued challenges with scoliosis, bone fractures, and persistent muscle weakness—conditions that underscore the urgent need for more comprehensive therapeutic strategies with combination therapies that can support skeletal health. To date, no molecular map exists of the changes that occur in SMA patient bone and cartilage, impeding the ability of finding targeted therapies. To address this clinical need, we profiled the transcriptome of the vertebral bone and cartilage in a cohort of 11 Type II SMA patients who were undergoing surgery for scoliosis correction and compared them to 7 idiopathic scoliosis and 2 DMD controls. Additionally, we characterized the skeletal health of a mouse model of type I SMA. We find that multisystemic factors including liver and muscle health affect the underlying SMA bone pathology. Specifically, we detect alterations in the balance between osteoclasts and osteoblasts, changes in PPARγsignaling, mitochondrial oxidative phosphorylation and fatty acid beta-oxidation, and alterations in the muscle-derived factor Irisin that play a role in overall SMA bone pathology.
Pair creation, backreaction, and resummation in strong fields
Authors: Copinger Patrick , Edwards James P. , Ilderton Anton , Rajeev Karthik
Published: February 2025

We revisit particle creation in strong fields, and backreaction on those fields, from an amplitudes perspective. We describe the strong field by an initial coherent state of photons which we explicitly evolve in time, thus going beyond the background-field approximation, and then consider observables which quantify the effects of backreaction. We present expressions for the waveform, vacuum persistence probability, and number of produced photons at next-to-leading order, all of which are impacted by backreaction, along with the number and statistics of produced pairs. We find that converting between in-out (amplitude) and in-in (expectation value) expressions requires explicit resummation of an infinite number of disconnected loop diagrams.

Published by the American Physical Society
2025
Leader–member exchange and emotional exhaustion in registered construction engineers: mediating role of active management by exception and moderating role of self-esteem
Authors: Feng Kai , Wang Shengnan , He Lina , Li Yongxin
Published: February 2025

Purpose

This study investigated the impact of leader-member exchange (LMX) on emotional exhaustion among Chinese registered construction engineers by examining the mediating role of active management by exception (AMbE) and the moderating role of self-esteem.

Design/methodology/approach

Using a sample of 304 registered construction engineers, the study applies the job demands-resources (JD-R) model to explore how LMX, AMbE and self-esteem interact to influence emotional exhaustion.

Findings

The findings indicate a significant negative relationship between LMX and emotional exhaustion, suggesting that higher-quality exchanges between leaders and members reduce emotional exhaustion. Additionally, AMbE was found to mediate this relationship, where high-quality LMX relationships decrease the extent of AMbE, subsequently lowering emotional exhaustion. Self-esteem was also found to moderate the relationship between AMbE and emotional exhaustion, with high self-esteem exacerbating the negative impact of AMbE and low self-esteem buffering this impact.

Originality/value

These results extend the JD-R model by incorporating leadership quality and management style as critical factors influencing emotional well-being. The study underscores the need for balanced management approaches that consider both supportive and corrective behaviors and highlights the importance of tailoring interventions based on individual differences in self-esteem. The findings provide valuable insights for both theory and practice in managing stress and enhancing the well-being of professionals in high-stress industries. Future research should aim to replicate these findings with larger samples to further validate and extend the results.
Revisiting the impact of Islamic finance on economic growth: a decomposition analysis using Indonesia as a testing ground
Authors: Rofik Mochamad , Boulanouar Zakaria , Yuli Sri Budi Cantika , Wardani Dyah Titis Kusuma
Published: February 2025

Purpose

This study aims to examine the impact of Sharia-compliant (SC) finance on economic growth by decomposing it into working capital, investment and household finance. The goal is to understand not only the general impact of Islamic financing but also how its various components contribute to economic development.

Design/methodology/approach

Using annual data from 33 provinces in Indonesia from 2010 to 2021, the authors use the fixed effects model, accounting for cross-sectional heterogeneity. The study explores the competitive dynamics between Islamic and conventional banking, focusing on how Sharia financing market share affects economic growth. Robustness checks ensure the reliability of the findings.

Findings

The results show that total Islamic financing and its components (working capital, investment and household finance) positively impact economic growth. However, a higher market share of Sharia financing can constrain growth, suggesting an underdeveloped market for SC products. This finding emphasizes the need for a balanced development of both Islamic and conventional financial sectors to support sustainable economic growth.

Research limitations/implications

Future research could extend the time frame or investigate other emerging markets to confirm these results. Further studies could also explore how different types of Sharia financing affect specific sectors, such as agriculture or manufacturing, to offer more targeted insights for policymakers and investors.

Practical implications

Policymakers could use the insights from this study to create incentives for Islamic financial institutions to develop tailored products for critical sectors, such as microfinance for smallholder farmers or investment financing for sustainable agriculture. These initiatives would enhance access to finance, stimulate local economies and align with Indonesia’s development goals.

Social implications

Understanding the role of Sharia financing in growth can help devise strategies that promote ethical investment and reduce poverty. The findings highlight the potential of SC finance to contribute to social welfare and economic equity.

Originality/value

This study provides a unique analysis of how different forms of SC finance affect economic development, filling a gap in the literature. It offers valuable insights for academics, policymakers and practitioners in the field of Islamic finance, emphasizing the nuanced relationship between financial structure and economic growth.

Contribution to impact

This study contributes to the literature by analyzing the decomposition of Sharia financing into specific categories and their distinct impacts on growth. It suggests that existing models need to account for market development and competitive dynamics when evaluating the role of Islamic finance in economic development.
Reacting to the Past as a leadership pedagogy tool
Authors: Hart Joy L. , Bryk Mary , Fine Leigh E. , Garbutt Keith , Kotinek Jonathan , Bott-Knutson Rebecca C.
Published: February 2025

Purpose

Applying practices from online role-playing games with multiple players, we employed Reacting to the Past (RTTP) pedagogy to engage students at several universities in a multi-week experience. As a pedagogical method, RTTP is ripe for potential use across an array of leadership education initiatives, including interinstitutional collaborations.

Design/methodology/approach

In this essay, we describe this student learning and engagement experience as well as address innovations and potential applications in similar leadership education contexts, preliminary student and facilitator feedback and lessons learned.

Findings

As part of The Justice Challenge’s eight-week Colloquium, students developed an understanding of food justice, systems thinking and transdisciplinary collaboration, as well as skills in perspective-taking, persuasion and teamwork. Through the RTTP gameplay, students engaged firsthand with multiple perspectives and goals, differing ways of interpreting information and situations, diverse factions and political pressures.

Originality/value

We believe our use of RTTP in The Justice Challenge is novel for two reasons. First, although RTTP fits remarkably well with the basic philosophy of honors education, it is less explored as a pedagogical approach in leadership education contexts. Second, our use of RTTP in an online, multi-institutional program highlights it as a useful pedagogical tool to foster leadership learning that can work regardless of group size or modality.
Dr Who? Identity Crucibles and the DBA Doctoral Degree
Authors: Kirk Susan , Foster Carley , Kougiannou Nadia , Parry Emma , Collins Claire
Published: February 2025

This paper explores the triggers and identity crucibles facing professional doctorate students pursuing a Doctorate in Business Administration (DBA). Unlike prior research, which centres on full‐time PhD students, our study examines the identity work of DBA students, many of whom do not foresee a transition to academia. Through 35 semi‐structured interviews, we explore the identity work involved in ‘becoming a doctor’ and the identity crucibles that DBA students encounter. We identify the internal and external triggers that lead to identity work and identity crucibles, with their accompanying emotions, and examine how these crucibles are resolved. This research develops current thinking in critical management education, revealing how DBA students do not uniformly aspire to become practitioner‐scholars or academics. Instead, they start and end their doctoral studies from various and different identity positions, highlighting the complexity of these long, intellectually challenging programmes. By exploring the triggers, identity crucibles and resolutions, this study offers a nuanced understanding of the DBA student experience and provides valuable insights into how these individuals can be supported throughout their doctoral studies. This support enhances retention and completion rates for those tasked with managing these programmes and reduces the likelihood of losing exceptional scholars/practitioners.
Teachers and teacher training for inclusive pedagogies in England. Mainstream and SEND schools providing their own solutions
Authors: Smythe Fiona
Published: February 2025

In England, a vertical equity model of inclusive schooling has been increasingly visible in both educational policy and school practices since the 2019 education reforms. Within this mixed model of provision, alongside and in complementarity to mainstream schooling, alternative provision (AP) and special educational needs and disabilities (SEND) settings offer schooling for disabled or excluded children. Within this national context, teachers across mainstream, AP and SEND schools were interviewed in a 2021‐2022 study about their views and experiences of training for inclusive pedagogies. The findings reveal that teachers across the sectors face similar problems, such as a lack of time for further training in inclusive pedagogies and the difficulty of meeting all pupils' needs (both those with and without SEND). Teachers in both mainstream and specialised settings favoured in‐house training to promote specific skills, while those working in the AP and SEND sectors also wanted more sharing of best practices through inter‐school networks. Both mainstream and specialised settings further identified a place for university‐based training in supporting teachers' understanding of diversity and inclusion, in addition to schools‐based professional development. Teachers' views suggest that initial teacher training insufficiently prepares teachers for working with diverse pupils, and it is only by real‐world practice that effective skills are developed.
Firm responses to an interest barrier: empirical evidence
Authors: Harju Jarkko , Kauppinen Ilpo , Ropponen Olli
Published: February 2025

In this paper, we study the effects of an interest barrier (IB) that was introduced in Finland in 2014 to restrict the profit‐shifting opportunities of multinational enterprises (MNEs). We employ data from the Orbis database on Finnish, Swedish and Danish MNEs and a difference‐in‐differences methodology, where Swedish and Danish MNEs serve as a control group. We examine the effects of the IB on financial expenses, debt levels and overall economic activity of firms. We find that Finnish MNEs responded to the IB by decreasing their financial expenses. We also find that the most affected firms decreased their debt levels due to the reform. Our results also suggest that the financial expense response is followed by a change in the use of transfer pricing as a method to shift profits between tax jurisdictions. We do not find evidence of total output changes among treated firms, which suggests that the IB did not affect the real activity of the treated MNEs.
Survey to assess present practice and address challenges in gynaecological brachytherapy in Australia and New Zealand
Authors: Kain Mollie , Govindarajulu Geetha , Johnson Carol , Xu‐Holland April , Lapuz Carminia
Published: February 2025

Introduction

This survey assessed gynaecological brachytherapy caseloads, local training requirements and quality assurance processes across Australia and New Zealand.

Methods

The survey was developed by the Gynaecological Oncology Radiation Oncology Collaboration (GOROC) and emailed to all centres offering gynaecological brachytherapy across Australia and New Zealand. It covered 9 areas including caseloads per centre and per radiation oncologist, techniques practised, local training requirements and quality assurance processes over a 2‐year period – 2019 and 2020.

Results

The response rate was 18 out of 25 centres. All centres offered vaginal vault brachytherapy and 89% treated an average of at least 10 patients per annum. Intracavitary and/or interstitial brachytherapy was offered at 89% of centres of which 31% treated less than an average of 10 patients per annum and 23% of radiation oncologists did less than an average of 5 or more insertions per annum as recommended in the GOROC guidelines. Most centres required only Fellowship from the Royal Australian and New Zealand College of Radiologist to practice gynaecological brachytherapy. Peer review of volumes and dosimetry was routinely performed in 28% and 17% of centres, respectively.

Conclusion

This survey adds to the limited literature available regarding practice patterns of brachytherapy worldwide. Ensuring adequate training and robust quality assurance processes with volume and dosimetry review may support all centres and clinicians to continue to safely offer this complex technique.
Intubating conditions during rapid sequence induction with either rocuronium or suxamethonium in elderly patients. A randomised study
Authors: Vested Matias , Creutzburg Andreas , Meyhoff Christian S. , Rovsing Marie Louise , Nielsen Tatiana , Rosa Fabio , Aasvang Eske K , Mollerup Hannah , Fuchs‐Buder Thomas , Rasmussen Lars Simon
Published: February 2025

Background

During rapid sequence induction, either rocuronium 1.0 mg kg−1 or suxamethonium 1.0 mg kg−1 can be administered to facilitate endotracheal intubation. We hypothezised that rocuronium provided a larger proportion of excellent intubating conditions compared to suxamethonium in elderly patients.

Methods

A total of 90 patients 80 years or above with American Society of Anesthesiologists physical health Classes I–IV, and a body mass index < 35 kg m−1−2 were randomised to either rocuronium 1.0 mg kg−1 or suxamethonium 1.0 mg kg−1 during rapid sequence induction with intubation using a video laryngoscope. After 60 s, tracheal intubating conditions were evaluated using the Fuchs‐Buder scale by a blinded investigator, and the primary outcome was the proportion of patients with excellent intubating conditions. Further outcomes included first pass success rate, intubating conditions according to the intubating difficulty scale (IDS), onset time and postoperative occurrence of muscle soreness, hoarseness and sore throat.

Results

All patients were evaluated for the primary outcome. Excellent intubating conditions occurred in 36 patients (73%) versus 31 (75%) in the rocuronium group and suxamethonium group, respectively (95% confidence interval [CI]: −16 to 20) (p = .82). The first pass success rate was 48 (98%) versus 40 (98%) comparing the rocuronium group with the suxamethonium group, respectively (p = .90). No difference in IDS score was found; median 0 (interquartile ranges [IQR]: 0–1) versus median 0 (IQR: 0–1) (p = .48). Onset time was significantly shorter in the suxamethonium group 99 versus 131 s (p = .01) (95% CI: 7 to 57). Finally, no difference was found in the occurrence of muscle soreness, hoarseness or sore throat postoperatively.

Conclusion

No important difference in intubating conditions was found during rapid sequence induction after the administration of either rocuronium 1.0 mg kg−1 or suxamethonium 1.0 mg kg−1 in patients 80 years or above.

Editorial Comment

This reports a superiority trial comparing standardised doses of rocuronium and suxamethonium at 60 s for quality of intubating conditions in the rapid sequence context, and this in an elderly cohort. The findings showed no difference between the drugs concerning intubation outcomes, though the onset or time to peak effect was shorter for suxamethonium, again demonstrated in a cohort 80 years old or older.