bluuebunny/crossref_metadata_2025_split huggingface dataset:
“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

Abstract

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

ABSTRACTBy 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

AbstractPurposeRPE65is 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.Methods30 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.ResultsThere 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.ConclusionThis 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

ABSTRACTBackgroundThe 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.MethodsLocal 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.ResultsThe 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.ConclusionsThe 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.
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

AbstractHigh-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

SummaryThe 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

SummaryViral 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

ABSTRACTMany 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

SummaryRegulated 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

ABSTRACTSpinal 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.
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

PurposeThis 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/approachUsing 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.FindingsThe 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/valueThese 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.