bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Evaluation for the Development of a Scoring System to Predict Homozygous M694V Genotype in Familial Mediterranean Fever Patients
Authors: Tunce Eray , Uçar Sıla Atamyıldız , Coşkuner Taner , Baykal Gülcan Özomay , Yiğit Ramazan Emre , Türkmen Şeyma , Pirim Gülşah , Ulu Kadir , Sözeri Betül 
Published: November 2024

Objective
The aim of this study was to identify key parameters of a scoring system to be developed to predict the homozygous M694V genotype in patients clinically diagnosed with familial Mediterranean fever.

Methods
This study was a cross-sectional analysis of 472 pediatric familial Mediterranean fever patients with a homozygous genotype on exon 10, followed at our tertiary pediatric rheumatology clinic between June 2016 and June 2023. The patients were categorized into 2 groups based on their genotypes: group 1 comprised 402 patients (85.2%) with the homozygous M694V genotype, whereas group 2 consisted of 70 patients (14.8%) with other homozygous genotypes. Demographic information, clinical manifestations, MEFV (Mediterranean fever) gene variant analysis, and treatment responses were recorded from the patients' medical charts.

Results
The odds ratios for age at disease onset, arthritis, and chest pain were 0.892 (95% confidence interval [CI]: 0.832–0.958, p = 0.002), 2.565 (95% CI: 1.109–5.934, p = 0.028), and 2.351 (95% CI: 1.123–4.922, p = 0.023), respectively. A total of 60.7% of patients in group 1 had arthralgia, and 25% had erysipelas-like erythema, with these percentages were higher in group 1 compared with group 2 (p = 0.002, p = 0.001, respectively). Protracted febrile myalgia syndrome was detected in 1.5% of patients, all of whom had homozygous M694V genotype. Colchicine resistance was detected in 13.3% of patients, and all had homozygous M694V genotype.

Conclusions
This preliminary evaluation identified key parameters for a scoring system designed to predict the homozygous M694V genotype. A multicenter national study will further refine these parameters and develop the scoring system, which will aid clinicians in disease prognosis and therapeutic decision-making.
Papillary Tumor of the Pineal Gland With Discordant FDG and FAPi Uptake
Authors: Preet Komal , Purohit Priyavrat , Mittal Bhagwant Rai , Kumar Rajender , Singh Harmandeep , Shukla Jaya , Bal Amanjit , Madan Renu 
Published: November 2024

Abstract
In recent years, 68Ga-FAP inhibitor has emerged as a possible substitute radiotracer to FDG for imaging of most of the tumors. Here, we report a 7-year-old girl diagnosed with recurrent papillary tumor of the pineal gland, presenting with complaints of headache and vomiting. 18F-FDG PET/CT revealed an FDG-avid enhancing lesion in the posterior part of the third ventricle. Negligible FAPI uptake was noted on the corresponding 68Ga-FAPI-46 PET/CT images, highlighting the scope of 18F-FDG PET/CT in this realm.
Open abdomen versus primary closure in nontrauma patients: A weighted analysis of a single-center experience
Authors: Bunino Francesca Margherita , Zulian Davide , Famularo Simone , Persichetti Giorgia Willy Ladini , Mauri Giulia , Del Fabbro Daniele 
Published: November 2024

INTRODUCTION
The open abdomen (OA) technique is nowadays a worldwide strategy both for trauma and emergency general surgery. Despite the attempt at conducting prospective studies, a high level of evidence is far from established. The aim of this study was to investigate if we overused this strategy and if it improved the postoperative course of our patients.

METHODS
Emergency laparotomies from 2017 and 2023 were reviewed and stratified according to OA and closed abdomen (CA). Differences were balanced by inverse probability weighting, and the 90-day mortality was estimated. Subgroup analysis was carried out for patients with a Mannheim Peritonitis Index (MPI) of >26, bowel obstruction, bowel ischemia (BI) and gastrointestinal perforation.

RESULTS
Of the 320 patients, 167 were CA and 153 were OA. Groups were different for American Society of Anesthesiologists, comorbidities, transfusion rate, Physiologic and Operative Severity Score for the Study of Mortality and Morbidity score, MPI, Clinical Frailty Scale score, diagnosis, and resection. Two balanced pseudo-populations were created. The 90-day survival rate was 50.8% for CA and 60.8% for OA (hazard ratio [HR], 0.79; confidence interval [CI], 0.40–1.55; p = 0.502). At the Cox regression, the Clinical Frailty Scale score (HR, 1.125; 95% CI, 1.01–1.25; p = 0.033) and BI (HR, 5.531; 95% CI, 2.37–12.89; p < 0.001) were independent risk factors for mortality. Transfusion rate (odds ratio [OR], 3.44; 95% CI, 1.44–8.23; p < 0.006) and length of stay in the intensive care unit (OR, 1.13; 95% CI, 1.07–1.20; p < 0.001) were associated with major complications. Open abdomen did not modify mortality in the case of bowel obstruction, MPI >26, or gastrointestinal perforation. Finally, OA (HR, 0.056; 95% CI, 0.01–0.22; p = 0.001) and large bowel resection (HR, 6.442; 95% CI, 1.28–32.31; p = 0.040) were predictors of longer survival in the subgroup of patients with BI.

CONCLUSION
Open abdomen was not associated with a higher complication rate or higher mortality but did result in a longer in-hospital stay. The only setting where OA seemed to be advantageous was in the BI population.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Hospital-based violence intervention programs: An analysis of costs and key components
Authors: O'Toole Megan J. , Schnippel Kathryn , Larson Bruce 
Published: November 2024

BACKGROUND
Firearm assaults contribute to nearly 18,000 deaths and at least twice as many injuries annually, with immense human and financial costs. Gun violence survivors especially face unique and long-term physical, mental, economic, and safety-related challenges. Hospital-based violence intervention programs (HVIPs) connect survivors with violence prevention professionals at their hospital bedsides, then provide them with wraparound services in the months to come. Promising research shows that HVIPs reduce risks of reinjury, retaliation, and recidivism.

METHODS
This report provides a cost analysis of HVIPs, to inform researchers and implementers of the budget and key resources necessary for the first three years of implementation. Researchers employ an ingredients-based costing approach and base-case assumptions for a hospital-linked HVIP situated in a mid-sized city emergency department, serving 100 participants annually.

RESULTS
Results indicate that this base-case HVIP costs an estimated $1.1 million annually, or just under $10,800 per participant. Staffing accounts for the majority of HVIP budgets, followed by operations, crisis support, and finally transportation. Upfront costs are limited to technical assistance, first-time equipment, and accreditation courses, leaving annual costs relatively stable across the first 3 years of implementation. A customizable workbook is provided, through which users can adjust this study’s assumptions to reflect their own program’s specifications, which may vary.

CONCLUSION
While a full cost-savings analysis remains needed, HVIP enrollment costs less per person than a single year of medical fees for nonfatal firearm assault-related injuries. This research can inform future cost, benefit, and savings analyses, and empower more communities to implement lifesaving HVIPs.

LEVEL OF EVIDENCE
Economic and Value-Based Evaluation; Level II.
Large language models (LLMs) as agents for augmented democracy
Authors: Gudiño Jairo F. , Grandi Umberto , Hidalgo César 
Published: November 2024

We explore an augmented democracy system built on off-the-shelf large language models (LLMs) fine-tuned to augment data on citizens’ preferences elicited over policies extracted from the government programmes of the two main candidates of Brazil’s 2022 presidential election. We use a train-test cross-validation set-up to estimate the accuracy with which the LLMs predict both: a subject’s individual political choices and the aggregate preferences of the full sample of participants. At the individual level, we find that LLMs predict out of sample preferences more accurately than a ‘bundle rule’, which would assume that citizens always vote for the proposals of the candidate aligned with their self-reported political orientation. At the population level, we show that a probabilistic sample augmented by an LLM provides a more accurate estimate of the aggregate preferences of a population than the non-augmented probabilistic sample alone. Together, these results indicate that policy preference data augmented using LLMs can capture nuances that transcend party lines and represents a promising avenue of research for data augmentation.
This article is part of the theme issue ‘Co-creating the future: participatory cities and digital governance’.
Complex systems perspective in assessing risks in artificial intelligence
Authors: Kondor Daniel , Hafez Valerie , Shankar Sudhang , Wazir Rania , Karimi Fariba 
Published: November 2024

In this article, we identify challenges in the complex interaction between artificial intelligence (AI) systems and society. We argue that AI systems need to be studied in their socio-political context to be able to better appreciate a diverse set of potential outcomes that emerge from long-term feedback between technological development, inequalities and collective decision-making processes. This means that assessing the risks from the deployment of any specific technology presents unique challenges. We propose that risk assessments concerning AI systems should incorporate a complex systems perspective, with adequate models that can represent short- and long-term effects and feedback, along with an emphasis on increasing public engagement and participation in the process.
This article is part of the theme issue ‘Co-creating the future: participatory cities and digital governance’.
Co-designing transport models as a heuristic planning tool
Authors: Maheshwari Tanvi , Fourie Pieter 
Published: November 2024

Recently the transportation sector has witnessed several new technologically driven disruptions that have amplified the complexity of city planning and policymaking. Traditional well-established processes of decision-making in urban planning and transportation are proving insufficient to deal with this degree of complexity and uncertainty. This paper proposes an alternative approach, combining qualitative and normative urban design, with quantitative and predictive transport modelling. This requires urban designers and transport modellers to co-create goal-driven and agile transport models that act as a heuristic tool to guide planning decisions in early design stages. Heuristic modelling is informed by design optioning and vice versa in an iterative loop. A case study is presented to demonstrate how this approach is operationalized to study the impacts of automated vehicles on urban planning. Design workshops are used as a method to elicit responses from stakeholders, which are used to co-create the simulation models. This collaborative process grounds the research in real-world practice and enhances the communication of design proposals and research findings across disciplines. By integrating design thinking methods with agent-based transport simulations, this approach provides a better understanding of emergent effects in complex urban systems and improves stakeholder engagement in the planning process.
This article is part of the theme issue ‘Co-creating the future: participatory cities and digital governance’.
Quantifying body size estimation accuracy and body dissatisfaction in body dysmorphic disorder using a digital avatar
Authors: Karsan Sameena , Diaz-Fong Joel P. , Ly Ronald , Hellemann Gerhard , Feusner Jamie D. 
Published: November 2024

AbstractA core feature of body dysmorphic disorder (BDD) is body image disturbance. Many with BDD misperceive and are dissatisfied with the sizes and shapes of body parts, but detailed quantification and analysis of this has not yet been performed. To address this gap, we appliedSomatomap 3D,a digital avatar tool, to quantify body image disturbances by assessing body size estimation (BSE) accuracy and body dissatisfaction. Sixty-one adults (31 with BDD, 30 healthy controls) created avatars to reflect their perceived current body and ideal body by altering 23 body part sizes and lengths usingSomatomap 3D.Physical measurements of corresponding body parts were recorded for comparison. BSE accuracy (current minus actual) and body dissatisfaction (ideal minus current) were compared between groups and in relation to BDD symptom severity using generalized estimating equations. Individuals with BDD significantly over-and under-estimated certain body parts compared to healthy controls. Individuals with BDD overall desired significantly thinner body parts compared to healthy controls. Moreover, those with worse BSE accuracy had greater body dissatisfaction and poorer insight. In sum, this digital avatar tool revealed disturbances in body image in individuals with BDD that may have perceptual and cognitive/affective components.
Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations
Authors: Kho Pik Fang , Wary Neil , Zanetti Daniela , Abbasi Fahim , Knowles Joshua W. , Panyard Daniel J. , Watson Katie T. , Stell Laurel , Lazzeroni Laura C. , Gustafsson Stefan , Lind Lars , Petrie John R , Assimes Themistocles L. 
Published: November 2024

AbstractBackgroundWe previously reported significant correlations between a direct measure of insulin sensitivity (IS) and blood levels of proteins measured using the Proximity Extension Assay (PEA) in two European cohorts. However, protein correlations with IS within non-European populations, in response to short-term interventions that improve IS, and any causal associations with IS have not yet been established.MethodsWe measured 1,470 proteins using the PEA in the plasma of 1,015 research participants at Stanford University who underwent one or more direct measures of IS. Association analyses were carried out with multivariable linear regression within and across Stanford subgroups and within each of the two European cohorts. Association statistics were also meta-analyzed after transformation and harmonization of the two direct measures of IS. Lastly, we performed genome-wide association studies of IS and used genetic instruments of plasma proteins from the UK Biobank to identify candidate causal proteins for IS through Mendelian Randomization (MR) analysis.ResultsIn age and sex adjusted model, 810 proteins were associated with baseline IS among 652 self-reported European participants in the Stanford cohort at a false discovery rate (FDR) < 0.05. Effect sizes for these proteins were highly correlated with those observed in 122 South Asian, 92 East Asian, 85 Hispanic, and 52 Black/African American persons (r= 0.68 to 0.83, all P≤4.3×10-113). Meta-analysis of the full Stanford cohort with the two European cohorts (N=2,945) yielded 247 significant protein associations (FDR < 0.05), with 75 remaining significant after further adjustment for body mass index. In a subset of Stanford participants undergoing insulin sensitizing interventions (N=53 taking thiazolidinediones, N=66 with weight loss), 79.6% of protein level changes were directionally consistent with the respective baseline association (observed/expected p=6.7x10-16). MR analyses identified eight candidate causal proteins for IS, among which were SELE and ASGR1, proteins with established drug targets currently under investigation.ConclusionPlasma proteins measured using the PEA provide a robust signature for IS across diverse populations and after short-term insulin sensitizing interventions highlighting their potential value as universal biomarkers of insulin resistance. A small subset of markers provided insights into potential causal molecular mechanisms and therapeutic targets.HighlightsInsulin sensitivity-related plasma proteins are consistent across diverse populations.Protein changes from interventions align with baseline, aiding insulin sensitivity tracking.SELE and ASGR1 are potential targets for insulin sensitivity.
Master regulators governing protein abundance across ten human cancer types
Authors: Wang Zishan , Wojciechowicz Megan , Rosen Jordan , Elmas Abdulkadir , Song Won-Min , Liu Yansheng , Huang Kuan-lin 
Published: November 2024

ABSTRACTProtein abundance correlates only moderately with mRNA levels, and are modulated post-transcriptionally by a network of regulators including ribosomes, RNA-binding proteins (RBPs), and the proteasome. Here, we identifiedMasterProtein abundanceRegulators (MaPRs) across ten cancer types by devising a new computational pipeline that jointly analyzed transcriptomes and proteomes from 1,305 tumor samples. We identified 232 to 1,394 MaPRs per cancer type, mediating up to 79% of post- transcriptional regulatory networks. MaPRs exhibit high network connectivity, strong genetic dependency in cancer cells, and significant enrichment for RBPs. Combining tumor up-regulation, druggability, and target network analyses identified cancer-specific vulnerabilities. MaPRs predict tumor proteomic subtypes more accurately than other proteins. Finally, significant portions of RBP MaPR-target relationships were validated by experimental evidence from eCLIP binding and knockdown assays. Our findings uncover central MaPRs that govern post-transcriptional networks, highlighting diverse processes underlying human proteome regulation and identifying key regulators in cancer biology.
Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors
Authors: Jolma Arttu , Laverty Kaitlin U. , Fathi Ali , Yang Ally W.H. , Yellan Isaac , Vorontsov Ilya E. , Inukai Sachi , Kribelbauer-Swietek Judith F. , Gralak Antoni J. , Razavi Rozita , Albu Mihai , Brechalov Alexander , Patel Zain M. , Nozdrin Vladimir , Meshcheryakov Georgy , Kozin Ivan , Abramov Sergey , Boytsov Alexandr ,   The Codebook Consortium, Fornes Oriol , Makeev Vsevolod J. , Grau Jan , Grosse Ivo , Bucher Philipp , Deplancke Bart , Kulakovskiy Ivan V. , Hughes Timothy R. 
Published: November 2024

SUMMARYWe describe an effort (“Codebook”) to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiplein vitroandin vivoassays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both incisandtrans, and identify tens of thousands of conserved, base-level binding sites in the human genome. The use of multiple assays provides an unprecedented opportunity to benchmark and analyze TF sequence specificity, function, and evolution, as further explored in accompanying manuscripts. 1,421 human TFs are now associated with a DNA binding motif. Extrapolation from the Codebook benchmarking, however, suggests that many of the currently known binding motifs for well-studied TFs may inaccurately describe the TF’s true sequence preferences.
Targeting synthetic lethality between non-homologous end joining and radiation in very high-risk SHH medulloblastoma
Authors: DeCarlo Alexandria , MacLeod Graham , Fernandes da Silva Carolina , Shen Lily , Aragao Lucas , Sie Mariska , Termini Deborah , Magee Jon , Gudenas Brian , Sukumaran Sneha , Charron Frederic , Marcellus Richard , Al-Awar Rima , Aman Ahmed , Tabori Uri , Nör Carolina , Northcott Paul A. , Dirks Peter , Angers Stephane , Ramaswamy Vijay 
Published: November 2024

SummarySpecific and biologically informed treatments for medulloblastoma, especially the highly lethalTP53mutant SHH subgroup, remain elusive, where radiotherapy is the primary treatment option. Applying genome-wide CRISPR-Cas9 screening in combination with lethal doses of radiotherapy, we identified the main driver of radiation resistance in SHH medulloblastoma is loss of p53. A negative selection CRISPR-Cas9 screen across multiple models ofTrp53-deficient SHH medulloblastoma revealed a strong synthetic lethal interaction between components of the non-homologous end-joining pathway and radiation, particularly DNA protein kinase (DNA-PK) and its binding partners. Both genetic and pharmacological perturbation of DNA-PK enhanced radiosensitivity inTP53-deficient SHH medulloblastoma, leading to cell death.In vivotreatment of somatic and germlineTP53-mutant SHH medulloblastoma models with peposertib, a small-molecule inhibitor of DNA-PK, significantly improved survival when combined with radiotherapy, strongly supporting further clinical investigation.
Human single-neuron activity is modulated by intracranial theta burst stimulation of the basolateral amygdala
Authors: Campbell Justin M. , Cowan Rhiannon L. , Wahlstrom Krista L. , Hollearn Martina K. , Jensen Dylan , Davis Tyler , Rahimpour Shervin , Shofty Ben , Arain Amir , Rolston John D. , Hamann Stephan , Wang Shuo , Eisenman Lawrence N. , Swift James , Xie Tao , Brunner Peter , Manns Joseph R. , Inman Cory S. , Smith Elliot H. , Willie Jon T. 
Published: November 2024

AbstractDirect electrical stimulation of the human brain has been used for numerous clinical and scientific applications. Previously, we demonstrated that intracranial theta burst stimulation (TBS) of the basolateral amygdala (BLA) can enhance declarative memory, likely by modulating hippocampal-dependent memory consolidation. At present, however, little is known about how intracranial stimulation affects activity at the microscale. In this study, we recorded intracranial EEG data from a cohort of patients with medically refractory epilepsy as they completed a visual recognition memory task. During the memory task, brief trains of TBS were delivered to the BLA. Using simultaneous microelectrode recordings, we isolated neurons in the hippocampus, amygdala, orbitofrontal cortex, and anterior cingulate cortex and tested whether stimulation enhanced or suppressed firing rates. Additionally, we characterized the properties of modulated neurons, patterns of firing rate coactivity, and the extent to which modulation affected memory task performance. We observed a subset of neurons (∼30%) whose firing rate was modulated by TBS, exhibiting highly heterogeneous responses with respect to onset latency, duration, and direction of effect. Notably, location and baseline activity predicted which neurons were most susceptible to modulation, although the impact of this neuronal modulation on memory remains unclear. These findings advance our limited understanding of how focal electrical fields influence neuronal firing at the single-cell level and motivate future neuromodulatory therapies that aim to recapitulate specific patterns of activity implicated in cognition and memory.