bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming Political Upheaval to Deliver Pediatric Surgical Care in Afghanistan: A Prospective Analysis of the First 1000 Procedures
Authors: Moghul Dunya , Hsu Phillip J , Bryce Emma , Obaidy Yalda , Hellman Zane , Sherzad Ajmal , Poenaru Dan , Cheung Maija 
Published: February 2025

Background:
Pediatric surgical care is limited in Afghanistan. Few details are known about the state of pediatric surgery in Afghanistan. We explore the impact of a newly installed pediatric operating room by a children’s charity on the provision of pediatric surgery in Afghanistan.

Study Design:
Following the opening in March 2023 of the new KidsOR operating room at Ataturk Hospital in Kabul, Afghanistan, perioperative clinical data was prospectively collected until December 2023. All children (age <14 years) undergoing surgical procedures were included in a REDCap database, and descriptive analyses were performed.

Results:
1,014 operations were performed during the study period. The patients originated (73%) from Kabul Province; 80% were male. 34% of the surgeries were emergencies. Mean age was 6.5 years old. Those who received elective surgery were on average younger (age 5.2 years) compared to those receiving emergency surgery (age 7.6 years (p<0.0001). The most common emergent diagnoses were appendicitis (52%), intussusception (9%), genitourinary pathologies (8.7%), and neurosurgical trauma (6.1%). The most common elective cases were hernias 27%, undescended testes (18%), hypospadias/epispadias (9%), urinary tract stones (8%), hydrocele/spermatocele/varicocele (7%), gastrointestinal pathologies (7%), and neurosurgical disorders (6%). The most frequent procedures were appendectomy (18%), inguinal hernia repair (17%), and orchidopexy (13%). Mortality and infectious complication rates were both 0.3%.

Conclusions:
This is the largest study on the provision of pediatric surgical care in Afghanistan, demonstrating the successful implementation of infrastructure for surgical capacity in a low-resource setting with a complex political status. Future efforts to quantify the burden of untreated pediatric surgical disease in this setting should assist advocacy efforts towards resource allocation and public health initiatives.

Level of Evidence:
Level 3 retrospective review
Determination of protein transporter function using Raman spectroscopy
Authors: Gilchrist Dominic , Islam Meez , Akram Muhammad Safwan , Dean Paul 
Published: February 2025

Graphical Abstract
A summary of the workflow for identifying the function of a protein transporter using Raman spectroscopy. A putative transporter gene (ThNTT4) is cloned into a suitable expression vector [] and transformed into a heterologous expression system []. Protein expression is induced [] and confirmed [], followed by an uptake assay using alkyne-labelled substrates such as N6pATP []. Following washing and lysis of the heterologous host cell [], the lysate is spotted onto a steel slide, dried down and analysed with the Raman microscope.
Cancer cells suppress NK activity by actin-driven polarisation of inhibitory ligands at the synapse
Authors: Hoffmann Céline , Filali Liza , Wurzer Hannah , Fernandes Diogo Pereira , Mgrditchian Takouhie , Moreau Flora , Krecké Max , Thomas Clément 
Published: February 2025

AbstractNatural killer (NK) cells engage target cells via the immunological synapse, where inhibitory and activating signals determine whether NK cell cytotoxicity is suppressed or activated. We report that cancer cells can rapidly remodel their actin cytoskeleton upon NK cell engagement, leading to F-actin accumulation at the synapse. This process inhibits NK cell activation as indicated by impaired MTOC and lytic granule polarization. Exploring the underlying mechanism, we found that actin remodelling drives the recruitment of inhibitory ligands, such as HLA-A, -B, and -C, to the synapse. Disrupting HLA interaction with their cognate inhibitory receptors KIRs restored NK cell activation. Using NK cells expressing inhibitory KIR receptors, matched or unmatched to HLA molecules on cancer cells, we show that synaptic F-actin accumulation and matching KIR-HLA interactions jointly suppress NK cell cytotoxicity. Our findings reveal a novel immune evasion strategy in which cancer cells impair NK cell activation by altering synaptic signalling through actin cytoskeleton-driven recruitment of inhibitory signals to the immunological synapse.
Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders
Authors: Goodman Alexander C. , Michel Kylie M. , MacBeth Morgan L. , Turner Jaqueline A. , Tobin Richard P. , Robinson William A. , Couts Kasey L. 
Published: February 2025

AbstractObjectivesThis study investigates the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response.MethodsIn a retrospective cohort study, serum samples from 43 stage III and stage IV melanoma patients treated at the University of Colorado Hospital from 2010 to 2023 were analyzed via ultra-high-pressure liquid chromatography-mass spectrometry. Melanoma patients were treated anti-PD-1 monotherapy or combination immune checkpoint inhibitor therapy and response was assessed using RECIST 1.1 criteria.ResultsUsing mass spectroscopy, we determined global oxylipin metabolite profiles are largely uniform pre-and post-treatment across melanoma subtypes including cutaneous, acral, mucosal, and uveal melanoma. Across subtypes, 33 oxylipin metabolites were analyzed, with limited variation observed overall. Prostaglandin J2was more abundant in rare melanoma subtypes including acral, mucosal, and uveal melanoma compared to cutaneous melanoma.ConclusionsDespite limited variation of serum oxylipin molecular species by subtype and response status, we observed significant differences in Prostaglandin J2which could serve as a potential biomarker for immune checkpoint inhibitor therapy response in melanoma. However, further investigation is warranted to explore the role of oxylipins in immune response modulation.
Strategies for Mitigating Radiation Damage and Improving Data Completeness in 3D Electron Diffraction of Protein Crystals
Authors: Shaikhqasem Alaa , Hamdi Farzad , Machner Lisa , Parthier Christoph , Breithaupt Constanze , Kyrilis Fotis L. , Feller Stephan M. , Kastritis Panagiotis L. , Stubbs Milton T. 
Published: February 2025

AbstractWhile 3D electron diffraction (3D-ED or microcrystal electron diffraction, MicroED) has emerged as a promising method for protein structure determination, its applicability is hindered by high susceptibility to radiation damage, leading to decreasing signal-to-noise ratio in consecutive diffraction patterns that limits the quality (resolution and redundancy) of the data. In addition, data completeness may be restricted due to the geometrical limitations of current sample holders and stages. In this work, we introduce an approach that addresses these issues using a commonly available 200keV cryo-electron microscope. The multi-position acquisition technique we present here combines (a) multiple data acquisitions from a single crystal over several tilt ranges and (b) merging data from a small number of crystals, each tilted about a different axis. The robustness of this approach is demonstrated by thede novoelucidation of a protein-peptide complex structure from only two orthorhombic microcrystals.
Spatial biomarkers of response to neoadjuvant therapy in muscle-invasive bladder cancer: the DUTRENEO trial
Authors: Grande Enrique , Sibai Mustafa , Andrada Elena , Grases Daniela , Reig Oscar , Escobosa Marc , Azueta Ainara , Castellano Daniel , Puente Javier , Villarreal Jaime Martínez de , Font Albert , Alonso-Gordoa Teresa , Benítez Raquel , Moreno-Oya Ane , Álvarez-Maestro Mario , Burgos Javier , Climent M. Angel , Domínguez Mario , Galván Patricia , Galante Isabel , García Juan F. , Perez Elena , Muro Xavier García del , Guerrero-Ramos Félix , Marqués Miriam , Maroto Pablo , Paramio Jesús M. , Pinto Alvaro , Prat Aleix , Malats Núria , Durán Ignacio , Porta-Pardo Eduard , Real Francisco X. 
Published: February 2025

AbstractMany studies have reported biomarkers predictive of response to immune checkpoint inhibitors (ICI) based on retrospective analyses. However, few clinical trials have tested their value prospectively. The DUTRENEO trial (EudraCT: 2017-002246-6) investigated whether an 18-gene Tumour Inflammation Signature (TIS) that can robustly identify patients who respond to ICI in multiple tumour types could stratify patients with localized muscle-invasive bladder cancer (MIBC) to receive neoadjuvant ICI (durvalumab+tremelimumab) or standard cisplatin-based neoadjuvant chemotherapy (NAC). Patients with TIS-high tumors were randomized to ICI or NAC, while patients with TIS-low tumors received NAC. A total of 73 patients were treated. Pathological complete response (pCR) rates were 38.5% (TIS-High, ICI), 30% (TIS-High, NAC), and 55% (TIS-Low, NAC) (p = 0.349), indicating that - as applied - the TIS score did not significantly enrich in responders to ICI. Post-hoc analysis showed that higher TIS thresholds improved prediction of response to ICI but excluded many responders. Multi-omics analyses of pre-treatment samples, including whole-exome sequencing, bulk RNA sequencing, and spatial transcriptomics (Visium, Xenium), revealed that bulk RNA response signatures originated mainly from cancer cells. Spatial transcriptomics showed that ICI response was associated with proximity between cancer cells and adaptive immune cells, while resistance to NAC was linked to phenotypic plasticity of cancer cells despite low genetic diversity. The unique design of the DUTRENEO trial underscores the challenges of translating retrospective biomarkers into clinical practice and highlights the importance of spatial features in understanding tumour-immune interactions. These findings suggest that integrating spatial and multi-modal biomarkers in well-designed clinical trials could improve stratification and response prediction to select neoadjuvant therapy.
Real-world experience on the use of nivolumab monotherapy for advanced renal cell carcinoma: a multicenter retrospective cohort study in Spain
Authors: Fernández-Díaz Natalia , Mateos-González María , Pertejo-Fernández Ana , Cacho-Lavín Juan Diego , Juan-Fita María José , Chirivella-González Isabel , Arruti-Ibarbia Mikel , Fernández-Calvo Ovidio , Fernández-Núñez Natalia , Méndez-Vidal María José , Lázaro-Quintela Martín , Molina-Díaz Aurea , Del Pozo-Alonso Nieves , Etxaniz-Ulazia Olatz , García-Acuña Silvia Margarita , Betancor Yoel Z. , Azueta-Etxebarria Ainara , Calatrava-Fons Ana , Lombardía-Rodríguez Helena , Alarcón-Molero Lorena , Etxegarai-Ganboa Leire , Antón-Cameselle Abraham , Bello-Giz José Antonio , Neira-De Paz Carlos Manuel , Cabaleiro Teresa , González-Serrano Teresa , Ortiz-Rey José Antonio , Sacristán-Lista Felipe , García-Rubín Silvia , Ortega Elisa , Carrato-Moñino Cristina , Aguín-Losada Santiago , León-Mateos Luis , García-González Jorge , Pinto-Marín Álvaro , Duran Ignacio , López-López Rafael , Anido-Herranz Urbano , Ruiz-Bañobre Juan 
Published: February 2025

AbstractThe safety and efficacy of nivolumab in treating advanced renal cell carcinoma (aRCC) patients have been evaluated in real-world evidence (RWE) studies across various European countries, but no such data from Spain have been reported until now. We conducted a multicenter, retrospective study on 222 previously treated aRCC patients to assess the efficacy of nivolumab and the impact of pre-treatment factors on therapy outcomes in a real-world clinical practice scenario in Spain. Our results were then compared with other significant clinical experiences involving aRCC patients treated with nivolumab monotherapy. With a median follow-up of 14.6 months, the median overall survival (OS) was 18.1 months (95% confidence interval [CI], 14.2-23.7 months), and the median progression-free survival (PFS) was 4.96 months (95% CI, 3.98-7.13 months). The disease control rate was 51% (95% CI, 45-58%) and the objective response rate 23% (95% CI, 18-30%). Poor IMDC risk score was independently associated with worse OS, while prior nephrectomy with better OS. Poor IMDC risk score and ≥3 metastatic sites were independently associated with worse PFS; ≥3 metastatic sites was also associated with lower disease control. Consistent with prior clinical trials and RWE studies, this research confirms the efficacy and safety of nivolumab in daily clinical practice for a cohort of unselected previously treated aRCC patients in Spain.
Assessing sustainable and healthy diets in large-scale surveys: validity and applicability of a dietary index based on a brief food group propensity questionnaire representing the EAT-Lancet planetary health diet
Authors: Miranda Agustin , Murante Anna Maria , Manca Federica , Consalez Fabio , Jani Anant , DeClerck Fabrice , Maillot Matthieu , Verger Eric 
Published: February 2025

AbstractIntroductionEnsuring healthy diets within planetary boundaries is essential. However, current instruments measuring adherence to the EAT-Lancet planetary health diet are unsuitable for large-scale surveys. Simplified tools assessing consumption frequency can improve response rates, lower costs, and facilitate administration. This study aimed to develop a practical and concise index for evaluating relative adherence to the EAT-Lancet diet across large-scale multi-country surveys.MethodsFirst, the EAT-Lancet Consumption Frequency Index (ELFI) was developed using a brief food propensity questionnaire of 14 food groups representing the planetary health diet from the FEAST survey, which encompassed 27 European countries (n□=□27,417). Subsequently, ELFI was further validated using 24-hour dietary recalls from the INCA3 survey (n = 1,645), correlating it with the valid EAT-Lancet Index (ELI), which evaluates absolute adherence, as well as with food group consumption, measures of nutritional health (nutrient adequacy and diet quality), and environmental impact. Analyses included assessment of reliability, structural validity, concurrent validity, and nomological validity.ResultsELFI showed strong reliability (alpha > 0.80) and factor analysis revealed a two-factor solution: “foods to encourage” and “foods to balance and to limit”. Confirmatory factor analysis demonstrated that ELFI is structurally valid. Concurrent validity was confirmed as it was associated with sex, age, education, income, household size, physical activity and smoking habit (p < 0.05). ELFI correlated with ELI (0.44, p < 0.0001) and food group consumptions. Regarding nomological validity, the ELFI subscores for “foods to encourage” and “foods to balance and to limit” were associated with better nutritional health (β = 0.62 and 0.23, respectively; p < 0.0001) and a lower environmental impact (β = −0.16 and −0.36, respectively; p < 0.0001).ConclusionELFI approach represents a valuable and easy-to-implement index for evaluating relative adherence to sustainable and healthy diets in large-scale multi-country studies.
Approaches to early intervention for common mental health problems in young people: a systematic review
Authors: Appleton Rebecca , Barnett Phoebe , Clarke Connor , Yang Jialin , Begum Sadiya , Edbrooke-Childs Julian , Emptage Isobel , Foye Una , Griffiths Jessica , Hanson Isabel , Hunt Nima Cas , Jarvis Ruby , McAuliffe Maeve , Maynard Emma , Mitchell Lizzie , Mostafa Irina , Pemovska Tamara , Saunders Rob , Trevillion Kylee , Waite Polly , Lloyd-Evans Brynmor , Johnson Sonia 
Published: February 2025

AbstractEffective early support for children and young people is a high priority. Early intervention approaches for young people with psychosis or eating disorders have substantial supporting evidence, but well-established approaches to delivering a prompt, effective response to young people presenting with early symptoms of anxiety and depression are lacking. We conducted a systematic review of outcomes of early interventions or approaches for young people (between 11 and 25 years) with initial symptoms of depression, anxiety and other common mental health difficulties. Five bibliographic and two grey literature databases were searched for papers relating to youth, early intervention and common mental health problems. We conducted a narrative synthesis of models and assessed quality using CASP checklists. We included 38 studies (43 publications): of these, randomised controlled trials were high quality but other studies tended to lack control groups and be of lower quality. Approaches broadly aimed provide a more comprehensive and effective early response to symptom onset, with primary goals falling into one of: 1) Making care more comprehensive and joined up, 2) Increasing speed or ease of access to support, or 3) Providing targeted support for specific needs in addition to anxiety and depression. Some evidence indicates that these approaches may facilitate access and reduce waiting times in the short-term, whilst decreasing burden on other mental health or emergency services. Significant improvements in mental health and wellbeing compared to controls were also reported across most studies with comparator groups, alongside high acceptability. Overall, models of early intervention for depression and anxiety show promise in improving access, experience and outcomes of care for young people. However, high heterogeneity of interventions and outcomes measured limits certainty. More robust controlled studies are needed, alongside comprehensive details of support received by young people through the intervention, and evidence of what works for whom in which settings.
A preliminary attempt to harmonize using physics-constrained deep neural networks for multisite and multiscanner MRI datasets (PhyCHarm)
Authors: Lee Gawon , Ye Dong Hye , Oh Se-Hong 
Published: February 2025

AbstractIn magnetic resonance imaging (MRI), variations in scan parameters and scanner specifications can result in differences in image appearance. To minimize these differences, harmonization in MRI has been suggested as a crucial image processing technique. In this study, we developed an MR physics-based harmonization framework, Physics-Constrained Deep Neural Network for Multisite and multiscanner Harmonization (PhyCHarm). PhyCHarm includes two deep neural networks: (1) the Quantitative Maps Generator to generate T1- and M0-maps and (2) the Harmonization Network. We used an open dataset consisting of 3T MP2RAGE images from 50 healthy individuals for the Quantitative Maps Generator and a traveling dataset consisting of 3T T1w images from 9 healthy individuals for the Harmonization Network. PhyCHarm was evaluated using the structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), and normalized-root-mean square error (NRMSE) for the Quantitative Maps Generator, and using SSIM, PSNR, and volumetric analysis for the Harmonization network, respectively. PhyCHarm demonstrated increased SSIM and PSNR, the highest Dice score in the FSL FAST segmentation results for gray and white matter compared to U-Net, Pix2Pix, and CALAMITI. PhyCHarm showed a greater reduction in volume differences after harmonization for gray and white matter than U-Net, Pix2Pix, or CALAMITI. As an initial step toward developing advanced harmonization techniques, we investigated the applicability of physics-based constraints within a supervised training strategy. The proposed physics constraints could be integrated with unsupervised methods, paving the way for more sophisticated harmonization qualities.
EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes
Authors: Gonzalez-Lozano Miguel A. , Schmid Ernst W. , Whelan Enya Miguel , Jiang Yizhi , Paulo Joao A. , Walter Johannes C. , Harper J. Wade 
Published: February 2025

ABSTRACTEarly/sorting endosomes are dynamic organelles that play key roles in proteome control by triaging plasma membrane proteins for either recycling or degradation in the lysosome1,2,3. These events are coordinated by numerous transiently-associated regulatory complexes and integral membrane components that contribute to organelle identity during endosome maturation4. While a subset of the several hundred protein components and cargoes known to associate with endosomes have been studied at the biochemical and/or structural level, interaction partners and higher order molecular assemblies for many endosomal components remain unknown. Here, we combine cross-linking and native gel mass spectrometry5-8of purified early endosomes with AlphaFold9,10and computational analysis to create a systematic human endosomal structural interactome. We present dozens of structural models for endosomal protein pairs and higher order assemblies supported by experimental cross-links from their native subcellular context, suggesting structural mechanisms for previously reported regulatory processes. Using induced neurons, we validate two candidate complexes whose interactions are supported by crosslinks and structural predictions: TMEM230 as a subunit of ATP8/11 lipid flippases11and TMEM9/9B as subunits of CLCN3/4/5 chloride-proton antiporters12. This resource and its accompanying structural network viewer provide an experimental framework for understanding organellar structural interactomes and large-scale validation of structural predictions.
A haplotype-resolved reference genome forEucalyptus grandis
Authors: Lötter Anneri , Bruna Tomas , Duong Tuan A. , Barry Kerrie , Lipzen Anna , Daum Chris , Yoshinaga Yuko , Grimwood Jane , Jenkins Jerry W. , Talag Jayson , Borevitz Justin , Lovell John T. , Schmutz Jeremy , Wegrzyn Jill L. , Myburg Alexander A. 
Published: February 2025

AbstractE. grandisis a hardwood tree used worldwide as pure species or hybrid partner to breed fast-growing plantation forestry crops that serve as feedstocks of timber and lignocellulosic biomass for pulp, paper, biomaterials and biorefinery products. The current v2.0 genome reference for the species (Bartholome et al., 2015; Myburg et al., 2014) served as the first reference for the genus and has helped drive the development of molecular breeding tools for eucalypts. Using PacBio HiFi long reads and Omni-C proximity ligation sequencing, we produced an improved, haplotype phased assembly (v4.0) for TAG0014, an early-generation selection ofE. grandis.The two haplotypes are 571 Mbp (HAP1) and 552 Mbp (HAP2) in size and consist of 37 and 46 contigs scaffolded onto 11 chromosomes (contig N50 of 28.9 and 16.7 Mbp), respectively. These haplotype assemblies are 70 to 90 Mbp smaller than the diploid v2.0 assembly but capture all except one of the 22 telomeres, suggesting that substantial redundant sequence was included in the previous assembly. A total of 35,929 (HAP1) and 35,583 (HAP2) gene models were annotated, of which 438 and 472 contain long introns (>10 kbp) in gene models previously (v2.0) identified as multiple smaller genes. These and other improvements have increased gene annotation completeness levels from 93.8% to 99.4% in the v4.0 assembly. We found that 6,493 and 6,346 genes are within tandem duplicate arrays (HAP1 and HAP2, respectively, 18.4% and 17.8% of the total) and >43.8% of the haplotype assemblies consists of repeat elements. Analysis of synteny between the haplotypes and theE. grandisv2.0 reference genome revealed extensive regions of collinearity, but also some major rearrangements, and provided a preview of population and pan-genome variation in the species.Paper summaryWe assembled a haplotype-phased genome forEucalyptus grandisthat will serve as reference for the most widely planted hardwood crop globally. It includes more than 430 new gene models with long introns and has 6% higher annotation completeness. The phased assembly provides a more accurate look at genome variation at DNA and transcript level and will better support future studies of genome structure and function. The improved assembly contains more tandem duplicate genes compared to the previous unphased reference. Finally, major genomic rearrangements between the two phased genomes provide a preview of pangenome and structural variation inE. grandis.