bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adults With Head and Neck Burns Experience Worse Long-Term Outcomes and Require More Reconstructive Surgeries
Authors: Choe Deborah , McMullen Kara , Stewart Barclay T. , Kowalske Karen , Schneider Jeffrey C. , Ryan Colleen M. , Kazis Lewis E. , Orton Caitlin M. , Yenikomshian Haig A. 
Published: December 2024

Background
Adults living with head and neck burn injuries experience psychosocial consequences due to scarring as well as functional disabilities. However, the impact of head and neck burns on long-term self-reported psychosocial outcomes, return to work, and need for reconstructive surgery has not been well described. This study investigates the unique longitudinal problems in psychosocial and functional recovery faced by adults with head and neck burn injuries.

Methods
Utilizing the multicenter Burn Model System (BMS) National Database, long-term psychosocial and functional outcomes as well as postdischarge reconstructive surgery rates between adult participants with and without head and neck burns injured after 2014 were compared.

Results
Of 1247 participants, 579 had head and neck burns and 668 had non–head and neck burns. Head and neck burn was a significant predictor of worse anxiety (β = 1.63, P = 0.049) and body image (β = −0.30, P = 0.011) at 6 months post burn; worse anxiety (β = 2.68, P = 0.004), depression (β = 2.14, P = 0.021), and body image (β = −0.41, P = 0.001) at 12 months post burn; and worse life satisfaction (β = −1.64, P = 0.036) at 24 months post burn. Head and neck burn participants reported significantly worse anxiety (P = 0.001), depression (P = 0.0026), and life satisfaction (P < 0.001) at 12 months post burn and worse body image at 6 (P < 0.001), 12 (P < 0.001), and 24 (P < 0.001) months post burn. The head-and-neck group had a significantly greater proportion of participants who had undergone contracture surgery at 12 months post burn (P < 0.001) and a smaller proportion who had returned to work by 6 (P < 0.001) and 12 (P < 0.001) months post burn.

Conclusions
This study suggests that adults with head and neck burns might strongly benefit from additional counseling, psychotherapy, and greater aftercare.
Chimeric Free Flaps Based on End-to-Side Anastomosis for Complex Lower Extremity Reconstruction
Authors: Gu Yingluo , Sun Yongyang , Xu Ke , Yi Nan , Qin Jianzhong , Zhang Yong , Zhao Jiaju , Jiang Bo 
Published: December 2024

Background
Complex lower extremity defects are difficult to cover and often require multiple free tissue transfers. Chimeric anterolateral thigh free flaps (ALTF) and peroneal artery perforator free flaps (PAPF) have been designed specifically as an alternative for reconstruction with arterial end-to-side (ETS) anastomosis. We aimed to assess our institutional experience with this technique and to define its role in complex lower extremity reconstruction.

Methods
From July 2012 to March 2023, 27 patients with complex lower extremity defects underwent reconstruction with chimeric ALTF or PAPF. Patients were performed with retrograde flaps for repairing refractory wounds of tibia plateau fracture and antegrade flaps for distal 2/3 tibia and beyond. Demographic, clinical, and follow-up data on the patients were recorded with a special focus on complication profiles during a follow-up of 6 to 60 months.

Results
The mean defect size measured 121.1 ± 215.1 cm2, and the chimeric ALTF or PAPF flaps measured 143.9 ± 177.8 cm2. One patient lost the first free flap but successfully had a chimeric PAPF then. Three patients suffered partial free flap loss, and another 3 had minor complications. All 6 survived after an additional exploration, wound dressing, or antibiotics treatment. The retrograde flaps achieved similar blood flow to the antegrade flaps. Patients are all satisfied with functional and aesthetic outcomes.

Conclusions
Given the incidence of complications, utilizing chimeric ALTF and PAPF either with retrograde or antegrade flow based on arterial ETS anastomosis is a reliable surgical option for complex lower extremity reconstructions.
Effect of Autogenous Auricular Cartilage Composite Skin Graft for Bilateral Cleft Lip Nose Deformity Repair
Authors: Yuan Mei , Jin Jie , Han Yixiang , Ge Xiuyu , Zhao Shuhan , Jia Mengna , Han Zhiqiang , Tian Li , Xu Jing 
Published: December 2024

Objective:
Bilateral cleft lip nose deformity often involves nasal alar retraction. The use of autogenous auricular cartilage for correction further aggravated nasal alar retraction caused by nasal lining defects after the operation. A novel graft was developed to address bilateral cleft lip nose deformity. This graft effectively addresses the lining defect and avoids nasal alar retraction following surgical intervention.

Methods:
Seventeen patients (7 males and 10 females) with bilateral cleft lip nose deformity were treated at the authors' institution. All patients underwent repair with an auricular cartilage-composite skin graft. The surgical effect was evaluated from 4 aspects: nasal flange position, postoperative appearance satisfaction, nasal aesthetic subunit index, and three-dimensional difference.

Results:
Postoperatively, 17 patients with bilateral cleft lip nose deformity were followed up from 3 months to 1 year, none of them had any obvious inward collapse or recession of the nasal margin (P > 0.05), and all of them showed satisfactory results. The satisfaction rate was above 90% (P < 0.01). The nasal tip angle and nasolabial angle were significantly smaller postoperatively than those preoperatively (P < 0.01). The nostril height and nasal columellar height were greater postoperatively than those preoperatively (P < 0.01). A comparison of the three-dimensional spatial differences revealed that the appearance of the nasal deformity was noticeably better after surgery (P < 0.01).

Conclusions:
Auricular cartilage-composite skin graft repair is highly effective for enhancing nasal support, correcting nasal tip shape, effectively resolving nasal flange recession, and preventing nasal flange retraction in the postoperative period.

Level of Evidence:
Level IV.
Treatment of Paraclinoid Aneurysms With Stent-Assisted Coiling Versus Flow Diversion Techniques: A Systematic Review and Meta-Analysis
Authors: Tang Kai , Liu Xiao-meng , Zhang Chao , Ma Shuang-ju , Song Xiao-lei , Du Hai-long , Hu Yu-hua , Wu Jian-liang 
Published: December 2024

Background:
The stent-assisted coiling (SAC) and flow-diverter stent (FDS) techniques are widely used in the endovascular treatment of paraclinoid aneurysms. This article compares the occlusion rate, periprocedural complications, and clinical outcomes of SAC and FDSs.

Methods:
Between January 2010 and December 2020, a systematic search of electronic databases identified 2283 articles for screening. After the application of inclusion and exclusion criteria, data were extracted for a meta-analysis of the proportions.

Results:
Of 23 articles containing 4 comparative studies, 27 cohorts were included, and 1208 patients with 1328 aneurysms were analyzed: In 10 cohorts, 381 (28.7%) patients were treated with SAC, whereas in 17 cohorts, 947 (71.3%) patients were treated with FDSs. In the comparative studies, no significance was observed between the 2 treatments. In the pooled cohorts, complete occlusion was achieved in 85% of aneurysms after treatment with FDSs (95% CI: 0.81–0.88, I
2=34.7%) and 76% after treatment with SAC (95% CI: 0.70–0.81, I
2=16.6%); the subgroup analysis was statistically significant (P=0.003). New visual complications were observed in 5% of the FDS-treated group (95% CI: 0.02–0.09, I
2=76.9%) and in 1% of the SAC-treated group (95% CI: 0.00–0.02, I
2=0%); the subgroup analysis was statistically significant (P=0.018). Other observational indices, including total procedure-related complications; hemorrhagic, thrombotic, and ischemic complications; permanent morbidities, and favorable neurological outcomes, showed no statistical significance between the groups.

Conclusion:
Compared with SAC, treatment with FDSs may have a higher complete occlusion rate at follow-up. The similarly low rates for procedure-related complications and permanent morbidities indicate that both treatments are safe. A higher rate of new visual complications was noted in the FDS-treated group. Further research is required for direct comparisons along with a complete ophthalmological examination.
Strong evidence for multiple horizontal transfers of immune genes between teleost fishes
Authors: Policarpo Maxime , Salzburger Walter , Maumus Florian , Gilbert Clément 
Published: December 2024

AbstractHorizontal gene transfer (HGT) is less frequent in eukaryotes than in prokaryotes, yet can have strong functional implications and was proposed as causal factor for major adaptations in several eukaryotic lineages. Most cases of eukaryote HGT reported to date are inter-domain transfers and only few studies have investigated eukaryote-to-eukaryote HGTs. Furthermore, the extent to which HGT has contributed to the gene repertoire of some lineages such as vertebrates remains unclear. Here, we performed a large-scale survey of HGT among 242 species of ray-finned fishes. We found strong evidence supporting 18 teleost-to-teleost HGT events that involve 17 different genes in 11 teleost fish orders. The genes involved in these transfers show lower synonymous divergence than expected under vertical transmission, their phylogeny is inconsistent with that of teleost fishes, and high nucleotide similarity on these genes between donor and recipient lineages extends to non-coding regions. The distribution of HGT events in the teleost tree is heterogenous, with eight of the 18 transfers occurring between the same two orders (Osmeriformes and Clupeiformes). Besides the previously reported transfer of an antifreeze protein, most transferred genes play roles in immunity, suggesting that such genes are more likely than others to confer strong selective advantage to the recipient species. Overall, our work shows that teleost-to-teleost HGT has occurred on multiple occasions and it will be worth further quantifying these transfers and evaluating their impact on teleost evolution as more genomes are being sequenced.
Mitochondrial damage triggers therapy-induced senescence
Authors: Baltira Chrysiida , Alkan Ferhat , Mayayo-Peralta Isabel , Guillen-Navarro Miriam , Thijssen Bram , Lempers Rose , Pello Kimberley , Fedorushkova Daria M. , Their Anna , Jochems Fleur , Rozing Kicky , Bleijerveld Onno B. , Janssen Hans , Kuil Laura E. , Beijnen Jos H. , Faller William J. , Silva Joana , Bernards Rene , van Tellingen Olaf , de Gooijer Mark C. 
Published: December 2024

AbstractGlioblastoma (GBM) is a fatal brain tumor with a critical need for better therapies. It is known that the PI3K, MAPK, and CDK4/6 signaling pathways are hyper-activated in these tumors; however, previous studies have used very high concentration of inhibitors to assess their importance, with mixed results. Here we developed PMCi, a combination approach that targets all three pathways simultaneously, at clinically-relevant doses. PMCi effectively suppresses GBM cell proliferation in vitro and in vivo, and outperforms monotherapies and dual combinations. PMCi acts by inducing cellular senescence, which is mediated solely by the mitochondria, and, unlike other forms of senescence, is independent of nuclear damage. This phenotype is caused by a reactive oxygen species (ROS)\cGAS-STING\senescence-associated secretory phenotype (SASP) signaling cascade, that acts in a paracrine manner to establish and maintain senescence. Our results demonstrate that mitochondrial damage is sufficient to drive senescence, and that this can be leveraged to target GBM cells.
The last resort antibiotic daptomycin exhibits two independent antibacterial mechanisms of action
Authors: Buttress Jessica A. , Schäfer Ann-Britt , Koh Alan , Wheatley Jessica , Mickiewicz Katarzyna , Wenzel Michaela , Strahl Henrik 
Published: December 2024

ABSTRACTDaptomycin is a lipopeptide antibiotic, commonly used as last resort treatment against multidrug resistant Gram-positive pathogens. Despite its clinical success, the mechanism through which daptomycin exerts its antibacterial properties has remained controversial. Much of the debate is focused around daptomycin’s ability to depolarise the cytoplasmic membrane, potential formation of large membrane pores, and its more recently discovered capability to inhibit cell wall synthesis and disturb membrane lipid domain organisation through interactions with cell wall precursor lipids. Here we show that, rather than representing different facets of a single underlying activity, daptomycin exhibits two independent antibacterial mechanisms of action: (i) targeting of cell wall precursor lipids that leads to cell wall synthesis inhibition and (ii) membrane depolarisation that does not rely on interactions with cell wall precursor lipids. This dual mechanism of action provides an explanation for the frequently disagreeing findings obtained throughin vivoandin vitrostudies and explains why resistance development towards daptomycin is slow and multifactorial. In a broader context, this demonstrates that dual mechanism antibiotics can be clinically successful and exhibit favourable characteristics in terms of real-world, clinically relevant resistance development.
WWOX deficiency impairs neurogenesis and neuronal function in human organoids
Authors: Steinberg Daniel J. , Zonca Asia , Rosh Idan , Kustanovich Irina , Maroun Kian , Stern Shani , Davila-Velderrain Jose , Aqeilan Rami I. 
Published: December 2024

AbstractWOREE and SCAR12 syndromes are rare neurodevelopmental disorders caused by WWOX mutations, severely impairing brain development. The pleiotropic nature of WWOX complicates identifying specific mechanisms. Using neural organoids and single-cell transcriptomics, we identified radial glial cells (RGs) as preferentially affected, with disrupted cell cycle dynamics leading to an accumulation of cells in the G2/M and S phases, overexpression of the proto-oncogene MYC, and concomitant reduction in neuronal generation. Patient-derived organoids exhibited milder phenotypes compared to knockout organoids, showing functional neuronal impairments like hyperexcitability and delayed differentiation rather than RG dysfunction. Remarkably, gene therapy restored neuronal function, normalizing hyperexcitability and promoting maturation, without disturbing RG populations. We propose a model in which WWOX mutations impair neurogenesis via RG through cell-type specific dysregulation of the MYC and Wnt signaling pathways. These insights highlight potential therapeutic strategies for WWOX-related disorders and open avenues for interventions targeting these key molecular pathways.TeaserWWOX mutations disrupt radial glial function and neurogenesis via MYC dysregulation, with gene therapy offering targeted restoration.
SHEN-LONG, a novel cardiac regulatory locus, regulates cardiac master transcription factor NKX2-5 in pluripotent stem cell derived cardiomyocytes
Authors: Scarafía María Agustina , Halek Julia , Smucler Joaquín , Waisman Ariel , Moro Lucía , Sevlever Gustavo , Miriuka Santiago , La Greca Alejandro 
Published: December 2024

AbstractCardiac development is a finely regulated process, transforming undifferentiated cells into the specialized cell components of the heart. Super-Enhancers (SE), clusters of enhancers densely populated with transcription factors, play a central role in cell fate decisions, including cardiogenesis. In this work, we studied a cardiac SE in chr3q25.31. This locus also contains a cardiac specific long non-coding RNA: LINC00881 (LINC881). We termed this region of interest SHEN-LONG (SuperHeartENhancer andLONGnon-coding LINC881), and selected it for further functional characterization. Our analysis revealed SHEN-LONG is a hotspot of cardiac kernel transcription factor binding sites. Cardiac differentiation of human iPSC with partial Knock Out of SHEN-LONG resulted in cardiomyocytes with reduced NKX2-5 expression, a master cardiac transcription factor, suggesting a significant role of SHEN-LONG in this process. Whole transcriptome sequencing of SHEN-LONG KO cardiomyocytes produced 134 differentially expressed genes located at great distances (>4Mb) emphasizing its long-range functional impact. A regulation mediated essentially by the SE and not by LINC881 was confirmed when LINC881 overexpression did not recover NKX2-5 expression. These findings provide insights into a novel NKX2-5 regulatory mechanism. The knowledge gained in this work may pave the way for advances in therapeutic interventions for cardiovascular disorders.
IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2
Authors: Lee Cadence , Khan Rachel , Mantsounga Chris S. , Sharma Sheila , Pierce Julia , Amelotte Elizabeth , Butler Celia A. , Farinha Andrew , Parry Crystal , Caballero Olivya , Morrison Jeremi A. , Uppuluri Saketh , Whyte Jeffrey J. , Kennedy Joshua L. , Zhang Xuming , Choudhary Gaurav , Olson Rachel M. , Morrison Alan R. 
Published: December 2024

ABSTRACTCoronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection. We developed a humanizedACE2(hACE2) mouse wherebyhACE2cDNA was cloned into the mouseACE2locus under control of the native promoter. We validated the susceptibility ofhACE2mice to SARS-CoV-2 infection relative to wild-type mice and an establishedK18-hACE2model of acute fulminating disease. Intranasal exposure to SARS-CoV-2 led to pulmonary consolidations with cellular infiltrate, edema, and hemorrhage, consistent with pneumonia, yet unlike theK18-hACE2model,hACE2mice survived and maintained stable weight. InfectedhACE2mice also exhibited a unique plasma chemokine, cytokine, and growth factor inflammatory signature relative toK18-hACE2mice. InfectedhACE2mice demonstrated evidence of viral replication in infiltrating lung macrophages, and infection of macrophages in vitro revealed a transcriptional profile indicative of altered RNA and ribosomal processing machinery as well as activated cellular antiviral defense. Macrophage IL-1β-driven NF-κB transcription of ACE2 was an important mechanism of dynamic ACE2 upregulation, promoting macrophage susceptibility to infection. Experimental models of COVID-19 that make use of native hACE2 expression will allow for mechanistic insight into factors that can either promote host resilience or increase susceptibility to worsening severity of infection.
Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors
Authors: Yu Xinjian , Sarabia Stephen , Urbicain Martin , Somvanshi Sonal , Patel Roma , Tran Tuan M , Yeh Yen-Ping , Chang Keng-Shih , Lo Yi-Tzu , Epps Jessica , Scorsone Kathleen A. , Chiu Hua-Sheng , Hollingsworth Emporia Faith , Perez Cintia R. , Najaf Panah Mohammad Javad , Zorman Barry , Finegold Milton , Goss John A. , Alaggio Rita , Roy Angshumoy , Fisher Kevin E. , Heczey Andras , Woodfield Sarah , Vasudevan Sanjeev , Patel Kalyani , Chen Ting-Wen , Lopez-Terrada Dolores , Sumazin Pavel 
Published: December 2024

ABSTRACTMost malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC1–3. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features4–6. Their outcomes and cellular composition remain an open question7–9. The heterogeneous histological and molecular profiles of hepatoblastomas with carcinoma features (HBCs)4may result from cells with combined HB and HCC characteristics (HBC cells) or from mixtures of cells displaying either HB or HCC signatures. We used multiomics profiling to show that HBCs are mixtures of HB, HBC, and HCC cell types. HBC cells are more chemoresistant than HB cells, and their chemoresistance—a driver of poor outcomes10–12—is determined by their cell types, genetic alterations, and embryonic differentiation stages. We showed that the prognosis of HBCs is significantly worse than that of HBs. We also showed that HBC cells are derived from HB cells at early hepatoblast differentiation stages, that aberrant activation of WNT-signaling initiates HBC transformation, and that WNT inhibition promotes differentiation and increases sensitivity to chemotherapy. Furthermore, our analysis revealed that each HBC is the product of multiple HB-to-HBC and HBC-to-HCC transitions. Thus, multiomics profiling of HBCs provided key insights into their biology and resolved major questions regarding the etiology of these childhood liver tumors.
High-resolution mastigoneme structure reveals 5’,5’-phosphodiesters stabilized glycan folding
Authors: Huang Junhao , Tao Hui , Chen Jikun , Pan Junmin , Yan Chuangye , Yan Nieng 
Published: December 2024

AbstractGlycans play a crucial role in structure organization, energy metabolism, and signal transduction in living organisms. Compared with proteins and nucleic acids, glycans exhibit remarkable molecular heterogeneity, extensive conformational flexibility, and diverse linkages. These properties pose significant challenges for obtaining high-resolution structure of glycans. Here, we report a cryo-EM structure of the heavily glycosylatedChlamydomonasmastigoneme at 2.3-2.5 Å resolutions. In addition to enabling analysis of accurate interactions for glycosyl packing, the high resolution map reveals an unprecedented 5’,5’-phosphodiester bond that links adjacent glycan chains attached to hydroxyproline (Hyp) residues n and n+3. Structural analysis reveals a secondary structural element for glycoconjugates, which we name the poly-Hyp (pHP) glycohelix. Our work represents an important advancement in deciphering glycan folding.
DOMON domain-containing proteins control root development upon phosphate deficiency and ammonium stress by modulating iron dynamics
Authors: Clúa Joaquín , Poirier Yves 
Published: December 2024

AbstractPhosphorous and nitrogen are the main nutrients limiting plant growth in natural and agricultural systems. Plants typically uptake phosphorous in the form of inorganic phosphate, whereas the main nitrogen sources are nitrate and ammonium. Roots show a high degree of developmental plasticity in response to nutritional stresses, directly influencing plant fitness and stress resilience. InArabidopsis thaliana, phosphate deficiency and high levels of ammonium in the media triggers a strong inhibition of the primary root growth. This developmental response is initiated by the accumulation of apoplastic iron in specific cell types, which triggers the inhibition of meristem maintenance and cell elongation. In this report, we show that DOMON domain-containing proteins are key molecular players controlling root development upon phosphate deficiency and ammonium toxicity via iron dynamics.