bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computed Tomography of the Head Before Lumbar Puncture in Adults With Suspected Meningitis in High–HIV Prevalence Settings
Authors: Milburn James , Williams Christopher G , Lechiile Kwana , Siamisang Keatlaretse , Owen Leah , Gwakuba Ezekiel , Milton Thandi , Machiya Tichaona , Leeme Tshepo , Barton Hannah E , Ponatshego Ponego , Seatla Kaelo K , Boitshepo Gerald , Suresh Rachita , Rulaganyang Ikanyeng , Hurt William , Ensor Samuel , Ngoni Kebatshabile , Doyle Ronan , Grint Daniel , Miller Wallace T , Tenforde Mark W , Mine Madisa , Goldfarb David M , Mokomane Margaret , Jarvis Joseph N 
Published: September 2024

Abstract

Background
The role of computed tomography (CT) before lumbar puncture (LP) is unclear, with limited evidence for a causal link between LP and cerebral herniation or for the ability of CT to identify individuals at risk of herniation. The risks of LP delay or deferral are potentially greater in high–HIV prevalence, resource-limited settings; we analyzed data from such a setting to determine the impact of CT on time to LP and treatment, as well as mortality.

Methods
Adults with suspected central nervous system (CNS) infection were enrolled prospectively into the Botswana National Meningitis Survey between 2016 and 2019. Inpatient mortality and clinical data including time of treatment initiation and CT were captured from medical records. Associations between preceding CT and outcomes were assessed using logistic regression.

Results
LPs were performed in 711 patients with suspected CNS infection; 27% had a CT before LP, and 73% were HIV positive. Time from admission to LP and time from admission to appropriate treatment were significantly longer in patients who had a CT before LP compared with those who did not (2.8 hours and 13.2 hours, respectively). There was some evidence for treatment delays being associated with increased mortality; however, there was no significant difference in mortality between those who had or did not have CT.

Conclusions
Patients who had a CT had delays to diagnostic LP and initiation of appropriate treatment; although treatment delays were associated with increased mortality, our observational study could not demonstrate a causal association between delays in diagnosis and treatment introduced by CT and mortality.
Genetic Isolation among Four Lineages of Silene nutans
Authors: Postel Zoé , Martin Hélène , Roux Camille , Godé Cécile , Genete Mathieu , Schmitt Éric , Monnet François , Vekemans Xavier , Touzet Pascal 
Published: September 2024

Abstract
Speciation is the process leading to the emergence of new species. While being usually progressive, it can sometimes be fast with rapid emergence of reproductive barriers leading to high level of reproductive isolation. Some reproductive barriers might leave signatures in the genome, through elevated level of genetic differentiation at specific loci. Similar signatures might also be the results of linked selection acting in low recombination regions. Nottingham catchfly (Silene nutans) is a Caryophyllaceae species composed of four genetically differentiated lineages for which strong and asymmetric levels of reproductive isolation have been identified. Using population transcriptomic data from several individuals of the four lineages, we inferred the best evo-demographic scenario leading to the current reproductive isolation of these four lineages. We also tested whether loci exhibiting high level of genetic differentiation represented barrier loci or were located in low recombination regions, evolving under strong influence of linked selection. Overall, the four lineages of S. nutans have diverged in strict isolation, likely during the different glacial period, through migration in distinct glacial refugia. Speciation between these four lineages appeared to be particularly fast, likely due to fast evolving plastid genome accelerating plastid-nuclear co-evolution and the probability of plastid-nuclear incompatibilities in inter-lineage hybrids.
Feruloyl-CoA 6′-hydroxylase-mediated scopoletin accumulation enhances cotton resistance to Verticillium dahliae
Authors: Gao Linying , Wang Ping , Yan Xin , Li Jingmin , Ma Li , Hu Menghui , Ge Xiaoyang , Li Fuguang , Hou Yuxia 
Published: September 2024

Abstract
Verticillium dahliae is a widespread and destructive soilborne fungus that can cause vascular wilt disease and substantially reduce cotton (Gossypium hirsutum) yield and quality. Scopoletin, a natural coumarin, exhibits antifungal activity against V. dahliae; however, the mechanisms of action remain unclear. In this study, we reveal the regulatory activities of feruloyl-CoA 6′-hydroxylase 1 (GhF6′H1) in enhancing V. dahliae resistance by modulating scopoletin accumulation. Silencing GhF6′H1, encoding the pivotal enzyme in scopoletin biosynthesis, through virus-induced silencing resulted in increased susceptibility to V. dahliae and decreased scopoletin accumulation. In transgenic cotton plants expressing GhF6′H1 under the CaMV 35S promoter, GhF6′H1 modulated scopoletin accumulation, affecting cotton resistance to V. dahliae, with increased resistance associated with increased scopoletin accumulation. GhF6′H1 has been identified as a direct target of the transcription factor GhWRKY33-like, indicating that GhWRKY33-like can bind to and activate the GhF6′H1 promoter. Moreover, GhWRKY33-like overexpression in cotton-enhanced resistance to V. dahliae through scopoletin accumulation, phenylpropanoid pathway activation, and upregulation of defense response genes. Ectopic expression of GhF6′H1 resulted in effective catalysis of scopoletin synthesis in enzyme assays using substrates like feruloyl coenzyme A, while molecular docking analysis revealed specific amino acid residues playing crucial roles in establishing salt-bridge interactions with the substrate. These findings suggest that GhF6′H1, regulated by GhWRKY33-like, plays a crucial role in enhancing cotton resistance to V. dahliae by modulating scopoletin accumulation.
Genomes of autotetraploid wild and cultivated Ziziphus mauritiana reveal polyploid evolution and crop domestication
Authors: Guo Mingxin , Bi Guiqi , Wang Huan , Ren Hui , Chen Jiaying , Lian Qun , Wang Xiaomei , Fang Weikuan , Zhang Jiangjiang , Dong Zhaonian , Pang Yi , Zhang Quanling , Huang Sanwen , Yan Jianbin , Zhao Xusheng 
Published: September 2024

Abstract
Indian jujube (Ziziphus mauritiana) holds a prominent position in the global fruit and pharmaceutical markets. Here, we report the assemblies of haplotype-resolved, telomere-to-telomere genomes of autotetraploid wild and cultivated Indian jujube plants using a 2-stage assembly strategy. The generation of these genomes permitted in-depth investigations into the divergence and evolutionary history of this important fruit crop. Using a graph-based pan-genome constructed from 8 monoploid genomes, we identified structural variation (SV)-FST hotspots and SV hotspots. Gap-free genomes provide a means to obtain a global view of centromere structures. We identified presence–absence variation-related genes in 4 monoploid genomes (cI, cIII, wI, and wIII) and resequencing populations. We also present the population structure and domestication trajectory of the Indian jujube based on the resequencing of 73 wild and cultivated accessions. Metabolomic and transcriptomic analyses of mature fruits of wild and cultivated accessions unveiled the genetic basis underlying loss of fruit astringency during domestication of Indian jujube. This study reveals mechanisms underlying the divergence, evolution, and domestication of the autotetraploid Indian jujube and provides rich and reliable genetic resources for future research.
Everettian quantum mechanics and the ghost of fission
Authors: Quirke Josh 
Published: September 2024

Abstract
Arguments from fission cases, most notably made by Parfit, have historically been utilized in discussions of Everettian quantum mechanics (EQM) in an attempt to illuminate details of familiar accounts in which an agent ‘splits’. Whilst such imagery is often seen as an innocuous depiction of Everett's theory, it is in fact a poisoned chalice. I argue firstly that the fission case analogy is responsible for the conceptual foundations of probability arguments in EQM and secondly, following a number of disanalogies between fission cases and Everettian branching, I argue that the analogy is unfounded. I conclude that much of the discussion of the probability problem over the past 20 years has been predicated on a problematic analogy and its effects are still apparent today.
Biological properties and characterization of several variations of a clinical human plasma-based skin substitute model and its manufacturing process
Authors: Sierra-Sánchez Álvaro , Cabañas-Penagos Jorge , Igual-Roger Sandra , Martínez-Heredia Luis , Espinosa-Ibáñez Olga , Sanabria-de la Torre Raquel , Quiñones-Vico María I , Ubago-Rodríguez Ana , Lizana-Moreno Antonio , Fernández-González Ana , Guerrero-Calvo Jorge , Fernández-Porcel Natividad , Ramírez-Muñoz Arena , Arias-Santiago Salvador 
Published: September 2024

Abstract
Human plasma is a natural biomaterial that due to their protein composition is widely used for the development of clinical products, especially in the field of dermatology. In this context, this biomaterial has been used as a scaffold alone or combined with others for the development of cellular human plasma-based skin substitutes (HPSSs). Herein, the biological properties (cell viability, cell metabolic activity, protein secretion profile and histology) of several variations of a clinical HPSS model, regarding the biomaterial composition (alone or combined with six secondary biomaterials – serine, fibronectin, collagen, two types of laminins and hyaluronic acid), the cellular structure (trilayer, bilayer, monolayer and control without cells) and their skin tissue of origin (abdominal or foreskin cells) and the manufacturing process [effect of partial dehydration process in cell viability and comparison between submerged (SUB) and air/liquid interface (ALI) methodologies] have been evaluated and compared. Results reveal that the use of human plasma as a main biomaterial determines the in vitro properties, rather than the secondary biomaterials added. Moreover, the characteristics are similar regardless of the skin cells used (from abdomen or foreskin). However, the manufacture of more complex cellular substitutes (trilayer and bilayer) has been demonstrated to be better in terms of cell viability, metabolic activity and wound healing protein secretion (bFGF, EGF, VEGF-A, CCL5) than monolayer HPSSs, especially when ALI culture methodology is applied. Moreover, the application of the dehydration, although required to achieve an appropriate clinical structure, reduce cell viability in all cases. These data indicate that this HPSS model is robust and reliable and that the several subtypes here analysed could be promising clinical approaches depending on the target dermatological disease.
Product Market Competition and Convertible Debt Financing
Authors: Lei Cheng , Lyandres Evgeny , Veld Chris , Xia Ying 
Published: September 2024

Abstract
Competitive threats motivate firms to use convertible debt because the possibility of future conversion enhances financial flexibility. Consistent with this intuition, we find that the intensity of competitive threats is positively associated with convertible debt financing at both the extensive and intensive margins. By using large tariff reductions as exogenous shocks to competition we show that this relation is likely causal. Convertible debt usage in response to competitive threats strongly depends on a firm’s relative financial and competitive conditions. In addition, firms increase the probability of future conversion by tailoring convertible debt features. (JEL D34, G30, G32, G39)
Received: 11 September 2023; Editorial decision: 15 June 2024 Editor: Isil Erel
Structural models predict a significantly higher binding affinity between the NblA protein of cyanophage Ma-LMM01 and the phycocyanin of Microcystis aeruginosa NIES-298 compared to the host homolog
Authors: Meza-Padilla Isaac , McConkey Brendan J , Nissimov Jozef I 
Published: September 2024

Abstract
Horizontal gene transfer events between viruses and hosts are widespread across the virosphere. In cyanophage-host systems, such events often involve the transfer of genes involved in photosynthetic processes. The genome of the lytic cyanophage Ma-LMM01 infecting the toxic, bloom-forming, freshwater Microcystis aeruginosa NIES-298 contains a homolog of the non-bleaching A (nblA) gene, which was probably transferred from a cyanobacterial host. The function of the NblA protein is to disassemble phycobilisomes, cyanobacterial light harvesting complexes that can comprise up to half of the cellular soluble protein content. NblA thus plays an essential dual role in cyanobacteria: it protects the cell from high light intensities and increases the intracellular nitrogen pool under nutrient limitation. NblA has previously been shown to interact with phycocyanin, one of the main components of phycobilisomes. Using structural modeling and protein-protein docking, we show that the NblA dimer of Ma-LMM01 is predicted to have a significantly higher binding affinity for M. aeruginosa NIES-298 phycocyanin (αβ)6 hexamers, compared to the host homolog. Protein-protein docking suggests that the viral NblA structural model is able to bind deeper into the phycocyanin groove. The main structural difference between the virus and host NblA appears to be an additional α-helix near the N-terminus of the viral NblA, which interacts with the inside of the phycocyanin groove and could thus be considered partly responsible for this deeper binding. Interestingly, phylogenetic analyses indicate that this longer nblA was probably acquired from a different Microcystis host. Based on infection experiments and previous findings, we propose that a higher binding affinity of the viral NblA to the host phycocyanin may represent a selective advantage for the virus, whose infection cycle requires an increased phycobilisome degradation rate that is not fulfilled by the NblA of the host.
Development of a Referral Pathway to Address Health-Harming Legal Needs at a Federally Qualified Health Center
Authors: Bulatovic Marija J. , Sallen Sarah , Reising Virginia 
Published: September 2024

ABSTRACT

Background:
Health-harming legal needs are legal burdens that negatively affect a person's overall health. Medical–legal partnerships (MLPs) are a cost-effective way for health care systems to improve overall health and access to health care and empower health care providers to become more active in addressing health-harming legal needs and social determinants of health. This article describes the implementation of a referral pathway to an MLP in a nurse-managed community health center. This pathway was used by the health center's clinical team to help connect patients who had burdensome legal needs with legal professionals who could further help evaluate those needs.

Methods:
An MLP team developed a referral pathway in which all adult patients were asked to complete a legal screening tool to assess whether they had legal needs that could be addressed by an MLP's intervention. If a legal need was identified, the patient would meet with the community health worker for further assessment. The community health worker would then present these cases for further review to the MLP team. The Plan–Do–Study–Act approach was used to make improvements to the pathway throughout the initiative.

Results:
The referral pathway was used in 70.8% of patient visits in the first seven weeks of implementation, with 209 legal screenings completed. Of those, 38 patients (18.2%) reported a legal need, 12 of whom (31.6%) were referred to the MLP.

Conclusions:
The referral pathway is a useful means of determining legal needs while also screening for social determinants of health. This process allows health care teams to address both health-harming legal needs and social determinants of health in a community health center.
Clinical Importance of Redundant Nerve Roots in Patients with Symptomatic Lumbar Spinal Stenosis
Authors: Franssen Eric , Weber Clemens , Myklebust Tor Åge , Austevoll Ivar Magne , Brisby Helena , Hellum Christian , Storheim Kjersti , Aaen Jørn , Banitalebi Hasan , Brox Jens Ivar , Indrekvam Kari , Hermansen Erland 
Published: September 2024

Study Design.
Post-hoc analysis of data from a randomized clinical trial.

Objective.
To compare preoperative symptoms of patients with lumbar spinal stenosis (LSS) with and without redundant nerve roots (RNR), and to compare the change in clinical outcomes between those two groups 2 years after decompression surgery.

Summary of Background Data.
RNR are often seen on MRI in patients with spinal stenosis. Previous studies have reported that patients with RNR are older and have worse symptoms at baseline. A meta-analysis from 2018 concluded that this radiological sign could be seen as a negative predictor of outcome. High quality prospective studies are lacking.

Methods.
Patient characteristics and reported pain and function scores were compared between LSS groups with (RNR+) and without RNR (RNR-) at baseline and after 2 years follow-up. Primary outcome was the mean change in the Oswestry Disability Score (ODI). Secondary outcomes included mean change in scores of the Zurich Claudication Questionnaire (ZCQ) and the numeric rating scale (NRS) for leg and back pain.

Results.
Out of 416 patients included in the present analysis, 163 (39%) had RNR at baseline. Both groups were similar in regard to patient age, smoking habits, BMI and duration of symptoms. Both groups also showed similar pain and function scores at baseline. The RNR+ group contained a significantly higher proportion of men, patients with severe stenosis and multiple stenotic levels on MRI. At 2-year follow-up the mean change of ODI was −22.1 in the RNR+ group and −17.4 in RNR- group (mean difference 4.7 (95%CI 1.3-8.2) P=0.007). Statistically significant differences were also found for secondary outcomes ZCQ, and NRS leg and back pain favouring the RNR+ group.

Conclusion.
Patients with RNR had similar baseline characteristics and similar symptoms as patients without. RNR before surgery were associated with better clinical improvement 2 years after decompression.
The actin-binding protein drebrin disrupts NF2-LATS kinases complex assembly to facilitate liver tumorigenesis
Authors: Sun Yang , Wei Henan , Yu Wentao , Gao Haoran , Li Jinhui , Li Xiaoyu , Zhang Haijiao , Zhang Haoen , Miao Sen , Zhao Lihua , Yang Ruizeng , Xu Jinjin , Lu Yi , Wei Fang , Zhou Hu , Gao Daming , Jin Yunyun , Zhang Lei 
Published: September 2024

Background and Aims:
The Hippo signaling has emerged as a crucial regulator of tissue homeostasis, regeneration, and tumorigenesis, representing a promising therapeutic target. Neurofibromin 2 (NF2), a component of Hippo signaling, is directly linked to human cancers but has been overlooked as a target for cancer therapy.

Approach and Results:
Through a high-content RNA interference genome-wide screen, the actin-binding protein Drebrin (DBN1) has been identified as a novel modulator of YAP localization. Further investigations have revealed that DBN1 directly interacts with NF2, disrupting the activation of large tumor suppressor kinases (LATS1/2) by competing with LATS kinases for NF2 binding. Consequently, DBN1 knockout considerably promotes YAP nuclear exclusion and repression of target gene expression, thereby preventing cell proliferation and liver tumorigenesis. We identified three lysine residues (K238, K248, and K252) essential for DBN1-NF2 interaction and developed a mutant DBN1 (DBN1-3Kmut) that is defective in NF2 binding and incompetent to trigger NF2-dependent YAP activation and tumorigenesis both in vitro and in vivo. Furthermore, BTP2, a DBN1 inhibitor, successfully restored NF2-LATS kinase binding and elicited potent antitumor activity. The combination of sorafenib and BTP2 exerted synergistic inhibitory effects against HCC.

Conclusions:
Our study identifies a novel DBN1-NF2-LATS axis, and pharmacological inhibition of DBN1 represents a promising alternative intervention targeting the Hippo pathway in cancer treatment.
Optimizing surgical performance and safety in endoresection of uveal melanoma.
Authors: Romano Mario R , Ferrara Mariantonia , Feo Alessandro , Merico Anna , Angi Martina 
Published: September 2024

Purpose:
To present a standardized surgical technique for endoresection of uveal melanoma (UM) minimizing the risk of serious adverse events, including fatal gas embolism.

Methods:
Ten UM patients underwent endoresection following proton beam radiotherapy for radiotherapy-related vascular complications. Vortex veins located in correspondence of the tumor base had been cauterized at the time of tantalum markers placement. Endoresection was performed following complete 25G vitrectomy, endolaser and endodiathermy. The tumor was removed using a subretinal or transretinal approach depending on retinal infiltration. If needed, perfluorodecalin (PFD) was injected to stabilise the retina. Fluid-silicone oil (SO) or PFD-SO exchange was performed, avoiding air.

Results:
Endoresection was successfully performed in all eyes with no intraoperative complications. Mean follow-up (FU) was 10.8 ± 3.2 months. One patient was enucleated due to neovascular glaucoma. At the last FU, the remaining patients had the eye preserved and no signs of local recurrence or neovascular glaucoma.

Conclusion:
Our standardized surgical technique for UM endoresection appeared to be safe, minimizing the risk of serious intraoperative and postoperative adverse events.
THREE-DIMENSIONAL HILL OF VISION OF RETINAL SENSITIVITY IN PARTICIPANTS WITH X-LINKED RETINITIS PIGMENTOSA UNDER SCOTOPIC AND MESOPIC CONDITIONS
Authors: Yaghy Antonio , Alibhai A. Yasin , De Pretto Lucas R. , Curtiss Darin , Birch David G. , Waheed Nadia K. 
Published: September 2024

Purpose:
To evaluate the utility of three-dimensional hill of vision (HOV) analysis in assessing retinal sensitivity in patients with X-linked retinitis pigmentosa (XLRP) under scotopic cyan, scotopic red, and mesopic microperimetry conditions.

Methods:
Baseline microperimetry data from 31 eyes of 16 patients with XLRP enrolled in the Horizon study were analyzed. HOVs were generated using thin plate spline interpolation. Grid volumes of the central 20° (V20) were compared between lighting conditions using the Wilcoxon signed-rank test with Bonferroni correction. Central and global deficits were evaluated across age groups and genotypes.

Results:
The mesopic group showed the highest mean V20 (1.3 dB-Sr), followed by scotopic red (0.6 dB-Sr) and scotopic cyan (0.5 dB-Sr). Significant differences were found between mesopic and scotopic conditions (P < 0.01), but not between scotopic conditions (P = 0.26). Central and global deficits were more prevalent under scotopic conditions and increased with age.

Conclusion:
HOV analysis provides a comprehensive assessment of retinal sensitivity in XLRP, enabling detection of localized changes and quantification of sensitivity gradients. This volumetric approach offers advantages over traditional methods for diagnosis, monitoring progression, and evaluating treatment response.