bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Perfusion Index in Ugandan Children With Plasmodium falciparum Severe Malaria: Secondary Analysis of Outcomes in a 2014–2017 Cohort Study
Authors: Boland Wesley , Datta Dibyadyuti , Namazzi Ruth , Bond Caitlin , Conroy Andrea L. , Mellencamp Kagan A. , Opoka Robert O. , John Chandy C. , Rivera Michael Lintner 
Published: September 2024

OBJECTIVES:
Continuous, noninvasive tools to monitor peripheral perfusion, such as perfusion index (PI), can detect hemodynamic abnormalities and assist in the management of critically ill children hospitalized with severe malaria. In this study of hospitalized children with severe malaria, we aimed to assess whether PI correlates with clinical markers of perfusion and to determine whether combining PI with these clinical measures improves identification of children with greater odds of mortality.

DESIGN:
Post hoc analysis of a prospective, multicenter, cohort study conducted between 2014 and 2017.

SETTING:
Two referral hospitals in Central and Eastern Uganda.

PATIENTS:
Six hundred children younger than 5 years old with severe malaria and 120 asymptomatic community children.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
PI was measured at 6-hour intervals for the first 24 hours of hospitalization. We compared PI to standard clinical perfusion measures such as capillary refill time, presence of cold peripheral limbs, or temperature gradient. Admission PI was highly correlated with clinical measures of perfusion. Admission PI was lower in children with severe malaria compared with asymptomatic community children; and, among the children with severe malaria, PI was lower in those with clinical features of poor perfusion or complications of severe malaria, such as shock and hyperlactatemia (all p < 0.02). Among children with severe malaria, lower admission PI was associated with greater odds of mortality after adjustment for age, sex, and severe malaria criteria (adjusted odds ratio, 2.4 for each log decrease in PI [95% CI, 1.0–5.9]; p = 0.045). Diagnostically, the presence of two consecutive low PI measures (< 1%) predicted mortality, with a sensitivity of 50% and a specificity of 76%.

CONCLUSIONS:
In severe malaria, PI correlates with clinical complications (including shock and elevated serum lactate) and may be useful as an objective, continuous explanatory variable associated with greater odds of later in-hospital mortality.
Long-Term Three-Dimensional Morphometric Outcome Study of Nasal Bone in Cleft Patients
Authors: Enomoto Kei , Sakamoto Yoshiaki , Miyamoto Junpei 
Published: September 2024

Cleft lip nose deformities are characterized by underlying features in the bony skeleton as well as the soft tissues; however, no previous study has focused on the evaluation of the nasal bone. The aim of this study was to compare nasal bone features among adult patients with unilateral cleft lip with or without cleft palate, those with bilateral cleft lip and palate, and controls. Included in this retrospective study were patients aged ≥16 years with nonsyndromic cleft who underwent long-term orthodontic treatment and controls aged 18–45 years who underwent surgery for jaw deformities at Keio University Hospital. Piriform width, nasal width, and nasomaxillary angle values measured on CT were compared among the groups using the Wilcoxon rank sum test. Nine patients had unilateral cleft lip and alveolar cleft, 19 had unilateral cleft lip and cleft palate, and 14 had bilateral cleft lip and palate (BCLCP). There were 18 controls. Mean piriform width and mean nasomaxillary angle were significantly greater in the BCLCP group than the control group (20.1±2.54 mm versus 18.8±1.35 mm, P<0.05; and 105.8±8.13 degrees versus 100.4±7.95 degrees, P<0.05, respectively). There was no significant difference in mean nasal width among the groups. Nasal bone morphology was not affected by initial cleft lip alone or by the presence or absence of cleft palate. Patients with bilateral cleft lip and palate have a wider and lower nose than those without cleft deformity and might benefit more from reduction of the bony nasal width than from treatment of the soft tissues.
Three-Part Analysis for Designing Nasal Alar Reduction Surgery in Asian Patients
Authors: Yang Jie , Dai Chuan-Chang , Yu Bao-Fu 
Published: September 2024

Background:
The external nasal alar reduction can be associated with many complications, such as nostril malformation and significant scarring. The authors proposed a 3-part analysis method for the design of nasal alar reduction surgery with the aim of improving nasal alar morphology more precisely.

Methods:
The 3-part analysis was based on the patient’s flared nose, wide nasal base, and drooping ala, respectively. We included 20 patients who underwent this surgery between January 2021 and January 2022. The visual analog scale (VAS) and the Stony Brook Scar Evaluation Scale (SBSES) were used to assess postoperative scar outcomes. The preoperative and postoperative ratios of the interalar distance to intercanthal distance and nostril shape were analyzed. Patient-reported satisfaction with the esthetic outcome was also assessed.

Results:
All operations were successfully completed. There were no postoperative complications, such as wound infection or skin necrosis. Both VAS and SBSES assessment of postoperative scarring suggested keloid hyperplasia at 3 months postoperatively. At 12 months postoperatively, the scarring was insignificant and improved significantly over 3 months postoperatively. The mean ratio of the interalar distance to intercanthal distance decreased significantly from 1.15 preoperatively to 1.01 postoperatively (P<0.05). The shape of the patient’s nostrils was also significantly improved after surgery compared with the preoperative period. Patient-reported satisfaction after surgery was high at long-term follow-up.

Conclusions:
The 3-part analysis to design an external nasal alar reduction procedure can accurately improve the morphology of nasal flaring, excessively wide nasal alar base, and nasal ptosis in Asian patients.

Level of Evidence:
IV.
Social determinants of injection drug use-associated bacterial infections and treatment outcomes: systematic review and meta-analysis
Authors: Brothers Thomas D. , Lewer Dan , Bonn Matthew , Kim Inhwa , Comeau Emilie , Figgatt Mary , Eger William , Webster Duncan , Hayward Andrew , Harris Magdalena 
Published: September 2024

ABSTRACTBackgroundIndividual injecting practices (e.g., intramuscular injecting, lack of skin cleaning) are known risk factors for injection drug use-associated bacterial and fungal infections; however, social contexts shape individual behaviours and health outcomes. We sought to synthesize studies assessing potential social determinants of injecting-related infections and treatment outcomes.MethodsWe searched five databases for studies published between 1 January 2000 and 18 February 18 2021 (PROSPERO CRD42021231411). We included studies of association (aetiology), assessing social determinants, substance use, and health services exposures influencing development of injecting-related infections and treatment outcomes. We pooled effect estimates via random effects meta-analyses.ResultsWe screened 4,841 abstracts and included 107 studies. Several factors were associated with incident or prevalent injecting-related infections: woman/female gender/sex (adjusted odds ratio [aOR] 1.57, 95% confidence interval [CI] 1.36-1.83; n=20 studies), homelessness (aOR 1.29, 95%CI 1.16-1.45; n=13 studies), cocaine use (aOR 1.31, 95%CI 1.02–1.69; n=10 studies), amphetamine use (aOR 1.74, 95%CI 1.39-2.23; n=2 studies), public injecting (aOR 1.40, 95%CI 1.05–1.88; n=2 studies), requiring injecting assistance (aOR 1.78, 95%CI 1.40–2.27; n=8 studies), and use of opioid agonist treatment (aOR 0.92, 95%CI 0.89–0.95; n=9 studies). Studies assessing outcomes during treatment (e.g., premature hospital discharge) or afterward (e.g., rehospitalization; all-cause mortality) typically had smaller sample sizes and imprecise effect estimates.ConclusionsInjecting-related infections and treatment outcomes may be shaped by multiple social contextual factors. Approaches to prevention and treatment should look beyond individual injecting practices towards addressing the social and material conditions within which people live, acquire and consume drugs, and access health care.
Evaluation of Sex-Related Differences in Cerebrovascular Bypass Patency: An Institutional Review of 357 Direct Cerebral Bypasses
Authors: McGuire Laura Stone , Abou-Mrad Tatiana , Du Xinjian , Alaraj Ali , Amin-Hanjani Sepideh , Atwal Gursant , Charbel Fady T. 
Published: September 2024

ABSTRACTIntroductionDemographics and comorbid conditions play a role in vascular health, yet their specific impact on cerebrovascular bypass patency remains unclear.MethodsAn institutional database of 357 patients with intracranial bypass procedures between 08/2001-05/2022 was retrospectively reviewed. Patients with bypass for all causes (e.g., aneurysm, atherosclerotic disease, Moyamoya disease) were included. Medical history, surgical technique, and flow-related measurements (intraoperatively and on quantitative MRA at follow-up) were compared across biological sex and in relation to bypass patency.ResultsOf 357 patients, 141 were male (39.5%) and 216 were female (60.5%) with average age 49.0+/-16.7. Bypass patency at last follow-up was 84.4% for men vs. 69.2% for women (p=0.001). Significant differences were seen in underlying diagnoses, with more aneurysm and Moyamoya cases represented in female sex (p<0.001); irrespective of diagnosis, lower patency rates were seen in women when considering bypass for aneurysm (p=0.032), Moyamoya disease (p=0.035), and for atherosclerotic disease (p=0.159). Medical comorbidities were seen at higher rates in men, with comorbidity score 2.7 vs. 2.1 (p<0.001). Cut flow was higher in men 59.2 vs. 51.1 (p=0.028), but no significant differences were seen in intraoperative bypass flow, cut flow index (CFI), or follow-up QMRA. After removing cases using interposition grafts, similar differences were redemonstrated. Propensity score matched analysis found females have a 2.71 higher chance of bypass occlusion after adjusting for CFI (p=0.017, 95% CI: 1.19-6.18).ConclusionBiological sex appears to play a significant role in bypass patency, across diagnoses. Women were significantly less likely to have patent bypasses at last follow-up, despite having less medical comorbidities than men and despite having similar intraoperative and perioperative flows. Further study is required to better elucidate the influence of sex on long-term bypass patency.
Prevalence and Determinants of E-Cigarette Use Among Diploma Students in a Vocational College: A Cross-Sectional Study
Authors: Mohd Shoaib Siti Munisah , Ahmad Norliza , Mahmud Aidalina 
Published: September 2024

ABSTRACTIntroductionThe prevalence of e-cigarette use is increasing globally, particularly among young adults which can predispose them to various health risks. This study aimed to determine the prevalence and factors associated with e-cigarette use among diploma students in a vocational college in a state in Malaysia.MethodologyA cross-sectional study using probability proportionate to size sampling was conducted among 700 diploma students at a vocational college in Malaysia. A validated, self- administered questionnaire was distributed through the online method from April to May 2024. Bivariate analysis was done using Pearson’s chi-square test or Fisher’s exact and simple logistic regression. Multivariable analysis was performed using multiple logistic regression for variables with a p<0.25 in the bivariate analysis. A value of p<0.05 was considered statistically significant, with a 95% confidence interval.ResultsThe response rate was 87.7% with the prevalence of e-cigarette use was 29.0%. Factors significantly associated with e-cigarette use included male (aOR = 5.2, 95% CI: 2.7- 10.1), other races (aOR = 83.1, 95% CI: 2.2-3146.3), perceived e-cigarette aids in quit smoking (aOR = 1.6, 95% CI: 1.2-2.1), perceived e-cigarette does not contain the toxic chemicals found in conventional cigarette (aOR = 1.4, 95% CI: 1.0-2.0), having close friends who use conventional cigarette (aOR = 2.1, 95% CI: 1.0-4.1) or e-cigarette (aOR = 8.0, 95% CI: 2.3- 28.1), e-cigarette exposure on television (aOR = 2.1, 95% CI: 1.0-4.2), positive attitude towards e-cigarette (aOR = 1.2, 95% CI: 1.1-1.2), higher willingness to use (aOR = 1.2, 95% CI: 1.0-1.3), and higher intention to use (aOR = 1.4, 95% CI: 1.2-1.5).ConclusionFactors associated with e-cigarette use among diploma students included being male, other races (Bumiputera Sabah and Sarawak), positive health risks perceptions, peer influence, and exposure to e-cigarettes on television. Targeted interventions addressing these factors may be more effective in changing social norms and reducing e-cigarette use among this population.
Macrophages redeploy functional cancer cell surface proteins following phagocytosis
Authors: Volk Regan F. , Casebeer Sara W. , Condon Andrew C. , Zirak Bahar , Manon Nayelis , Irkliyenko Iryna , Liao Huajun , Tao Shao , Pollini Tommaso , Ramani Vijay , Maker Ajay V. , Fidler Trevor , Goodarzi Hani , Zaro Balyn W. 
Published: September 2024

AbstractMacrophage-mediated phagocytosis is a vital innate immune process altered in cancer. We show here that tumor-associated macrophages (TAMs) redeploy intact cell surface proteins from cancer cells to their own cell surface. We initially observed the canonical epithelial cancer surface marker EpCAM on the surface of TAMs in primary human solid tumors but not paired peripheral blood macrophages. In a murine model of metastatic breast cancer, we also observed EpCAM on the surface of primary TAMs that have phagocytosed breast cancer cells. In a model of a myeloproliferative neoplasm, we again found engulfed cell-derived surface proteins on the surface of macrophages following phagocytosis. A co-culture system and proteomics assay that tags proteins based on their cell-of-origin revealed hundreds of cell surface proteins synthesized in cancer cells are present and fully intact on the surface of macrophages following phagocytosis. Using a biotin transfer assay, we determined that these proteins were on the surface of the cancer cell prior to redeployment by the macrophage following phagocytosis. Furthermore, macrophages that redeploy a neutral amino acid transporter correspondingly show increased transport of an unnatural amino acid substrate. Widespread acquisition of proteins from engulfed cells may contribute to two critical TAM phenotypes: the inability to phagocytose and reprogrammed metabolism.
Independent evolution of ipecac alkaloid biosynthesis
Authors: Colinas Maite , Morweiser Clara , Dittberner Olivia , Chioca Bianca , Alam Ryan , Leucke Helena , Nakamura Yoko , Guerrero Delia Ayled Serna , Heinicke Sarah , Kunert Maritta , Wurlitzer Jens , Ploss Kerstin , Hong Benke , Grabe Veit , Lopes Adriana A. , O’Connor Sarah E. 
Published: September 2024

AbstractIpecac alkaloids are medicinal monoterpenoid-derived tetrahydroisoquinoline alkaloids found in two distantly related plants:Carapichea ipecacuanha(Gentianales) andAlangium salviifolium(Cornales). We have elucidated ipecac alkaloid biosynthesis in both species, conclusively demonstrating that biosynthesis of the structurally complex ipecac alkaloid protoemetine has evolved independently. We show that although protoemetine biosynthesis proceeds via the same chemical logic in both species, each plant uses a distinct monoterpene precursor. Moreover, we provide evidence that both plants initiate ipecac biosynthesis by a non-enzymatic Pictet-Spengler reaction, and we elucidate the biosynthetic fate of both the 1Rand 1Sstereoisomers that are produced in this non-stereoselective reaction. Phylogenetic analyses clearly show independent pathway evolution through parallel and convergently evolved enzymes. This work provides insight into how nature can capitalize on highly reactive starting substrates, the manner in which multi-step pathways can arise, and also lays the foundation for metabolic engineering of these important medicinal compounds.
Molecular changes in agroinfiltrated leaves ofNicotiana benthamianaexpressing suppressor of silencing P19 and coronavirus-like particles
Authors: Hamel Louis-Philippe , Poirier-Gravel Francis , Paré Marie-Ève , Tardif Rachel , Comeau Marc-André , Lavoie Pierre-Olivier , Langlois Andréane , Goulet Marie-Claire , Michaud Dominique , D’Aoust Marc-André 
Published: September 2024

SummaryThe production of coronavirus disease 2019 vaccines can be achieved by transient expression of the Spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 in agroinfiltrated leaves ofNicotiana benthamiana. Relying on bacterial vectorAgrobacterium tumefaciens, this process is favored by the co-expression of viral silencing suppressor P19. Upon expression, the S protein enters the cell secretory pathway, before being trafficked to the plasma membrane where formation of coronavirus-like particles (CoVLPs) occurs. We previously characterized effects of influenza virus hemagglutinin forming VLPs through similar processes. However, leaf samples were only collected after six days of expression and it remains unknown whether influenza VLPs and CoVLPs induce similar responses. Here, time course sampling was used to profile responses ofN. benthamianaleaf cells expressing P19 only, or P19 along with the S protein. The latter triggered early, but transient activation of the unfolded protein response and waves of transcription factor genes involved in immunity. Accordingly, defense genes were induced with different expression kinetics, including those promoting lignification, terpene biosynthesis, and oxidative stress. Crosstalk between stress hormone pathways also occurred, notably leading to the repression of jasmonic acid biosynthesis genes after agroinfiltration, and dampening of salicylic acid-inducible responses upon S protein accumulation. Overall, influenza VLP- and CoVLP-induced responses broadly overlapped, suggesting nanoparticle production to have the most effects on plant immunity, regardless of the virus surface proteins expressed. Taking advantage of RNAseq inferences, we finally show the co-expression of Kunitz trypsin inhibitors to reduce CoVLP-induced defense and leaf symptoms, with no adverse effect on plant productivity.
Do Protein Language Models Learn Phylogeny?
Authors: Tule Sanjana , Foley Gabriel , Bodén Mikael 
Published: September 2024

AbstractDeep machine learning demonstrates a capacity to uncover evolutionary relationships directly from protein sequences, in effect internalising notions inherent to classical phylogenetic tree inference. We connect these two paradigms by assessing the capacity of protein-based language models (pLMs) to discern phylogenetic relationships without being explicitly trained to do so. We evaluate ESM2, ProtTrans and MSA-Transformer relative to classical phylogenetic methods, while also considering sequence insertions and deletions (indels) across 114 Pfam datasets. The largest ESM2 model tends to outperform other pLMs (including the multimodal ESM3) by recovering phylogenetic relationships among homologous protein sequences in both low- and high-gap settings. pLMs agree with conventional phylogenetic methods in general, but more so for protein families with fewer implied indels, highlighting indels as a key factor differentiating classical phylogenetics from pLMs. We find that pLMs preferentially capture broader as opposed to finer evolutionary relationships within a specific protein family, where ESM2 has a sweet spot for highly divergent sequences, at remote distance. Less than 10% of neurons are sufficient to broadly recapitulate classical phylogenetic distances; when used in isolation the difference between the paradigms is further diminished. We show these neurons are polysemantic, shared among different homologous families but never fully overlapping. We highlight the potential of ESM2 as a complementary tool for phylogenetic analysis, especially when extending to remote homologs that are difficult to align and imply complex histories of insertions and deletions.
Epitranscriptome Mapping of m6A RNA Modifications in Glioma Tumor Tissue
Authors: Batool Syeda Maheen , Khan Saad Murtaza , Muralidharan Koushik , Escobedo Ana K. , Lee Hanna , Ekanyake Emil , Hsia Tiffaney , Carter Bob S. , Balaj Leonora 
Published: September 2024

AbstractGlioma represents the most common primary central nervous system (CNS) neoplasm in adults. IDH1 mutation is recognized as a hallmark alteration with important diagnostic and prognostic implications. There is considerable evidence for global DNA hypermethylation induced secondary to IDH mutation. However, there is limited understanding of the RNA methylation patterns and its role in glioma biology. In this study, we performed transcriptome wide profiling of N6-methyladenosine (m6A) modifications across IDH mutant (n = 8) and wild-type (n = 7) gliomas using Oxford Nanopore Technologies’ direct RNA sequencing platform. Our approach enabled high-depth coverage of native transcripts, revealing nearly twice as many full-length transcripts in IDH mutant gliomas compared to wild-type. Notable differences in alternative splicing were observed across glioma subtypes, with truncated and non-coding isoforms more prevalent in glioblastoma (GBM). We further identified significant changes in isoform usage within key metabolic (NAMPT, PKM) and immune (CD63, CD151, CD81) pathways. Chromosomal distribution of m6A sites showed a higher prevalence of m6A modifications in IDH mutant gliomas, with the most pronounced differences on chromosomes 19 and 16. Further stratification by TERT, MGMT, and TP53 mutations revealed similar patterns of increased m6A site numbers in mutant groups, highlighting the importance of integrating epigenomic and epitranscriptomic data in glioma research. These findings highlight the role of m6A modifications in the metabolic reprogramming unique to IDH mutant gliomas, providing insights into potential mechanisms of tumorigenesis and therapeutic resistance.
Perceptions of students on artificial intelligence-generated content avatar utilization in learning management system
Authors: Tan Saw Fen 
Published: September 2024

PurposeThis study aims to explore students’ perceptions of the use of an artificial intelligence-generated content avatar (AIGC avatar) within a learning management system (LMS).Design/methodology/approachThis qualitative research involved seven postgraduate students. Data were collected through individual, in-depth interviews. The videos of the AIGC avatar, created using Leonardo, ChatGPT and Heygen, were uploaded to the LMS to communicate with students for the purposes of a welcome note, assignment guide, assignment feedback, tutorial reminders and preparation as well as to provide encouragement and study tips. Students were interviewed at the end of the semester.FindingsThe findings of this study indicated that the majority of participating students held positive perceptions regarding the use of the AIGC avatar in the LMS. They reported that it enhanced their perceived instructor’s social presence and motivation to learn. The assignment guide and feedback were particularly valued by the participants. While some students noted the AIGC avatar’s lack of naturalness, others appreciated the clear and professional speech it delivered.Research limitations/implicationsThe study was confined to seven students from a single course at one institution, which may limit the generalizability of the findings. Future research could involve a larger and more diverse group of participants.Practical implicationsThe findings may offer education providers an alternative solution for engaging students in an LMS.Originality/valueThis study highlights the potential of AIGC avatars to replace text-based communication in LMS and enhance students’ perceived instructor social presence.