bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in Opioid Prescribing Among Plastic Surgery Residents After Bilateral Breast Reduction
Authors: Fiscella Kimberly , Awad Amanda N. , Shihadeh Hanaa , Patel Ashit 
Published: August 2023

Background
Prescription opioid misuse in the United States accounts for significant avoidable morbidity and mortality. Over one third of all prescriptions written by surgeons are for opioids. Although opioids continue to provide needed analgesia for surgical patients, there are few guidelines in the plastic surgery literature for their safe and appropriate use after surgery. The consequence is wide variability and excessive opioid prescriptions. Understanding patterns of prescribing among plastic surgery residents is a crucial step toward developing safer practice models for managing postoperative pain.

Methods
The authors performed a retrospective analysis of discharge opioid prescriptions after bilateral breast reduction at a single academic medical center from 2018 to 2021. Single factor 1-way analysis of variance was used to evaluate prescribing patterns by resident, postgraduate year, attending of record, and patient characteristics for 126 patients. A multivariate analysis was performed to determine the degree to which these factors predicted opioid prescriptions.

Results
This analysis revealed significant variability among residents prescribing opioids after bilateral breast reductions (P < 0.001) irrespective of patient comorbidities and demographics. Residents were found to be the main predictor of opioid prescriptions after surgery (P < 0.001) with a greater number of morphine milligram equivalents prescribed by the more junior residents (P < 0.001).

Conclusions
Excessive and variable opioid prescriptions among plastic surgery residents highlight the need for opioid prescribing education early in surgical training and improved oversight and communication with attending surgeons. Furthermore, implementation of evidence-based opioid-conscious analgesic protocols after common surgical procedures may improve patient safety by standardizing postoperative analgesic prescriptions.
Let-Down Rhinoplasty in Patients With Cleft Lip Nose
Authors: Tapan Mehmet , Şeker Yunus Emre , Zöhre Cihan Taylan , İşler Vedat Can , Özpar Ege Bora , Özkan Özlenen , Özkan Ömer 
Published: August 2023

Background and Objectives
Rhinoplasty in patients with cleft lip nose (CLN) deformity is challenging. Cleft lip nose deformity primarily affects the nasal tip, columella, nostrils, alar base, floor, and septum. The needs of patients with CLN are quite different from those of patients who undergo primary rhinoplasty. Recently, the dorsal preservation rhinoplasty technique has gained popularity. We applied this technique to patients with CLN deformity to obtain better aesthetic and functional results.

Patients and Methods
Ten consecutive patients with indication for primary CLN reconstruction underwent let-down rhinoplasty. Rhinoplasties were performed using either the closed or open approach, with costal cartilage grafts and full-thickness skin grafts. A rhinoplasty outcome evaluation questionnaire was used to assess the results. Moreover, the use of the same questionnaire in prior patients allowed us to compare results between our previous and new techniques.

Results
The study included 6 female and 4 male patients, with ages ranging from 18 to 25 years. Only 1 patient had a history of bilateral cleft lip. Seven patients had a history of left-sided cleft lip, and 2 patients had right-sided cleft lip. Open-approach let-down rhinoplasty with costal cartilage grafts and full-thickness skin grafts was performed in 8 patients, whereas closed-approach let-down rhinoplasty with costal cartilage grafts was performed in 2 patients. Columellar struts and affected-side onlay costal cartilage grafts were used in all patients. All patients reported being satisfied with the let-down rhinoplasty outcome, and none complained of functional problems. However, nostril symmetry was not observed in some patients, particularly in patients who underwent closed-approach rhinoplasty.

Conclusions
Combining open approach, full-thickness skin graft, costal cartilage graft, and let-down rhinoplasty shows promising and satisfactory outcomes in patients with CLN. However, further studies are required to confirm this observation.
Dynamic Changes in Metabolic Status Are Associated With Risk of Ocular Motor Cranial Nerve Palsies
Authors: Choi Daye Diana , Park Kyung-Ah , Han Kyungdo , Oh Sei Yeul 
Published: August 2023

Background:
To investigate whether recovery from or development of metabolic syndrome (MetS) in a population is associated with an altered risk for ocular motor cranial nerve palsy (CNP).

Methods:
This cohort study included 4,233,273 adults without a history of ocular motor cranial nerve palsy (ocular motor CNP) who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2011. They were followed up until December 31, 2018. Participants were categorized into a MetS-free, MetS-developed, MetS-recovered, or MetS-chronic group. A multivariable Cox proportional hazard regression model was used. Model 3 was adjusted for age, sex, smoking status, alcohol consumption, and physical activity.

Results:
Compared with the MetS-free group, the MetS-chronic group had the highest risk of ocular motor CNP (hazard ratio [HR]: 1.424; 95% confidential interval [CI]: 1.294–1.567, Model 3), followed by the MetS-developed group (HR: 1.198, 95% CI: 1.069–1.343), and the MetS-recovered group (HR: 1.168, 95% CI: 1.026–1.311) after adjusting for potential confounders. The hazard ratio of ocular motor CNP in men with chronic MetS was 1.566 (95% CI, 1.394–1.761) while that of women with chronic MetS was 1.191 (95% CI, 1.005–1.411). Among age groups, those in their 30s and 40s showed the highest association between dynamic MetS status and ocular motor CNP.

Conclusions:
In our study, recovering from MetS was associated with a reduced risk of ocular motor CNP compared with chronic MetS, suggesting that ocular motor CNP risk could be managed by changing MetS status.
Explainable AI in Deep Learning-based Detection of Aortic Elongation on Chest X-ray Images
Authors: Ribeiro Estela , Cardenas Diego A. C. , Dias Felipe M. , Krieger Jose E. , Gutierrez Marco A. 
Published: August 2023

AbstractAimAortic Elongation can result from age-related changes, congenital factors, aneurysms, or conditions affecting blood vessel elasticity. It is associated with cardiovascular diseases and severe complications like aortic aneurysms and dissection. We aim to assess qualitatively and quantitatively explainable methods in order to understand the decisions of a deep learning model for Aortic Elongation detection with Chest X-Ray (CXR) images.Methods and ResultsIn this work, we evaluated the performance of deep learning models (DenseNet and EfficientNet) for aortic elongation detection based on transfer learning and fine-tunning techniques using CXR as input. DenseNet achieved higher accuracy (84.7% ± 0.7), precision (75.6% ± 1.3), sensitivity (88.7% ± 2.7), specificity (82.3% ± 1.6), F1-score (81.6% ± 1.0), and AUROC (93.1% ± 0.4) than EfficientNet. To gain insights into the decision-making process of the deep learning models, we employed Grad-CAM and LIME explainability methods. Through these techniques, we were able to successfully identify the expected location of aortic elongation in the x-ray images. Moreover, we used the pixel-flipping method to assess quantitatively the interpretations providing valuable insights into models behavior.ConclusionOur study presents a comprehensive strategy for analyzing CXR by integrating Aortic Elongation detection models with explainable methods. By incorporating explainable AI techniques, we enhanced the interpretability and understanding of the models’ decisions. This approach holds promise for aiding clinicians in timely and accurate diagnosis, potentially improving patient outcomes in clinical practice.
CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain
Authors: Elizaldi Sonny R. , Hawes Chase E , Verma Anil , Dinasarapu Ashok R. , Lakshmanappa Yashavanth Shaan , Schlegel Brent T , Rajasundaram Dhivyaa , Li Jie , Durbin-Johnson Blythe P , Ma Zhong-Min , Beckman Danielle , Ott Sean , Lifson Jeffrey , Morrison John H. , Iyer Smita S. 
Published: August 2023

ABSTRACTCD4 T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4 T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4 T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside other CNS border tissues. Sequestering TCMcells in lymph nodes using FTY720 led to reduced CCR7+ CD4 T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL57 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4 T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4 T cells in CNS immune surveillance and their decline during chronic SIV-induced neuroinflammation highlights their responsiveness to neuroinflammatory processes.GRAPHICAL ABSTRACTIn BriefUtilizing single-cell and spatial transcriptomics on adult rhesus brain, we uncover a unique CCR7+ CD4 T cell subset resembling central memory T cells (TCM) within brain and border tissues, including skull bone marrow. Our findings show decreased frequencies of this subset during SIV- induced chronic neuroinflammation, emphasizing responsiveness of CCR7+ CD4 T cells to CNS disruptions.HighlightsCCR7+ CD4 T cells survey border and parenchymal CNS compartments during homeostasis; reduced presence of CCR7+ CD4 T cells in cerebrospinal fluid leads to immune activation, implying a role in neuroimmune homeostasis.CNS CCR7+ CD4 T cells exhibit phenotypic and functional features of central memory T cells (TCM) including production of interleukin 2 and the capacity for rapid recall proliferation. Furthermore, CCR7+ CD4 T cells reside in the skull bone marrow.CCR7+ CD4 T cells are markedly decreased within the brain parenchyma during chronic viral neuroinflammation.
Analysis of Moonlighting Proteins Regulated by Curcumin and Resveratrol in Cancer
Authors: Sumantran Venil N. , Kannadasan Anand Babu 
Published: August 2023

ABSTRACTMultitasking proteins or moonlighting proteins (MLP) play a major role in human disease and many are drug targets. MLPs have a single polypeptide with two different biochemical functions and often have different cellular localizations. Analysis of MultitaskProtDB-II and Comparative Toxicogenomics databases and Gene Ontology and STRING analysis, showed that curcumin and resveratrol regulate 3 groups of MLPs. Group 1 MLPs drive epithelial mesenchymal transition (EMT), whereas MLPs in groups 2 and 3 regulate tumour growth and suppression, respectively. The 3 groups of MLPs form a complex self-regulating network due to regulatory interactions between MLPs and the presence of transcription factors (CTNNB1, p53, NRF2) with their regulators and targets. Curcumin and/or resveratrol downregulate MLPs which drive EMT (CTNNB1, FASN, SMADs 2,3,4, MECP2, MMP2, TGFβR1, HES1) and promote growth and inflammation (MMP2, EGFR, FGF2, MDR1). Second, curcumin and/or resveratrol modulate pleiotropic, regulatory ‘hub’ MLPs (GSK3β, NOTCH1, HMGB1). Third, both phytochemicals upregulate tumour suppressor CDH1, and CYCS, which triggers apoptosis. Fourth, both phytochemicals modulate p53 expression, activity, and independently downregulate tumorigenic gene targets of p53 in groups 1 and 2. This dual mechanism can permit regulation of p53 activity in cells with wild type or mutant p53. Fifth, moonlighting functions of specific MLPs can cause unpredictable effects. These results add insights into synergistic and pleiotropic anti-cancer mechanisms of curcumin and resveratrol. It has clinical relevance because both phytochemicals are chemo-preventive agents and chemosensitizers in clinical trials.
Identification of Potential Therapeutic targets for Stroke and Its Subtypes by Integrating Proteomes and Genetics from Human Plasma
Authors: Liu Hanchen , Zhang Xiaoxi , Ma Hongyu , Nguyen Thanh N. , Hua Weilong , Mo Shaojun , Huang Qinghai , Liu Jianmin , Zhou Yu , Yang Pengfei 
Published: August 2023

ABSTRACTBackgroundPrevious genome-wide association studies (GWAS) have identified several risk genes for stroke; however, it remains unclear how they confer risk for the disease. We conducted an integrative analysis to identify candidate genes for stroke and stroke subtypes by integrating blood-derived multi-omics data with genetic data.MethodWe systematically integrated the latest stroke GWAS database (73,652 patients and 1,234,808 controls) with human plasma proteomes (N=7,213) and performed proteome-wide association studies (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, and transcriptome-wide association study (TWAS) to prioritize genes that associate the risk of stroke and its subtypes with their expression and protein abundance in plasma. Cell-type specificity and functional enrichment analysis using single-cell RNA sequencing (scRNA-seq) and Gene Ontology (GO) databases were then performed to select target genes. A two-step MR analysis was followed to explore the potential mechanisms.ResultsWe found that the protein abundance of seven genes (MMP12, F11, SH3BGRL3, ENGASE, SCARA5, SWAP70,andSPATA20) in the plasma was associated with stroke and its subtypes, with six genes (MMP12, F11, SH3BGRL3, SCARA5, SWAP70,andSPATA20) causally related with stroke and its subtypes (P < 0.05/proteins identified for PWAS; P < 0.05/8 for MR; posterior probability of hypothesis 4 ≥ 75 % for Bayesian colocalization). The effect ofF11, SH3BGRL, SPATA20,andSWAP70on each subtype was mediated by Factor XI inhibitors (FXI), atrial fibrillation, T2D, and SBP respectively (p<0.05). We also found thatSCARA5andSWAP70were related to stroke and ischemic stroke at the transcriptome level.ConclusionsOur present proteomic findings have identified new causal genes in the pathogenesis of stroke, which may offer potential future therapeutic targets for stroke prevention.
Characterization of Identified Dopaminergic Neurons in the Mouse Forebrain and Midbrain
Authors: Lau Maggy Yu Hei , Gadiwalla Sana , Jones Susan , Galliano Elisa 
Published: August 2023

AbstractDopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing, and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta, SNC, and Ventral Tegmental Area, VTA) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Emerging evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity, and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings inex vivobrain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential firing across midbrain and forebrain DA subtypes. We found that each DA subgroup within midbrain and forebrain was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression andin vivodatasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.
Impact of Infectious Diseases on Wild Bovidae Populations in Thailand: Insights from Population Modelling and Disease Dynamics
Authors: Horpiencharoen Wantida , Marshall Jonathan C. , Muylaert Renata L. , John Reju Sam , Hayman David T. S. 
Published: August 2023

AbstractThe wildlife and livestock interface is vital for wildlife conservation and habitat management. Infectious diseases maintained by domestic species may impact threatened species such as Asian bovids, as they share natural resources and habitats. To predict the population impact of infectious diseases with different traits, we used stochastic mathematical models to simulate the population dynamics 100 times over 100 years for a model gaur (Bos gaurus) population with and without disease. We simulated repeated introductions from a reservoir, such as domestic cattle. We selected six bovine infectious diseases; anthrax, bovine tuberculosis, hemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis, all of which have caused outbreaks in wildlife populations. From a starting population of 300, the disease-free population increased by an average of 228% over 100 years. Brucellosis with frequency-dependent transmission showed the highest average population declines (−97%), with population extinction occurring 16% of the time. Foot and mouth disease with frequency-dependent transmission showed the lowest impact, with an average population increase of 200%. Overall, acute infections with very high or low fatality had the lowest impact, whereas chronic infections produced the greatest population decline. These results may help disease management and surveillance strategies support wildlife conservation.
Comparative GWAS identifies a role for Mendel’s green pea gene in the nonphotochemical quenching kinetics of sorghum, maize, and arabidopsis
Authors: Sahay Seema , Shrestha Nikee , Dias Henrique Moura , Mural Ravi V. , Grzybowski Marcin , Schnable James C. , Głowacka Katarzyna 
Published: August 2023

AbstractPhotosynthetic organisms must cope with rapid fluctuations in light intensity. Nonphotochemical quenching (NPQ) enables the dissipation of excess light energy as heat under high light conditions, whereas its relaxation under low light maximizes photosynthetic productivity. We quantified variation in NPQ kinetics across a large sorghum (Sorghum bicolor) association panel in four environments, uncovering significant genetic control for NPQ. A genome-wide association study (GWAS) identified 20 unique regions in the sorghum genome associated with NPQ. We detected strong signals from the sorghum ortholog ofArabidopsis thaliana SUPPRESSOR OF VARIEGATION3(SVR3) involved in plastid–nucleus signaling and tolerance to cold. By integrating GWAS results for NPQ across maize (Zea mays) and sorghum association panels, we identified a second gene,NON-YELLOWING 1(NYE1), originally identified by Gregor Mendel in pea (Pisum sativum) and involved in the degradation of photosynthetic pigments in light-harvesting complexes, along withOUTER ENVELOPE PROTEIN 37(OEP37), that encodes a transporter in chloroplast envelope. Analysis ofnye1insertion alleles inA. thalianaconfirmed the effect of this gene on NPQ kinetics across monocots and eudicots. We extended our comparative genomics GWAS framework across the entire maize and sorghum genomes, identifying four additional loci involved in NPQ kinetics. These results provide a baseline for engineering crops with improved NPQ kinetics and increasing the accuracy and speed of candidate gene identification for GWAS in species with high linkage disequilibrium.
From neglecting to including cultivar-specificper setemperature responses: Extending the concept of thermal time for plant development modeling
Authors: Roth Lukas , Binder Martina , Kirchgessner Norbert , Tschurr Flavian , Yates Steven , Hund Andreas , Kronenberg Lukas , Walter Achim 
Published: August 2023

AbstractPredicting plant development, a longstanding goal in plant physiology, involves two interwoven components: continuous growth and the progression of growth stages (phenology). Current models, like thermal time, assume species-level growth responses to temperature. We challenge this assumption, suggesting that cultivar-specific temperature responses significantly affect phenology. To investigate, we collected field-based growth and phenology data in winter wheat and soybean over multiple years. We used diverse models, from linear to neural networks, to assess growth responses to temperature at various trait and covariate levels. Cultivar-specific non-linear models best explained phenology-related cultivar-environment interactions. With cultivar-specific models, additional relations to other stressors than temperature were found. The availability of the presented field phenotyping tools allows incorporating cultivar-specific temperature response functions in future plant physiology studies, which will deepen our understanding of key factors that influence plant development. Consequently, this work has implications for crop breeding and cultivation under adverse climatic conditions.
Rice yellow mottle virusis a suitable amplicon vector an efficient production of an anti-leishmianiasis vaccine inNicotiana benthamianaleaves
Authors: Bamogo PKA , Tiendrébéogo F , Brugidou C , Sérémé D , Djigma FW , Simporé J , Lacombe S 
Published: August 2023

AbstractThe suitability of rice yellow mottle virus RYMV as a gene expression vector in plant was assessed using a construct carrying promastigote surface antigen (PSA) C-terminal coding sequence of the parasite protozoan Leishmania. RYMV ORF1 encoding P1 protein has been deleted from the RYMV native genome. The C-terminal PSA gene was substituted for the viral coat protein. PSA is present at the surface of the parasite and displays vaccine properties against canine and human leishmaniosis. RYMV-based vector allowed PSA expression inNicotiana benthamiana. Q-pcr analysis showed that chimeric RYMV carrying PSA gene is able to replicate inN. benthamianaleaves. P19 silencing suppressor in combination with the lacked viral vector ORF encoding RYMV Coat Protein (CP) enhanced significantly RYMV tool replication inN. benthamiana. RYMV CP played a key role on viral RNA stabilization and acts as a weak silencing suppressor.The original RYMV-based expression vector allowed PSA protein expression enhancement in N. benthamianawithout any symptoms. RYMV-based vector could be suitable for functional genomic studies in monocots by VIGS (Viral Induced Gene Silencing) technology.