bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice
Authors: Zhang Xiaolin , Cao Ruijuan , Li Changye , Zhao Hongchun , Zhang Ruyi , Che Juan , Xie Jinwen , Tang Na , Wang Yanfei , Liu Xiuzhen , Zheng Qingyin 
Published: February 2024

Objective
Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism.

Methods
Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot.

Results
The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1β, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae.

Conclusions
Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.
Social media influenced self-application of cyanoacrylate for double chin reduction in an adolescent girl: an unusual case of post-inflammatory hyperpigmentation
Authors: Agrawal Saurav , Pant Ved Prakash , Pandey Anup , Acharya Sabin , Sitaula Seema , Rayamajhi Aadesh , Pant Deepak Raj 
Published: February 2024

Introduction:
Cyanoacrylate, used as a topical adhesive for wound closure in clinical settings, can result in poor cosmetic outcome on application to skin. Lack of formal medical or dermatological training among social media influencers poses risks of improper diagnosis, incorrect treatments, ineffective home remedies, and potential self-injury or long-term skin effects, especially among adolescents.

Case presentation:
The authors present a case of a young girl with a persistent post-inflammatory hyperpigmentation after using cyanoacrylate on her chin as a home remedy to reduce her double chin problem after learning from a video on social media. Biopsy findings were consistent with post-inflammatory hyperpigmentation in dermis.

Clinical discussion:
Application of cyanoacrylate over skin can result in allergic reactions, burn injuries, infections, itching, skin blistering, and aesthetic issues. Persistent post-inflammatory hyperpigmentation can be a poor cosmetic outcome on application of cyanoacrylate over skin.

Conclusion:
Inadequate social media safety regulations require healthcare professionals to be aware of social trends among adolescents and to encourage them for open conversations and professional help-seeking during times of distress in this digital era.
Competency-Based Education in RN to BSN Programs
Authors: Robinson Jamie , Jagiello Karen P. , McElroy Lori , LoVerde Janet , Jowell Vicki , Good Palmira , Brink Stephanie 
Published: February 2024

Background:
The call for nursing education reform has never been louder. National organizations recognize the urgent need to prepare nursing students to practice competently, moving away from traditional teaching and curricula and to competency-based education (CBE) strategies to prepare future nurses for independent clinical practice.

Problem:
The 2021 American Association of Colleges of Nursing Essentials do not account for the competencies achieved in registered nurse (RN) associate degree and diploma programs. This presents a challenge for RN to bachelor of science in nursing (BSN) program administrators and faculty when designing curricula to meet the new Essentials.

Approach:
The Essentials crosswalk created by the National RN-Baccalaureate Faculty Forum serves as a foundational guide for the development of the template models discussed in this article.

Conclusion:
This article provides a template of instructional models for implementing CBE in RN to BSN programs.
Epidemiology of community-acquired pneumonia caused by Streptococcus pneumoniae in older adults: a narrative review
Authors: Elias Christelle , Nunes Marta C. , Saadatian-Elahi Mitra 
Published: February 2024

Purpose of review
This review covers updated perspectives on different aspects of pneumococcal community-acquired pneumonia (pCAP), including the epidemiology, clinical presentation, risk factors, antibiotic treatment, and existing preventive strategies in older adults.

Recent findings
pCAP remains the most prevalent condition among lower respiratory tract infections in the older adults according to Global Burden of Diseases 2019. Older adults can display atypical symptoms such as confusion, general clinical deterioration, new onset of and exacerbation of underlying illness that might trigger clinical suspicion of pCAP. Older adults with pCAP often experience increased disease severity and a higher risk of pulmonary complications compared with younger individuals, owing to age-related changes in immunity and a higher prevalence of comorbidities. Vaccination stands fundamental for prevention, emphasizing the need for effective immunization strategies, specifically tailored for older adults. There is a pressing need to reinforce efforts aimed at boosting pneumococcal vaccination rates.

Summary
Despite a high morbidity and mortality, the burden of pCAP, in particular hospital admission and occurrence of invasive infections, among the elderly population is not sufficiently documented. This review findings emphasize the substantial burden of pCAP in this vulnerable population, driven by factors such as advancing age and underlying comorbidities. The emergence of antibiotic-resistant pneumococcal strains further complicates treatment decisions and highlights the importance of tailored approaches for managing pCAP in older adults.
COMPREHENSIVE THERAPEUTIC EFFICACY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN IN TREATING SEPSIS-INDUCED COAGULOPATHY: A SINGLE-CENTER, RETROSPECTIVE OBSERVATIONAL STUDY
Authors: Fang Jingyun , Huang Peng , Cui Wanfu , Lin Ye , Rong Dan , Li Xu 
Published: February 2024

ABSTRACT

Objective: The aim of the study is to investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy (SIC). Methods: A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People’s Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared with the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days after admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. Results: On day 3 of treatment, both groups exhibited reduced platelet and thromboelastogram (TEG) maximum amplitude (MA) levels, with the control group showing a more significant decrease (P < 0.05). By the fifth day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 (P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 (P < 0.05). The levels of prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimer, fibrinogen, fibrin degradation products, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group (P < 0.05). In addition, both groups showed a reduction in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, disseminated intravascular coagulation, and lactate (LAC) levels on day 3, but the test group’s scores decreased significantly more by day 7 (P < 0.05). Within the test group, white blood cell count, C-reactive protein, procalcitonin, IL-6, and T
max levels were lower (P < 0.05). Furthermore, the test group demonstrated shorter duration for intensive care unit stay, mechanical ventilation, and continuous renal replacement therapy (P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group (P < 0.05). Conclusion: IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC.
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">Bioinformatics analysis of the antigenic epitopes of&#160;L7/L12 protein in the B- and T-Cells active against &#160;Brucella melitensis
</xhtml:span>
Authors: Zhang Jingjie , Baigued Huricha , Chen Shana , Borigen Haiyan , Tana Tana , Quan Fu , Yang Dezhi 
Published: February 2024

Objective: To analyze the physicochemical properties, spatial structure, and protein–protein interactions (PPIs) of L7/L12 protein using bioinformatics methods and predict their B- and T-cell epitopes to lay a theoretical foundation for developing a novel multiepitope vaccine. Methods: The NCBI database was searched for the amino acid sequences of L7/L12 from Brucella melitensis. In addition, the online softwares, ProtParam and ProtScale, were used to predict the physicochemical properties; NetPhos3.1 and CD-search to predict the phosphorylation sites and conserved domains; SOMPA and SWISS-MODEL to predict the secondary and tertiary structures; the STRING database to analyze the PPIs; and the IEDB, ABCpred, SVMTrip, and SYFPEITHI databases to predict the B- and T-cell epitopes.Results: L7/L12, consisting of 124 amino acids, was determined to be a stable, intracellular, hydrophilic protein containing 11 phosphorylation sites and ribosomal protein-related conserved domains. α-helices accounted for 70.16%, β-turns for 2.42%, extended strands for 8.87%, and irregular coils for 18.55% of the secondary structure. The PPIs indicated that L7/L12 was involved in the constitution of ribosomes and regulating the accuracy of the translation process. Three B-cell and six T-cell epitopes were finally screened by comparing multiple databases. Conclusions: L7/L12, which governs the ac translation curate of proteins, possesses several potentially advantageous epitopes, laying a theoretical foundation for designing multiepitope vaccines.
Mesenchymal stem cell-derived extracellular vesicles attenuate symptoms in dextran sodium sulfate-induced ulcerative colitis mouse model
Authors: Zhai Yanhua , Liu Guowu , Cui Chuang , Yi Yuan , Yan Yu , Zhang Lei , Wang Wan , He Xinjun , Xu Ke 
Published: February 2024

AbstractInflammatory bowel disease (IBD) refers to a group of multifactorial and chronic inflammation affecting intestinal tract. Based on the pathogenic mechanisms, IBD mainly comprised of two categories: ulcerative colitis (UC) and Crohn’s disease (CD). In this study, we established a dextran sulfate sodium (DSS)-induced colitis model to mimic UC. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as therapeutic vectors have shown regenerating effect of damaged tissues. Here, intravenous administration of MSC-EVs ameliorated IBD symptoms including gaining weight, reducing disease activity index and restoring colon length. In addition, the protective effect of MSC-EVs were demonstrated by repairing colon mucosa and reducing the infiltration of macrophages in submucosa. Collectively, MSC-EV shows a therapeutic potential for IBD.
The global root exudate carbon flux
Authors: Chari Nikhil R. , Tumber-Dávila Shersingh Joseph , Phillips Richard P. , Bauerle Taryn L. , Brunn Melanie , Hafner Benjamin D. , Klein Tamir , Obersteiner Sophie , Reay Michaela K. , Ullah Sami , Taylor Benton N. 
Published: February 2024

AbstractRoot exudation, the export of low-molecular weight organic carbon (C) from living plant roots to soil, influences microbial activity, nutrient availability, and ecosystem feedbacks to climate change, but the magnitude of this C flux at ecosystem and global scales is largely unknown. Here, we synthesizein situmeasurements of root exudation rates and couple those to estimates of fine root biomass to estimate global and biome-level root exudate C fluxes. We estimate a global root exudate flux of 15.2 PgC y-1, or about 10% of global annual gross primary productivity. We found no differences in root mass-specific exudation rates among biomes, though total exudate fluxes are estimated to be greatest in grasslands owing to their high density of absorptive root biomass. Our synthesis highlights the global importance of root exudates in the terrestrial C cycle and identifies regions where morein situmeasurements are needed to improve future estimates of root exudate C fluxes.
Selective epithelial expression ofKRASG12Dmutation drives ductal pancreatic neoplasia in Oncopigs
Authors: Jara Carlos P , Al-Gahmi Al-Murtadha , Lazenby Audrey , Hollingsworth Michael A. , Carlson Mark A. 
Published: February 2024

ABSTRACTBackgroundPancreatic ductal adenocarcinoma (PDAC) remains a formidable challenge in oncology, characterized by a high mortality rate, largely attributable to delayed diagnosis and the intricacies of its tumor microenvironment. Innovations in modeling pancreatic epithelial transformation provide valuable insights into the pathogenesis and potential therapeutic strategies for PDAC.MethodsWe employed a porcine (Oncopig) model, utilizing the Ad-K8-Cre adenoviral vector, to investigate the effects of variable doses (107to 1010pfu) on pancreatic epithelial cells. This vector, the expression from which being driven by a Keratin-8 promoter, will deliver Cre-recombinase specifically to epithelial cells. Intraductal pancreatic injections in transgenic Oncopigs (LSL-KRASG12D-TP53R167H) were performed with histologically based evaluation at 2 months post-injection.ResultsSpecificity of the adenoviral vector was validated through Keratin-8 expression and Cre-recombinase activity. We confirmed that the Ad-K8-Cre adenoviral vector predominantly targets ductal epithelial cells lining both large and small pancreatic ducts, as evidenced by Keratin 8 and CAM5.2 staining. Higher doses resulted in significant tissue morphology changes, including atrophy, and enlarged lymph nodes. Microscopic examination revealed concentration-dependent proliferation of the ductal epithelium, cellular atypia, metaplasia, and stromal alterations. Transgene expression was confirmed with immunohistochemistry. Desmoplastic responses were evident through vimentin, α-SMA, and Masson’s trichrome staining, indicating progressive collagen deposition, particularly at the higher vector doses.ConclusionOur study suggests a distinct dose-response relationship of Ad-K8-Cre in inducing pancreatic epithelial proliferation and possible neoplasia in an Oncopig model. All doses of the vector induced epithelial proliferation; the higher doses also produced stromal alterations, metaplasia, and possible neoplastic transformation. These findings highlight the potential for site-specific activation of oncogenes in large animal models of epithelial tumors, with the ability to induce stromal alterations reminiscent of human PDAC.
Cerebra: a computationally efficient framework for accurate protein structure prediction
Authors: Hu Jian , Wang Weizhe , Gong Haipeng 
Published: February 2024

AbstractRemarkable progress has been made in the field of protein structure prediction in the past years. State-of-the-art methods like AlphaFold2 and RoseTTAFold2 achieve prediction accuracy close to experimental structural determination, but at the cost of heavy computational consumption for model training. In this work, we propose a new protein structure prediction framework, Cerebra, for improving the computational efficiency of protein structure prediction. In this innovative network architecture, multiple sets of atomic coordinates are predicted parallelly and their mutual complementary is leveraged to rapidly improve the quality of predicted structures through a novel attention mechanism. Consequently, Cerebra markedly reduces the model training consumption, achieving a training acceleration of at least 7 folds, in comparison to OpenFold, the academic version of AlphaFold2. When evaluated on the CAMEO and CASP15 sets, the Cerebra model insufficiently trained on a single GPU only shows slight performance inferiority to the published OpenFold model.
GraphCompass: Spatial metrics for differential analyses of cell organization across conditions
Authors: Ali Mayar , Kuijs Merel , Hediyeh-zadeh Soroor , Treis Tim , Hrovatin Karin , Palla Giovanni , Schaar Anna C. , Theis Fabian J. 
Published: February 2024

AbstractSpatial omics technologies are increasingly leveraged to characterize how disease disrupts tissue organization and cellular niches. While multiple methods to analyze spatial variation within a sample have been published, statistical and computational approaches to compare cell spatial organization across samples or conditions are mostly lacking. We present GraphCompass, a comprehensive set of omics-adapted graph analysis methods to quantitatively evaluate and compare the spatial arrangement of cells in samples representing diverse biological conditions. GraphCompass builds upon the Squidpy spatial omics toolbox and encompasses various statistical approaches to perform cross-condition analyses at the level of individual cell types, niches, and samples. Additionally, GraphCompass provides custom visualization functions that enable effective communication of results. We demonstrate how GraphCompass can be used to address key biological questions, such as how cellular organization and tissue architecture differ across various disease states and which spatial patterns correlate with a given pathological condition. GraphCompass can be applied to various popular omics techniques, including, but not limited to, spatial proteomics (e.g. MIBI-TOF), spot-based transcriptomics (e.g. 10x Genomics Visium), and single-cell resolved transcriptomics (e.g. Stereo-seq). In this work, we showcase the capabilities of GraphCompass through its application to three different studies that may also serve as benchmark datasets for further method development. With its easy-to-use implementation, extensive documentation, and comprehensive tutorials, GraphCompass is accessible to biologists with varying levels of computational expertise. By facilitating comparative analyses of cell spatial organization, GraphCompass promises to be a valuable asset in advancing our understanding of tissue function in health and disease.
Indexing Healthcare Access and Quality for Surgically Amenable Causes of Death: A Global Analysis of 204 Countries and Territories from 1990 to 2019
Authors: Zadey Siddhesh , Smith Emily R. , Staton Catherine A. , Fitzgerald Tamara N. , Vissoci Joao Ricardo Nickenig 
Published: February 2024

AbstractBackgroundWe analyzed the healthcare access and quality (HAQ) index for surgically amenable causes, its progress over time, and the gap compared to non-surgical HAQ across 204 countries and territories from 1990 to 2019 for children (up to 14 years) and overall populations.Study DesignThe Global Burden of Disease 2019 study provided mortality-to-incidence ratios and risk-standardized death rates for 32 causes with preventable mortality. Of these, 14 (18) and 9 (17) causes were considered surgical (non-surgical) for overall population and children, respectively. We constructed composite indices ranging from 0 (worst) to 100 (best) using the adjusted Mazziotta Pareto index methodology. The ratio of surgical HAQ in 2019 to that in 1990 noted change over time. Surgical-to-non-surgical HAQ ratio gave the relative gap in 2019. Ratios >1 depicted improvement over time or better performing surgical care systems.ResultsIn 2019, the overall surgical HAQ varied from 18.00 for the Central African Republic to 98.25 for Canada. The child surgical HAQ index varied from 39.87 for Chad to 99.41 for San Marino. For both surgical HAQ indices, 202 countries noted progress from 1990 to 2019. Only 31 countries (15.2%) had greater surgical HAQ index values than their non-surgical counterparts. The child surgical HAQ index lagged behind non-surgical for 61.28% of countries.ConclusionLow-income countries had limited progress in surgical HAQ indices since 1990 and lagged behind non-surgical HAQ index in 2019 the most. These findings are valuable for global evaluations, policymaking, and advocacy for investing in surgical care.
Whole Exome and Transcriptome Sequencing of Stage-Matched, Outcome-Differentiated Cutaneous Squamous Cell Carcinoma Identifies Gene Expression Patterns Associated with Metastasis and Poor Outcomes
Authors: Nassir Shams , Yousif Miranda , Li Xing , Severson Kevin , Hughes Alysia , Kechter Jacob , Hwang Angelina , Boudreaux Blake , Bhullar Puneet , Zhang Nan , Butterfield Duke , Ma Tao , Ogbaudu Ewoma , Costello Collin M , Nelson Steven , DiCaudo David J , Sekulic Aleksandar , Baum Christian , Pittelkow Mark , Mangold Aaron R 
Published: February 2024

AbstractCutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in humans and kills as many people annually as melanoma. The mutational and transcriptional landscape of cSCC has identified driver mutations associated with disease progression as well as key pathway activation in the progression of pre-cancerous lesions. The understanding of the transcriptional changes with respect to high-risk clinical/histopathological features and outcome is poor. Here, we examine stage-matched, outcome-differentiated cSCC and associated clinicopathologic risk factors using whole exome and transcriptome sequencing on matched samples. Exome analysis identified key driver mutations includingTP53,CDKN2A,NOTCH1,SHC4,MIIP,CNOT1,C17orf66,LPHN22, andTTC16and pathway enrichment of driver mutations in replicative senescence, cellular response to UV, cell-cell adhesion, and cell cycle. Transcriptomic analysis identified pathway enrichment of immune signaling/inflammation, cell-cycle pathways, extracellular matrix function, and chromatin function. Our integrative analysis identified 183 critical genes in carcinogenesis and were used to develop a gene expression panel (GEP) model for cSCC. Three outcome-related gene clusters included those involved in keratinization, cell division, and metabolism. We found 16 genes were predictive of metastasis (Risk score ≥ 9 Met & Risk score < 9 NoMet). The Risk score has an AUC of 97.1% (95% CI: 93.5% - 100%), sensitivity 95.5%, specificity 85.7%, and overall accuracy of 90%. Eleven genes were chosen to generate the risk score for Overall Survival (OS). The Harrell’s C-statistic to predict OS is 80.8%. With each risk score increase, the risk of death increases by 2.47 (HR: 2.47, 95% CI: 1.64-3.74; p<0.001) after adjusting for age, immunosuppressant use, and metastasis status.