bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the Development of the Fourth Edition of the Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline Using GRADE Methods
Authors: Haesler Emily , Cuddigan Janet , Carville Keryln , Moore Zena , Kottner Jan , Ayello Elizabeth A. , Berlowitz Dan , Carruth Althea , Yee Chang Yee , Cox Jill , Creehan Sue , Nixon Jane , Ngan Hau Lan , Balzer Katrin 
Published: November 2023

ABSTRACT
The National Pressure Injury Advisory Panel, European Pressure Ulcer Advisory Panel, and the Pan Pacific Pressure Injury Alliance are commencing a new (fourth) edition of the Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline. The fourth edition of the International Pressure Injury (PI) Guideline will be developed using GRADE methods to ensure a rigorous process consistent with evolving international standards. Clinical questions will address prevention and treatment of PIs, identification of individuals at risk of PIs, assessment of skin and tissues, and PI assessment. Implementation considerations supporting application of the guidance in clinical practice will be developed. The guideline development process will be overseen by a guideline governance group and methodologist; the guideline development team will include health professionals, educators, researchers, individuals with or at risk of PIs, and informal carers.
This article presents the project structure and processes to be used to undertake a systematic literature search, appraise risk of bias of the evidence, and aggregate research findings. The methods detail how certainty of evidence will be evaluated; presentation of relative benefits, risks, feasibility, acceptability, and resource requirements; and how recommendations will be made and graded. The methods outline transparent processes of development that combine scientific research with best clinical practice. Strong involvement from health professionals, educators, individuals with PIs, and informal carers will enhance the guideline’s relevance and facilitate uptake. This update builds on previous editions to ensure consistency and comparability, with methodology changes improving the guideline’s quality and clarity.
Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure
Authors: Li Shuang , Wang Hu , Guo Na , Su Bin , Lambotte Olivier , Zhang Tong 
Published: November 2023

Abstract
Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.
Use of Stroke Alert Sticker in the Field Decreases Time to Acute Interventions for Ischemic Stroke Patients
Authors: Davis Nicolle W. , Bailey Meghan , Hester Jeannette M. , Bonnell Gabriel , Khanna Anna , Wilson Christina , Jones Jason , Cowart Michael , Singh Amita 
Published: November 2023

ABSTRACT

BACKGROUND: Stroke is a medical emergency requiring timely intervention to optimize patient outcomes. The only treatments currently Food and Drug Administration approved for acute stroke are intravenous (IV) thrombolytics, which require obtaining specific medical history to be administered safely. This medical history may be overlooked in the prehospital setting or lost during patient handoff between emergency medical services (EMS) personnel and hospital staff, delaying treatment. We evaluated whether utilization of a “stroke alert sticker” by EMS to capture key information in the field would decrease door-to-needle (DTN) time. METHODS: Bright-orange “stroke alert stickers” were disseminated to our local EMS agency to be placed on all suspected stroke patients in the field prompting documentation of key elements needed for timely treatment decisions. The “stroke alert sticker” included time last known well, contact information, presenting symptoms, and relevant medications. We evaluated the impact of the “stroke alert sticker” on acute stroke metrics, including DTN time. RESULTS: The project included 220 consecutive stroke alert patients brought to our comprehensive stroke center by a single EMS agency from May 2021 through February 2022. Twenty-one patients were treated with an IV thrombolytic. Overall “stroke alert sticker” use compliance was 40%; for the subgroup of patients who were given an IV thrombolytic, the “stroke alert sticker” was used 60% of the time. In patients who received an IV thrombolytic, prehospital EMS notification was 100% with “stroke alert sticker” use, compared with 75% without (P = .13). In addition, with “stroke alert sticker” utilization, DTN time was reduced by 20 minutes (31 [11] minutes with sticker vs 51 [21] minutes without, P = .04). CONCLUSION: Utilization of the “stroke alert sticker” significantly improved DTN times compared with patients without the sticker. This evidence supports continued use of the “stroke alert sticker” to improve DTN times and patient outcomes.
Effects of Pain Beliefs on Postoperative Pain and Analgesic Consumption in Spine Surgery Patients
Authors: Kose Gulsah , Şirin Keziban 
Published: November 2023

ABSTRACT

PURPOSE: This study evaluates the impact of pain belief on postoperative pain and analgesic consumption in patients undergoing spine surgery. METHODS: This descriptive and cross-sectional study was conducted on 71 patients undergoing spine surgery, who were admitted to the neurosurgery department of a university hospital between January 2021 and April 2022. Descriptive information form, Pain Beliefs Questionnaire, visual analog scale, pain evaluation form, and verbal category scale were used for data collection. RESULTS: Participant mean age was 53 years, and 40.8% underwent spinal disc surgery. A total of 60.2% of the participants experienced moderate postoperative pain, and severe pain was noted during the second postoperative hour, after rest and coughing, which decreased significantly during consecutive hours. Besides, 70.4% of the participants expressed that the level of pain decreased, 43.7% had pain as they expected, 69.0% had intermittent pain, and 53.5% experienced pain at the surgical site. The mean scores obtained from the Organic and Psychological Beliefs subscales of the Pain Beliefs Questionnaire were 4.25 and 4.21, respectively. There was a statistically significant relationship between the Psychological Beliefs and visual analog scale scores after coughing measured in the postoperative 24th and 36th hours. There was also a significant relationship between organic beliefs and working status. There was no statistically significant relationship between analgesic consumption and pain belief. CONCLUSION: Patients undergoing spine surgery experienced moderate pain and had a relatively high level of pain beliefs. Regular evaluation of pain levels and beliefs is required for effective pain management.
Serum trimethylamine N-oxide levels among coronary artery disease and acute coronary syndrome patients: a systematic review and meta-analysis
Authors: Dean Yomna E. , Rouzan Samah S. , Loayza Pintado Jose J. , Talat Nesreen Elsayed , Mohamed Alaa R. H. , Verma Suman , Anwar Kamdi Zainab , Gir Deepak , Helmy Ahmed , Helmy Zakaria , Afzal Ahson , Mady Tamer , Hazimeh Yusef , Aiash Hani 
Published: November 2023

Background and Aim:
Recent studies have linked trimethylamine N-oxide (TMAO) to cardiovascular diseases; our study aimed to analyze the association between coronary artery disease (CAD), acute coronary syndrome (ACS), and TMAO.

Methods:
PubMed, Scopus, Embase, and Web of Science were searched using terms such as ʻCADʼ and ʻTMAOʼ. Only observational controlled studies were included. RevMan software version 5.4 was used for the analysis.

Results:
A significant association was found between the CAD group and increased serum TMAO levels compared with the control group (MD=1.16, 95% CI=0.54–1.78, P=0.0003). This association remained significant among acute coronary syndrome patients (MD=0.98, 95% CI=0.73–1.23, P<0.00001) and was also detected among young and old CAD patients (MD=0.35, 95% CI=0.06–0.64, P=0.02 and MD=1.36, 95% CI=0.71–2.01, P<0.0001, respectively). On further analysis of intestinal metabolites, the authors detected an insignificant association between choline, betaine, carnitine, and CAD. According to our sensitivity analysis, TMAO is an acceptable diagnostic marker for CAD (0.721, SE was 0.0816, 95% CI: 0.561–0.881).

Conclusion:
TMAO is an acceptable diagnostic marker for CAD, with significantly higher levels among these patients regardless of their age. Other metabolites did not show such an association. The role of serum level TMAO in the early diagnosis of CAD should be further explored.
Mixed connective tissue and ovarian cancer: a case report
Authors: Kudsi Maysoun , Khalayli Naram , Hola Leen , Aldeeb Maria , Aziz Aghiad 
Published: November 2023

Background:
Mixed connective tissue disease (MCTD) is characterized by high titres of distinct antibodies: U1 ribonucleoprotein with variable clinical features seen in rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis, and dermatomyositis. Limited case reports revealed the association between MCTD and cancer, like lymphoma, lung cancers, and others.

Case presentation:
A 22-year-old female presented with enlargement of the abdomen and oedema of the lower extremities, gradually started 25 days The patient had been diagnosed to have rheumatoid arthritis. She was treated with 7.5 mg/week MTX for 6 months. Physical examination revealed: pallor, lower limb oedema, with synovitis and deformities of hands. The laboratory tests showed anaemia, elevated levels of creatine phosphokinase ESR, positivity of antinuclear antibody, anti-ds DNA, and antinuclear ribonucleoprotein. Urinary protein excretion was 1625 mg/24 h. Chest X-ray showed bilateral pleural effusion. Echocardiography revealed pericardial effusion Thoracic-abdominal and pelvic tomography showed a heterogeneous mass with a diameter of 5 × 6 cm at the expense of the right ovary. The mass was removed surgically, and a biopsy was taken, and was compatible with ovarian high-grade serous adenocarcinoma. A course of solumedrol 1 g/IV/3 days was applied, and then continue with 60 mg/day oral predlone. Later on discharge, she was taken 25 mg/day predlone, and methotrexate 10 mg.

Conclusions:
Our case showed that the patient had no risk factors for developing ovary cancer. On the contrary, our patient was a young, non-smoker, without any previous treatment before the RA diagnosis was taken, and finally, she had 3 children with full-term pregnancy, and well health. This case highlights the importance of maintaining a high index of suspicion for malignancy in MCTD patients. However, further investigation on the role of the immune system in the development of ovarian cancer in women with autoimmune diseases including MCTD remains necessary.
Exploring the mechanism of Si-Ni-San against depression by UPLC-Q-TOF-MS/MS integrated with network pharmacology: experimental research
Authors: Jia Keke , Li Changyin , Xu Meijuan , Dai Guoliang , Zhou Jinyong , Chen Biqing , Zou Jiandong , Li Jia , Zhang Qingyu , Ju Wenzheng 
Published: November 2023

Background:
Depression is becoming an urgent mental health problem. Si-Ni-San has been widely used to treat depression, yet its underlying pharmacological mechanism is poorly understood. Thus, we aim to explore the antidepressant mechanism of Si-Ni-San by chemical analysis and in-silico methods.

Methods:
Compounds in Si-Ni-San were determined by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Then, bioactive compounds were obtained from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform and SwissADME, and the potential targets of which were acquired from SwissTargetPrediction. Depression-related targets were collected from GeneCards. The intersection between compound-related targets and depression-related targets were screened out, and the overlapped targets were further performed protein-protein interaction, biological functional and pathway enrichment analysis. Finally, networks of Si-Ni-San against depression were constructed and visualized by Cytoscape.

Results:
One hundred nineteen compounds in Si-Ni-San were determined, of which 24 bioactive compounds were obtained. Then, 137 overlapped targets of Si-Ni-San against depression were collected. AKT1, PIK3R1, PIK3CA, mTOR, MAPK1 and MAPK8 were the key targets. Furthermore, PI3K-Akt signalling pathway, serotonergic synapse, MAPK signalling pathway and neurotrophin signalling pathway were involved in the antidepressant mechanism of Si-Ni-San. It showed that components like sinensetin, hesperetin, liquiritigenin, naringenin, quercetin, albiflorin and paeoniflorin were the mainly key active compounds for the antidepressant effect of Si-Ni-San.

Conclusions:
This study demonstrated the key components, key targets and potential pharmacological mechanisms of Si-Ni-San against depression. These results indicate that Si-Ni-San is a promising therapeutic approach for treatment of depression, and may provide evidence for the research and development of drugs for treating depression.
Predictive Modeling of Resistant Hypertension Risk: Incorporating the TyG Index and Clinical Factors
Authors: Yang Hai-Tao , Liu Jing-Kun , Yang YI , Zheng Ying-Ying , Xie Xiang 
Published: November 2023

AbstractBackgroundResistant hypertension (RH), a form of high blood pressure that remains uncontrolled despite maximum medication, poses a significant cardiovascular risk. This paper introduces a novel predictive model, combining the triglyceride-glucose (TyG) index with traditional clinical factors, to anticipate the development of RH in patients with newly diagnosed primary hypertension.MethodsThe study included hospitalized patients with newly diagnosed primary hypertension and stable blood pressure after medication treatment from August 2019 to early August 2021. After screening, a total of 1635 cases were finally included and divided into development and validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression was applied to select potential risk factors. Multivariate Cox regression analysis was used to identify independent hazard factors constructed by the predictive nomogram. Receiver operating characteristic curve analysis (ROC), calibration curve, and C-index were used to evaluate the performance of the nomogram.ResultsA total of 1227 patients were assigned to the development queue, while 408 patients were assigned to the validation queue. The constructed column line chart includes five clinical variables: age, apnea-hypopnea index (AHI), uric acid, fasting blood glucose, and TyG index. Multivariate Cox regression analysis revealed that compared to the other four risk factors, TyG index (HR=3.97, 95% CI: 2.81 - 5.62, P < 0.01) was significantly associated with RH. ROC curve analysis showed prediction values of 0.895 and 0.837 for RH in the development cohort and prediction values of 0.854 and 0.832 in the validation cohort respectively. The C-index was found to be 0.76 in the development cohort and 0.66 in the validation cohort. Furthermore, Kaplan-Meier analysis indicated that compared to the low-risk group, there was a higher likelihood of developing RH in the high-risk group.ConclusionsBased on the TyG index and electronic health record data, a model can be constructed to accurately and reliably predict the occurrence of RH in patients with stable blood pressure after initial diagnosis of primary hypertension and drug treatment.
DeepGSEA: Explainable Deep Gene Set Enrichment Analysis for Single-cell Transcriptomic Data
Authors: Xiong Guangzhi , LeRoy Nathan John , Bekiranov Stefan , Zhang Aidong 
Published: November 2023

AbstractGene set enrichment (GSE) analysis allows for an interpretation of gene expression through pre-defined gene set databases and is a critical step in understanding different phenotypes. With the rapid development of single-cell RNA sequencing (scRNA-seq) technology, GSE analysis can be performed on fine-grained gene expression data to gain a nuanced understanding of phenotypes of interest. However, due to the extreme heterogeneity of single-cell gene expression, current statistical GSE analysis methods sometimes fail to identify enriched gene sets. Meanwhile, deep learning has gained traction in specific applications like clustering and trajectory inference in single-cell studies due to its prowess in capturing complex data patterns. However, its use in GSE analysis remains limited, primarily due to interpretability challenges. In this paper, we present DeepGSEA, an explainable deep gene set enrichment analysis approach which leverages the expressiveness of interpretable, prototype-based neural networks to provide an in-depth analysis of GSE. DeepGSEA learns the ability to capture GSE information through our designed classification tasks, and significance tests can be performed on each gene set, enabling the identification of enriched sets. The underlying distribution of a gene set learned by DeepGSEA can be explicitly visualized using the encoded cell and cellular prototype embeddings. We demonstrate the expressiveness of DeepGSEA over commonly used GSE analysis methods by examining their sensitivity and specificity with four simulation studies. In addition, we test our model on three real scRNA-seq datasets and illustrate the interpretability of DeepGSEA by showing how its results can be explained. The source code of DeepGSEA is available athttps://github.com/Teddy-XiongGZ/DeepGSEA.
Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study
Authors: Demirkan Ayşe , van Dongen Jenny , Finnicum Casey T. , Westra Harm-Jan , Jankipersadsing Soesma , Willemsen Gonneke , Ijzerman Richard G. , Boomsma Dorret I. , Ehli Erik A. , Bonder Marc Jan , Fu Jingyuan , Franke Lude , Wijmenga Cisca , de Geus Eco J.C. , Kurilshikov Alexander , Zhernakova Alexandra 
Published: November 2023

AbstractBoth gene methylation and the gut microbiome are partially determined by host genetics and partially by environment. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbiome composition using data generated by shotgun metagenomic sequencing (n = 683). We then investigated if genetic and environmental factors can explain the methylation–microbiota associations in a set of 78 associated CpG–taxa pairs from the EWAS meta-analysis. In both cohorts, blood and stool samples were collected within 2 weeks of each other. Methylation was profiled in blood samples using the Illumina 450K array. Methylation and microbiome analysis pipelines were harmonized across cohorts. Epigenome-wide association study (EWAS) of microbial features were analysed using linear regression with adjustment for technical covariates.Discovery and replication analysis using 16s data identified two independent CpGs associated with the genusEggerthella: cg16586104 (Pmeta-analysis= 3.21 × 10-11) and cg12234533 (Pmeta-analysis= 4.29 × 10-10). While we did not find human genetic variants that could explain the associated CpG–taxa/pathway pairs, we show that microbiome can mediate the effect of environmental factors on epigenetics.In this first association study linking epigenome to microbiome, we found and replicated the associations of two CpGs to the abundance of genusEggerthellaand identified microbiome as a mediator of the exposome.
Using large language models to study human memory for meaningful narratives
Authors: Georgiou Antonios , Can Tankut , Katkov Mikhail , Tsodyks Misha 
Published: November 2023

ABSTRACTOne of the most impressive achievements of the AI revolution is the development of large language models that can generate meaningful text and respond to instructions in plain English with no additional training necessary. Here we show that language models can be used as a scientific instrument for studying human memory for meaningful material. We developed a pipeline for designing large scale memory experiments and analyzing the obtained results. We performed online memory experiments with a large number of participants and collected recognition and recall data for narratives of different lengths. We found that both recall and recognition performance scale linearly with narrative length. Furthermore, in order to investigate the role of narrative comprehension in memory, we repeated these experiments using scrambled versions of the presented stories. We found that even though recall performance declined significantly, recognition remained largely unaffected. Interestingly, recalls in this condition seem to follow the original narrative order rather than the scrambled presentation, pointing to a contextual reconstruction of the story in memory.