bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analysis of the characteristic of lipid metabolism-related genes for the prognostic prediction of hepatocellular carcinoma
Authors: Zhu Peng , Zhang Feng , Deng Weijie , Chen Wenbiao 
Published: September 2022

Background:
Dysregulation of lipid metabolism is implicated in the progression of hepatocellular carcinoma (HCC). We therefore investigated the molecular characteristics of lipid-metabolism-related genes in HCC.

Methods:
Multi-dimensional bioinformatics analysis was conducted to comprehensively identify the lipid metabolism-related genes (LMRGs) from public databases, as well as the clinical information, immune features, and biological characteristics of HCC. The IMGR were then used to classify HCC into molecular phenotypes. Six lipid metabolism-related genes sets with the potential to predict the prognosis of HCC patients were identified.

Results:
A total of 770 HCC patients with complete clinical information and corresponding 776 LMRGs were downloaded from 3 databases. Univariate cox and non-negative matrix factorization analyses were used to classify HCC patients into 2 clusters. This molecular classification was associated with overall survival, clinical characteristics, and immune cells. The biological function of the differentially expressed LMRGs in the 2 clusters showed the genes associated with tumor-related metabolism pathways. A combination of multivariate/univariate cox regression and least absolute shrinkage and selection operator analyses were conducted to build a 6 LMRGs signature (6-IS) to predict the prognosis of HCC. The 6-IS signature was found to be an independent prognostic factor. Performance of the 6-IS prognostic signature was verified in a validation set and compared with an external data set. Results revealed the 6-IS signature could effectively predict the prognosis of patients with HCC.

Conclusions:
This study provides new insights into the role of LMRG in the pathogenesis of HCC and presents a novel prognostic signature 6-IS monitoring the clinical course of HCC.
Clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate Alzheimer disease: A protocol of a randomized controlled trial
Authors: Zhou Kangmei , He Jierong , Quan Lin , Guo Rong 
Published: September 2022

Background:
Alzheimer disease (AD) is a common cause of dementia, and there are still a lack of treatment options to reverse or prevent disease progression. Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict placebo-controlled clinical study to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD.

Methods:
This is a prospective randomized, a single-blind, sham-acupuncture controlled trial to study the clinical efficacy of acupuncture combined with Western medicine in the treatment of mild to moderate AD. Participants will be randomly divided into treatment and control groups. The treatment group using acupuncture combined with donepezil hydrochloride orally, and the control group using sham acupuncture combined with donepezil hydrochloride orally, followed up for 24 weeks after 24 weeks of continuous treatment. Outcome measures included: AD assessment scale-cognitive subscale, mini-mental state examination, activities of daily living, neuropsychiatric inventory questionnaire, serum superoxide dismutase, and homocysteine levels. Finally, SPASS 21.0 software was used for statistical analysis of the data.

Discussion:
This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients. The results of this study will verify whether the efficacy of acupuncture in the treatment of AD belongs to the placebo effect, which will also provide a reference for the clinical use of acupuncture combined with Western medicine in the treatment of AD.

Trial registration:
The TCTR identification number is TCTR20220817004.
Durable response to olaparib combined low-dose cisplatin in advanced hepatocellular carcinoma with FANCA mutation: A case report
Authors: Lai Yi-Hsuan , Tung Kai-Che , Chen San-Chi 
Published: September 2022

Rationale:
To date, there is no actionable gene has been discovered in hepatocellular carcinoma (HCC). Tumor cells with DNA damage response and repair (DDR) gene loss-of-function mutation is sensitivity to poly-ADP-ribose polymerase (PARP) inhibitors and platinum chemotherapy in ovarian, prostate and pancreatic cancers. There is a case report demonstrated the efficacy of PARP inhibitor for BRCA2 mutation that belongs to DDR gene in HCC, which suggested the potential role of PARP inhibitor for HCC with DDR gene mutation.

Patient concerns:
We reported a 44-year-old woman with non-viral HCC who was refractory to multiple treatment including target therapy, immunotherapy, and chemotherapy. The tumor tissue was submitted to next-generation sequencing using the commercially available ACTOnco®+ (ACT Genomics, Taiwan) assay that interrogates 440 and 31 cancer-related genes and fusion genes, respectively.

Diagnosis:
A truncating mutation FANCA p.Q1307fs was also observed. The tumor was microsatellite stable and had low tumor mutational burden of 4.5 muts/Mb.

Interventions and outcomes:
Given FANCA belongs to DDR genes, the inactivation evoked the idea of using PARP inhibitor and cisplatin. Therefore, the patient started to use olaparib combined with low-dose cisplatin (30 mg/m2, every 4 weeks) therapy in December 2019. Significant reduction in the tumor marker level in 1 month (PIVKA-II from 17,395 to 411 ng/dL) and follow-up CT scan showed stable disease. Her tumor did not progress until December 2020 with a progression-free survival of 12 months.

Lessons:
We report the first case of FANCA-mutated HCC that responded well to olaparib and low-dose cisplatin. This addressed the potential therapeutic role of DDR gene mutation in HCC and the possible synergistic effect of PARP inhibitor and cisplatin. These findings highlight areas where further investigation and effort are needed.
A case report of severe adverse reaction of exenatide: Anaphylactic shock
Authors: Liu Xujing , Zhai Aihua , Zhang Bai 
Published: September 2022

Background:
Anaphylactic shock is the severe state of the allergic reaction, which is rapid in onset and fatal. This is the first study that discusses the anaphylactic shock of exenatide reexposure in the patient who has interrupted exenatide treatment.

Patient concerns:
A 47-year-old man was treated with exenatide owing to high blood glucose and obesity. Then he developed localized urticarial on the face, white lip, hands tremble, nausea, vomit, chest stuffiness, dizziness, accompanying with confusion and dyspnea. His blood glucose was 4.6 millimole per liter (mmol/L) and blood pressure was 85/50 millimeters of mercury (mm Hg).

Diagnosis:
Exenatide-induced anaphylactic shock was considered.

Interventions:
The emergency electrocardiogram was performed. The patient was treated with dexamethasone sodium phosphate and calcium gluconate, combined with exenatide withdrawal. He also received oral antiallergic agents and intravenous nutrition treatment.

Outcomes:
After antishock treatment, the clinical response gradually alleviated.

Lessons:
Although exenatide is not prone to anaphylaxis, it is the synthetic peptide that can induce antibody formation. Exenatide has immunogenicity with the potential to elicit an allergic reaction upon administration. Clinicians should always pay more attention to the anaphylactic shock of exenatide, when prescribing for diabetics.
Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme
Authors: Wu Gang , Hao Qingpei , Liu Bo , Zhou Jingru , Fan Cungang , Liu Ruen 
Published: September 2022

Background:
Evodiae fructus has been shown to have anti-glioblastoma multiforme (GBM) effects. However, its anti-GBM active components and mechanism remain unclear. In this study, the active components of evodiae fructus were screened by network pharmacology to explore the possible molecular mechanism of resistance to GBM.

Materials and methods:
The main active ingredients of evodiae fructus were derived from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Batch-traditional Chinese medicine (TCM). TCMSP and Swiss absorption, distribution, metabolism and elimination (ADME) predict genetic targets for ingredients that meet pharmacological criteria. GBM-related targets were obtained from DisGeNet, GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and TCGA. A Venn diagram was used to obtain the common targets of evodiae fructus and GBM. Protein–protein interaction (PPI) networks and component-disease target networks were constructed using Cytoscape 3.8.1 software for visualization. GBM gene differential expression was visualized by VolcaNoseR, and potential targets were enriched by Gene Ontology (GO) function and annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by SRplot. Molecular docking verification was conducted using AutoDock Vina software.

Results:
According to the screening conditions, 24 active components and 80 drug targets were obtained. The PPI network contains 80 proteins. The molecular docking verification showed the molecular docking affinity of the core active compounds in evodiae fructus with CASP3, JUN, EGFR, and AKT1.

Conclusions:
This study preliminarily identified the various molecular targets and multiple pathways of evodiae fructus against GBM.
Research status, hotspots and trends of acupuncture and moxibustion in the treatment of Alzheimer’s disease: A bibliometric analysis
Authors: Yue Jinhuan , Li Xiao-Ling , Gao Rui-Xue , Zhang Qinhong , Li Ang , Zhao Wei-Wei , Li Yan , Li Shu-Lin 
Published: September 2022

Background:
Acupuncture and moxibustion (AM) are utilized to treat Alzheimer’s disease (AD). However, no bibliometric analysis has explored this issue. Thus, this study investigated the status, hotspots and trends of AM in the treatment of AD.

Methods:
CiteSpace and VOSviewer softwares were used to analyze the literature on the AM for AD in the Web of Science Core Collection database. We analyzed the data of countries/regions, institutions, journals, authors, keywords, and cited references.

Results:
After removing duplicates, 193 articles were retrieved. The number of publications on this topic has increased gradually. The most productive and collaborative country was China (143 documents), followed by South Korea (19). The top 3 active academic institutions were Beijing University of Chinese Medicine, Capital Medicine University, and Guangzhou University of Chinese Medicine. The most productive journal was Evidence-based Complementary and Alternative Medicine (13 documents), followed by the Frontiers in Aging Neuroscience (10), Medicine (10), and Neural Regeneration Research (10). The top 3 co-cited journals were Evidence-based Complementary and Alternative Medicine (156 citations), Acupuncture Electro-therapeutics Research (152), and Acupuncture in Medicine (146). The research hotspots in this domain are dementia, memory, hippocampus, mouse models, and Parkinson’s disease. Major frontiers are comparing the therapeutic effects of acupuncture and donepezil and electroacupuncture at different frequencies in this field.

Conclusion:
This bibliometric study identified relevant hotspots and trends in research on AM in the treatment of AD, which can provide researchers with key information in this domain and help further explore new research directions.
The effectiveness of multimedia combined with teach-back method on the level of knowledge, confidence and behavior of professional caregivers in preventing falls in elderly patients: A randomized non-blind controlled clinical study
Authors: Wang Qinqin , Zou Huixiang , Wang Qin 
Published: September 2022

Background:
Teach-back is a teaching method that can quickly improve the acknowledge of target audience and change their behaviors effectively. However, this approach has not been reported in previous studies that were dedicated to reducing the incidence of falls in elderly inpatients. Therefore, we aimed to evaluate the effectiveness of the teach-back method for improving the knowledge, confidence, and behaviors (KCB) of professional caregivers on the fall prevention in elderly inpatients and to provide practical evidence for reducing the incidence of falls.

Methods:
This is a prospective study. At the recruitment, the demographic data of the professional caregivers were completely collected. Questionnaire about KCB of professional caregivers on fall prevention in elderly inpatients was used as an assessment scale, and the differences between the scores were analyzed. At the end of the study, the fall rate of the patients cared by different groups was counted and analyzed.

Results:
A total of 100 professional caregivers were recruited, all of which participated in the whole study process. There was no statistical differences in demographic data. Three or six months after the courses, the knowledge scores, confidence scores, and behavior scores of the two groups were significantly improved, and the observation group scores were significantly higher than it was in the control group (P < .05). During the study period, the incidence of falls in the observation group was 1.32%, while it was 0.30% in the control group (P < .05).

Conclusion:
Teach-back method can rapidly improve KCB of professional caregivers about fall prevention in elderly inpatients, which is worthy of clinical practice.
Hyperkalemia in a Hemolyzed Sample in Pediatric Patients
Authors: Kaila Rahul , Hendrickson Marissa , Avendano Pablo , Davey Cynthia , Cullen Ryan , Colbenson Gretchen , Louie Jeffery 
Published: September 2022

Objective
The aim of the study is to analyze whether repeat testing is necessary in healthy children presenting to a pediatric emergency department (ED) who are found to have hyperkalemia on a hemolyzed specimen.

Methods
A 5-year retrospective analysis of pediatric ED patients found to have elevated potassium values on laboratory testing of a sample reported to be hemolyzed. All patients aged 0 to 17 years who had an elevated potassium level after an intravenous draw resulted from a serum sample that was reported as hemolyzed during an ED visit were included in the study.

Results
One hundred eighty-seven patients with some degree of both hemolysis and hyperkalemia were included in the final analysis. The median age was 1.9 years of age. The most common race among all patients was White, followed by African American, and Asian. One hundred forty-five children had repeat sampling for hemolyzed hyperkalemia, 142 children, 97.9% (95% confidence interval, 95.6%–100%) had a normal potassium on repeat and 3 children, 2.1% (95% confidence interval, 0.0%–4.4%) had true hyperkalemia. The frequency of true hyperkalemia in our study population was 2% (3/145). All 3 of these patients had underlying conditions that would appropriately have raised clinician suspicion for hyperkalemia.

Conclusions
It may be unnecessary to obtain repeat samples to confirm normal potassium in a hemolyzed sample with normal blood urea nitrogen and creatinine.
Donor Side Preference in Maxillary Reconstruction With the Free Fibula Flap
Authors: Weitgasser Laurenz , Barton Richard , Ricketts Sophie , Murray Simon S. , Matros Evan , Morrison Edwin J. 
Published: September 2022

Background:
The implications on the choice of donor side when using the free fibula flap for reconstruction of unilateral maxillectomy defects has not been discussed in the literature so far.

Methods:
A unilateral maxillectomy reconstruction was replicated using a 3D-printed skull model and fresh cadaveric dissections of left and right osteomyocutaneous fibula flaps for comparison. Detailed photo documentation was conducted to analyze and illustrate the anatomical differences of performing a reconstruction using the ipsilateral or contralateral sides and their relative benefits and risks.

Results:
A more favorable lie of the septum and skin paddle and flexor hallucis longus muscle is attainable depending on which donor side is used and the planned direction of the pedicle.

Conclusion:
This study demonstrates why it is preferable to use the ipsilateral fibula if anastomosis is to the ipsilateral facial or neck recipient vessels, or the contralateral fibula where the contralateral recipient vessels are preferred.
A tradeoff between enterovirus A71 particle stability and cell entry
Authors: Catching Adam , Yeh Ming Te , Bianco Simone , Capponi Sara , Andino Raul 
Published: September 2022

AbstractA central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturbed this equilibrium in a non-enveloped virus, enterovirus A71 to determine its structural basis. We isolated a single-point mutation variant with increased particle thermotolerance and decreased efficiency of cell entry. Using cryo-electron microscopy and molecular dynamics simulations, we determined that the thermostable native particles have acquired an expanded conformation that results in a significant increase in protein dynamics. Examining the uncoating intermediate states of the thermostable variant suggests a pathway, where the lipid pocket factor is released first, followed by internal VP4 and finally the viral RNA.
Horizontal detection of post-translational modifications to an amino acid with a nanopore based on analyte volume and translocation-time
Authors: Sampath G. 
Published: September 2022

AbstractA method is proposed for the detection of post-translational modifications (PTMs) in single amino acids (AAs) for three types of PTMs (methylation, acetylation, and phosphorylation). It is preceded by a precursor step in which the terminal residue cleaved from a peptide is identified with a set of transfer RNAs (tRNAs) in a method proposed earlier (doi: 10.36227/techrxiv.19318145.v3). The identified AA (unmodified or modified) is separated from its cognate tRNA and translocated through a nanopore under electrophoresis. The resulting current blockade level (a proxy for analyte volume) and its width (a proxy for analyte translocation time) are measured and used to identify any PTM that might be present. The theoretical volumes of the 20 proteinogenic AAs and their PTMs are computed from crystallographic data and the ratio of the volume of a modified AA to that of an unmodified one obtained. The theoretical translocation time for the 20 AAs and their PTMs through a nanopore with a bilevel voltage profile is calculated with a Fokker-Planck drift-diffusion model. A 2-D scatter plot with these two quantities is generated for each AA type. Experimentally measured blockade levels and widths for an AA, modified or unmodified, can now be compared with the AA’s scatter plot to assign a PTM for a modified AA. PTM assignment is horizontal across the PTMs for the AA because the latter has already been identified from its cognate tRNA in the precursor step, the other 19 AA types and their PTMs are not involved. Computational results are presented for 49 PTMs covering all 20 AAs and the three PTM types mentioned above.
Temperature-triggeredin situforming lipid mesophase gel for local treatment of ulcerative colitis
Authors: Carone Marianna , Spalinger Marianne R. , Gaultney Robert A. , Mezzenga Raffaele , Mookhoek Aart , Krebs Philippe , Rogler Gerhard , Luciani Paola , Aleandri Simone 
Published: September 2022

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colonic mucosa. There is no cure for UC and its chronic relapsing/remitting nature strongly affects patient quality of life. Current treatment options frequently have significant side effects and remission rates are limited raising a demand for new treatment strategies. Novel therapeutic approaches that could maximize the drug concentration at the site of inflammation with minimal systemic exposure, like topical applications, would address this unmet clinical need. To date, few drug delivery systems (DDSs) have been designed to topically convey small molecules to the rectum and left-sided colon. Here, we developed and tested a drug delivery platform for topical treatment of UC based on a temperature-triggeredin situforming adhesive lipid gel (TIF-Gel). Due to its soft, gel-like consistency, its high encapsulation efficacy, and its drug-controlled release, TIF-Gel suggests a more patient-friendly and effective application with respect to the rectal formulations currently available.Capitalizing on the biocompatible and biodegradable self-assembled structure of lipid mesophases (LMPs), we loaded TIF-Gel with tofacitinib (TOFA; a hydrophilic inhibitor of the enzymes Janus kinase 1 and 3) or TAC (a hydrophobic immunosuppressive drug), both of which are indicated in the treatment of UC. We designed and fully characterized our biocompatible lipid formulationin vitroand tested itin vivousing two different murine models of inflammatory bowel disease: chemically-induced and T cell transfer-mediated. Both approaches (TIF-Gel-TOFA and TIF-Gel-TAC) led to reductions in colitis disease severity and intestinal inflammation compared to vehicles, therefore showing therapeutic efficacy.Overall, our findings show that TIF-Gel can deliver drugs locally to the colonic mucosa to mitigate intestinal inflammatory disease in a pre-clinical model. They also suggest that, in a clinical setting, TIF-Gel might provide a patient-friendly approach to improve colitis while allowing for a reduction of the adverse effects associated with a systemic therapy.